BACKGROUND Familial hemophagocytic lymphohistiocytosis (FHL) is a primary immunodefici-ency disease caused by gene defects. The onset of FHL in adolescents and adults may lead clinicians to ignore or even misdiagnose the disease. To the best of our knowledge, this is the first report to detail the clinical features of type 2 FHL (FHL2) with compound heterozygous perforin ( PRF1 ) defects involving the c.163C>T mutation, in addition to correlation analysis and a literature review. CASE SUMMARY We report a case of a 27-year-old male patient with FHL2, who was admitted with a persistent fever and pancytopenia. Through next-generation sequencing technology of hemophagocytic lymphohistiocytosis (HLH)-related genes, we found compound heterozygous mutations of PRF1 : c.65delC (p.Pro22Argfs*29) (frameshift mutation, paternal) and c.163C>T (p.Arg55Cys) (missense mutation, maternal). Although he did not receive hematopoietic stem cell transplantation, the patient achieved complete remission after receiving HLH-2004 treatment protocol. To date, the patient has stopped taking drugs for 15 mo, is in a stable condition, and is under follow-up observation. CONCLUSION The delayed onset of FHL2 may be related to the PRF1 mutation type, pathogenic variation pattern, triggering factors, and the temperature sensitivity of some PRF1 mutations. For individual, the detailed reason for the delay in the onset of FHL warrants further investigation.

Background Study of the molecular biological characteristics of chronic neutrophilic leukemia complicated with plasma cell disorder (CNL‐PCD) and lymphocytic proliferative disease (CNL‐LPD). Methods The clinical data of a patient with chronic neutrophilic leukemia complicated with monoclonal gammopathy of undetermined significance (CNL‐MGUS) in our hospital were reviewed, and the Chinese and/or English literature about CNL‐PCD and CNL‐LPD in PubMed and the Chinese database CNKI in the past 10 years was searched to analyze the molecular biological characteristics of this disease. Results A 73‐year‐old male had persistent leukocytosis for 18 months. The white blood cell count was 46.77 × 109/L and primarily composed of mature neutrophils; hemoglobin: 77 g/L; platelet count: 189 × 109/L. Serum immunofixation electrophoresis showed IgG‐λ monoclonal M protein. A CT scan showed splenomegaly. Next‐generation sequencing (NGS) showed that CSF3R T618I, ASXL1 and RUNX1 mutations were positive. It was diagnosed as CNL‐MGUS. We summarized 10 cases of CNL‐PCD and 1 case of CNL‐LPD who underwent genetic mutation detection reported in the literature. The CSF3R mutational frequency (7/11, 63.6%) was lower than that of isolated CNL. The ASXL1 mutations were all positive (3/3), which may represent a poor prognostic factor. The SETBP1 mutation may promote the progression of CNL‐PCD. We also found JAK2, RUNX1, NRAS, etc. in CNL‐PCD. Conclusions Chronic neutrophilic leukemia may be more inclined to coexist with plasma cell disorder. The CSF3R mutation in CNL‐PCD is still the most common mutated gene compared with isolated CNL. Mutations in SETBP1 and ASXL1 may be poor prognostic factors for CNL‐PCD.

To describe myelodysplastic syndrome (MDS)/myeloproliferative neoplasm (MPN) combined with monoclonal gammopathy of undetermined significance (MGUS) in order to investigate the potential association between these 2 diseases. Two cases of confirmed chronic myelomonocytic leukemia (CMML) combined with MGUS were reported. In addition, prior publications of cases with combined MDS or MPN with MGUS were reviewed. The first case was of a 77-year-old man whose routine blood tests showed abnormal hemogram results. The diagnosis was CMML combined with IgM monoclonal gammopathy, and the disease course was 4 years. The CMML gradually progressed and the patient presented with anemia, thrombocytopenia, autoimmune hemolysis, and an increase in the number of immature cells in the bone marrow. Although the MGUS caused fluctuations in the concentrations of IgM, no IgM-associated organ damage was observed. Eventually, this patient died from a lung infection. The second case was of a 78-year-old man who sought treatment because of fever and a cough. An increase in the number of monocytes was discovered in the peripheral blood. Bone marrow smear results suggested obvious active granulocytes and an increase in the percentages of promyelocytes, myelocytes, and metamyelocytes. Unhealthy granulocytes and immature monocytes could also be observed, and the percentage of monocytes was increased. In addition, serum IgG levels were increased, and immunofixation electrophoresis results showed IgG-κ type M proteins. The diagnosis was CMML combined with IgG monoclonal gammopathy. These diseases were stable and follow-up was conducted for 1 year after diagnosis. The cases in this study combined with those that were reviewed in the relevant literature indicate that the presence of these 2 diseases in the same patient might not be a coincidence. The development of the 2 diseases in case 1 was different, and we speculate that they might have had different clonal origins. Whether CMML is a risk factor for MGUS and the role of clonal plasma cells in the occurrence and development of MDS and MDS/MPN requires further studies on a larger number of cases.