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CASE REPORT article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1501217

A case of pulmonary ALK-positive histiocytosis combined with Birt-Hogg-Dubé syndrome carrying an EML4::ALK gene fusion: a case report and literature review

Provisionally accepted
Shuzhe Yang Shuzhe Yang 1Zhongyuan Bai Zhongyuan Bai 1*Qi Zhao Qi Zhao 2*Yajing Wang Yajing Wang 2*Yanfeng Xi Yanfeng Xi 2*
  • 1 Shanxi Medical University, Taiyuan, China
  • 2 Department of Pathology, Shanxi Provincial Cancer Hospital, Taiyuan, Shanxi Province, China

The final, formatted version of the article will be published soon.

    【Abstract】In this article, we report the first case of a 61-year-old woman who was diagnosed with both nodules and cystic lesions in her lungs. The lung nodules were diagnosed as ALK-positive histiocytosis (APH) carrying an EML4::ALK gene fusion, which microscopically displayed a mixed morphology of foamy cells, spindle cells, and Touton's giant cells. Immunohistochemistry showed expression of CD163, CD68, and ALK, while fluorescence in situ hybridization (FISH) with second-generation sequencing (NGS) showed the ALK gene fusion with the FLCN gene variant. The patient also had bilateral multiple cystic lesions in the lungs, which were morphologically consistent with pulmonary bullae. The FLCN gene variant, in combination with the results of NGS, led to the diagnosis of Birt-Hogg-Dubé syndrome (BHD). APH and BHD are very rare, and it is easy to misdiagnose or miss the diagnosis altogether if one is not familiar with the associated histology and immunohistochemistry. It is essential for pathologists to recognize the presence of these two diseases and understand the associated histomorphologic, immunohistochemical, and cytogenetic features to enable an accurate diagnosis and differential diagnosis.【Keywords】 ALK-positive histiocytosis, Birt-Hogg-Dubé syndrome (BHD), EML4-ALK, FLCN gene mutation, case report 【Introduction】APH is an unusual type of histiocytic neoplasm that can affect organs such as the liver and nervous system, as well as the spleen and bone marrow. While ALK-positive histiocytosis (APH) is often associated with involvement in various organs, the presentation of APH as an isolated lung nodule is extremely rare. In the available reported literature on the subject, there is great variability in the age, site of onset, and pathohistologic features of patients who develop APH. The

    Keywords: ALK-positive histiocytosis, Birt-Hogg-Dubé syndrome (BHD), EML4- ALK, FLCN gene mutation, case repoort

    Received: 24 Sep 2024; Accepted: 26 Dec 2024.

    Copyright: © 2024 Yang, Bai, Zhao, Wang and Xi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Zhongyuan Bai, Shanxi Medical University, Taiyuan, China
    Qi Zhao, Department of Pathology, Shanxi Provincial Cancer Hospital, Taiyuan, Shanxi Province, China
    Yajing Wang, Department of Pathology, Shanxi Provincial Cancer Hospital, Taiyuan, Shanxi Province, China
    Yanfeng Xi, Department of Pathology, Shanxi Provincial Cancer Hospital, Taiyuan, Shanxi Province, China

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