Endocrine Abstracts

Introduction: Pheochromocytomas (PHEOs) and paragangliomas (PGLs) are rare neuroendocrine tumors arising from chromaffin cells within adrenal medulla and autonomic paragranglia respectively. Recent evidences show that nearly one-third patients harbour germline mutation, namely in von Hippel-Lindau (VHL), REarranged during Transfection (RET), neurofibromatosis type 1 (NF 1) and succinate dehydrogenase (SDH) complex genes. However, the tumor morphology arising in various syndromes has been scarcely documented. Can histology provide a clue to the genotype or more importantly help to target patients, especially with clinically sporadic tumors, who would require genetic testing?

Methods: We tested 63 (40 PHEOs, 20 PGLs, three both PHEOs and PGLs) consenting patients for germline mutation in VHL, RET or SDH genes. The corresponding tumor histology (available in 41) is evaluated by two pathologists blinded to the mutation status.

Results: Germline mutations have been detected in 37 (58.73%) patients; 11, 8, 16 and 2 with VHL, RET, SDHB and SDHD gene mutations respectively. The tumors in multiple endocrine neoplasia type 2 have large cells with abundant eosinophilic cytoplasm, frequent hyaline globules, anisonucleosis and scant vascularised stroma in septa. The VHL-mutated tumors are stroma-rich, contain vessels in septa as well as admixed with cells which are medium to large, often having clear cytoplasm, fairly uniform nuclei and presence of background adrenomedullary hyperplasia (AMH). The SDH-mutated tumors, much akin to the sporadic ones, show diverseness in morphological appearance.

Conclusions: A vessel and stroma rich tumor with at least focal cytoplasmic clearing may hint to the possibility of an underlying VHL mutation in an apparently sporadic tumor. AMH is important corroborative evidence that must be diligently looked for both in gross specimens and histology sections. Likewise MEN 2 associated tumors display histological features that in conjunction may prompt to test for its presence. Histological heterogeneity, however, precludes successful prediction of SDH mutation.