垂体Crooke型促肾上腺皮质激素分化特异性转录因子谱系神经内分泌肿瘤6例临床病理学分析

Pituitary Crooke cell neuroendocrine tumor of adrenocorticotropic hormone differentiation-specific transcription factor lineage:a clinicopathological analysis of six cases

目的探讨垂体Crooke型促肾上腺皮质激素分化特异性转录因子(TPIT,又称transcription factor 19,TBX19)谱系神经内分泌肿瘤的临床及病理学特点。方法收集中国科学技术大学附属第一医院2019年10月至2023年10月诊断的垂体Crooke型TPIT谱系神经内分泌肿瘤6例,分析其临床及病理学特点。结果6例中男性1例,女性5例,年龄26~75岁,平均年龄44岁,均发生于鞍内。临床表现为视觉障碍2例,月经紊乱1例,库欣综合征1例,头痛1例,无症状体检发现1例。术前血清学检查2例皮质醇、促肾上腺皮质激素(ACTH)同时升高,2例皮质醇升高,1例ACTH升高,1例仅出现垂体柄效应引起的泌乳素轻度升高。磁共振成像均显示增强扫描不均匀强化占位,直径1.7~3.2 cm,均为大腺瘤。镜下观察:肿瘤细胞呈不规则多边形,实性片状或围绕血管呈假乳头状排列,细胞核偏位或居中,大小不一,细胞质丰富,部分肿瘤细胞可见核周环状透明样变区域。免疫组织化学显示TPIT 5例弥漫强阳性,1例局灶弱阳性,ACTH细胞膜或细胞质弥漫强阳性,少数细胞核周可见淡染区,细胞角蛋白(CK)8/18可见>50%肿瘤细胞呈环状、戒圈状强阳性,p53局灶性弱阳性表达,Ki-67阳性指数1%~5%。过碘酸雪夫染色显示细胞质近胞膜处阳性,核周阴性。结论垂体Crooke型TPIT谱系神经内分泌肿瘤是一种罕见的垂体神经内分泌肿瘤,病理学特点主要表现为特征性核周环状透明样变及免疫标记CK8/18环状、戒圈状强阳性。该肿瘤属垂体神经内分泌肿瘤的高危亚型之一,侵袭性强,易复发,明确诊断对患者术后随访及多模式治疗具有重要意义。

Objective To investigate the clinicopathological features of Crooke cell tumor of adrenocorticotropic hormone differentiation specific transcription factor(TPIT,also known as transcription factor 19,TBX19)lineage neuroendocrine tumors.Methods Six cases of Crooke cell tumor diagnosed at the First Affiliated Hospital of University of Science and Technology of China,Hefei,China from October 2019 to October 2023 were collected.The clinical and pathological features of these cases were analyzed.Results Among the six cases,one was male and five were female,with ages ranging from 26 to 75 years,and an average age of 44 years.All tumors occurred within the sella turcica.Clinical presentations included visual impairment in two cases,menstrual disorders in one case,Cushing′s syndrome in one case,headache in one case,and one asymptomatic case discovered during a physical examination.Preoperative serum analyses revealed elevated levels of cortisol and adrenocorticotropic hormones in two cases,elevated cortisol in two cases,elevated adrenocorticotropic hormone in one case,and one case with a mild increase in prolactin due to the pituitary stalk effect.Magnetic resonance imaging revealed uneven enhancement of masses with maximum diameters ranging from 1.7 to 3.2 cm,all identified as macroadenomas.Microscopically,tumor cells exhibited irregular polygonal shapes,solid sheets,or pseudo-papillary arrangements around blood vessels.The cell nuclei were eccentric or centrally located,varying in size,with abundant cytoplasm.Some tumor cells showed perinuclear halo.Immunohistochemistry demonstrated diffuse strong positivity for TPIT in five cases,focal weak positivity for TPIT in one case,diffuse strong positivity for adrenocorticotropic hormone in all cases,and faint staining around the nuclei in a few cells.CK8/18 showed a strong positive ring pattern in more than 50%of tumor cells,focal weak positive expression of p53,and the Ki-67 positive index ranged 1%-5%.Periodic acid-Schiff staining revealed positive cytoplasm and negative perinuclear areas.Conclusions Crooke cell tumor is a rare type of pituitary neuroendocrine tumors.Its pathological characteristics include a distinctive perinuclear clear zone and immunohistochemical markers,such as CK8/18 exhibiting a ring or halo pattern.This entity represents a high-risk subtype among pituitary neuroendocrine tumors,displaying a high risk of invasion and a propensity for recurrence.Accurate diagnosis is crucial for the postoperative follow-up and multimodal treatment planning.