The Utility of Phosphohistone-H3 Immunohistochemistry (PHH3) in Pheochromocytomas

Abstract

Abstract Introduction/Objective Most pheochromocytomas (PCC) are sporadic; ~40% present as part of familial syndromes and some cases are associated with germline mutations of succinate dehydrogenase (SDH) genes. Few cases are malignant. The Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) is a scoring system to predict behavior that includes evaluation of mitotic count, among other parameters. PHH3 has been used to assess mitosis in breast and glial tumors. The aim of this study was to assess the potential utility of PHH3 in pheochromocytomas. Methods/Case Report 50 cases of PCC diagnosed between 2016 and 2020 at our institution were included in the study. Clinicopathologic data was recorded. One hematoxylin and eosin (H&E) slide was selected per case and mitotic count was evaluated at 40x high power-fields (HPF). PHH3 was performed on the same block to assess mitoses. Cells with dark and coarsely clumped staining were considered positive for PHH3. PHH3-positive cells were counted also at 40x HPF. In one case with bilateral pheochromocytomas, the largest tumor was evaluated. Follow-up was available in 39 cases and recorded as no evidence of disease (NED), alive with disease (AWD), or dead of disease (DOD). Results (if a Case Study enter NA) 21 patients were female, 29 were males. Age ranged from 24 to 95 (mean: 56). Tumor size ranged from 1.1 to 16.0 cm (mean: 5.6 cm). Mean follow-up was 13.6 months (1-32 months range). Mitotic count ranged from 0 to 7 and 0 to 21 per 10 HPFs, on H&E and PHH3, respectively. PHH3 showed higher mitotic count in 33 cases compared to H&E. In 11 cases, mitotic count was equal on H&E and PHH3, and in the remaining cases, mitotic count was higher on H&E than PHH3. In cases with PASS score ≥ 4, 50% and 27% of cases had mitotic count >3/10HPF on PHH3 and H&E, respectively. Follow-up showed two patients AWD and one DOD, all of whom had PASS score ≥ 4, with mitotic count on H&E 7, 1 and 6 and mitotic count on PHH3 8, 4, and 21 respectively. Conclusion This is the first study evaluating the use of PHH3 in pheochromocytomas. Overall, mitotic count was higher on PHH3 than on H&E. This indicates PHH3 is a helpful tool in counting mitosis. Since the PASS score is an imperfect system to predict outcome, additional studies are needed to evaluate the use of PHH3 in prognostic scoring systems for PCC.