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9 November 2022 - Case of the Month #521

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Thanks to Drs. Leandro Freitas, Ana Grizotto and Athanase Billis, State University of Campinas (Unicamp), Campinas, Brazil and the Genitourinary Pathology Society (GUPS), for contributing this case and discussion and to Dr. Debra Zynger, Ohio State University, Columbus, Ohio, USA for reviewing the discussion.






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Case of the Month #521

Clinical history:
A 76 year old man with an incidental renal tumor in the lower pole of the right side of a horseshoe kidney underwent a partial nephrectomy.

Histopathology images:


What is your diagnosis?

Click here for diagnosis, test question and discussion:



Diagnosis: Well differentiated neuroendocrine tumor (renal carcinoid)

Test question (answer at the end):
Which of these statements is true about well differentiated neuroendocrine tumor of the kidney (renal carcinoid)?

A. Classic histology of trabeculae and cords, monotonous cells, “salt and pepper” chromatin and minimal stroma
B. Many patients present with symptoms of carcinoid syndrome
C. Metastases have not been described
D. This tumor is fairly common


Stains:
Synaptophysin, chromogranin, CAM5.2

Synaptophysin, chromogranin, CAM5.2




Discussion:
Well differentiated neuroendocrine tumor (renal carcinoid) is a very rare tumor. Our case had the classic appearance including areas with a morphologic pattern of anastomosing trabeculae and cords of cells composed of monotonous cells with “salt and pepper” chromatin with minimal stroma (histopathology image 1). In some areas the stroma was prominent (histopathology image 2). Focally, areas of solid growth with nest formation were present (histopathology image 3). In some areas the tumor formed gland-like lumina (histopathology image 4). Synaptophysin was diffusely positive (stains image), chromogranin focally positive, CAM5.2 positive, vimentin positive, CK7 negative, CK20 negative, TTF1 negative, WT1 negative, racemase negative and PAX8 negative.

In a study of 21 patients with ages ranging from 27 to 78 years (average 52 years) and no gender predominance, the signs and symptoms associated with the tumor included back or flank pain, hematuria, enlarging abdominal mass, anemia and fever. However, most of the patients were asymptomatic and tumors were discovered incidentally on workup for other conditions (Am J Surg Pathol 2007;31:1539). None of the patients had clinical signs or symptoms of carcinoid syndrome. Most of the tumors were unifocal and only one was multifocal. Interestingly, our patient had horseshoe kidney which was similar to 4 of the 21 patients in the study.

Well differentiated neuroendocrine tumors may metastasize but the prevalence of metastatic spread is not known. The prognosis and the potential for metastases may be related to the mitotic activity and cytologic atypia. In the study of 21 patients, most of the cases demonstrated similar mitotic rates, ranging from 0 - 3 / 10 high power field (hpf); the one case that demonstrated the highest mitotic rate (4 mitoses / 10 hpf) belonged to the patient who died of the disease at 8 months post surgery. In other organs, neuroendocrine tumors are classified into three grades based on the number of mitoses / 10 hpf or percentage of the Ki67 index that provides prognostic information. Ki67 index ≤ 3% is considered low grade, between 3 and 20% intermediate and ≥ 20% high grade. In our case the Ki67 index was 2.4%. Our patient had no metastases at the time of diagnosis and the follow up since surgery is too short for any prognostic analysis.

The main differential diagnosis includes small cell carcinoma, primitive neuroectodermal tumor (PNET), paraganglioma, intrarenal neuroblastoma and nephroblastoma (Wilms tumor). Small cell carcinoma has a brisk mitotic rate, apoptotic activity, cellular molding and lacks the typical organized architecture of the carcinoid tumor. PNET shows a monotonous cellular population containing bland, rounded nuclei, variable mitotic activity and is strongly positive for CD99. Paraganglioma commonly contains a nested pattern of neuroendocrine cells with granular cytoplasm surrounded by S100 positive sustentacular cells. Neuroblastoma contains a background of neurofibrillary stroma and demonstrates Homer-Wright rosettes. TTF1 and WT1 were both negative in our case which excludes lung metastasis or adult nephroblastoma (Wilms tumor).

Test question answer:
A. Answer A is correct because well differentiated neuroendocrine tumor of the kidney has the classic appearance of carcinoid tumor at other sites, namely anastomosing trabeculae and cords of monotonous cells with “salt and pepper” chromatin and minimal stroma. Answer B is incorrect because most patients are asymptomatic. Answer C is incorrect because these tumors may metastasize but the prevalence of metastatic spread is unknown. Answer D is incorrect because this tumor is very rare.

References:
Am J Surg Pathol 2007;31:1539, BJU Int 2007;100:1030, Cancer 1993;72:2660, Diagn Pathol 2019;14:12

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