Sex cord-stromal tumors of the testis with entrapped germ cells: a lesion mimicking unclassified mixed germ cell sex cord-stromal tumors

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.     

DNA ploidy in testicular germ cell neoplasms. Histogenetic and clinical implications.

Flow cytometry was used to determine the DNA ploidy pattern of 148 testicular germ cell neoplasms (seminomas and nonseminomas in pure and mixed histologic phenotypes) and in situ carcinoma (CIS) adjacent to these tumors. The great majority (96.0%) manifested aneuploid DNA contents with minimal intratumoral heterogeneity (2.5%). The mean DNA indices (DI) of CIS (1.7 +/- 0.18), pure seminoma (1.82 +/- 0.55), and the seminoma component of mixed germ cell neoplasms (1.76 +/- 0.13) were statistically similar. The mean DI of nonseminomas pure (1.46 +/- 0.29) or as a component of mixed tumors (1.43 +/- 0.32) was significantly lower (p greater than 0.001) than those of CIS and seminomas. Our data suggest that the similarity between the DNA indices of CIS and seminomas provide evidence that both lesions constitute a temporal evolutionary step in the progression of germ cell tumors and that nonseminomas may subsequently arise from either CIS or seminoma by further loss of chromosomal DNA. These characteristic findings support the nonstochastic theory for germ cell evolution and progression and may be useful in the clinicopathologic evaluation of testicular masses.     

Testicular Microlithiasis Associated with Teratocarcinoma and Intratubular Germ Cell Neoplasia: A Case Report

Testicular microlithiasis is a rare condition that has characteristic sonographic and histologic features. It is often associated with premalignant changes and malignant neoplasms of the testes. We report a case of testicular microlithiasis associated with teratocarcinoma and intratubular germ cell neoplasia. Three previously reported cases documented development of malignant germ cell tumor during the clinical follow-up period of patients with testicular microlithiasis. We think that testicular microlithiasis is strongly associated with testicular neoplasms, and that coexistence of intratubular germ cell neoplasia and malignant germ cell tumors with testicular microlithiasis is common.     

Association of intratubular seminoma and intratubular embryonal carcinoma with invasive testicular germ cell tumors

The classification of intratubular germ cell neoplasia of the testis includes an unclassified type (IGCNU), in addition to various other intratubular lesions that show specific forms of differentiation, such as intratubular seminoma and intratubular embryonal carcinoma. Although IGCNU is recognized as a precursor lesion for testicular germ cell tumors, the relationship between differentiated types of intratubular germ cell neoplasia and invasive germ cell tumors of the testis is not well established. The aim of the present study was to examine the association between invasive testicular germ cell tumors and intratubular neoplastic lesions, with particular emphasis on differentiated types of intratubular germ cell neoplasia. The seminiferous tubules adjacent to 42 testicular germ cell tumors were evaluated for the presence of various forms of intratubular germ cell neoplasia. IGCNU was observed in 37 (88%) of 42 cases, whereas intratubular seminoma and intratubular embryonal carcinoma were seen in 19% and 7% of the cases, respectively. Intratubular seminoma was associated primarily with seminomas or mixed germ cell tumors with a seminomatous component, but was also present in a case of a nonseminomatous germ cell tumor. Intratubular embryonal carcinoma was associated exclusively with nonseminomatous germ cell tumors. All cases of intratubular embryonal carcinoma were identified morphologically and exhibited histologic features corresponding to traditional definitions of this lesion. No examples of intratubular embryonal carcinoma as defined by CD30 expression alone in the absence of an intratubular proliferation were observed. The presence of intratubular seminoma in a nonseminomatous germ cell tumor suggests that it is a true preinvasive lesion rather than a manifestation of intratubular spread of an established invasive seminoma. The low incidence of intratubular embryonal carcinoma supports the theory that most nonseminomatous germ cell tumors evolve initially as seminomas, rather than directly from a differentiated intratubular neoplastic lesion.     

Epigenetics: A way to understand the origin and biology of testicular germ cell tumors

Testicular germ cell tumors are neoplasms carrying two unique features. First, testicular germ cell tumors have a pluripotential nature and show protean histology ranging from that of germ cells to embryonal and differentiated somatic cells. Therefore, testicular germ cell tumors are interesting resources positioned at a crossroad in developmental and neoplastic processes. The second unique feature of testicular germ cell tumors is their exquisite sensitivity to cisplatin‐based chemotherapy. This review summarizes recent research progress in the epigenetics of testicular germ cell tumors in an attempt to explain the abovementioned biological and clinical characteristics of testicular germ cell tumors.     

Testicular seminoma metastasizing to the parotid gland: report of a case

BACKGROUND: Among salivary glands, the parotid gland is the most common site for secondary neoplastic involvement, and carcinomas and melanomas are the two most common secondary tumors. METHODS: We present a case of testicular seminoma metastasizing to the parotid gland. The patient, who had a remote history of testicular seminoma, was initially seen with a parotid mass. A primary parotid lesion was anticipated, and excisional biopsy was performed. The diagnosis of testicular seminoma metastasizing to the parotid gland was established on the basis of histologic findings and was confirmed by immunohistochemical analysis. RESULTS: Metastatic and primary seminomas have the same morphologic features and cellular composition, and granulomatous reaction is often present in both neoplasms. Extragonadal seminoma often occurs in the midline (presacral, retroperitoneal, anterior mediastinal, and pineal regions); when present in any other locations, the tumor should be considered to be metastatic. Placenta alkaline phosphatase is a useful immunohistochemical stain to confirm the diagnosis, and cytokeratin immunohistonegativity rules out carcinomas or epithelioid sarcomas. CONCLUSIONS: To our knowledge, this is the first published case of metastatic testicular seminoma to the parotid gland. Cytomorphologic features of seminoma and the presence of granulomatous giant cells are important diagnostic clues. Two other neoplasms with granulomatous reactions, nasopharyngeal carcinoma and epithelioid sarcoma, should be considered in the differential diagnosis.     

A case of bilateral testicular germ cell tumors of different cell types with maturation in the metastatic region

A case of bilateral testicular germ cell tumors of different cell types and maturation in the metastatic region is described. A 42-year-old man with bilateral testicular swelling visited our clinic. Bilateral high orchiectomy was performed. Subsequent histological examination revealed seminoma and embryonal carcinoma in the right testis and seminoma and mature teratoma in the left. Then bilateral retroperitoneal lymphadenectomy was performed and 7 metastatic regions were found in the para-aortic lymph nodes. One of these revealed histopathologically a mature teratoma containing cartilage constituents. After the operation, multiple drug treatment with Cis-DDP, vinblastine and pepleomycin was started. The patient has been in complete remission for about 1.5 year. In addition, we reviewed the literature about bilateral testicular germ cell tumors and maturation in the metastatic region.     

Seminoma With Bronchial Involvement and Superior Vena Cava Syndrome: A Rare Combination

We describe the case of a 45-year-old male who was admitted with clinical signs of superior vena cava syndrome (SVCS). Physical examination showed collar of Stokes and extensive collateral circulation in the neck and anterosuperior thoracic region, as well as a large testicular mass. Fibrobronchoscopy revealed an endobronchial tumor, histopathologically diagnosed as seminoma, with the same characteristics as the testicular biopsy. Treatment was initiated with surgery, chemotherapy and radiotherapy, resulting in a major clinical improvement. We indicate the importance of considering SVCS as an entity related with less common neoplasms such as germ cell tumors.     

Testicular seminoma occurring 8 years after treatment of a metastatic extragonadal germ cell tumor

A 30-year-old man was admitted with a chief complaint of left-sided scrotal enlargement, and was diagnosed as having testicular seminoma after orchiectomy. Eight years earlier, he had been treated with chemotherapy for an extragonadal germ cell tumor, without orchiectomy, leading to complete remission. His histological diagnosis at that time was a germ cell tumor, composed of choriocarcinoma and embryonal carcinoma. He was followed up without testicular biopsy. Routine pretreatment testicular biopsy in patients with extragonadal germ cell tumor is controversial, but regular long-term follow up and information on the risk of developing a metachronous testicular tumor are needed after treatment of extragonadal germ cell tumors, even when there seems to be a partial or complete clinical response.     

Correlation between expression of metastasis-related genes and lymph node metastasis in testicular cancer

To investigate the factors related to lymph node metastasis of testicular germ cell tumors, we first established a seminoma orthotopic model with lymph node metastasis in SCID mice by inoculating small fragments from subcutaneous xenografts. Second, we compared the expression patterns of metastasis-related genes of the seminoma xenografts and of the TCam-2 cells which were established as a seminoma cell line from a primary testicular seminoma. Third, we immunohistochemically analyzed human germ cell tumors (25 seminomas, 17 nonseminomas) using monoclonal antibodies to CD34, VEGF, VEGF-C, Flt-4, MMP-2 and E-cadherin. Testicular seminoma xenografts grew in 32/32 (100%) of the inoculated mice, of which 15 (47%) developed macroscopic metastasis to the renal hilar lymph node. Circulating tumor cells were detectable by using a PCR assay for the human beta-globin gene in 25/32 (78%) mice, although metastatic foci were not histologically evident in the visceral organs, including lungs, liver, kidneys and spleen. This may reflect the lymphophilic characteristics of the seminoma cells used. Regarding mRNA expression of metastasis-related genes, an increased expression of MMP-2 and VEGF compared with that in the s.c. xenografts was demonstrated by RT-PCR assay in the testicular seminoma xenografts. In addition, uPAR, MMP-1, MMP-2, MT1-MMP and MT3-MMP showed a a stronger expression and PAI-2 a weaker expression in the seminoma xenografts than did TCam-2 cells. These results suggest a higher metastatic potential of the seminoma xenografts, especially testicular xenografts, as compared with TCam-2 cells. In the immunohistochemical study, a significant correlation was found between MMP-2 expression and lymph node metastasis, which is compatible with the results for the metastasis-related gene expression from the seminoma xenografts.     

Metastases from testicular carcinoma Study of 78 autopsied cases

The necropsy records of 78 patients with histologically proved germ cell tumors of the testis, who died as a direct result of their malignant disease, were reviewed to determine the usual modes of spread, distribution of metastasis, the histologic characteristics of the metastatic foci as compared with the morphology of the primary tumor and the specific cause of death. The sites of metastases in order of decreasing frequency for all cases were lung, retroperitoneal lymph nodes, liver, mediastinal lymph nodes, brain, kidney, gastrointestinal tract, bones, adrenals, peritoneum, and spleen. The absence of metastases solely in the anterior mediastinum without involvement of other mediastinal nodes (middlelposterior) strongly supports the premise for a primary extragonadal origin whenever the anterior mediastinum alone is involved with malignant disease having the histologic appearance of a primary germ cell tumor. The histologic features of the metastatic lesions were usually similar in nature to those of the primary tumor except for seminoma in which the metastatic lesions proved to be of a different histologic pattern in almost one third of the patients dying from the disease. It should be axiomatic that whenever a patient with seminoma fails to respond appropriately to radiotherapy thet his treatment be immediately discontinued and that appropriate biopsies be obtained to substantiate the histologic pattern present.     

Calretinin,a more sensitive but less specific marker than alpha-inhibin for ovarian sex cord-stromal neoplasms: an immunohistochemical study of 215 cases

Although inhibin has been shown to be a sensitive marker for ovarian sex cord-stromal and fibrous neoplasms, it may be negative in some cases. Calretinin, a mesothelial marker, has shown promise as a marker for sex cord-stromal neoplasms. The aim of this study was to evaluate and compare calretinin and inhibin as immunohistochemical markers for sex cord-stromal and fibrous neoplasms. A total of 215 ovarian neoplasms were immunostained with commercially available antibodies to calretinin and inhibin. These tumors included 87 sex cord-stromal (39 granulosa cell, 13 Sertoli-Leydig, 4 Sertoli, 9 thecomas, 14 fibrothecomas, and 8 other stromal tumors), 37 fibrous (20 fibromas, 9 adenofibromas, and 8 fibrosarcomas), 65 epithelial, 22 germ cell, and 4 miscellaneous neoplasms. The staining was evaluated on a 0-4 scale based on percentage of neoplastic cells labeling: 0 = none; 1+ = 1-25%; 2+ = 26-50%; 3+ = 51-75%; 4+ = 76-100%. Calretinin reactivity was detected in 100% of sex cord-stromal and 90% of fibrous neoplasms, including 32 that were inhibin negative (2 granulosa cell tumors, 1 Sertoli-Leydig cell tumor, 1 thecoma, 3 fibrothecomas, 16 fibromas, 6 adenofibromas, and 3 fibrosarcomas). All four calretinin-negative fibrous neoplasms were inhibin negative. Calretinin staining was also detected in 22% of epithelial neoplasms but none of the germ cell and miscellaneous neoplasms tested. Inhibin staining was detected in 92% of sex cord-stromal neoplasms, 22% of fibrous neoplasms, 2% of epithelial neoplasms, and none of the germ cell and miscellaneous neoplasms tested. Calretinin has a 97% sensitivity and 85% specificity for sex cord-stromal and fibrous neoplasms, whereas inhibin has a 71% sensitivity and 99% specificity. This study shows that both calretinin and inhibin are useful in the diagnosis of ovarian sex cord-stromal and fibrous neoplasms. Calretinin is a more sensitive but less specific immunohistochemical marker than inhibin. Calretinin is particularly useful in the diagnosis of sex cord-stromal and fibrous neoplasms that are inhibin negative. The high frequency of calretinin in fibrous neoplasms suggests that a subgroup of these neoplasms may be derived from specialized gonadal stromal cells, perhaps thecal cells.     

Massive upper gastrointestinal bleeding from pure metastatic choriocarcinoma in patient with mixed germ cell tumor with subclinical intestinal metastasis

Although testicular germ cell tumors have become curable neoplasms, a better understanding of the clinicopathologic features is needed for the rare manifestations associated with treatment failure. We report a rare case of metastatic pure choriocarcinoma involving the small intestine arising from a testicular mixed germ cell tumor. In a patient who developed massive upper gastrointestinal hemorrhage during treatment, the intestinal metastases and focus of bleeding could only be determined by laparotomy. We propose an approach for the determination of subclinical intestinal metastases of testicular germ cell tumor; the case is discussed in light of similar reports in literature.     

Intrascrotal tumors: a clinicopathologic study of 15 cases

PURPOSE: We reviewed cases of intrascrotal tumors treated at our institution except for germ cell testicular tumors. PATIENTS AND METHODS: From 1977 to 1998 (22 years), 120 cases of intrascrotal tumors treated at the University of Tsukuba. Of these, 15 cases (12.5%) were not germ cell testicular tumors. The patients' ages varied between 2 and 77 years with a mean of 49.6. RESULTS: The most common complaint regarding symptoms was painless testicular enlargement. Tumor weight ranged from 2 to 200 g, with an average of 104.6 g. The histological diagnoses of 15 patients were 8 malignant lymphomas, 2 paratesticular rhabdomyosarcomas, 2 metastatic tumors (origin; stomach and prostate), 1 epidermoid cyst, 1 cyst of tunica testis, and 1 adenomatoid tumor. As for the cases with malignant lymphoma, all of them were non-Hodgkin's lymphoma whose clinical stages were stage I in 2 cases and stage IV in 6 cases. Five 8 patients died in spite of systemic chemotherapy after an orchiectomy, whereas 2 cases with metastatic tumors died of primary cancer, and two cases with paratesticular rhabdomyosarcoma are still alive and have had no evidence of disease. CONCLUSIONS: Intrascrotal tumors except for germ cell testicular tumors are not common, and consist of various diseases. In particular, some kinds of malignant lymphoma mimic anaplastic seminoma histopathologically. Therefore, accurate diagnosis and precise treatment is important in the patient with intrascrotal tumors.     

Population based incidence and age distribution of spermatocytic seminoma

PURPOSE: Spermatocytic seminoma is a rare subtype of testicular germ cell tumor which has been reported to occur in elderly men. We report the first population based estimate of incidence, temporal trends and age distribution of this tumor. MATERIALS AND METHODS: All cases of primary testicular cancer identified by cancer registries in Australia between 1982 and 2002 were available for analysis. The International Classification of Diseases for Oncology code M-9063/3 was used to identify spermatocytic seminomas. Incidence trends were modeled using Poisson regression. RESULTS: There were 58 cases of spermatocytic seminoma out of 9,658 cases of primary malignant testicular neoplasms identified by the cancer registries. This tumor comprised 1.1% of all seminoma and the age standardized incidence rate was 0.4 per million (95% CI 0.3-0.6). A temporal increase in incidence was found but not one reaching statistically significance. Age at diagnosis ranged from 19 to 92 years with a mean of 53.5 (SD 16.7) and a median of 54 years. CONCLUSIONS: Spermatocytic seminoma should be considered in the differential diagnosis for testicular germ cell tumors presenting in young adults because this tumor occurs as often in men younger than 55 years as it does in older men. Although rare, the occurrence of this tumor is not as singular as the current literature suggests.     

Burn out bilateral testicular tumor

Differentiating a primary retroperitoneal seminoma from a metastatic testicular tumor with an occult testicular primary or a burned out testicular cancer remains difficult. We present a case of a burned out tumor. The patient had a retroperitoneal seminoma with ultrasonically and pathologically demonstrated abnormalities in both testes, but without evidence of tumor. The patient received chemotherapy and underwent surgery of the residual retroperitoneal mass and bilateral orchiectomy. All surgical specimens were negative for testis cancer. CONCLUSION: Primary extragonadal germ cell tumors in the retroperitoneum are a rare entity. The presence of a retroperitoneal tumor with ultrasonographical abnormalities in testicular evaluation should be considered as a metastases of a burned out testicular cancer, and biopsy is mandatory. Surgical evaluation and orchiectomy should be evaluated in a individual setting.     

睾丸生殖细胞肿瘤中CD117的表达及其对精原细胞瘤的鉴别意义

目的:探讨CD117在睾丸生殖细胞肿瘤中的表达及其在鉴别睾丸精原细胞瘤和非精原细胞瘤中的价值和生物学意义。方法:采用CD117单克隆抗体对74例睾丸生殖细胞肿瘤和20例正常睾丸组织进行免疫组化染色,测定不同组织中CD117表达的阳性率、染色密度和染色强度,采用免疫反应积分(IRS)对结果进行分析比较。结果:74例睾丸生殖细胞肿瘤中,45例(60.8%)CD117表达阳性,IRS为(3.89±3.41)分。32例精原细胞瘤中,CD117阳性表达31例,阳性率为96.9%,IRS(6.82±2.76)分,表达部位以细胞膜为主;11例混合性精原细胞瘤中,CD117阳性表达10例,阳性率为90.9%,均为在精原细胞瘤成分中呈弱阳性表达,IRS为(1.25±0.42)分;31例非精原细胞瘤中CD117表达阳性者仅4例,阳性率为12.9%,并且均为胞质内弱阳性染色,IRS仅为(0.60±0.16)分。不同组织来源的睾丸生殖细胞肿瘤两两之间CD117表达差异均有统计学意义(P<0.05)。20例正常睾丸组织CD117均为阳性表达,IRS为(7.30±1.89)分。结论:CD117在睾丸精原细胞瘤细胞膜上有较为特异的表达,其在睾丸生殖细胞肿瘤中的表达对于鉴别精原细胞瘤和非精原细胞瘤有重要价值。     

A case of simultaneous bilateral germ cell tumors arising from cryptorchid testes

We report a rare case of simultaneous bilateral testicular germ cell tumors arising from uncorrected cryptorchid testes. Each side had a different histological type, which consisted of pure high grade seminoma on the left side, and teratocarcinoma with choriocarcinoma and yolk sac tumor elements in addition to seminoma on the right side. Patients with cryptorchidism are known to have a higher risk of germ cell tumors. Genetic factors also may have a role in the oncogenesis in our patient, since his older brother had had a seminoma in the left cryptorchid testis previously. Both patients had the HLA-Aw24 antigen. The characteristics of familial testicular tumors are discussed.