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Flashcards in Histiocytic Disorders Deck (14)
1

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

2

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

3

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

4

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

5

LCH outcomes

Low Risk
Mortality 0%
EFS 50%

High risk

10% mortality
EFS - 50%

6

Rosai- Dorfman

Disorder of macrophage proliferation

Emperipoleisis

Viable lymphocytes trafficking through histiocytes cD163+ and S 100A+

Presents with massive lymphadenopathy
AA children

7

RDD treatment

Observation
Steroids
Clofarabine

8

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

9

HLH

Too much inflammation
T- cell dysfunction

50% will survive if treated
If not treated or recognize they will not survive

10

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

11

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

12

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,

13

Treatment of high risk multisystemic LCH?

Induction (6 weeks): VBL and prednisone
Can be repeated if partial response
Continuation (12 months): VBL, prednisone, 6MP

14

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