Michalova, Kvetoslava

Aims Testicular sex cord‐stromal tumours (TSCSTs) are rare neoplasms that arise from (or show differentiation to) elements derived from the sex cords or intertubular stroma. The current classification (World Health Organization, 2022) is based almost entirely on morphology, with many tumour types such as granulosa cell tumours being defined based on their resemblance to ovarian counterparts. Recent studies have uncovered new clinicopathological, molecular and biological nuances within this group of tumours, underscoring differences with ovarian homologues. Methods and results Considering the new data, a group of genitourinary pathology experts (Testicular Sex Cord‐Stromal Tumour [TESST] group) has proposed a revised ‘TESST classification’ that incorporates the best available evidence. This classification is structured and hierarchical, composed of the following tiers: (1) group, (2) category, (3) entity and (4) histological pattern. ‘Group’ refers to the histological compartment a specific tumour belongs to (sex cords, stroma or both), whereas ‘category’ is defined by the phenotype of the tumour, taking non‐neoplastic elements of the ovary and testis as a reference. The third tier, ‘entity’, refers to neoplasms with shared clinicopathological and/or molecular features that justify classifying them as distinct types. Lastly, ‘histological patterns’ are recurrent morphological variations within entities that are not linked to distinct clinicopathological or molecular features. Conclusions We propose a classification that will provide a framework to improve current clinical management and guide future research in the field.

Aims Testicular sex cord‐stromal tumours (TSCSTs) are relatively rare, accounting for ~5% of all testicular neoplasms. They were historically classified into Leydig cell tumour, Sertoli cell tumour, granulosa cell tumour, and unclassified sex cord‐stromal tumour. More recently, classification was expanded to incorporate additional histologic types, including some associated with inherited cancer predisposition syndromes. However, the classification of TSCSTs still relies entirely on morphology, with some tumour types being defined based on their resemblance to ovarian counterparts. In recent years, molecular studies have identified drivers and genomic alterations associated with aggressive behaviour and progression; however, these findings have not yet impacted classification and management. Methods and results Under sponsorship of the International Society of Urological Pathology (ISUP) and the Genitourinary Pathology Society (GUPS), a group of genitourinary pathologists was assembled in 2023 with the aim of assessing how to use these new data to improve the classification and management of TSCSTs. Conclusions This paper summarizes the recommendations derived from the consensus activities and the first meeting of the te sticular s ex cord‐ s tromal t umour (TESST) group (held at Johns Hopkins Hospital, Baltimore, USA, 3/23/2024).

Juxtaglomerular cell tumor (JxGCT) is a rare type of renal neoplasm demonstrating morphologic overlap with some mesenchymal tumors such as glomus tumor (GT) and solitary fibrous tumor (SFT). Its oncogenic drivers remain elusive, and only a few cases have been analyzed with modern molecular techniques. In prior studies, loss of chromosomes 9 and 11 appeared to be recurrent. Recently, whole-genome analysis identified alterations involving genes of MAPK-RAS pathway in a subset, but no major pathogenic alterations have been discovered in prior whole transcriptome analyses. Considering the limited understanding of the molecular features of JxGCTs, we sought to assess a collaborative series with a multiomic approach to further define the molecular characteristics of this entity. Fifteen tumors morphologically compatible with JxGCTs were evaluated using immunohistochemistry for renin, single-nucleotide polymorphism array (SNP), low-pass whole-genome sequencing, and RNA sequencing (fusion assay). In addition, methylation analysis comparing JxGCT, GT, and SFT was performed. All cases tested with renin (n=11) showed positive staining. Multiple chromosomal abnormalities were identified in all cases analyzed (n=8), with gains of chromosomes 1p, 10, 17, and 19 and losses of chromosomes 9, 11, and 21 being recurrent. A pathogenic HRAS mutation was identified in one case as part of the SNP array analysis. Thirteen tumors were analyzed by RNA sequencing, with 2 revealing in-frame gene fusions: TFG::GPR128 (interpreted as stochastic) and NAB2::STAT6. The latter, originally diagnosed as JxGCT, was reclassified as SFT and excluded from the series. No fusions were detected in the remaining 11 cases; of note, no case harbored NOTCH fusions previously described in GT. Genomic methylation analysis showed that JxGCT, GT, and SFT form separate clusters, confirming that JxGCT represents a distinct entity (ie, different from GT). The results of our study show that JxGCTs are a distinct tumor type with a recurrent pattern of chromosomal imbalances that may play a role in oncogenesis, with MAPK-RAS pathway activation being likely a driver in a relatively small subset.

Abstract 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.

The term “idiopathic calcifying tenosynovitis” (ICT) refers to a clinically and radiologically defined syndrome of pain and tendinous calcifications, most often involving the shoulder joint. A distinctive subset of ICT cases, termed “tenosynovitis with psammomatous calcifications” (TPC), occurs in the distal extremities and shows characteristic morphology, in particular psammomatous calcifications. As only 14 cases have been reported to date, TPC remains poorly recognized by both pathologists and clinicians. Twenty-three well-characterized cases of TPC along with all available radiologic and clinical information, including follow-up, were collected. Cases occurred in 21 females and 1 male (1 patient of unknown sex), aged 16 to 75 years (mean: 41), and almost exclusively involved the fingers and toes, except for one case in the elbow and one in the knee joint. The lesions ranged from 2 to 30 mm in size (mean: 10 mm). Pain was the most common presenting symptom (12/16 patients). A history of trauma or repetitive activity was present in 6 of 15 patients. None of the individuals was known to have disorders in calcium or phosphate metabolism. Radiographic studies showed a nonspecific, calcified mass. Typical morphologic features of TPC were invariably present, with degenerating tendinous tissue containing psammomatous calcifications, surrounded by a variably cellular, CD68/CD163/CD4-positive histiocyte-rich granulomatous host reaction. HUMARA assay in one case showed a polyclonal pattern. Clinical follow-up (19 patients; mean: 5.2 y; range: 1 to 14 y) showed no local recurrences. In this, the largest study of TPC to date, we confirm striking predilection of this distinctive pseudoneoplasm for the fingers and toes of young to middle-aged women. TPC should be rigorously distinguished from other forms of ICT, which typically involve large, proximal joints, and show simply dystrophic calcification involving tendinous tissues, and from tumoral calcinosis, which also involves large joints and often is associated with calcium and/or phosphate abnormalities. TPC appears to be related to trauma and/or repetitive activity and is cured with simple excision.