Delfin Luvy, Mete Ozgur, Asa Sylvia L
Department of Pathology, University Hospitals Cleveland Medical Center, Cleveland, OH, 44106, USA; Case Western Reserve University School of Medicine, Cleveland, OH, 44106, USA.
Department of Pathology, University Health Network, University of Toronto, Toronto, M5G 2C4, Canada.
Hum Pathol. 2021 Aug;114:1-8. doi: 10.1016/j.humpath.2021.05.002. Epub 2021 May 12.
Follicular cells (FCs) are thought to be agranular, non-hormone-producing stellate cells distributed throughout the adenohypophysis, occasionally arranged around colloid-filled follicles, and thought to be more prominent in the vicinity of necrosis and apoptotic cells. A distinct but similar cell type, the folliculostellate cell (FSC), is a sustentacular cell that is negative for keratins and stains for S100, GFAP, and SOX10. While several studies have examined FSCs in pituitary neuroendocrine tumors (PitNETs), the distribution and derivation of FCs in these lesions is unclear. We examined the presence and distribution of FCs in 104 PitNETs obtained by trans-sphenoidal surgery, using immunohistochemistry for keratins as well as the full complement of immunohistochemical stains for tumor characterization. The tumors included 9 somatotroph, 5 mammosomatotroph, 7 lactotroph, 7 immature PIT1-lineage, 2 acidophil stem cell, 17 corticotroph, 53 gonadotroph, 2 null cell, and 2 unusual plurihormonal tumors. CK-positive FCs were only identified in gonadotroph PitNETs and were found in 12 (23%) of those tumors; all other tumor types were negative for FCs. FCs express keratins identified by CAM5.2, AE1/AE3, CK18, and CK19 antibodies. FCs were identified scattered singly among hormone-producing neuroendocrine cells, in small clusters of 3-5 cells and surrounding colloid-filled follicles, as well as linearly along intratumoral blood vessels. Sequential stains showed that FCs express nuclear SF1 and GATA3, transcription factors of gonadotrophs, and multiplex immunohistochemistry confirmed colocalization of SF1 in the nucleus of keratin-positive FCs. In this series, FCs were exclusively found in gonadotroph PitNETs and occurred in 23% of those tumors. Co-expression of gonadotroph transcription factors in FCs supports the concept of cellular plasticity and transformation of neoplastic hormone-producing neuroendocrine cells to FCs. Further studies are required to determine if and why gonadotrophs alone undergo this transformation, the function of these cells and whether they have prognostic value.
滤泡细胞（FCs）被认为是无颗粒、不产生激素的星状细胞，分布于整个腺垂体，偶尔围绕充满胶体的滤泡排列，并且在坏死和凋亡细胞附近更为突出。一种独特但相似的细胞类型，即滤泡星状细胞（FSC），是一种支持细胞，对角蛋白呈阴性，对S100、GFAP和SOX10呈阳性染色。虽然有几项研究检测了垂体神经内分泌肿瘤（PitNETs）中的FSCs，但这些病变中FCs的分布和来源尚不清楚。我们使用角蛋白免疫组织化学以及用于肿瘤特征描述的全套免疫组织化学染色，检测了经蝶窦手术获得的104例PitNETs中FCs的存在和分布。这些肿瘤包括9例生长激素细胞、5例泌乳生长激素细胞、7例催乳素细胞、7例未成熟PIT1谱系、2例嗜酸性干细胞、17例促肾上腺皮质激素细胞、53例促性腺激素细胞、2例无功能细胞和2例不寻常的多激素肿瘤。CK阳性的FCs仅在促性腺激素细胞PitNETs中被鉴定出来，在其中12例（23%）肿瘤中发现；所有其他肿瘤类型的FCs均为阴性。FCs表达由CAM5.2、AE1/AE3、CK18和CK19抗体鉴定的角蛋白。FCs被鉴定为单个散在于产生激素的神经内分泌细胞之间、3 - 5个细胞的小簇中以及围绕充满胶体的滤泡，并且沿肿瘤内血管呈线性分布。连续染色显示FCs表达促性腺激素细胞的核转录因子SF1和GATA3，多重免疫组织化学证实SF1在角蛋白阳性FCs的细胞核中共定位。在本系列中，FCs仅在促性腺激素细胞PitNETs中发现，且在其中23%的肿瘤中出现。FCs中促性腺激素细胞转录因子的共表达支持了细胞可塑性以及肿瘤性产生激素的神经内分泌细胞向FCs转化的概念。需要进一步研究来确定是否以及为何只有促性腺激素细胞会发生这种转化、这些细胞的功能以及它们是否具有预后价值。
