Myelodysplastic Neoplasm with Increased Blasts-1 Presenting with Concurrent Diagnostic and Prognostically Relevant Morphologic Features: A Case Report

Abstract

Introduction

Myelodysplastic neoplasms (MDS) are clonal hematopoietic disorders characterized by ineffective hematopoiesis, cytopenias, and morphologic dysplasia, with a variable risk of progression to acute myeloid leukemia. Despite advances in molecular diagnostics, bone marrow morphology remains a cornerstone of diagnosis and risk stratification.

Case Presentation

We report the case of a 72-year-old woman who presented with progressive fatigue and pancytopenia. Bone marrow examination revealed prominent dyserythropoiesis, dysgranulopoiesis, numerous micromegakaryocytes with unilobed nuclei, scattered atypical spindle-shaped mast cells, and 5–7% blasts. These findings fulfilled the diagnostic criteria for myelodysplastic neoplasm with increased blasts-1 (MDS-IB1) according to the WHO 2022 classification. Conventional cytogenetics demonstrated a normal female karyotype.

Conclusion

This case illustrates the diagnostic and prognostically relevant value of concurrent morphologic abnormalities across multiple hematopoietic lineages in MDS. It underscores the enduring importance of meticulous bone marrow morphologic assessment, particularly when comprehensive molecular data are not immediately available.

Introduction

Myelodysplastic neoplasms (MDS) comprise a heterogeneous group of clonal hematopoietic disorders characterized by ineffective hematopoiesis, persistent cytopenias, morphologic dysplasia, and a variable risk of progression to acute myeloid leukemia [1]. According to the 2022 World Health Organization (WHO) classification, morphologic assessment remains a central component in the diagnosis and subclassification of MDS, alongside cytogenetic and molecular findings [2].

Despite substantial advances in ancillary diagnostic modalities, including cytogenetics, next-generation sequencing (NGS), and flow cytometry, careful morphologic evaluation of bone marrow aspirates continues to play an indispensable role in daily clinical practice. In particular, the recognition of dysplastic changes across multiple hematopoietic lineages provides essential diagnostic information and contributes to risk stratification, especially in settings where comprehensive molecular data may not be immediately available [3].

Characteristic morphologic abnormalities include dyserythropoiesis, such as nuclear irregularities, budding, and multinuclearity, as well as dysmegakaryopoiesis manifested by micromegakaryocytes with hypolobated or unilobed nuclei – findings that are highly suggestive of an underlying clonal myeloid process [4, 5]. Additionally, the presence of atypical mast cells, including spindle-shaped forms with elongated nuclei, represents an uncommon but noteworthy morphologic finding in myeloid neoplasms and has been described mainly in advanced disease settings, suggesting potential clinicopathologic relevance rather than a disease-defining feature [6].

While each of these morphologic features has been described individually in the context of MDS, their concurrent and prominent demonstration within a single bone marrow specimen is uncommon. Such a constellation offers a valuable opportunity to illustrate the integrative diagnostic and prognostic contribution of morphology [4, 7]. Herein, we report a case of myelodysplastic neoplasm with increased blasts-1 (MDS-IB1) exhibiting simultaneous diagnostic and prognostically relevant morphologic findings, highlighting the enduring importance of meticulous morphologic assessment in the modern era of hematopathology. The aim of this case report was to illustrate the diagnostic and prognostically relevant value of concurrent morphologic abnormalities across multiple hematopoietic lineages in myelodysplastic neoplasms, emphasizing the continued importance of bone marrow morphology in routine clinical practice.

Case Presentation

Presentation and History

A 72-year-old woman presented with a 2-month history of progressive fatigue, exertional dyspnea, and easy bruising. Her past medical history included long-standing type-2 diabetes mellitus and well-controlled hypertension. She denied fever, weight loss, night sweats, or recent infections.

Physical Examination

On examination, she appeared pale and had scattered ecchymoses over the extremities. Mild splenomegaly was noted (tip palpable 2 cm below the costal margin), and no lymphadenopathy was detected.

Laboratory Findings

Initial complete blood count revealed macrocytic pancytopenia:

• Hemoglobin: 8.1 g/dL (MCV: 108 fL)

• White blood cell count: 2.3 × 10⁹/L (absolute neutrophil count: 0.9 × 10⁹/L)

• Platelet count: 82 × 109/L

• Reticulocyte count: 0.5% (absolute count 25 × 109/L)

Peripheral blood smear showed anisopoikilocytosis, hypolobated neutrophils with occasional pseudo-Pelger-Huët forms, and thrombocytopenia with occasional giant platelets. Serum vitamin B12, folate, thyroid function, liver function, and copper levels were within normal limits. Serology for hepatitis B, hepatitis C, and HIV was negative.

Bone Marrow Examination

Due to persistent cytopenias and dysplastic peripheral findings, bone marrow aspiration and biopsy were performed (Fig. 1).

• Cellularity: normocellular to mildly hypercellular for age.

• Erythropoiesis: prominent dyserythropoiesis was observed, characterized by megaloblastoid changes, nuclear budding, and multinuclearity (Fig. 1a1, a2).

• Granulopoiesis: reduced in number with evident dysplasia, including hypogranular cytoplasm, nuclear hypolobation, and occasional ring-shaped nuclei.

• Megakaryopoiesis: numerous micromegakaryocytes with unilobed nuclei were present (Fig. 1b), a specific finding for clonal dysmegakaryopoiesis.

• Mast cells: scattered atypical mast cells displaying spindle-shaped morphology and coarse granules were identified (Fig. 1c).

• Blast count: blasts accounted for 5–7% of nucleated cells.

Fig. 1.

a1 and a2 show marked dyserythropoiesis with nuclear budding and multinucleated erythroid precursors, a diagnostic hallmark of myelodysplastic neoplasm (MDS). b demonstrates a micromegakaryocyte with a unilobed nucleus, a pathognomonic feature of dysmegakaryopoiesis. c shows spindle-shaped atypical mast cells with elongated nuclei and coarse granules, indicating an adverse prognostic finding.

Based on these findings, a diagnosis of myelodysplastic neoplasm with increased blasts-1 (MDS-IB1) was established according to the WHO 2022 classification.

Treatment and Follow-Up

The patient was started on azacitidine (75 mg/m² subcutaneously for 7 days every 28 days) as first-line therapy.

• Cytogenetics: conventional karyotyping revealed a normal female karyotype (46,XX). Targeted NGS was not available at the time of diagnosis.

Discussion

MDS represent a biologically heterogeneous group of clonal myeloid disorders in which bone marrow morphology remains fundamental to diagnosis, classification, and risk stratification, even in the era of advanced molecular diagnostics [4, 8]. The present case illustrates how the concurrent presence of diagnostic, lineage-specific, and prognostically suggestive morphologic abnormalities across multiple hematopoietic lineages can provide a comprehensive snapshot of disease biology, particularly when comprehensive cytogenetic and molecular studies are not immediately available.

Dyserythropoiesis – manifested by nuclear budding, multinuclearity, and irregular nuclear contours – is a well-established diagnostic criterion for MDS and reflects ineffective erythropoiesis [6, 8]. In this patient, these features were prominently observed in the bone marrow aspirate (Fig. 1a1, a2). Equally characteristic was the presence of micromegakaryocytes with unilobed or hypolobated nuclei (Fig. 1b), a finding that is highly specific for clonal dysmegakaryopoiesis and considered pathognomonic for a myelodysplastic process [9]. The detection of both erythroid and megakaryocytic dysplasia in the same specimen strongly supports the diagnosis of a myelodysplastic neoplasm, even in the absence of definitive cytogenetic abnormalities [10].

In addition to the classic dysplastic features, the bone marrow aspirate contained scattered spindle-shaped atypical mast cells with elongated nuclei and coarse cytoplasmic granules (Fig. 1c). Although these morphologic findings are not diagnostic of systemic mastocytosis, the presence of atypical mast cells in myelodysplastic neoplasms has been increasingly recognized as a morphologic feature encountered predominantly in advanced disease settings and in association with adverse clinicopathologic characteristics [11, 12]. When identified in the context of multilineage dysplasia, such atypical mast cells are thought to reflect underlying clonal evolution or bone marrow microenvironmental dysregulation rather than a distinct disease-defining entity [13]. In the present case, immunohistochemical characterization of mast cells (including CD117 and tryptase) as well as molecular testing for KIT D816V mutation were not available at the time of diagnosis, representing a limitation of this report. Nevertheless, the morphologic identification of atypical mast cells adds an additional layer of prognostic concern and supports the need for close clinical follow-up and completion of comprehensive molecular studies.

Blast enumeration revealed 5–7% blasts, fulfilling the diagnostic criteria for myelodysplastic neoplasm with increased blasts-1 (MDS-IB1) according to the WHO 2022 classification [2]. This category represents a higher risk subtype of MDS for which hypomethylating agents are the recommended first-line therapy in patients who are not immediate candidates for allogeneic stem-cell transplantation [14, 15].

Initial cytogenetic analysis showed a normal female karyotype (46,XX). While a normal karyotype places the patient in an intermediate-risk category by the Revised International Prognostic Scoring System (IPSS-R), the severity of morphologic dysplasia – especially the coexistence of severe dyserythropoiesis, pathognomonic micromegakaryocytes, and atypical mast cells – raises the possibility of underlying genetic complexity that may not be captured by conventional karyotyping [16, 17].

The main limitation of this report is the absence of complete molecular profiling at the time of writing. Therefore, any definitive prognostic statements must await the results of NGS. Nevertheless, the case retains significant educational value: it underscores how a single composite image can vividly illustrate concurrent morphologic abnormalities across three hematopoietic lineages, reinforcing the continued relevance of meticulous morphologic examination in routine clinical practice. In resource-limited settings or while awaiting advanced tests, such morphologic clues can alert clinicians to the potential for high-risk biology and prompt earlier initiation of appropriate therapy.

This case primarily serves an educational purpose by illustrating how careful morphologic assessment can guide diagnosis, risk assessment, and clinical management of myelodysplastic neoplasms, particularly when comprehensive molecular data are not immediately available.

Conclusion

This case highlights the continued importance of bone marrow morphology in the diagnosis and risk assessment of myelodysplastic neoplasms. The concurrent presence of diagnostic dyserythropoiesis, pathognomonic micromegakaryocytic abnormalities, and atypical mast cells demonstrates how morphology can provide an integrated view of disease biology. Although a normal karyotype currently places the patient in an intermediate-risk category, the severity of morphologic abnormalities warrants close monitoring and completion of molecular studies. Overall, this report reinforces morphology as a practical tool for clinical decision-making when comprehensive molecular data are not immediately available.

Statement of Ethics

This study protocol was reviewed and approved by the Ethics Committee of Yasuj University of Medical Sciences (Department of Internal Medicine) on 10/09/2025. Written informed consent was obtained from the patient for publication of this case report and any accompanying images. The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000551290).

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

This study was not supported by any sponsor or funder.

Author Contributions

A.R.: conceptualization of the study, primary morphologic evaluation of bone marrow specimens, and drafting of the initial manuscript. B.N.: clinical data collection, patient management, and critical interpretation of hematologic findings. M.M.S.A.: literature review, contribution to the discussion section, and critical revision of the manuscript for important intellectual content. S.J.: study supervision, final diagnostic confirmation, critical revision of the manuscript, and approval of the final version for submission. All authors read and approved the final manuscript.

Funding Statement

This study was not supported by any sponsor or funder.

Data Availability Statement

All data generated or analyzed during this study are included in this published article. Further inquiries can be directed to the corresponding author.