垂体多激素PIT1谱系神经内分泌肿瘤临床病理学观察

Plurihormonal PIT1-lineage pituitary neuroendocrine tumors:a clinicopathological study

目的:探讨垂体多激素PIT1谱系神经内分泌肿瘤的临床病理学特点。方法:收集首都医科大学三博脑科医院2018年1月至2022年4月病理数据库中诊断为多激素PIT1谱系肿瘤的垂体神经内分泌肿瘤病例,整理相关临床及影像学资料,进行HE、免疫组织化学及特殊染色。结果:48例多激素PIT1谱系肿瘤纳入研究,成熟性多激素PIT1谱系肿瘤13例,不成熟性PIT1谱系肿瘤35例,研究显示两组肿瘤的临床及病理学特征均存在明显差异。临床特征:(1)成熟性多激素PIT1谱系肿瘤几乎均有垂体激素分泌增多的临床症状,而不成熟性PIT1谱系肿瘤少见,但有62.9%(22/35)的患者存在血清垂体激素低水平升高;(2)不成熟性PIT1谱系肿瘤患者偏年轻化,肿瘤体积更大,影像学易见侵袭周围组织。病理学特征:(1)成熟性多激素PIT1谱系肿瘤由大的嗜酸性细胞组成,生长激素表达比例高,而不成熟性PIT1谱系肿瘤由嫌色性细胞组成,催乳素表达比例更高;(2)成熟性多激素PIT1谱系肿瘤表现为一致性、弥漫性胞质广谱细胞角蛋白阳性,而不成熟性PIT1谱系肿瘤细胞角蛋白表达则具多样性;(3)不成熟性PIT1谱系肿瘤增殖明显活跃;(4)25.0%(12/48)多激素PIT1谱系肿瘤存在性激素的异常表达。使用Kaplan-Meier法进行肿瘤无进展时间分析,两组肿瘤间差异无统计学意义( P=0.648)。 结论:多激素PIT1谱系肿瘤属于少见的PIT1谱系垂体神经内分泌肿瘤类型,以不成熟性PIT1谱系肿瘤多见。依据垂体激素分泌增多的临床症状、嗜酸性肿瘤细胞、高比例生长激素表达、细胞角蛋白弥漫性胞质阳性和低增殖活性,可以协助成熟性多激素PIT1谱系肿瘤与不成熟性PIT1谱系肿瘤的鉴别。不成熟性PIT1谱系肿瘤临床病理学比较复杂。

ObjectiveTo investigate the clinicopathological characteristics of plurihormonal PIT1-lineage pituitary neuroendocrine tumors.MethodsForty-eight plurihormonal PIT1-lineage tumors were collected between January 2018 and April 2022 from the pathological database of Sanbo Brain Hospital,Capital Medical University.The related clinical and imaging data were retrieved.H&E,immunohistochemical and special stains were performed.ResultsOut of the 48 plurihormonal PIT1-lineage tumors included,13 cases were mature PIT1-lineage tumors and 35 cases were immature PIT1-lineage tumors.There were some obvious clinicopathological differences between the two groups.Clinically,the mature plurihormonal PIT1-lineage tumor mostly had endocrine symptoms due to increased hormone production,while a small number of immature PIT1-lineage tumors had endocrine symptoms accompanied by low-level increased serum pituitary hormone;patients with the immature PIT1-lineage tumors were younger than the mature PIT1-lineage tumors;the immature PIT1-lineage tumors were larger in size and more likely invasive in imaging.Histopathologically,the mature PIT1-lineage tumors were composed of large eosinophilic cells with high proportion of growth hormone expression,while the immature PIT1-lineage tumors consisted of chromophobe cells with a relatively higher expression of prolactin;the mature PIT1-lineage tumors had consistently diffuse cytoplasmic positive staining for keratin,while the immature PIT1-lineage tumors had various expression for keratin;the immature PIT1-lineage tumors showed more mitotic figures and higher Ki-67 proliferation index;in addition,25.0%(12/48)of PIT1-positive plurihormonal tumors showed abnormal positive staining for gonadotropin hormones.There was no significant difference in the progression-free survival between the two groups(P=0.648)by Kaplan-Meier analysis.ConclusionsPlurihormonal PIT1-lineage tumor belongs to a rare type of PIT1-lineage pituitary neuroendocrine tumors,most of which are of immature lineage.Clinically increased symptoms owing to pituitary hormone secretion,histopathologically increased number of eosinophilic tumor cells with high proportion of growth hormone expression,diffusely cytoplasmic keratin staining and low proliferative activity can help differentiate the mature plurihormonal PIT1-lineage tumors from the immature PIT1-lineage tumors.The immature PIT1-lineage tumors have more complicated clinicopathological characteristics.