Chromophobe renal cell carcinoma with neuroendocrine differentiation/morphology: A clinicopathological and genetic study of three cases

• Published in: Human pathology : case reports 2014-09, Vol.1 (3), p.31-39
• Main Authors: Ohe, Chisato, MD, Kuroda, Naoto, MD, Matsuura, Keiko, MD, PhD, Kai, Tomoki, MD, Moriyama, Masatsugu, MD, PhD, Sugiguchi, Shun, MD, Terahata, Shintaro, MD, Hosaka, Naoki, MD, PhD, Hes, Ondrej, MD, PhD, Michal, Michal, MD, Matsuda, Tadashi, MD, Uemura, Yoshiko, MD
• Format: Article
• Language: English
• Subjects: Chromophobe renal cell carcinoma; Comparative genomic hybridization analysis; Immunohistochemicalstain; Neuroendocrine differentiation; Pathology; Ultrastructure
• ISSN: 2214-3300; 2214-3300
• DOI: 10.1016/j.ehpc.2014.08.003

Abstract Chromophobe renal cell carcinoma (ChRCC) with neuroendocrine differentiation/morphology (NED/NEM) is exceedingly rare. We present three cases of ChRCC with NED/NEM, two of which showed positivity for neuroendocrine markers on immunohistochemical analysis. Patients ranged in age from 49 to 79 years (mean: 64.3 years). One of the three patients died of metastatic disease to multiple organs. Of the remaining two patients, one is currently alive without disease and the other is alive with disease. Histologically, all three tumors were composed of conventional ChRCC and NEM showed glandular and rosette formation. Immunohistochemically, tumor cells were positive for CK7, KAI1, E-cadherin, and c-kit in both ChRCC and neuroendocrine areas in three cases. CD56 and synaptophysin immunoreactivity were detected in two cases; in only the neuroendocrine area in one case and in both components in the other. Neuroendocrine granules were ultrastructurally observed at both neuroendocrine and conventional areas of ChRCC. Array comparative genomic hybridization (CGH) study indicated losses of chromosomes 1, 2, 6, 10, 17, 21, and Y in both conventional ChRCC and NED in one case. In addition, losses of chromosomes 1, 2, 4, 6, 9, 10, 13, 16p, 17, and 21 were observed in both components of the remaining one tumor. Furthermore, loss of chromosome 5 was identified only in the neuroendocrine area in this case. We concluded that the neuroendocrine area may reflect dedifferentiation within ChRCC. It is possible that losses of chromosomes 4, 5, and 16p may be involved in the neuroendocrine differentiation or progression of ChRCC.