Department of Pathology, University of California San Francisco, San Francisco, California; Department of Pathology, Genentech, Inc, South San Francisco, California.
Department of Pathology, Stanford University School of Medicine, Stanford, California.
Mod Pathol. 2023 Dec;36(12):100324. doi: 10.1016/j.modpat.2023.100324. Epub 2023 Sep 3.
Adenoid cystic carcinoma (AdCC) is a rare triple-negative breast cancer analogous to its extramammary counterparts. Diagnosis of the more aggressive solid-basaloid variant of AdCC (SB-AdCC) can be challenging due to poorly defined histopathologic and molecular features. We characterized 22 invasive and in situ basaloid carcinomas by morphology, immunohistochemistry, genetics, and MYB status using multiple platforms and assessed clinical behavior and neoadjuvant chemotherapy responses. After consensus review, 16/22 cases were classified as SB-AdCC. All SB-AdCC had predominantly solid growth and at least focal myxohyaline stroma and were immune-poor. Eosinophilic squamoid cells (69%, 11/16) and basement membrane-like secretions (69%, 11/16) were common, and intercalated ducts (31%, 5/16) were less frequent. SB-AdCC typically expressed SOX10 (100%, 16/16) and luminal markers (100%, 16/16 CK7; 88%, 14/16 CD117; 93%, 13/14 CAM5.2). SMA (40%, 6/15) expression was less common, and SMM (27%, 3/11), GATA3 (20%, 3/15), and p63 (25%, 4/16) were mostly negative. MYB protein and/or MYB RNA overexpression was universal in evaluable cases (13/13), with RNA in situ hybridization (10/10) more reliable than immunohistochemistry (10/11, plus 4 excisions inconclusive). Fluorescence in situ hybridization and/or next-generation sequencing identified MYB rearrangements (20%, 3/15) and amplifications/copy gains (60%, 9/15) but no MYB::NFIB fusions. SB-AdCC often had aberrations in Notch pathway (60%, including 40% NOTCH1 and 20% NOTCH2) and/or chromatin modifier (60%, including 33% CREBBP) genes, with relatively infrequent TP53 mutations (27%). Unclassified invasive basaloid carcinomas lacking described histologic features of SB-AdCC (n = 4) and basaloid ductal carcinoma in situ (n = 2) showed similar immunoprofiles and genetics as SB-AdCC, including Notch aberrations and MYB overexpression with MYB rearrangements/amplifications. Overall, nodal (22%) and distant (33%) metastases were common, and 23% of patients died of disease (mean follow-up, 35 months; n = 22). Responses were poor in all 7 neoadjuvant chemotherapy-treated patients, without any achieving pathologic complete response. The data highlight the histopathologic spectrum of basaloid carcinomas including SB-AdCC and reveal shared genetics and MYB activation, which can be diagnostically useful. Aggressive behavior and poor treatment responses emphasize a need for additional treatment approaches.
腺样囊性癌（AdCC）是一种罕见的三阴性乳腺癌，与其乳房外的对应物类似。由于其组织病理学和分子特征定义不明确，诊断侵袭性实性基底样变体的 AdCC（SB-AdCC）可能具有挑战性。我们通过形态学、免疫组织化学、遗传学和 MYB 状态使用多种平台对 22 例侵袭性和原位基底样癌进行了特征描述，并评估了临床行为和新辅助化疗反应。经过共识审查，16/22 例病例被归类为 SB-AdCC。所有 SB-AdCC 均具有主要的实性生长，至少有局灶性黏液样基质，并免疫缺陷。嗜酸性鳞状细胞（69%，11/16）和基底膜样分泌物（69%，11/16）很常见，而中间导管（31%，5/16）则较少见。SB-AdCC 通常表达 SOX10（100%，16/16）和腔标志物（100%，16/16 CK7；88%，14/16 CD117；93%，13/14 CAM5.2）。SMA（40%，6/15）的表达较少见，SMM（27%，3/11）、GATA3（20%，3/15）和 p63（25%，4/16）大多为阴性。可评估病例中 MYB 蛋白和/或 MYB RNA 过表达普遍存在（13/13），RNA 原位杂交（10/10）比免疫组织化学（10/11，外加 4 例切除结果不确定）更可靠。荧光原位杂交和/或下一代测序确定了 MYB 重排（20%，3/15）和扩增/拷贝增益（60%，9/15），但没有 MYB::NFIB 融合。SB-AdCC 常伴有 Notch 通路（60%，包括 40% NOTCH1 和 20% NOTCH2）和/或染色质修饰剂（60%，包括 33% CREBBP）基因的异常，而 TP53 突变相对较少（27%）。缺乏 SB-AdCC 描述性组织病理学特征的未分类侵袭性基底样癌（n=4）和基底样导管原位癌（n=2）与 SB-AdCC 具有相似的免疫表型和遗传学特征，包括 Notch 异常和 MYB 过表达伴 MYB 重排/扩增。总体而言，淋巴结（22%）和远处（33%）转移很常见，23%的患者死于疾病（平均随访 35 个月；n=22）。所有 7 例接受新辅助化疗治疗的患者的反应均较差，无任何患者达到病理完全缓解。这些数据突出了包括 SB-AdCC 在内的基底样癌的组织病理学谱，并揭示了共同的遗传学和 MYB 激活，这在诊断上可能很有用。侵袭性行为和治疗反应不佳强调需要额外的治疗方法。
