Lymph nodes - not lymphoma
Primary immunodeficiency disorders
Omenn syndrome

Author: Shamayel Mohammed, M.D. (see Author page)

Revised: 9 December 2015, last major update December 2015

Copyright: (c) 2003-2015, PathologyOutlines.com, Inc.

PubMed Search: Omenn syndrome [title] lymph nodes
Definition / General
  • Rare, autosomal recessive form of severe combined immunodeficiency (SCID) of infancy
  • Recurrent infections, early diffuse erythrodermia, failure to thrive, protracted diarrhea, hepatosplenomegaly, elevated serum IgE and eosinophilia, lymphadenopathy, oligoclonal T cell expansions
  • Often recombinase activating gene mutations (Clin Immunol 2005;116:246)
Pathophysiology
  • Most common genetic alteration is the partial loss of function for recombinase activating genes RAG (RAG1 and RAG2)
  • The RAG genes are essential for gene recombination in the T cell receptor and B cell receptor
  • This mutation leads to the Inability to productively rearrange VDJ regions in T cell and B cell receptors, which leads to abnormal T cell proliferation and absent B cells
  • As a result, the immune system has difficulty recognizing specific pathogens
  • An impaired V(D)J recombination process leads to the generation of a few T cells expanding in the periphery, infiltrating target organs such as skin and gut, resulting in the erythroderma and colitis typical of this syndrome
  • The disease is characteristically associated with an oligoclonal expansion of Th2 population
Clinical Features
  • Recurrent infections
  • Early diffuse erythrodermia, failure to thrive, protracted diarrhea, hepatosplenomegaly
  • Elevated serum IgE and eosinophilia, lymphadenopathy, oligoclonal T cell expansions
  • Suppurative lymphadenitis and disseminated sometimes fatal tuberculosis as a reaction to the immunization for Bacille Calmette-Guerin (BCG)
  • Lymphoproliferative disorders associated with Primary Immune Disorders (PID) such as SCID
Diagnosis
  • WBC count may be normal or elevated with a predominance of lymphocytes
  • Eosinophilia is invariably present
  • Molecular studies show presence of an oligoclonal set of activated antigen stimulated Th2 cells
  • B cells are absent, and NK cells are present
  • Immunoglobulin levels show absent immunoglobulin A (IgA) and immunoglobulin M (IgM), elevated IgE levels, and immunoglobulin G (IgG) that is maternal in origin
  • IgG antibodies against T dependent antigens, such as tetanus, are nonprotective
  • Specific IgM antibodies, such as isohemagglutinins, are absent
Case Reports
Treatment
  • Isolation to prevent infection
  • Prophylactic treatment with nystatin, antiviral agents (e.g. acyclovir) or antibiotics may be considered
  • Immunosuppression with cyclosporine (Arch Dis Child 2002;87:231)
  • Bone marrow or other stem cell reconstitution is first line conventional therapy
  • Diagnosis at birth may lead to protection from infection and improve transplantation outcome (Blood 2011;117:3243)
Clinical Images
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Pre- and post-treatment

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Alopecia and erythroderma

Micro Description
  • Total effacement of nodal architecture with no distinct cortex and no follicles
  • Also B cell depletion and accumulation of interdigitating reticulum cells (Am J Surg Pathol 1995;19:1082)
  • Hassall corpuscles are poorly formed, and lymphocytes are deficient in the thymus
  • Paracortical lymphocytes are absent in the spleen
  • The spleen, skin and mucosa associated lymphoid tissues contain only a few scattered CD3+ T lymphocytes, and B cells are totally absent (Blood 1999;94:3468)
  • Non caseating granulomatous inflammation with BCG / Bacille Calmette-Guerin lymphadenitis (Am J Clin Pathol 2000;113:703)
  • Lymphoproliferative disease associated with primary immune disorders:
    • EBV is involved in most cases
    • Morphology includes reactive lymphoid hyperplasia, polymorphous infiltrate with immunoblast proliferation and overt lymphoma
      • Diffuse Large B-cell Lymphoma (DLBCL) is the most common type of lymphoma
      • May present as Fatal Infectious Mononucleosis (FIM)
Micro Images

Images hosted on PathOut server courtesy of Shamayel Mohammed, M.D.:

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Distinct cortex

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Diffuse histiocytic infiltrate

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Patient with SCID

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Ziehl Neelsen+

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EBV+

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CD30+ immunoblasts

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CD20+



Images hosted on Other servers:

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Parakeratosis and
lymphohistocytic infiltrate

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H&E, S100

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CD30

Cytology Description
  • Large number of histiocytes with abundant streaked cytoplasm
  • Ziehl-Neelsen (ZN) stain for acid-fast bacilli positive (Diagn Cytopathol 2001;24:333)
Cytology Images

Images hosted on PathOut server courtesy of Shamayel Mohammed, M.D.:

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Ziehl-Neelsen+

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Histiocytes

Positive Stains
Differential Diagnosis