What is the significance of Reed-Sternberg cells in distinguishing between Acute Myeloid Leukemia (AML) and Hodgkin lymphoma?

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Reed-Sternberg Cells: Diagnostic Hallmark of Hodgkin Lymphoma

Reed-Sternberg cells are pathognomonic for classical Hodgkin lymphoma and are NOT found in AML—their presence definitively distinguishes Hodgkin lymphoma from acute myeloid leukemia. 1, 2

Diagnostic Significance

Classical Hodgkin Lymphoma (CHL)

  • The identification of Reed-Sternberg cells on histological examination is the standard requirement for diagnosing classical Hodgkin lymphoma, and cytological diagnosis alone is unacceptable. 1
  • Reed-Sternberg cells are large, often multinucleated cells with peculiar morphology embedded in an inflammatory background of non-malignant reactive cells, representing only a small fraction of the total cellular population. 2, 3
  • These cells are positive for CD30 and CD15, and negative for CD45/LCA, which is their characteristic immunophenotypic signature. 1, 4

Acute Myeloid Leukemia (AML)

  • AML is a completely different hematologic malignancy arising from myeloid precursors and does NOT contain Reed-Sternberg cells. [@General Medicine Knowledge]
  • AML diagnosis relies on identifying myeloblasts with Auer rods, myeloperoxidase positivity, and myeloid lineage markers (CD13, CD33, CD117)—features entirely distinct from lymphoid malignancies. [@General Medicine Knowledge]

Critical Diagnostic Pitfall: Reed-Sternberg-Like Cells

A major diagnostic challenge occurs when Reed-Sternberg-like cells (RSLCs) appear in non-Hodgkin lymphomas, which can mimic Hodgkin lymphoma but require different treatment. 5, 4, 6

Key Distinguishing Features:

  • In non-Hodgkin lymphomas with RSLCs, the typical inflammatory background microenvironment of classical Hodgkin lymphoma is absent, and RSLCs appear as scattered cells or small clusters rather than the characteristic pattern seen in HL. 4, 6
  • The background cellular population in NHL is monomorphic with strong CD20 positivity throughout, whereas in classical Hodgkin lymphoma, the background consists of reactive inflammatory cells (T cells, eosinophils, histiocytes). 5
  • RSLCs in NHL maintain CD45/LCA positivity and show strong uniform B-cell marker expression, while true Reed-Sternberg cells in classical HL are typically CD45 negative. 5, 4

Mandatory Diagnostic Approach

Excisional lymph node biopsy is required for definitive diagnosis—core needle biopsy may be adequate only if diagnostic tissue is obtained, but fine-needle aspiration is insufficient. 1, 2, 7

Essential Immunohistochemistry Panel:

  • CD30, CD15, CD45, CD20, and EMA must be evaluated to distinguish classical Hodgkin lymphoma from non-Hodgkin lymphomas and anaplastic large cell lymphoma. 1
  • In lymphocyte-depleted subtypes, additional T and B markers are recommended to avoid misdiagnosing anaplastic large cell lymphoma. 1

Clinical Implications

  • Classical Hodgkin lymphoma is now curable in at least 80% of patients, making accurate diagnosis critical for appropriate treatment selection. 1, 2
  • Different therapeutic protocols and prognosis between Hodgkin lymphoma and non-Hodgkin lymphomas mandate precise distinction, as treatment approaches differ fundamentally. 5, 4
  • In difficult cases where the diagnosis remains uncertain, review by a specialist hematopathologist is recommended. 1

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Hodgkin and Non-Hodgkin Lymphoma Diagnosis and Treatment

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

The Hodgkin and Reed/Sternberg cell.

The international journal of biochemistry & cell biology, 2005

Research

Hodgkin Reed-Sternberg-Like Cells in Non-Hodgkin Lymphoma.

Diagnostics (Basel, Switzerland), 2020

Research

Reed-Sternberg-Like Cells in Non-Hodgkin Lymphomas.

Archives of pathology & laboratory medicine, 2015

Guideline

Pathophysiology and Genetics of Pediatric Nodular Lymphocyte-Predominant Hodgkin Lymphoma (NLPHL)

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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