Lymphoplasmacytic lymphoma in a patient with Birt–Hogg–Dubé syndrome

• Published in: International journal of hematology 2020-12, Vol.112 (6), p.864-870
• Main Authors: Kurata, Keiji, Matsumoto, Hisayuki, Jimbo, Naoe, Yakushijin, Kimikazu, Yamamoto, Katsuya, Ito, Mitsuhiro, Nakamachi, Yuji, Matsuoka, Hiroshi, Saegusa, Jun, Seyama, Kuniaki, Itoh, Tomoo, Minami, Hironobu
• Format: Article
• Language: English
• Subjects: Anemia; Antigens, CD20; Biomarkers, Tumor; Birt-Hogg-Dube Syndrome - complications; Birt-Hogg-Dube Syndrome - genetics; Bone marrow; Cancer; Case Report; CD20 antigen; Cell proliferation; Cysts; Exons - genetics; Female; Fluorine isotopes; Genetic Predisposition to Disease; Germ-Line Mutation; Health risks; Hematology; Humans; Hybridization; Immunohistochemistry; Kidney cancer; Lymph nodes; Lymphadenopathy; Lymphocytes; Lymphoid cells; Lymphoma; Malignancy; Medicine; Medicine & Public Health; Middle Aged; mRNA; Mutation; MyD88 protein; Myeloid Differentiation Factor 88 - genetics; Nonsense mutation; Oncology; Pneumothorax; Point mutation; Positron emission; Positron emission tomography; Positron Emission Tomography Computed Tomography; Proto-Oncogene Proteins - genetics; Skin diseases; Spleen; Syndecan-1; Tomography; Tumor suppressor genes; Tumor Suppressor Proteins - genetics; Waldenstrom Macroglobulinemia - diagnosis; Waldenstrom Macroglobulinemia - etiology; Waldenstrom Macroglobulinemia - genetics; Waldenstrom Macroglobulinemia - pathology
• ISSN: 0925-5710; 1865-3774
• DOI: 10.1007/s12185-020-02970-2

Birt–Hogg–Dubé (BHD) syndrome is an autosomal dominant disease characterized by benign skin hamartomas, pulmonary cysts leading to spontaneous pneumothorax, and an increased risk of renal cancer. BHD syndrome is caused by germline mutations in the folliculin ( FLCN ) gene, a putative tumor suppressor, which result in loss of function of the folliculin protein and may cause cancer predisposition. In a 45-year-old woman with anemia, lymphadenopathy, and a history of recurrent spontaneous pneumothorax, 18 F-FDG PET/CT detected diffuse and slight 18 F-FDG accumulation in the bone marrow, enlarged spleen, and systemic multiple enlarged lymph nodes. Genetic examination identified a germline nonsense mutation [c.998C > G (p.Ser333*)] on exon 9 of FLCN. Pathological examination of the lymph node revealed a diffuse neoplastic proliferation of plasmacytoid lymphocytes. The neoplastic lymphoid cells were positive for CD20, CD138, and light chain kappa as per immunohistochemistry and mRNA in situ hybridization, and a MYD88 gene mutation [c.755T > C (p.L252P)] was identified. Accordingly, she was diagnosed with lymphoplasmacytic lymphoma concomitant with BHD syndrome. To the best of our knowledge, this is the first report describing the development of hematological malignancy in a patient with BHD syndrome. The FLCN mutation might contribute lymphomagenesis as an additional mutation cooperating with the MYD88 mutation.