Objective:To investigate the clinicopathological characteristics and molecular variants of chromophobe renal cell carcinoma with small cell components/neuroendocrine-like features (ChRCC-SC/ND-L).Methods:There were 7 cases of ChRCC-SC/ND-L diagnosed by light microscopy and immunohistochemical staining were collected from the Affiliated Hospital of Qingdao University (5 cases) and 971 Hospital of the People′s Liberation Army Navy (2 cases) between January 2010 and December 2023. The clinical data, histological characteristics, and immunohistochemical staining results of the patients were summarized. Among them, 4 cases underwent whole exome sequencing.Results:Among the 7 cases, 5 cases were male and 2 cases were female. The mean age was 53 (43,58)years,with a range of 36 to 76 years. Gross examination showed that the mean maximum tumor diameter was 7.9 (6.0,9.0) cm,with a range of 5.5 to 13.0 cm. The tumors were nodular, well-defined, gray, red or yellow in color with a solid cut surface, except for 1 case with cystic and solid on cut surface. One case showed visible necrosis, and 1 case invaded the renal pelvis and sinus. Microscopically, the tumors had clear boundaries. Typical ChRCC components (5 cases of classical type, 2 cases of eosinophilic type) were found in all cases, accompanied by varying amounts of small cell components (5%-90%). The two components were mixed in 6 cases or directly adjacent to each other in 1 case. The small cell components were arranged in clusters, dense acinar and nest-like structures, beam-like, fence-like, chrysanthemum-shaped clusters, and ribbon-like patterns. Three cases exhibited patchy necrosis. Intravascular tumor thrombus was found in 1 case. Immunohistochemically, EMA was expressed consistently in the small cell and typical ChRCC components (7/7); whilst both CK7 and CD117 were negative in 1 case with typical ChRCC component (6/7). Small cell components in 3 cases were positive for CD56, whereas all 7 cases were negative for CgA, Syn, and INSM1. The Ki-67 proliferation index was less than 1% in both components. Whole exome sequencing revealed that the 4 cases exhibited different genetic aberrations including 1 case with multiple chromosomal deletions, while 2 cases showed amplification of chromosome 12 and deletion of chromosome 11, respectively. The 7 cases were followed up for 25 to 172 months. Except for 1 patient that died with unknown causes 25 months after surgery, the remaining 6 cases were still alive (average 103.8 months, median 101 months).Conclusions:ChRCC-SC/ND-L is a very rare subtype of ChRCC. The small cell component does not represent true neuroendocrine differentiation and might indicate a morphological heterogeneity of the tumor. The presence of typical chromophobe cell carcinoma components is helpful for the diagnosis of ChRCC-SC/ND-L and they do not have consistent molecular characteristics. ChRCC-SC/ND-L has a good prognosis and the small cell components/neuroendocrine-like components might not have a significant impact on the outcome of patients with the tumor.

Objective:To investigate the clinicopathological characteristics and molecular variants of chromophobe renal cell carcinoma with small cell components/neuroendocrine-like features (ChRCC-SC/ND-L).Methods:There were 7 cases of ChRCC-SC/ND-L diagnosed by light microscopy and immunohistochemical staining were collected from the Affiliated Hospital of Qingdao University (5 cases) and 971 Hospital of the People′s Liberation Army Navy (2 cases) between January 2010 and December 2023. The clinical data, histological characteristics, and immunohistochemical staining results of the patients were summarized. Among them, 4 cases underwent whole exome sequencing.Results:Among the 7 cases, 5 cases were male and 2 cases were female. The mean age was 53 (43,58)years,with a range of 36 to 76 years. Gross examination showed that the mean maximum tumor diameter was 7.9 (6.0,9.0) cm,with a range of 5.5 to 13.0 cm. The tumors were nodular, well-defined, gray, red or yellow in color with a solid cut surface, except for 1 case with cystic and solid on cut surface. One case showed visible necrosis, and 1 case invaded the renal pelvis and sinus. Microscopically, the tumors had clear boundaries. Typical ChRCC components (5 cases of classical type, 2 cases of eosinophilic type) were found in all cases, accompanied by varying amounts of small cell components (5%-90%). The two components were mixed in 6 cases or directly adjacent to each other in 1 case. The small cell components were arranged in clusters, dense acinar and nest-like structures, beam-like, fence-like, chrysanthemum-shaped clusters, and ribbon-like patterns. Three cases exhibited patchy necrosis. Intravascular tumor thrombus was found in 1 case. Immunohistochemically, EMA was expressed consistently in the small cell and typical ChRCC components (7/7); whilst both CK7 and CD117 were negative in 1 case with typical ChRCC component (6/7). Small cell components in 3 cases were positive for CD56, whereas all 7 cases were negative for CgA, Syn, and INSM1. The Ki-67 proliferation index was less than 1% in both components. Whole exome sequencing revealed that the 4 cases exhibited different genetic aberrations including 1 case with multiple chromosomal deletions, while 2 cases showed amplification of chromosome 12 and deletion of chromosome 11, respectively. The 7 cases were followed up for 25 to 172 months. Except for 1 patient that died with unknown causes 25 months after surgery, the remaining 6 cases were still alive (average 103.8 months, median 101 months).Conclusions:ChRCC-SC/ND-L is a very rare subtype of ChRCC. The small cell component does not represent true neuroendocrine differentiation and might indicate a morphological heterogeneity of the tumor. The presence of typical chromophobe cell carcinoma components is helpful for the diagnosis of ChRCC-SC/ND-L and they do not have consistent molecular characteristics. ChRCC-SC/ND-L has a good prognosis and the small cell components/neuroendocrine-like components might not have a significant impact on the outcome of patients with the tumor.

Objective:To investigate the clinicopathological features and immunohistochemical phenotypes of hybrid oncocytic/chromophobe tumor (HOCT) of the kidney and its associations with renal oncocytoma (RO) and eosinophilic chromophobe renal cell carcinoma (eChRCC).Methods:A total of 8 HOCT cases were collected from 2008 to 2019 at the Affiliated Hospital of Qingdao University (5 cases) and 971 Hospital of PLA Navy (3 cases), Qingdao, China for morphological studies, immunohistochemical staining and follow-up. The immunohistochemical results of HOCT were compared with those of 27 typical RO and 17 eChRCC.Results:Among the 8 patients, 3 were male and 5 were female. Their ages ranged from 39 to 75 years (median: 56 years). All cases were sporadic. Seven patients were asymptomatic and one suffered from lumbago. During a mean follow-up of 37 months in 7 patients, none of them developed tumor recurrence or metastasis. Seven cases were solitary and one was multiple. The tumor size ranged from 1.4 to 5.7 cm (mean, 3.6 cm). The cut surface of the tumors was dark red or yellowish. Histologically, the tumors were well-defined. Six cases were directly adjacent to the surrounding renal tissue, 2 cases had pseudocapsule, 3 cases showed entrapped renal tubules at the edge of tumor tissue, and one circumscribed with focal infiltrating borders. There were two types of histological morphology: one type (4 cases) was composed of mixed areas of otherwise typical RO and areas resembling chromophobe renal cell carcinoma; another type (4 cases) showed the morphological characteristics of both RO and eChRCC. Three second-type tumors showed nest-like, trabecular, and solid growth patterns with conspicuous edematous stroma. The cell border was conspicuous and the cytoplasm showed an eosinophilic appearance. The nuclei were small and round with clear perinuclear halo. One tumor showed a multi-nodular and solid growth pattern, and the cytoplasm was eosinophilic, hypochromatic or transparent. The nuclei were small and round, and some of them had obvious perinuclear halo. Immunohistochemically, the tumor cells in all 8 cases were positive for Ksp-cad but negative for vimentin. CD117 was diffusely positive in 6/8 cases. CK7 staining showed patchy positivity in 6/8 cases. S-100A1, cyclin D1 and claudin7 showed variable positivity in 4/8, 6/8 and 5/8 cases, respectively, but the range and intensity were narrower and weaker than those in RO and eChRCC.Conclusions:HOCT is a low-grade eosinophilic renal tumor with morphological characteristics resembling RO and eChRCC. The combined application of immunohistochemical stains of CK7, CD117, Ksp-cad, cyclin D1, claudin7 and S-100A1 may play an auxiliary role in the differentiation of the three tumors. HOCT has a good prognosis after surgical resection and can be regarded as a tumor with uncertain malignant potential.