Kimura Noriko, Muroya Koji, Yonamine Masato, Takekoshi Kazuhiro, Sato Takeshi, Hirose Rei, Sasaki Takato, Tamai Kana, Mabe Hiroyo, Kawashima Junji, Kijima Hiromichi, Naruke Yuki, Katabami Takuyuki
Department of Clinical Research, and Department of Diagnostic Pathology, National Hospital Organization Hakodate Medical Center, Hakodate 041-8512, Japan.
Department of Endocrinology and Metabolism, Kanagawa Children's Medical Center, Yokohama 232-8555, Japan.
Endocr J. 2025 Apr 1;72(4):399-412. doi: 10.1507/endocrj.EJ24-0584. Epub 2025 Feb 1.
Pediatric patients with pheochromocytoma (PCC)/paraganglioma (PGL) (PPGL) are rare, and clinicopathological investigations, especially the relationship between gene analysis and histological features, are insufficient. We comprehensively examined the clinical data, germline/somatic variants (mutations), and pathological characteristics of operated tumors using immunohistochemical expression and histological grading by Grading of Adrenal PCC and PGL score. This study included 28 patients (15 males and 13 females) aged <19 years. The age at the diagnosis was 12.8 ± 4.5 years. The included patient often had multiple PPGLs, with 39 tumors, including 21 PCCs and 18 PGLs, with average tumor sizes of 45.0 ± 22.8 and 42.6 ± 23.6 mm, respectively. Genomic types examined by gene mutations and immunohistochemistry of CA9 for VHL, SDHB for SDHx, and MAX for MAX, classified them into 14 VHL (50%), ten SDHx (35.7%), one MAX (3.6%), and three unknown (10.7%) types. Tumor metastasis was limited to two SDHB-related PPGLs, but not to VHL-related PPGLs. In both patients, the metastatic sites were the bones. The average GAPP score of the PPGLs was 2.9 ± 1.5 in VHL and 5.3 ± 1.7 in SDHB, and histological grades were well-differentiated in VHL and moderately differentiated in SDHB. SSTR2 expression was positive in 90% of SDHB-related PPGLs, but negative in 75% and weakly or focally positive in 25% of VHL-related PPGLs. Most pediatric PPGLs (90%) demonstrated mutations in VHL, SDHB, and MAX, with histological features depending on the mutation type. Combined genetic and immunohistochemical examination is desirable for accurate genomic diagnosis, and clinicopathological study.
患有嗜铬细胞瘤（PCC）/副神经节瘤（PGL）（PPGL）的儿科患者较为罕见，临床病理研究，尤其是基因分析与组织学特征之间的关系尚不充分。我们通过肾上腺PCC和PGL评分的免疫组化表达和组织学分级，全面检查了手术肿瘤的临床数据、种系/体细胞变异（突变）和病理特征。本研究纳入了28例年龄＜19岁的患者（15例男性和13例女性）。诊断时的年龄为12.8±4.5岁。纳入的患者常患有多个PPGL，共39个肿瘤，其中包括21个PCC和18个PGL，平均肿瘤大小分别为45.0±22.8和42.6±23.6mm。通过基因突变以及针对VHL的CA9、针对SDHx的SDHB和针对MAX的MAX进行免疫组化检查的基因组类型，将它们分为14种VHL型（50%）、10种SDHx型（35.7%）、1种MAX型（3.6%）和3种未知型（10.7%）。肿瘤转移仅限于2个与SDHB相关的PPGL，而与VHL相关的PPGL未发生转移。在这两名患者中，转移部位均为骨骼。VHL相关PPGL的平均GAPP评分为2.9±1.5，SDHB相关PPGL的平均GAPP评分为5.3±1.7，VHL相关PPGL的组织学分级为高分化，SDHB相关PPGL的组织学分级为中分化。90%的与SDHB相关的PPGL中SSTR2表达为阳性，而75%的与VHL相关的PPGL中SSTR2表达为阴性，25%的与VHL相关的PPGL中SSTR2表达为弱阳性或局灶性阳性。大多数儿科PPGL（90%）在VHL、SDHB和MAX中存在突变，其组织学特征取决于突变类型。联合基因和免疫组化检查对于准确的基因组诊断和临床病理研究是可取的。
