2020-31 / August 3
(Contributor: Nathanael de Freitas Pinheiro Jr & Daniel Athanazio)

A 55-year old male patient underwent a total nephrectomy due to a 7.5 cm solid tumor. Imaging suggested intratumoral calcifications.


1. What is the diagnosis?

a. Adult nephroblastoma with predominant epithelial component

b. Metanephric adenoma

c. Papillary renal cell carcinoma

d. Well-differentiated neuroendocrine tumor (carcinoid)

e. Oncocytoma

1. Well-differentiated neuroendocrine tumor (carcinoid)

Well-differentiated neuroendocrine tumors of the kidney are rare. In this case, extensive imaging work up did not reveal other tumors or potential other primary sites. This case was referred for consultation after a first immunohistochemistry panel performed in another laboratory. It showed the following results: positivity for CD56, chromogranin, synaptophysin, neuron-specific enolase, and vimentin; negativity for cytokeratin 7, cytokeratin 20, INI-1, PAX8, TFE3 and AMACR. We also performed additional immunohistochemical reactions, and, in our hands, the tumor was positive for synaptophysin (strong and diffuse); negative for chromogranin, cytokeratin 7, WT1 and PAX8; and showed a proliferative index (Ki67) of 2%. Interestingly, PAX8 negativity in this case argues against a renal cell carcinoma but also against a potential metastasis of a pancreatic primary neuroendocrine tumor.

Ossification within this tumor was noted; an uncommon feature shared with other slow growing masses of the kidney such as oncocytoma.

Few studies have evaluated the prognosis of well-differentiated neuroendocrine tumors of the kidney. Recent data suggest that, as in other sites, higher Ki67 index is associated with metastatic potential. A recent study focusing on the DNA sequencing of 11 cases did not show specific gene alterations.

Moch H, Humphrey PA, Ulbright TM, Reuter VE. Chapter 1 Tumours of the Kidney. In: WHO Classification of Tumours of the Urinary system and male genital organs. Lyon: IARC; 2016. p. 72.

Teegavarapu PS, Rao P, Matrana M, Cauley DH, Wood CG, Tannir NM. Neuroendocrine tumors of the kidney: a single institution experience. Clin Genitourin Cancer. 2014 Dec;12(6):422-7.

Kim B, Kim HS, Moon KC. Primary renal well-differentiated neuroendocrine tumors: report of six cases with an emphasis on the Ki-67 index and mitosis. Diagn Pathol. 2019;14(1):12. Published 2019 Feb 7. doi:10.1186/s13000-019-0791-7

Pivovarcikova K, Agaimy A, Martinek P, et al. Primary renal well-differentiated neuroendocrine tumour (carcinoid): next-generation sequencing study of 11 cases. Histopathology. 2019;75(1):104-117.

Sangoi AR, Ohgami RS, Pai RK, Beck AH, McKenney JK, Pai RK. PAX8 expression reliably distinguishes pancreatic well-differentiated neuroendocrine tumors from ileal and pulmonary well-differentiated neuroendocrine tumors and pancreatic acinar cell carcinoma. Mod Pathol. 2011;24(3):412-424.

Nathanael de Freitas Pinheiro Jr
Daniel Athanazio
Imagepat, Laboratory of Pathology
Salvador, Bahia, Brazil


Kidney; Kidney Neoplasms; Well differentiated neuroendocrine tumor