Abstract
Myeloid sarcoma is a rare extramedullary tumoral infiltration of immature myeloid cells and can occur in different sites of the body, without leukemic infiltration A 38-year-old woman patient presented at emergency with a pleural effusion and bicytopenias. In the following days, she worsened with a chylothorax and pancytopenias.
Pleural puncture cytologically revealed promyelocytes with Auer rods. Cytogenetic and molecular analyses subsequently confirmed the presence of the t(15:17) translocation. However, no circulating phase of these atypical promyelocytes was found. Similarly, no other origin was identified.
We conclude that the patient had a myeloid sarcoma of unknown etiology in the form of a pleural effusion with pathological promyelocytes. The patient was treated with a combination of oral all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) with a cytological and molecular remission persisting 3 months after diagnosis.
We report here the first case of a promyelocytic myeloid sarcoma of pleural origin without concomitant evidence of acute promyelocytic leukemia. We also show the efficacy of ATRA/ATO treatment in this etiology.
Abstract word count: 166 / Manuscript word count: 984
Number of references: 5. / Number of figures and tables: 2
Number of supplemental illustrations/tables: No
What is the new aspect of your work?
This is the first case of a promyelocytic sarcoma diagnosed on pleural effusion
What is the central finding of your work?
Promyelocytic sarcoma could be treated by ATRA/ATO based therapy like APL
What is the specific clinical relevance of your work?
Patient with promyelocytic sarcoma have a good and well tolerated answer to ATRA/ATO based treatment.
The data that support the findings of this study are available from the corresponding author, AA, upon reasonable request.
The research leading to these results has not received funding.
All co-authors have seen and agree with the contents of the manuscript and there is no financial interest to report. We certify that the submission is original work and is not under review at any other publication.
There is no ethics approval statement for this case report.
We have obtained the informed consent from the patient.
There is no required permission to reproduce material from other sources nor clinical trial registration to this case report.
Written informed consent was obtained from the patient to publish this report in accordance with the journal’s patient consent policy
Myeloid sarcoma (MS), also known as granulocytic sarcoma or chloroma, is a rare extramedullary tumoral infiltration of immature myeloid cells that can occur in different sites of the body, without leukemic infiltration of the bone marrow (which however can be observed subsequently). The most common affected sites are skin, lymph nodes, gastrointestinal tract, bone, soft tissues, and testes. MS is characterized by a slight male predominance (sex ratio 1.2:1) and affects patients at any age. MS may develop de novo or in association with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), myeloproliferative neoplasms (MPN), myelodysplastic/myeloproliferative neoplasms (MDS/MPNs). It could be detected months or years before the myeloid malignancies. MS can also be the initial manifestation of relapse in patients treated for AML while in remission1. Without intensive chemotherapy, most patients with MS have a higher risk to develop AML in association with shorter survival2. Some cases were reported in literature of MS with t(15;17) promyelocytes. APL with MS as the initial presentation where the most common infiltrated sites were spine, skin and tongue3. All evolved in Acute promyelocytic leukemia (APL) and combination ATRA-ATO was made, the reference to treat APL4.
We report here the first case of de novo myeloid sarcoma arising from abnormal promyelocytes with t(15;17) (q24;q21) diagnosed on pleural fluid.
A 38-year-old woman was admitted in emergency for dyspnea and neutropenia. She had a history of Gorham’s disease with lytic pelvis involvement. Three years ago, she was diagnosed with an invasive ductal carcinoma HER2+ of the left breast. She was initially treated by a combination of Epirubicin and Cyclophosphamide (4 cycles of EC) followed by Taxol plus Trastuzumab®. Subsequently, she had a mastectomy, parietal radiotherapy and hormonal maintenance therapy since. A rapidly -in two weeks- progressive dyspnea revealed a right pleural effusion without pulmonary embolism. A chylous pleural effusion was diagnosed with no sign of bacterial infection neither presence of breast malignant cells. CA 15-3 dosage was normal.
The patient also presented bicytopenia with neutrophils = 1.7 x 109/L and hemoglobin = 11.3 g/dL without abnormal circulating cells. On the following days, a thrombocytopenia appeared (platelets = 136 x 109/L). Haemostasis tests showed (Table 1) normal value of prothrombin time (PT), normal fibrinogen, increased D-dimers (Ddi) and prolonged activated partial thromboplastin time (aPTT) related to prophylactic heparin treatment. A sternal bone marrow (BM) aspiration was realized on D10 but it was non contributive due to hemodilution. No qualitative cytological abnormality on blood smear was noticed. We performed Next-Generation Sequencing (NGS) on BM sample which did not detect any mutation. Taken together, these results did not allow us to identify the origin of cytopenias.
On D13, another pleural puncture was carried out: a lactescent, hemorrhagic, and sterile liquid was collected with 1100 leucocytes/µL. Cytological analysis revealed a granulocytic contingent composed of promyelocytes containing intense azurophilic granulations and bundles of Auer rods (Fig 1a & 1b). These results suggested an extramedullary location of promyelocytic acute myeloid leukemia (APL). Flow cytometric analysis performed on this sample revealed an immature myeloid population expressing CD45dim, CD117, CD33, CD13 and partially CD7 whereas CD34 and HLA-DR were negative. Fluorescence in situ hybridization (FISH) confirmed the presence of a t(15;17) (q24;q21) translocation in 20% of the analyzed nuclei (Fig 1c). Results of molecular biology subsequently confirmed the presence of the fusion transcript PML-RARΑ (bcr2 breakpoint) at high level in the pleural effusion sample whereas blood and bone marrow samples were negative.