Pediatric recurrent Rosai-Dorfman disease with germline heterozygous SLC29A3 and somatic MAP2K1 mutations
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LETTER TO THE EDITOR
Pediatric recurrent Rosai-Dorfman disease with germline heterozygous SLC29A3 and somatic MAP2K1 mutations Shruthi Suryaprakash 1
&
Amy George 2 & Scott Langenburg 3 & Süreyya Savaşan 2,4
Received: 28 August 2020 / Accepted: 7 September 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Dear Editor, Rosai-Dorfman disease (RDD) is a rare non-Langerhans cell histiocytosis (LCH), disorder listed under the “R group” of histiocytosis including familial and sporadic forms by the Histiocyte Society. Patients with RDD classically present with cervical lymphadenopathy, and some have extranodal disease. Somatic KRAS and MAP2K1 mutations were reported in RDD patients [1]. We report a patient with recurrent RDD with underlying germline and somatic mutations. A currently 7-year-old African-American male patient presented with cervical lymphadenopathy at 19 months of age. He had dysgammaglobulinemia with increased IgG, IgA, and IgE levels and elevated C-reactive protein and erythrocyte sedimentation rate. He tested positive for human herpesvirus 6 (HHV6). Lymph node biopsy findings were consistent with RDD and negative for HHV6 staining. Due to the progression, he was treated on oral steroids with improvement. He presented 2 1/2 years later with recurrent lymphadenopathy and also had been diagnosed with autism spectrum disorder. Repeat scans and biopsy confirmed the recurrence of RDD (Fig. 1a–c). A sizeable population of CD5-dim lymphocytes and clonal T-cell receptor (TCR) rearrangement pattern suggested
* Süreyya Savaşan [email protected] 1
Department of Pediatrics, Children’s Hospital of Michigan, Detroit, MI, USA
2
Division of Hematology/Oncology, Children’s Hospital of Michigan, Detroit, MI, USA
3
Division of Pediatric Surgery, Children’s Hospital of Michigan, Detroit, MI, USA
4
Division of Hematology/Oncology and Blood and Marrow Transplant Program, Department of Pediatrics, Barbara Ann Karmanos Cancer Center, Central Michigan University College of Medicine, Children’s Hospital of Michigan, 3901 Beaubien Blvd, Detroit, MI 48201, USA
T-cell large granular lymphocyte (T-LGL) expansion (Fig. 1d). He failed intravenous steroids, and has had two debulking surgeries so far. Vitamin B12 levels were very high and methylmalonic acid within normal levels. He has decreased lymphocyte responses to phytohemagglutinin, concanavalin A, tetanus and candida antigens with currently normal immunoglobulin levels, and small lymphadenopathy. Tumor tissue 596 gene mutational analysis revealed MCL1 copy number increase and a known pathologic somatic MAP2K1 missense mutation (c.159T > A p.F53L), along with overexpression of MAP2K1, NF-κB1, and NF-κB2 mRNA level; whole-exome sequencing showed likely pathogenic germline heterozygous mutations in SLC29A3 (c.45delC) and ACSF3 (c.1075G > A) genes. This patient has dysgammaglobulinemia and increased inflammatory markers, which has correlated with disease burden and shown improvements following debulking surgeries. Increased T-LGL (18-41%) with clonal TCR r
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