FINAL DIAGNOSIS: NEUROENDOCRINE CARCINOMA OF THE KIDNEY.
Renal neuroendocrine tumors (NETs) are very rare. Although the first case of renal carcinoid tumor was reported 40 years ago, so far there are less than 100 cases reported (1-9). The clinical behavior of renal NETs remains undetermined due to the rarity of these lesions although it has been shown that these tumors are rarely associated with neuroendocrine symptoms. These tumors usually present in the fourth decade and affect males and females equally. The most common presenting symptoms are abdominal pain, abdominal mass, weight loss, and hematuria. Because neuroendocrine cells are not found within normal renal parenchyma, it has been proposed that the origin of primary renal NETs include entrapped neural crest cells in the metanephros during embryogenesis (10), neuroendocrine differentiation of a primitive totipotential stem cell (11 -12), and hyperplasia of preexisting neuroendocrine cells within metaplastic or teratomatous epithelium (13 -15). A recent study showed that renal carcinoid tumors are negative for paired box gene 2 (PAX-2) and paired box gene 8 (PAX-8), which are thought to be renal cell-lineage-specific transcription factors (16).
Renal NETs can have a varying degree of NE differentiation [carcinoid, atypical carcinoid, small cell carcinoma (SCC), and large cell neuroendocrine carcinoma (LCNEC)] like their counterparts in other anatomical sites. Renal carcinoid tumors are most common and considered to be a low-grade NET, although it can have an aggressive clinical course. Similar to their counterparts in other anatomical sites, renal SCC and LCNEC are highly aggressive tumors with advance disease and/or distal metastases and the prognosis is usually dismal.
Renal carcinoid tumor and SCC have characteristic histological features and often can be diagnosed based on morphology. Immunostains for NE markers can be used to confirm the diagnosis. Synaptophysin seems to be the most sensitive marker for diagnostic confirmation of a renal NET. Other markers such as chromogranin and CD56 can also be used, although less sensitive. LCNEC is more difficult to diagnose and can be mistaken for high-grade renal cell carcinoma or urothelial carcinoma. A correct diagnosis can be achieved with the awareness of the occasional occurrence of LCNEC in the kidney and careful sampling. Positive immunostain with one of the NE markers (synaptophysin, chromogranin and CD56) and negative stain for CD10 favor the diagnosis of LCNEC.
The primary treatment for primary renal NETs is complete surgical resection and can be curative for localized disease. However, SCC and LCNEC often present with larger size tumor and extrarenal extension and might not be amenable to complete resection. No standard treatment has been approved for locally advanced or metastatic renal NETs. Residual local disease can be treated with radiotherapy and chemotherapy or palliation can be used for metastatic renal NETs.
Contributed by Zaibo Li, MD, PhD, Amber Henry Hughes, MD and Rajiv Dhir, MD