3. Second case
The second case was a 45-year-old man with no significant medical history presenting for several months with an increasingly painful right hip with functional limitations. No traumatism, barotraumastism, microtraumatism or corticosteroid treatment was reported. Both pelvis and hip radiographs taken four months apart were normal. Bone scintigraphy revealed incomplete and non-displaced broken neck of the left thighbone. The right hip scan confirmed the results of the scintigraphy with osteolytic lesions of the lower part of the femoral neck and of the great trochanter and no bone callus or fracture displacement. In this context of pathologic bone lesions,18F-FDG PET/CT was performed showing multiple hypermetabolic bone lesions (cervical thoracic spine, humeral heads, pelvis, femurs and left internal tibial fracture) but no organ was appreciably involved (Figure 1).
The bone biopsy of the right femur suggested a bone localization of HCL with BRAF mutation negative by FISH but pV600E/K/R exon 15 positive in molecular search (qqPCR), CD20 Annexin-A1 and DB44 were also positive, as shown in Figure 2. Hematologic malignancy was not expected, taking into account the normal complete blood count: white blood cell count was 6.1x109/L composed of 3.46x109neutrophils/L, 1.99x109 lymphocytes/L, 0,58x109 monocytes/L and no malignancy cells, hemoglobin 15,1g/dL and platelets 202x109/L. Moreover, biochemistry and protein electrophoresis were strictly normal and there was no splenomegaly or lymphadenopathy at medical examination. More surprisingly, the bone marrow biopsy was within normal morphological limits without tumor cell infiltration. The bone marrow cytology in the center in charge of the patient found normal cytology with a smear of medium richness on which the different myeloid cell lines were correctly represented without any morphological abnormalities, no excess of blasts or abnormal lymphoid cells, plasma cells involvement was low and consisted in rare plasma cells with any dystrophy. A bone marrow sample was sent to a French expert center which, using multicolor multiparameter flow cytometry, showed 4,7x10-4kappa-restricted monotypic B cells of small-sized cells with CD11c, CD103, CD123 and CD25 expression (immunologic score: 4/4). Given the poor infiltration of the bone marrow, Nest Generation Sequencing (NGS) could not be performed. Flow cytometry was negative in the peripheral blood.
Although usual criteria of treatment were not met, a treatment was indicated because of the bone fracture. The patient received first-line therapy of HCL with purine analog, cladribine 0,14mg/kg J1 to J5 in sub-cutaneous to which monoclonal antibody anti-CD20, rituximab was added once a week during eight weeks. No surgical or radiotherapy indication was given. No side effects were observed. The response to treatment has been favorable with resolution of bone pain. On the blood count, only lymphopenia at 0,58x109/L was observed due to the treatment, the rest was normal: white blood cells at 4.7x109/L in which 3.32x109neutrophils/L and 0,42x109 monocytes/L, hemoglobin at 16g/dL and platelet count at 235x109/L. The evaluation performed two months after treatment initiation was suggested a complete response. The 18F-FDG PET/CT objectified absence of tumor infiltration and non-significant residual hypermetabolic fixations (humeral heads and left tibia), Figure 1. The bone marrow aspirate was normal in cytology with undetectable minimal residual disease. The bone marrow biopsy was normal and confirmed the CR.