Abstract
Background: Myeloid Sarcoma (MS) are tumors containing myeloid blasts occurring in a location other than the bone marrow, including lymph nodes, skin, and soft tissues. MS presenting as polyserositis however is very rare, with only a few cases in the literature. Case Report: A 20-year-old male presented with cough, shortness of breath and was found to have left upper lobe consolidation, left pleural effusion, pericardial effusion, and a large anterior mediastinal mass. A transthoracic echocardiogram showed pericardial effusion with tamponade physiology. He underwent emergent pericardiocentesis and thoracentesis. The fluid studies showed flow cytometry findings consistent with MS/ acute myeloid leukemia (AML) phenotype. A bone marrow aspirate and biopsy were unremarkable and showed no immunophenotypic findings diagnostic of acute leukemia or a lymphoproliferative disorder. Cytogenetics was negative for AML abnormalities per FISH analysis. Videoassisted thoracoscopy surgery (VATS) with biopsy of the mediastinal mass, pericardium, and left upper lobe of the lung was consistent with MS. He was treated with induction cytarabine and idarubicin, and a follow up PET-CT scan showed complete remission. He is currently day 200 + post stem cell transplant with no evidence of disease recurrence. Conclusion: To the best of our knowledge, this is the first case of isolated myeloid sarcoma presenting as polyserositis, without prior leukemia/ bone marrow involvement. Hence, fluid studies should involve cytometry analysis and MS should be entertained as a differential for polyserositis, even without a history of prior leukemia. Timely diagnosis can expedite aggressive chemotherapy required for a potentially life-threatening disease.
- Myeloid sarcoma
- acute myeloid leukemia
- pericardial effusion
- cardiac tamponade
- pleural effusion
- polyserositis
Myeloid sarcomas (MS) are tumors comprising myeloid blasts occurring in a location other than the bone marrow. MS may occur in isolation, or more commonly in patients with a history of acute myeloid leukemia (AML), myeloproliferative neoplasm (MPN), myelodysplastic syndrome (MDS), or MPN/MDS. Isolated MS is extremely rare with an incidence of 2 cases per million adults. Hence, most information is limited to case reports and small retrospective series (1). Most common sites include lymph nodes, skin, soft tissues, bones, gastrointestinal tract, and the peritoneum (1). However, involvement of serous membranes is an extremely uncommon presentation of AML, with only a few cases in the literature (2, 3). We report the first case to our knowledge of myeloid sarcoma presenting as polyserositis (pericardial effusion and pleural effusion) in absence of any antecedent hematological disorder or bone marrow involvement.
Case Report
A 20-year-old male had presented with cough and shortness of breath for two weeks. Vitals on presentation showed tachycardia were otherwise unremarkable. Physical examination showed distant heart sounds and decreased breath sounds in the left lung fields. Workup showed normal complete blood count and chemistry. A chest x-ray showed left upper lobe (LUL) and lower lobe consolidation (LLL), left-sided pleural effusion, and enlarged cardiac silhouette. A computed tomography (CT) scan of the chest showed similar findings along with a 7.7 cm anterior mediastinal mass and a large pericardial effusion (Figure 1A). A transthoracic echocardiogram (TTE) revealed a large pericardial effusion (Figure 1B) with tamponade physiology. An emergent pericardiocentesis with removal of 1,240 ml pericardial fluid was performed. A follow-up TTE showed resolution of pericardial tamponade, and a left ventricular ejection fraction of 40-44%, with left ventricular global hypokinesis. The pericardial fluid cytology showed atypical hematopoietic cells with flowcytometry showing 71% CD45 moderate cells consistent with blasts and MS or AML immunophenotype. Thoracentesis fluid analysis showed a blastic infiltrate consistent with MS/AML. Given these findings, he underwent a bone marrow aspirate and biopsy which showed mildly hypercellular marrow for age with full trilineage maturation. Flow cytometry was unremarkable. Cytogenetics revealed a normal male karyotype and was negative for AML abnormalities per FISH analysis. Molecular Panel showed NRAS G12D and PHF6 mutations, classified as variants of unknown clinical significance. Video-assisted thoracoscopy surgery (VATS) with biopsy of the mediastinal mass (Figure 2A and B), pericardium (Figure 3A and B), and wedge resection of the left upper lobe of the lung (Figure 4) were performed, which were consistent with MS.
Imaging showing pleural effusion, pericardial effusion, anterior mediastinal mass, and left lung mass. (A) Computed tomography scan of the chest showing the anterior mediastinal mass (blue arrow), peripheral left upper lobe mass (yellow arrow), and left sided pleural effusion (orange arrow). (B) Transthoracic echocardiogram showing massive pericardial effusion (blue double-arrow).
Biopsy of mediastinal mass. (A) CD34 stain of mediastinal mass showing endothelial cells/blood vessels (blue arrow) and blasts (black arrow). (B) Positive myeloperoxidase stain of mediastinal mass suggesting myeloid lineage.
Biopsy of pericardial tissue. (A) H and E staining of pericardium tissue showing adipocytes/fat with a dense cellular infiltrate. (B) CD34 stain of pericardial tissue showing faint membranous positivity of tumor cells.
H and E staining of lung biopsy specimen showing involved lung with diffuse infiltrate and uninvolved lung parenchyma (black arrow).
He was treated with induction cytarabine and idarubicin, followed by a positron emission tomography-CT (PET-CT) scan which showed complete remission. This was followed by matched unrelated donor allogeneic peripheral blood stem cell transplantation (PBSCT) with myeloablative conditioning. Radiation therapy was not used given cardiac involvement and concerns for radiation-induced cardiotoxicity. Post-transplant bone marrow biopsy showed no evidence of leukemia, and full donor chimerism in CD3, CD33, and CD56. The patient is currently day 200 + post-transplant and with no evidence of recurrence of his disease.
This case report has used de-identified data and was considered exempt from human protection oversight by the institutional review board. The patient provided informed consent to use de-identified patient information and use of images to be published.
Discussion
Polyserositis secondary to myeloid sarcoma is very rare, with only a few cases documented to date (2, 3). Pleural fluid involvement is known in hematological malignancies like Hodgkin and Non-Hodgkin lymphoma (NHL), but uncommon in leukemias. A 2-year retrospective analysis of pleural fluid cytological specimens in India reported that 164 (18%) of 898 samples were malignant, with AML being an uncommon cause (2). Similar findings have been reported in some other studies (4, 5). Isolated MS presenting as pleural effusion is extremely rare, with only a few case reports in the literature (6, 7). Similarly, pericardial effusion is very uncommon in AML with only about a 0.5% resulting in a pericardial tamponade (8). Cardiac involvement by MS without bone marrow involvement has been documented in case reports in the form of epicardial, atrial, septal mass or ventricular mass, and myocardial infiltration. However, very few cases had concomitant pericardial effusion (9).
Our patient was found to have both pericardial effusions resulting in cardiac tamponade, and pleural effusion due to MS, with no evidence of bone marrow involvement by the disease. This to our knowledge is the first case where isolated myeloid sarcoma presented as polyserositis. In addition to polyserositis, our patient also had lung parenchyma and mediastinum involvement by MS.
No large prospective studies exist on the prognosis of MS given its rarity, variability of tumor location, genetics, presentation, and treatment modalities. A study by Ganzel et al. reporting outcomes in patients with AML treated in consecutive ECOG-ACRIN Cancer Research Group frontline trials showed that extramedullary disease (EMD) was not an independent prognostic factor. Notably, the study excluded patients with isolated EMD in absence of bone marrow disease, and cardiac involvement was not described in the sites involved (10). A pediatric study suggested better outcomes in isolated MS than in those with concomitant AML (11). Treatment of MS depends on factors related to tumor, patient factors like age, performance status, and timing of diagnosis in relation to AML (1). Systemic therapy is the principal treatment even in isolated MS given the high rate of progression to acute leukemia with local methods (surgery/radiotherapy). Chemotherapy regimens used in AML remission induction have been used in MS, including idarubicin and cytarabine, which were used in our patient. The comparison of different regimens in the setting of MS is very limited. No consensus exists on the type of regimen most suitable for cardiac MS, given the cardiotoxicity associated with conventional anti-leukemia agents (9). Our patient had a low ejection fraction but the given cardiac involvement with MS and its role in cardiomyopathy, along with the aggressive nature of his disease, the benefit of treatment outweighed the risk of possible cardiotoxicity with an anthracycline-containing regimen.
No controlled trials have evaluated the role of allogeneic hematopoietic stem cell transplantation (allogenic-SCT) in isolated MS, however retrospective studies have shown encouraging outcomes, suggesting it’s use as a first-line treatment in MS after induction of remission, particularly in those who achieve a complete remission with an AML induction protocol (12). Our patient achieved complete remission with induction protocol and subsequently underwent allogeneic-PBSCT and remains disease-free. Given the absence of bone marrow involvement on initial presentation, we employed a PET-CT scan to assess response.
Conclusion
MS should be entertained as a differential for polyserositis in the correct clinical context, even without a history of prior leukemia. Fluid studies should involve routine flow cytometry analysis in patients with polyserositis. This intervention could avoid delay in diagnosis and treatment, as timely intervention with the pericardiocentesis followed by aggressive chemotherapy resulted in the resolution of a potentially lifethreatening disease in our patient. Prospective studies are needed to delineate management decisions for MS, especially in the setting of cardiac involvement given concerns of cardiac toxicity with standard anthracycline-containing regimens.
Footnotes
Authors’ Contributions
All Authors had full access to all the data and take responsibility for the integrity of the data. Drafting of the manuscript: Palash Asawa, Urwat Vusqa, Kirtivardhan Vashistha, Tanveer Mian, Rahul Karna. Critical revision of the manuscript: All Authors. Pathology photos: Feifan Chen. Administrative and technical support: Yazan Samhouri, Salman Fazal. Supervision: Yazan Samhouri, Salman Fazal.
Conflicts of Interest
Salman Fazal: Consultant Speakers Bureau Jazz Pharmaceuticals, Servier, BMS. All other Authors have no conflicts of interests to declare in relation to this study.
- Received May 8, 2022.
- Revision received May 25, 2022.
- Accepted May 27, 2022.
- Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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