Clear cell renal cell carcinoma with BAP1 mutation: a report of two cases.

Clear cell renal cell carcinoma is the most common subtype of renal cell carcinomas (RCCs) and accounts for 60%-70% of all RCCs cases in adults. Aberrations in the von Hippel-Lindau (VHL) gene on chromosome 3p occurred in > 90% of clear cell RCCs. Other tumor suppressor genes located on chromosome 3p, such as BAP1, PBRM1, and SETD2, also contribute to tumorigenesis. Clear cell RCCs with both BAP1 and VHL mutations may display distinctive histopathological features. Here, we report two cases of clear cell RCCs with BAP1 mutation. One tumor had VHL, BAP-1, and RAF1 mutations and the tumor nests and alveoli of tumor cells were surrounded by proliferative vessels and the optically clear cytoplasm contained numerous eosinophilic granules and hyaline globules of varying sizes. The other tumor had BAP1 and ATM mutations, and demonstrated clear cells with numerous eosinophilic granules and other typical histopathological features of conventional clear cell RCC. Furthermore, many tumor nodules with dense peripheral lymphocytic infiltrates contained rhabdoid cells. Sarcomatoid cells were also observed. Both tumor cells showed high-grade nuclei. Clear cell RCCs with BAP1 mutation exhibit aggressive clinical behaviors.

Synchronous Occurrence of Splenic Pleomorphic Mantle Cell Lymphoma and Esophageal Adenocarcinoma with Overexpression of BCL1 Protein.

Synchronous occurrences of mantle cell lymphoma (MCL), or intermediate lymphocytic lymphoma, and other malignancies are rare. Such cases present diagnostic and especially therapeutic challenges, making them of particular interest to study. We report a case of synchronic MCL and an esophageal tumor in an elderly male patient. Morphologically, the tumors were classified as splenic pleomorphic MCL and adenocarcinoma of the esophagus occurring concurrently. The pleomorphic MCL mimicked diffuse large B cell lymphoma (DLBCL) but lacked larger centroblast- or immunoblast-like cells. Curiously, both tumors overexpressed cyclin D1 by immunohistochemistry. This is an important feature that distinguishes MCL pathologically from two of its closest entities in the differential diagnosis: chronic lymphocytic leukemia and DLBCL, the latter of which mantle cells cannot transform into. The lymphoproliferation revealed IGH/CCND1 translocation by FISH, but the esophageal adenocarcinoma only showed CCND1 aneuploidy without break-apart signals. Since the gastrointestinal (GI) tract is a common site of extranodal involvement by MCL and lymphomatous polyposis can present as GI polyps, adequate care was taken to differentiate the esophageal adenocarcinoma from advanced stagings of MCL, as well as metastatic adenocarcinoma. Despite numerous immunohistochemical stainings studied, only BCL1 was demonstrated to have partial overlap in both tumors. The patient underwent esophagectomy and splenectomy. A subsequent metastatic primary lung squamous cell carcinoma was diagnosed, after which the patient expired. MCL typically presents at an advanced stage and has been deemed incurable with a prognosis of only several years. It is unclear whether the patient succumbed to complications of his MCL or the metastatic squamous cell carcinoma. Furthermore, he was lost to follow-up for a year and only received treatment after his third cancer was diagnosed. We have reviewed previous reports of synchronic mantle cell lymphoma and other solid tumors or hematological malignancies in the literature.

Renal cell carcinoma with leiomyomatous stroma: a review of an emerging entity distinct from clear cell conventional renal cell carcinoma.

Clear cell renal cell carcinomas accounts for 65 to 75% of all malignant renal tumors. The International Society of Urological Pathology 2012 Vancouver Classification of renal neoplasia and the World Health Organization 2016 Classification of renal tumors have included renal cell carcinoma with leiomyomatous stroma in a category of emerging/provisional entities of renal cell carcinoma. Macroscopically, renal cell carcinomas with leiomyomatous stroma are well circumscribed tumors with a cut surface of gray-white fibrotic tissues. Microscopically, the tumors are composed of nodules and anastomosing tubules of renal cells with clear cytoplasms. The carcinoma cells are embedded in a cellular stroma composed of intertwining bundles of smooth muscle. Immunohistochemically, the neoplastic cells are typically positive for CK7 and CD10 immunomarkers. Biomarkers including CAIX, pankeratin, vimentin, and HIF1-alpha stain positively in many renal cell carcinomas with leiomymomatous stroma. Molecular genetic studies of this variant of tumor reveal no VHL mutation, trisomy 7 or trisomy 17. However, a TCEB1 mutation has been demonstrated in a subset of tumors and rare cases are reported from patients with a family history of tuberous sclerosis. The biological behavior of this variant of tumor is indolent and the prognosis is favorable.

Prostatic adenocarcinoma with novel NTRK3 gene fusion: a case report.

TMPRSS2-ERG gene fusion occurs in approximately 50% of prostatic adenocarcinoma and their expression is associated with aggressive phenotype, higher tumor stage, and tumor metastasis. A case of prostatic adenocarcinoma with IRF2BP2-NTRK1 translocation was previously reported. We report a prostatic adenocarcinoma with novel NTRK3 gene fusion that occurs in a 71-year-old male patient with aggressive histologic phenotype and multiple bony metastases. Prostatic biopsy revealed that there is a prostatic adenocarcinoma with a Gleason score of 9 (4+5), grade group 5, and multiple sites of perineural and ganglional invasion. Fluorescence in-situ hybridization (FISH) and next-generation sequencing were performed. FISH studies showed a breakage within the NTRK3 gene in prostatic adenocarcinoma cells. Next-generation sequencing confirmed that there is a PRPSAP1-NTRK3 translocation in the prostatic adenocarcinoma. In addition, ASXL1, KIF5B, MED12, PIK3CA mutations were found. NTRK alterations or dysregulation of PI3K signaling pathway were found in many types of cancers. TRK inhibitors including larotrectinib and entrectinib were approved by the US Food and Drug Administration for treating TRK fusion-positive malignant tumors and PI3K/AKT/mTOR pathway inhibitors were under clinical studies on various cancers including prostate cancer. In our current case, both NTRK3 and PIK3CA may serve as biomarkers for precision targeted therapy.

Rare Metastatic Testicular Cancer in a Veteran.

Testicular yolk sac tumor (YST) is a nonseminomatous germ cell tumor that predominantly affects prepubescent boys. Pure endometrioid variant YST is rare, with only 1 report in the literature. We present the first reported case of en-dometrioid variant YST with mature teratoma in the retro-peritoneal specimen.