Histiocytosis Syndromes

Question 1

Common to all histiocytosis syndromes

Answer 1

Prominent proliferation or accumulation of cells of monocyte-macrophage system, of bone marrow origin

Question 2

Langerhans cell histiocytosis

Cellular characteristics of lesions

Answer 2

Langerhans-like cells CD1a+, CD207 + with birbeck granules

CD207: APC to T cells
Uniformly present in LCH lesions

Langerhans cells are normal antigen presenting cells in skin, and express CD1a

LCH lesions : clonal proliferation of cells of monocyte lineage containing Birbeck granule, which expresses CD1a. Also contain lymphocytes, granulocytes, eosinophils, monocytes

Question 3

Langerhans cell histiocytosis

Clinical features

Answer 3

Skeleton involved in 80%, commonly skull

Pain & local swelling 
Pathological fracture
Mastoid involvement: chronically draining ears
Scaly, papular seborrheic dermatitis 
Lymphadenopathy 
Hepatosplenomegaly
Pituitary dysfunction 

Risk organs: liver, spleen, haematopoietic, lung

Question 4

Langerhans histiocytosis

Treatment for single system disease

Answer 4

Usually bone, lymph node, or skin

Curretage, or less often local steroid injection or radiotherapy

High rate of spontaneous remission

Question 5

Langerhans histiocytosis

Treatment for multi system disease

Answer 5

Systemic chemo

Vinblastine
Steroids

85%+ survival rate

Question 6

HLH

Accumulation of what cell type

Classic cellular characteristics

Answer 6

Activated antigen processing cells - macrophages & lymphocytes

Tissue infiltration with activated CD8 T cells, macrophages, and cytokinaemia

Normal morphology, CD1a, CD207, birbeck granule negative

Cytolytic lymphocyte defects

Question 7

HLH

Two types

Answer 7

Familial HLH

• AR
• 25%
• mutation affects T cell and NK cell ability to synthesize & release perforin & granzymes

Infection associated HLH
(also drug, BMT, chemo, immunodeficiency states)

Question 8

HLH

Clinical manifestations
Lab findings

Answer 8

Fever
Maculopapular or petechial rash
Hepatosplenomegaly
Lymphadenopathy 
Respiratory distress
CNS involvement

Cytopenia of 2 lines
Hyper triglycerides 
Low fibrinogen 
High ferritin
Elevated CD25 (IL2 receptor)
Reduced or absent NK cells
BM, LN, or CSF evidence of hemophagocytosis

Question 9

Genetic markers of FHLH

Answer 9

Gene mutations in perforin or Munc13-4