Large BLPDs

Question 1

Subtypes of Large BCLs

Answer 1

1. LBCL with genetic lesions
2. Site Specific
3. NOS

Question 2

Subtypes of Large BCL with genetic lesions

4

Answer 2

1. Double Hit (MYC & BCL2) DLBCL
2. LBCL with IRF4 (young, GC markers and MUM1)
3. HGBCL with 11q abberstions (BL-like morphology, B markers with CD10+, BCL6+, BCL2- and MYC-)
4. ALK+ LBCL (immunoblastic, aggressive with CD3+ and CD30+)

Question 3

What are the site specific Large BCL

11

Answer 3

1. 1’ LBCL of immune priveileged sites
2. PBL(#)
3. EBV+ DLBCL(#)
4. 1’ mediastinal LBCL
5. Mediastinal Grey Zone lymphoma
6. Fibrin associated LBCL(#)
7. Lymphomatoid granulomatosis(#)
8. DLBCL ass. with chronic inflammation(#)
9. Fluid overload LBCL
10. Intravascular LBCL
11. 1’ cutaneous DLBCL leg type

(#) = EBV associated

Question 4

Subtypes of Large BCL, NOS

3

Answer 4

I. DLBCL, NOS
* GCB and Non-GCB
* Morphological variants
* Immunoblastic
* Centroblastic
* Anaplastic

II. HGBCL, NOS
* and 11q abberations (BL-like)

III. TCHR BCL

Question 5

Features of TCHR LBCL

Answer 5

• Large Bs in the background of Ts and Histiocytes (CD68 and CD163+)
• Relationship with NLP HL
• IMPT: Positive for PanB, BCL6. Variable BCL2, MUM1 and EMA. Negative for CD15, CD30, CD138 and EBV-

Question 6

Subtypes of BL

Answer 6

I. EBV+ BL
* > somatic hypermutation
* < driver mutations
* < BCR expression

II. EBV- BL
* inverse of EBV+ BL

Question 7

Features of BL

Answer 7

1. t(8;14), t(8;22), t(2;8) (MYC to IgH/K/L gene promoter)
2. Medium, prominent nucleoli, lipid vacuoles
3. Starry sky - tingible body macrophages
4. IMPT: Positive for PanB, CD10, BCL6, CD43 (aberrant) and > Ki67 (>95%)
5. Tx: R-CODOXM + IVAC or R-Da-EPOCH or HyperCVAD

Question 8

Hanz Classifier

Answer 8

CD10+ = GCB
CD10-, BCL6+ and MUM1- = GCB
CD10-, BCL6- = Non GCB
CD10-, BCL6+ and MUM1+ = Non GCB

Question 9

Prognosis of LBCL

IPI (APLES)

Answer 9

IPI:
* Age >60
* Performance Status
* LDH >
* Extranodal sites
* Stage

ECOG:
0 - Fully active
1 - Light work
2 - Self care, no work
3 - Completely disabled

IPI Age Adjusted (<60)
Revided IPI (= IPI - predicts outcome of pts on Ritux)
NCCN IPI (=IPI - different LDH, sites not nr of extranodal)
CNS IPI (=IPI + Renal and adrenal involvement) 4-6 = High risk - CNS prophylaxis (High dose systemic/intrathecal MTX PLUS leucovorin)

Question 10

CNS prophylaxis in LBCL

Answer 10

CNS IPI
* IPI + Renal and adrenal involvement
* 4-6 = High risk = CNS prophylaxis
* High dose systemic/intrathecal MTX
* PLUS leucovorin

Question 11

Treatment of LBCL

Answer 11

I. R-CHOP & PET adapted approach

II. Mabs
* CD19 (Tafasitamab)

III. ADC
* CD79a (Polatuzumab)
* CD19

IV. Bispecific Abs
* Glofitamab