Histiocyte and DC neoplasms

Question 1

Blastic Plasmacytoid Dendritic Cell Neoplasm IMPT

Answer 1

Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN):

• CD123 + 1 pDC marker (303, 304 or TCF4) + CD4 ± CD56

Or

• 3 pDC markers

Question 2

Definition of Histiocytes

Answer 2

• Archaic term for tissue macrophages
• Now encompassing term for macrophages and DCs

Question 3

IMPT for Macrophages

Answer 3

Positive for CD45, CD14, lysozyme, CD68 and CD163

Question 4

IMPT for Conventional DCs

Answer 4

Positive for S100, CD1a, CD207, CD4

Note: CD207 (Langerin) and Birbeck granules on EM

Question 5

IMPT for plasmacytoid DCs

Answer 5

Positive for CD123, CD303, CD304 and TCF4

Question 6

Features of Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)

Answer 6

• Skin with systemic dissemination
• Immature
• Vacuolation (string of pearls) with cytoplasmic pseudopods

Question 7

Discuss Pathophysiology of HLH

Answer 7

Abnormal prolif and activation of:
I. Macrophages:
* Fever
* Splenomegaly
* Cyopenias

II. cytoToxicTs
* > inflammatory cytokines
* CD8Ts and NK dysfx

Question 8

Types of HLH

Answer 8

1’ = Familial HLH
* AR, PRF1 - FHLH2

2’ HLH
* Infection
* Malignancies
* AI D/O (Macrophage activation s/d)
* Systemic juvebile idiopath. arthritis (SJIA)
* SLE
* Kawasaki
* Tx = C/S ± cyclosporine

Question 9

Dx criteria of HLH

Answer 9

I. Mol Dx consistent with 1’ HLH (FamHLH)

Or

II. 5+ of the following:
* Fever
* Splenomeg
* Cytopenias
* HyperTrigliseridaemia ± hypoFbg
* Haemophagocytosis
* Low/No NK activity
* Ferritin > 500
* Soluble CD25 (IL2Receptopt) > 2400

Question 10

Gauchers Disease pathophysiology

Answer 10

• Lipid storage d/o
  
  • Undigested lipids accum in Monos and Macroph.
• AR
  
  • > in Ashkanizi Jews
  • Def of gluco-cerebro-sidase (0-30%)
  • Hydrolises gluco-cerebro-side

Subtypes:
* Type 1 = No neuro (cytopenias, HSM and bone deform)
* Type 2= acute neuro
* Type 3 = in between

Question 11

Treatment of Gauchers:

Answer 11

1. Enzyme replacement therapy ERT (rGluco-cerebro-sidase)
2. Oral substrate reduction OSR (Miglustat)

Question 12

Types of macrophage d/o

5

Answer 12

1. JXG = skin
2. ECD = MultiOrgan & BRAF
3. RDD = Nodal/Extranodal S100+
4. ALK+ Histiocytosis
5. Histiocytic sarcoma

Question 13

Features of Langerhans cell histiocytosis

Answer 13

• Nuclear groove
• Abundant eosinophilic cytoplasm
• Background of Eos, lymphos and Giant cells
• BRAF V600E mutation