HISTIOCYTOSISHISTIOCYTOSIS

Masatoshi Kida, M.D.Dept. of Pathology

University of Vermont

““Histiocytosis”Histiocytosis”

a variety of proliferative disorders of “histiocytes” or “macrophages”

Histiocyte/Dendritic CellHistiocyte/Dendritic Cell

• histiocyte/macrophage

• dendritic cell (“Langerhans cell”)

Langerhans Cell Langerhans Cell (dendritic antigen presenting cell)(dendritic antigen presenting cell)

• dendritic

• antigen presenting

• expresses HLA-DR and CD1a

• cytoplasmic HX bodies (Birbeck granules)

Langerhans CellLangerhans Cell

• dendritic

• antigen presenting

• expresses HLA-DR and CD1a

• cytoplasmic HX bodies (Birbeck granules)

Cotran, Kumar, Collins: Pathologic Basis of Disease 1999

Dendritic Cells (Reticular Cells)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

““Histiocytosis”Histiocytosis”old classificationold classification

Histiocytosis X

i. Letterer-Siwe disease

ii. Hand-Schüller-Christian disease

iii. Eosinophilic granuloma

““Histiocytosis”Histiocytosis”classificationclassification

Langerhans Cell Histiocytosis

three (3) clinicopathologic entities1. acute disseminated Langerhans cell hitiocytosis (Letterer-Siwe disease)

2. multifocal Langerhans cell histiocytosis (multifocal eosinophilic granuloma)

3. unifocal Langerhans cell histiocytosis (unifocal eosinophilic granuloma)

Acute Disseminated Langerhans Cell Acute Disseminated Langerhans Cell Histiocytosis (Letterer-Siwe disease)Histiocytosis (Letterer-Siwe disease)

• mainly occurs before 2 yrs of age

• skin involvement (trunk, scalp)

• hepatosplenomegaly, lymphadenopathy, lung involvement

• destructive osteolytic bone lesions

Acute Disseminated Langerhans Cell Acute Disseminated Langerhans Cell Histiocytosis (Letterer-Siwe disease)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

Acute Disseminated Langerhans Cell Acute Disseminated Langerhans Cell Histiocytosis (Letterer-Siwe disease)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

Multifocal Langerhans Cell Histiocytosis Multifocal Langerhans Cell Histiocytosis (multiple eosinophilic granuloma)(multiple eosinophilic granuloma)

• multiorgan involvementbone (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

Multifocal Langerhans Cell Histiocytosis Multifocal Langerhans Cell Histiocytosis (multiple eosinophilic granuloma)(multiple eosinophilic granuloma)

Histology:• mainly involving medullary cavity of bone• expanding, erosive accumulation of Langerhans cells

Multifocal Langerhans Cell Histiocytosis Multifocal Langerhans Cell Histiocytosis (multiple eosinophilic granuloma)(multiple eosinophilic granuloma)

Histology:• mainly involving medullary cavity of bone• expanding, erosive accumulation of Langerhans cells• variably admixed with eosinophils, lymphocytes, plasma

cells, neutrophils

Multifocal Langerhans Cell Histiocytosis Multifocal Langerhans Cell Histiocytosis (multiple eosinophilic granuloma)(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

Unifocal Langerhans Cell Histiocytosis Unifocal Langerhans Cell Histiocytosis (unifocal eosinophilic granuloma)(unifocal eosinophilic granuloma)

• usually affects skeletal system• may be asymptomatic or may cause pain and tenderness• an indolent disease

Unifocal Langerhans Cell Histiocytosis Unifocal Langerhans Cell Histiocytosis (unifocal eosinophilic granuloma)(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

Histiocytic/Dendritic Cell Neoplasms Histiocytic/Dendritic Cell Neoplasms (1999 WHO classification)(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