1 / 41

Histiocytic Disorders Diagnosis and Treatment

Histiocytic Disorders Diagnosis and Treatment. Resident Education Lecture Series. Histiocytosis. Group of Disorders- Clonal proliferation of cells of mononuclear phagocyte system (histiocytes) Histiocyte- central cell Form of a WBC. Classes of Histiocyte Disorders. Class I

Jimmy
Download Presentation

Histiocytic Disorders Diagnosis and Treatment

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. Histiocytic DisordersDiagnosis and Treatment Resident Education Lecture Series

  2. Histiocytosis • Group of Disorders- • Clonal proliferation of cells of mononuclear phagocyte system (histiocytes) • Histiocyte- central cell • Form of a WBC

  3. Classes of Histiocyte Disorders • Class I • Langerhans cell histiocytosis • Class II • Non-Langerhans cell histiocytosis • Hemophagocytic Lymphohistiocytosis (HLH) • Class III • Malignant Histiocytic Disorder

  4. Class I:Langerhans Cell Histiocytosis (LCH) • Other names: • Histiocytosis-X • Eosinophilic granuloma • Hand-Schüller-Christian syndrome • Letterer-Siwe disease

  5. LCH • LCH can be local and asymptomatic, as in isolated bone lesions, or it can involve multiple organs and systems with significant symptomatology and consequences • Thus, clinical manifestations depend on the site(s) of the lesions, the organs and systems involved, and their function(s) • Restrictive vs. Extensive LCH

  6. Restricted LCH • Skin lesions without any other site of involvement • Monostotic lesion with or without diabetes insipidus, adjacent lymph node involvement, or rash • Polyostotic lesions involving several bones or more than 2 lesions in one bone, with or without diabetes insipidus, adjacent lymph node involvement, or rash

  7. Extensive LCH • Visceral organ involvement +/- bone lesions, diabetes insipidus, adjacent lymph node involvement, and/or rash • without signs of organ dysfunction of the lungs, liver, or hematopoietic system • Visceral organ involvement +/- bone lesions, diabetes insipidus, adjacent lymph node involvement, and/or rash • with signs of organ dysfunction of the lungs, liver, or hematopoietic system

  8. LCH-diagnosis • S100 protein • CD1 antigen • Birbeck granule positive cells by Electron Microscopy

  9. LCH- sites of involvement • Skin (rash) • Bone (single or multiple lesions) • Lung, liver and spleen (dysfunction) • Teeth and gums • Ear (chronic infections or discharge) • Eye (vision problem or bulging) • CNS (Diabetes Insipidus) • Fever, weakness and failure to gain weight

  10. Bone involvement • Bone involvement is observed in 78% of cases and often includes the skull 49%, innominate bone 23%, femur 17%, orbit 11%, and ribs 8%. • Single or multiple lesions. • Vertebral collapse can occur. • Long bone involvement can induce fractures.

  11. Skull lytic lesions with LCH

  12. Characteristic rash of LCH

  13. Characteristic Scalp Rash with LCH

  14. LCH TREATMENT • Localized disease-skin, bone, lymph nodes • Good prognosis • Minimal/no treatment • Localized skin lesions, especially in infants, can regress spontaneously • If treatment is required, topical corticosteroids may be tried • Intralesional steroids

  15. LCH Treatment-Extensive • Multiple Organ disease • Benefit from chemotherapy and/or steroids • 80% survival using prednisone, 6MP, VP16 or vinblastine (Velban™). • If you do not respond to chemotherapy in the first 12 weeks- 20% survival.

  16. Sinus histiocytosis with massive lymphadenopathy: Rosai-Dorfman disease • A persistent massive enlargement of the nodes with an inflammatory process characterizes this condition. The disease rarely is familial

  17. Rosai-Dorfman disease • The male-to-female ratio is 4:3, with a higher prevalence in blacks than in whites. • Fever, weight loss, malaise, joint pain, and night sweats may be present. • Cervical lymph nodes • Other areas, including extranodal regions, can be affected. • These disorders can manifest with only rash or bone involvement

  18. Rosai-Dorfman disease • Immunologic abnormalities in conjunction with the disease can be observed • Leukocytosis; mild normochromic, normocytic, or microcytic anemia; increased Immune globulins (Igs); abnormal rheumatoid factor; and positive lupus erythematosus

  19. Treatment • The disease is benign and has a high rate of spontaneous remission, but persistent cases requiring therapy have been observed

  20. Class III:Malignant Histiocytic Disorders • True neoplasms • Extremely rare • Acute monocytic leukemia, malignant histiocytosis, true histiocytic lymphoma • Symptoms • fever, wasting, LAD, hepatosplenomegaly, rash • Treatment- • Induction • prednisone, cyclophosphamide, doxorubicin • Maintenance • vincristine, cyclophosphamide, doxorubicin

  21. Class II:HLH • Underlying immune disorder • Uncontrolled activation of the cellular immune system • Defective triggering of apoptosis • Incidence 1.2/ 1,000,000 • M=F • Age: Familial: usually present < 1yr Secondary: may present at any age

  22. HLH • Familial Hemophagocytic Lymphohistiocytosis (FHLH) • Primary HLH • Infection Associated Hemophagocytic Syndrome (IAHS) • Secondary HLH

  23. Familial HLH • FHLH, FHL, FEL • Hereditary transmitted disorder • Autosomal recessive • Affects immune regulation • Family history often negative • Triggered by infections • Presence of perforin gene mutation leads to deficiency in triggering of apoptosis • Only 20-40% of familial HLH have perforin mutation • H-Munc 13-4 (17q25) discovered 2003 assoc FHLH

  24. Perforin • Membranolytic protein expressed in the cytoplasmic granules of cytotoxic T cells and NK cells. • Responsible for the translocation of granzyme B from cytotoxic cells into target cells; granzyme B then migrates to target cell nucleus to participate in triggering apoptosis. • Without perforin, cytoxic T cells & NK cells show reduced or no cytolytic effect on target cells.

  25. Infection-associated HLH • VAHS • Develops as the result of infection • Viral (most common), bacterial, fungal, parasites • Often in immunocompromised hosts (HIV, oncologic, Crohn’s disease)

  26. Clinical Presentation • Fever • Hepatosplenomegaly • Neurological symptoms (seizures) • Large lymph nodes • Skin rash • Jaundice • Edema

  27. CNS disease • CNS infiltration • most devastating consequence(s) of HLH • Seizures • Alteration in consciousness-coma • CNS deficits-cranial nerve palsies, ataxia • Irritability • Neck stiffness • Bulging fontanel

  28. Laboratory Abnormalities • Cytopenias (Platelets, Hgb,WBC) • High Triglycerides • Prolonged PT, PTT, low Fibrinogen • High AST, ALT • CSF- high protein, high WBC • Low Natural Killer cell activity • High Ferritin

  29. Histopathological Findings • Increased numbers of lymphocytes & mature macrophages • Prominent hemophagocytosis • Spleen, lymph nodes, bone marrow, CNS

  30. Diagnostic Criteria • Clinical criteria: fever, splenomegaly. • Laboratory Criteria • Cytopenia (> 2 of 3 cell lines) • Hgb < 9 gm/dl, plts < 100, anc < 1000 • High triglycerides (> 3SD of normal for age) +/- low fibrinogen (<150) • Pathology Criteria • hemophagocytosis - bone marrow, spleen or lymph nodes • No evidence of malignancy

  31. Additional Laboratory Criteria • CSF-high WBC, high protein • Liver-histiological- chronic persistent hepatitis • Low Natural Killer Cell activity • Familial etiology cannot be determined in first affected infant

  32. Treatment • Without treatment FHLH is rapidly fatal Median survival- 2 months

  33. Continuation therapy, BMT if donor Familial Disease 8 wks chemo Persistent non-familial HLH Pts Continuation therapy, BMT if donor If 2nd HLH Resolved non-familial Stop therapy Treat cause of immune reactivation Reactivation If persistent consider 1st HLH Continuation therapy, BMT if donor

  34. Treatment • Initial therapy (8 weeks)-induction • Decadron (8wks), CSA • VP16 (2x/wk x 2 wks, 1x/wk x 6wks) • ITM and steroids if CNS disease is present after 2 wks of therapy for 4 doses In non -familial cases treatment is stopped after 8 weeks if complete resolution of disease

  35. Treatment • Continuation Therapy • Week 9-52 • VP16 every other week • Decadron pulses every 2 wks for 3 days • CSA (level 300) QD

  36. Bone Marrow Transplant • In FHLH BMT - only curative therapy • BMT performed ASAP: • acceptable donor • disease is non-active • Non-familial disease • BMT offered at relapse

  37. HLH-94 Protocol Results • 113 patients treated on protocol • 56% (63/113) alive at median 37.5 m. • 3 year OS 55% +/- 9% • BMT patients (n=65) • 3 year OS 62% • Only 15 /65 patients had matched related donors. The majority were unrelated.

  38. From ABP Certifying Exam Content Outline Histiocytosis syndromes of childhood • Recognize the clinical manifestations of childhood histiocytosis syndromes

  39. Credits • Julie An Talano MD

More Related