Diffuse large B-cell lymphoma

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Diffuse large B-cell lymphoma
Diagnosis in short

DLBCL - cytology.

LM large lymphoid cells (>=2x resting lymphocyte), nucleolus, sheeting architecture
LM DDx follicular lymphoma, Hodgkin lymphoma, PTLD, primary effusion lymphoma, carcinoma
IHC CD20+, CD10+/-, BCL6+/-, CD45+
Molecular t(14;18)(q32;q21)/IGH-BCL2 - esp. when arising from follicular lymphoma
Site Lymph node

Blood work +/- cytopenia
Radiology lymphadenopathy
Prognosis poor
Clin. DDx metastatic carcinoma, reactive lymphadenopathy, infective lymphadenopathy

Diffuse large B-cell lymphoma, abbreviated DLBCL, is a very common lymphoma with a poor prognosis.

General

  • Poor prognosis.
  • May arise from follicular lymphoma.
  • Most common form of non-Hodgkin lymphoma (in the USA).[1]
  • Most common lymphoma of the spleen.[2]
  • Obesity is a risk factor.[3]
  • Suscepibility loci located on 6p, 2p and 8q.[4]

Microscopic

Features:[1][5]

  • Large lymphoid cells:
    • >= 2x the diameter of a small lymphocytes.
    • Marked cell-to-cell variation in size and shape.
    • Cytoplasm usually basophilic and moderate in abundance.
    • +/-Prominent nucleoli, may be peripheral and/or multiple.
  • Not follicular/nodular arrangement.

Notes:

  • Large bizarre cells can occasionally mimic Reed-Sternberg cells, seen in Hodgkin lymphoma.

Differential diagnosis

Images

Special subtypes of diffuse large B-cell lymphoma

IHC

Subclassification

There is a subclassification based on molecular testing:

  1. Germinal centre (GC) subtype.
  2. Non-germinal centre (Non-GC) subtype.

The following IHC algorithm has been subsequently developed to reproduce the molecular categorization:[7]

 
 
 
 
 
 
DLBCL
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CD10 -ve
 
 
 
CD10 +ve
GC
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
BCL6 -ve
Non-GC
 
 
 
BCL6 +ve
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
MUM1 -ve
GC
 
 
 
MUM1 +ve
Non-GC

A panel

  • H&E 2 micrometers.
  • CD20 -- B cells.
  • CD10 -- follicular lymphoma (membrane).
  • BCL6 -- follicular lymphoma (nucleus).
  • BCL2 -- follicular lymphoma (membrane/cytoplasm).
  • MUM1 -- B cells.
  • CD21 -- highlight FDC networks if present.
  • CD23 -- highlight FDC networks if present.
  • MIB1 -- proliferative rate.
  • EBER -- EBV.
  • CD3 -- T cells (membrane/cytoplasm).
  • CD5 -- T cells (membrane).
  • Unstained x4.

Molecular

  • Rearrangements of BCL6.[8]
    • Can be assessed with an ISH break apart probe.
  • Translocation typical of follicular lymphoma: t(14;18)(q32;q21)/IGH-BCL2.[9]

Sign out

RETROPERITONEAL MASS, RIGHT, CORE BIOPSIES:
- DIFFUSE LARGE B-CELL LYMPHOMA.

COMMENT:
The tumour consists of cells approximately 2x the size of mature 
lymphocytes.  Mature lymphocytes are intermixed with the tumour. 
There is no gland formation. Follicle formation is not apparent.
SPLEEN, SPLENECTOMY:
- DIFFUSE LARGE B-CELL LYMPHOMA.

COMMENT:
Architecture: no gland formation, no follicle formation apparent, dyscohesive.
Tumour cell size: 1.5-2x resting lymphocyte.
Nucleoli: present.
Cytoplasm: scant-to-moderate basophilic/grey.
Proliferation: mitoses easily identified.

Positive stains (tumour cells):
CD45, CD20, BCL-2, BCL-6.

Negative stains (tumour cells):
pankeratin, S-100, MUM-1, CD3, CD5, CD10, CD21, CD30.

Ki-67: 20% of cells.

Preliminary

RETROPERITONEAL MASS, LEFT, CORE BIOPSIES:
- MORPHOLOGICALLY CONSISTENT WITH LARGE CELL LYMPHOMA -- PENDING IHC.

COMMENT:
Tumour cells: size ~2x mature lymphocyte, small nucleoli present, moderate
quantity of grey/basophilic cytoplasm.
Cells intermixed with tumour: mature lymphocytes.
Architecture: no gland formation, discohesive, no follicles apparent.

See also

References

  1. 1.0 1.1 Mitchell, Richard; Kumar, Vinay; Fausto, Nelson; Abbas, Abul K.; Aster, Jon (2011). Pocket Companion to Robbins & Cotran Pathologic Basis of Disease (8th ed.). Elsevier Saunders. pp. 321. ISBN 978-1416054542.
  2. Shimizu-Kohno, K.; Kimura, Y.; Kiyasu, J.; Miyoshi, H.; Yoshida, M.; Ichikawa, R.; Niino, D.; Ohshima, K. (Sep 2012). "Malignant lymphoma of the spleen in Japan: a clinicopathological analysis of 115 cases.". Pathol Int 62 (9): 577-82. doi:10.1111/j.1440-1827.2012.02844.x. PMID 22924843.
  3. Castillo, JJ.; Ingham, RR.; Reagan, JL.; Furman, M.; Dalia, S.; Mitri, J. (Apr 2014). "Obesity is associated with increased relative risk of diffuse large B-cell lymphoma: a meta-analysis of observational studies.". Clin Lymphoma Myeloma Leuk 14 (2): 122-30. doi:10.1016/j.clml.2013.10.005. PMID 24360912.
  4. Cerhan, JR.; Berndt, SI.; Vijai, J.; Ghesquières, H.; McKay, J.; Wang, SS.; Wang, Z.; Yeager, M. et al. (Nov 2014). "Genome-wide association study identifies multiple susceptibility loci for diffuse large B cell lymphoma.". Nat Genet 46 (11): 1233-8. doi:10.1038/ng.3105. PMID 25261932.
  5. Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 676 (???). ISBN 0-7216-0187-1.
  6. Gualco, G.; Natkunam, Y.; Bacchi, CE. (Jan 2012). "The spectrum of B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma: a description of 10 cases.". Mod Pathol. doi:10.1038/modpathol.2011.200. PMID 22222636.
  7. Choi, WW.; Weisenburger, DD.; Greiner, TC.; Piris, MA.; Banham, AH.; Delabie, J.; Braziel, RM.; Geng, H. et al. (Sep 2009). "A new immunostain algorithm classifies diffuse large B-cell lymphoma into molecular subtypes with high accuracy.". Clin Cancer Res 15 (17): 5494-502. doi:10.1158/1078-0432.CCR-09-0113. PMID 19706817.
  8. Online 'Mendelian Inheritance in Man' (OMIM) 109565
  9. Vitolo U, Ferreri AJ, Montoto S (June 2008). "Follicular lymphomas". Crit. Rev. Oncol. Hematol. 66 (3): 248–61. doi:10.1016/j.critrevonc.2008.01.014. PMID 18359244.