Difference between revisions of "Diffuse large B-cell lymphoma"
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*Most common form of non-Hodgkin lymphoma (in the USA).<ref name=Ref_PCPBoD8_321>{{Ref PCPBoD8|321}}</ref> | *Most common form of non-Hodgkin lymphoma (in the USA).<ref name=Ref_PCPBoD8_321>{{Ref PCPBoD8|321}}</ref> | ||
*Most common lymphoma of the [[spleen]].<ref name=pmid22924843>{{Cite journal | last1 = Shimizu-Kohno | first1 = K. | last2 = Kimura | first2 = Y. | last3 = Kiyasu | first3 = J. | last4 = Miyoshi | first4 = H. | last5 = Yoshida | first5 = M. | last6 = Ichikawa | first6 = R. | last7 = Niino | first7 = D. | last8 = Ohshima | first8 = K. | title = Malignant lymphoma of the spleen in Japan: a clinicopathological analysis of 115 cases. | journal = Pathol Int | volume = 62 | issue = 9 | pages = 577-82 | month = Sep | year = 2012 | doi = 10.1111/j.1440-1827.2012.02844.x | PMID = 22924843 }}</ref> | *Most common lymphoma of the [[spleen]].<ref name=pmid22924843>{{Cite journal | last1 = Shimizu-Kohno | first1 = K. | last2 = Kimura | first2 = Y. | last3 = Kiyasu | first3 = J. | last4 = Miyoshi | first4 = H. | last5 = Yoshida | first5 = M. | last6 = Ichikawa | first6 = R. | last7 = Niino | first7 = D. | last8 = Ohshima | first8 = K. | title = Malignant lymphoma of the spleen in Japan: a clinicopathological analysis of 115 cases. | journal = Pathol Int | volume = 62 | issue = 9 | pages = 577-82 | month = Sep | year = 2012 | doi = 10.1111/j.1440-1827.2012.02844.x | PMID = 22924843 }}</ref> | ||
*Obesity is a risk factor.<ref>{{Cite journal | last1 = Castillo | first1 = JJ. | last2 = Ingham | first2 = RR. | last3 = Reagan | first3 = JL. | last4 = Furman | first4 = M. | last5 = Dalia | first5 = S. | last6 = Mitri | first6 = J. | title = Obesity is associated with increased relative risk of diffuse large B-cell lymphoma: a meta-analysis of observational studies. | journal = Clin Lymphoma Myeloma Leuk | volume = 14 | issue = 2 | pages = 122-30 | month = Apr | year = 2014 | doi = 10.1016/j.clml.2013.10.005 | PMID = 24360912 }}</ref> | |||
*Suscepibility loci located on 6p, 2p and 8q.<ref>{{Cite journal | last1 = Cerhan | first1 = JR. | last2 = Berndt | first2 = SI. | last3 = Vijai | first3 = J. | last4 = Ghesquières | first4 = H. | last5 = McKay | first5 = J. | last6 = Wang | first6 = SS. | last7 = Wang | first7 = Z. | last8 = Yeager | first8 = M. | last9 = Conde | first9 = L. | title = Genome-wide association study identifies multiple susceptibility loci for diffuse large B cell lymphoma. | journal = Nat Genet | volume = 46 | issue = 11 | pages = 1233-8 | month = Nov | year = 2014 | doi = 10.1038/ng.3105 | PMID = 25261932 }}</ref> | |||
==Microscopic== | ==Microscopic== | ||
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**Cytoplasm usually basophilic and moderate in abundance. | **Cytoplasm usually basophilic and moderate in abundance. | ||
**+/-Prominent nucleoli, may be peripheral and/or multiple. | **+/-Prominent nucleoli, may be peripheral and/or multiple. | ||
*'''Not''' follicular | *'''Not''' follicular/nodular arrangement. | ||
**Follicular arrangement = [[follicular lymphoma]]. | **Follicular arrangement = [[follicular lymphoma]]. | ||
| Line 48: | Line 50: | ||
*Large bizarre cells can occasionally mimic Reed-Sternberg cells, seen in [[Hodgkin lymphoma]]. | *Large bizarre cells can occasionally mimic Reed-Sternberg cells, seen in [[Hodgkin lymphoma]]. | ||
===Differential diagnosis=== | |||
*[http:// | *[[Carcinoma]] - esp. [[small cell carcinoma]]. | ||
*[[Anaplastic large cell lymphoma]] (ALCL). | |||
*[[Follicular lymphoma]]. | |||
**If a nodular architecture is present it is follicular lymphoma. | |||
*[[Post-transplant lymphoproliferative disorder]] (PTLD) - in organ transplant recipients. | |||
*Primary effusion lymphoma - seen in [[HIV]] infections. | |||
*Mixed cellularity [[Hodgkin lymphoma]] - esp. for T-cell/histiocyte-rich large B cell lymphoma. | |||
*B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma.<ref name=pmid22222636>{{Cite journal | last1 = Gualco | first1 = G. | last2 = Natkunam | first2 = Y. | last3 = Bacchi | first3 = CE. | title = 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. | journal = Mod Pathol | volume = | issue = | pages = | month = Jan | year = 2012 | doi = 10.1038/modpathol.2011.200 | PMID = 22222636 | URL = http://www.nature.com/modpathol/journal/vaop/ncurrent/full/modpathol2011200a.html }}</ref> | |||
*Other [[small round cell tumours]]. | |||
===Images=== | |||
<gallery> | |||
Image: Diffuse large B cell lymphoma (1) tonsil.jpg | DLBCL. (WC/KGH) | |||
Image: Diffuse large B cell lymphoma (2) tonsil.jpg | DLBCL. (WC/KGH) | |||
Image: Diffuse large B cell lymphoma (3) tonsil.jpg | DLBCL. (WC/KGH) | |||
</gallery> | |||
<gallery> | |||
Image: DLBCL of testis - 2 -- intermed mag.jpg | DLBCL (testis) - intermed. mag. (WC) | |||
Image: DLBCL of testis - 2 -- high mag.jpg | DLBCL (testis) - high mag. (WC) | |||
Image: DLBCL of testis - 2 -- very high mag.jpg | DLBCL (testis) - very high mag. (WC) | |||
</gallery> | |||
<gallery> | |||
Image:Diffuse_large_B_cell_lymphoma_-_cytology_low_mag.jpg | DLBCL - cytology (WC) | |||
</gallery> | |||
==Special subtypes of diffuse large B-cell lymphoma== | ===Special subtypes of diffuse large B-cell lymphoma=== | ||
*[[Primary mediastinal B-cell lymphoma]] (PMBL) - esp. in young adults. | *[[Primary mediastinal B-cell lymphoma]] (PMBL) - esp. in young adults. | ||
*T-cell/histiocyte-rich large B cell lymphoma. | *T-cell/histiocyte-rich large B cell lymphoma. | ||
| Line 62: | Line 86: | ||
*Plasmablastic lymphoma. | *Plasmablastic lymphoma. | ||
*LBCL arising in [[HHV-8]] associated multicentric [[Castleman disease]]. | *LBCL arising in [[HHV-8]] associated multicentric [[Castleman disease]]. | ||
*Primary effusion lymphoma. | *Primary effusion lymphoma - associated with [[human immunodeficiency virus]]. | ||
*Lymphomatoid granulomatosis. | *Lymphomatoid granulomatosis. | ||
==IHC== | ==IHC== | ||
| Line 92: | Line 106: | ||
{{familytree/end}} | {{familytree/end}} | ||
=== | ===A panel=== | ||
*H&E 2 micrometers. | *H&E 2 micrometers. | ||
*CD20 -- B cells. | *CD20 -- B cells. | ||
| Line 100: | Line 114: | ||
*MUM1 -- B cells. | *MUM1 -- B cells. | ||
*CD21 -- highlight FDC networks if present. | *CD21 -- highlight FDC networks if present. | ||
*CD23 -- highlight FDC networks if present. | *[[CD23]] -- highlight FDC networks if present. | ||
*MIB1 -- proliferative rate. | *MIB1 -- proliferative rate. | ||
*EBER -- [[EBV]]. | *EBER -- [[EBV]]. | ||
Latest revision as of 10:46, 29 March 2017
| 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
- 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.
- Follicular arrangement = follicular lymphoma.
Notes:
- Large bizarre cells can occasionally mimic Reed-Sternberg cells, seen in Hodgkin lymphoma.
Differential diagnosis
- Carcinoma - esp. small cell carcinoma.
- Anaplastic large cell lymphoma (ALCL).
- Follicular lymphoma.
- If a nodular architecture is present it is follicular lymphoma.
- Post-transplant lymphoproliferative disorder (PTLD) - in organ transplant recipients.
- Primary effusion lymphoma - seen in HIV infections.
- Mixed cellularity Hodgkin lymphoma - esp. for T-cell/histiocyte-rich large B cell lymphoma.
- B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma.[6]
- Other small round cell tumours.
Images
DLBCL. (WC/KGH)
DLBCL. (WC/KGH)
DLBCL. (WC/KGH)
_tonsil.jpg)
_tonsil.jpg)
_tonsil.jpg)
DLBCL (testis) - intermed. mag. (WC)
DLBCL (testis) - high mag. (WC)
DLBCL (testis) - very high mag. (WC)
DLBCL - cytology (WC)
Special subtypes of diffuse large B-cell lymphoma
- Primary mediastinal B-cell lymphoma (PMBL) - esp. in young adults.
- T-cell/histiocyte-rich large B cell lymphoma.
- Primary DLBCL of the CNS.
- EBV-positive DLBCL of the elderly.
- DLBCL associated with chronic inflammation.
- Intravascular LBCL.
- ALK-positive LBCL.
- Plasmablastic lymphoma.
- LBCL arising in HHV-8 associated multicentric Castleman disease.
- Primary effusion lymphoma - associated with human immunodeficiency virus.
- Lymphomatoid granulomatosis.
IHC
Subclassification
There is a subclassification based on molecular testing:
- Germinal centre (GC) subtype.
- 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
- Haematopathology.
- Lymph nodes.
- Lymph node pathology.
- Lymphoma.
- Small round cell tumours.
- Post-transplant lymphoproliferative disorder (PTLD).
References
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ Online 'Mendelian Inheritance in Man' (OMIM) 109565
- ↑ 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.