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.