Extramedullary chronic myeloid leukemia – A rare cause of ascites

Vinoth Sermadurai; Kannan Mariappan; Ramani Ratinavel; Vijai Shankar Chidambara Manivasagam

doi:10.4103/ghep.ghep_7_22

CASE REPORT

Year : 2022 | Volume : 2 | Issue : 2 | Page : 74-77

Extramedullary chronic myeloid leukemia – A rare cause of ascites

Vinoth Sermadurai, Kannan Mariappan, Ramani Ratinavel, Vijai Shankar Chidambara Manivasagam
Department of Medical Gastroenterology, Madurai Medical College, Madurai, Tamil Nadu, India

Date of Submission	09-Feb-2022
Date of Decision	25-Feb-2022
Date of Acceptance	26-Feb-2022
Date of Web Publication	23-Mar-2022

Correspondence Address:
Vijai Shankar Chidambara Manivasagam
Assistant professor, Department of Medical Gastroenterology, Government Rajaji hospital, Madurai - 625 020, Tamil Nadu
India

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ghep.ghep_7_22

Abstract

Chronic myeloid leukemia (CML) is a hematopoietic stem cell disease characterized by anemia, extreme blood granulocytosis and granulocytic immaturity, basophilia, often thrombocytosis, and splenomegaly. Extramedullary disease (EMD) occurs in CML blast crisis. In literature, peritoneal involvement in CML chronic phase is reported very rarely to the best of our knowledge. A 60-year-old male patient presented with complaints of significant weight loss over 1-month duration and abdomen distension for 7 days. The patient was pale and had massive ascites on presentation. Blood investigations showed a total count of 61.9 × 10⁹ L, and liver disease was ruled out on imaging. Ascitic fluid analysis showed high protein, elevated adenosine deaminase, ascitic fluid acid-fast bacillus staining was negative, and GeneXpert negative for tuberculosis. Upper gastrointestinal endoscopy and colonoscopy were normal. Ascitic fluid cytology, though negative for malignant cells, showed myeloid precursor cells. Peripheral smear showed a leukemoid reaction. Bone marrow aspiration showed blast <3%. BCR/ABL1 was detected in leukocytes of peripheral blood. The patient was diagnosed with CML – chronic phase with peritoneal involvement as massive ascites – and was started tablet imatinib 400 mg OD and had favorable response to treatment after 3 months with the resolution of ascites and on follow-up. Extramedullary CML such as peritoneal disease serves as a predictor of future blast crisis, and close monitoring is needed for patients with EMD at initial presentation.

Keywords: Ascites, chronic myeloid leukemia, chronic phase, extramedullary disease, imatinib

How to cite this article:
Sermadurai V, Mariappan K, Ratinavel R, Chidambara Manivasagam VS. Extramedullary chronic myeloid leukemia – A rare cause of ascites. Gastroenterol Hepatol Endosc Pract 2022;2:74-7

How to cite this URL:
Sermadurai V, Mariappan K, Ratinavel R, Chidambara Manivasagam VS. Extramedullary chronic myeloid leukemia – A rare cause of ascites. Gastroenterol Hepatol Endosc Pract [serial online] 2022 [cited 2022 May 24];2:74-7. Available from: http://www.ghepjournal.com/text.asp?2022/2/2/74/340398

Introduction

Chronic myeloid leukemia (CML) is a hematopoietic stem cell disease characterized by anemia, extreme blood granulocytosis and granulocytic immaturity, basophilia, often thrombocytosis, and splenomegaly. CML progresses through three stages: chronic phase, accelerated phase, and blast phase. Philadelphia chromosome t (9;22) (q32; q11.2) is detected in 90% of CML. Patients with CML can develop extramedullary involvement during the course of the illness. This usually occurs during the accelerated phase or blast crisis. Lymph nodes, bone, skin, central nervous system, and subcutaneous tissues were the most frequent sites of extramedullary disease (EMD). In literature, peritoneal involvement in CML chronic phase is reported very rarely to the best of our knowledge. We report a case of a 60-year-old male with extramedullary disease of CML who presented with massive ascites, BCR-ABL1 positive, and heavy infiltration of the ascitic fluid with myeloid precursor cells, peripheral smear showing a leukemoid reaction and bone marrow showing blasts <3%. Presentation of the extramedullary disease usually occurs with blast crisis, but this case did not show any evidence of blast crisis on marrow analysis and had favorable treatment response with imatinib. Extramedullary manifestations of CML presentation as ascites, though is a rarity, may serve as a poor prognostic indicator for subsequent blast crisis and require close monitoring.

Case Report

A 60-year-old man, a farmer by occupation, presented to our department with complaints of significant weight loss over 1 month and abdomen distension for 7 days. The patient was apparently normal 1 month ago. Then, he noticed weight loss of around 10 kg over 1 month and developed abdomen distension which was sudden onset, progressive, uniform distension, and no aggravating and relieving factors not associated with features of bowel obstruction and jaundice. The patient was not an alcoholic or smoker. The patient had no significant past illness. On general examination, the patient was pale, not icteric, and had no generalized lymphadenopathy or pedal edema. His vitals were stable. Abdomen examination showed massive ascites without any organomegaly. Blood analysis revealed total count – 61.9 × 10⁹ L, differential count of polymorphs – 96% lymphocytes 2%, eosinophils – 2%, hemoglobin – 8.6 g/dl, and platelet count – 518 × 10⁹ L; renal and liver function tests were normal. Viral markers for hepatitis B and C viruses were negative. Total serum protein was 6.8 g/dl, albumin – 4.5 g/dl, globulin – 2.3 g/dl, and prothrombin time 16 secs – 1.1. The urine routine was normal. Contrast-enhanced computed tomography of the abdomen showed multiple biliary hamartomas, gross ascites with mild splenomegaly, and diffuse omental thickening with multiple bilateral para-aortic and mesenteric nodes, largest measuring 1 cm in the short axis in the right para-aortic region. The patient's echocardiography was normal. Computed tomography of the chest was normal. Ascitic fluid analysis showed protein 4.1 g, blood sugar 91 mg/dl, cell count 1000 with polymorphs 86%, lymphocytes 14%, adenosine deaminase 64U/ml, ascitic fluid gram staining and acid-fast bacillus staining were negative, and GeneXpert and tuberculosis culture were negative. The patient was evaluated for malignant ascites. Upper gastrointestinal endoscopy passed up to the second part of the duodenum and colonoscopy passed up to cecum were normal. Ascitic fluid cytology, though negative for malignant cells, showed myeloid precursor cells. [Figure 1] showed ascitic fluid myeloid precursor cells. Peripheral smear showed hypochromic microcytic anemia, white blood cells count is increased with a shift to left in neutrophilic series, activated lymphocytes seen, DC showed neutrophils – 64%, lymphocytes – 8%, eosinophils – 03%, myelocytes – 06%, metamyelocytes – 05%, band forms – 04%, and platelets had an increase in count and morphology. Bone marrow aspiration done showed hypercellular marrow with a myeloid erythroid ratio of 9:1. Erythropoiesis showed micronormoblastic and normoblastic maturation. Leukopoiesis is active and shows a normal pattern of maturation with blast <3%. Overall picture was suggestive of myeloid leukemoid reaction with myeloid hyperplasia and active megakaryopoiesis in the bone marrow. BCR/ABL1 was detected in leukocytes of the peripheral blood by reverse transcription–polymerase chain reaction method with genomic break point observed e13a2 corresponding p210. [Figure 2] showed bone marrow aspiraton smear of the patient. All other causes of high-protein ascites were ruled out. A final diagnosis of CML in the chronic phase was made on the basis of clinical features, laboratory investigations, and review of the literature. The patient was started on tablet imatinib 400 mg OD. The patient was followed up every month after discharge. The patient had no adverse effect on imatinib. The patient's ascites were completely reduced, and the total count became normal after 3 months. The patient was on further follow-up for monitoring of disease progression.

Figure 1: Ascitic fluid cytology shows myelocytes, metamyelocytes, and band forms

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Figure 2: Bone marrow aspiration shows hypercellular marrow with blasts <3%

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Discussion

CML is a disease that originates in the bone marrow, but EMD occurs due to tumor infiltrates of immature myeloid or lymphoid cells at sites other than bone marrow, spleen, or liver.^{[1],[2],[3],[4]} Lymph nodes, bone, skin, central nervous system, and subcutaneous tissues were the most frequent sites of EMD.^{[5],[6],[7],[8],[9]} It is generally accepted that the development of EMD represents a sign of poor prognosis in the natural history of CML.^[7],[8],[10] EMD in CML usually occurs during the accelerated phase or blast crisis.^[10] CML progresses through three phases: chronic, accelerated, and blast phases.^[1] The chronic phase is diagnosed when blasts <10%.^[2],[4] Hepatosplenomegaly in CML patients is not considered as EMD.^[11] Extramedullary blast crisis is the first manifestation of accelerated phase even though bone marrow is in the chronic phase.^[8] However, significant ascites in the chronic phase of CML at the time of diagnosis have been reported very rare.^{[11],[12],[13],[14],[15]} In literature there are four mechanisms for the development of ascites and effusion in patients with CML. The first mechanism is the leukemic infiltration of the peritoneal cavity. The second mechanism is secondary to bleeding into the peritoneal and pleural cavity because of leukostasis and platelet dysfunction. The third mechanism is extramedullary hematopoiesis. The fourth mechanism is the infectious cause.^{[16],[17],[18]} Imatinib mesylate, a competitive inhibitor of the BCR-ABL tyrosine kinase, is highly effective in treating chronic phase CML but less effective against CML in its advanced phases.^{[19],[20],[21],[22],[23],[24]} However, its use in extramedullary blast crises is not fully studied.^[25]

Our case is massive ascites with myeloid precursor cells in ascitic fluid with a peripheral smear showing leukemoid reaction and bone marrow showing blasts <3% and BCR/ABL1 positive. No features of liver disease, portal hypertension, and other causes of ascites were excluded. Bansod et al. had reported a patient who presented with massive splenomegaly and massive ascites and was diagnosed with extramedullary blast crisis without bone marrow involvement and showed a favorable response after imatinib therapy.^[12] Aleem and Siddiqui reported a patient with massive ascites, peritoneal thickening and bone marrow in chronic phase, and favorable response to imatinib.^[11] In Kaur et al., a patient presented with splenomegaly with normal count and bone marrow with pleural effusion and ascites; CML was diagnosed by leukemic cells in pleural fluid cytology. Yuguda saleh reported a patient presented with hepatosplenomegaly, massive ascites was diagnosed as an accelerated phase of CML, and started on combination chemotherapy and hydroxyurea. In our study, the patient had elevated total count at presentation and myeloid precursors in ascitic fluid.^[26] Most of the patients in literature presented with organomegaly, massive ascites with blast crisis. Our patient presented only with massive ascites. Most studies showed favorable responses with imatinib. Our patient also showed a good response to imatinib. In literature, peritoneal involvement in CML chronic phase is reported very rarely to the best of our knowledge.^[11],[12] Based on the review of the literature and the clinical presentation as well as the laboratory results, our patient most likely had leukemic infiltration of the peritoneal cavity by the leukemic cells as the cause of the massive ascites.

Patients with EMD as the initial presentation may develop blast crisis very early during the course of the disease. Hence, those patients should be followed up to prevent blast crisis.^[2],[9]

Conclusion

Ascites in CML chronic phase are reported very rarely. Elderly presenting with high-protein ascites and high leukocyte count may need workup for CML after ruling out malignant ascites. Proper cytological examination of ascitic fluid, including myeloid precursor cells, is essential. Early prediction of future blast crisis and close monitoring are needed for patients with EMD at initial presentation.

Informed consent statement

Informed written consent was obtained from the patient for publication of this report and any accompanying images.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published, and due efforts will be made to conceal the identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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