Lymph nodes & spleen, nonlymphoid
Lymph nodes-inflammatory disorders
Clofazimine induced changes

Topic Completed: 1 November 2017

Minor changes: 21 July 2020

Revised: 4 February 2019, last major update November 2017

Copyright: 2003-2020,, Inc.

PubMed Search: Clofazimine induced changes

Jayalakshmi Balakrishna, M.D.
Abdelsalam Sharabi, M.D.
Page views in 2019: 125
Page views in 2020 to date: 111
Cite this page: Balakrishna J. Clofazimine induced changes. website. Accessed September 23rd, 2020.
Definition / general
  • Clofazimine induced crystal storing histiocytosis
ICD coding
  • Rare condition in patients taking clofazimine, an antileprosy medication
  • Most commonly subcutaneous tissue, spleen, lymph nodes, liver, lung and gastrointestinal tract
Clinical features
  • Red discoloration of skin and other tissues, mass formation, lymphadenopathy
  • History of clofazimine intake, biopsy
Radiology description
  • Enlarged lymph nodes, particularly intra-abdominal lymph nodes
Prognostic factors
  • Extent of involvement
Case reports
  • Excision of affected lymph node
  • Cessation of treatment apparently does not reverse the process
Gross description
  • Enlarged lymph node with light brown to dark red discoloration
  • Fixative and solutions used for processing the specimen turn red with the crystals dissolving in them
Microscopic (histologic) description
  • Marked interfollicular plasmacytosis and histiocytes containing crystals in their cytoplasm, which are elongated with irregular edges, some forming bundles
  • Crystals are typically deep red, but depending on the fixative and processing can be clear and colorless (crystals dissolve in alcohol)
  • Crystals show bright red birefringence if polarized
  • They can be seen in extra and intracellular locations
Microscopic (histologic) images

Images hosted on other servers:
Missing Image

Diffuse eosinophilic histiocytes

Missing Image

Cell death induced in macrophages by clofazimine

Missing Image

Histiocytes are strongly CD68+

Missing Image

Crystalline inclusions within the histiocytes

Positive stains
  • Plasma cells are highlighted by CD138 and are polyclonal by kappa and lambda light chain stains
  • Lymphocytes are mixed B and T cells and histiocytes show positive staining with CD68 and CD163
Negative stains
  • Crystals are negative for PAS and immunoglobulin heavy and light chains
Electron microscopy description
  • Transmission electron microscopy shows the empty spaces which crystals have been occupying
  • Crystals show some osmiophilic material which appear to be granular or multivesicular bodies
  • Upon higher magnification, these crystals show a multilamellar core or a lattice with elements spaced periodically
Electron microscopy images

Images hosted on other servers:
Missing Image

Elongated and rhomboid shaped dense crystals

Molecular / cytogenetics description
  • No clonal populations of cells
Differential diagnosis
  • Crystal storing histiocytosis with immunoglobulin crystals, which is usually associated with a lymphoid or plasma cell neoplasm
  • Fungi
  • Parasites
Board review style question #1
    In crystal storing histiocytosis, the cell type which accumulates crystals is:

  1. Histiocytes
  2. Lymphocytes
  3. Neutrophils
  4. Plasma cells
Board review answer #1
A. The crystals in CSH in tissues get phagocytosed by histiocytes where they form collections. When these cells accumulate, they form a mass lesion.
Back to top
Image 01 Image 02