Department of Pathology, University of British Columbia, Vancouver, British Columbia, Canada.
Department of Pathology, Vancouver General Hospital, Vancouver, British Columbia, Canada.
Cancer Cytopathol. 2020 Feb;128(2):126-132. doi: 10.1002/cncy.22221. Epub 2019 Dec 10.
The separation of benign from malignant mesothelial proliferations on effusion cytology can be difficult. Loss of methylthioadenosine phosphorylase (MTAP) by immunohistochemistry is an established marker of malignancy in mesothelial proliferations, but to the authors' knowledge largely has been applied only to biopsies. The current study was conducted to determine the usefulness of MTAP immunohistochemistry in the diagnosis of malignant mesothelioma in effusion cytology specimens.
A total of 21 effusion cytology cases of malignant mesothelioma were stained for MTAP and BRCA-associated protein 1 (BAP1), with 15 reactive mesothelial cytology cases used as a control. Fourteen cases had a paired surgical specimen for comparison, and 7 cases were run for CDKN2A deletion by fluorescence in situ hybridization.
Complete loss of MTAP cytoplasmic staining was noted in 7 of 21 effusion samples (33%), and no loss was observed in 11 effusion samples (52%); 11 of these cases had a matching surgical specimen and all 11 specimens demonstrated the same MTAP pattern. Partial loss was observed in 3 effusion specimens (80%, 40%, and 40% intact staining, respectively), but in all 3 the surgical specimen demonstrated 100% staining. None of the 15 reactive mesothelial cytology specimens demonstrated MTAP cytoplasmic loss. CDKN2A FISH demonstrated concordance in 5 of 7 cases (71%). MTAP immunohistochemistry had a sensitivity of 33% and a specificity of 100% for this differential diagnosis.
MTAP staining demonstrated generally good concordance between the cytologic and surgical specimens and appears to be useful in the diagnosis of mesothelioma on effusion specimens. Complete loss of MTAP is a reliable marker of malignancy, but the significance of partial loss of MTAP staining is unclear.
在胸腔积液细胞学检查中，良性间皮增生与恶性间皮增生的分离可能具有一定难度。免疫组织化学检测甲基硫腺苷磷酸化酶（MTAP）缺失是间皮增生恶性肿瘤的一种既定标志物，但据作者所知，该标志物主要应用于活检标本。本研究旨在确定 MTAP 免疫组化在胸腔积液细胞学标本中诊断恶性间皮瘤的作用。
共对 21 例恶性间皮瘤胸腔积液细胞学病例进行 MTAP 和 BRCA 相关蛋白 1（BAP1）染色，以 15 例反应性间皮细胞病例作为对照。其中 14 例有配对的手术标本进行比较，7 例进行 CDKN2A 缺失荧光原位杂交。
21 例胸腔积液样本中，有 7 例（33%）观察到 MTAP 细胞质染色完全缺失，11 例（52%）未见缺失；其中 11 例有配对的手术标本，所有 11 例标本均显示相同的 MTAP 模式。3 例胸腔积液样本中观察到部分缺失（分别为 80%、40%和 40%完整染色），但所有 3 例手术标本均显示 100%染色。15 例反应性间皮细胞细胞学标本均未见 MTAP 细胞质缺失。CDKN2A FISH 在 7 例中的 5 例（71%）中显示一致性。MTAP 免疫组化在这种鉴别诊断中的敏感性为 33%，特异性为 100%。
MTAP 染色在细胞学和手术标本之间具有较好的一致性，似乎可用于胸腔积液标本中诊断间皮瘤。MTAP 完全缺失是恶性肿瘤的可靠标志物，但 MTAP 染色部分缺失的意义尚不清楚。
