Letter to the Editor

Ann Lab Med 2024; 44(2): 179-182

Published online March 1, 2024

Copyright © Korean Society for Laboratory Medicine.

Concurrent Pleural and Pericardial Involvement in a Patient With De Novo Pure Erythroid Leukemia

Yun Zhang, B.S. Med.1 , Kechao Li, B.S. Med.1 , Xue Li, B.S. Med.2 , Hui Wang, M. Med.3 , Ting Li, M. Med.4 , and Fang Long, M. Med.5

1Department of Clinical Laboratory, The District People’s Hospital of Zhangqiu, Jinan, Shandong, China; 2Department of Health Ward, The District People’s Hospital of Zhangqiu, Jinan, Shandong, China; 3Department of Laboratory Medicine, Hebei Yanda Ludaopei Hospital, Langfang, China; 4Department of Laboratory Medicine, Beijing Ludaopei Hospital, Beijing, China; 5Department of Clinical Laboratory, Sichuan Provincial Maternity and Child Health Care Hospital, The Affiliated Women’s and Children’s Hospital of Chengdu Medical College, Chengdu, Sichuan, China

Correspondence to: Fang Long, M. Med.
Department of Clinical Laboratory, Sichuan Provincial Maternity and Child Health Care Hospital, The Affiliated Women’s and Children’s Hospital of Chengdu Medical College, No. 290, Shayan West Second Street, Wuhou District, Chengdu, Sichuan Province 610000, China

Ting Li, M. Med.
Department of Laboratory Medicine, Beijing Ludaopei Hospital, No. 22, Tongji South Road, Yizhuang Economic-Technological Development Area, Beijing 100176, China

Received: June 22, 2023; Revised: July 12, 2023; Accepted: September 12, 2023

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Dear Editor,

Pure erythroid leukemia (PEL) is a rare subtype of AML, accounting for <1% of all AML cases. PEL cases have distinct morphology and immunophenotype, complex karyotypes, and poor prognosis, which are captured in the 2016 WHO definition. It can occur de novo but more often evolves from a prior myelodysplastic syndrome or therapy-related disease. We describe an uncommon case of de novo PEL with pleural and pericardial involvement. This case emphasizes the importance of fluid analysis, such as cytomorphology, in diagnosing leukemic serous effusions and highlights that a chest computed tomography (CT) scan and pericardium ultrasound should be routinely performed in patients diagnosed as having hematolymphoid malignancies, particularly when typical clinical manifestations are absent. The ethics committee of The District People’s Hospital of Zhangqiu, Jinan, China (approval number: 2022019) approved the study and waived the need for patient consent as the patients’ personal information was not included.

A 46-year-old male patient was admitted to The District People’s Hospital of Zhangqiu in April 2022, with complaints of bleeding gums and general fatigue lasting for seven days. Hematological analysis revealed a leukocyte count of 5.64×109/L, Hb level of 58 g/L, and platelet count of 7×109/L. Examination of peripheral blood smears showed 9% large circulating blasts characterized by deeply basophilic cytoplasm, occasionally displaying large violet cytoplasmic inclusions (Fig. 1A). Bone marrow aspiration demonstrated a significant increase in the number of “blasts” (constituting 81%) exhibiting morphological features indicative of proerythroblasts. These intermediate- to large-sized blasts displayed round nuclei, dispersed chromatin, one to several prominent nucleoli, agranular basophilic cytoplasm, and a high nuclear-to-cytoplasmic ratio. Some blast cells exhibited purple inclusions and microvacuoles (Fig. 1B). Myeloperoxidase staining yielded negative results, whereas periodic acid-Schiff staining revealed prominent globular inclusions (Fig. 1C). Cytogenetic analysis revealed a complex karyotype of 52,XY,-4,-5, add(5)(q13),+14,add(15)(p11.2),-16,+19,add(19)(p13.1), add(19)(p13.1),-21,+mar1–8[10] (Fig. 1D). Bone marrow biopsy revealed a sheet of blasts with fine chromatin and prominent nucleoli (Fig. 1E), and immunohistochemistry showed positive E-cadherin staining (Fig. 1F). Flow-cytometric analysis for immunophenotyping showed 17.19% blasts expressing CD13, CD33, CD36, CD71, CD105, and CD117, with partial expression of CD34, CD38, and human leukocyte antigen DR isotype, suggesting an erythroid differentiation (Fig. 2). TP53 mutations [c.995T>G (p.I332S)] were detected, with a median variant allele frequency of 58.2%, using next-generation sequencing. These findings collectively confirmed the diagnosis of PEL.

Figure 1. Results of peripheral blood and bone marrow aspirate analysis. (A) Peripheral blood smears show 9% large circulating blasts with deeply basophilic cytoplasm and large violet cytoplasmic inclusions (Wright–Giemsa stain, ×1000). (B) Bone marrow aspirate exhibits markedly increased “blasts” (constituting 81%) of intermediate to large size, a high nuclear-to-cytoplasmic ratio, round nuclei, dispersed chromatin, one to several prominent nucleoli and agranular basophilic cytoplasm, with occasional multiple purple inclusions and microvacuoles on some blasts (Wright–Giemsa stain, ×1000). (C) Periodic acid-Schiff staining reveals prominent globular inclusions (×1000). (D) Cytogenetics revealing a complex karyotype. (E) Bone marrow biopsy showing a sheet of blasts with fine chromatin and prominent nucleoli (hematoxylin–eosin stain, ×100). (F) Immunohistochemical staining positive for E-cadherin (×400).

Figure 2. Results of bone marrow immunophenotyping analysis for (A) CD34/CD38, (B) CD117/HLA-DR, (C) CD71/CD235a, (D) CD71/CD33, (E) CD45/CD13, and (F) CD105/CD36 combinations. Flow-cytometric analysis for immunophenotyping showed blasts expressing CD13, CD33, CD36, CD71, CD105, and CD117, with partial expression of CD34, CD38, and human leukocyte antigen DR isotype, suggesting erythroid differentiation.

The patient underwent chemotherapy regimens involving daunorubicin (60 mg, days 1–3) and cytarabine (0.1 g q12 h, days 1–7) but failed to achieve complete remission. The patient experienced chest tightness and shortness of breath during the treatment, prompting the performance of pulmonary CT and pericardium ultrasound. The images revealed pleural and pericardial effusions, in which abundant leukemic blasts were observed via Wright–Giemsa staining. The patient succumbed to severe myelosuppression and lung infection after the last chemotherapy session.

PEL cases lacking morphological evidence of erythroid maturation are difficult to distinguish from other AML subtypes. The morphological overlap between PEL and acute megakaryoblastic leukemia has posed difficulties for hematologists, especially when both erythroid and megakaryoblastic differentiations are concurrent. Wang and Hasserjian [1] have provided detailed descriptions of the distinctive morphological, immunophenotypic, and cytogenetic features of these two entities. Additionally, PEL can closely resemble acute lymphoblastic leukemia, myelodysplastic syndrome (MDS), multiple myeloma, and metastatic tumors [2-4]. Currently, an immunostaining panel, including E-cadherin, CD117, and CD34, aids in identifying lineage-specific myeloblasts in cases of MDS with left-shifted erythroid hyperplasia [2]. Moreover, distinguishing PEL from florid reactive erythroid hyperplasia, such as hyperplasia resulting from erythroid growth factor application or megaloblastic anemia, is imperative.

Serous effusions are rarely observed in patients with acute leukemia, chronic leukemia, MDS, or myeloproliferative neoplasms. When they do occur, they are typically caused by various infections, disease progression, or infiltration of the serosal cavity by leukemic cells [5]. Concurrent pleural, pericardial, and/or peritoneal cavity involvement in patients with hematologic malignancies has been sporadically reported, with the pleural cavity being the most commonly affected site, followed by the peritoneal and pericardial cavities [6, 7]. Pleural fluid occurrence is more frequent in T-lymphoblastic leukemia/lymphoma, followed by AML. He, et al. [8] reported a male patient diagnosed as having B-cell acute lymphoblastic leukemia, in whom pericardial effusion was incidentally discovered during follow-up.

PEL prognosis is typically dire, with a median overall survival of merely three months [9]. Our patient passed away within three months of the initial diagnosis. Given the extreme rarity of PEL, its highly aggressive clinical behavior, and the challenges encountered in its diagnosis, further investigations into the clinical course, diagnosis, and pathophysiology are crucial for the development of novel treatment options.

The diagnosis of PEL presents a significant challenge, particularly when it involves simultaneous erythroid and megakaryoblastic differentiation. The concurrent invasion of the pleural and pericardial regions observed in this case of PEL is an infrequent occurrence. This case underscores the importance of utilizing flow cytometry and fluid analysis for the diagnosis of these rare entities presenting with leukemic serous effusions. Additionally, it highlights the value of conducting routine chest CT scans and pericardium ultrasounds in patients with leukemia, especially when typical clinical manifestations, such as shortness of breath, are absent.

The authors thank Yulei Shen (Department of Pathology and Laboratory Medicine, Henry Ford Hospital) for revising the article.

All authors contributed to study conception and design. Zhang Y, Long F, Li K, and Li X collected the clinical and histological data. Li T and Wang H drafted the manuscript. All authors have read and approved the final manuscript.

This work was supported by the Shandong Province Medical and Health Technology Plan Project (202211000347).

  1. Wang SA and Hasserjian RP. Acute erythroleukemias, acute megakaryoblastic leukemias, and reactive mimics: a guide to a number of perplexing entities. Am J Clin Pathol 2015;144:44-60.
    Pubmed CrossRef
  2. Ohgami RS, Chisholm KM, Ma L, Arber DA. E-cadherin is a specific marker for erythroid differentiation and has utility, in combination with CD117 and CD34, for enumerating myeloblasts in hematopoietic neoplasms. Am J Clin Pathol 2014;141:656-64.
    Pubmed CrossRef
  3. Laura CS, Ana FM, Ines LH. Pure erythroid leukaemia mimicking metastatic carcinoma. Br J Haematol 2022;198:617.
    Pubmed CrossRef
  4. Song G, Wang Y, Tian X, Wang Y, Zhao J, Liu J. A patient with pure erythroid leukemia with leukemic cells mimicking myeloma cells. Turk J Haematol 2022;39:264-5.
    Pubmed KoreaMed CrossRef
  5. Kaur K, Patel T, Patra S, Trivedi P. Cytomorphology, immunophenotype, and cytogenetic profile of leukemic serous effusions. Diagn Cytopathol 2021;49:948-58.
    Pubmed CrossRef
  6. Savvidou K, Dimitrakopoulou A, Kafasi N, Konstantopoulos K, Vassilakopoulos T, Angelopoulou M, et al. Diagnostic role of cytology in serous effusions of patients with hematologic malignancies. Diagn Cytopathol 2019;47:404-11.
    Pubmed CrossRef
  7. Das DK, Gupta SK, Ayyagari S, Bambery PK, Datta BN, Datta U. Pleural effusions in non-Hodgkin's lymphoma. A cytomorphologic, cytochemical and immunologic study. Acta Cytol 1987;31:119-24.
  8. He J, Zhang Y, Wang Z, Liu J. Pericardial involvement in a common B-cell acute lymphoblastic leukemia patient. Int J Lab Hematol 2022;44:1003-4.
    Pubmed CrossRef
  9. Liu W, Hasserjian RP, Hu Y, Zhang L, Miranda RN, Medeiros LJ, Wang SA. Pure erythroid leukemia: a reassessment of the entity using the 2008 World Health Organization classification. Mod Pathol 2011;24:375-83.
    Pubmed CrossRef