We report 2 primary renal sarcomas demonstrating BCOR-CCNB3 gene fusions that have recently been identified in undifferentiated round cell sarcomas of bone and soft tissue. These neoplasms occurred in male children aged 11 and 12 years, and both were cystic as a result of entrapment and dilatation of native renal tubules. Both cases were composed of variably cellular bland spindle cells with fine chromatin set in myxoid stroma and separated by a branching capillary vasculature. Both neoplasms demonstrated immunoreactivity for BCOR, cyclin D1, TLE1, and SATB2 in the spindle neoplastic cells and negativity in the prominent capillary vasculature. One case was extensively cystic and had hypocellular areas that simulated cystic nephroma; this neoplasm recurred 3 years later as a solid, highly cellular spindle cell sarcoma in the abdominal cavity. The morphology and immunoprofile of these renal neoplasms was compared with a control group of other sarcomas with BCOR genetic abnormalities, including clear cell sarcoma of the kidney (CCSK), infantile undifferentiated round cell sarcomas of soft tissue/primitive myxoid mesenchymal tumor of infancy, and bone/soft tissue sarcomas with BCOR-CCNB3 gene fusion; along with primary renal synovial sarcoma. Our findings show that the renal sarcomas with BCOR-CCNB3 gene fusion overlap with CCSK. These results are in keeping with a "BCOR-alteration family" of renal and extrarenal neoplasms which includes CCSK and undifferentiated round cell sarcomas of soft tissue/primitive myxoid mesenchymal tumor of infancy (which typically harbor BCOR internal tandem duplication), and BCOR-CCNB3 sarcomas, all of which are primarily driven by BCOR overexpression and have overlapping (but not identical) clinicopathologic features.
Ducts of Luschka are a developmental abnormality found within the gallbladder fossa in up to 10% of cholecystectomy specimens. They are most often encountered by surgeons when injured during laparoscopic or open cholecystectomy, leading to bile leakage and subsequent peritonitis. Histologically, they are typically composed of lobular aggregates of small ductules lined by bland, cuboidal-to-columnar biliary-type epithelium, associated with centrally located, larger ductules surrounded by concentric fibrosis. We have identified 6 cases of florid Luschka duct proliferation in which the ductules demonstrated irregular growth pattern, loss of characteristic concentric fibrosis, and epithelial atypia that strongly suggested the diagnosis of invasive pancreatobiliary adenocarcinoma or metastatic adenocarcinoma involving the gallbladder serosa. Two of the cases were initially diagnosed as invasive adenocarcinoma, whereas the other 4 were sent for consultation to rule out adenocarcinoma. All cases were associated with marked acute and chronic cholecystitis with mucosal ulceration, cholelithiasis, and thickening of the gallbladder wall. The ducts of Luschka were located within the rim of adherent liver in all 6 cases and the gallbladder serosa in 5 cases. Limited follow-up information was available for all patients with no documentation of progressive disease. Awareness and proper recognition of the anatomic location and histologic features are imperative in distinguishing florid ducts of Luschka from both non-neoplastic conditions and most importantly adenocarcinoma.
The solid variant of papillary renal cell carcinoma (PRCC) is distinguishable genetically from mucinous tubular and spindle cell carcinoma (MTSC) of the kidney by the presence of trisomy for chromosomes 7 and 17; however, at the morphologic and immunohistochemical levels, these neoplasms overlap significantly. The key morphologic feature distinguishing these two is thought to be the low grade of the spindle cell areas of MTSC; spindle cell areas in PRCC generally signify sarcomatoid change and are high grade. We report 5 cases of PRCC with low-grade spindle cell foci, closely mimicking MTSC. All patients were male, and ranged in age from 17 to 68 years. All tumors were predominantly solid, featuring compact areas of low-grade spindle cells lining thin, angulated tubules. Mucinous stroma was not appreciated in any case. All cases were diffusely immunoreactive for cytokeratin 7, and focally CD10 positive. All 5 cases showed trisomy of chromosome 7, and 3 of 5 showed trisomy of chromosome 17 by fluorescence in situ hybridization, supporting classification as PRCC. These cases further reported morphologic overlap between MTSC and PRCC. Before a diagnosis of metastatic MTSC or MTSC with unusual morphology is rendered, the possibility of PRCC with low-grade spindle cell foci should be considered. Fluorescence in situ hybridization analysis effectively separates these morphologically very similar yet genetically distinctive entities.
Aims Mucinous tubular and spindle cell carcinoma ( MTSC ) of the kidney is a distinct entity characterized by bland tightly packed elongated tubules and spindle cells with low nucleolar grade in a basophilic mucinous stroma. Several case studies have reported MTSC with high‐grade features and have brought into question whether they represented MTSC or a variant of papillary renal cell carcinoma. Methods and results We searched our pathology database and identified seven cases: six MTSC with high International Society of Urological Pathology ( ISUP ) nucleolar grade and one MTSC with overall low nucleolar grade but extensive necrosis. DNA samples were extracted from paraffin blocks and analysed using a single nucleotide polymorphism ( SNP ) array platform. Six of seven patients were female, aged between 46 and 82 years. Tumour sizes ranged from 3 to 7.5 cm. One case showed involvement of renal sinus fat and a second case showed involvement of the perinephric fat. All cases shared common chromosomal abnormalities observed with the more typical MTSC , with monosomy of chromosomes 1, 4, 6, 8, 9, 13, 14, 15 and 22. Trisomy of chromosomes 7, 17 and loss of Y chromosome were not observed in any of the cases. None of the patients showed evidence of recurrence or metastasis. Discussion The molecular analysis performed in this study supports that MTSC of the kidney can have high nucleolar grade or extensive necrosis, and that they are not papillary renal cell carcinoma. We support modifying the definition of MTSC to include those with higher nucleolar grade.
We report 15 primary renal neoplasms with morphologic, immunohistochemical, and molecular features identical to those of synovial sarcoma. These tumors form a distinct subset of the entity previously designated as embryonal sarcoma of the kidney. Most were diagnosed between the ages of 20 and 50 years. On gross examination, tumors are large, partially necrotic, and usually contain smooth-walled cysts. Microscopically, tumors are characterized by mitotically active, monomorphic plump spindle cells with indistinct cell borders growing in short, intersecting fascicles. Grossly identified cysts are lined by mitotically inactive polygonal eosinophilic cells with apically oriented nuclei ("hobnailed epithelium"). The spindle cells are immunoreactive for vimentin, often immunoreactive for EMA, but typically non-immunoreactive for desmin, actin, S100, or cytokeratins, whereas the cyst epithelium is cytokeratin-positive. These findings are consistent with monophasic, spindled synovial sarcoma encircling dilated native renal collecting ducts. The presence of an SYT-SSX gene fusion resulting from the t(X;18) characteristic of synovial sarcoma was demonstrated by reverse transcriptase polymerase chain reaction in three of three tumors in which adequate RNA could be obtained from paraffin blocks. An additional case demonstrated the characteristic t(X;18) translocation on cytogenetic analysis, but adequate material to perform molecular studies was not available in this case or the remaining 11 cases. Primary renal synovial sarcoma is a distinctive clinicopathologic entity confirmed by molecular detection of SYT-SSX fusion transcripts.
Abstract This abstract is being presented as a short talk in the scientific program. A full abstract is printed in the Proffered Abstracts section (PR001) of the Conference Program/Proceedings. Citation Format: Adrianna Amaral de Aragao Mendes, Hans Liu, Juhyung Woo, Kaushal Asrani, Avi Rosenberg, Pedram Argani, Tamara Lotan. Development and characterization of novel pre-clinical models of SFPQ-TFE3-driven renal cell carcinoma [abstract]. In: Proceedings of the AACR Special Conference: Advances in Kidney Cancer Research; 2023 Jun 24-27; Austin, Texas. Philadelphia (PA): AACR; Cancer Res 2023;83(16 Suppl):Abstract nr A019.
