Histiocytosis refers to a variety of proliferative disorders involving histiocytes or macrophages. There are three main types of Langerhans cell histiocytosis: acute disseminated (Letterer-Siwe disease), multifocal (eosinophilic granuloma), and unifocal. Acute disseminated mainly affects young children and can involve multiple organs, leading to high mortality without chemotherapy. Multifocal typically involves bones and other organs in children, while unifocal usually causes solitary bone lesions in a more indolent form.

1. HISTIOCYTOSIS www.freelivedoctor.com

2. “ Histiocytosis” a variety of proliferative disorders of “histiocytes” or “macrophages” www.freelivedoctor.com

3. Histiocyte/Dendritic Cell histiocyte/macrophage dendritic cell (“Langerhans cell”) www.freelivedoctor.com

4. Langerhans Cell (dendritic antigen presenting cell) dendritic antigen presenting expresses HLA-DR and CD1a cytoplasmic HX bodies (Birbeck granules) www.freelivedoctor.com

5. Langerhans Cell dendritic antigen presenting expresses HLA-DR and CD1a cytoplasmic HX bodies (Birbeck granules) Cotran, Kumar, Collins: Pathologic Basis of Disease 1999 www.freelivedoctor.com

6. Dendritic Cells (Reticular Cells) antigen-presenting cells 1. dendritic reticulum cells (dendritic follicular cells) 2. interdigitating reticulum cells (dendritic interdigitating cells, dendritic cells) 3. fibroblastic reticulum cells 4. histiocytic reticulum cells 5. other “reticulum” cells www.freelivedoctor.com

7. “ Histiocytosis” old classification Histiocytosis X i. Letterer-Siwe disease ii. Hand-Schüller-Christian disease iii. Eosinophilic granuloma www.freelivedoctor.com

8. “ Histiocytosis” classification Langerhans Cell Histiocytosis three (3) clinicopathologic entities 1. acute disseminated Langerhans cell hitiocytosis (Letterer-Siwe disease) 2. multifocal Langerhans cell histiocytosis (multifocal eosinophilic granuloma) 3. unifocal Langerhans cell histiocytosis (unifocal eosinophilic granuloma) www.freelivedoctor.com

9. Acute Disseminated Langerhans Cell Histiocytosis (Letterer-Siwe disease) mainly occurs before 2 yrs of age skin involvement (trunk, scalp) hepatosplenomegaly, lymphadenopathy, lung involvement destructive osteolytic bone lesions www.freelivedoctor.com

10. Acute Disseminated Langerhans Cell Histiocytosis (Letterer-Siwe disease) mainly occurs before 2 yrs of age skin involvement (trunk, scalp) hepatosplenomegaly, lymphadenopathy, lung involvement destructive osteolytic bone lesions Cotran, Kumar, Collins: Pathologic Basis of Disease 1999 www.freelivedoctor.com

11. Acute Disseminated Langerhans Cell Histiocytosis (Letterer-Siwe disease) when extensive BM involvement occurs: anemia, thrombocytopenia, recurrent infection (otitis media, mastoiditis) if untreated ---> rapidly fatal with intensive chemotherapy ---> 50% 5-yr-survival www.freelivedoctor.com

12. Multifocal Langerhans Cell Histiocytosis (multiple eosinophilic granuloma) multiorgan involvement bone ( calvaria , ribs, femur),skin, lungs, stomach mainly occurs in children fever, diffuse eruptions (scalp, ear canals) frequent bouts of otitis media, mastoiditis, upper respiratory tract infections lymphadenopathy, hepatomegaly, splenomegaly diabetes insipidus <--- post pituitary stalk involvement (~50% of cases) “ Hand-Schüller-Christian triad” Hand-Schuller-Christian triad 1. Calvarial defects 2. Diabetes insipidus 3. Exophthalmos www.freelivedoctor.com

13. Multifocal Langerhans Cell Histiocytosis (multiple eosinophilic granuloma) Histology: mainly involving medullary cavity of bone expanding, erosive accumulation of Langerhans cells www.freelivedoctor.com

14. Multifocal Langerhans Cell Histiocytosis (multiple eosinophilic granuloma) Histology: mainly involving medullary cavity of bone expanding, erosive accumulation of Langerhans cells variably admixed with eosinophils, lymphocytes, plasma cells, neutrophils www.freelivedoctor.com

15. Multifocal Langerhans Cell Histiocytosis (multiple eosinophilic granuloma) Histology: mainly involving medullary cavity of bone expanding, erosive accumulation of Langerhans cells variably admixed with eosinophils, lymphocytes, plasma cells, neutrophils Treatment: 1. may undergo spontaneous regression 2. chemotherapy www.freelivedoctor.com

16. Unifocal Langerhans Cell Histiocytosis (unifocal eosinophilic granuloma) usually affects skeletal system may be asymptomatic or may cause pain and tenderness an indolent disease www.freelivedoctor.com

17. Unifocal Langerhans Cell Histiocytosis (unifocal eosinophilic granuloma) usually affects skeletal system may be asymptomatic or may cause pain and tenderness an indolent disease Treatment: 1. may undergo spontaneous regression 2. local excision 3. local irradiation www.freelivedoctor.com

18. Histiocytic/Dendritic Cell Neoplasms (1999 WHO classification) Macrophage/histiocytic neoplasm Histiocytic sarcoma Dendritic cell neoplasms Langerhans cell histiocytosis Langerhans cell sarcoma Interdigitating dendritic cell sarcoma/tumor Follicular dendritic cell sarcoma/tumor Dendritic cell sarcoma, NOS www.freelivedoctor.com