title: Diagnostic dilemma of IgG4-related primary localized cervical lymphadenopathy associated with aberrant IL-6 expression level.
abstract: BACKGROUND
  Immunoglobulin G4-related disease (IgG4-RD) is a recently recognized inflammatory condition with single- or multi-organ involvement. The disease is characterized by tumefactive lesions with dense IgG4 plasmacytic infiltration (an elevated IgG4(+)/IgG(+) cell ratio of > 40 %), storiform fibrosis, and obliterative phlebitis, with or without elevated serum IgG4 levels. The diagnostic criteria for IgG4-RD, proposed in 2011, were quite comprehensive and practical; however, it is important to remember that other diseases, such as hyper-interleukin (IL)-6 syndromes, may have common histopathological findings. Therefore, the histopathology of suspected IgG4-RD is occasionally not diagnostic. Here, we report a case of IgG4-related primary localized cervical lymphadenopathy without any other organ involvement. To our knowledge, there have been no previous reports of this. Additionally, the disease was associated with a 20-fold increase in IL-6 levels compared to that of the normal range.
  
  
  METHODS
  We report the case of a 52-year-old Japanese man who presented with a painless, somewhat diffuse swelling in the left submandibular region. Although the case fulfilled diagnostic criteria for IgG4-RD, the diagnosis was not straightforward due to abnormally high levels of serum IL-6. After systematic evaluation of the patient, a final diagnosis of IgG4-RD was established. Since then, a specialist in connective tissue disorders has evaluated the patient on a regular basis. Two years after his initial visit, no disease progress or systemic involvement has been noted.
  
  
  CONCLUSIONS
  We present a case of an IgG4-related primary localized cervical lymphadenopathy mimicking hyper-IL-6 syndrome. This case can serve as an excellent reminder that the definitive diagnosis of IgG4-RD should be established using a systematic approach, in particular when it appears as an atypical manifestation.
authors.affiliation: Dental and Oral Medical Center, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan. nakamura_moriyoshi@kurume-u.ac.jp.
authors.forename: Moriyoshi
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Dental and Oral Medical Center, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Iwamoto
authors.affiliation: Department of Biomedical Sciences, University of the Pacific, Arthur A. Dugoni School of Dentistry, 155 fifth St, San Francisco, CA, 94103, USA.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Chino
authors.affiliation: Dental and Oral Medical Center, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Todoroki
authors.affiliation: Dental and Oral Medical Center, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan.
authors.forename: Jingo
authors.initials: J
authors.lastname: Kusukawa
mesh_terms: D005871:Castleman Disease / Q000000981:diagnostic imaging* / Q000378:metabolism; D003937:Diagnosis, Differential; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism*; D007249:Inflammation; D015850:Interleukin-6 / Q000097:blood*; D000072281:Lymphadenopathy / Q000000981:diagnostic imaging* / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009333:Neck / Q000473:pathology; D014057:Tomography, X-Ray Computed
chemical_list: C508600:IL6 protein, human; D007074:Immunoglobulin G; D015850:Interleukin-6
keywords: Castleman’s disease; IL-6; IgG4; IgG4-related disease; Lymphadenopathy