在2021年世界卫生组织(WHO)胸部肿瘤分类中,高分化乳头状间皮肿瘤(WDPMT)的命名和诊断标准已更改,和一个新的实体,原位间皮瘤(MIS),介绍。从组织学上讲,这两个实体可能相似。然而,MIS被认为是侵袭性间皮瘤的前兆,需要证明BAP1和/或MTAP/CDKN2A的缺失才能诊断。而这些辅助测试的性能是可取的,但不是必要的诊断WDPMT,其中BAP1和/或MTAP/CDKN2A损失的意义没有很好理解或很好定义。在这种背景下,我们调查了21例WDPMT,从我们的病例档案中确定并根据2021年世卫组织标准诊断,探讨组织学及BAP1、MTAP/CDKN2A表达与石棉暴露等临床特征的关系,肿瘤的病灶和临床结果。有18个女人和3个男人,年龄在23-77岁之间(中位数为62岁),其中六个有石棉接触史,两个没有暴露,在13个暴露历史是不可用的。在20个腹膜肿瘤和一个胸膜肿瘤中,在手术时偶然发现了13例无关的疾病,在诊断时发现了8例腹膜肿瘤。在所有21个肿瘤中进行BAP1免疫组织化学(IHC),9例肿瘤显示BAP1表达缺失。MTAP/CDKN2A测试在14个肿瘤中进行,包括12个MTAPIHC和两个CDKN2A荧光原位杂交(FISH),三个肿瘤显示MTAP/CDKN2A表达缺失。两个具有MTAP/CDKN2A缺失的肿瘤也显示BAP1表达缺失。四名患者进展为侵袭性间皮瘤,包括一名患有胸膜肿瘤和石棉暴露的男性,三名女性患有多灶性腹膜肿瘤,两个有石棉暴露,一个没有暴露。在所有进展为侵袭性间皮瘤的患者的肿瘤中都观察到BAP1表达缺失,而其中两个肿瘤显示保留的MTAPIHC和两个未检测。有一名患有MTAP丢失并保留BAP1的肿瘤的患者在诊断后5个月死于无关原因。除初始切除外,八名患者还接受了WDPMT特异性治疗。所有患者的生存期为4-218个月,一名患者在49个月时死于间皮瘤。根据我们在根据2021年WHO标准诊断的21例WDPMT患者中的结果,我们建议,BAP1表达缺失的WDPMT最好被视为乳头状MIS,并且在诊断为WDPMT的患者中,石棉暴露史和多灶性肿瘤的存在应提示BAP1IHC辅助检测.此外,我们建议BAP1IHC在WDPMT的诊断中应该是必不可少的,诊断仅限于那些显示保留BAP1表达的肿瘤。然而,需要在更大的患者队列中进行更多的研究来探索WDPMT中BAP1表达与MTAP丢失之间的关系,这将有助于定义这个实体,并更清楚地将其与MIS和侵袭性间皮瘤分开。
The nomenclature and diagnostic criteria of well-differentiated papillary mesothelial tumour (WDPMT) have been changed in the 2021 World Health Organization (WHO) classification of thoracic tumours, and a new entity, mesothelioma in situ (MIS), introduced. Histologically these two entities may be similar. However, MIS is regarded as a precursor to invasive mesothelioma and requires demonstration of loss of BAP1 and/or MTAP/
CDKN2A for diagnosis, whereas performance of these ancillary tests is desirable but not essential for a diagnosis of WDPMT, in which the significance of BAP1 and/or MTAP/
CDKN2A loss is not well understood or well defined. Against this backdrop, we undertook an investigation of 21 cases of WDPMT, identified from our case files and diagnosed according to 2021 WHO criteria, to explore the relationship between histology and BAP1 and MTAP/CDKN2A expression with clinical features including asbestos exposure, focality of tumours and clinical outcome. There were 18 women and three men, with ages ranging from 23-77 years (median 62 years), in which six had a history of asbestos exposure, two had no exposure, and in 13 exposure history was unavailable. Of 20 peritoneal tumours and one pleural tumour, 13 were detected incidentally at the time of surgery for unrelated conditions and eight peritoneal tumours were multifocal at the time of diagnosis. BAP1 immunohistochemistry (IHC) was performed in all 21 tumours, with nine tumours showing BAP1 expression loss. MTAP/
CDKN2A testing was performed in 14 tumours, comprising MTAP IHC in 12 and
CDKN2A fluorescence in situ hybridisation (FISH) in two, with three tumours showing MTAP/
CDKN2A expression loss. Two tumours with MTAP/
CDKN2A loss also showed BAP1 expression loss. Four patients progressed to invasive mesothelioma, including one male with a pleural tumour and asbestos exposure, and three females with multifocal peritoneal tumours, two with asbestos exposure and one without exposure. BAP1 expression loss was seen in all tumours from the four patients who progressed to invasive mesothelioma, whilst two of these tumours showed retained MTAP IHC and two were not tested. There was one patient with a tumour with MTAP loss and retained BAP1 who died from unrelated causes 5 months after diagnosis. Eight patients received WDPMT-specific treatment in addition to the initial excision. Survival for all patients ranged from 4-218 months, with one patient dying of mesothelioma at 49 months. Based on our results in this series of 21 patients with WDPMT diagnosed according to 2021 WHO criteria, we propose that WDPMT with BAP1 expression loss may best be regarded as papillary MIS and that a history of asbestos exposure and the presence of multifocal tumours in patients diagnosed with WDPMT should prompt ancillary testing with BAP1 IHC. Further we propose that BAP1 IHC should be essential in the diagnosis of WDPMT, with the diagnosis restricted to those tumours which show retained BAP1 expression. However more studies in larger cohorts of patients are needed to explore the relationship between BAP1 expression and MTAP loss in WDPMT, which will help to define this entity and separate it more clearly from MIS and invasive mesothelioma.