Spermatocytic Seminoma Research Articles

Mechanisms of Germline Stem Cell Competition across Species.

In this review, we introduce the concept of cell competition, which occurs between heterogeneous neighboring cell populations. Cells with higher relative fitness become "winners" that outcompete cells of lower relative fitness ("losers"). We discuss the idea of super-competitors, mutant cells that expand at the expense of wild-type cells. Work on adult stem cells (ASCs) has revealed principles of neutral competition, wherein ASCs can be stochastically lost and replaced, and of biased competition, in which a winning ASC with a competitive advantage replaces its neighbors. Germline stem cells (GSCs) are ASCs that are uniquely endowed with the ability to produce gametes and, therefore, impact the next generation. Mechanisms of GSC competition have been elucidated by studies in Drosophila gonads, tunicates, and the mammalian testis. Competition between ASCs is thought to underlie various forms of cancer, including spermatocytic tumors in the human testis. Paternal age effect (PAE) disorders are caused by de novo mutations in human GSCs that increase their competitive ability and make them more likely to be inherited, leading to skeletal and craniofacial abnormalities in offspring. Given its widespread effects on human health, it is important to study GSC competition to elucidate how cells can become winners or losers.

Analysis of MicroRNA-371-373 supports that a subset of spermatocytic tumors demonstrates biologic features similar to those of GCNIS-derived germ cell tumors

Spermatocytic tumors are rare testicular tumors occurring predominantly in older men. Most show a classical tripartite morphology (different from seminoma) and are benign. However, well-documented cases of malignant spermatocytic tumors exist. Our previous work showed that a subset of spermatocytic tumors exhibiting TP53 mutations, DNA methylation profiles closer to seminomas, and/or gains in chromosome 12p exhibited aggressive characteristics, including sarcomatoid transformation and metastatic dissemination. The microRNA-371-373 cluster is a promising biomarker which is upregulated in non-teratoma germ cell tumors with malignant behavior. In this work we analyze microRNAs-371-373 b y quantitative real-time polymerase chain reaction in 18 spermatocytic tumors representative of the whole clinical spectrum, including 6 with aggressive features (sarcomatoid transformation, metastases, or gains in chromosome 12p). The levels of microRNAs-371-373 were significantly higher in non-teratoma germ cell tumors compared to spermatocytic tumors, overall (p < 0.0001). Importantly, levels of microRNA-371-373 were higher in spermatocytic tumors with aggressive features compared to non-aggressive neoplasms. The highest levels were observed in one tumor showing isochromosome 12p. These results further support our previous findings that a subset of spermatocytic tumors are intermediate between so-called type II and type III germ cell tumors and that embryonic microRNAs play a role in aggressive behavior in spermatocytic tumors. Accordingly, this subset of tumors may behave aggressively and require close follow up. In the future, this opens an opportunity for microRNA testing in serum of spermatocytic tumor patients for risk stratification purposes.

New analysis of atypical spermatocytic tumours reveals extensive heterogeneity and plasticity of germ cell tumours†.

Testicular germ cell tumours (TGCTs) derived from immature (type I) and pluripotent germ cell neoplasia in situ (GCNIS, type II) are characterised by remarkable phenotypic heterogeneity and plasticity. In contrast, the rare spermatocytic tumour (SpT, type III), derived from mature spermatogonia, is considered a homogenous and benign tumour but may occasionally present as an anaplastic or an aggressive sarcomatoid tumour. While various oncogenic processes had been proposed, the precise mechanism driving malignant progression remained elusive until the molecular characterisation of a series of atypical SpTs described in a recent issue of The Journal of Pathology. The emerging picture suggests the presence of two distinct trajectories for SpTs, involving either RAS/mitogen-activated protein kinase pathway mutations or a ploidy shift with secondary TP53 mutations and/or gain of chromosome 12p, the latter known as pathognomonic for type II GCNIS-derived TGCTs. Here, we discuss the implications of these findings, seen from the perspective of germ cell biology and the unique features of different TGCTs. The evolving phenotype of SpTs, induced by genomic and epigenetic changes, illustrates that the concept of plasticity applies to all germ cell tumours, making them inherently heterogenous and capable of significant transformation during progression. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Ternate and Trine - Spermatocytic Tumour

Spermatocytic Tumour emerges as a polymorphous, tripartite germ cell neoplasm reminiscent of developing spermatogonia, non-concordant to germ cell neoplasia in situ and demonstrates favorable prognostic outcomes. Tumefaction demonstrates aneuploidy and tumour cells characteristically lack anomalies within chromosome 12p. Cytological examination exhibits a cellular neoplastic component of variable magnitude as miniature cells, predominant intermediate cells and enlarged cells. Upon microscopy, pathognomonic tripartite cellular component is constituted of cells of variable magnitude described as miniature cells, intermediate cells and giant cells. Tumour configures nodules, cord-like pattern or peripheral inter-tubular cells enmeshed within a fibrinous perimeter.

Histological Typing and Morphological Characterization of Canine Seminomas

The aim of this study was to evaluate seminomas based on cell morphology and histological structures and classify them into subtypes. Thirty canine seminomas were stained with hematoxylin-eosin (HE) and Periodic Acid Schiff (PAS). PAS-positive cases were classified as Classical seminoma (CS) (n:5), while PAS-negative cases were categorized as Spermatocytic seminoma (SS) (n:23). Cases exhibiting both positive and negative staining were evaluated as Spermatocytic/Classical seminoma (n:2). Carcinoma in situ were observed in the cases with Classical seminoma (n:3). The cell morphology and mitotic indices of each case were given in detail. Canine seminomas were classified into three subtypes: intratubular (n:12), diffuse (n:1), and intratubular/diffuse (n:10). As a result, it was thought that SS and CS types could be observed together, and it was observed that the intratubular/diffuse subtype is a third type characterized by its transformation from intratubular to diffuse form.

Genomic analysis of spermatocytic tumors demonstrates recurrent molecular alterations in cases with malignant clinical behavior.

Spermatocytic tumor (ST) is a rare type of germ cell tumor that occurs exclusively in the postpubertal testis and typically affects elderly men. Most STs are benign, but rare cases exhibit aggressive clinical behavior, often in association with transition to sarcomatoid histology. Limited molecular analyses have been performed on STs; therefore, their genomic and epigenomic features remain incompletely described. Twenty-seven samples from 25 individual patients were analyzed with a combination of DNA sequencing panels, genomic methylation profiling, SNP array, isochromosome (12p) [i(12p)] FISH, and immunohistochemistry. The series included five metastasizing tumors (three with sarcomatoid transformation, one anaplastic, and one conventional) and 20 non-metastasizing tumors (14 anaplastic and six conventional). Anaplastic tumors comprised a monomorphic population of intermediate-sized neoplastic cells, as previously described. Multiomic analyses demonstrated that there were two genomic subgroups of STs: one with diploid genomes and hotspot RAS/RAF variants and the other with global ploidy shift and absence of recurrent mutations. Relative gain of chromosome 9 was a consistent finding in both subgroups. A comparison of metastasizing and non-metastasizing cases demonstrated that aggressive behavior was associated with the acquisition of pathogenic TP53 mutations and/or relative gains of 12p/i(12p). In cases with sarcomatoid transformation, TP53 mutations seem to underlie the transition to sarcomatoid histology. Genomic methylation analysis demonstrated that aggressive cases with gains of 12p cluster closer to pure seminomas than to STs without gains of 12p. In conclusion, STs include two genomic subgroups, characterized by global ploidy shifts without recurrent mutations and diploid genomes with RAS/RAF hotspot mutations, respectively. Biologic progression was associated with relative gains of 12p and TP53 mutations. The findings in STs with relative gains of 12p suggest that they may exhibit biologic characteristics akin to those seen in germ cell neoplasia in situ-related germ cell tumors rather than non-germ cell neoplasia in situ-derived STs. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

SPERMATOCYTIC SEMINOMA-A RARE CASE REPORT

A rare yet distinct testicular germ cell tumor is spermatocytic seminoma which represent less than 1% of testicular cancers. It was first recognized by Masson et.al in 1946. It is between 25 and 40 times less frequent than the typical seminoma. An older presentation age and a decreased propensity to metastasis are the clinical characteristics that set out spermatocytic seminoma from classical seminoma. Spermatocytic seminoma never arises in any location other than the testis that is unrelated to other varieties of germ cell cancers, in contrast to the typical seminoma, which develops in the extragonadal sites as a primary tumor (where it is known as a germinoma) and typically occurs with other forms of germ cell tumor. It has a better prognosis.. The preferred treatment is orchidectomy. Radiotherapy is not required to be given after it.

Spermatocytic Tumor: A Review.

Spermatocytic tumor (ST) is a very rare disease, accounting for approximately 1% of testicular cancers. Previously classified as spermatocytic seminoma, it is currently classified within the non-germ neoplasia in-situ-derived tumors and has different clinical-pathologic features when compared with other forms of germ cell tumors (GCTs). A web-based search of MEDLINE/PubMed library data was performed in order to identify pertinent articles. In the vast majority of cases, STs are diagnosed at stage I and carry a very good prognosis. The treatment of choice is orchiectomy alone. Nevertheless, there are two rare variants of STs having very aggressive behavior, namely anaplastic ST and ST with sarcomatous transformation, that are resistant to systemic treatments and their prognosis is very poor. We have summarized all the epidemiological, pathological and clinical features available in the literature regarding STs that have to be considered as a specific entity compared to other germ GCTs, including seminoma. With the aim of improving the knowledge of this rare disease, an international registry is required.

SOME PATHOMORPHOLOGICAL FEATURES OF GERM CELL TUMORS OF TESTICLE

Objective: This study aims at identifying the main individual clinical and morphological features of germ cell testicular tumours through a detailed pathomorphological analysis of biopsy and postoperative material.&#x0D; Materials and Methods: The study involved the examination and analysis of archival biopsy and post- operative material of testicular cancer cases in Poltava and the Poltava region between 2018 and 2022. The samples were obtained from the Poltava Regional Pathology Bureau. Histological preparations were made using standard methods, stained with haematoxylin and eosin, and subjected to microscopic examination.&#x0D; Results: A total of 22 cases of testicular cancer were registered in the Poltava Regional Pathology Bureau between 2018 and 2022. The average age of men diagnosed with these tumours was 43.6±14.9 years. The study identified different types of germ cell testicular tumours, including typical seminoma, spermatocytic seminoma, embryonal cancer, and mixed germinative tumours (combinations of spermatocytic seminoma, embryonal cancer, and teratoma; combinations of typical seminoma and embryonal cancer; combinations of embryonal cancer and teratoma). Microscopic examination revealed histological features specific to each of these tumour types.&#x0D; Conclusions: Among germ cell tumours of the testicles in the Poltava region over the past 5 years, typical seminoma was the most frequently detected type, an average age of patients with the diagnosis is 50 years. The youngest patient diagnosed with testicular cancer was 21 years old, who had embryonal cancer. Germ cell testicular tumours have a heterogeneous structure, posing challenges in making pathomorphological di- agnoses. However, detailed microscopic examination enables the verification of the histological type of the tumour and identification of individual features of germinogenic neoplasias.

Clinicopathological features and the diagnostic value of SSX_CT immunohistochemistry on testicular spermatogenic tumors

目的： 探讨精母细胞性肿瘤（spermatocytic tumour，ST）的临床病理特征，并评估SSX_CT免疫组织化学抗体在ST诊断及鉴别诊断中的作用。 方法： 对2007年1月至2022年3月空军军医大学第一附属医院手术治疗的60例发生于睾丸的肿瘤进行HE及免疫组织化学染色，并收集患者的临床病理信息。 结果： ST共6例，其中1例可见肉瘤样成分。SSX_CT在6例ST中均为弥漫强阳性，肉瘤样变区域为阴性；在7例精原细胞瘤（7/17，41.1%）中呈灶性弱阳性表达；在其余肿瘤中均不表达。 结论： SSX_CT是诊断ST的高度灵敏的生物学标志物。.

The value of contrast-enhanced ultrasonography in differential diagnosis of primary testicular germ cell tumors and non-germ cell tumors over 50 years old.

Unlike young and middle-aged patients, seminoma is not common in patients with primary testicular tumors over the age of 50, so it cannot follow the general ideas and norms for diagnosing and treating testicular tumors, and its characteristics need to be considered separately. The conventional ultrasonography and contrast-enhanced ultrasonography (CEUS) findings of primary testicular tumors in patients over 50 years old were retrospectively analyzed and compared with the pathological results to compare the diagnostic value of these two methods. Of the 13 primary testicular tumors, 8 were primary lymphomas. Conventional ultrasound of 13 cases of testicular tumors showed hypoechoic with rich blood flow, and it was difficult to identify the type accurately. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of conventional ultrasonography in diagnosing non-germ cell tumors (lymphoma and Leydig cell tumor) were 40.0%, 33.3%, 66.7%, 14.3%, and 38.5%, respectively. CEUS findings: 7 of 8 lymphomas showed uniform hyperenhancement. 2 cases of Leydig cell tumors showed uniform high enhancement. 2 cases of seminoma and 1 case of spermatocytic tumor showed heterogeneous enhancement, with necrosis in the interior. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy rate of non-germ cell tumor diagnosis according to the non-necrotic area of CEUS were 90.0%, 100.0%, 100.0%, 75.0% and 92.3%, respectively. Compared with conventional ultrasound, the difference was statistically significant (P=0.039). Primary testicular tumors in patients over 50 years old are mainly lymphoma, and CEUS is significantly different between germ cell tumors and non-germ cell tumors. Compared with conventional ultrasound, CEUS can distinguish testicular germ cell tumors from non-germ cell tumors more accurately. Preoperative ultrasonography is significant for accurate diagnosis and can guide clinical treatment.

Clinicopathological Study of Testicular Lesions in a Tertiary Care Centre of Dakshina Kannada, India

Introduction: Testicular biopsies are performed for both diagnostic and therapeutic purposes. Diagnostic testicular biopsies are usually performed as a part of a male infertility work-up. Therapeutic testicular excision biopsies are performed for a wide range of disorders, including neoplastic lesions, inflammatory lesions, cryptorchidism, testicular trauma, and as a part of prophylactic treatment of carcinoma prostate. Aim: To evaluate the indications for orchidectomy and diagnostic testicular biopsies and to understand the histopathological spectrum of testicular lesions and concordance with clinical diagnosis. Materials and Methods: This was a retrospective study conducted in the Department of Pathology, Father Muller Medical College, Mangalore, Karnataka, India. The study period is from July 2017 to June 2020. Data was collected and analysed in August 2020. All testis’ biopsies, including excision and diagnostic biopsies, are included in the study. Histopathological findings and the clinical diagnosis were evaluated for concordance. Data were tabulated and statistically evaluated for age distribution, laterality, and frequency using Microsoft Excel 2021. Percentages for the variables and concordance rate were calculated. Results: A total of 139 cases (mean age 54.5 years) were included in the study. Prophylactic orchidectomy for carcinoma prostate (64/139=46.04%) was the most common clinical indication. Non neoplastic lesions account for 48.20% (67/139). Frequent non neoplastic lesions are testicular torsion (23/139=16.55%) and abscess (12/139=8.63%), followed by cryptorchidism (9/139=6.47%). Left-sided lesions are more frequent than right-sided lesions. Histopathology confirmed two cases of suspected male infertility and Androgen Insensitivity Syndrome (AIS). Neoplastic lesion accounts to 6.47% (9/139). Frequent neoplasm in the study was seminoma (3/139=2.16%), followed by lymphoma (2/139=1.44%). Other neoplasms included in the study were mixed germ cell tumours, post-pubertal teratoma, and spermatocytic tumour. Testicular tuberculosis accounts to 1.44% (2/139) in the present population. Conclusion: Non neoplastic lesions were common compared to testicular neoplasms. Testicular torsion, followed by abscess, was the most common indication for orchidectomy. Testicular Tuberculosis can mimic a neoplasm on clinical and radiological work-up. Hence, careful evaluation has to be performed in young suspected cases of tuberculosis.

The value of contrast-enhanced ultrasonography in the diagnosis of primary testicular non-neoplastic and neoplastic lesions in adults

BackgroundDifferent pathological types of testicular tumors are treated differently. Malignant germ cell tumors require radical orchiectomy, while benign tumors may only need mass enucleation. Contrast-enhanced ultrasonography (CEUS) is more sensitive than conventional ultrasonography in displaying tumor microvessels, which helps distinguish between benign and malignant tumors.MethodsThis was a retrospective analysis of 35 patients with pathological-confirmed primary testicular non-neoplastic and neoplastic lesions in our hospital from February 2017 to February 2022. Conventional ultrasonography and CEUS imaging findings of included lesions were retrospectively analyzed and their diagnostic values were compared with the pathological results.ResultsThere were 13 cases of benign testicular lesions (including 1 case of spontaneous hematoma, 2 cases of segmental infarctions, 5 cases of epidermoid cysts, 2 cases of Sertoli cell tumors, and 3 cases of Leydig cell tumors) and 23 cases of malignant testicular lesions (including 10 cases of seminomas, 1 case of embryonal carcinoma, 2 cases of mixed germ cell tumors, 2 cases of spermatocytic tumors, and 8 cases of lymphomas). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy rates of conventional ultrasound in diagnosing benign testicular tumors by "onion skin-like" echo (epidermoid cysts) and peripheral annular blood flow were 30.8%, 100.0%, 100.0%, 71.9% and 75.0%, respectively. All testicular non-neoplastic lesions and epidermoid cysts showed no enhancement by CEUS. All Sertoli-Leydig cell tumors (SLCTs)’ CEUS imaging showed uniform high enhancement (no necrosis area), fast forward, and slow backward. 80.0% (12/15) malignant germ cell tumors showed heterogeneous enhancement and fast forward and fast backward in CEUS. All lymphomas showed fast forward and fast backward, and 87.5% (7/8) of them showed uniform high levels of enhancement in CEUS. According to CEUS without enhancement (non-neoplastic lesions and epidermoid cysts) and uniform high enhancement with fast forward and slow backward (SLCT), the sensitivity, specificity, positive predictive value, negative predictive value and accuracy rates for diagnosing benign testicular tumors were all 100.0%. Compared with conventional ultrasound, the difference was statistically significant (p = 0.004).ConclusionsCEUS could accurately distinguish between benign and malignant testicular tumors, as well as differentiate specific pathological types (testicular focal infarction, epidermoid cysts, spermatocytic tumors, SLTC and lymphoma). Accurate preoperative diagnosis is critical for guiding the selection of appropriate treatment plans for different pathological types of testicular tumors.

First cytogenomic characterization of murine testis tumor cell line MLTC-1

The cell line MLTC-1 was established in 1982 as a transplantable Leydig cell tumor from a C57BL/6 mouse. The cell line has already been applied in &amp;gt;100 studies: still, the only information about its genetic content is given in the first description: MLTC-1 initially had a polyploid karyotype. Here, a molecular karyotyping and multicolor banding-based molecular cytogenetic study was done to provide the first chromosomal/ (molecular) cytogenetic characterization of MLTC-1. A hexaploid karyotype with 72 to 105 chromosomes was hereby characterized. Besides polyploidy, unbalanced two- and three-way translocations, dicentrics and one neocentric derivative were identified. Also, no Y-chromosome could be detected in this clearly male derived cell line. Overall, a completely unbalanced genome is present in MLTC-1 with ~20 regions being subject to copy number losses or gains. After translating these imbalances into the human genome in a standardized way, a 40% match of imbalances with human Leydig cell tumors was evident; however, about the same rate of concordance was detectable for human spermatocytic seminomas and non-seminomas as well as testicular germ cell tumor. Accordingly, MLTC-1 is better suited as an advanced testicular germ cell tumor model in general, rather than specifically for human Leydig cell tumors.

Spermatocytic tumor of testis: A case series of 26 cases elucidating unusual patterns with diagnostic and treatment dilemmas.

Spermatocytic tumours are a rare subset of testicular tumours seen in elderly patients with distinct clinicopathological features and a favourable outcome. The typical presentation and characteristic histological features usually suffice for the diagnosis. Most of the cases are amenable to surgical excision. However, occasional cases which have a sarcomatous transformation may behave more aggressively and warrant adjuvant therapy. We present the clinicopathological features of a series of 26 cases diagnosed as Spermatocytic tumour at our tertiary cancer institute from 2002-2019. Twenty-four of these cases had the typical cytological features of a spermatocytic tumour while two cases showed sarcomatous change, one with rhabdomyosarcomatous differentiation and the other being an undifferentiated spindle cell sarcoma. Although the tumor can show varied patterns, the tripartite cytomorphology is typical in all cases. Careful note of these patterns and variations in histology is essential to prevent an erroneous diagnosis of other testicular neoplasms and guide the therapy.

Malignant germ cell tumors in men aged 50 years and over are associated with adverse pathologic features and higher stage at presentation

BackgroundGerm cell tumors (GCT) are the most common malignancy in men in the third and fourth decades of life. The occurrence of malignant GCT in men aged 50 years or over is rare, and their histopathologic characteristics and outcome is insufficiently characterized in the medical literature. Hence, we report the histopathologic features and clinical outcome of malignant GCTs in men aged ≥50 years at our institution. DesignWe performed a retrospective search of our database from 2005 to 2021 to identify men aged 50 years or older with malignant GCT. Cases of spermatocytic tumor were excluded. Clinical and histopathologic features of the tumors were reviewed. ResultsForty-seven cases were identified, showing a sharp decline in incidence over the age of 65. Thirty-nine (83 %) tumors were testicular while eight (17 %) were non-testicular in presentation. Cases included 26 (55 %) seminomas, 15 (32 %) non-seminoma/mixed malignant GCT, and 5 (11 %) regressed testicular germ cell tumors. The most common component in mixed malignant GCTs was embryonal carcinoma (77 %), followed by seminoma and yolk sac tumor (62 % each). Germ cell neoplasia in situ (GCNIS) accompanied 57 % of the cases. Aggressive pathologic features, including lymphovascular invasion, retroperitoneal/lymph node involvement and higher stage at presentation, were identified in a significant proportion of cases (36/47, 77 %). Clinical follow up showed six patients (14 %) died of disease-related causes. ConclusionOur findings expand and corroborate the previously reported data on malignant GCT in older men. Unique characteristics include tendency for higher stage at presentation with adverse pathologic features and more aggressive clinical course.

Clinical and Histological Findings of Non-Experimentally Induced Seminomas in Adult Zebrafish

The present study investigated the macroscopical and histological features of two spontaneous seminomas developed by zebrafish adults. Two wild-type male zebrafish of AB/TU strain aged 2 and 3 years, respectively, developed gross pathological signs consisting of asymmetrical swollen abdomens. In one fish, named fish 1, the testicular alteration is referred to as one testis (the right one), while in fish 2, both testes were altered in their size and shape. No signs of invasion were reported. The histological analysis revealed an extensive differentiation of germ cells in various developmental stages without any oocyte, and both lesions were compatible with spermatocytic and intratubular seminomas. The etiology and the pathogenesis of the reported lesions could be related to an intricate and interconnected network of intrinsic and extrinsic factors, including the housing condition, diet, genetic background, and operator training.

Widespread metastasis of a spermatocytic seminoma with concomitant hepatic peliosis in a Southern African hedgehog ( Atelerix frontalis )

A six-year-old intact male Southern African hedgehog (Atelerix frontalis) presented with a history of chronic mild to moderate weight loss, and sub-acute hind limb ataxia that progressed to complete paralysis, at which point the hedgehog was euthanised. At autopsy, a large multinodular pale mass had completely replaced the left testicle and transcoelomically metastasised to the diaphragm and the peri-renal area, from where it then invaded the vertebral column and spinal cord. Multifocal, irregular to round, well-demarcated, blood-filled, proliferative lesions were also present in the hepatic parenchyma. Histological analysis of both the testis and metastatic lesions revealed diffuse sheets of neoplastic cells with moderate pale cytoplasm, large irregular to round nuclei and mostly one prominent magenta nucleolus, consistent with metastatic seminoma. The neoplastic cells were negative for periodic acid-Schiff (PAS) stain and positive for CD117 by immunohistochemistry (IHC). Taken together with the morphology of the neoplastic cells and the advanced age of the animal, this is suggestive of a spermatocytic seminoma. Histological analysis of the liver revealed multifocal lesions consisting of large anastomosing blood-filled spaces bordered by compressed hepatocytes, consistent with hepatic peliosis. This is the first report of a neoplasm in the Southern African hedgehog (Atelerix frontalis), the first report of a metastatic seminoma in a hedgehog, together with diagnosis of spermatocytic subtype, and the first report of a hedgehog with concomitant hepatic peliosis.

Cytogenetics of spermatocytic tumors with a discussion of gain of chromosome 12p in anaplastic variants

Most spermatocytic tumors (STs) have an excellent prognosis. In rare instances, metastatic disease has been documented. However, it is unclear if aggressive tumors have specific molecular alterations. Herein, we have studied primary STs with (n=4) and without (n=3) anaplasticfeatures, including single-nucleotide polymorphism microarrays for 5 ST (nonanaplastic: 3; anaplastic: 2). The mean age at orchiectomy and tumor size was 49 years and 6.5cm, respectively. Lymphovascular invasion and necrosis were identified in 3 (of 4, 75%) anaplastic STs, including one with clinically metastatic disease and one with locally aggressive disease. None of the cases in this study exhibited sarcomatoid change. The mean mitotic count was higher in anaplastictumors (59/10 versus 10/10 high-power fields). All STs in this study were positive for SALL4 and CD117 and negative for OCT3/4 and CD30 (7/7, 100%). SSX-C positivity was identified in all but the locally aggressive anaplastic ST (5 of 6, 83%). All STs showed a consistent gain of chromosome 9 including the locus for the DMRT1 gene (5 of 5 cases, 100%), while gains of chromosome 12p were only seen in 2 (of 2) anaplasticvariants. Gains of 12p in anaplasticSTs may represent a biomarker of transformation into more aggressive tumors. Alternatively, STs with gain of 12p may represent an intermediate state between type II and type III germ cell tumors. Future studies are needed to validate whether gain of 12p is a consistent feature of STs with anaplasticmorphology and its association with aggressive clinical behavior.

First Cytogenomic Characterization of the Murine Testicular Tumor Cell Line I-10

After being established in 1967, the commercially available murine Leydig cell tumor line I-10 has been used in almost 50 published studies. I-10 has not been characterized, either at the chromosomal/ cytogenetic level or the genetic level, similar to many other murine tumor cell lines. In this study, we performed molecular karyotyping and multicolor banding-based molecular cytogenetics. A slightly hyperdiploid karyotype with 43 chromosomes was described. The main aberrations comprised several unbalanced translocations and three unusual rearrangements (two dicentric derivatives and one neocentric derivative). Nine regions showed copy number gains, and only five small chromosomal parts showed loss of copy numbers. A standardized translation of these imbalances in the human genome was performed, which showed a 63% overlap of the detected imbalances with testicular germ cell tumors, a 53% concordance with human spermatocytic seminomas and non-seminomas, and only a 36% overlap (approx.) of large copy number gains and losses were similar to the corresponding human Leydig cell tumors. However, no Y-chromosome was detected in this male-derived cell line. Overall, the I-10 cell line was found to be a testicular germ cell tumor model and cannot be treated as a model that is specific to human Leydig cell tumors. At best, it might be suited as a model for an early onset of Leydig cell tumors.