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.

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.

Sarcomatoid Spermatocytic Tumour: Report of a Rare Case and Literature Review.

Spermatocytic tumour (ST) accounts for 1% of testicular germ cell tumours. It is an indolent neoplasm with good prognosis. In approximately 6% of STs, sarcomatous dedifferentiation may occur, portending an aggressive behaviour and representing a significant diagnostic challenge that can lead to its misdiagnosis. Herein, we report the clinicopathological features of a patient with a sarcomatoid spermatocytic tumor, initially diagnosed as mixed germ cell tumour, who was referred to our institution with lung metastases mainly composed of rhabdomyosarcomatous elements. This case report illustrates the importance of recognizing this entity for adequate management of these patients.