Stenman Adam, Zedenius Jan, Juhlin Carl Christofer
Department of Oncology-Pathology, Karolinska Institutet, CCK, Karolinska University Hospital, R8:04, 171 76, Solna, Stockholm, Sweden.
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Langenbecks Arch Surg. 2018 Sep;403(6):785-790. doi: 10.1007/s00423-018-1679-9. Epub 2018 May 19.
Pheochromocytomas (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.
PASS 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.
Six 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.
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 MEN 2A cases until the results are reproduced in larger numbers.
嗜铬细胞瘤（PCC）具有恶性潜能，但目前用于准确检测侵袭性行为的组织学方法存在争议。两种最广泛使用的算法是“肾上腺嗜铬细胞瘤分级评分”（PASS）和“肾上腺嗜铬细胞瘤和副神经节瘤分级系统”（GAPP），两者大多依靠组织学参数来识别有播散性疾病风险的PCC患者。由于这些算法来自主要使用散发性PCC的研究，对于PASS或GAPP评分能否预测遗传性病例的恶性潜能知之甚少。
对41例PCC应用PASS和GAPP；13例PCC诊断于10例携带已确定的种系RET原癌基因突变的2A型多发性内分泌腺瘤（MEN 2A）患者，以及28例假定的散发性PCC。
13例MEN 2A肿瘤中有6例（46%）的PASS评分≥4，表明有侵袭性行为的可能性。此外，7/13例肿瘤（54%）的GAPP评分≥3，表明为“中度分化型”，有未来复发风险。所有PASS评分升高的MEN 2A PCC的GAPP评分也升高。相比之下，28例散发性PCC中有4例（14%）的PASS评分≥4，9/28例（32%）的GAPP评分≥3。随访发现研究中的所有病例均无转移或复发性疾病。
我们得出结论，PASS和GAPP评分系统在确定具有遗传性RET突变的PCC的真正恶性潜能方面可能并非最佳选择，并主张在MEN 2A病例中谨慎使用这些评分，直到在更多病例中得到验证。
