FIGURE 1
(A) MGG stained cytospin (50X) from pleural puncture at D13 showing a pathological promyelocyte with Auer rods in a mixed inflammatory cells infiltrate including mesothelial cells and lymphocytes (B) MGG stained smear from the pleural puncture (50X) showing another pathognomonic APL promyelocyte with numerous Auer rods (C) FISH analysis with PML and RARA double fusion probes demonstrating the presence of PML-RARAfusion rearrangement.
Gorham’s disease is a rare disorder of unknown etiology characterized by massive osteolysis, angiomatosis involving blood vessels and more rarely lymph vessels5. Bone involvement is variable and can lead to destruction of osseous matrix. Pleural effusions or chylothorax may occur. Our patient was affected by a disabling osteolysis of pelvic bone treated by bisphosphonates which contraindicated iliac bone marrow puncture or biopsy. The previous thoracic radiotherapy and the angiogenesis associated with Gorham’s disease, may explain the recurrent non contributive diluted sternal aspirations. Blood molecular tests did not allow us to confirm the diagnosis of APL, NGS myeloid panel did not detect any somatic mutation in agreement with the absence of abnormal circulating cells. FISH analysis performed on D10 BM puncture was negative for PML-RARA fusion.
Considering the absence of circulating blasts and the observation of typical pathological promyelocytes only in the pleural fluid, the diagnosis of myeloid sarcoma (extramedullary APL) was retained. On D17, oral all-trans retinoic acid (ATRA) treatment 45 mg/m²/day (60 mg) was started with addition three days later of arsenic trioxide (ATO) 0.15 mg/Kg intravenous over 2 hours daily according to APL0406 protocol. Treatment was well tolerated.
Pleural fluid collected at D27 revealed differentiated granulocytic cells with persistent Auer rods, hypergranular cells and a significant eosinophilic contingent up to 35% of putative reactive origin. Thereafter, we confirmed the absence of pathological cells on two consecutive pleural punctures realized at D33 and D38. The treatment by ATRA/ATO combination was thus found to be well tolerated and efficient in our patient. Three months after the diagnosis, the patient was in cytological and molecular remission. She had oral ATRA (70 mg/day) 2 weeks per month as consolidation treatment.
BM sternal puncture was not contributive due to Gorham’s disease, and it could not be repeated on iliac crest due to the osteolysis associated with this disease. When myeloid sarcoma is diagnosed in association with bone marrow leukemic infiltration in favor of APL, a circulating phase with the presence of blasts should be observed in association with t(15;17) (q24;q21) translocation and the presence of the PML-RARAfusion transcript. In our case, no involvement of peripheral blood and diluted BM were observed. However, the demonstration of characteristic promyelocytes, without concomitant circulating blasts, nor cytogenetic anomaly or molecular criteria on blood and diluted BM, was in the line with the diagnostic of de novo MS without concomitantly APL. Due to therapeutic emergency of this clinical presentation, ATRA-ATO based chemotherapy should be required, and has been rapidly initiated with success and good tolerance.
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