Myoepithelial tumors of soft tissue and bone in children and young adults: A clinicopathologic study of 40 cases occurring in patients ≤ 21 Years of age.

Myoepithelial tumors of the soft tissue and bone occurring in patients 21 years of age and younger are rare, and their clinicopathologic features remain incompletely understood. We studied a well-characterized series of 40 such tumors. Cases were retrieved from our archives for the period 2009-2022 and re-reviewed. Available immunohistochemical and molecular genetic data was collected. Clinical information including available follow-up was obtained. The tumors occurred in 18 males and 22 females, ranging from 3 months to 21 years of age (median 11.5 years), and involved a wide variety of soft tissue (n = 36) and bone (n = 4) locations. Histologically benign myoepithelial tumors tended to occur in adolescents (median age 14.5 years; range 5-21 years), whereas myoepithelial carcinomas occurred in younger patients (median age 8.5 years; range 3 months-20 years). Microscopically, the tumors showed a complex admixture of epithelioid, plasmacytoid and spindled cells in a variably hyalinized, myxoid, chondroid or chondromyxoid background. Small subsets of histologically malignant tumors had rhabdoid or "round cell" features. Immunohistochemistry showed 35/40 (88%) cases to be positive with at least one keratin antibody. The 5 keratin-negative tumors were uniformly positive for S100 protein and/or SOX10 and expressed EMA (4 cases) and/or p63 (3 cases). EMA, SMA and GFAP were positive in 21/25 (84%), 13/21 (62%), and 8/21 (38%) tumors, respectively. SMARCB1 and SMARCA4 expression was retained in 29/31 (94%) and 22/22 (100%) of cases, respectively. FISH for EWSR1 gene rearrangement was positive in 6/18 (33%) tested cases. Two EWSR1-negative tumors were also FUS-negative. NGS identified EWSR1::POU5F1, FUS::KLF17, and BRD4::CITED1 gene fusions in 3 tested cases. Clinical follow-up (22 patients; median 23 months; range 1-119 months) showed 3 patients with local recurrences and 5 with distant metastases (lymph nodes, lung, and brain). Three patients died of disease, 3 were alive with recurrent or unresectable disease, and 16 were disease-free. Adverse clinical outcomes were seen only in patients with malignant tumors. We conclude that myoepithelial neoplasms of soft tissue and bone are over-repesented in patients ≤21 years of age, more often histologically malignant, and potentially lethal. Histologic evaluation appears to reliably predict the behavior of these rare tumors.

Recurrent MTOR Mutations in Renal Cell Carcinoma With Fibromyomatous Stroma: A Report of 2 Tumors.

Renal cell carcinoma with fibromyomatous stroma, recognized as a provisional entity in the current 2022 World Health Organization classification of renal neoplasms, is rare. Recent evidence suggests recurrent alterations in the mTOR pathway, supporting its recognition as a distinct entity. Herein, we report 2 renal cell carcinomas with fibromyomatous stroma with MTOR mutations occurring in 62- and 72-year-old women and review the literature to support its recognition as a distinct entity, focusing on the characteristic morphology, immunohistochemical staining patterns as well as genetic alterations.

Adamantinoma-Like Ewing Sarcoma Mimicking Merkel Cell Carcinoma in the Parotid Gland: A Diagnostic Pitfall.

Adamantinoma-like Ewing sarcoma (ALES) is a newly described rare entity, which shows EWSR1::FLI1 rearrangement characteristic of Ewing sarcoma. This can be diagnostically challenging as it manifests histologically with epithelial differentiation and has diffuse keratin expression as well as p40 and p60 positivity. We hereby report a case of ALES in a 33-year-old woman with a past medical history of breast carcinoma who presented with a right-sided parotid mass. CT scan of the neck showed a heterogenous mass within the superficial lobe, measuring 17 mm in diameter for which the patient underwent superficial parotidectomy. Histopathology of the mass revealed a malignant neoplasm formed of solid nests, cords and sheets of cells with minimal cytoplasm and monomorphic nuclei with granular chromatin and indistinct nucleoli. Brisk mitotic activity and tumor necrosis were also present. The tumor showed strong and diffuse reactivity for pankeratin (clone AE1/AE3) and keratin 20, both in a dot-like pattern, raising the suspicion of metastatic Merkel cell carcinoma; however, molecular studies showed EWSR1::FLI1 rearrangement, supporting the diagnosis of ALES. In summary, it is prudent to have knowledge about this entity to avoid its misdiagnosis as other malignancies of the head and neck region which exhibit a different clinical course, prognosis and hence treatment modalities.

Adipocytic Differentiation in a Sertoli Cell Tumor.

Testicular sex cord-stromal tumors are clonal neoplasms, with the majority being of Leydig cell followed by Sertoli cell origins. In Leydig cell tumors, adipocytic differentiation has been previously reported as a possible distinguishing feature, which has not been reported in other sex cord-stromal tumors. Herein, we report a case of a 48-year-old man who presented with an incidentally discovered 1.1 cm testicular mass, for which he underwent partial orchiectomy. Microscopically, the tumor showed features consistent with sex cord-stromal tumor with strong and diffuse nuclear and cytoplasmic reaction for B-catenin immunohistochemistry, supporting the diagnosis of Sertoli cell tumor. A novel adipocytic differentiation, reported previously in Leydig cell tumors, was present in this tumor.

Paratesticular Dedifferentiated Liposarcoma with Epithelioid Features: A Diagnostic Pitfall.

Well-differentiated/dedifferentiated liposarcoma (WDLPS/DDLPS) represent a significant number of sarcomas arising within the paratesticular region. DDLPS is notorious for a broad histologic spectrum, but epithelioid morphology is rare. Herein, we describe a unique case of paratesticular DDLPS with prominent epithelioid features and molecular confirmation. The patient is 71-year-old-male who presented with multiple paratesticular masses. Morphologic review of the resection specimen revealed a biphasic adipocytic neoplasm consistent with DDLPS. Additionally, epithelioid foci with acinar and nested architecture and focal keratin expression were noted. These areas raised the possibility of a secondary neoplasm including sex cord stromal tumor, germ cell tumor, and paraganglioma. However, MDM2 immunohistochemistry and FISH showed these areas to express MDM2 and exhibit MDM2 amplification, respectively, confirming that they represented a component of DDLPS. This case further highlights the morphologic diversity of DDLPS as well as the utility of MDM2 studies.

EWSR1-PATZ1 fusion renal cell carcinoma: a recurrent gene fusion characterizing thyroid-like follicular renal cell carcinoma.

Thyroid-like follicular renal cell carcinoma is an uncommon kidney tumor with no distinct molecular alteration described to date. This cohort of eight women with mean and median ages of 45 and 46 years, respectively (range 19-65 years), had unencapsulated, well-circumscribed tumors composed of tightly packed anastomosing follicle-like cysts filled with eosinophilic colloid-like material and lined by cuboidal cells with high nuclear to cytoplasmic ratios, oval to elongated nuclei with perpendicular arrangement toward the lumens, and prominent nuclear overlapping. The stroma between these was minimal with the exception of two tumors. Calcifications and necrosis were absent. Immunohistochemically, the tumors were positive for KRT19 (7/7), PAX8 (5/5), cyclin D1 (6/6), KRT7 (5/7), and AMACR (1/5; focal, weak), and were negative for WT1, TTF1 (transcription termination factor-1), and thyroglobulin. In three of three tumors tested molecularly, EWSR1-PATZ1 fusion was identified by RNA sequencing and confirmed by RT-PCR and Sanger sequencing. Over a follow-up period of 1-7 years, no evidence of recurrence or metastasis has been detected. The EWSR1-PATZ1 fusion has been recognized as a recurrent alteration in a subset of round to spindle cell sarcomas with EWSR1-non-ETS fusions (EWSR1-PATZ1 sarcoma) and in several central nervous system tumors. The finding of an EWSR1-PATZ1 fusion in all three of the thyroid-like follicular renal cell carcinomas for which sufficient tissue was available for genomic profiling provides the first distinct molecular abnormality in thyroid-like follicular renal cell carcinomas, supporting its designation as a distinct diagnostic entity.

Appendageal tumors and tumor-like lesions of the testis and paratestis: a 32-year experience at a single institution.

The testicular hilum and paratestis contain several embryologically diverse anatomic structures, including the spermatic cord, tunica vaginalis, epididymis, rete testis, and several other embryonic remnants. Several benign and malignant lesions arise from these morphologically distinct structures, and owing to their proximity, it is challenging to classify and subsequently stage these tumors. Herein, we conducted a retrospective review of the paratesticular appendageal and rete testis tumors and tumor-like lesions diagnosed at our department from 1985 to 2016. Soft-tissue lesions/tumors were excluded. A total of 146 paratesticular appendageal and rete testis tumors and tumor-like lesions were identified. Most were benign (n = 107; 73%). Adenomatoid tumor (26%) was the most common benign tumor, followed by different types of cysts (19%), mesothelial hyperplasia (18%), serous cystadenoma (5.5%), and rete testis adenoma (4%). Malignant lesions comprised 23% of the cases, with mesothelioma the most common (15%), followed by adenocarcinoma of the rete testis (4%), serous cystadenocarcinoma (2%), and papillary and clear cell adenocarcinoma of the epididymis (2%). Finally, serous borderline tumors and melanotic neuroectodermal tumor (retinal anlage tumors) comprised the remaining 4% of cases. In conclusion, a wide range of benign and malignant lesions can arise from the paratesticular region. Awareness of these lesions and their histologic spectrum is crucial to avoid diagnostic pitfalls and to allow pathologists to establish a correct diagnosis and subsequent treatment plan.

Primary Renal Mesenchymal Neoplasms in Nephrectomy Specimens: A 16-Year Survey of Primary and Incidental Cases From a Single Institution.

Context. Primary renal mesenchymal neoplasms are rare but diverse. Several neoplasms of mesenchymal derivation can arise as a primary renal mass; however, incidental tumors are identified in nephrectomies performed for end-stage renal disease or other malignant epithelial renal neoplasms. In this article, we document their frequencies with demographic information in nephrectomy specimens. Design. We retrospectively searched our database for nephrectomy specimens from the year 2000 to 2016. Results. A total of 224 cases were identified with an incidence rate of 4.4% (224/5128). One hundred ninety (85%) neoplasms were benign, 27 (12%) were malignant, and 7 (3%) were of intermediate biologic behavior. The majority of cases occurred in adults (93%, 208/224), and 39% of cases represented an incidental finding. The most common neoplasms were angiomyolipoma (58%) and renomedullary interstitial cell tumor (17%). Malignant mesenchymal kidney tumors are rare (0.39% of nephrectomy specimens). The most common adults' malignant tumors in our survey were synovial sarcoma and Ewing's sarcoma. Conclusion. Primary renal mesenchymal tumors are rare and are mostly benign in nature with many incidentally identified lesions. They arise in different age groups with malignant lesions usually presenting at a younger mean age.