Kleinschmidt-DeMasters B K, Turin Christie G
Department of Pathology, Neurology, Neurosurgery.
Division of Endocrinology, Metabolism and Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO.
Am J Surg Pathol. 2024 Dec 1;48(12):1600-1616. doi: 10.1097/PAS.0000000000002306. Epub 2024 Sep 5.
Plurihormonal pituitary adenomas/neuroendocrine tumors express multiple pituitary hormones and/or transcription factors, as determined by immunohistochemistry (IHC). Three types exist based on Endocrine WHO 2022 classification: mature plurihormonal PIT1 (pituitary-specific POU-class homeodomain factor-1), immature PIT1-lineage tumors, and a third type with unusual combinations of pituitary hormones and/or transcription factors. However, since then, "somatogonatotroph"/"multilineage" tumors with PIT1/SF1 (steroidogenic factor 1) co-expression have been described, possibly confounding this classification. We performed a database search, from 2018 to 2023, to identify and reclassify tumors, correlating with neuroimaging and endocrinological features at presentation. We identified 22 cases: M 9:F 13, mean age at surgery 51±16 years. The most common symptoms at initial presentation were headaches and/or vision changes (6/22) and acromegaly (5/22). All tumors were macroadenomas, mean diameter of 25±17mm; 11/22 (50%) had cavernous sinus invasion. More than 70% of tumors clinically secreted at least 1 hormone, and 27% tumors secreted at least 2 different hormones. Four patients underwent >1 surgical intervention. Reclassification by IHC yielded almost exclusively 2 types: immature PIT1-lineage (9/22) and "somatogonadotroph"/"multilineage tumors" with PIT1/SF1 co-expression (12/22), the latter replacing mature plurihormonal tumors. One true unusual plurihormonal tumor was identified. The extent of growth hormone, prolactin, thyroid stimulating hormone, PIT1, and SF1 IHC was variable, but immunopositivity for follicle-stimulating hormone and/or luteinizing hormone was nearly confined to co-expressors, distinguishing these from immature PIT1-lineage tumors. In conclusion, tumor size, invasiveness, and endocrinopathies do not distinguish PIT1/SF1 co-expressing tumors from immature PIT1-lineage tumors preoperatively; only full IHC pituitary workup allows distinction.
多激素垂体腺瘤/神经内分泌肿瘤通过免疫组织化学（IHC）检测可表达多种垂体激素和/或转录因子。根据世界卫生组织2022年内分泌分类，存在三种类型：成熟的多激素PIT1（垂体特异性POU类同源结构域因子-1）、未成熟的PIT1谱系肿瘤，以及第三种具有垂体激素和/或转录因子异常组合的类型。然而，从那时起，已描述了具有PIT1/SF1（类固醇生成因子1）共表达的“生长促性腺激素细胞型”/“多谱系”肿瘤，这可能会混淆这种分类。我们在2018年至2023年期间进行了数据库检索，以识别和重新分类肿瘤，并将其与就诊时的神经影像学和内分泌特征相关联。我们共识别出22例病例：男性9例，女性13例，手术时的平均年龄为51±16岁。初次就诊时最常见的症状是头痛和/或视力改变（6/22）以及肢端肥大症（5/22）。所有肿瘤均为大腺瘤，平均直径为25±17mm；11/22（50%）侵犯海绵窦。超过70%的肿瘤在临床上分泌至少一种激素，27%的肿瘤分泌至少两种不同的激素。4例患者接受了不止一次手术干预。通过免疫组织化学重新分类几乎只产生了两种类型：未成熟的PIT1谱系（9/22）和具有PIT1/SF1共表达的“生长促性腺激素细胞型”/“多谱系肿瘤”（12/22），后者取代了成熟的多激素肿瘤。识别出1例真正的异常多激素肿瘤。生长激素、催乳素、促甲状腺激素、PIT1和SF1免疫组织化学的范围各不相同，但促卵泡激素和/或促黄体生成素的免疫阳性几乎仅限于共表达者，这将它们与未成熟的PIT1谱系肿瘤区分开来。总之，肿瘤大小、侵袭性和内分泌病变在术前无法将PIT1/SF1共表达肿瘤与未成熟的PIT1谱系肿瘤区分开来；只有完整的免疫组织化学垂体检查才能进行区分。
