A 69-year-old caucasian woman was admitted to our hospital for the removal of giant dorsal haemangiomas. Multiple scattered cutaneous vascular lesions had emerged in recent years (Fig. 1) and prompted excision surgery before. There was also a medical background of immune thrombocytopenic purpura for more than 30 years, under long-term treatment with corticosteroids and immunosuppressants (cyclosporine and azathioprine), and multinodular goitre associated with hyperthyroidism. There was no history of smoking and besides the haemangiomas, there were no other lung, skin or constitutional symptoms.
At admission, the platelet count was 75,000/muL (reference range [RR] 150-400); however, after the procedure, it dropped to 19,000/muL, and there was active bleeding from the surgical incisions. Methylprednisolone pulses were administered, and immunosuppressive therapy was maintained with the platelet count increasing to 47,000/muL and successful bleeding control. Nevertheless, during the following weeks, the patient's condition kept worsening with ascites and bilateral relapsing pleural effusion development. Paracentesis, thoracentesis, and bronchofibroscopies were performed, but although with characteristic exudative fluids, no pathological agents or malignant cells were ever identified.
At this point, blood analysis showed Hb 7.6 g/dL (RR 11.5-16.5), white blood count 14.9 x 109/L (RR 4-11), platelet count 3,000/muL, D-dimers 35,923 mug/L (RR <500), fibrinogen 1.2 g/dL (RR 1.5-4.0), C-reactive protein 5.97 mg/dL (RR <0.30), FT4 3.02 ng/mL (RR 0.8-1.76) and TSH 0.006 mIU/L (0.55-4.78). Blood and urine cultures were positive for Enterococcus faecium. A diagnosis of disseminated intravascular coagulopathy (DIC) in a patient with KMS and sepsis was made. Immunoglobulin, methylprednisolone, plasma, and cryoprecipitate, together with broad-spectrum antibiotics were administered. Platelets stabilized at around 30,000/muL, but a consumptive state with marked weight loss and clinical worsening kept progressing. A full-body CT scan was performed with no evidence of tumours, lymphadenopathies, or bone lesions.
After weeks, a Lowenstein-Jensen culture from bronchoalveolar lavage became positive for Mycobacterium tuberculosis. Standard antibacillary treatment was initiated; however, due to hepatotoxicity, the therapeutic scheme had to be readjusted. More than 4 months after admission, the patient was discharged on maintenance antibacillaries, corticosteroids, immunosuppressive therapy, and antithyroid drugs.
Within 2 months she was readmitted due to an extensive left pleural effusion causing dyspnoea and respiratory insufficiency. Blood analysis showed Hb 10.1 g/dL, platelet count of 3,000/muL, alkaline phosphatase 196 IU/L (RR 50-136), GGT 308 IU/L (RR 5-55) and C-reactive protein 11.10 mg/dL. Although no bone lesions had been identified so far, a bone marrow aspirate was performed and showed only a reactive bone marrow without signs of pathogens or malignant cells.
Active gastrointestinal bleeding eventually arose with the haemoglobin level dropping to 4 g/dL. Rescue therapy with rituximab was attempted with a platelet count increase to 42,000/muL and a D-dimer drop to 2,400 mug/L. Despite all the diagnostic and therapeutic efforts the patient died.
A post-mortem examination revealed bone marrow infiltration by large cells with an irregular core and large cytoplasm (Fig. 2a, b). Immunohistochemistry was positive for CD1a, S100, and CD5, and negative for markers of plasmacytic, B- and T-cell differentiation (Fig. 2c). Electron microscopy identified Birbeck granules (Fig. 2d). The cause of death was established as LCH.