Hematology

Primary immunodeficiency disorders

Omenn syndrome



Topic Completed: 1 December 2015

Minor changes: 14 May 2021

Copyright: 2003-2021, PathologyOutlines.com, Inc.

PubMed Search: Omenn syndrome [title] lymph nodes

Shamayel Mohammed, M.D.
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Cite this page: Mohammed, S. Omenn syndrome . PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/lymphnodesomennssyndrome.html. Accessed September 21st, 2021.
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

Microscopic (histologic) 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)
Microscopic (histologic) images

Contributed by 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+



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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

Contributed by Shamayel Mohammed, M.D.
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Ziehl-Neelsen+

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Histiocytes

Positive stains
Differential diagnosis
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