The Fingerland Department of Pathology, Faculty of Medicine Hradec Kralove, University Hospital, Charles University, Hradec Kralove, Czech Republic.
Department of Neurosurgery, Faculty of Medicine Hradec Kralove, University Hospital, Charles University, Hradec Kralove, Czech Republic.
Histopathology. 2021 Sep;79(3):406-415. doi: 10.1111/his.14366. Epub 2021 May 21.
In somatotroph pituitary neuroendocrine tumours (adenomas), a pattern of cytokeratin (CK) 18 expression is used for tumour subclassification, with possible clinical implications. Rare somatotroph tumours do not express CK 18. We aimed to characterise this subset clinically and histologically.
Clinical and pathological data for the study were derived from a previously published data set of a cohort of 110 patients with acromegaly. Data included serum levels of insulin-like growth factor 1 (IGF1), growth hormone (GH), prolactin and thyroid-stimulating hormone (TSH), tumour diameter, tumour invasion defined by Knosp grade and immunohistochemical data concerning the expression of Ki67, p53, E-cadherin, somatostatin receptor (SSTR)1, SSTR2A, SSTR3, SSTR5 and D2 dopamine receptor. Additional immunohistochemical analysis (AE1/3, CK 8/18, vimentin, neurofilament light chain, internexin-α) was performed. CK 18 was negative in 10 of 110 (9.1%) tumours. One of these tumours was immunoreactive with CK 8/18 antibody, while the remainder expressed only internexin-α intermediate filament in patterns similar to CK 18 (perinuclear fibrous bodies). CK-negative tumours showed no significant differences with respect to biochemical, radiological or pathological features. They showed significantly higher expression of SSTR2A compared to the sparsely granulated subtype and significantly lower expression of E-cadherin compared to the non-sparsely granulated subtypes of tumours. The tumours showed divergent morphology and hormonal expression: two corresponded to densely granulated tumours and three showed co-expression of prolactin and morphology of either mammosomatotroph or somatotroph-lactotroph tumours. Four tumours showed morphology and immunoprofile compatible with plurihormonal Pit1-positive tumours.
CK-negative somatotroph tumours do not represent a distinct subtype of somatotroph tumours, and can be further subdivided according to their morphology and immunoprofile.
在生长激素细胞垂体神经内分泌肿瘤（腺瘤）中，细胞角蛋白（CK）18 的表达模式用于肿瘤分类，可能具有临床意义。罕见的生长激素细胞肿瘤不表达 CK 18。我们旨在从临床和组织学上对这一部分进行描述。
本研究的临床和病理数据来自先前发表的 110 例肢端肥大症患者队列的数据集中。数据包括胰岛素样生长因子 1（IGF1）、生长激素（GH）、催乳素和促甲状腺激素（TSH）的血清水平、肿瘤直径、Knosp 分级定义的肿瘤侵袭程度以及关于 Ki67、p53、E-钙粘蛋白、生长抑素受体（SSTR）1、SSTR2A、SSTR3、SSTR5 和 D2 多巴胺受体表达的免疫组织化学数据。进行了额外的免疫组织化学分析（AE1/3、CK 8/18、波形蛋白、神经丝轻链、中间丝-α）。在 110 个肿瘤中，有 10 个（9.1%）的 CK18 为阴性。其中一个肿瘤对 CK 8/18 抗体呈免疫反应性，而其余肿瘤仅表达 CK 18 相似的中间丝-α（核周纤维体）。CK 阴性肿瘤在生化、放射学或病理特征方面无显著差异。与稀疏颗粒亚型相比，它们显示出 SSTR2A 的表达显著增加，与非稀疏颗粒亚型相比，E-钙粘蛋白的表达显著降低。肿瘤表现出不同的形态和激素表达：两个肿瘤与致密颗粒肿瘤相对应，三个肿瘤表现为催乳素的共表达和催乳素-生长激素细胞肿瘤或生长激素细胞-催乳素细胞肿瘤的形态。四个肿瘤表现出形态和免疫表型与多激素 Pit1 阳性肿瘤相符。
CK 阴性生长激素细胞肿瘤不代表生长激素细胞肿瘤的一个独特亚型，可以根据其形态和免疫表型进一步细分。
