Abstract：
OBJECTIVE: Diagnosis of mesothelioma in situ (MIS) is historically controversial and, until recently, specific features defining the entity have not been well characterized. Most reported cases of MIS occurred in the pleura; peritoneal MIS is very rare. This study investigates the morphologic features and results of ancillary testing in peritoneal MIS.
METHODS: We present three patients with peritoneal MIS, as defined by a single layer of mesothelial cells with loss of nuclear BRCA-1-associated protein-1 (BAP1) immunostaining and without evidence of invasive tumour by microscopic evaluation, imaging, or direct examination of the peritoneum. Histology and immunostains were reviewed by three expert thoracic pathologists with multidisciplinary input. Next-generation sequencing (NGS) was performed in all three cases. A literature review was conducted to characterize this rare precursor lesion.
RESULTS: BAP1 was lost in all three lesions, while methylthioadenosine phosphorylase (MTAP) was retained in two (not performed in the third). NGS revealed BAP1 pathogenic alterations in all three cases as well as mutations of SMO, ERCC3, TET2, and U2AF1. Progression to invasive mesothelioma occurred in one patient at 13 months postdiagnosis (case 1). One patient was diagnosed at age 24 and was later found to harbour a BAP1 germline mutation (case 3).
CONCLUSIONS: This work describes the histologic features and clinicopathologic characteristics of peritoneal MIS in three cases, highlights BAP1 somatic and germline mutations in peritoneal MIS, and strengthens the importance of ancillary studies (including immunohistochemical and molecular studies) in the diagnosis of MIS.
METHODS: We present three patients with peritoneal MIS, as defined by a single layer of mesothelial cells with loss of nuclear BRCA-1-associated protein-1 (BAP1) immunostaining and without evidence of invasive tumour by microscopic evaluation, imaging, or direct examination of the peritoneum. Histology and immunostains were reviewed by three expert thoracic pathologists with multidisciplinary input. Next-generation sequencing (NGS) was performed in all three cases. A literature review was conducted to characterize this rare precursor lesion.
RESULTS: BAP1 was lost in all three lesions, while methylthioadenosine phosphorylase (MTAP) was retained in two (not performed in the third). NGS revealed BAP1 pathogenic alterations in all three cases as well as mutations of SMO, ERCC3, TET2, and U2AF1. Progression to invasive mesothelioma occurred in one patient at 13 months postdiagnosis (case 1). One patient was diagnosed at age 24 and was later found to harbour a BAP1 germline mutation (case 3).
CONCLUSIONS: This work describes the histologic features and clinicopathologic characteristics of peritoneal MIS in three cases, highlights BAP1 somatic and germline mutations in peritoneal MIS, and strengthens the importance of ancillary studies (including immunohistochemical and molecular studies) in the diagnosis of MIS.
摘要：
目的：原位间皮瘤（MIS）的诊断历来存在争议，直到最近,定义实体的特定特征尚未得到很好的表征。大多数报道的MIS病例发生在胸膜；腹膜MIS非常罕见。本研究调查了腹膜MIS的形态学特征和辅助测试结果。
方法：我们介绍了3例腹膜MIS患者，如由核BRCA-1相关蛋白-1（BAP1）免疫染色丢失且显微镜评估无浸润性肿瘤证据的单层间皮细胞定义，成像,或直接检查腹膜.组织学和免疫染色由三位专家的胸部病理学家在多学科的输入下进行了审查。在所有三种情况下都进行了下一代测序(NGS)。进行了文献综述以表征这种罕见的前体病变。
结果：BAP1在所有三个病变中均丢失，而甲硫腺苷磷酸化酶（MTAP）保留在两个中（第三个未进行）。NGS揭示了所有三例病例中的BAP1致病性改变以及SMO的突变，ERCC3、TET2和U2AF1。1例患者在诊断后13个月发展为侵袭性间皮瘤（病例1）。一名患者在24岁时被诊断出，后来被发现携带BAP1种系突变（病例3）。
结论：这项工作描述了3例腹膜MIS的组织学特征和临床病理特征，强调腹膜MIS中的BAP1体细胞和种系突变，并加强辅助研究（包括免疫组织化学和分子研究）在MIS诊断中的重要性。
方法：我们介绍了3例腹膜MIS患者，如由核BRCA-1相关蛋白-1（BAP1）免疫染色丢失且显微镜评估无浸润性肿瘤证据的单层间皮细胞定义，成像,或直接检查腹膜.组织学和免疫染色由三位专家的胸部病理学家在多学科的输入下进行了审查。在所有三种情况下都进行了下一代测序(NGS)。进行了文献综述以表征这种罕见的前体病变。
结果：BAP1在所有三个病变中均丢失，而甲硫腺苷磷酸化酶（MTAP）保留在两个中（第三个未进行）。NGS揭示了所有三例病例中的BAP1致病性改变以及SMO的突变，ERCC3、TET2和U2AF1。1例患者在诊断后13个月发展为侵袭性间皮瘤（病例1）。一名患者在24岁时被诊断出，后来被发现携带BAP1种系突变（病例3）。
结论：这项工作描述了3例腹膜MIS的组织学特征和临床病理特征，强调腹膜MIS中的BAP1体细胞和种系突变，并加强辅助研究（包括免疫组织化学和分子研究）在MIS诊断中的重要性。
