1 / 40

Sinus Histiocytosis with Massive Lymphoadenopathy (Rosai-Dorfman Disease)

Sinus Histiocytosis with Massive Lymphoadenopathy (Rosai-Dorfman Disease). Clinical Pathology Conference November 4, 2005 Dean Fong, DO. Disorder of Histiocytic and Dendritic Derivation. Spectrum from benign to frank malignant Problems with diagnosis: Scarcity of specific markers

wilson
Download Presentation

Sinus Histiocytosis with Massive Lymphoadenopathy (Rosai-Dorfman Disease)

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Sinus Histiocytosis with Massive Lymphoadenopathy (Rosai-Dorfman Disease) Clinical Pathology Conference November 4, 2005 Dean Fong, DO

  2. Disorder of Histiocytic and Dendritic Derivation • Spectrum from benign to frank malignant • Problems with diagnosis: • Scarcity of specific markers • Lack of consistent means for detection of monoclonality • Clinicopathologic overlap with reactive and infectious proliferations

  3. Non-Malignant Histocytoses • Group of disorders involving a pathologic increase in the number of histiocytes • Mononuclear phagocytic cells • Circulating monocyte • Alveolar macrophages of the lung • Kupffer cells of the liver • Osteoclasts • Microglial cells

  4. Non-Malignant Histocytoses • Mainly-antigen presenting cells • Interdigiting reticulum cells and dendritic reticulum cells in the spleen and lymph nodes • Langerhans cells in skin and bronchial epithelium • Bone marrow origin

  5. Non-Malignant Histocytoses • Three group of disease • Dendritic cell-related histiocytoses • Langerhans cell histiocytoses • Histiocytosis X • Eosinophilic granuloma • Hand-Schuller-Christian disease • Letterer-Siwe disease • Single system disease • Multisystem disease • Juvenile xanthogranuloma-dermal dendrocyte phenotype

  6. Non-Malignant Histocytoses • Three group of disease (cont.): • Macrophage-related histiocytoses • Hemophagocytic Lymphohistiocytosis • Primary hemophagocytic lymphohistiocytosis or familial hemophagocytic lymphohistiocytosis • Sporadic or familial • Associated with infection • Secondary hemophagocytic lymphohistiocytosis • Infection-associated hemophagocytic syndrome • Malignancy associated hemophagocytic syndrome • Others, including fat overload syndrome • Rosai-Dorfman disease

  7. Sinus Histiocytosis with Massive Lymphoadenopathy (SHML) • First described by Rosai and Dorfman in 1969. • Nonmalignant proliferation of distinctive histiocytic/phagocytic cells within lymph node sinuses and lymphatics in extranodal sites

  8. Sinus Histiocytosis with Massive Lymphoadenopathy (SHML) • Clinical features • Worldwide • Primarily disease of childhood and early adulthood • Peak age  20 years • Increased incidence of serum auto-immune antibodies during active disease • No specific gender, ethnic, or socioeconomic predilection • Some reports of M > F

  9. Sinus Histiocytosis with Massive Lymphoadenopathy (SHML) • Clinical features • Registry of 423 cases: • Caucasian = African • Asian  Less common • Occasional familial cases

  10. Pathogenetic Mechanism • Early  3 of 6 cases found serologic evidence of EBV • In 7 of 9 pts.  HHV-6 DNA found • Unfavorable outcome in patients with immune dysfunction • Exuberant response of hematopoietic system to undetermined immunologic trigger • ? Defective Fas/FasL signaling leading to defective apoptosis  ? histiocytic proliferation

  11. Sinus Histiocytosis with Massive Lymphoadenopathy (SHML) • Most frequent presenting symptoms • Cervical region painless lymphadenopathy • Up to 90% of cases • Axillary, para-aortic, inguinal and mediastinal lymph nodes are commonly affected • Extranodal disease in 43% of patients

  12. From the SHML Registry:

  13. From the SHML Registry:

  14. Skin Involvement Firm indurated papules

  15. Sinus Histiocytosis with Massive Lymphoadenopathy (SHML) • Antecedent non-specific fevers and pharyngitis may herald the onset of SHML • Occasionally accompanied by pain, tenderness, malaise, night sweats or weight loss

  16. Pathological Features • Laboratory findings: • Normocytic or microcytic anemia • Immunologic abnormalities  significant number of pts.  unfavorable prgnosis • 90% pts.  elevated ESR • Most frequent immune dysfunction  AIHA • Polyarthralgia, RA, glomerulopathies, asthma, DM  complicate SHML • Polyclonal hypergammaglobinemia  90% of pts. • Rare  RF, ANA, reversal of CD4/CD8 • Small subset  NHL, other histiocytic proliferations, myeloma, melanoma, CA • Reported EBV and HHV-6

  17. Pathology • Gross • Yellow-white with frequent capsular and pericapsular fibrosis

  18. Microscopic • Normal lymph node architecture preserved • Effacement seen only in pts. with long-standing lymphadenopathy • Lymph node sinuses expanded by proliferation of distinctive histiocytes

  19. Histiocytes • Enlarged round or oval vesicular nuclei with well defined, delicate nuclear membranes and a single prominent nucleolus • Multilobulated nuclei, nucleus with multiple nucleoli, nuclear atypia rare • Mitoses infrequent  but increased mitotic activity can be apparent occasionally • Abundant pale eosinophilic cytoplasm • Occasional numerous histiocytes with foamy cytoplasm may predominat cellular milieu

  20. Histiocytes

  21. Histiocytes • Hallmark  lymphophagocytosis or emperipolesis • Lymphocytic penetration and movement within another cell • Often housed within vacuoles  escape degradation • Plasma cells, PMNs, RBCs  may also be present

  22. Emperipolesis

  23. Emperipolesis

  24. Emperipolesis

  25. Other Histopathological Features • Plasma cells often aggregated around post-capillary venules • Eosinophils not usually seen  if seen, think: • LCH, HL, T-cell lymphoma • Collections of PMNs, eosinophilic microabscess, reactive germinal centers  seen but not prominent features • Extranodal sites  more fibrosis, and fewer histiocytes with emperipolesis

  26. Differential Diagnosis • Langerhans Cell Histiocytosis • Lymph node sinuses expanded by histiocytes seen in both LCH and SHML but… • LCH cells are frequently folded or grooved nuclei and associated with eosinophilic microabscess • Histocytic sarcoma • Storage disease • Gaucher’s disease • Hodgkin Lymphoma

  27. Differential Diagnosis • Metastatic melanoma • Carcinoma • Infections caused by: • Histoplasma • Mycobacterial organism • Reactive sinus histiocytosis

  28. Differential Diagnosis • Emperipolesis rare outside setting of SHML but is seen in reactive, neoplastic histiocytic proliferation, LCH

  29. Immunohistiologic Studies • Most useful immunologic marker  histiocytes with expression of S100 • Histiocytes • Pan-macrophages antigens  CD68, HAM 56, CD14, CD64, CD15 • Antigens associated with phagocytosis  CD64, Fc receptor for IgG • Lysosomal activity  Lysozyme, A1A • Immune activation  Transfering receptor, IL-2 receptor • CD163  hemoglobin scavenger receptor and acute phase-regulated transmembrane protein found on tissue macrophages and monocytes

  30. CD68

  31. CD68

  32. Immunohistiologic Studies • Effector cells in SHML • Functionally activated macrophages • Distinct from Langerhans cells, follicular dendritic cells, interdigiting dendritic cells

  33. Immunohistiologic Studies

  34. Summary of Histiocytoses

  35. Clinical course and treatment • Characterized by spontaneous resolution in most cases • Usually indolent for many years, with spontaneous regression • Do not usually threaten life or organ function • Few pts.  disease progressive and require treatment • Some pts.  episodes of exacerbation alternating with periods of remission that continue for many years

  36. Clinical course and treatment • Persistent lymphadenopathy or progression • Associated with involvement of the kidney, lower respiratory tract or liver with associated immunologic dysfunction • Poor prognosis

  37. Clinical course and treatment • SHML registry  423 cases  17 deaths • Only few pts. warrant treatment  no randomized trials • “Wait-and-see” approach • Antibiotics or anti-tuberculosis drugs  no response • Steroids  reduction in lymphoadenopathy and associated fevers • Associated autoimmune conditions usually resolve as the primary condition responds to steroid therapy

  38. Clinical course and treatment • Radiation • 3  complete remission • 3  persistent SHML • 3  death • Chemotherapy • 10  no response • 2  complete and durable remission • Surgery and radiation • 1  complete remission • 6  partial remission • High dose interferon α  long-term remission • No ideal treatment  more data needed

  39. Late Sequelae and Follow-Up • Few pts. require prolonged or intermittent treatment with corticosteroids • Long term steroid effects • No increased incidence of secondary tumors • Follow-up • Monitor disease with clinical examination and CXR

  40. References • Henter JI, Tondini C et. al., “Histiocyte disorders”, Critical Reviews in Oncology Hematology, 2004; 50: 157-174. • Mills SE et. al., Sternberg’s Diagnostic Surgical Pathology, 4th Ed., 2004; 479. • McClain KL, Natkunam Y, et. al., “Atypical Cellular Disorders”, Hematology 2004. • Weitzmann S, Jaffe F, “Uncommon Histiocytic Disorders: The Non-Langerhans Cell Histiocytosis”, Pediatr Blood Cancer, 2005; 45: 256-264.

More Related