Pulmonary peripheral glandular papilloma and mixed squamous cell and glandular papilloma frequently harbour the BRAF V600E mutation.

AIMS: Pulmonary peripheral glandular papilloma (GP) and mixed squamous cell and glandular papilloma (MP) have very similar histological features to pulmonary ciliated muconodular papillary tumour (CMPT)/bronchiolar adenoma (BA). The underlying genetic relationships between GP/MP and CMPT/BA have rarely been characterised. We aimed to reveal the relationship between them. METHODS AND RESULTS: We performed a clinicopathological review and next-generation sequencing (NGS) study of two GPs and five MPs. Histologically, GPs/MPs showed similar cellular and architectural features to CMPTs/BAs, such as bilayered epithelium, bronchiole-associated lesions and skipping (discontinuous) growth pattern. One MP showed partial and inconspicuous endobronchiolar growth and more glandular structures, which was very similar to the appearance of CMPT/BA. BRAF V600E mutation was detected in four papillomas (57.1%, one GP and three MPs). CONCLUSIONS: Overlapping morphological features and comparable mutation profiles support that peripheral GPs/MPs and CMPTs/BAs are on the same disease spectrum. We propose expanding the concept of CMPT/BA and including GP and MP in the CMPT/BA family.

Bronchiolar adenoma-like tumour with monolayered component: Represent malignant transformation of bronchiolar adenoma? A series of five cases.

Pulmonary bronchiolar adenoma (BA) is a rare lung tumour, it is unclear whether BA can develop into a malignancy. We presented five cases of BA-like tumour with monolayered components. This type of tumour may represent the malignant transformation of BA. Histologically, these tumours showed acinar and lepidic growth patterns. The acinar components were well-differentiated. The glandular tumour cells in these tumours contained cuboidal to columnar cells resembling type II pneumocytes or club (Clara) cells. A small number of mucinous cells were found in two cases. A few scattered ciliated cells were detected in three cases. The ciliated cells only existed in the bilayered components. The basal cells were highlighted by CK5/6 and p40 in a partial region of the tumour rather than in the entire tumour. The glandular tumour cells, including those in the bilayered component, were diffusely positive for TTF-1 and napsin-A. EGFR Exon19 deletions were found in four cases, and BRAF V600E mutation was found in one case. These BA-like tumours have biphasic morphological and molecular characteristics of BA and lung adenocarcinoma, suggesting distal-type BA may develop into a malignancy. More cases should be studied and especially cases with metastasis should be searched to further prove the malignant transformation.

Clinicopathological, Radiological, and Molecular Features of Primary Lung Adenocarcinoma with Morule-Like Components.

BACKGROUND: Morule-like component (MLC) was a rare structure in primary lung adenocarcinoma. We aimed to reveal the clinicopathological, radiological, immunohistochemical, and molecular features of lung adenocarcinoma with MLCs. METHODS: Twenty lung adenocarcinomas with MLCs were collected, and computed tomographic and histological documents were reviewed. Immunohistochemistry, targeted next-generation sequencing, and Sanger sequencing for ß-catenin gene were performed. RESULTS: There were 9 lepidic adenocarcinomas, 8 acinar adenocarcinomas, 2 papillary adenocarcinomas, and 1 minimally invasive adenocarcinoma. Most patients (16/17) were shown a pure solid nodule, and 1 patient was shown a partly solid nodule on chest computed tomography (CT). Nine cases were accompanied with micropapillary components, and 3 were with cribriform components in which 2 suffered a worse prognosis. No significant association was found between the MCLs and the overall survival of lung adenocarcinoma (P = 0.109). The MLCs were often arranged in whorled or streaming patterns. The cells in MLCs showed syncytial and mild appearance. The MLCs were positive for E-cadherin, CK7, TTF-1, napsin-A, vimentin, and ß-catenin (membrane), and negative for CK5/6, p40, p63, Synaptophysin, chromogranin A, and Cdx-2. EGFR mutation, ALK-EML4 fusion, HER2 amplification, and PIK3CA mutation were detected in 16 cases, 2 cases, 1 case, and 1 case, respectively. EGFR mutation was more frequent in adenocarcinomas with MLCs than those without MLCs (P = 0.040). ß-catenin gene mutation was not detected in any patients. CONCLUSIONS: MLC is often observed in the background of acinar, lepidic, and papillary adenocarcinomas. Lung adenocarcinomas with MLCs tend to appear as a solid mass on CT and harbor EGFR gene mutations. The micropapillary components and cribriform components may cause poor prognosis of lung adenocarcinomas with MLCs. Vimentin is always positive in MLCs, and it is a useful marker for the identification of MLCs.

Primary mucinous cystadenocarcinoma of the breast with endocervical-like mucinous epithelium.

BACKGROUND: Primary mucinous cystadenocarcinoma of the breast is an extremely rare entity. To the best of our knowledge, only 17 patients have been described in the PubMed database. CASE REPORT: Here, we report a primary breast mucinous cystadenocarcinoma with endocervical-like mucinous epithelium in a 62-year-old woman. The patient was followed for 5 months without any adjuvant treatment and she continues to be disease free. CONCLUSIONS: Primary breast mucinous cystadenocarcinoma usually displays unique pathologic and immunohistochemical characteristics simulating its ovarian counterparts; it seems to have a good prognosis after complete resection.