Bronchiolar Adenoma: Expansion of the Concept of Ciliated Muconodular Papillary Tumors With Proposal for Revised Terminology Based on Morphologic, Immunophenotypic, and Genomic Analysis of 25 Cases.
Bronchiolar Adenoma: Expansion of the Concept of Ciliated Muconodular Papillary Tumors With Proposal for Revised Terminology Based on Morphologic, Immunophenotypic, and Genomic Analysis of 25 Cases.
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DOI：
10.1097/pas.0000000000001086
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发表时间：
2018-08
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影响因子：
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通讯作者：
Rekhtman N
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作者：
Chang JC;Montecalvo J;Borsu L;Lu S;Larsen BT;Wallace WD;Sae-Ow W;Mackinnon AC;Kim HR;Bowman A;Sauter JL;Arcila ME;Ladanyi M;Travis WD;Rekhtman N
我们已经确定了 25 个涉及肺泡肺实质的病变，其特征是含有连续层基底细胞的平淡双层细支气管型上皮的结节性增殖。这些病变与最近描述的纤毛粘液结节乳头状瘤（CMPT）有一些共同的组织学特征；然而，大多数病变并不符合所有诊断标准，因为它们仅表现出局灶性或缺乏乳头状结构，并且具有不同数量的纤毛和粘液细胞，有些病变完全缺乏这些成分中的一种或两种。形态学和免疫组织化学特征范围从类似于近端细支气管的那些（近端型：中等至丰富的粘液和纤毛细胞；管腔细胞中TTF1阴性或弱；n=8）到那些类似于呼吸性细支气管的那些（远端型：粘液和纤毛细胞很少或缺失；管腔细胞中TTF1阳性；n=17）。所有病变的标志是连续的基底细胞层（p40 和 CK5/6 阳性）。我们暂时将这些病变命名为细支气管腺瘤，并分析了它们的临床病理学和分子特征。所有细支气管腺瘤均为离散的、边界清晰的病变，中位大小为 0.5 厘米（范围：0.2 – 2.0 厘米）。大多数病变要么完全平坦（n = 14），要么包含局灶性乳头状结构（n = 7）；只有 4 个病变，全部为近端型，主要为乳头状，符合 CMPT 的经典描述。值得注意的是，在提交冰冻切片评估的 9 个病变中，7 个被诊断为腺癌。没有观察到任何病变的术后复发（中位随访 11 个月）。 21 个细支气管腺瘤接受了 BRAF V600E 的新一代测序和/或免疫组织化学检查，揭示了与之前描述的 CMPT 相似的突变谱，包括 BRAF V600E 突变 (n=8, 38%)、异常 EGFR 外显子 19 缺失 (n=2, 10%)、EGFR 外显子 20 插入 (n=2, 10%)、KRAS 突变(n=5, 24%) 和 HRAS 突变 (n=1, 5%)。近端和远端类型病变的突变谱相似。总之，我们描述了一个假定良性克隆增殖家族，其形态谱概括了细支气管树的各个级别，其中只有一小部分符合 CMPT 的经典描述。这些病变范围内可比的突变谱和部分重叠的形态特征支持了它们的疾病学关系。我们建议将整个病变家族指定为细支气管腺瘤，目前指定为 CMPT 的病变代表该家族的一个亚组。
We have identified 25 lesions involving alveolar lung parenchyma characterized by nodular proliferation of bland bilayered bronchiolar-type epithelium containing a continuous layer of basal cells. These lesions shared some histologic features with the recently described entity of ciliated muconodular papillary tumor (CMPT); however, the majority did not fit all diagnostic criteria in that they exhibited only focal or absent papillary architecture, and they had variable number of ciliated and mucinous cells, with some lesions entirely lacking one or both of these components. The morphologic and immunohistochemical features ranged from those resembling proximal bronchioles (proximal-type: moderate to abundant mucinous and ciliated cells; negative or weak TTF1 in luminal cells; n=8) to those resembling respiratory bronchioles (distal-type: scant or absent mucinous and ciliated cells; positive TTF1 in luminal cells; n=17). The hallmark of all lesions was a continuous layer of basal cells (p40 and CK5/6-positive). We provisionally designated these lesions as bronchiolar adenomas and analyzed their clinicopathologic and molecular features. All bronchiolar adenomas were discrete, sharply circumscribed lesions with a median size of 0.5 cm (range: 0.2 – 2.0 cm). Most lesions were either entirely flat (n=14) or contained focal papillary architecture (n=7); only 4 lesions, all proximal-type, were predominantly papillary, fitting the classic description of CMPT. Notably, of 9 lesions submitted for frozen section evaluation, 7 were diagnosed as adenocarcinoma. No post-surgical recurrences were observed for any lesions (median follow-up 11 months). Twenty-one bronchiolar adenomas underwent next-generation sequencing and/or immunohistochemistry for BRAF V600E, revealing mutation profiles similar to those previously described for CMPTs, including BRAF V600E mutations (n=8, 38%), unusual EGFR exon 19 deletions (n=2, 10%), EGFR exon 20 insertions (n=2, 10%), KRAS mutations (n=5, 24%), and HRAS mutations (n=1, 5%). The mutation profiles were similar in proximal- and distal-type lesions. In conclusion, we describe a family of putatively benign clonal proliferations with a spectrum of morphology recapitulating various levels of the bronchiolar tree, of which only a minor subset fits the classic description of CMPT. Comparable mutation profiles and partially overlapping morphologic features across the spectrum of these lesions support their nosological relationship. We propose designating this entire family of lesions as bronchiolar adenomas, and that lesions currently designated CMPTs represent a subgroup of this family.