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Familial haemophagocytic lymphohistiocytosis-related plasma cell neoplasm: a case report
  1. Marco Pizzi1,
  2. Elena Sabattini2,
  3. Gaia Goteri3,4,
  4. Paolo Pierani5,
  5. Francesco Bacci2,
  6. Carlo Sagramoso2,
  7. Simona Righi2,
  8. Stefano A Pileri2
  1. 1Department of Medicine–DIMED, Surgical Pathology and Cytopathology Unit, University of Padova, Padova, Italy
  2. 2Hematopathology Section, Department of Hematology and Oncological Sciences, ‘L. and A. Seràgnoli’, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
  3. 3Department of Biomedical Sciences and Public Health, Polytechnic University of Marche Region, Ancona Hospital, Ancona, Italy
  4. 4Department of Pathological Anatomy, Polytechnic University of Marche Region, Ancona Hospital, Ancona, Italy
  5. 5Division of Pediatric Hematology/Oncology, G Salesi Women's and Children's Hospital, Institute of Mother and Child Health, Polytechnic University of Marche, Ancona, Italy
  1. Correspondence to Dr Marco Pizzi, Surgical Pathology and Cytopathology Unit, Department of Medicine–DIMED, University of Padova, Via Aristide Gabelli 61, Padova 35121, Italy; marcopizzi2002{at}

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Haemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome sustained by extreme immunological activation and associated with specific symptoms and pathological findings (box 1).1–3

Box 1

Diagnostic criteria for HLH. The diagnosis of HLH can be established if one of either A or B below is fulfilled

A. A molecular diagnosis consistent with HLH: pathological mutations in PRF1, MUNC13-4, MUNC 18-2, Rab27a, STX11, SH2D1A, or BIRCA.


B. Diagnostic criteria for HLH fulfilled (five out of the eight criteria listed below):

  1. Fever ≥38.5°C

  2. Splenomegaly

  3. Cytopenias (affecting at least two of three lineages in the peripheral blood):

    • Haemoglobin <90 g/l (in infants <4 weeks: haemoglobin <100 g/l)

    • Platelets <100×109/l

    • Neutrophils <1×109/l

  4. Hypertriglyceridemia (fasting, >3.0 mmol/l) and/or hypofibrinogenemia (<1.5 g/l)

  5. Haemophagocytosis in bone marrow, spleen lymph nodes, or liver

  6. Low or absent natural killer cell activity

  7. Ferritin >500 μg/l

  8. sCD25 >24×103 U/l

Adapted from Henter et al,1 according to Jordan et al2

First described in 1952 as a familial syndrome,4 HLH is now regarded both as a primary and a secondary disease, triggered by various neoplastic and non-neoplastic disorders. Primary HLH are caused by specific mutations in genes involved in the cytotoxic immune response: up to 30% of cases are linked to MUNC13-4 loss, which leads to familial haemophagocytic lymphohistiocytosis type 3 (FHL3).2

We report the unique case of a monoclonal plasma cell disorder that arose in a patient with FHL3. To our knowledge, such an association has never been reported …

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  • Competing interests None.

  • Patient consent Obtained.

  • Provenance and peer review Not commissioned; externally peer reviewed.