Rosai-Dorfman Disease



Rosai-Dorfman Disease


L. Jeffrey Medeiros, MD

Roberto N. Miranda, MD





Key Facts


Terminology



  • Rosai-Dorfman disease (RDD) and sinus histiocytosis with massive lymphadenopathy are equivalent terms


Etiology/Pathogenesis



  • Unknown; histologic features are suggestive of virus


Clinical Issues



  • Spontaneous regression occurs in most patients


  • No specific therapy required


Macroscopic Features



  • Large, often massive lymph nodes


  • Often matted with capsular fibrosis


Microscopic Pathology



  • Lymph nodes show dilated sinuses


  • Associated small lymphocytes and plasma cells


  • RDD histiocytes characterized by



    • Abundant eosinophilic cytoplasm


    • Central vesicular nucleus


    • Small but distinct central nucleolus


    • Emperipolesis


  • In extranodal sites



    • Emperipolesis often focal or absent


Ancillary Tests



  • Immunohistochemistry



    • S100(±), CD1a(-)


Top Differential Diagnoses



  • Langerhans cell histiocytosis


  • Chronic granulomatous inflammation


  • IgG4-related disease


  • Metastatic neoplasms to lymph node sinuses






Lymph node biopsy specimen is involved by Rosai-Dorfman disease (RDD). The RDD histiocytes have abundant eosinophilic cytoplasm and show prominent emperipolesis image in this field.






S100 stain highlights the cytoplasm of RDD histiocytes. S100 negatively outlines intracytoplasmic lymphocytes image in cells with emperipolesis.


TERMINOLOGY



Abbreviations



  • Rosai-Dorfman disease (RDD)


Synonyms



  • Sinus histiocytosis with massive lymphadenopathy (SHML)


  • Histiocytose lipidique ganglionnaire pseudotumorale de Destombes



Definitions



  • Benign proliferation of histiocytes with characteristic cytologic features



    • Histiocytes show emperipolesis (engulfment of lymphocytes)


    • Histiocytes express S100 protein


ETIOLOGY/PATHOGENESIS


Infectious Agents



  • Histologic similarities between Salmonella infection and RDD have been observed



    • No culture evidence or other data to support


    • Other infectious agents are possible


  • One study has reported SV40 polyoma virus in subset of cases of soft tissue-based RDD


Genetic



  • RDD has been reported in identical twins or families, suggesting genetic predisposition


  • Rare familial forms of RDD have been reported



    • SLC29A3 mutations have been identified


  • Faisalabad histiocytosis is genetic syndrome that is similar to RDD


Autoimmune



  • An autoimmune etiology has been suggested



    • Subset of RDD patients have coexistent autoimmune disease


    • Association with autoimmune lymphoproliferative syndrome


Tumor-Associated



  • RDD, typically focal, can be associated with lymphomas, most commonly



    • Nodular lymphocyte-predominant Hodgkin lymphoma


    • Follicular lymphoma


Unknown



  • Most cases of RDD are of unknown etiology


CLINICAL ISSUES


Epidemiology



  • Incidence



    • Rare; worldwide geographic distribution


  • Age



    • Wide range



    • Newborn to ˜ 75 years; more common in children


  • Gender



    • M:F = 3:2


  • Ethnicity



    • All races affected


Site



  • Lymph nodes


  • Extranodal sites in ˜ 20% of patients



    • Head and neck region common



      • Upper respiratory tract, skin


    • Other common sites



    • Skin, soft tissues, gastrointestinal tract


    • Bones, breast, dura


Presentation



  • Lymphadenopathy, often without any symptoms



    • Usually localized


    • Cervical lymph nodes most often involved


    • Often bilateral with massive enlargement



  • B symptoms are uncommon but can occur



    • Fever, night sweats can precede lymphadenopathy


  • Laboratory abnormalities in subset of patients



    • Polyclonal hypergammaglobulinemia common


    • Blood lymphocytes with low CD4 to CD8 ratio


    • Hemolytic anemia



Treatment



  • In most patients, RDD regresses spontaneously



    • Usually no specific therapy needed


    • RDD can persist for months or, rarely, years before regression


  • Rare subset of patients have aggressive RDD and require therapy



    • Therapies: Steroids, radiation therapy, chemotherapy



      • Patients have been reported with rapid response to steroids


      • Rituximab (anti-CD20) has been used with response in some patients


    • Surgical excision for patients with obstruction/compression-type symptoms


Prognosis



  • Excellent for most affected patients


  • Rare cases can be clinically aggressive



    • No effective therapy for these rare aggressive cases


    • Fatalities can occur as a result of



    • Accompanying immune dysregulation


    • Mass effect in vital organs


IMAGE FINDINGS


Radiographic Findings



  • Lymphadenopathy


MACROSCOPIC FEATURES


General Features



  • Enlarged lymph nodes: Often massive



    • Often matted with capsular fibrosis


MICROSCOPIC PATHOLOGY


Histologic Features



  • Lymph nodes



    • Overall lymph node architecture is intact but distorted


    • Marked dilatation of sinuses



      • Filled with RDD histiocytes


      • Associated with small lymphocytes and plasma cells


      • Granulocytes not present, unless superimposed necrosis or infection


    • RDD histiocytes show emperipolesis



      • Engulf cells that become located in histiocyte cytoplasm


      • Small lymphocytes, plasma cells, or erythrocytes


      • Cells surrounded by intracytoplasmic vacuole that appears as a halo


      • Engulfed cells are usually viable


    • Often marked plasmacytosis between sinuses


    • Sclerosis is common (˜ 75% of cases)


    • Reactive follicles often present


    • Eosinophils rare or absent; mitoses are uncommon


    • Rarely, affected lymph nodes can undergo infarct


  • Extranodal sites



    • RDD histiocytes can be sparse in areas



      • Emperipolesis can be absent


    • Small lymphocytes and plasma cells often numerous


    • Fibrosis can be prominent


  • RDD can be associated with Hodgkin or non-Hodgkin lymphomas



    • RDD is often a small focus in this setting


    • Incidental finding usually without impact on prognosis


Cytologic Features



  • RDD histiocytes are characterized by



    • Large size with abundant eosinophilic cytoplasm



      • Well-defined cell borders


    • Central, often round nucleus



      • Distinct central nucleolus



    • Emperipolesis ±/-, with small lymphocytes in histiocyte cytoplasm



    • Halos around lymphocytes not seen in cytologic preparations


    • Halos are result of fixation artifact in routine histologic sections


  • Associated with many inflammatory cells



    • Early lesions: Many small lymphocytes and immunoblasts


    • Late lesions: More plasma cells; cytoplasmic globules (± Russell bodies)


Predominant Pattern/Injury Type



  • Sinusoidal


Predominant Cell/Compartment Type



  • Histiocyte


ANCILLARY TESTS


Immunohistochemistry

Tags:
Jul 8, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Rosai-Dorfman Disease

Full access? Get Clinical Tree
Get Clinical Tree app for offline access