Histiocytic disorders

Question 1

What is the diagnostic work up for LCH?

Answer 1

• CBC
• Liver function tests; abdo US if abnormal
• Chest X-R (CT-scan if pulmonary abnormalities)
• Skeletal survey, PET-scan
• Specific gravity on morning urine sample
• MRI of the head if Sx or DI
• Bone marrow if abnormal CBC
• Biopsies of involved lesions if needed

Question 2

Which organs are considered high risk in LCH?

Answer 2

• Spleen
• Liver
• Bone marrow

Question 3

What is the most common presentation of LCH?

Answer 3

Monostotic bone lesion

Question 4

What are the immunophenotypic hallmarks of LCH?

Answer 4

CD1a, langerin, S100, fascin

60%: BRAF V600E (+)ve

Question 5

What is the current standard of care for low-risk multisystem LCH?

Answer 5

Prednisone + vinblastine for 12 months

Question 6

What is the natural history of DI in LCH?

Answer 6

Usually irreversible, and not improved by systemic therapy (same as other endocrinopathies in LCH)

Question 7

What is the immunophenotype of juvenile xanthogranuloma?

Answer 7

CD1a (-), S100 (-), langerin (-)

CD68+, CD163+, fascin +

Question 8

What are the diseases associated with juvenile xanthogranuloma?

Answer 8

NF1, Noonan, JMML

Question 9

What is the natural history of juvenile xanthogranuloma?

Answer 9

Mostly spontaneous regression; occasional fatalities in cases involving CNS or liver (but extranodal involvement rare, about 5% of cases)

Question 10

What is the immunophenotype of Rosai-Dorfman disease?

Answer 10

CD1a(-), Langerin (-)ve

S100+, fascin+, CD68+, CD163+

Question 11

What is the most common clinical presentation of Rosai-Dorfman disease? What organs are most often affected?

Answer 11

Painless, massive cervical lymphadenopathy

Extra-nodal involvement (40%): skin, upper respiratory tract, bone

Question 12

Treatment of HLH

Answer 12

Etoposide, glucocorticoids, cyclosporine, IT MTX
(based on HLH-1994 and HLH-2004)
Recurrent or familial HLH: allogeneic HSCT

Question 13

Prognosis of familial HLH

Answer 13

Fatal without HSCT

50% with HSCT

Question 14

Causes of familial HLH (list 5)

Answer 14

Non-syndromic HLH: FHL1 to FHL5
(includes FLH2, perforin gene, and FHL4, syntaxin gene)
Syndromic: Chediak-Higashi, Griscelli type 2, lysinuric protein intolerance, XLP1 - 2

Question 15

Causes of secondary HLH

Answer 15

• Infection: EBV (55%), herpervirus, more rarely bacteria, fungi, protozoa
• Malignancy: T-cell malignancies
• Auto-immune disease: JIA, SLE
• Drug-induced: following blinatumomab