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Surgical Pathology Criteria

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Sinus Histiocytosis with Massive Lymphadenopathy


  • Predominantly sinusoidal proliferation of S100 positive large histiocytic cells

Alternate / historical names

  • Rosai-Dorfman Disease
  • Juan-Ron Fever

Diagnostic Criteria

  • Capsular thickening with fibrosis and distended sinuses
    • Occasional cases with prominent germinal centers
    • Microabscesses may be seen in the sinuses
  • Large histiocytes with abundant cytoplasm
    • S100 positive
    • Predominantly intra-sinusoidal
    • Large, round or oval vesicular nuclei
      • Prominent nucleoli, single or multiple
      • May show moderate atypia or multiple nuclei
  • Emperipolesis prominent in nodes
    • Intact, engulfed lymphocytes and plasma cells may be numerous
    • Occasional engulfed neutrophils and RBCs
    • Less prominent in extranodal disease
  • Plasma cells prominent in medullary cords or adjacent soft tissue in extranodal cases
    • May surround prominent vessels
  • Extranodal cases may have less prominent sinuses
    • Emperipolesis may be more difficult to find
    • Stromal fibrosis, germinal centers and prominent plasma cells should prompt S100 stain and close search for characteristic histiocytes
  • SHML has rarely been reported to coexist in the same node with lymphoma

Yasodha Natkunam MD PhD
Ronald F Dorfman MBBCh FRCPath
Robert V Rouse MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342

Original posting:: May 1, 2006

Supplemental studies


  • Large histiocytes
    • S100 positive
    • CD68 positive
    • CD163 positive
    • CD1a negative to rare
  • Lymphocytes and plasma cells polyclonal

Differential Diagnosis


Reactive sinus hyperplasia

  • S100 staining of large vesicular nuclei is rarely seen in reactive sinus hyperplasia


Langerhans cell histiocytosis is composed of S100 positive histiocytes that may have a sinusoidal distribution
Langerhans Cell Histiocytosis Sinus Histiocytosis with Massive Lymphadenopathy
Small to medium sized nuclei Large nuclei
Grooved, folded nuclei Round, vesicular nuclei
Inconspicuous nucleoli Prominent nucleoli
CD1a positive CD1a negative
No emperipolesis Prominent emperipolesis
Eosinophils frequent Eosinophils not frequent
Capsular fibrosis infrequent Capsular fibrosis frequent
Plasmacytosis infrequent Plasmacytosis frequent
Both are S100 positive.


Hemophagocytic lymphohistiocytosis



  • Median age 20 years
    • Range from congenital to 74 years
  • Rare reports in siblings
  • World-wide distribution
    • Original reports from Africa
  • 90% involve cervical nodes
  • May present with extranodal disease
    • Most commonly in skin, upper airways, bone
  • Associated laboratory abnormalities
    • Polyclonal hypergammaglobulinemia frequent
    • Elevated sedimentation rate frequent
    • Mild anemia
  • Spontaneous regression frequent
  • Some patients die with progressive disease

Grading / Staging / Report

Grading and staging are not relevant

The pathology report should contain the following information:

  • Results of supplementary studies if performed
  • Relationship to other specimens from the same patient


Histiocytic and dendritic cell disorders

  • Langerhans cell histiocytosis
  • Langerhans cell sarcoma
  • Sinus histiocytosis with massive lymphadenopathy
  • True histiocytic sarcoma
  • Interdigitating dendritic cell sarcoma/tumor
  • Follicular dendritic cell sarcoma/tumor
  • Dendritic cell sarcoma, not otherwise specified (indeterminate cell tumor)


  • Warnke RA, Weiss LM, Chan JKC, Cleary ML, Dorfman RF . Tumors of the Lymph Nodes and Spleen, Atlas of Tumor Pathology, AFIP Third Series, Fascicle 14, 1995
  • Lu D, Estalilla OC, Manning JT Jr, Medeiros LJ. Sinus histiocytosis with massive lymphadenopathy and malignant lymphoma involving the same lymph node: a report of four cases and review of the literature. Mod Pathol 2000 Apr;13(4):414-9Eisen RN, Buckley
  • Eisen RN, Buckley PJ, Rosai J. Immunophenotypic characterization of sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease). Semin Diagn Pathol 1990 Feb;7(1):74-82
  • Paulli M, Rosso R, Kindl S, Boveri E, Marocolo D, Chioda C, Agostini C, Magrini U, Facchetti F. Immunophenotypic characterization of the cell infiltrate in five cases of sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease). Hum Pathol 1992 Jun;23(6):647-54
  • Foucar E, Rosai J, Dorfman R. Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease): review of the entity. Semin Diagn Pathol 1990 Feb;7(1):19-73
  • McClain KL, Natkunam Y, Swerdlow SH. Atypical cellular disorders. Hematology (Am Soc Hematol Educ Program). 2004;:283-96.
  • Rosai J, Dorfman RF. Sinus histiocytosis with massive lymphadenopathy: A newly recognized benign clinicopathological entity. Arch Pathol 1969 87:63-70
  • Rosai J, Dorfman RF. Sinus histiocytosis with massive lymphadenopathy: A psuedolymphomatous benign disorder. Analysis of 34 cases. Cancer 1972 30:1174-1188
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