The patient, a 44-year-old woman, was admitted to our center in December 2011 suffering from cough, asthma, and asthenia. Peripheral blood studies showed severe iron-deficiency anemia, elevations of C-reactive protein, and polyclonal hypergammaglobulinemia. Computed tomogram demonstrated diffuse (lung, axillary, and mediastinal) lymphadenopathy, interstitial pneumonitis, and splenomegaly (Figures 1 and 1). Histology of left pulmonary nodule accessed by thoracic surgery revealed atretic follicles with plasmacytosis, prominent paracortical vascularity, and sinus histiocytosis with an overall appearance consistent with MCD (Figures 1 and 1). Immunohistochemistry for IgG and CD138 was positive, and IgG4 was negative (Figures 1 and 1). Based on clinical and pathological suspicion of Castleman disease, further testing revealed high interleukin-6 (IL-6) of 23.0 pg/mL and normal IgG4 of 1.28 g/L. The patient's serum tested negative for HIV, and no cytomegalovirus, Epstein-Barr virus, or human herpes virus-8 (HHV-8) replication was detected. She was diagnosed with HIV-negative and HHV-8-negative multicentric Castleman disease of plasma cell variant. She was started on monotherapy chemotherapy with low-dose cyclophosphamide, accompanied by oral steroids from March 2012.
Unfortunately, she was later readmitted to our hospital for severe abdominal pain and skin and mucous membrane bleeding in August 2015 with a history of type-II diabetes for two years. Just one month ago, she followed the doctors' advice of cessation of the cyclophosphamide for severe anemia (Hb, 4.4 g/dL). Continued monitoring of routine blood count showed normocytic normochromic anemia (Hb, 6.0-8.0 g/dL), severe thrombocytopenia (PLT, 10,000-20,000/muL), and mild leukocytosis (10,000-12,000/muL), while monocytes were at normal levels. Bone marrow (BM) study showed an increased number of megakaryocytes, and myeloid series hypercellularity and dysplastic change were evident. Abdominal CT showed severe splenomegaly and multifocal and wide-area infarction. Subsequently, she underwent laparoscopic splenectomy, and the pathological section demonstrated the structural breakdown and significant hypercellularity (Figures 2 and 2). In next nine months, there was a stable increase of WBC (20,000-100,000/muL), especially peripheral blood monocytes (1,500-10,000/muL), which was still accompanied by decreased platelet counts (15,000-60,000/muL) and anemia (Hb, 6.0-8.0 g/dL). At this period, BM examination was again performed and revealed a significant increase in monocytes (12%) and prominent dysplastic changes in myeloid lineages. High expression levels of CD13, CD33, CD14, CD64, and CD56 were detected in her bone marrow cells. The karyotype was normal, and BCR/ABL fusion gene was not detected by the fluorescent in situ hybridization. At the same time, molecular studies were negative for TET2, SRSF2, ASXL1, and SETBP1 mutations, which are reported in about 90% of patients with CMML. According to World Health Organization (WHO) classification, a diagnosis of CMML and MCD, which were simultaneously present, was made. Then, she received front-line treatment with decitabine (DAC, 20 mg/m2 for 5 d in a 4-week cycle) for CMML. Surprisingly, after just one cycle, the WBC count had declined to 15,000/muL and the Hb increased to 9.0 g/dL and PLT to 220,000/muL (Figure 3). She also was recommended allogeneic hematopoietic stem cell transplant (HSCT) as the only potentially curative option.