A unique case of combined papillary renal cell carcinoma (PRCC) and mucinous tubular and spindle cell carcinoma (MTSCC) presenting in a man aged 67 years is reported. The two separate components were distinct on morphological, immunohistochemical (IHC), and genetic grounds, while type 2 PRCC predominated. Three years after the initial diagnosis, the PRCC component metastasized to the lungs where it morphologically mimicked a pulmonary neuroendocrine tumor. Retrospectively focal neuroendocrine differentiation was demonstrated by IHC in the PRCC component of the primary neoplasm.
PRCC and MTSCC constitute, respectively, 18% and <1% of all renal tumors [
A 67-year-old man with a significant smoking history presented with a 4.5 cm enhancing left upper pole renal mass detected on CT scan and treated by radical nephrectomy (Figure
(a) Contrast enhanced CT shows a 4.5 cm left upper pole renal mass. (b) Chest CT shows an ill-defined obstructive right perihilar mass, which is inseparable from the extensive mediastinal and hilar lymphadenopathy. There is irregular and nodular inter-/intra-lobular septal thickening predominantly in the right middle and lower lobe with ipsilateral pleural effusion, suggestive of lymphangitic carcinomatosis.
Gross examination revealed a gray-white, circumscribed, encapsulated, focally necrotic mass measuring 4.8 cm in largest dimension in the superior pole of the kidney. The tumor focally invaded perinephric tissues but was completely resected. Microscopically, the majority (95%) of the tumor showed the morphology of a Type 2 PRCC with a prominent papillary architecture. The cells were polygonal in shape and exhibited abundant eosinophilic granular cytoplasm and Fuhrman grade 3 nuclei (Figure
Photomicrographs of the primary kidney tumour. (a) There were two distinct morphologies. The main tumour showed a prominent papillary structure, eosinophilic cytoplasm, Fuhrman grade 3 nuclei (left). The smaller focus of tumour showed long tubular profiles or cord-like growth pattern of uniform, bland, low cuboidal cells with eosinophilic, focally vacuolated cytoplasm which transition to anastomosing spindle cells, with stroma showing myxoid and bubbly with abundant extracellular mucin (right). (b) The PRCC component showed positive staining for CD10 (left). The MTSCC component was negative for CD10 (right). (c) The PRCC component had small foci positive for synaptophysin. (d) Fluorescent in situ hybridization analysis showing three centromere 17 signals consistent with trisomy 17 in the PRCC component (left, green dots), while the MTSCC component was negative for trisomy 17 (right, green dots).
The recent transbronchial biopsy showed an infiltrative tumour with nested and trabecular architecture but no papillary component. Nests and cords of small polygonal cells were surrounded by delicate fibrovascular stroma. The cells had a moderate amount of vacuolated, granular eosinophilic cytoplasm (Figure
Photomicrographs of the lung metastasis. (a) A very infiltrative tumour in the submucosa of the bronchus with a nested and trabecular architecture and no definite papillary architecture. (b) The tumour was diffusely positive for synaptophysin. (c) The tumour was strongly positive for PAX8. (d) The tumour showed positive staining for CD10.
PRCC is thought to be derived from the renal tubular epithelium [
MTSCC is an unusual renal carcinoma of probable distal nephron differentiation with prominent spindle cell change and a myxoid stroma. The histologic spectrum and IHC profile are variable. MTSCC is characterized by an elongated tubular and cord-like architecture, cuboidal to spindled cells with low nuclear grade, and a myxoid/mucinous stroma [
The tumour that presented in the lung/mediastinum three years later posed a diagnostic challenge. While the cells lacked the “salt-and-pepper” chromatin pattern typically seen in neuroendocrine tumours, the architecture, vascular pattern, and eosinophilic granular cytoplasm suggested the possibility of an endocrine neoplasm. IHC showed strong positive staining for synaptophysin, focal staining for chromogranin, and CD56. The negative TTF-1 and strong staining for PAX8 and RCC supported a metastatic tumour from the kidney, rather than a primary neuroendocrine carcinoma of the lung or metastasis from other sites. The strong staining of the lung tumour for CD10 suggested a metastasis from the primary PRCC component that had undergone neuroendocrine differentiation. Despite careful retrospective examination of the Hematoxylin and Eosin-stained sections of all blocks, the primary tumor in our case did not show morphological evidence of neuroendocrine differentiation. However, retrospective IHC detected focal positivity for synaptophysin in the PRCC component and these foci are presumed to be the source for the pulmonary metastases. Neuroendocrine differentiation of RCC (not primary neuroendocrine carcinoma of the kidney) is rare. Peckova et al. presented 18 ChRCCs with morphologic features suggestive of neuroendocrine differentiation. Four were confirmed by IHC [
Since the literature on RCC with neuroendocrine differentiation is based on case reports and small series, their prognosis and management are unclear [
The authors report no conflicts of interest.
Gang Wang conceived and designed the study, collected data, and wrote, edited, and reviewed the manuscript. Ren Yuan, Tracy Tucker, and Malcolm Hayes collected data and edited and reviewed the manuscript. All authors gave final approval for publication. Gang Wang takes full responsibility for the work as a whole, including the study design, access to data, and the decision to submit and publish the manuscript.