We reviewed the clinico-pathological features of a series of 13 cases of benign spindle stromal tumors (BSSTs) of the breast relating to a basic common theme consisting of a well-circumscribed proliferation of vimentin+/CD34+/BCL-2+/CD99+ spindly to oval-epithelioid cells, variably arranged in haphazard to short fascicular growth pattern, with interspersed thick or thin collagen bands. Morphological variations included atypical mono- or multi-nucleated cells in five cases and a mature lipomatous tumor component, varying from focal to prominent, in eight cases. Based on morphological and immunophenotypical features, a distinction was made between two main subtypes of these tumors--fibroblastic and myofibroblastic. The former subtype included two cases respectively represented by a typical solitary fibrous tumor (SFT) and a neoplasm labeled "spindle-cell lipoma (SCL)-like tumor", closely reminiscent of soft tissue SCL. Both tumors had cells with fibroblastic-like appearance, haphazardly arranged and immunoreactive for vimentin, CD34, BCL-2, and CD99. The latter subtype, comprised nine cases exhibiting evidence of myofibroblastic differentiation (desmin and alpha-smooth muscle actin) which were classified as myofibroblastomas (MFBs). The remaining two cases were defined as "mixed BSSTs", having typical features of diverse neoplasms, respectively represented by a case of MFB with focal SFT and pleomorphic/SCL-like areas, and SFT with focal MFB-like component. The common basic morpho-immunophenotypical features, the possibility that both fibroblastic and myofibroblastic tumors may contain an additional mature lipomatous component, and the existence of hybrid stages (mixed BSSTs) strongly support the view that such tumors belong to the same category of lesions. We postulate that the precursor of all these neoplasms is the vimentin+/CD34+ cells of the mammary stroma, the well-known inherent plasticity of which to differentiate toward several mesenchymal lines, provides the explanation for the phenotypic heterogeneity of these neoplasms. Accordingly, the encompassing term "benign spindle stromal tumors of the breast" is advocated for such tumors.

No abstract

The spectrum of the renal oncocytic tumors has been expanded in recent years to include several novel and emerging entities. We describe a cohort of novel, hitherto unrecognized and morphologically distinct high-grade oncocytic tumors (HOT), currently diagnosed as "unclassified" in the WHO classification. We identified 14 HOT by searching multiple institutional archives. Morphologic, immunohistochemical (IHC), molecular genetic, and molecular karyotyping studies were performed to investigate these tumors. The patients included 3 men and 11 women, with age range from 25 to 73 years (median 50, mean 49 years). Tumor size ranged from 1.5 to 7.0 cm in the greatest dimension (median 3, mean 3.4 cm). The tumors were all pT1 stage. Microscopically, they showed nested to solid growth, and focal tubulocystic architecture. The neoplastic cells were uniform with voluminous oncocytic cytoplasm. Prominent intracytoplasmic vacuoles were frequently seen, but no irregular (raisinoid) nuclei or perinuclear halos were present. All tumors demonstrated prominent nucleoli (WHO/ISUP grade 3 equivalent). Nine of 14 cases were positive for CD117 and cytokeratin (CK) 7 was either negative or only focally positive in of 6/14 cases. All tumors were positive for AE1-AE3, CK18, PAX 8, antimitochondrial antigen, and SDHB. Cathepsin K was positive in 13/14 cases and CD10 was positive in 12/13 cases. All cases were negative for TFE3, HMB45, Melan-A. No TFEB and TFE3 genes rearrangement was found in analyzable cases. By array CGH, complete chromosomal losses or gains were not found in any of the cases, and 3/9 cases showed absence of any abnormalities. Chromosomal losses were detected on chromosome 19 (4/9), 3 with losses of the short arm (p) and 1 with losses of both arms (p and q). Loss of chromosome 1 was found in 3/9 cases; gain of 5q was found in 1/9 cases. On molecular karyotyping, 3/3 evaluated cases showed loss of heterozygosity (LOH) on 16p11.2-11.1 and 2/3 cases showed LOH at 7q31.31. Copy number (CN) losses were found at 7q11.21 (3/3), Xp11.21 (3/3), Xp11.22-11.21 (3/3), and Xq24-25 (2/3). CN gains were found at 13q34 (2/3). Ten patients with available follow up information were alive and without disease progression, after a mean follow-up of 28 months (1 to 112 months). HOT is a tumor with unique morphology and its IHC profile appears mostly consistent. HOT should be considered as an emerging renal entity because it does not meet the diagnostic criteria for other recognized eosinophilic renal tumors, such as oncocytoma, chromophobe renal cell carcinoma (RCC), TFE3 and TFEB RCC, SDH-deficient RCC, and eosinophilic solid and cystic RCC.

No abstract

A clinicopathologic study of 108 cases of high-grade urothelial carcinomas of the renal pelvis is presented. Of the 108 tumors, 44 (40%) showed unusual morphologic features, including micropapillary areas (four cases), lymphoepithelioma-like carcinoma (two cases), sarcomatoid carcinoma (eight cases, including pseudoangiosarcomatous type), squamous differentiation and squamous cell carcinoma (15 cases), clear cells (two cases), glandular differentiation (two cases), rhabdoid, signet-ring or plasmacytoid cells (four cases), pseudosarcomatous stromal changes (four cases) and intratubular extension into the renal pelvis (three cases). Pathological staging was available in 62 patients; of these, 46 cases (74%) were in high stage (pT2-pT4) and 16 (26%) were in low stage (pTis, pTa, pT1). Clinical follow-up ranging from 1 to 256 months (median: 50 months) was available in 42 patients; of these, 26 (61%) died of tumor with a median survival of 31 months. The patients who did not die of their tumors showed only minimal or focal infiltration of the renal parenchyma by urothelial carcinoma, whereas those who died of their tumors showed massive infiltration of the kidney by the tumor. High-grade urothelial carcinomas of the renal pelvis can show a broad spectrum of histologic features similar to those seen in the urinary bladder. Our results support the finding that, unlike urothelial carcinomas of the bladder, the majority of primary urothelial carcinomas of the renal pelvis are of high histologic grade and present in advanced stages. Our study further highlights the fact that, in the renal pelvis, urothelial carcinomas show a tendency to frequently display unusual morphologic features and metaplastic phenomena. The importance of recognizing these morphologic variants of urothelial carcinoma in the renal pelvis is to avoid confusion with other conditions. The possibility of a high-grade urothelial carcinoma should always be considered in the evaluation of a tumor displaying unusual morphologic features in the renal pelvis, and attention to proper sampling as well as the use of immunohistochemical stains will be of importance to arrive at the correct diagnosis.

Hybrid oncocytic/chromophobe tumors (HOCT) of the kidney have been described in patients with Birt-Hogg-Dubé syndrome (BHD) and in association with renal oncocytosis without BHD. HOCT in patients without evidence of BHD or renal oncocytosis is exceedingly rare, and these cases have been poorly characterized. We have identified and studied 14 cases of HOCT from previously diagnosed renal oncocytomas (398 cases) and chromophobe renal cell carcinomas (351 cases) without evidence of BHD or renal oncocytosis. Immunohistochemical, ultrastructural, and molecular genetic studies analyzing numerical chromosomal changes, loss of heterozygosity for chromosome 3p, and mutation status of VHL, c-kit, PDGFR, and folliculin (FLCN) genes were performed. HOCTs were identified in nine men and five women (age range 40-79 years). The size of tumors ranged from 2 to 11 cm. All tumors displayed a solid alveolar architecture and were composed of cells with abundant granular eosinophilic oncocytic cytoplasm with perinuclear halos. Occasional binucleated neoplastic cells were present, but irregular, hyperchromatic, wrinkled (raisinoid) nuclei were absent. The cytoplasm contained numerous mitochondria of varying sizes, but only sparse microvesicles with amorphic lamellar content were found. Tumors were positive for CK7 (12/14), AE1-AE3 (14/14), anti-mitochondrial antigen (14/14), E-cadherin (11/13), parvalbumin (12/14), and epithelial membrane antigen (14/14). Tumors were generally negative for racemase, CK20, CD10, and carboanhydrase IX. Interphase fluorescence in situ hybridization revealed multiple chromosomal losses and gains with a median of four (range 1-9) chromosomal aberrations per case. Monosomy of chromosome 20 was common and found in 7 of 14 cases. Monosomy of chromosomes 6 and 9 was present in 4 of 14 cases each, of which two cases displayed monosomy for both chromosomes 6 and 9. Polysomy of chromosomes 10, 21, and 22 was found in 4/14 cases each, of which one case displayed polysomy for all these three chromosomes. No pathogenic mutations were found in the VHL, c-kit, PDGFR, and folliculin (FLCN) genes. (1) We have shown that hybrid oncocytic/chromophobe tumors of the kidney do occur, albeit rarely, outside the Birt-Hogg-Dubé syndrome and without associated renal oncocytosis. (2) These tumors constitute a relatively homogenous group with histomorphologic features of both chromophobe renal cell carcinoma and renal oncocytoma. (3) Sporadic hybrid oncocytic/chromophobe renal tumors are characterized by multiple numerical aberrations (both mono- and polysomies) of chromosomes 1, 2, 6, 9, 10, 13, 17, 21, and 22 and lack of mutations in the VHL, c-kit, PDGFRA, and FLCN genes. (4) The tumors seem to behave indolently as no evidence of malignant behavior was documented in our series, although admittedly, the follow-up was too short to fully elucidate the biological nature of this rare neoplasm. At worst, these tumors could have a low malignant potential, which only can be found out with longer follow-up.

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For LMS involving the skin, it is advisable to recognize and indicate in the histopathology report the depth of dermal and/or subcutaneous extension, since even minimal subcutaneous involvement may be associated with late local recurrences and/or distant metastases, and therefore appropriate and long-term follow-up is needed.