Primary renal well-differentiated neuroendocrine tumors: report of six cases with an emphasis on the Ki-67 index and mitosis

Abstract

BackgroundPrimary renal well-differentiated neuroendocrine tumors (WDNETs) also called carcinoid and atypical carcinoid are extremely rare, and little is known about parameters that may predict prognosis at diagnosis.MethodsSix cases of primary renal WDNET were collected. After reviewing slides stained with hematoxylin and eosin, proportions of each growth pattern were determined. Synaptophysin, chromogranin, CD56, and Ki-67 immunostaining and Ki-67 morphometric analysis were performed.ResultsPatients included three female and three males, mean age was 53.3 years. The mean tumor size was 4.5 cm, three cases were greater than 5 cm. At the time of initial surgery, lymph node and/or distant metastasis was confirmed in two cases. In a third case, no metastasis was initially found, but lymph node metastasis was identified during follow-up. The remaining three cases did not exhibit metastasis. Histopathologically, the renal WDNETs were primarily composed of ribbon-like and sheet-like growth patterns. Most of the tumors were diffusely positive for neuroendocrine markers. Mitotic count was high (≥2/10HPF) in cases with lymph node or distant metastasis but was low (< 2/10HPF) in non-metastatic cases. Furthermore, the Ki-67 index was also higher (≥3%) in the cases with metastases than in cases without metastasis.ConclusionThree out of the six primary renal WDNETs demonstrated aggressive behavior and exhibited increased mitotic counts and Ki-67 indices. These results suggest that mitosis and the Ki-67 index could be used as prognostic indicators for renal WDNET.

A Rare Case of a Large Primary Renal Neuroendocrine Tumour: A Case Report and Brief Review of Literature

“…Histological features can be more heterogeneous and less specific to renal neuroendocrine neoplasia, but those described include trabecular and rosette-like architectural patterns mixed with nests and cords of cells, palisading and tubal formation, and round nuclei with stippled (salt-and-pepper) chromatin [ 4 , 6 ]. The proposed significant adverse prognostic factors include age > 40 years, tumour size > 4 cm, purely solid tumours on the cut surface, a mitotic rate higher than 1/10 HPF, metastasis at initial diagnosis and tumours extending throughout the renal capsule [ 13 , 15 ]. Unfortunately, several of these poor prognostic indicators were present in the case presented here.…”

Primary renal neuroendocrine neoplasms: A systematic literature review, report of four local cases, and original survival analysis of 63 patients from a national registry 2012–2018

“…31 In symptomatic patients, abdominal pain is the most common presenting symptom, followed by haematuria, abdominal mass, and constitutional symptoms such as weight loss and fever. 1,[11][12][13][14]16,17,24,27,[30][31][32][33][37][38][39][40][41][42][43][44][45][46]48,49 Although multiple other series have also noted an increased incidence of renal NEN in the right kidney some with higher proportions than others, 14,21,32,35,36 there are several included studies reporting relatively similar rates in each kidney. 12,18,31,32…”

“…Several case reviews, case series and review articles of primary renal NET show no significant sex predilection. 11,12,16,18,20,21,27,28,[30][31][32]39,42 However, in their literature review, Omiyale et al 13 noted that 62% of the 29 cases of renal NET occurred in females. Some other case series suggest a female predisposition to NET [34][35][36]40,50 ; however, these involved small patient numbers.…”

“…Surgical intervention has been the mainstay of management in cases of primary renal NEN 2,6,[12][13][14]16,17,[31][32][33][34]36,40,42,46,49,50 with nephrectomy the established standard of care. Partial nephrectomy may be used in select patients based on tumour size and location.…”

“…A high mitotic count has also been suggested as a poor prognostic marker. In the study of six well-differentiated neuroendocrine tumours by Kim et al, 42 a high mitotic count (> 2/10 high power field [HPF]) was found in patients with metastatic disease, but not in those with localized disease. This was also seen by Aung et al 31 in a series of 11 patients.…”