Diagnostic Histopathology

Testicular Tumours: Large Cell Calcifying Sertoli Cell Tumour

2008-11-11T07:26:00.000-08:00

Large Cell Calcifying Sertoli Cell Tumour:

This subtype of Sertoli cell tumour is associated in almost half of the reported cases with other endocrine lesions, such as pituitary adenomas, bilateral primary adrenocortical hyperplasia, and testicular Leydig cell tumours.
Cardiac myxomas and spotty mucotaneous pigmentation have also been reported.
The clinical associations have included acromegaly, gigantism, hypercortisolemia, sexual precocity, sudden death, and the Peutz-Jeghers syndrome.
The large cell calcifying Sertoli cell tumour is usually 4 cm or less in diameter and is multifocal or bilateral in almost half of the cases.
Sectioning discloses firm yellow to tan tissue in which granular calcific foci may be detectable. The tumours appear grossly well circumscribed in most cases.
Microscopic examination reveals that the neoplastic cells are arranged in sheets, nests, trabeculae, cords, small clusters, or solid tubules. The characteristic feature is the presence of calcification, which is usually conspicuous and sometimes massive, with the formation of large, wavy, laminated nodules. The neoplastic cells are typically large and rounded, but occasionally are cuboidal or columnar, and rarely are spindle shaped. In most of the cases, the cytoplasm is abundant, eosinophilic, and finely granular. The nuclei are round or oval without conspicuous nucleoli. Mitotic figures are generally rare.
Features of malignant and benign large cell calcifying Sertoli cell tumours have also been studied. It showed that the malignant tumours were unilateral and solitary and occurred at a mean age of 39 years, whereas the benign neoplasms were more often bilateral and multifocal in some of the cases and occurred at a mean age of 17 years.
There were strong associations of a malignant behavior with size larger than 4 cm, extratesticular growth, gross or microscopic necrosis, high-grade cytologic atypia, vascular space invasion, and a mitotic rate of more than 3 mitoses per 10 high-power fields. All of the malignant cases exhibited at least 2 of these features, whereas all of the benign cases lacked any of them. The presence of any 1 of these features in a solitary large cell calcifying Sertoli cell tumour, especially in a patient older than 25 years, should be considered suspicious for a malignant behavior, whereas 2 or more of these indicate a strong probability of a malignant course.

Abstract:
Large cell calcifying Sertoli cell tumor of the testis: contrasting features of six malignant and six benign tumors and a review of the literature. Am J Surg Pathol. 1997 Nov;21(11):1271-80.
We report six malignant and six benign large cell calcifying Sertoli cell tumors of the testis and compare the features of malignant and benign cases based on these cases and those in the literature. All the tumors in this report consisted of sheets, nests, solid tubules, and cords of eosinophilic cells, with focal calcifications, as well as a substantial neutrophilic infiltrate in 11 of them. Analysis of our cases and those in the literature showed that the malignant tumors were unilateral and solitary and occurred at a mean age of 39 years (range 28-51 years), whereas the benign neoplasms were bilateral and multifocal in 28% of cases and occurred at a mean age of 17 years (range 2-38 years). Only one malignant tumor occurred in a patient with evidence of a genetic syndrome (Carney syndrome), whereas 36% of benign tumors had various genetic syndromes or endocrine abnormalities. Most of the tumors in the latter cases were bilateral and multifocal. There were strong associations of malignant behavior with size >4 cm, extratesticular growth, gross or microscopic necrosis, high-grade cytologic atypia, vascular space invasion, and mitotic rate greater than three mitoses per 10 high-power fields. All malignant cases exhibited at least two of these features, whereas all benign cases lacked any of them. The presence of any one of these features in a solitary large cell calcifying Sertoli cell tumor, especially in a patient >25 years of age, should be viewed as suspicious for malignant behavior, whereas the presence of two or more of these features indicates a strong probability of a malignant course. "Low" percentages (< or ="35%)">

Abstracts:
Utility of immunostaining for S-100 protein subunits in gonadal sex cord-stromal tumors, with emphasis on the large-cell calcifying Sertoli cell tumor of the testis. Hum Pathol.2002 Mar;33(3):285-9.
This study concerns the immunohistochemical localization of S-100 alpha, S-100 beta, and whole brain S-100 (wbS-100) in testicular large-cell calcifying Sertoli cell tumor (LCCSCT). We examined 8 LCCSCTs (7 benign and 1 malignant), 6 Sertoli cell tumors not otherwise specified (SCTs-NOS), 6 Leydig cell tumors (LCTs), 5 ovarian Sertoli-Leydig cell tumors (SLCTs), and 7 gonadoblastomas (GBLs). The 8 LCCSCTs showed immunoreactivity for S-100 alpha, S-100 beta, and wbS-100. Five of the 6 LCTs and the Leydig cell components in the ovarian SLCTs stained positively for S-100 alpha and wbS-100 but were negative for S-100 beta. SCTs-NOS and the Sertoli cell components in the SLCTs occasionally showed focal and weak/moderate positivity for S-100 alpha, S-100 beta, and wbS-100. Sex cord cells of the GBLs were positive for S-100 beta and wbS-100 and negative for S-100 alpha. Germ cell elements of the GBLs were negative for S-100 alpha, S-100 beta, and wbS-100. In nonneoplastic testicular parenchyma adjacent to the above-mentioned tumors, there was S-100 alpha reactivity in Leydig cells, rete testis, and a few Sertoli cells. S-100 beta reactivity was seen in a few Sertoli cells, Schwann cells, and some endothelial cells. WbS-100 reactivity was present in Leydig cells, a few Sertoli cells, rete testis, Schwann cells, and some endothelial cells. The results indicate that S-100 alpha and S-100 beta can potentially be used as immunohistochemical markers for LCCSCT, especially when differentiating it from LCT, which may mimic LCCSCT on routine histopathology. Although the biological significance of both S-100 subunits expression in LCCSCT remains unknown, these notable calcium-binding proteins may be associated with the characteristic calcification in LCCSCT through regulation of calcium levels in the tumor cells.

Abstract:
Large cell calcifying Sertoli cell tumor of the testis. A clinicopathologic, immunohistochemical, and ultrastructural study of two cases. Am J Clin Pathol. 1991 Dec;96(6):717-22.
The clinicopathologic, immunohistochemical, and electron microscopic study of two patients with large cell calcifying Sertoli cell tumors (LCCSCT) of the testis is reported to elucidate the histogenesis of this rare tumor. Both tumors occurred in young individuals (16 and 32 years); case 1 was found incidentally, and the patient in case 2 presented with a 3-4-week history of testicular pain. Evidence of testosterone production was demonstrated in one case. In the same case, at the ultrastructural level Charcot-Böttcher crystalloids were observed. These data support previous reports that LCCSCT shows Sertoli cell differentiation.

Testicular Tumours: Sertoli Cell Tumour

2008-10-26T10:13:00.000-07:00

Sertoli Cell Tumors (Androblastoma):

These are uncommon tumours, composed of Sertoli cells or a mixture of Sertoli and Leydig cells. One-third of Sertoli cell tumours have admixed Leydig cells and are regarded as mixed gonadal stromal tumors.

These tumours usually develop in the first four decades of life, with only a few cases reported in older patients.

Tumours may elaborate androgens or estrogens but rarely in sufficient quantity to produce precocious masculinization or feminization.
Grossly, the tumour present as well-circumscribed, homogeneous gray-white-to-yellow masses of variable size.

Microscopically, the tumour consists of tubular arrangement, with solid cords of cells and a fibrous trabecular framework.

Most cases are benign. 10% cases demonstrate invasion, metastases, or both.

The malignant variant exhibits greater cellular pleomorphism, areas of necrosis, and a reduced tendency to form cords and tubules.

Testicular Tumours

2008-10-25T11:58:00.000-07:00

A wide range of histologic types of testicular tumours are recognized, giving rise to many different classification schemes.

Tumours can be divided into two major groups:

1. Germ cell tumours (accounting for approximately 95% of cases)
2. Nongerminal tumours (stromal or sex cord tumours)

Most germ cell tumours are aggressive lesions, although outlook has improved considerably with current therapy.Most neoplastic scrotal masses ultimately prove to be germ cell tumours and are recognisable with routine haematoxylin and eosin-stained sections.The differential diagnosis may be focused, even before reviewing histological sections, by knowledge of patient age, medical history, tumour site (testicular vs paratesticular) and gross findings.Some cases may prove to be diagnostically challenging, including rare tumours, a common tumour with an unusual pattern, a metastatic tumour, or a neoplasm with features that mimic another tumour.Several morphological patterns are seen with some frequency and these generate recurring sets of differential diagnostic considerations. These common patterns include testicular tumours with a predominant diffuse arrangement of cells with pale to clear cytoplasm, tumours with a glandular/tubular pattern, tumours with a microcystic pattern and tumours composed of oxyphilic cells. Intratubular proliferations of atypical cells, paratesticular glandular and/or papillary tumours, or tumours with spindle cell morphology can also be challenging to diagnose correctly.In some problematic cases, immunohistochemical staining may be useful to resolve these differential diagnoses.

The following are the risk factors for testicular carcinoma:
i) Previous history of testicular tumor; ii) positive family history; iii) cryptorchidism; iv) infertility, and v) intersex syndromes (gonadal dysgenesis, true hermaphroditism, and pseudohermaphroditism). If a patient has had carcinoma in one testis, his risk for developing a contralateral tumour is more than 20 times that of the general population.A history of testicular carcinoma in a first-degree relative increases the risk factor several times.

Cryptorchidism (incomplete descent of the testicles from the retroperitoneum into the scrotum) has a strong association with testicular carcinoma. The majority of undescended testes lie distal to the external inguinal ring and are palpable. They generally descend into the scrotum by 1 year of age. Nonpalpable testicles are usually within the inguinal canal but can be anywhere along the path of descent from the retroperitoneum. Although the overall occurrence of cryptorchidism is low (<1%).

The use of immunohistochemistry in the differential diagnosis of tumors of the testis and paratestis. Semin Diagn Pathol. 2005 Feb;22(1):33-50.
Although most testicular and paratesticular tumors can be recognized by their light microscopic features, some raise significant differential diagnostic questions. Immunohistochemical staining has proved of significant value in this situation. There is still a role for the traditional markers, including placental-like alkaline phosphatase and alpha-fetoprotein, but newer markers provide additional support and often have greater sensitivity and specificity for many diagnoses. OCT4 is virtually 100% sensitive and specific for seminoma, embryonal carcinoma, and intratubular germ cell neoplasia, unclassified type. Inhibin-alpha, among testicular tumors, is limited to those in the sex cord-stromal category or those having adrenocortical-type differentiation (testicular tumor of the adrenogenital syndrome) or of trophoblastic lineage. Calretinin is another positive marker for the sex cord-stromal tumors but has less specificity. Additional markers, including differential cytokeratins, c-kit, CD30, epithelial membrane antigen, S-100, melan-A, and others, are useful in specific situations. This article reviews the application of immunohistochemical markers for a number of differential diagnostic considerations in the testis and paratestis categorized according to their light microscopic patterns.

Abstract:
From the archives of the AFIP: tumors and tumorlike lesions of the testis: radiologic-pathologic correlation. Radiographics. 2002 Jan-Feb;22(1):189-216.
Testicular carcinoma represents only 1% of all neoplasms in men, but it is the most common malignancy in the 15-34-year-old age group. Germ cell tumors constitute 95% of all testicular tumors. Germ cell tumors are a varied group of neoplasms whose imaging features reflect their underlying histologic characteristics. Seminomas are generally well-defined homogeneous lesions, whereas the nonseminomatous tumors (embryonal carcinoma, yolk sac tumor, choriocarcinoma, teratoma, and mixed germ cell tumor) have a much more varied appearance. Germ cell tumors follow a predictable pattern of spread via the lymphatic drainage to the retroperitoneal nodes. Choriocarcinoma, which has a proclivity for early hematogenous spread, is a notable exception. Testicular tumors may also arise from the sex cords (Sertoli cells) and stroma (Leydig cells). Although 90% of these tumors are benign, there are no reliable imaging criteria to differentiate them from malignant masses. Some benign testicular masses can be recognized, obviating an unwarranted orchiectomy. A dilated rete testis is a normal variant and appears as a series of small tubules near the mediastinum testis. Other benign lesions that can be suspected on the basis of imaging findings and history include intratesticular cysts, epidermoid cysts, congenital adrenal hyperplasia, and sarcoidosis.

Testicular Tumours: Granulosa Cell Tumour :Juvenile-type Granulosa Cell Tumour

2008-10-25T09:32:00.000-07:00

II Juvenile Granulosa Cell Tumour:

Juvenile granulosa cell tumours occur in the first few months of life. These tumours are most common neonatal testicular tumour (6% of childhood testicular tumours) and may pose major problems in differential diagnosis. These neoplasms may occur in infants with mixed gonadal dysgenesis, (tumours may be associated with trisomy 12 and sex chromosome mosaicism)
Gross features: On gross examination, these tumours vary greatly in size, with many of them replacing most or all of the testis. They are usually well circumscribed and are composed of white to yellow, often lobulated tissue. Cysts may be present.
Microscopic features: Microscopic examination reveals a spectrum of patterns , ranging from predominantly epithelial to predominantly stromal. A mixed pattern, usually with at least focally prominent follicles, is most common. The follicles are often variable in both size and shape. In some cases, lipid vacuoles are conspicuous within the tumour cells. One may see solid or hollow tubules, or cords composed of or lined by cells resembling Sertoli cells. Occasionally, a more diffuse pattern is seen. In these cases the cells are small with hyperchromatic nuclei and mitotic activity may be prominent. Usually, the nuclei of the granulosa cells lack the features of those of ovarian adult granulosa cell tumours, such as nuclear grooves.
Special stains: Positive stains: vimentin, low molecular weight cytokeratin, actin, desmin, CD99.
Differential diagnosis: Juvenile granulosa cell tumour was occasionally misdiagnosed as yolk sac tumour. The follicular pattern of juvenile granulosa cell tumour is the major clue to the diagnosis. It is also crucial to be aware of the existence of juvenile granulosa cell tumour as an entity in the testis and its great tendency to occur in the first few months of life, whereas the yolk sac tumour occurs generally from 1 year on.
The mitotic activity of this tumour and spindle cells may lead to the misdiagnosis of rhabdomyosarcoma. The gross appearance is important - sarcomas are almost always paratesticular rather than testicular. It may not always be possible to make this distinction when the sarcoma reaches a large size.

Abstract:
Juvenile granulosa cell tumor of the infantile testis. A report of 14 cases.Am J Surg Pathol.1985;9(2):87-94.
Fourteen testicular tumors diagnosed in infants less than 6 months of age had a distinctive appearance resembling that of the juvenile granulosa cell tumor of the ovary. One of them was discovered at autopsy in an infant of 30 weeks' gestational age; seven were diagnosed during the first few days of life, and the remainder between 3 weeks and 4 1/2 months of age. Enlargement of a scrotal testis was the presenting manifestation in 10 cases and abdominal swelling in one case; one tumor was found in a descended testis that had undergone torsion and one was discovered in an inguinal testis at the time of inguinal herniorrhaphy. The tumors ranged from 0.8 to 5.0 cm in diameter and were cystic or partly cystic and partly solid. Microscopic examination disclosed both follicular and solid components. The follicles were of varying sizes and contained eosinophilic or basophilic fluid that stained positively for mucin in some of the cases. The solid foci typically had a nodular arrangement and occasionally were hyalinized or had a basophilic background due to the presence of intercellular mucin. The neoplastic cells contained moderate to large amounts of eosinophilic cytoplasm and round to oval hyperchromatic nuclei, which typically lacked grooves. The mitotic rate varied from less than 1-24/10 high-power fields. Limited follow-up examination revealed no evidence of recurrence. The microscopic features of these neoplasms warrant their designation as "juvenile granulosa cell tumor.

Abstract:
Juvenile granulosa cell tumor of the infantile testis. Evidence of a dual epithelial-smooth muscle differentiation. Am J Surg Pathol. 1996 Jan;20(1):72-9.
We report the ultrastructure and immunohistochemical profile of seven juvenile granulosa cell tumors of the infantile testis. The infants' ages ranged from 1 day to 11 months. All tumors had characteristics ultrastructure with a mixture of spindle smooth-muscle and theca cells and polygonal granulosa cells. Clusters of polygonal granulosa cells were invested by a continuous basal lamina and contained bundles of distinct cytoplasmic filaments with evenly distributed dense bodies resembling smooth muscle. These filaments were occasionally attached to well-developed, prominent desmosomes. Tumor cells had a conspicuous rough endoplasmic reticulum and Golgi complex and occasional neutral fat droplets. In all tumors, mitochondria had laminated cristae and only rarely were there cristae with a tubulovesicular pattern characteristic of steroid secreting cells. Tumor cells stained focally with low-molecular-weight cytokeratins (8,18, and 19), smooth-muscle-specific actin, desmin, and more noticeably with vimentin. These ultrastructural and immunohistochemical features of dual epithelial-mesenchymal differentiation and distinct muscle-like filaments with dense bodies are characteristic of the juvenile granulosa cell tumor of the infantile testis.

Abstract:
Testicular juvenile granulosa cell tumor in an infant with X/XY mosaicism clinically diagnosed as true hermaphroditism. Am J Surg Pathol. 1994 Mar;18(3):316-22.
We report a testicular juvenile granulosa cell tumor (T-JGCT) with characteristic clinical and histopathological features. The tumor was present in the left abdominal testis of a 7-month-old infant with a 45,X/46,XY karyotype and ambiguous genitalia. Preoperatively, the infant was diagnosed as having functional testicular and ovarian elements based on elevated levels of serum testosterone and estradiol following human chorionic gonadotropin and human menopausal gonadotropin administration, respectively. Histologically, the left gonad contained a tumorous lesion composed of an admixture of cellular areas and multiple cystic follicles that had some continuity with the adjacent testicular tubules. Some tumor cells showed immunoreactivity for estradiol. The right gonad was a streak gonad containing small irregular nests of sex cord-type cells. No maturing ovarian follicle was present in either gonad. To our knowledge, this is the fifth reported case of T-JGCT with abnormal sex chromosomes, and the first case of T-JGCT confirmed to have not only the morphological but also the functional characteristics of granulosa cells.

Abstract:
Congenital testicular juvenile granulosa cell tumor in a neonate with X/XY mosaicism. Am J Surg Pathol. 1986 Aug;10(8):577-83.
A congenital sex cord-stromal tumor of the testis with morphologic features of juvenile granulosa cell tumor is reported. The tumor occurred in an abdominal testis of a newborn infant with an X/XY karyotype and ambiguous genitalia and presented as a partially cystic mass associated with ascites. Histologically the tumor was comprised of an admixture of solid, cellular, poorly differentiated lobules mimicking graafian follicles. Residual hypoplastic testicular tissue was present at the periphery. This is the 19th reported case of testicular juvenile granulosa cell tumor and the fourth with an underlying sex chromosome anomaly, further emphasizing the relationship of this uncommon neoplasm to abnormal sexual or gonadal development.

Testicular Tumours: Granulosa Cell Tumour : Adult-type Granulosa Cell Tumour

2008-10-22T12:01:00.000-07:00

Granulosa cell tumour
This tumour is morphologically similar to the ovarian counterpart. It is exceedingly rare in the testis.
Granulosa cell tumours are divided into 2 types, adult and juvenile, and both types represent a distinct group of the sex cord–stromal tumours of the gonads.

I Adult Granulosa Cell Tumour:

Adult-type granulosa cell tumour is considered a very rare testicular tumour. The tumours are usually non functional and may be associated with gynecomastia.
Age: 20-50 years.
Gross features: The tumour mass is often partially encapsulated and come in direct contact with the tunica albuginea. The cut surface may be homogeneous, beige, firm, and fleshy. There is usually no evidence of necrosis or hemorrhage. In some cases there may be a small area of ossification. A central round nodule with a yellow surface and firm consistency may be present. The mass usually do not infiltrate the adjacent testicular tissue.
Microscopic features: Histologic examination from the tumour reveal a wide variety of patterns which included gyriform, macrofollicular, insular, trabecular, solid, pseudosarcomatous, and microfollicular. The microfollicular pattern is characterized by the presence of numerous cavities simulating Call-Exner bodies. These cavities contain eosinophilic fluid and sometimes hyalinized basement membrane material. The microfollicles are separated by well-differentiated granulosa cells that contained scant cytoplasm and pale, angular, or oval, often grooved nuclei arranged haphazardly in relation to one another and to the follicle. Rare theca cells may be seen scattered in between the neoplastic granulosa cells. Few mitotic figures are seen, but no abnormal forms are noted. Necrosis is usually not present. The yellow nodule consist of interlacing bundles of spindle cells with cigar-shaped nuclei that contain similar grooves (these are not as prominent as other areas) and eosinophilic cytoplasm. Mitotic figures in the spindle cell area are more prominent.
It does have the potential to metastasize, even a long time after the initial presentation, and it is usually associated with a long survival period.
By immunophenotyping, membranous staining with MIC2 (O13) is helpful in differentiating this tumour from other gonadal tumours. Reactions for desmin, epithelial membrane antigen, S100 protein, and leukocyte common antigen are negative.

Abstract:
Anti-Müllerian hormone is a specific marker of sertoli- and granulosa-cell origin in gonadal tumors. Hum Pathol.2000 Oct;31(10):1202-8.
Sex cord stromal tumors are gonadal neoplasms containing Sertoli, granulosa, Leydig, or thecal cells, which originate from cells derived from either the sex cords (Sertoli and granulosa cell tumors) or the specific mesenchymal stroma (Leydig and thecal cell tumors) of the embryonic gonad. Only granulosa and Sertoli cells produce anti-Müllerian hormone (AMH). Our purpose was to investigate whether AMH can be used as a specific marker of human granulosa or Sertoli cell origin in gonadal tumors, to distinguish them from other primary or metastatic neoplasms, using immunohistochemistry. We studied 7 juvenile and 6 adult-type granulosa cell tumors of ovarian localization and 3 extraovarian metastases, 20 other ovarian tumors, 6 testicular Sertoli cell tumors, 2 gonadoblastomas, and 13 extragonadal tumors. Granulosa cell tumors, both juvenile- and adult-type of either ovarian or metastatic localization, showed an heterogeneous pattern of AMH immunoreactivity: Areas containing intensely or weakly AMH-positive cells were intermingled with AMH-negative areas. Although in most cases AMH-positive areas represented a minor proportion of tumor cells, we found a positive reaction in all the cases examined. In testes, although normal prepubertal Sertoli cells were intensely positive, testicular Sertoli cell tumors showed large areas of negative reaction, with few positive cells scattered throughout the tumor. AMH was also reactive in most of the cells of sex-cord origin in gonadoblastomas. No AMH immunoreaction was observed in other gonadal and extragonadal tumors. We conclude that AMH expression is conserved in only a small proportion of tumor cells of granulosa or Sertoli cell origin; however, a positive reaction in a few cells helps to distinguish between granulosa or Sertoli cell tumors or gonadoblastomas and other gonadal tumors of different origin.

Abstract:
Granulosa cell tumor of the adult type: a case report and review of the literature of a very rare testicular tumor. Arch Pathol Lab Med.2000 Oct;124(10):1525-8.
We report a case of testicular granulosa cell tumor of the adult type in a 48-year-old man. Microscopically, the tumor consisted of round to ovoid cells with grooved nuclei that were arranged in several patterns, including microfollicular, macrofollicular, insular, trabecular, gyriform, solid, and pseudosarcomatous. These cells demonstrated strong immunopositivity with MIC2 (O13) antibody, vimentin, and smooth muscle actin and focal positivity with cytokeratin. Although this type of sex cord-stromal tumor is relatively common in the ovaries, it is still extremely unusual in the testis, and it probably represents the rarest type of testicular sex cord-stromal tumor.

Abstract:
Granulosa cell tumor of the adult testis: a clinicopathologic study of seven cases and a review of the literature.Hum Pathol.1993 Oct;24(10):1120-5.
We report a study of seven men, aged 16 to 76 years (average age, 47.4 years) with granulosa cell tumor (GCT) of the testis. Three patients presented with testicular enlargement of several years' duration and a fourth presented with a testicular enlargement of unknown duration. The tumors in three patients were detected during routine physical examination. None of the patients had endocrine-related symptoms. All tumors were well circumscribed and showed the solid, cystic, microfollicular, gyriform, insular, and trabecular patterns typical of GCT of the ovary. Call-Exner bodies were present in three tumors and two tumors had a focal spindle-cell component. In one case the surrounding testicular parenchyma showed Leydig's cell hyperplasia and a Sertoli cell nodule. The tumor cells revealed strong immunoreactivity for vimentin but showed no expression for keratin or epithelial membrane antigen. One patient developed liver and retroperitoneal lymph node metastases 121 months after initial diagnosis and died 13 months later. Another patient initially presented with retroperitoneal lymph node metastasis and developed metastasis to the inguinal lymph nodes 12 months later. Three patients are alive at 1, 4, and 37 months with no evidence of disease. Another patient died of an unrelated condition. Follow-up information was not available for the seventh patient. Twelve cases of GCT of the adult testis have been reported in the literature, with metastases occurring in two: one of these two patients had a tumor for 8 years and died of disease 5 months after diagnosis with multiple metastases and the other had metastasis at the time of diagnosis, but was free of disease for 14 years. Our findings and a review of the literature indicate that GCT of the adult testis is a rare and slow-growing neoplasm with the potential to form distant metastases. Because recurrence or distant metastasis may occur late in the clinical course, long-term follow-up of these patients is recommended.

Testicular Tumours : Testicular Fibroma

2008-10-22T09:38:00.000-07:00

Intratesticular fibroma of gonadal stromal origin, with or without minor sex cord elements, must be considered, analogous to similar tumours in ovary, as a benign tumour.

Histologic and/or immunohistochemical evidence of sex cord differentiation confirms that it could constitute a distinct clinicopathologic entity among unclassified sex cord–stromal tumours. It could be considered the testicular equivalent to ovarian fibroma.

On gross examination, the lesions are circumscribed, firm, whitish, and intratesticular. They usually measure 0.8 and 1.5 cm in diameter. Gross necrosis and hemorrhage are usually absent.

On light microscopy, the tumours consists of a nonencapsulated proliferation of irregularly intermixed fusiform cell bundles separated by a hyalinized fibrocollagenous stroma containing scattered blood vessels. Cellularity may fluctuate in the various sites. The spindle cells are arranged in some areas in a storiform or hemangiopericytoma-like pattern. They have scant, slightly eosinophilic cytoplasm and elongated nuclei with tapered ends. Mitotic figures usually range from 1 to 2 per 10 high-power fields. In some cases after examination of multiple-level sections a minor sex cord component may be found in the periphery of the tumour. It may be composed of small cells with scant basophilic cytoplasm and an elongated hyperchromatic nucleus, as in indifferentiated cells of sex cord type. In adjacent testicular parenchyma, spermatogenesis may be normal or immature in seminiferous tubules.

By immunohistochemistry, spindle cell tumours are positive for vimentin, smooth muscle actin, and sometimes for desmin, cytokeratin, and S100 protein.

Differential diagnosis includes rare cases of intratesticular leiomyoma. Both intratesticular fibroma and leiomyoma of the testis are spindled neoplasms with potential immunoreactivity for vimentin, smooth muscle actin, and desmin. The finding of a minor sex cord component or a positive reaction for MIC2 and inhibin in intratesticular fibroma can be very helpful features in differentiating these 2 entities.

Differential diagnosis also includes intraparenchymatous growth of neurofibroma and solitary fibrous tumor of the tunica vaginalis. Neurofibroma contains spindle cells positive for S100 protein, but negative for smooth muscle actin, desmin, MIC2, and anti-inhibin.

Solitary fibrous tumor of tunica vaginalis contains spindle cells positive for CD34, unlike intratesticular fibroma.

Abstract

Testicular fibroma of gonadal stromal origin with minor sex cord elements: clinicopathologic and immunohistochemical study of 2 cases. Arch Pathol Lab Med.1999 May;123(5):391-4.

OBJECTIVE: To report the histologic and immunohistochemical features of 2 cases of intratesticular fibromatous tumors. RESULTS: Microscopically, these tumors were composed of short, randomly interweaving fascicles of spindle cells dispersed within a fibrocollagenous stroma. A sex cord component was detected in one case by microscopic examination and in both cases by immunohistochemical study using MIC2 and anti-inhibin antibodies. CONCLUSIONS: The presence of minor sex cord elements, morphologically or by immunohistochemistry, suggests that these fibromatous tumors are related to and are a subset of sex cord-stromal tumors. Intratesticular fibromatous tumors, of which 11 other cases lacking sex cord elements have been reported, could be considered as the testicular equivalent of ovarian fibroma. These tumors could then be referred to as testicular fibroma of gonadal stromal origin, with or without minor sex cord component.

Abstract:

Benign fibromatous tumors of the testis and paratesticular region: a report of 9 cases with a proposed classification of fibromatous tumors and tumor-like lesions. Am J Surg Pathol.1997 Mar;21(3):296-305.

Benign intrascrotal fibrous proliferations are uncommon, with most arising from the paratesticular region and falling into the category of so-called fibrous pseudotumor. We describe two neoplastic forms of benign fibrous tumor of the testis and its adnexa: fibroma of gonadal stromal origin and fibroma of the testicular tunics. Three patients with gonadal stromal fibroma were 28, 33, and 35 years of age and presented with painless masses. The tumors were circumscribed, intratesticular, yellow-white or white lesions 0.9 to 4.0 cm in diameter and had microscopic features identical to those of the ovarian fibroma. Immunohistochemically, the tumor cells were strongly positive for vimentin (3/3 cases), focally positive for actin and desmin (2/3 cases) and negative for S-100, keratin, and CD34 (3/3 cases). Six fibromas of the testicular tunics arose in patients 22, 34, 60, 68, 70, and 74 years old and were also asymptomatic masses. Four of them were circumscribed, whorled, white masses arising from the tunica albuginea with variable areas of myxoid change; one was pedunculated and grew exclusively into the cavity of the tunica vaginalis, whereas the other three at least partially extended into the testis as well. The other two tumors were unattached to the tunica albuginea and presented as circumscribed, white-tan paratesticular masses, partially covered by tunica vaginalis. Microscopically, the tumors were slightly to moderately cellular, with bland spindle or stellate cells lying in a myxoid or collagenous stroma with prominent vessels. The two paratesticular tumors had features typical of solitary fibrous tumor. Immunohistochemically, the fibromas of the testicular tunics were negative for S-100, keratin, and desmin. Focal, weak reactivity for actin was present in one case. CD34 was positive in three cases; in the two tumors resembling solitary fibrous tumors it was strong, and in the other it was focal and was limited to the region just below the tunica vaginalis. Eight tumors were treated by radical orchiectomy and one by excision of the mass alone. The outcome was benign in the seven cases in which followup information is available.

Abstract:

Benign fibrous tumor of the tunica vaginalis testis. Report of a case with light, electron microscopic, and immunocytochemical study, and review of the literature.Arch Pathol Lab Med.1992 Mar;116(3):277-80.

Benign fibrous tumor of the tunica vaginalis testis is an uncommon lesion of unknown pathogenesis and histogenesis, frequently described as fibrous pseudotumor. We describe a case of a fibrous tumor of the tunica vaginalis testis studied with light, immunocytochemical, and electron microscopy in a 64-year-old man who also developed a metachronous renal cell carcinoma. To our knowledge, this is the first such case to be presented. We describe the cell of origin of this rare entity and its similarity to fibrous tumors of pleura and extrapleural sites, with a review of the English-language literature and emphasize that not all intrascrotal tumors are malignant.

Testicular Tumours: Regressed Germ Cell Tumours

2008-10-17T11:44:00.000-07:00

Regressed Germ Cell Tumours
The phenomenon of regressed or "burned-out" germ cell tumour is well known but incompletely understood. The patient may present with widespread metastases even though the primary tumour has involuted. The pathogenesis of this phenomenon may be that the high metabolic rate of the tumour causes it to rapidly outgrow its blood supply. These tumours are clinically occult, with the testis being normal to small upon palpation.
The germ cell tumours undergo apparent spontaneous regression, resulting in complete or almost complete hyaline scarring. (This is variously referred to as spontaneous regression or “burnt-out” germ cell tumour).
In these cases, the testis typically is firm and white and on microscopic examination hyaline scarring is seen, sometimes with a minor component of associated viable neoplasia, such as seminoma, teratoma, or intratubular germ cell neoplasia - the latter may be a subtle clue to the diagnosis that what one is observing is something more specific than just an old hyalinized infarct on nonspecific atrophy.
Sometimes, the scar shows rather prominent vessels , hemosiderin-laden macrophages, chronic inflammatory cells and, particularly in cases that are presumptively “dead” embryonal carcinoma, intratubular calcification.
Although these regressed tumours may be sometimes clinically apparent as testicular abnormalities on palpation, they often only diagnosed on ultrasound.
Example: A patient is investigated after presenting with a retroperitoneal germ cell tumour, which is ultimately shown to be a metastasis from the regressed testicular primary.

Testicular Tumours: Mixed Germ Cell Tumour

2008-10-17T11:03:00.000-07:00

Mixed Germ Cell Tumour
Mixed germ cell tumours contain more than one germ cell component.
Of the nonseminomatous germ cell tumours, mixed germ cell tumours are much more common than any of the pure histologic forms and represent 32%–60% of all germ cell tumours.
Essentially, any admixture of the germ cell tumours as seen in pure form may be seen, one of the most common admixtures being embryonal carcinoma and teratoma (the old teratocarcinoma). Minor foci of yolk sac tumor are common, although it is usually overshadowed by other components, such as embryonal carcinoma. As is typical of embryonal carcinoma when seen in pure form, epithelium is often associated with syncytiotrophoblast giant cells when seen as part of a mixed germ cell tumour.
Although seminoma may be seen as part of a mixed germ cell tumour, in some cases one sees seminoma separate from a dominant mass of nonseminomatous mixed germ cell neoplasia, and in such cases it is probably truly multicentric neoplasia, although for sign-out purposes it is probably sufficient to consider the seminoma together with the other neoplastic components under the one designation of mixed germ cell tumour with the traditional rough quantitation of the various components in descending order of frequency.
Note: Embryonal carcinoma is the most common component and is often combined with one or more components of teratoma, seminoma, and yolk sac tumour.
The average age of presentation for patients with mixed germ cell tumours is 30 years.

Abstract:
Mixed testicular germ cell tumor in an adult with cryptorchidism and Down's syndrome. APMIS. 2007 Nov;115(11):1292-5.
We here present a case of mixed testicular germ cell tumor in an adult with cryptorchidism and Down's syndrome. A 20-year-old Japanese man with a mass in the left inguinal region underwent orchidectomy as a left testicular tumor was suspected. Histology showed a mixed germ-cell tumor with embryonal carcinoma and yolk sac tumor with syncytiotrophoblastic giant cells occurring in a cryptorchid testis. Chromosomal analysis of peripheral lymphocytes disclosed a karyotype of 47,XY,+21[20]. Our case provides further evidence that these three conditions-Down's syndrome, cryptorchidism and testicular germ cell tumor-may be closely associated. To our knowledge this is the first case of mixed germ cell tumor arising in a patient with Down's syndrome and cryptorchidism.

Testicular Tumours: Leydig (Interstitial) Cell Tumours

2008-10-16T09:17:00.000-07:00

Leydig cell tumours are relatively uncommon neoplasms, accounting for 2% of all testicular tumours.
They occur in two age groups (but may be found at any age) :
- Boys younger than four years of age.
- Most occur between the ages of 20 and 60 years.
The tumours elaborate androgens or mixtures of androgen and other steroids (estrogens, corticosteroids).
The endocrine effects from these interstitial cell (Leydig cell-derived) tumours in prepubertal children lead to precocoious physical and sexual development. By contrast, feminization, such as gynecomastia, is observed in some adults with this tumour.
Clinical manifestations include a testicular mass and changes referable to hormonal abnormalities.
In pre-pubertal boys there is precocious physical and sexual development.
In adults it causes gynecomastia.
Grossly, the tumors are circumscribed nodules with a homogeneous, golden brown cut surface. Necrosis and hemorrhage may be seen and cause concern for malignancy.
Microscopic features: The most common microscopic pattern is diffuse. Insular, trabecular, pseudotubular, and ribbonlike arrangements of the tumour cells are occasionally noted. Necrosis may impart a pseudopapillary appearance. The stroma may be hyalinized and occasionally edematous or myxoid. The neoplastic cells resemble normal Leydig cells in most cases. They typically have abundant eosinophilic, slightly granular cytoplasm, but the cytoplasm may be spongy as a result of lipid accumulation. Crystals of Reinke are found in approximately one third of the cases.
Microscopically, they are composed of polygonal cells with abundant granular, eosinophilic or cytoplasm and indistinct cell borders. Lipochrome pigment, lipid droplets and characteristic cytoplasmic inclusion “Reinke crystalloids” (well defined rectangular eosinophilic structure) are commonly present.
Ten percent of tumours invade, metastasize or both invade and metastasize.
-No single pathologic criterion reliably distinguishes between benign and malignant Leydig cell tumors.However, the latter are typically larger, have infiltrative margins, invade lymphatics or blood vessels, and contain foci of necrosis. They also have a mitotic rate of more than 3 per 10 high-power fields and significant nuclear atypicality much more often than benign tumors. Rarely, however, a tumour with little or no suggestion of malignancy on gross or microscopic examination metastasizes, usually late in the course of the disease.
- Perhaps the most important remains the occasional confusion of this neoplasm with the remarkable nonneoplastic entity, the so-called testicular tumour of the adrenal genital syndrome. Individual fields may be indistinguishable. A triad of microscopic findings, if all present, lead to serious consideration of the nonneoplastic lesion particularly: i) broad fibrous bands ; ii) spotty nuclear atypia without mitotic activity , and iii) cytoplasmic lipochrome pigment. The latter, when conspicuous, may result in the nonneoplastic lesion having a particularly dark brown colour. Should a mass lesion be bilateral and have any extra testicular nodularity, the nonneoplastic lesion should be strongly considered, particularly if any of the microscopic findings already noted are seen.
- Occasionally, true Leydig cell hyperplasia or at least relative prominence of Leydig cells in an atrophic testis may suggest a small Leydig cell tumour, but these are typically multifocal and separated by seminiferous tubules - this should always favour a nonneoplastic proliferation.
- Rarely, malakoplakia may be mistaken as Leydig cell tumour, but associated inflammatory cells, sometimes even abscess formation, as well as, the distinctive Michaelis-Gutmann bodies, should be diagnostic.

Testicular Tumours: Intratubular Germ Cell Neoplasia

2008-10-15T11:46:00.000-07:00

Intratubular germ cell neoplasia:
Intratubular germ cell neoplasia is thought to be the precursor of most germ cell tumours. It is the testicular equivalent of carcinoma in situ. Fifty percent of patients with intratubular germ cell neoplasia will develop an invasive tumour in 5 years.
Intratubular germ cell neoplasia (ITGCN) is now well established as a precursor to invasive germ cell tumours, with the exception of spermatocytic seminoma and possibly infantile germ cell tumours that include infantile yolk sac tumour and infantile mature teratoma.
Among all the invasive germ cell tumours in adults, spermatocytic seminoma is the one type that is not associated with ITGCN, unclassified type.
ITGCN is seen adjacent to an invasive tumour in most cases or in the contralateral testis following orchiectomy for invasive germ cell tumour in a few cases.
It can also be seen in the following settings:
i) cryptorchid testes ; ii) dysgenetic testes ; iii) testes of infertile males and testes of healthy males.
The atypical germ cells commonly extend into the rete testis in a pagetoid pattern.
ITGCN has been classified similarly to invasive germ cell tumours as :
I) undifferentiated or unclassified ITGCN and
II) differentiated ITGCN.
The differentiated category is further subdivided as intratubular classic seminoma, intratubular spermatocytic seminoma, intratubular embryonal carcinoma, intratubular yolk sac tumour, and intratubular syncytiotrophoblast cells.
Microscopic features: There is a pagetoid pattern of large cells with clear cytoplasm, hyperchromatic nuclei, prominent nucleoli and frequent mitoses. The cells may resemble seminoma cells and are present along thickened / hyalinized tubular basement membrane. The cells displace Sertoli cells toward the lumen. Spermatogenesis is usually absent. Some calcifications (microliths) may be present.

Abstract:
Pagetoid spread of intratubular germ cell neoplasia into rete testis: a morphologic and histochemical study of 100 orchiectomy specimens with invasive germ cell tumors. Hum Pathol. 1994 Mar;25(3):235-9.
Intratubular germ cell neoplasia (ITGCN) is now considered to be the preinvasive phase of testicular germ cell tumors with the exceptions of spermatocytic seminoma, pure yolk sac tumor, and mature teratoma. Pagetoid spread of ITGGN into rete testis is a common yet unpublished finding in these cases. We reviewed 100 cases of testicular germ cell tumors from the Surgical Pathology service of Parkland Memorial Hospital (Dallas, TX) to evaluate the frequency of this pattern of spread. Additional sections were obtained from selected cases and were stained with anti-placental alkaline phosphatase, anti-low molecular weight keratin (clone AE1), and various lectins to highlight the process. Pagetoid spread of ITGCN into rete testis was identified in 24 of 60 cases (40%) in which histologic sections contained both ITGCN and rete testis. The incidence of pagetoid ITGCN involvement of the rete testis was lower in pure seminoma (seven of 25 cases [28%]) than in testes containing nonseminomatous germ cell tumors (17 of 35 cases [49%]). AE1 stained the epithelial cells of the rete testis but not the cells of the ITGCN, whereas placental alkaline phosphatase stained the neoplastic cells but not the epithelial cells of the rete testis. These stains were useful in delineating two cases in which the pagetoid involvement was so extensive that they were misdiagnosed as invasive seminomas. Pagetoid spread of ITGCN is a relatively common finding in testicular germ cell tumors and rarely can be mistaken for invasive seminoma. Immunohistochemistry can be helpful in distinguishing florid pagetoid spread from invasive seminoma.

Abstract:
Intratubular germ cell neoplasia (ITGCN) with p53 and PCNA expression and adjacent mature teratoma in an infant testis. An immunohistochemical and morphologic study with a review of the literature.Am J Surg Pathol.1994 Sep;18(9):947-52.
Intratubular germ cell neoplasia (ITGCN) and mature teratoma of the testis are uncommon findings in children. We report a case of a 3-year-old boy with both ITGCN and mature teratoma--a unique finding in our experience. Immunohistochemical markers, including placental alkaline phosphatase (PLAP), 43-9F, p53, and proliferating cell nuclear antigen (PCNA), as well as the periodic acid-Schiff (PAS) stain, were applied to the ITGCN. PLAP and 43-9F were not detected, whereas p53 and PCNA nuclear expression was detected in approximately 5% of atypical germ cells. Abundant clumped intracytoplasmic glycogen deposits were identified within atypical germ cells. Our findings indicate that both PCNA and p53, in addition to a PAS stain, may be useful markers in detecting malignant intratubular germ cells.

Abstract:
The prepubertal testis (prenatal and postnatal): its relationship to intratubular germ cell neoplasia: a combined Pediatric Oncology Group and Children's Cancer Study Group.1: Hum Pathol.1997;28(4):404-10.
Seminiferous tubules adjacent to germ cell tumors (GCT) in prepubertal boys frequently contain increased germ cells with abundant, clear cytoplasm. These cells are placental alkaline phosphatase (PLAP) negative and are usually not considered to represent intratubular germ cell neoplasia (ITGCN). A recent case report found p53 and proliferating cell nuclear antigen (PCNA) positivity in such cells and equated these PLAP-negative cells with ITGCN. Because the proto-oncogene c-kit is also a marker of ITGCN, immunohistochemical tests for c-kit and PLAP were performed on 28 testes adjacent to prepubertal GCT in children aged 2 to 45 months. Additional slides from testes not associated with GCT from 18 preterm infants and children ages 19 weeks to 7 years were also tested. An adult testis with seminoma and ITGCN served as a positive control. PCNA, PLAP, and p53 were tested on available slides. No intratubular germ cells adjacent to GCT in prepubertal children were positive for PLAP or c-kit; five of seven were positive for PCNA; p53 was present in the two examined. These results indicate that germ cells adjacent to infantile GCT are proliferative but not neoplastic and offer additional evidence that intratubular germ cells and GCT in prepubertal boys are different from those of adolescents and adults.

Abstract:
Intratubular malignant germ cells in testicular biopsies: clinical course and identification by staining for placental alkaline phosphatase. Mod Pathol. 1988 Nov;1(6):475-9.
This study was undertaken to determine the clinical course of patients with intratubular malignant germ cells (ITMGCs) and to evaluate the reliability of placental alkaline phosphatase (PLAP) for detection of these cells. Eight patients with ITMGCs in testicular biopsy were followed. Four patients received no further immediate treatment. Two of these showed no evidence of disease after 190 and 132 mo; one developed seminoma at 38 mo, and one developed seminoma of the contralateral testis in 61 mo. The remaining four patients underwent immediate orchiectomy. Orchiectomy findings were invasive seminoma in three testes, intratubular seminoma in one, and residual ITMGCs in one testis (one patient had bilateral orchiectomy). Also studied were two testicular biopsies from patients with known retroperitoneal germ cell tumors, respectively, seminoma and teratoma. Both had ITMGCs in their testes. Immunoperoxidase stains for PLAP gave a positive result in all biopsies showing intratubular malignant germ cells. PLAP was not demonstrated in spermatogonia in 471 control biopsies which did not show germ cell neoplasia. Two other patients with incidental seminoma on biopsy for infertility are discussed. These results show that ITMGCs show a high rate of progression to invasive disease, but can show an indolent course. PLAP is a sensitive and specific marker for ITMGC, facilitating diagnosis.

Testicular Tumours: Placental Site Trophoblastic Tumours of the Testis

2008-10-10T12:07:00.000-07:00

This is an unusual form of testicular trophoblastic tumour. The tumour resembles the placental site trophoblastic tumour of the uterus.

Abstract:
Trophoblastic tumors of the testis other than classic choriocarcinoma: "monophasic" choriocarcinoma and placental site trophoblastic tumor: a report of two cases. Am J Surg Pathol.1997 Mar;21(3):282-8.
We report two unusual forms of testicular trophoblastic tumor. One was a mixed germ cell tumor in a 19-year-old man that had a predominant component of nodules of cytotrophoblast cells with only rare syncytiotrophoblast cells. These nodules of "monophasic" choriocarcinoma were diffusely positive for human chorionic gonadotropin (hCG), which stained the syncytiotrophoblast cells more intensely; stains for human placental lactogen (HPL) highlighted only the latter cells. The second tumor occurred in a 16-month-old boy. It consisted of a pure proliferation of intermediate trophoblast cells and was identical to the placental site trophoblastic tumor of the uterus. The tumor cells showed diffuse immunoreactivity for HPL and patchy staining for hCG. Despite the occurrence of vascular wall invasion, the patient was alive and well at 8 years follow-up with no treatment other than orchiectomy. These cases show that trophoblastic tumors other than classic choriocarcinoma occur rarely in the testis. The differential diagnosis of the "monophasic" choriocarcinoma included seminoma and the solid variant of yolk sac tumor, but the tumor had larger, more irregular nuclei than those of seminoma and was not associated with distinctive yolk sac tumor patterns. The placental site trophoblastic tumor may be confused with Leydig cell tumor or choriocarcinoma, but awareness of its occurrence in the testis and the immunohistochemical findings should permit its recognition.

Testicular Tumours: Primitive Neuroectodermal Tumours (PNETs)

2008-10-10T11:33:00.000-07:00

Primitive Neuroectodermal tumour of the testis is considered a monodermal teratoma. It is composed of immature neural tissue.

Abstract:
Primitive neuroectodermal tumors arising in testicular germ cell neoplasms.1: Am J Surg Pathol. 1997 Aug;21(8):896-904.
Twenty-nine young men (mean age 29 years) had primitive neuroectodermal tumors (PNETs) arising in germ cell tumors (GCTs). Nine patients had PNETs confined to the testis, eight patients had PNETs in the testis and at metastatic sites, and 12 patients had PNETs identified only at extratesticular sites. Immunohistochemistry was of use in the further classification of these PNETs as neuroblastoma, medulloepithelioma, peripheral neuroepithelioma, or ependymoblastoma. The histologic pattern of PNETs in the testis (neuroblastoma or medulloepithelioma) did not predict which tumors metastasized. PNETs localized to the testis did not affect prognosis. Eight patients with no PNETs outside the testis were free of disease 1 month to 10 years after diagnosis. PNETs in extratesticular sites were an adverse prognostic factor. Nineteen patients with extratesticular PNETs had adequate clinical follow-up. Thirteen are dead of disease from 4 months to 5 1/2 years (mean 26 months) after diagnosis, four are alive with disease 6 months to 2 years after diagnosis, and two have no evidence of disease with short follow-up (6 and 17 months). Mean survival was longer (34 months) for patients whose extratesticular PNET was neuroblastoma than for those with other types of PNETs (13 months). Chemotherapy directed against GCTs was not effective in patients who developed metastatic PNETs of GCT origin. We conclude that extratesticular PNETs in patients with testicular GCTs are usually fatal, but patients with neuroblastomatous metastases may have a more prolonged course.

Abstract:
Primitive neuroectodermal tumor of the testis. Report of a case.Arch Pathol Lab Med. 1983 ;107(12):643-5.
A 30-year-old man died of a testicular tumor with widespread metastases. Both the right testis and the adjoining epididymis were replaced by a mass that consisted mainly of small cells, but differentiated focally into medullary tubules, ependymal rosettes, and glia in which glial fibrillary acidic protein was demonstrated; rare foci of cartilage and cellular mesenchyme established the teratomatous nature of the neoplasm. We believe this is the first reported case of a primitive neuroectodermal tumor of the testis.

Testicular Tumours: Carcinoid Tumour of the Testis

2008-10-10T09:24:00.000-07:00

The most common monodermal teratoma is the carcinoid tumour of the testis.
Microscopically,there are islands of cells forming small acini and cords forming rosettes or sheets. The cells have granular eosinophilic cytoplasm, round nuclei with granular chromatin. Usually there is no intratubular germ cell neoplasia, no/minimal mitotic activity and usually minimal atypia or necrosis
The features of the primary tumour and those that distinguish them from metastatic carcinoid are well known- ( metastatic carcinoid: usually bilateral ; multifocal ; vascular invasion)
In contrast, it has been noted that primitive neuroectodermal components in testicular germ cell tumours may in some instances be conspicuous. It may even dominate the microscopic picture, rarely representing most of or the entire neoplasm. These foci of malignant small cell neoplasia with varyingly prominent differentiation of neuroectodermal type are usually recognized when there is an associated teratomatous component from which they arise, but when the latter are inconspicuous, problems in differential diagnosis may result.
Foci resembling various forms of central nervous system tumours, such as medulloepithelioma or ependymal neoplasms or neuroblastoma, may be noted.

Abstracts:
Neuroendocrine carcinomas (carcinoid tumor) of the testis. A clinicopathologic and immunohistochemical study of ten cases. Am J Clin Pathol.2003 Aug;120(2):182-7.
We studied 10 cases of primary pure testicular neuroendocrine carcinoma. Patients were between 16 and 48 years old and had testicular swelling with pain or a painless testicular mass and no history of neuroendocrine carcinoma or other malignant neoplasm. All underwent orchiectomy. The tumors were low (n = 9) and intermediate (n = 1) grades with a variegated histologic appearance characterized by a nesting pattern, cords of neoplastic cells with rosettes, or sheets of neoplastic cells. Mitotic activity was lacking in 9 cases. In 1 case, mitotic figures ranged from 7 to 8 per 10 high-power fields, and cellular atypia and comedo-like necrosis were present. Immunohistochemical studies using a keratin cocktail, chromogranin, synaptophysin, epidermal growth factor, p53, placental-like alkaline phosphatase, and CD117 (c-kit) were performed in all cases. Keratin, chromogranin, and synaptophysin were positive in all tumors. Clinical follow-up information was obtained for 6 patients (range, 12-60 months): 5 with low-grade tumors were alive 24 to 60 months after diagnosis; 1 with an intermediate-grade tumor died of tumor 12 months after initial diagnosis. The behavior of these tumors, while in the testicular region, correlates well with the histologic grade. We propose replacing the term testicular carcinoid with neuroendocrine carcinoma, which better reflects the nature of these neoplasms.

Abstract:
Primary malignant carcinoid of the testis. Arch Pathol Lab Med. 1981 Oct;105(10):515-7.
A primary malignant carcinoid in the testis of a 76-year-old man was studied. The clinical indication was the appearance of extensive, papular cutaneous metastases. A markedly enlarged, indurated left testis was discovered during evaluation of the skin lesions. There were no clinical features of carcinoid syndrome. Histochemically, the tumor cells were argyrophilic but nonreactive to an argentaffin stain. Electron microscopy revealed numerous round, neurosecretory-type granules that ranged from 70 to 300 nm. At the time of autopsy, metastases were found in the heart, lungs, and the opposite testis. Review of the literature failed to uncover any previous reports of a primary malignant carcinoid in the testis.

Testicular Tumours: Diffuse Embryoma of the Testis

2008-10-09T10:27:00.000-07:00

Diffuse embryoma of the testis, a distinct form of mixed-germ-cell tumour, is characterized by diffuse orderly arrangement of embryonal carcinoma and yolk sac tumour with scattered trophoblastic components.

Abstract:
Diffuse embryoma of the testis. An immunohistochemical study of two cases. Am J Clin Pathol.1994 Oct;102(4):402-5.
The authors report the histologic and immunohistochemical findings of two cases of diffuse embryoma of the testis, a distinct form of mixed-germ-cell tumor characterized by diffuse, orderly arrangement of embryonal carcinoma (EC) and yolk sac tumor (YST) with scattered trophoblastic components. The patients were 37 and 38 years old when they presented with a right testicular tumor, which was confined to the testis (stage I) in both cases. Histologically, the tumor was composed predominantly of intimately intermingled EC and YST components in almost equal proportion. The tumor cells were arranged in necklacelike fashion; the EC cells formed glandular structures rimmed by a single cell layer of YST cells. The YST component was highlighted by positive staining for alpha-fetoprotein and strong staining for cytokeratin, whereas the EC component was positive for Ki-1 (BerH2, CD30) antigen, was negative for alpha-fetoprotein, and stained more weakly for cytokeratin. The randomly distributed few trophoblastic elements stained for human chorionic gonadotropin. The patients are alive with no evidence of disease, 11 years and 9 months after surgery, respectively. This newly described but distinct variant of mixed-germ-cell tumor should be differentiated from polyembryoma, which is composed of multiple discrete embryoid bodies.
Abstract:
Diffuse embryoma of the testis. A distinctive form of mixed germ cell tumor.1: Am J Surg Pathol. 1983 Oct;7(7):633-42.
Two testicular tumors characterized by a diffuse, orderly arrangement of embryonal, yolk sac, and trophoblastic elements are described as examples of a newly recognized form of mixed germ cell neoplasia. In one case, ribbons of embryonal carcinoma and yolk sac tumor wound around one another to create a distinctive necklace pattern. In the second case, differentiation of the yolk sac component was more advanced with the formation of numerous clusters of cells resembling hepatocytes. Tumors with these patterns are appropriately designated diffuse embryomas to distinguish them from polyembryomas and other forms of malignant mixed germ cell tumor.

Testicular Tumours: Polyembryoma

2008-10-09T08:43:00.000-07:00

Polyembryoma is an exceptionally rare gonadal neoplasm. Polyembryoma may be present as a component in a mixed germ cell tumour.
It has been reported that polyembryoma may present grossly as a beefy mass in the testis.
These neoplasms are composed entirely or predominantly of embryoid bodies, (characterized by a central germ disc, underlain by yolk sac epithelium, and with recapitulation of the amniotic cavity anteriorly and the yolk sac cavity posteriorly).
Foci of polyembryoma often have a prominent loose myxomatous mesenchyme in the background upon which the embryoid bodies are set. Large, well-circumscribed lobules of embryoid bodies surrounded by the prominent mesenchyme produce a rather typical low-power appearance in many cases.
Cysts may be prominent.
The embryoid bodies themselves often are not perfectly formed and appear fragmented, as if they are breaking down.

Abstracts:
Polyembrioma of the testis: case report following chemotherapy for non-Hodgkin's lymphoma. G Chir.2002 Mar;23(3):65-70.
Testicular tumours represent 2% of all male malignancies, mostly concerning young men (20-40 years old). The polyembryoma is one of the uncommonest lesions and just recently it has been identified as autonomous nosographic entity. The reported case is peculiar because the patient was older than the most ones described in the literature and the tumour arose after polychemotherapy for non Hodgkins' disease. The Authors analyse some aspects concerning etiology, pathology and clinical approach to such rare neoplasm.

Testicular Tumours: Sex Cord - Stromal Tumours

2008-10-08T23:12:00.000-07:00

Classification of sex cord-stromal tumours is based on diffmerentiation into Leydig or Sertoli cells.
Sex cord-stromal tumors comprise a small minority of testicular neoplasms. It remains critically important not to confuse these neoplasms with testicular germ cell or metastatic tumors, and, again, recognition of the characteristic histologic features, immunohistochemical findings, and clinical information is diagnostic. The urologist can provide the pathologist with key clinical information in the attempt to make a correct diagnosis.
Classification:
Fibromas
Granulosa cell tumor (adult, juvenile)
Leydig (interstitial) cell tumor
Mixed or Unclassified Gonadal-Stromal Tumors
Sertoli cell tumors
Tumors of Adrenogenital Syndrome Type

Abstract:
Sex cord-stromal tumors of the ovary and testis: their similarities and differences with consideration of selected problems. Mod Pathol.2005 Feb;18 Suppl 2:S81-98.
Gonadal sex cord-stromal tumors contain some of the most morphologically interesting neoplasms of the gonads and these lead to many important issues in differential diagnosis. The pathology of these tumors is reviewed with emphasis on new information, similarities and differences in the two gonads, and diagnostic problems. Sertoli cell tumors occur in both gonads being more common in the testis where they usually exhibit a lobular pattern of hollow or solid tubules. In the ovary, tubular differentiation is usually the predominant feature but the lobulation typically seen in the testis is generally not as striking. One variant of Sertoli cell tumor, the large cell calcifying form, appears to be restricted to the male gonad and in contrast to other sex cord tumors is much more frequently bilateral and is associated in many cases with unusual clinical manifestations. In both sexes, patients with Peutz-Jeghers syndrome often have distinctive gonadal pathology. In females, it is in the form of the sex cord with annular tubules whereas in males, the lesion has features that are often intermediate between those of a sex cord tumor with annular tubules and a large cell calcifying Sertoli cell tumor. Sertoli-Leydig cell tumors are more morphologically diverse than pure Sertoli cell tumors and for practical purposes are an issue only in ovarian pathology being exceptionally rare in the testis. The classification proposed by Meyer into well, intermediate, and poor differentiation, remains important prognostically. More recently, heterologous and retiform differentiation has been described. Heterologous tumors most often contain mucinous epithelium, sometimes with small foci of carcinoid or less commonly, and generally in poorly differentiated neoplasms, rhabdomyosarcoma or fetal-type cartilage. Such tumors should be distinguished from pure sarcomas and teratomas. The retiform neoplasms, which tend to occur in young females, may mimic serous borderline tumors or even serous carcinomas. Granulosa cell tumors are much more common in females and in both gonads are divided into adult and juvenile forms. In females, granulosa cell tumors and other sex cord tumors may have markedly bizarre nuclei potentially leading to overdiagnosis as more malignant neoplasms. The juvenile granulosa cell tumor of the testis tends to occur in the first 6 months of life and should be carefully distinguished from the yolk sac tumor of the testis, which usually occurs in a slightly older age group. Occasional sex cord-stromal tumors cannot be readily categorized into the Sertoli or granulosa families and are diagnosed as sex cord-stromal tumors unclassified. In females, this is a relatively common placement for a neoplasm in a pregnant patient. Unclassified tumors are overall more common in males and may entrap residual normal germ cells potentially leading to the erroneous placement of the tumor in the category of a mixed germ cell sex cord-stromal tumor. From the practical viewpoint, the most helpful immunohistochemical findings are the negative staining of sex cord tumors for epithelial membrane antigen, and positive staining for inhibin and calretinin, findings that are converse to those seen in endometrioid carcinomas of the ovary, which commonly have formations that simulate sex cord tumors.

Abstract:
Incompletely differentiated (unclassified) sex cord/gonadal stromal tumor of the testis with a "pure" spindle cell component: report of a case with diagnostic and histogenetic considerations. Pathol Res Pract. 2007;203(10):759-62. Epub 2007 Sep 11.
The group of incompletely differentiated (unclassified) sex cord/gonadal stromal tumors includes rare cases with predominant spindle cell morphology. We report a rare case of a "pure" spindle cell tumor of the testis with morphological and immunohistochemical features consistent with the diagnosis of "incompletely differentiated sex cord/gonadal stromal tumor". Given the spindle cell morphology, the differential diagnosis with other benign and malignant spindle cell lesions is discussed. The concurrent presence of some morphological and immunohistochemical features of both Leydig and granulosa cell lines in the tumor suggests its origin from a stromal stem cell, possibly capable of dual differentiation, but with an arrest of maturation at an early phase of differentiation.

Abstract:
Sex cord-stromal tumors of the testis with entrapped germ cells: a lesion mimicking unclassified mixed germ cell sex cord-stromal tumors. Am J Surg Pathol.2000 Apr;24(4):535-42.
The authors describe 10 sex cord-stromal tumors of the testis that incorporated germ cells, thereby mimicking the unclassified type of mixed germ cell sex cord-stromal tumor (MGCSCST). These neoplasms occurred in patients from 3 to 48 years old (mean age, 26 years) who presented with testicular masses. On microscopic examination, nine tumors had a combination of tubular and cord-like arrangements of sex cord cells with transition to spindle-shaped tumor cells. They were diagnosed as either unclassified sex cord-stromal tumors (n = 5) or Sertoli-stromal cell tumors (n = 4). One tumor was a pure Sertoli cell tumor. The admixed germ cells were usually at the periphery and in clusters, but occasionally were in the center or more diffuse. In nine patients the germ cells resembled spermatogonia, having round nuclei with uniform, dusty chromatin and inconspicuous or small nucleoli. None of these cells stained with a variety of markers used for neoplastic germ cells, and in one case in which the non-neoplastic Sertoli cells were strongly reactive for inhibin but the neoplastic Sertoli cells were not, all the germ cells within the tumor occurred adjacent to inhibin-positive Sertoli cells. With static cytophotometry, a diploid deoxyribonucleic acid content was found in these germ cells in the two investigated cases. In one case the germ cells had the morphologic appearance of seminoma cells and they stained positively for the markers of neoplastic germ cells. This case was interpreted as a "collision" tumor between a Sertoli cell tumor and a seminoma. The authors conclude that sex cord-stromal tumors with entrapped germ cells of the testis are more common than unclassified MGCSCSTs--a bona fide testicular example of which has not been seen by any of the authors.

Testicular Tumours: Epidermoid Cyst

2008-10-07T11:51:00.000-07:00

Epidermoid cysts constitute approximately 1% of testicular tumours.
Although pathologically these lesions are true cysts, they are filled with cheesy laminated material.
Histogenesis of the epidermoid cyst of the testis is uncertain.
Epidermoid cysts may result from monodermal development of a teratoma, or, alternatively, they may be the result of squamous metaplasia of surface mesothelium.
Epidermoid cysts are composed of keratinizing, stratified, squamous epithelium with a well-defined fibrous wall.
They are one of the few benign intratesticular masses and, unlike mature teratoma, have no malignant potential.

Abstract:
Epidermoid cyst of the testis: a review of clinical and histogenetic considerations.Br J Urol.1994;73(4):436-41.
OBJECTIVE: To review the records of patients with epidermoid cysts and those with germ cell tumours to determine the most appropriate method of treatment. PATIENTS AND METHODS: The records of the patients treated for epidermoid cysts and testicular germ-cell tumours in a period covering 22 years were analysed retrospectively. Nine specimens with an epidermoid cyst were examined by immunohistology for the presence of testicular intraepithelial neoplasia (TIN) (or carcinoma in situ of the testis). RESULTS: Ten patients with a simple epidermoid cyst and 481 patients with testicular germ-cell tumour were treated during the observation period. The relative incidence of epidermoid cysts in relation to the number of patients with testicular germ-cell tumours was 2.1% (95% confidence interval 0.8-3.35%). The mean age of the 10 patients with an epidermoid cyst was 24.1 years. The right testis was affected in seven patients and the left in three. Six of these patients received conservative surgery with excellent cosmetic results. No relapse had occurred after a median observation period of 30 months. Immunohistological staining for placental alkaline phosphatase disclosed the absence of TIN in the parenchyma surrounding the cysts. CONCLUSION: The absence of TIN calls into question the common assumption that an epidermoid cyst constitutes a monodermal teratoma. Two distinct entities of epidermoid cyst are proposed--one occurring in conjunction with a teratoma or a germ cell tumour (a 'complex' or 'mixed' epidermoid cyst) and the other a 'simple' epidermoid cyst without TIN in the adjacent tissue and thus representing a benign neoplasm that is not a teratoma. The absence of TIN near a simple epidermoid cyst justifies testis-sparing surgery.

Abstract:

Testicular epidermoid cyst: orchiectomy or enucleation resection? Urologe A.1996 Jan;35(1):1-5.

Our experience with 18 patients with simple epidermoid cysts of the testis is reported. In each patient the tumour was enucleated completely and two biopsies of the adjacent parenchyma were obtained for exclusion of associated germ cell cancer, scars or carcinoma in situ. There was no evidence of malignancy in any of the biopsy specimens. Preoperative evaluation included physical examination, testicular sonography, and determination of AFP and hCG serum levels. Although epidermoid cyst can be strongly suspected on sonography the ultrasound appearance is not specific, and inguinal testicular exploration was required in these patients. In 1 patient multiple epidermoid cysts of the right testis were associated with an adult teratoma containing embryonal carcinoma and choriocarcinoma of the left testis; no similar case has been described in the literature. On the basis of our results and experience we consider tumour enucleation and biopsy of the adjacent parenchyma to be adequate treatment for benign epidermoid cyst. The world literature concerning organ-sparing surgery in testicular epidermoid cyst is reviewed.

Testicular Tumours: Teratomas

2008-10-06T09:02:00.000-07:00

Teratomas:
Teratomas are a group of tumours exhibiting evidence of simultaneous differentiation along endodermal, mesodermal, and ectodermal lines.
Morphologic features of teratomas are not directly related to their behavior.
Mature teratomas interpretated as benign, commonly behave in a malignant manner and metastasize.
By contrast, teratomas in infants and children with foci of undifferentiated cells are uniformly benign.
Teratoma may occur at any age.
Mature teratomas are composed of a haphazard array of differentiated mesodermal (Example: Muscle ; Cartilage ; Adipose tissue) , ectodermal (Example: Neural Tissue ; Skin) and endodermal (Example: Gut ; Bronchial epithelium) elements.
Mature teratomas are more common in infants and children.
Diagnosis of pure testicular teratoma should be made with extreme caution in adults, owing to the likelihood of concomitant malignant germ cell elements elsewhere in the tumour.
Immature teratoma: Immature teratomas contain elements of three germ layers in incomplete stage of differentiation. They should be regarded as malignant, even though cytologic features of malignancy may be inconspicuous.
Malignant teratoma: Malignant teratomas is characterized usually in the form of a carcinoma (Example: Squamous cell carcinoma ; Adenocarcinoma) developing within a mature teratoma.

Abstract:
Gonadal teratomas: a review and speculation. Adv Anat Pathol.2004 Jan;11(1):10-23.
Teratomas of the ovary and testis are confusing because, despite histologic similarities, they exhibit different biologic behaviors, depending mostly on the site of occurrence and the age of the patient. Thus, most ovarian teratomas are benign, and most testicular teratomas are malignant, with the exception of those occurring in children. These general statements, however, do not hold true for ovarian teratomas that are "immature" or exhibit "malignant transformation" and for dermoid and epidermoid cysts of the testis, categories of ovarian and testicular teratomas that are malignant and benign, respectively. This review concentrates on some of the "newer" observations concerning these interesting and confusing neoplasms, including diagnostically deceptive patterns. It is the author's opinion that much of the confusion regarding gonadal teratomas can be clarified by the concept that the usual ovarian teratoma derives from a benign germ cell in a parthenogenetic-like fashion, whereas the typical postpubertal testicular example derives from a malignant germ cell, mostly after evolution of that originally malignant cell to an invasive germ cell tumor (ie, embryonal carcinoma, yolk sac tumor, etc). The postpubertal testicular teratomas can therefore be thought of as an end-stage pattern of differentiation of a malignant germ cell tumor. The pediatric testicular teratomas, as well as dermoid and epidermoid cysts of the testis, however, must derive from benign germ cells, in a fashion similar to most ovarian teratomas. The teratomatous components of mixed germ cell tumors of the ovary, on the other hand, likely have a pathogenesis similar to that of postpubertal testicular teratomas.

Dermoids, which are the most common teratomatous lesion in the ovary, constitute only a small minority of testicular teratomas. The diagnosis should be reserved for lesions that are grossly typical of a dermoid cyst and are unassociated with adjacent intratubular germ cell neoplasia unclassified. The more common mature teratoma that has a malignant potential has a solid and cystic gross-sectioned surface contrasting with the predominantly cystic nature of the dermoid cyst.

Abstract:
Dermoid cyst of the testis: a study of five postpubertal cases, including a pilomatrixoma-like variant, with evidence supporting its separate classification from mature testicular teratoma.Am J Surg Pathol. 2001 Jun;25(6):788-93.
It is controversial if the rare dermoid cyst of the testis should be classified as a variant of mature teratoma or separately. The spectrum of findings is also ill defined, as is the relationship of dermoid cyst to intratubular germ cell neoplasia of the unclassified type (IGCNU). This study therefore reports the findings in five testicular dermoid cysts that occurred in five patients, 17-42 years of age, who presented with testicular masses. Four lesions consisted of a keratin-filled cyst with a thickened wall, whereas one had islands of "shadow" squamous epithelial cells with superimposed calcification and ossification (pilomatrixoma-like variant). Hair was identified grossly in two cases. On microscopic examination, four tumors had hair follicles with sebaceous glands showing a typical, cutaneous-type orientation to an epidermal surface, although no hair shafts were present in two. In addition, the fibrous wall contained smooth muscle bundles (all tumors) and eccrine or apocrine sweat glands (4 tumors). In some cases there were also glands lined by ciliated epithelium (4 tumors, including the pilomatrixoma-like variant), intestinal mucosa (1 tumor), and bone (2 tumors). There was no cytologic atypia or apparent mitotic activity, and no case had IGCNU in the seminiferous tubules. All patients were clinical stage I and were treated by orchiectomy without adjuvant therapy. All were well on follow-up from 1.5 to 9.5 years later. This study supports that dermoid cyst may have noncutaneous teratomatous elements and that an important criterion for its diagnosis is the absence of IGCNU. It also supports that it should be categorized separately from mature testicular teratoma because of the malignant nature of the latter in postpubertal patients. These observations suggest that there are at least two pathways for testicular teratomas in postpubertal patients: the more common being through IGCNU by differentiation from an invasive malignant germ cell tumor and the less common one, taken by dermoid cyst, by direct transformation from a nonmalignant germ cell.

The biologic behavior of teratomas is quite variable, depending on the pubertal status of the testis. In prepubertal testes, pure teratomas are considered benign even when they are histologically immature. This benign behavior has led some investigators to recommend a testis-sparing tumor enucleation rather than orchiectomy. However, such conservative treatment is not an option for teratomas in postpubertal testes. Of important distinction, every element in a postpubertal testicular teratoma (mature or immature) can metastasize, irrespective of its histologic characteristic.

Testicular Tumours: Choriocarcinoma

2008-10-04T12:34:00.000-07:00

Choriocarcinoma:
Choriocarcinoma is a highly malignant tumour composed of both cytotrophoblastic and syncytiotrophoblastic elements. It is a rare germ cell tumour.
It develops in patients in the 2nd and 3rd decades of life.
Similar neoplasms may occur in the ovary, placenta, or ectopic pleuripotential germ cell rests in other sites (Example: mediastinum, abdomen).
The neoplasm is rare in pure form within the testis. It is more often seen as a component of a mixed germ cell tumour.
The levels of human chorionic gonadotropin are elevated and cause gynecomastia in 10% of cases Grossly, the primary testicular tumour is often quite small even in the presence of widespread systemic metastases. The gross appearance ranges from a bulky, hemorrhagic mass to an inconspicuous lesion replaced by a fibrous scar.
Microscopically, it is composed of both polygonal, comparatively uniform cytotrophoblasts growing in sheets and cords, admixed with multinucleated syncytiotrophoblasts. Well-developed villi are not seen.
Syncytiotrophoblasts stain positively for chorionic gonadotropin.
Often, there is early widespread metastasis, and patients may present with symptoms referable to their metastases rather than a palpable testicular mass. Sites of metastases include the lung, liver, gastrointestinal tract, and brain. The primary tumour and metastases are often hemorrhagic.
Choriocarcinoma has the worst prognosis of any of the germ cell tumors, with death usually occurring within 1 year of diagnosis.

Abstracts: Metastatic testicular choriocarcinoma of the skin. Report and review of the literature.Am J Dermatopathol.1996 Dec;18(6):633-6.
Choriocarcinoma is a malignant growth of trophoblastic cells characterized by secretion of human chorionic gonadotropin. Choriocarcinoma usually arises from fetal trophoblasts and rarely arises from germ cells in the testis or ovary or derives from dedifferentiation of other carcinomas. Skin metastasis of choriocarcinoma is rare: only seven cases have been reported in the English and Japanese literature. We report the case of a 22-year-old Japanese man with pure choriocarcinoma of the testis who developed skin metastases that presented as multiple reddish nodules. Microscopic examination of both the primary lesion of the testis and the cutaneous metastasis demonstrated the typical histologic features of pure choriocarcinoma. The patient died 3 months after the initial onset of skin metastasis. Review of the literature indicates that skin metastasis of choriocarcinoma usually occurs as a nodular lesion with the histologically typical feature of the primary disease and signals of poor prognosis.

Testicular Tumours :Yolk Sac Tumours

2008-10-04T12:12:00.000-07:00

Yolk sac tumours : (Synonyms include infantile embryonal carcinoma and endodermal sinus tumour)
The totipotential germ cells that differentiate toward extraembryonic fetal membranes give rise to yolk sac tumours.
Yolk sac tumor is the most common testicular tumour in infants and young children.
Prognosis is good in children up to 3 years of age.
In its pure form, yolk sac tumor is rare in adults; however, it is present in 44% of adult cases of mixed germ cell tumour.
Alpha-fetoprotein is normally produced by the embryonic yolk sac, and thus serum alpha-fetoprotein levels are elevated in greater than 90% of patients with yolk sac tumour.
Grossly, pure forms present as infiltrative, homogeneous, yellow-white, mucinous lesions.
Microscopically, they are composed of cuboidal tumour cells, arranged in a lace-like (reticular) network, solid areas, multiple microcysts and papillae, all in a background of myxoid stroma. Structures resembling primitive glomeruli (Schiller-Duval bodies) , so-called endodermal sinuses, are seen in 50% of cases. These structures consist of a microcyst with a central fibrovascular core.
Immunocytochemically, eosinophilic, hyaline globules containing immunoreactive alpha-fetoprotein (AFP) and alpha-1-antitrypsin are present within and around the tumour cells.
The descriptive name endodermal sinus tumour and yolk-sac tumour reflects the histologic similarity of this tumour to the structure of the rat placenta.
If the yolk sac tumor is confined to the testis at the time of orchiectomy (as it is in over 80% of cases) and if the serum level of alpha-fetoprotein is not elevated, the patient can be closely monitored without further therapy and the prognosis is excellent. If relapse occurs, chemotherapy is the treatment of choice. The lungs are the most common site of recurrent disease.

Abstract: Hepatoid variant of yolk sac tumor of the testis. Pathol Int. 2000 Sep;50(9):754-8.

A case of testicular yolk sac tumor (endodermal sinus tumor) consisting predominantly of hepatoid cells is documented. A mass measuring approximately 4 x 3 cm was noted in the left testis of a 64-year-old man. Preoperative examination revealed an elevated serum level of alpha-fetoprotein (5479 ng/mL). Histologically, the lesion was composed predominantly of sheet-like or trabecular proliferation of hepatocyte-like cells with eosinophilic or clear cytoplasm. The tumor cells were immunoreactive for alpha-fetoprotein, antimitochondrial antibody, cytokeratin (AE1/AE3), alpha-1-antichymotrypsin, alpha-1-antitrypsin, albumin, carcinoembryonic antigen and epithelial membrane antigen. It was necessary to distinguish this variant lesion from metastatic hepatocellular carcinoma, embryonal carcinoma and hepatoid carcinoma.

Testicular Tumours : Embryonal carcinoma

2008-10-04T12:04:00.000-07:00

Embryonal carcinoma:
This tumour is composed of primitive anaplastic epithelial cells that resemble early embryonic cells. It is the second most common histologic type of testicular tumour after seminoma.
Peak incidence is in the 20 to 30 year, age group.
Embryonal carcinoma is often smaller than seminoma at the time of presentation but tends to be more aggressive in behavior, although developments of chemotherapy have improved the prognosis considerably.
Grossly, lesions may be small and confined to the testis, but most examples are poorly demarcated, gray-white masses punctuated by foci of hemorrhage, necrosis, or both.
They may extend through the tunica albuginea into epididymis or spermatic cord.
Microscopically, they are composed of primitive epithelial cells with indistinct cell borders, prominent nucleoli and coarse chromatin. The cells form irregular sheets, tubules, alveoli and papillary structures. Mitotic figures and neoplastic giant cells are common.
Histochemically, syncitial cells are positive for HCG and AFP may be detected, and when present, indicates a mixed germ cell tumour with concomitant trophoblastic or yolk sac differentiation.

Testicular Tumours: Anaplastic and Spermatocytic Seminomas

2008-10-03T13:25:00.000-07:00

Rare variants of the classic seminoma include anaplastic seminoma (5 to 10%) and spermatocytic seminoma (4 to 6%).

Anaplastic Seminomas : Anaplastic seminomas are distinguished from classic seminomas by greater nuclear atypia and a higher mitotic rate.

Spermatocytic Seminomas : Spermatocytic seminomas are uncommon tumours occurring in patients older than those with classic seminoma (more than 50 years old). These are indolent growths, with virtually no tendency to metastasize. The lesions tend to be larger than those of classic seminoma. These lesions are composed of mixed population of cells, including smaller (6 to 8 micro-meter) cells resembling secondary spermatocytes, (hence the spermatocytic designation), medium-sized (15 to 18 micro-meter) cells, and scattered giant cells.

Abstract: Spermatocytic seminoma. Hum Pathol.1994 Oct;25(10):1035-42.
Spermatocytic seminoma is a rare testicular neoplasm that occurs only in adults (range, 25 to 87 years; mean, 54). It has no ovarian homologue and is found only in descended testes. It is not associated with other types of germ cell neoplasia. Orchiectomy is curative in virtually all cases; of more than 200 known cases, only one has metastasized. In a dozen cases sarcomas have arisen in the testes in association with spermatocytic seminoma; most of these patients have died of metastatic sarcoma after short intervals. The gross appearance is characteristically edematous or gelatinous and more than half the tumors have been more than 5 cm in diameter. Microscopically, they are composed of sheets of small, medium, and large cells with spherical nuclei. The chromatin is dense in the small cells and filamentous in the medium and large ones. The cytoplasm is eosinophilic to amphophilic and lacks glycogen. It is not associated with intratubular germ cell neoplasia of the undifferentiated type. Analyses of DNA content have failed to show haploid populations and the lectin binding does not show maturation toward spermatocytes. Differing from seminoma in essentially all characteristics, it is not a variant of seminoma.

Abstract: Anaplastic variant of spermatocytic seminoma. Hum Pathol. 1996 Jul;27(7):650-5.
Four examples of spermatocytic seminoma with a predominant anaplastic component occurred in men 33 to 43 years of age, without histories of cyptorchidism. The seminomas presented with painless testicular masses recognized 3 to 18 months before orchiectomy. Preoperative serum measurements of human chorionic gonadotropin and alpha-fetoprotein were negative. All tumors contained areas (10% to 30% of the tumor) in which the three cell types characteristic of conventional spermatocytic seminoma could be identified under light microscopy. The predominant anaplastic component also contained the three cell types, but the nuclei had prominent nucleoli with granular and filamentous chromatin. In addition, sheets of cells with vesicular nuclei and prominent nucleoli superficially resembling embryonal carcinoma were found. There were numerous large mononuclear and multinucleated giant cells with bizarre nuclei and prominent nucleoli, but no sarcomatous elements. Many normal and abnormal mitotic figures were present. Tunical and vascular invasion and extensive necrosis were constant features. Immunohistochemistry documented p53 protein overexpression in two tumors, but neoplastic cells were negative with immunostains for placenta-like alkaline phosphatase, leukocyte common antigen, neuron-specific enolase, alpha-fetoprotein, human chorionic gonadotropin, vimentin, and cytokeratins. Ultrastructural examination of the anaplastic component showed large rope-like nucleoli, but the cytoplasmic features were similar to those of conventional spermatocytic seminoma. Despite the presence of a major anaplastic component, no patient has developed metastasis. Larger series and longer follow-up are needed to understand the natural history of these neoplasms.

Testicular Tumours : Seminoma:

2008-10-03T03:31:00.000-07:00

Seminoma:
Seminoma accounts for 50% of all testicular germ cell tumours.
It is the most likely germ cell tumour to present with a single histologic pattern.
Peak incidence is seen in the thirties.
Grossly, seminoma presents as a homogeneous, lobulated, gray-white mass, generally devoid of hemorrhage and necrosis. Tunica albuginea usually remains intact.
Microscopically, the mass is composed of large polyhedral seminoma cells with well-defined borders and abundant clear cytoplasm, large nuclei and prominent nucleoli.
Cytoplasmic glycogen is typically present.
The cells are arranged in solid sheets and may show a tendency to form tubular, papillary or glandular structures.
A fibrous stroma of variable density divides the tumor cells into irregular lobules; an accompanying lymphocytic infiltrate (usually T-cells) is present in most cases , granulomas may also be present. Neoplastic giant cells and syncytial cells, resembling placental syncytiotrophoblast may be seen in some cases.
Histochemically, Human chorionic gonadotropin (HCG) is present in such cells and presumably accounts for the elevated serum HCG levels detected in some patients with pure seminoma. The tumour cells contain placental alkaline phosphatase.
Classical seminoma cells do not contain alpha-fetoprotein (AFP).
Histologically, identical tumors may occur in the ovary (dysgerminomas) and central nervous system (germinoma).

Abstract: Seminoma with tubular, microcystic, and related patterns: a study of 28 cases of unusual morphologic variants that often cause confusion with yolk sac tumor. Am J Surg Pathol. 2005;29(4):500-5.
We report 28 testicular seminomas with cystic spaces of variable nature, sometimes accompanied by solid and hollow tubular patterns (12 cases). The spaces often suggested reticular or microcystic patterns of yolk sac tumor, and the solid and hollow tubular patterns often added to the diagnostic confusion. The tumors occurred in men 21 to 55 years old and on gross examination had the typical appearance of seminoma. On microscopic examination, the spaces ranged from small, closely packed and relatively regular to dilated, more dispersed and somewhat irregular. The hollow tubules appeared to result from central discohesion within nests of tumor. The spaces, particularly when large, often contained occasional tumor cells or inflammatory cells within pale edema fluid. The cytologic appearance of the cells lining the spaces, and in the surrounding tumor, retained the typical features of seminoma cells. Thirteen tumors (46%) either lacked (8 cases) or had very scant (5 cases) lymphocytes in the cystic and tubular areas, and hyaline globules were absent. Thirteen of 13 tumors were immunopositive for OCT-3/4 in the nontypical and typical areas; 9 of 10 were placental alkaline phosphatase positive, and 7 of 10 were c-Kit (CD117) positive. The same 13 cases were negative with cytokeratin (AE1/AE3) and alpha-fetoprotein stains. Distinction from yolk sac tumor is aided by the observation that the spaces of yolk sac tumor are often more irregular in their individual shapes and frequently form anastomosing channels. Additionally, the spaces of yolk sac tumor randomly merge with various other yolk sac tumor patterns. The cells lining spaces in yolk sac tumor are often flattened with compressed nuclei and lack the typical prominent nucleoli of seminoma cells. Paucity of lymphocytes and intracystic edema, however, are not differentially helpful, although basophilic fluid favors yolk sac tumor. A panel of immunostains (AE1/AE3, OCT-3/4, and alpha-fetoprotein) is helpful in the differential with yolk sac tumor in especially problematic cases. The edema and paucity of lymphocytes may suggest spermatocytic seminoma, but the varied cell types of that neoplasm are absent.

Abstract: Testicular seminoma: a clinicopathologic and immunohistochemical study of 105 cases with special reference to seminomas with atypical features. Int J Surg Pathol. 2002 Jan;10(1):23-32.
In spite of the high curability rates, rare cases of testicular seminoma behave in an unexpectedly aggressive manner. No effective markers are currently available that can predict such uncommon behavior. We studied 105 cases of testicular seminoma on whom the primary resection was performed at the Memorial Sloan-Kettering Cancer Center, New York, to investigate any relationship between morphology, immunohistochemical features, and clinical/pathological stages. Fifty-nine percent of the cases presented with pT stage 1 and 74 percent with American Joint Committee on Cancer (AJCC) stage I. In univariate analysis, tumor size, mitotic count, and presence of necrosis showed significant associations with pT stage (p = 0.0001, 0.0001, and 0.04, respectively), and the presence of vascular invasion (p = 0.0001, 0.0001, and 0.02, respectively). In multivariate analysis, both the tumor size and mitotic counts were independent predictors of pT stage (p = 0.0004 and 0.0001) and vascular invasion (p = 0.0004 and 0.0001). When tumors were separated on the basis of architectural and/or cytological atypia into "usual seminomas" and "seminomas with atypia", these were significantly associated with AJCC stage (p = 0.02), and c-kit protein (p = 0.0005) and CD30 expression (p = 0.02). In addition, "seminomas with atypia" also tended to show a higher proliferation activity as judged by Ki67 reactivity (p = 0.06), as well as express the marker of epithelial differentiation, Cam 5.2 (p = 0.09). In summary, we find that the morphologic features in testicular seminomas are associated with factors of clinical relevance. Also, "seminomas with atypia" differ from "usual seminomas" morphologically, present at a higher AJCC stage, and possibly represent an early step in transformation of seminomas toward a more aggressive phenotype. While not proposing a new entity, we suggest that when these atypical features are encountered in an otherwise classical seminoma, investigations must be performed to exclude an early carcinomatous differentiation or even earlier changes toward such a differentiation, such as lack of c-kit protein expression.

WORLD HEALTH ORGANIZATION - PATHOLOGIC CLASSIFICATION OF TESTICULAR TUMOURS

2008-10-03T01:54:00.000-07:00

The World Health Organization classification of testicular neoplasms is most widely used scheme.
Germ Cell Tumours :
Tumours of one histologic type:
1. Seminoma
2. Spermatocytic seminoma
3. Embryonal Carcinoma
4. Yolk sac tumor (embryonal carcinoma, infantile type)
5. Polyembryoma
6. Choriocarcinoma
7. Teratoma:
a) Mature
b) Immature
c) With malignant transformation
Tumours showing more than one histologic pattern:
1. Embryonal carcinoma plus teratoma (teratocarcinoma)
2. Choriocarcinoma and any other type (specify type)
3. Other combinations (specify)
Sex Cord-Stromal Tumours:
Well-differentiated forms:
1. Leydig cell tumour
2. Sertoli cell tumour
3. Granulosa cell tumour
Mixed forms (specify) :
Incompletely differentiated forms:

Abstract: WHO classification of testicular tumors. Verh Dtsch Ges Pathol.2002;86:67-75.
Twenty years after the first edition (1977), the WHO has presented the updated version of the "Histological typing of testis tumours". The revised classification was necessary because some clinically important new entities have been described in recent years. The most important is obviously the precursor lesion of germ cell tumors, which has been called "intratubular malignant germ cells". Such atypical cells appear in the tubules adjacent to the germ cell tumors, in some few cases (6%) also in the contra lateral healthy gonad and rarely in infertile men (1%). The precursor lesion can progress to franc germ cell tumor starting probably with seminoma, which still maintain the capability of differentiation (pluripotente cells) in all other types of non-seminomatous germ cell tumors. This lesion is missed in germ cell tumors of childhood and in spermatocytic seminomas, both seem to have a histogenetic history rather different from the other germ cell in adults. The categories used in the first classification have been preserved and some new diagnoses added. Most of the new diagnoses are subtypes--called "variants"--of well known tumors. Seminoma with syncytiotrophoblastic cells is a variant which should not be confused with choriocarcinoma. Spermatocytic seminomas are perfectly benign tumors but they become a life threatening disease when combined with sarcomas (new entity). In the group of mature teratomas the "dermoid cyst" appears as a benign subtype mostly observed in children. Unfortunately, however, the old term "teratoma with malignant transformation" was changed to "teratoma with malignant areas" in the 1998 classification. This is a harmless name for an extremely dangerous tumor in which one tissue overgrows the other and gives rise to somatic type sarcomas or carcinomas. Such tumors do not respond like germ cell tumors to the usual chemotherapy. Treatment should be tailored according to that used in standard management of the respective sarcoma or carcinoma. In the comments it is mentioned that the testis carcinoid could be a part of teratoma, but the diagnosis is listed in the group of "miscellaneous" tumors together with tumors of ovarian epithelial type. This is a very questionable decision because the normal testis does not contain neuroendocrine cells from which carcinoids would have to be able to develop. Teratomas, however, show plenty of them producing all kinds of typical hormones. "Large cell calcifying Sertoli cell tumour" has been recently described and can be sporadic or inherited. This morphologically peculiar tumor can be part of the Swiss syndrome also called Carney's complex. The patients have cardiac myxomas, spotty skin pigmentation, hormone active nodular hyperplasia of the adrenals and soft tissue myxomas. The newly appearing "mixed germ cell--sex cord/gonadal stromal tumours, unclassified" has a histology similar to the well known gonadoblastomas. In contrast to gonadoblastoma, however, these tumors occur in testes of genotypic and phenotypic normal males. From the practical, diagnostic point of view the new classification does not contain dramatic changes. For the therapy of germ cell tumor an assessment of risk factors found by the pathologists is extremely important. The most important independent predictors of relapse are tumor invasion of blood or lymph-vessels, absence of yolk sac elements and the presence of an embryonal carcinoma component. In the absence of such predictors a surveillance policy allows some patients to forgo chemotherapy.

Testicular Tumours: Germ Cell Tumours

2008-09-30T10:00:00.000-07:00

Germ Cell Tumours:
Germ cell tumour gives rise to either a seminoma (an undifferentiated germ cell tumour) or an embryonal carcinoma (a tumour of totipotent cells).
Embryonal carcinoma may undergo somatic differentiation and become a teratoma. Alternatively, extra-embryonic differentiation results in a yolk sac tumor (endodermal sinus tumour) or a choriocarcinoma.
Metastases of germ cell tumours may show a form of differentiation not present in the primary tumour.
Infants and children are most commonly afflicted with yolk sac tumours and teratomas. Choriocarcinomas are more frequent in the second or third decades, embryonal carcinoma in the third decade, and seminoma in the fourth decade.
Identification of tumour marker includes:
1. Chorionic gonadotropin : Typically found in patients with choriocarcinoma.
2. Alpha-fetoprotein: Found in patients with yolk sac tumour or embryonal carcinoma with yolk sac elements.
Pathogenesis:
Important risk factors are the following:
1. Cryptorchidism: Associated with 10% of testicular tumours.
2. Genetic factors: Higher risk of testicular neoplasia among siblings of patients with testicular tumours ; some familial clustering reported. Significant racial differences also exist (rare in African blacks).
3. Testicular dysgenesis: Includes testicular feminization and Klinefelter syndrome.
Cytogenetic abnormalities involving chromosome 12 are common; i(12p) is present in 90% of testicular germ cell tumors. In the remaining cases, extra genetic material derived from 12p is found in other chromosomes, thus implicating genes located on the short arm of chromosome 12.
Incidence:
Incidence of germ cell tumours is approximately 6: 100,000 men annually, with peak incidence between ages 15 to 34 years.
Germ cell tumours account for 10% of cancer deaths in this age group. Incidence is higher in whites than in blacks in all geographic locations.
Classification and histogenesis:
Diverse classification schemes are based on different morphologic patterns and variable concepts of histogenesis. Testicular germ cell tumours may contain a single histological pattern (40% of cases) or a mixture of patterns (60% of cases).
Most tumours arise from a focus of intratubular carcinoma in situ.
The neoplastic germ cells may give rise to seminoma or transform into a totipotential neoplastic cell (embryonal carcinoma) capable of further differentiation.
Germ cell neoplasms accordingly may be divided into seminomas and non-seminomatous tumours.
General characters of Germ cell Tumors:
Clinically, most cases present with painless enlargement of the testis.
Neoplasia should be considered in the differential diagnosis of all testicular masses, even those that are painful. Clinical evaluation, however, does not reliably distinguish between the various types of germ cell tumours.
Clinical staging is accomplished via physical examination, radiographic imaging of the retroperitoneum and chest, and assay of various tumour marker.
Clinical stages are as follows:
Stage I: Tumour confined to the testis
Stage II: Metastases limited to retroperitoneal nodes below the diaphragm.
Stage III: Metastases outside the retroperitoneal nodes or above the diaphragm.
Metastases: Lymphatic metastases are most common in retroperitoneal para-aortic nodes but may occur in more distant sites (Example: mediastinal and supraclavicular nodes).
The lungs are the most common site for hematogenous metastases, followed by liver, brain, and bone.
Biological behaviour: Biological behaviour of nonseminomatous germ cell tumours (NSGCTs) is in general, more aggressive than that of seminomas. Roughly 70% of seminomas present with localized (clinical stage I) disease, in contrast, 60% of NSGCTs present with advanced stage (stage II or III) disease. Extensive metastases may be present even with small primary lesions, particularly in the case of choriocarcinoma.
Immunology: Several peptides may be produced by germ cell tumours and can be detected in body fluids by sensitive assays. AFP and HCG are the most commonly assayed. Lactate dehydrogenase although not specific for testicular tumours, is produced by the tumour cells, and the degree of elevation provides a rough measure of tumour burden.

Serum markers are of value to:
i) Evaluate testicular masses
ii) Stage germ cell tumours
iii) Assess tumour burden
iv) Monitor the response of a germ cell tumour to therapy.

Treatment includes radiation and chemotherapy, depending on the histologic type of the tumour (seminoma versus NSGCT) and the stage of the disease, chemotherapy, in particular, has dramatically improved the prognosis of patients with NSGCT.

Abstracts: Germ cell tumors of the gonads: a selective review emphasizing problems in differential diagnosis, newly appreciated, and controversial issues.Mod Pathol. 2005 Feb;18 Suppl 2:S61-79.
Gonadal germ cell tumors continue to be the cause of diverse, diagnostically challenging issues for the pathologist, and their correct resolution often has major important therapeutic and prognostic implications. They are academically interesting because of the biological diversity exhibited in the two gonads and variation in frequency of certain neoplasms. The most dramatic examples of the latter are the frequency of dermoid cyst in the ovary compared to the testis and the reverse pertaining to embryonal carcinoma. Within the teratoma group, there is strong evidence that ovarian and prepubertal testicular teratomas are derived from benign germ cells, a pathogenesis that likely applies also to the rare dermoid cysts and uncommon epidermoid cysts of the testis. In contrast, postpubertal testicular teratomas derive from malignant germ cells, specifically representing differentiation within a preexistent nonteratomatous cancer. As expected, given the foregoing, teratomas in boys are clinically benign, whereas in postpubertal males they are malignant, independent of their degree of immaturity. On the other hand, immaturity is an important finding in ovarian teratomas, irrespective of age, although its significance in children has recently been challenged. It is usually recognized on the basis of embryonic-appearing neuroepithelium, which shows mitotic activity and apoptosis in contrast to differentiated neuroepithelial tissues, which may occur in mature ovarian teratomas. Rarely it is based on the presence of cellular, mitotically active glial tissue. Fetal-type tissues alone are not sufficient for a diagnosis of immature teratoma. Further differences between the teratomatous tumors in the two gonads are the relative frequency of monodermal teratomas in the ovary in contrast to the testis, where only one subset, carcinoids, is seen with any frequency. When uncommon somatic-type malignancies (usually squamous cell carcinoma) occur in mature cystic teratomas of the ovary, this is a de novo form of malignant transformation; similar tumors in the testis, a very rare event, represent overgrowth of teratomatous elements that originated from malignant, nonteratomatous germ cell tumors and, therefore, had previously undergone malignant transformation. Germinomas may have several unusual features in each gonad; these include microcystic arrangements that suggest yolk sac tumor, tubular patterns that mimic Sertoli cell tumor, apparent increased cytological atypia that causes concern for embryonal carcinoma, and prominent syncytiotrophoblast giant cells that suggest choriocarcinoma. Awareness of these variants, good technical preparations, the retained typical cytological features of germinoma cells, and the judicious use of tailored panels of immunohistochemical stains resolve these dilemmas in virtually all instances. Two aspects of germinomas are unique to the testis. Firstly, intertubular growth of small seminomas may cause them to be overlooked. Secondly, the distinctive spermatocytic seminoma occurs only in the testis. A newly recognized aspect of this tumor is the propensity for some to be relatively monomorphic, making them apt to be mistaken for usual seminoma or embryonal carcinoma, although the characteristic polymorphic appearance in some foci, absence of intratubular germ cell neoplasia, unclassified type, and immunohistochemical stains should prevent this error. Cytoplasmic membrane immunoreactivity for placental alkaline phosphatase and CD117, with usual negativity for AE1/AE3 cytokeratins, is helpful in the diagnosis of germinoma. The recently described marker, OCT3/4, a nuclear transcription factor, is especially helpful in the differential of germinoma and embryonal carcinoma with other neoplasms. Yolk sac tumor continues to be confused occasionally with clear cell carcinoma of the ovary. Glandular ('endometrioid-like') yolk sac tumors mimic endometrioid carcinomas; predominant or pure hepatoid yolk sac tumors cause concern for metastatic hepatocellular carcinoma or, in the ovary, primary hepatoid carcinoma, and solid patterns, especially in limited samplings, may be misinterpreted as germinoma. The usually younger age of patients with yolk sac tumors helps with the differential considerations with the nongerm cell tumors, as do other clinical and microscopic features and selected immunohistochemical stains. Choriocarcinoma is rare in both gonads, and those in the ovary must be distinguished from metastatic tumors of placental origin. Syncytiotrophoblast cells alone, admixed with other forms of germ cell tumor, still are confused with choriocarcinoma, but this phenomenon, which is much more frequent than choriocarcinoma, lacks the plexiform arrangement of different trophoblast cell types that typifies the latter. Mixed germ cell tumors (which may show almost any combination of components) are common in the testis but rare in the ovary. A separately categorized, rare form of mixed germ cell tumor seen in both gonads is the polyembryoma. It is perhaps the most photogenic of all gonadal germ cell tumors and is also intriguing because of its distinctive, organized arrangement of yolk sac tumor and embryonal carcinoma elements and recapitulation of very early embryonic development, even to the extent of having in its fundamental unit, the embryoid body, a miniature yolk sac, and amniotic cavity. These tumors, which are constituted by innumerable embryoid bodies, almost always contain teratomatous glands in minor amounts, and one way of viewing the polyembryoma is to consider it the most immature form of teratoma. Embryoid bodies are also common as a minor component of many mixed germ cell tumors, particularly in the testis, and the diffuse embryoma is another variant that has a particular arrangement of yolk sac tumor and embryonal carcinoma elements. Regression of gonadal germ cell tumors is a phenomenon restricted to the testis, for unknown reasons. These so-called 'burnt-out' germ cell tumors can be recognized by a distinctive constellation of findings, including sometimes minor foci of residual recognizable germ cell neoplasia, a well-defined zone of scarring (often having residual ghost tubules), associated lymphoplasmacytic infiltrate, intratubular calcification and, in about 50%, of in situ germ cell neoplasia.

Testis and Epididymis: Spermatic Granulomas

2008-09-29T10:30:00.000-07:00

Spermatic granulomas result from an intense inflammatory response to sperm that enter into the interstitial tissue of epididymis.
The cause of extravasation of the sperm is not clear but trauma or infection may play a role.
Clinically, patients present with scrotal pain and swelling of weeks or months duration.
Microscopically, a mixed inflammatory cell infiltrate is associated with numerous extravasated sperm fragments and phagocytosis of sperm by histiocytes. Ultimately the inflammatory process results in interstitial fibrosis and ductal obstruction.

Testis and Epididymis: Miscellaneous Lesions of Tunica Vaginalis

2008-09-29T09:29:00.000-07:00

Miscellaneous Lesions of Tunica Vaginalis :
Conditions include the following:
Hydrocele: Accumulation of serous fluid within the tunica vaginalis, either secondary to generalized edema or due to incomplete closure of the processus vaginalis. A hydrocele may become secondarily infected.
Hematocele: Accumulation of blood within the tunica vaginalis secondary to trauma, torsion, or hemorrhage; a generalized bleeding diathesis; or, rarely, invasion of the tunica by neoplasms.
Chylocele: Accumulation of lymphatic fluid within the tunica vaginalis, secondary to lymphatic obstruction (Example: In patients with elephantiasis).
Spermatocele: Local accumulation of semen in the spermatic cord, generally within a dilated duct in the head of the epididymis.
Varicocele: Local accumulation of blood within a dilated vein in the spermatic cord (internal spermatic veins that drain the testicle).It is a very common condition present in 15% of the general male population and 40% of men evaluated for infertility. A varicocele develops because of defective valves that normally allow for blood to flow away from the testicle toward the abdomen. Testicular injury occurs due to abnormal back flow of blood from the abdomen into the scrotum and this creates a hostile environment for sperm development.

Testis and Epididymis: Vascular Disturbances -Testicular Torsion

2008-09-28T10:59:00.000-07:00

Vascular disturbances : Testicular torsion
Torsion occurs secondary to twisting of the spermatic cord, resulting in venous obstruction.
Arteries may also be occluded but often remain patent due to thicker walls.
Torsion typically occurs in patients with preexisting structural lesions, such as incompletely descended testis, absence of scrotal ligaments, or testicular atrophy.
Torsion is generally precipitated by physical trauma or other violent movement.
Changes range from congestion and interstitial hemorrhage to extensive hemorrhagic necrosis, depending on the duration and severity of the process.

Testis and Epididymis: Specific Inflammations -Syphilis

2008-09-28T08:58:00.000-07:00

Syphilis
Syphilis always begins as orchitis with secondary involvement of the epididymis.
It may present as isolated orchitis without involvement of adnexal structures.
Orchitis may occur in both congenital and acquired syphilis.
Microscopically, syphilis may produce nodular gummas ( Syphilitic Gumma ) or diffuse interstitial inflammation. Interstitial changes include edema, lymphocytic and plasma cell infiltration and typical obliterative endarteritis with perivascular cuffing of lymphocytes and plasma cells. Gradually, there is complete loss of seminiferous tubules and interstitial cells.

Testis and Epididymis: Specific Inflammations -Tuberculosis

2008-09-28T05:01:00.000-07:00

Tuberculosis
Tuberculosis almost always begins in the epididymis and may spread to the testis.
Tuberculosis of testis is usually unilateral and may occur at any age.
They are commonly associated with the tuberculosis of lungs and genitourinary tract.
Discrete tubercles in the testis may be seen in generalized military tuberculosis.
Commonly earliest lesion is seen as an area of granuloma with caseous necrosis in the globus minor due to retrograde infection via vas deferens from seminal vesicle.
Blood-borne infection commences on the globus major.
This lesion usually regresses and becomes calcified.
Progressive lesion shows involvement of the entire epididymis.
Tunica vaginalis serves as a barrier against extension into the testis. It is often seen that there is complete destruction of the epididymis with no invasion of the testis.
Clinically, a firm often painless mass is felt behind the testis.
In 30% cases secondary hydrocele may be present.

Testis and Epididymis: Specific Inflammations - Mumps

2008-09-28T04:41:00.000-07:00

Mumps
Mumps is a systemic viral disease that most commonly affects school-aged children.
In adult males orchitis typically develops in about 1 week after onset of parotid inflammation, rarely, it may precede parotitis or occur in the absence of parotitis.
Orchitis occurs as a complication in 20 to 30% of cases of mumps and on 70% cases there is unilateral testicular involvement. Due to unilateral involvement and patchy interstitial inflammation, it is usually, not associated with sterility,
Grossly, The testis is enlarged with punctate hemorrhages in the tunica albuginea.
Microscopically, there are acute inflammatory cells together with infiltration of histiocytes in the interstitial tissue. Seminiferous tubules show no evidence of spermatogenesis and the cells in the lumen are Sertoli cells.
Neutrophils are usually not prominent but in the more intense inflammatory response, frank suppuration may develop with tubular lumen distended with pus.

Testis and Epididymis: Specific Inflammations - Gonorrhea

2008-09-27T12:46:00.000-07:00

Gonorrhea
1. Most cases of gonorrhea are due to retrograde extension of infection from the posterior urethra to prostate, seminal vesicles, and epididymis.
2. The inflammatory pattern is identical to that seen in nonspecific epididymitis and orchitis.
Infection may extend to the testis and produce suppurative orchitis in untreated cases.

Testis and Epididymis : Granulomatous (Autoimmune) Orchitis

2008-09-26T10:50:00.001-07:00

Granulomatous (Autoimmune) Orchitis:
Granulomatous orchitis is an uncommon cause of unilateral testicular enlargement in middle-aged men. It has a possible autoimmune origin.
Clinically, most cases present with sudden onset of tender testicular mass, sometimes associated with fever. It may be painless in some patients and difficult to distinguish from testicular neoplasia.
Microscopically, non-caseating granulomas occur within testicular tubules and adjacent connective tissue, accompanied by occasional plasma cells and neutrophils.
Epithelioid cells may originate from Sertoli cells.
Lesions must be differentiated from granulomas of tuberculosis.
Grossly, the testis is enlarged, grayish-white or brownish in colour with normal or thickened tunica albuginea.

Testis and Epididymis : Nonspecific Epididymitis and Orchitis

2008-09-26T09:57:00.000-07:00

Nonspecific epididymitis and orchitis:
Nonspecific epididymitis and orchitis are often associated with infection of the urinary tract, with secondary infection of the epididymis via vas deferens or lymphatics of the spermatic cord.
Causes vary with the age of the patient and include:
i) In pediatric patients it is usually associated with genitourinary malformations.
ii) In sexually active men, younger than age 35 years of age, the sexually transmitted pathogens, Chlamydia trachomatis (Chlamydial Infection; Chlamydial Infection of the Genital Tract) and Neisseria gonorrhoea are the frequent organisms.
iii) In older age, Escherichia coli and Pseudomonas species are responsible for most infections.
Microscopically, nonspecific interstitial congestion, edema and neutrophilic infiltrates occur in the early stage, with subsequent involvement of tubules. Severe cases may progress to generalized suppuration of the entire epididymis. Inflammation may extend to the testis via efferent ductules or local lymphatic channels. Scarring of the testis and epididymis may occur with resultant infertility. Leydig cells are less severely affected and sexual activity generally is not disturbed.

Testis and Epididymis : Inflammations

2008-09-25T11:02:00.000-07:00

Inflammations:
Inflammatory conditions are more common in the epididymis than in the testis; however, some infections notably syphilis (syphilitic gumma) , may begin in the testis with secondary involvement of the epididymis.
Inflammatory diseases include nonspecific epididymitis and orchitis, granulomatous (autoimmune) orchitis, and several specific infectious diseases (Eg: Gonorrhea, mumps, tuberculosis, syphilis) .

Testis and Epididymis : Atrophy

2008-09-25T10:46:00.000-07:00

Atrophy of the Testis:
Atrophy is the regressive change affecting the testis.
Causes include:
1. Progressive arteriosclerotic narrowing of the blood supply in old age.
2. End stage of orchitis
3. Cryptorchidism
4. Hypopituitarism
5. Generalized malnutrition or cachexia
6. Obstruction to the outflow of semen
7. Irradiation and chemotherapy
8. Prolonged administration of female sex hormones as in the treatment of carcinoma prostate.
9. Persistently elevated levels of follicle-stimulating hormone,
10. Primary developmental abnormality in patients with Klinefelter syndrome.
Gross and microscopic alterations are identical to those in cryptorchidism.

Testis and Epididymis: Cryptorchidism

2008-09-25T10:23:00.000-07:00

Cryptorchidism:
1. Cryptorchidism affects 1% of 1-year-old boys.
2. It is the failure of descent and testes may be found anywhere along the normal path of descent, from abdominal cavity to the inguinal canal.
3. Most cases are idiopathic; other causes include:
i) Genetic abnormalities (e.g., trisomy 13)
ii) Hormonal abnormalities
4. Most cases are unilateral; 25% are bilateral.
5. Microscopically, the changes may be apparent, as early as 2 years of age, including decreased germ cell development, thickening and hyalinization of seminiferous tubular basement membrane, interstitial fibrosis, and relative sparing of Leydig cells. Spermatogenesis is lacking but Sertoli cells fill the lumen of the seminiferous tubules (Fig 19-3). Regressive changes may also occur in the contralateral descended testis.
6. Clinically, cryptorchidism is asymptomatic and it is found only when the scrotal sac is discovered not to contain the testis. Its significance is related to high prevalence of inguinal hernia, sterility, and a 5- to-10-fold increased incidence of testicular neoplasms.
Surgical correction (orchiopexy) decreases the likelihood of sterility, if performed early but does not decrease the risk of neoplasia, which may occur in either testis.

Testis and Epididymis: Congenital Anomalies

2008-09-25T10:18:00.000-07:00

Congenital Anomalies:
Anomalies include cryptorchidism, aplasia, fusion (synorchism) and a variety of developmental cysts.

Penis: Malignant tumours

2008-09-25T10:13:00.000-07:00

Squamous cell carcinoma:
The frequency of squamous cell carcinoma shows a marked geographic variation, with the highest incidence in Asian countries, Africa, and Central America. The variation in frequency has been associated with personal, social, and religious practices, including personal hygiene and the practice of circumcision. In USA it accounts for about 1% of cancers in men between the ages 40 and 70 years. Carcinoma of the penis is extremely rare in Jews and Moslems.
Potential causes are carcinogens within smegma accumulating under the foreskin and HPV types 16 and 18 infection.
Grossly, it presents as epithelial thickening on the glans or inner surface of the prepuce near the coronal sulcus, progressing to ulceroinfiltrative or exophytic growth eroding the penile tip, shaft, or both.
Microscopically, it is identical to squamous cell carcinomas involving other cutaneous sites.
Clinically, it is characterized by slow growth with metastases to regional (inguinal and iliac) lymph nodes; distant metastases are common. This progression can be expected within 2 years of the initial diagnosis.
The 5-year survival rate is 66% for lesions confined to penis and 27% with regional node involvement.
Verrucous carcinomas:
Verrcous carcinomas, also called giant condyloma or Buschke-Lowenstein tumor, is an uncommon, well-differentiated form of squamous cell carcinoma with low malignant potential. This is seen with greater frequency in the larynx. The carcinoma cells show minimal atypia. Large penile carcinomas cause complete destruction of penis.

Penis: Bowenoid Papulosis

2008-09-25T09:57:00.000-07:00

Bowenoid Papulosis
Grossly, bowenoid papulosis presents as a multiple, pigmented (violet) papules in the penile shaft. It may mimic condyloma acuminatum grossly. Patients are generally two decades younger than those with Bowen's disease.
Bowenoid papulosis is histologically indistinguishable from Bowen's disease, but, in contrast to Bowen's disease, evolution into invasive carcinoma is rare.

Penis: Erythroplasia of Queyrat

2008-09-25T09:55:00.000-07:00

Erythroplasia of Queyrat:
Erythroplasia of Queyrat generally appears on the glans or prepuce as a single or multiple, shiny-red, sometimes velvety plaques. Histologic features and evolution are comparable to those of Bowen's disease. There is no association with visceral malignancy.

Penis: Bowen's Disease

2008-09-25T09:38:00.000-07:00

Bowen's disease
Bownen's disease may occur in the genital region in both men and women, generally those older than 35 years of age. In men it mainly involves the shaft of the penis and the scrotum.
Grossly, it appears as a solitary, thickened, gray-white, opaque plaque with shallow ulceration and crusting.
Microscopically, there is marked epidermal proliferation with numerous mitosis, some atypical. There is complete loss of normal surface maturation but the basement membrane is intact and there is no invasion of underlying stroma. Transition to invasive squamous cell carcinoma is estimated to occur in about 10% of cases; there is a possible association with visceral malignancies (about one-third of patients).

Penis: Carcinoma in situ

2008-09-25T09:15:00.000-07:00

Carcinoma in situ:
Carcinoma in situ is the histologic term used to describe cytologic evidence of malignancy (e.g. marked dysplasia, hyperchromasia, pleomorphism) confined to the epithelium with no invasion of underlying connective tissue or distant metastasis.
It shows extensive or patchy parakeratosis, hyperkeratosis, papillomatosis with broad epidermal papillae, thinning of the granular layer.
A chronic inflammatory cell infiltrate in the subjacent dermis is characteristic.
Variants include Bowen's disease ; Eryhtroplasia of Queyrat and Bowenoid papulosis.

Penis: Benign tumours - Condyloma Acuminatum

2008-09-25T08:55:00.000-07:00

Condyloma Acuminatum:
1. Condyloma acuminatum is a benign epithelial proliferation caused by human papilloma virus (HPV), especially type 6 and 11.
2. Condyloma acuminatum may involve mucocutaneous genital surfaces of either sex. Sexual contact is the most likely mode of transmission. It is most common after puberty. Its presence in prepubertal child should arouse suspicion of sexual abuse.
3. Grossly, the lesion is a sessile or pedunculated papillary excrescence. In male, it often involves the coronal sulcus or inner surface of the prepuce. Large condylomas are cauliflower-like in appearance and small ones require colposcopic detection.
4. Microscopic characteristics include branching fibrovascular stromal papillae covered by hyperplastic stratified squamous epithelium, often associated with prominent hyperkeratosis. Vacuolation of superficial epithelial cells (koilocytosis) is common. Maturation of epithelial cells is orderly, in contrast to carcinoma in situ.
5. Most lesions remain benign. They may recur due to persistence of HPV infection.
6. It has association with and possible etiologic role in the development of cervical dysplasia, carcinoma in situ, and squamous cell carcinoma. Type16, 18, and 31 have been found in the vast majority of high-grade precancerous lesions and invasive carcinomas.

Penis: Tumours

2008-09-25T08:52:00.000-07:00

Tumours of the penis include: Benign tumours ; Carcinoma in situ ; and malignant tumours.

Penis : Peyronie’s disease

2008-09-25T08:48:00.000-07:00

Peyronie’s disease is of unknown etiology and is characterized by focal asymmetric fibrosis induration of the shaft of the penis without significant change of the overlying skin.
Fibrosis results in curvature and discomfort of the penis at the time of erection.
It occurs in a young or middle aged man.
Rarely, it may be inherited with an autosomal dominant transmission.
Microscopically, dense dermal fibrosis focally replaces the muscle in the septum of the corpus cavernosum. Occasionally the fibrous tissue undergoes ossification.
No reliable therapy has emerged.

Penis: Balanoprosthitis

2008-09-25T08:24:00.000-07:00

Balanoprosthitis is the nonspecific infection of the glans penis and prepuce, generally associated with phimosis or a redundant prepuce, and resultant chronic accumulation of smegma.
It may be caused by a wide variety of bacteria, fungi, mycoplasmas and chlamydiae (Chlamydial Infection ; Chlamydial Infection of the Genital Tract) .
Such inflammation, if neglected may lead to ulceration of the mucosal surface of the glans.

Penis: Inflammations

2008-09-25T07:46:00.000-07:00

Inflammations characteristically involve both the glans penis and the prepuce.
Nonspecific inflammatory processes and specific sexually transmitted diseases (Example: Syphilis , gonorrhea, chancroid, lymphogranuloma venereum, genital herpes, granuloma inguinale) occur.

Penis : Congenital Anomalies

2008-09-25T07:31:00.000-07:00

Penis is the site of many congenital anomalies only some of which have clinical significance.
A variety of abnormalities occur in size and form, including aplasia or hypoplasia; hypertrophy; duplication; pin-hole meatus, and more commonly, hypospadias, epispadias, and phimosis.
Hypospadias and Epispadias:
Malformation of the urethral groove and urethral canal causes abnormal openings either on the ventral surface of the penis (hypospadias) or on the dorsal surface (epispadias). These may be associated with other urogenital malformations, including undescended testes.
Its clinical significance is as follows:
i) Constriction of this abnormal opening may produce partial urinary obstruction with spread of infection from penile urethra to bladder and the entire urinary tract.
ii) When the orifice is situated at the base of the penis, normal ejaculation and insemination are hampered or totally blocked producing sterility in men.
Phimosis:
Phimosis is the inability to retract the prepuce because of an abnormally small preputial orifice. It may arise as a primary developmental defect but is more commonly secondary to inflammatory scarring of the prepuce. Phimosis predisposes to secondary infection and carcinoma, due to chronic accumulation of secretions and other debris under the foreskin.
Paraphimosis:
Paraphimosis is the abnormal painful swelling of the glans penis after forceful retraction of a phimotic prepuce. It may cause urethral obstruction.
Circumcision is effective therapy for phimosis and the complication of balanoposthitis.

Anatomy and Embryology of Male Genital Tract

2008-09-25T07:13:00.000-07:00

Anatomy and Embryology:
In embryo, urinary system develops in 3 attempts (pronephros, mesonephros, metanephros).
Pronephros is replaced by mesonephros.
Metanephros utilizes only the distal mesonephric duct to complete the development of urogenital system.
Metanephros forms kidney with nephrons, renal pelvis, ureter, urinary bladder and urethra.
Mesonephros forms gonads, vas deferens, seminal vesicle, and ejaculatory duct.
Prostate is developed from the proximal part of urethra and composed of urethral (metanephros), urogenital sinus, mesonephros and paramesonephric tissue.