Abstract
PurposePheochromocytomas (PCCs) exhibit malignant potential, but current histological modalities for the proper detection of aggressive behavior are debated. The two most widespread algorithms are the “Pheochromocytoma of the Adrenal Gland Scaled Score” (PASS) and the “Grading System for Adrenal Pheochromocytoma and Paraganglioma” (GAPP), both which mostly rely on histological parameters to identify PCC patients at risk of disseminated disease. Since the algorithms are derived from studies using predominantly sporadic PCCs, little is known whether the PASS or GAPP scores can predict malignant potential in hereditary cases.MethodsPASS and GAPP were applied on 41 PCCs; 13 PCCs were diagnosed in ten multiple endocrine neoplasia type 2A (MEN 2A) patients carrying established germline RET proto-oncogene mutations, as well as 28 assumed sporadic PCCs.ResultsSix out of thirteen MEN 2A tumors (46%) exhibited PASS scores ≥ 4, indicative of a potential for aggressive behavior. In addition, 7/13 tumors (54%) exhibited GAPP scores ≥ 3, indicative of a “moderately differentiated type” with risk of future recurrence. All MEN 2A PCCs with an elevated PASS score also displayed an elevated GAPP score. In contrast, 4/28 (14%) sporadic PCCs demonstrated PASS scores ≥ 4, and 9/28 (32%) displayed GAPP scores ≥ 3. Follow-up found all cases in the study are free of metastatic or recurrent disease.ConclusionsWe conclude that the PASS and GAPP scoring systems might be suboptimal for determining true malignant potential in PCCs with constitutional RET mutations and advocate restrictive use of these scores in MEN 2A cases until the results are reproduced in larger numbers.
Highlights
Pheochromocytomas (PCCs) are rare endocrine tumors derived from the adrenal medulla
Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) and Grading system for adrenal pheochromocytoma and paraganglioma (GAPP) were applied on 41 PCCs; 13 PCCs were diagnosed in ten multiple endocrine neoplasia type 2A
We conclude that the PASS and GAPP scoring systems might be suboptimal for determining true malignant potential in PCCs with constitutional RET mutations and advocate restrictive use of these scores in multiple endocrine neoplasia type 2A (MEN 2A) cases until the results are reproduced in larger numbers
Summary
The majority of Department of Oncology-Pathology, Karolinska Institutet, CCK, Karolinska University Hospital, R8:04, 171 76, Solna, Stockholm, Sweden. Stockholm, Sweden tumors are sporadic, a large subset of cases displays a hereditary background [1]. The current WHO criteria from 2017 states that all PCCs are potentially malignant and should be risk stratified using one or both of the established algorithms: the Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) [2] and an alternative scoring system by Kimura et al (the Grading System for Adrenal Pheochromocytoma and Paraganglioma (GAPP)) [3]. When assessing malignant potential of PCCs, the PASS algorithm is probably the most widespread scoring system. A score from 0 to 20 points is acquired based on histological findings, in which tumors with a PASS score ≥ 4 have the potential for aggressive behavior. The GAPP score categorize PCCs into three different types, well-differentiated PCCs (score 0–2), moderately differentiated PCCs (score 3–6), and poorly differentiated
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