Perry A, Molberg K, Albores-Saavedra J
Department of Pathology, University of Texas Southwestern Medical Center at Dallas, USA.
Cancer. 1996 Feb 15;77(4):750-6. doi: 10.1002/(sici)1097-0142(19960215)77:4<750::aid-cncr22>3.0.co;2-z.
Although hyperplasia of C-cells has been described in association with various pathologic and physiologic conditions, criteria for its diagnosis are poorly defined. Both neoplastic and physiologic C-cell proliferations have been lumped together under the umbrella designation of C-cell hyperplasia (CCH), creating considerable confusion among clinicians and pathologists.
in order to compare the morphologic and immunohistochemical characteristics of the two major types of CCH, we examined thyroid sections of 17 patients with familial forms of C-cell hyperplasia and/or neoplasia and tissue sections of 19 thyroid glands known to have reactive or physiologic CCH (at least 50 C-cells per one low power field, 100X). Hematoxylin and eosin (H & E) stained sections and immunohistochemical stains for calcitonin were assessed in each case.
Physiologic or reactive CCH was not recognized with certainty on H & E stains in any of the cases due to morphologic similarities between C-cells and adjacent follicular cells. Detection of this form of hyperplasia, which was predominantly diffuse, required calcitonin immunostains and quantitative analysis. Conversely, nodular and diffuse neoplastic CCH was easily identified with conventional H & E stains at the periphery of 11/12 (92%) familial medullary thyroid carcinomas (MTC). In the other five cases, neoplastic C-cell hyperplasia was the only pathologic finding on thyroidectomy performed for elevated serum calcitonin levels detected via provocative biochemical screening or identification of the mutated RET proto-oncogene by genetic analysis. The C-cells in this neoplastic form of CCH were large, mildly to moderately atypical, and confined within the basement membrane of thyroid follicles. Moreover, these cells were cytologically indistinguishable from those of invasive MTC cells.
Physiologic and neoplastic CCH are biologically and morphologically distinct entities. The former cannot be recognized with certainty with conventional stains and requires immunohistochemistry and quantitative analysis for diagnosis. The latter consists of mildly to moderately atypical C-cells that can be identified with H & E stained sections. Consequently, the number of C-cells is of no importance for the diagnosis of neoplastic CCH which is considered to be the precursor (medullary carcinoma in situ) of invasive medullary carcinoma.
尽管已描述C细胞增生与多种病理和生理状况相关，但其诊断标准仍不明确。肿瘤性和生理性C细胞增殖都被归为C细胞增生（CCH）这一统称之下，给临床医生和病理学家造成了相当大的困惑。
为比较两种主要类型CCH的形态学和免疫组化特征，我们检查了17例患有家族性C细胞增生和/或肿瘤的患者的甲状腺切片，以及19个已知有反应性或生理性CCH（每低倍视野至少50个C细胞，100倍）的甲状腺组织切片。对每个病例评估苏木精和伊红（H&E）染色切片以及降钙素免疫组化染色。
由于C细胞与相邻滤泡细胞在形态学上相似，在任何病例中，通过H&E染色都无法确切识别生理性或反应性CCH。这种主要为弥漫性的增生形式的检测需要降钙素免疫组化染色和定量分析。相反，在12例家族性甲状腺髓样癌（MTC）中的11例（92%）周边，通过传统H&E染色很容易识别结节性和弥漫性肿瘤性CCH。在其他5例中，肿瘤性C细胞增生是因通过激发性生化筛查检测到血清降钙素水平升高或通过基因分析鉴定出RET原癌基因突变而进行甲状腺切除时唯一的病理发现。这种肿瘤性CCH形式中的C细胞较大，轻度至中度异型，且局限于甲状腺滤泡的基底膜内。此外，这些细胞在细胞学上与侵袭性MTC细胞无法区分。
生理性和肿瘤性CCH在生物学和形态学上是不同的实体。前者通过传统染色无法确切识别，需要免疫组化和定量分析来诊断。后者由轻度至中度异型的C细胞组成，可通过H&E染色切片识别。因此，C细胞数量对肿瘤性CCH的诊断并不重要，肿瘤性CCH被认为是侵袭性髓样癌的前体（原位髓样癌）。
