ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
The karate kata develops speed, agility, and strength. The authors studied heart rates during training to see if it develops cardiovascular fitness as well.
