What is the interpretation of cortical hyperplasia with sinus histiocytosis on lymph node biopsy?

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Last updated: February 13, 2025View editorial policy

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From the Guidelines

Cortical hyperplasia with sinus histiocytosis on lymph node biopsy is most likely indicative of Rosai-Dorfman Disease (RDD), a rare histiocytic disorder characterized by the accumulation of histiocytes in lymph nodes and other tissues 1.

Key Features of RDD

  • Sinus expansion of large histiocytes with ample pale or "watery-clear" cytoplasm and a large hypochromatic nucleus with prominent nucleolus
  • Emperipolesis, the trafficking of intact leukocytes through the cytoplasm of histiocytes, is a helpful finding but not required for diagnosis
  • Immunophenotype of RDD histiocytes is characterized by cytoplasmic and nuclear S100 positivity, with CD68 and variable CD163 and CD14 positivity
  • Clinical presentation often includes painless lymphadenopathy, B symptoms, and may be accompanied by extranodal involvement

Differential Diagnosis

Other histiocytic neoplasms, such as Erdheim-Chester Disease (ECD) and Langerhans Cell Histocytosis (LCH), should be considered in the differential diagnosis 1.

  • ECD is characterized by the presence of MAPK/ERK and phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) pathway mutations and typically involves the bones, kidneys, and central nervous system
  • LCH is characterized by the presence of BRAF V600E mutation and typically involves the bones, skin, and lungs

Diagnostic Evaluation

A comprehensive diagnostic evaluation, including imaging studies (e.g., PET-CT, MRI), histopathologic examination, and molecular profiling (e.g., next-generation sequencing), is necessary to establish a definitive diagnosis of RDD or other histiocytic neoplasms 1.

  • FDG PET-CT is the modality of choice to evaluate organ involvement
  • Brain MRI is recommended to evaluate for CNS, dural, and orbital involvement
  • Cardiac MRI is recommended in patients with suspected ECD to capture lesions that would otherwise be missed
  • Comprehensive evaluation for endocrinopathies is recommended due to high rates of CNS and orbital involvement.

From the Research

Cortical Hyperplasia with Sinus Histiocytosis

  • Cortical hyperplasia with sinus histiocytosis on lymph node biopsy can be associated with various conditions, including paraneoplastic lymphadenopathy 2, adult onset Still's disease 3, and sinus histiocytosis with massive lymphadenopathy (SHML) 4, 5, 6
  • In paraneoplastic lymphadenopathy, cortical hyperplasia is more commonly seen in T-cell lymphomas, while sinus histiocytosis is a universal finding that can be seen in various types of lymphomas 2
  • In adult onset Still's disease, lymph node lesions can show a dynamic histological spectrum, including paracortical hyperplasia, sinus histiocytosis, and follicular hyperplasia 3
  • SHML is a benign proliferating histiocytic disorder that can be associated with malignant lymphoma, although the presence of SHML does not always impact clinical decisions 5, 6

Diagnostic Considerations

  • The interpretation of cortical hyperplasia with sinus histiocytosis on lymph node biopsy requires consideration of the clinical context and histological patterns 2, 3
  • The presence of necrosis, prominent sinus histiocytosis, or prominent fibrosis in a lymph node biopsy should be considered as possible indications for a second biopsy 2
  • Immunohistochemical and molecular studies may be necessary to differentiate between benign and malignant conditions 3, 6

Association with Malignant Lymphoma

  • SHML can be associated with malignant lymphoma, although the presence of SHML does not always impact clinical decisions 5, 6
  • In some cases, SHML and malignant lymphoma can involve the same lymph node, although the SHML may be present as a small focus 6

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

[Paraneoplastic lymphadenopathy].

Terapevticheskii arkhiv, 2007

Research

Sinus histiocytosis with massive lymphadenopathy and malignant lymphoma involving the same lymph node: a report of four cases and review of the literature.

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 2000

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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