Primary Neuroendocrine Tumors of the Kidney. Morphological and Molecular Alterations of an Uncommon Malignancy
Phyu P Aung, William M Linehan, Cary O Poropatich, Maria J Merino. NCI/NIH, Bethesda, MD; Virginia Hospital Center, Arlington, VA
Background: Primary neuroendocrine tumors of the kidney (PNRT) are rare and frequently mistaken with other kidney and urothelial cancers. The cellular origin of these tumors remains unclear. Tumor cells might originate from the entrapped neural crests cells in the metanephros during embryogenesis, neuroendocrine (NE) differentiation of a primitive totipotential stem cells, preexisting NE cell hyperplasia from metaplastic/tetratomatous epithelium, or association with other congenital renal abnormalities (Horseshoe kidney). In this study, we evaluated morphological and molecular findings of 11 PNRT cases.
Design: Tumors were classified following the WHO definition of PNRTs: well (typical or atypical carcinoid) and poorly differentiated (small cell carcinoma). IHC studies for CD56, synaptophysin, chromogranin, inhibin, glucagon, somatostatin, insulin, pancreatic polypeptide, gastrin, NSE, P53, CK7, RCC markers, CD10, CD99, MIB1, P53, WT1, EMA, vimentin, myogenin, pankeratin, LCA, CK20 and TTF1 were performed. Molecular analysis by CGH and LOH on locus of chromosome 3p21 were performed in some cases.
Results: Patients ranged in age from 35-65 years. Male-female ratio was 5:6. Five tumors occurred in left kidney, 3 in right and 1 in a horseshoe kidney. Laterality was unknown in 2 cases. Clinical symptoms included: incidental (80%), flank pain, chronic anemia and weight loss. Tumor size ranged from 3.2-11 cm. Morphologically, tumors showed solid, trabecular and pseudoglandular patterns. Lymphovascular invasion was found in 3 cases. Tumors were 2 atypical carcinoids (>2 mitosis/10HPF) and 9 typical carcinoids. High proliferative index by MIB-1 was observed in 2 cases that metastasized. The remaining cases showed <1% proliferative rate. IHC for synaptophysin, chromogranin, CD56, CD99 and NSE were positive. The remaining immunostains performed were negative. Two patients developed metastasis and the remaining cases are alive with no evidence of disease. LOH on chr 3p21 was found in some tumors, however, CGH study did not demonstrate chromosomal imbalances.
Conclusions: We conclude that PNRT tumors are uncommon and frequently misdiagnosed as Papillary type I, mesonephroma, Wilm's tumor or undifferentiated carcinoma. The tumors are positive for NE markers and may have LOH on chr 3p21 similar to a clear cell renal carcinoma. The classification as other NE tumors is useful and a high proliferative rate is an indicator of aggressive behavior/metastasis of tumors.
Category: Genitourinary (including renal tumors)
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 86, Wednesday Morning