Histiocytic Disorders Flashcards

(14 cards)

1
Q

Classification of Histiocytic disorders

A

-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

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2
Q

LCH

A

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

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3
Q

LCH disease categories

A

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

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4
Q

LCH therapy

A

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
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5
Q

LCH outcomes

A

Low Risk
Mortality 0%
EFS 50%

High risk

10% mortality
EFS - 50%

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6
Q

Rosai- Dorfman

A

Disorder of macrophage proliferation

Emperipoleisis

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

Presents with massive lymphadenopathy
AA children

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7
Q

RDD treatment

A

Observation
Steroids
Clofarabine

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8
Q

Juvenile Xanthogranuloma

A
CD163+
Usually limited to the skin 
Can have tumors everywhere 
Can have disseminated AML LIKE DISEASE 
ASSOCIATED WITH NF1
Mutation in MAPK genes
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9
Q

HLH

A

Too much inflammation
T- cell dysfunction

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

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10
Q

HLH diagnostic criteria

A
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
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11
Q

Genes associated with HLH

A
PRF1- FHL2
UNC13D- FHL3
STX11- FHL4
RAB27A- Griscelli syndrome 
STXBP2- FHL5
AP3B1- Hermansky- Pudlack2
SHD1A - XLP1
XIAP- XLP2
ITK, CD27- T cell dysfunction
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12
Q

HLH EVALUATIONS

A

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,

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13
Q

Treatment of high risk multisystemic LCH?

A

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

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14
Q

What is the outcome of HR multisystemic LCH as per LCH III?

Name 1 important prognostic factor

A

OS: 84%, reactivation rates 27%

Response to therapy at 6 weeks

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