Histiocytic Disorders Flashcards
(14 cards)
Classification of Histiocytic disorders
-Dendritic cell proliferation
Langerhans Cell Histiocytosis LCH
-Macrophage proliferation Juvenile Xanthogranuloma Erdheim-Chester disease Rosai- Dorfman disease Hemophagocytic lymphohistiocytosis
-Histiocytic malignancies
Malignant histiocytosis
Histiocytic sarcoma
AML M7
LCH
Histology: Brubeck granules on electron microscopy, factor XIII
CD207+, CD1a, histiocytes among inflammatory infiltrate
Molecular- BRAF- V600E Ras- RAF- Mek-erk
Median age at presentation 2.4 yr
Very rare in African/ American
LCH disease categories
Risk based on organ involvement
- HR- liver, BM, spleen
- Multisystemic LR
- Single system LR
CNS risk -
Lesions in skull and pituitary
Risk of developing neurodegeneration
LCH therapy
Front line therapy-
Skin alone - oral MTX, VBL/Pred, hydroxyurea Low risk ( bone+/- skin, LN, CNS risk) - VBL/ pred 12 mo High Risk -VBL/pred/6-MP Radiotherapy - only for spine, femur or non- CNS risk isolated bone lesions
LCH outcomes
Low Risk
Mortality 0%
EFS 50%
High risk
10% mortality
EFS - 50%
Rosai- Dorfman
Disorder of macrophage proliferation
Emperipoleisis
Viable lymphocytes trafficking through histiocytes cD163+ and S 100A+
Presents with massive lymphadenopathy
AA children
RDD treatment
Observation
Steroids
Clofarabine
Juvenile Xanthogranuloma
CD163+ Usually limited to the skin Can have tumors everywhere Can have disseminated AML LIKE DISEASE ASSOCIATED WITH NF1 Mutation in MAPK genes
HLH
Too much inflammation
T- cell dysfunction
50% will survive if treated
If not treated or recognize they will not survive
HLH diagnostic criteria
5 of 8 Fever Splenomegaly Cytopenias ( at least 2 cell lines) Hypertriglyceridemia or hypofibrinogenemia Hemophagocytosis Ferritin >500 Elevated s-IL-2 Decreased NK cell activity Gene mutations
Genes associated with HLH
PRF1- FHL2 UNC13D- FHL3 STX11- FHL4 RAB27A- Griscelli syndrome STXBP2- FHL5 AP3B1- Hermansky- Pudlack2 SHD1A - XLP1 XIAP- XLP2 ITK, CD27- T cell dysfunction
HLH EVALUATIONS
Evaluate cytotoxic function
- NK CELL FUNCTION
CD107 mobilization assay
- Perforin, XLP protein ( xiap, sap) expression
- Targeted sequencing or whole genome sequencing
Virus, bacteria, fungal search
Focus on herpes viruses
Evaluate for malignancy
Evaluate for autoimmune disease
Damage from activation
CBC,
Treatment of high risk multisystemic LCH?
Induction (6 weeks): VBL and prednisone
Can be repeated if partial response
Continuation (12 months): VBL, prednisone, 6MP
What is the outcome of HR multisystemic LCH as per LCH III?
Name 1 important prognostic factor
OS: 84%, reactivation rates 27%
Response to therapy at 6 weeks