Chromophobe renal cell carcinoma (ChRCC) is typically composed of large leaf-like cells and smaller eosinophilic cells arranged in a solid-alveolar pattern. Eosinophilic, adenomatoid/pigmented, or neuroendocrine variants have also been described. We collected 10 cases of ChRCC with a distinct multicystic pattern out of 733 ChRCCs from our registry, and subsequently analyzed these by morphology, immunohistochemistry, and array comparative genomic hybridization. Of the 10 patients, 6 were males with an age range of 50-89 years (mean 68, median 69). Tumor size ranged between 1.2 and 20 cm (mean 5.32, median 3). Clinical follow-up was available for seven patients, ranging 1-19 years (mean 7.2, median 2.5). No aggressive behavior was documented. We observed two growth patterns, which were similar in all tumors: (1) variable-sized cysts, resembling multilocular cystic neoplasm of low malignant potential and (2) compressed cystic and tubular pattern with slit-like spaces. Raisinoid nuclei were consistently present while necrosis was absent in all cases. Half of the cases showed eosinophilic/oncocytic cytology, deposits of pigment (lipochrome) and microcalcifications. The other half was composed of pale or mixed cell populations. Immunostains for epithelial membrane antigen (EMA), CK7, OSCAR, CD117, parvalbumin, MIA, and Pax 8 were positive in all tumors while negative for vimentin, TFE3, CANH 9, HMB45, cathepsin K, and AMACR. Ki67 immunostain was positive in up to 1 % of neoplastic cells. Molecular genetic examination revealed multiple chromosomal losses in two fifths analyzable tumors, while three cases showed no chromosomal numerical aberrations. ChRCC are rarely arranged in a prominent multicystic pattern, which is probably an extreme form of the microcystic adenomatoid pigmented variant of ChRCC. The spectrum of tumors entering the differential diagnosis of ChRCC is quite different from that of conventional ChRCC. The immunophenotype of ChRCC is identical with that of conventional ChRCC. Chromosomal numerical aberration pattern was variable; no chromosomal numerical aberrations were found in three cases. All the cases in this series have shown an indolent and non-aggressive behavior.
Mucin and mucin-like material are features of mucinous tubular and spindle renal cell carcinoma (MTS RCC) but are rarely seen in papillary renal cell carcinoma (PRCC). We reviewed 1311 PRCC and identified 7 tumors containing extracellular and/or intracellular mucinous/mucin-like material (labeled as PRCCM). We analyzed these using morphological, histochemical, immunohistochemical, and molecular genetic methods (arrayCGH, FISH). Clinical data were available for six of the seven patients (five males and one female, age range 61-78 years). Follow-up was available for four patients (2-4 years); one patient died of widespread metastases. Tumor size ranged from 3 to 5 cm (mean 3.8). Of all cases, histological architecture showed a predominantly papillary pattern. Mucin or mucin-like was extracellular in one, intracellular in three, and both intra/extracellular in three cases. All tumors were positive for AMACR, vimentin, and OSCAR, while CK7 was positive in four. Mucicarmine stain was positive in all cases, PAS in six and Alcian blue in three cases. Five tumors were positive for MUC 1, but none were positive for MUC 2, MUC 4, or MUC 6. In only four cases, genetic analysis could be performed. Gain of chromosomes 7 and 17 was found in two cases; gain of 17 only was found in one case. Loss of heterozygosity of 3p was found in one case together with polysomy of chromosomes 7 and 17. No abnormalities of VHL, fumarate dehydrogenase, and TFE3 genes were detected. We conclude that PRCCM is a rare but challenging subtype of RCC that deserves to be further studied. In all the tumors, the mucin-like material was found in those stained with mucicarmin, but other conventional and immunohistochemical stains did not reveal consistent features of a single mucin. The molecular-genetic profile of these tumors was most consistent with that of typical papillary RCC, although one case had mixed genetic features of papillary and clear RCC. PRCCM has metastatic potential, as evidenced by one case with widespread metastases. It remains to be determined whether PRCCM represents a unique tumor subtype, deserving to be distinguished from other subtypes of PRCC.
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