Evaluation of SDHB Immunohistochemistry in the Evaluation of Pheochromocytomas and Paragangliomas from Patients with and without Succinate Dehydrogenase B (SDHB) Mutations.
Lauren Fishbein, Katherine Nathanson, Virginia A LiVolsi, Paul J Zhang, Kathleen T Montone. University of Pennsylvania, Philadelphia
Background: Pheochromocytomas and paragangliomas may arise in patients with germline mutations in succinate dehydrogenase (SDH) subunits B, C, and D as well as in patients with germline mutations in VHL, NF1, and ret. Recently, Gill et al (Human Pathol 41:805, 2010) reported loss or diminished expression of SDHB protein by immunohistochemistry in tumors from patients with germline mutations of SDH B, C, and D whereas those associated with other germline mutations showed strong cytoplasmic granular staining. We evaluated the utility of SDHB immunohistochemistry for evaluating a series of patients seen at our institution with genetically associated paraganglioma/pheochromocytomas.
Design: Eighteen paraganglioma/pheochromocytomas from 18 patients with known germline mutations of SDHB (6 patients), SDHD (4 patients), ret (4 patients) and NF1 (4 patients) were evaluated by immunohistochemistry using a commercially available SDHB antibody (Abcam 1:50). Staining was evaluated by light microscopy and signal was scored as negative (no staining), weak non-granular cytoplasmic positivity, weak granular cytoplasmic positivity and moderate to strong granular cytoplasmic positivity
Results: Moderate to strong granular cytoplasmic positivity was noted in all paragangliomas/pheochromcytomas from patients with ret, NF1 and SDHD germline mutations. In the tumors from patients with germline SDHB mutations, 5 tumors showed weak granular cytoplasmic positivity and 1 tumor showed weak non-granular cytoplasmic positivity.
Conclusions: By immunohistochemistry, we continued to observe weak, mostly granular cytoplasmic positivity for SDHB in tumors from patients with known SDHB germline mutations. In addition, strong granular reactivity was identified in tumors from patients with confirmed SDHD as well as NF-1 and ret mutations. While weak granular reactivity for SDHB may suggest the possibility of SDHB mutation, in our experience this immunostain does not replace testing for germline mutations and does not predict the presence of SDHD mutations.
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 49, Tuesday Afternoon