Kyrpychova Liubov, Carr Richard A, Martinek Petr, Vanecek Tomas, Perret Raul, Chottová-Dvořáková Magdalena, Zamecnik Michal, Hadravsky Ladislav, Michal Michal, Kazakov Dmitry V
*Sikl's Department of Pathology, Medical Faculty in Pilsen, Charles University in Prague, Pilsen, Czech Republic ‡Bioptical Laboratory ∥Biomedical Center, Faculty of Medicine in Pilsen and Charles University Medical Faculty Hospital, Pilsen ¶Agel Laboratory of Pathology, Novy Jicin, Czech Republic †Department of Histopathology, Warwick Hospital, Warwick, United Kingdom §Department of Pathology, University of Nantes, Nantes, France.
Am J Surg Pathol. 2017 Jun;41(6):738-749. doi: 10.1097/PAS.0000000000000841.
Basal cell carcinoma (BCC) with matrical differentiation is a fairly rare neoplasm, with about 30 cases documented mainly as isolated case reports. We studied a series of this neoplasm, including cases with an atypical matrical component, a hitherto unreported feature. Lesions coded as BCC with matrical differentiation were reviewed; 22 cases were included. Immunohistochemical studies were performed using antibodies against BerEp4, β-catenin, and epithelial membrane antigen (EMA). Molecular genetic studies using Ion AmpliSeq Cancer Hotspot Panel v2 by massively parallel sequencing on Ion Torrent PGM were performed in 2 cases with an atypical matrical component (1 was previously subjected to microdissection to sample the matrical and BCC areas separately). There were 13 male and 9 female patients, ranging in age from 41 to 89 years. Microscopically, all lesions manifested at least 2 components, a BCC area (follicular germinative differentiation) and areas with matrical differentiation. A BCC component dominated in 14 cases, whereas a matrical component dominated in 4 cases. Matrical differentiation was recognized as matrical/supramatrical cells (n=21), shadow cells (n=21), bright red trichohyaline granules (n=18), and blue-gray corneocytes (n=18). In 2 cases, matrical areas manifested cytologic atypia, and a third case exhibited an infiltrative growth pattern, with the tumor metastasizing to a lymph node. BerEP4 labeled the follicular germinative cells, whereas it was markedly reduced or negative in matrical areas. The reverse pattern was seen with β-catenin. EMA was negative in BCC areas but stained a proportion of matrical/supramatrical cells. Genetic studies revealed mutations of the following genes: CTNNB1, KIT, CDKN2A, TP53, SMAD4, ERBB4, and PTCH1, with some differences between the matrical and BCC components. It is concluded that matrical differentiation in BCC in most cases occurs as multiple foci. Rare neoplasms manifest atypia in the matrical areas. Immunohistochemical analysis for BerEP4, EMA, and β-catenin can be helpful in limited biopsy specimens. From a molecular biological prospective, BCC and matrical components appear to share some of the gene mutations but have differences in others, but this observation must be validated in a large series.
具有基质分化的基底细胞癌（BCC）是一种相当罕见的肿瘤，仅有约30例主要以个案报道形式记录在案。我们研究了一系列此类肿瘤，包括具有非典型基质成分的病例，这是一个迄今未报道过的特征。对编码为具有基质分化的BCC病变进行了回顾性研究；共纳入22例病例。使用抗BerEp4、β-连环蛋白和上皮膜抗原（EMA）的抗体进行了免疫组织化学研究。对2例具有非典型基质成分的病例（其中1例先前已进行显微切割以分别获取基质和BCC区域的样本），采用Ion AmpliSeq癌症热点Panel v2在Ion Torrent PGM上通过大规模平行测序进行了分子遗传学研究。患者有13名男性和9名女性，年龄在41至89岁之间。显微镜下，所有病变均至少表现出两种成分，即一个BCC区域（滤泡生发分化）和具有基质分化的区域。14例中BCC成分占主导，4例中基质成分占主导。基质分化表现为基质/超基质细胞（n = 21）、影细胞（n = 21）、鲜红色毛透明颗粒（n = 18）和蓝灰色角质形成细胞（n = 18）。2例中基质区域表现出细胞学非典型性，第3例表现为浸润性生长模式，肿瘤转移至淋巴结。BerEP4标记滤泡生发细胞，而在基质区域其表达明显降低或为阴性。β-连环蛋白则呈现相反的模式。EMA在BCC区域为阴性，但可染色一部分基质/超基质细胞。遗传学研究揭示了以下基因的突变：CTNNB1、KIT、CDKN2A、TP53、SMAD4、ERBB4和PTCH1，基质和BCC成分之间存在一些差异。得出的结论是，BCC中的基质分化在大多数情况下以多个病灶形式出现。罕见肿瘤在基质区域表现出非典型性。对BerEP4、EMA和β-连环蛋白进行免疫组织化学分析对有限的活检标本可能有帮助。从分子生物学角度来看，BCC和基质成分似乎有一些共同的基因突变，但在其他方面存在差异，但这一观察结果必须在大量病例中得到验证。
