Difference between revisions of "Diffuse large B-cell lymphoma"

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Diffuse large B-cell lymphoma (view source)

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'''Diffuse large B cell lymphoma''', abbreviated ''DLBCL'', is a very common [[lymphoma]].
{{ Infobox diagnosis
| Name = {{PAGENAME}}
| Image = Diffuse_large_B_cell_lymphoma_-_cytology_low_mag.jpg
| Width =
| Caption = DLBCL - cytology.
| Micro = large lymphoid cells (>=2x resting lymphocyte), nucleolus, sheeting architecture
| Subtypes =
| LMDDx = [[follicular lymphoma]], [[Hodgkin lymphoma]], [[PTLD]], primary effusion lymphoma, carcinoma
| Stains =
| IHC = CD20+, CD10+/-, BCL6+/-, CD45+
| EM =
| Molecular = t(14;18)(q32;q21)/IGH-BCL2 - esp. when arising from follicular lymphoma
| IF =
| Gross =
| Grossing =
| Site = [[Lymph node]]
| Assdx =
| Syndromes =
| Clinicalhx =
| Signs =
| Symptoms =
| Prevalence =
| Bloodwork = +/- cytopenia
| Rads = lymphadenopathy
| Endoscopy =
| Prognosis = poor
| Other =
| ClinDDx = 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).<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>
*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==
Features:<ref name=Ref_PBoD676>{{Ref PBoD|676 (???)}}</ref>
Features:<ref name=Ref_PCPBoD8_321>{{Ref PCPBoD8|321}}</ref><ref name=Ref_PBoD676>{{Ref PBoD|676 (???)}}</ref>
*Large lymphoid cells:
*Large lymphoid cells:
**4-5x the diameter of a small lymphocytes.
**>= 2x the diameter of a small lymphocytes.
**Marked cell-to-cell variation in size and shape.  
**Marked cell-to-cell variation in size and shape.  
**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 - nodular arrangement.
*'''Not''' follicular/nodular arrangement.
**Follicular arrangement = [[follicular lymphoma]].
**Follicular arrangement = [[follicular lymphoma]].


Line 14: 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]].


Images:
===Differential diagnosis===
*[http://commons.wikimedia.org/wiki/File:Diffuse_large_B_cell_lymphoma_-_cytology_low_mag.jpg DLBCL - cytology (WC)].
*[[Carcinoma]] - esp. [[small cell carcinoma]].
 
==Differential diagnosis==
*Carcinoma.
*[[Anaplastic large cell lymphoma]] (ALCL).
*[[Anaplastic large cell lymphoma]] (ALCL).
*[[Follicular lymphoma]].
*[[Follicular lymphoma]].
**If a nodular architecture is present it is follicular lymphoma.
**If a nodular architecture is present it is follicular lymphoma.
*[[Post-transplant lymphoproliferative disorder]] (PTLD) - in organ transplant recipients.
*[[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===
*[[Primary mediastinal B-cell lymphoma]] (PMBL) - esp. in young adults.
*T-cell/histiocyte-rich large B cell lymphoma.
*[[CNS lymphoma|Primary DLBCL of the CNS]].
*EBV-positive DLBCL of the elderly.
*DLBCL associated with chronic inflammation.
*[[Intravascular lymphoma|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==
==IHC==
==="UHN panel"===
===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:<ref>{{Cite journal  | last1 = Choi | first1 = WW. | last2 = Weisenburger | first2 = DD. | last3 = Greiner | first3 = TC. | last4 = Piris | first4 = MA. | last5 = Banham | first5 = AH. | last6 = Delabie | first6 = J. | last7 = Braziel | first7 = RM. | last8 = Geng | first8 = H. | last9 = Iqbal | first9 = J. | title = A new immunostain algorithm classifies diffuse large B-cell lymphoma into molecular subtypes with high accuracy. | journal = Clin Cancer Res | volume = 15 | issue = 17 | pages = 5494-502 | month = Sep | year = 2009 | doi = 10.1158/1078-0432.CCR-09-0113 | PMID = 19706817 }}</ref>
{{familytree/start}}
{{familytree | | | | | | |A11| | | | |A11 =DLBCL }}
{{familytree | | | | |,|-|-|^|-|-|.| |}}
{{familytree | | | | B11 | | | | B12 |B11=CD10 -ve|B12=CD10 +ve <br>GC }}
{{familytree | |,|-|-|^|-|-|.| | | | |}}
{{familytree | D11 | | | | D12 | | | |D11=BCL6 -ve <br>Non-GC|D12=BCL6 +ve }}
{{familytree | | | | |,|-|-|^|-|-|.| |}}
{{familytree | | | | F11 | | | | F12 |F11=MUM1 -ve<br>GC|F12=MUM1 +ve <br>Non-GC }}
{{familytree/end}}
 
===A panel===
*H&E 2 micrometers.
*H&E 2 micrometers.
*CD20 -- B cells.
*CD20 -- B cells.
*CD10 -- follicular lymphoma.
*CD10 -- follicular lymphoma (membrane).
*BCL6 -- follicular lymphoma.
*BCL6 -- follicular lymphoma (nucleus).
*BCL2 -- follicular lymphoma.
*BCL2 -- follicular lymphoma (membrane/cytoplasm).
*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]].
*CD3 -- T cells.
*CD3 -- T cells (membrane/cytoplasm).
*CD5 -- T cells.
*CD5 -- T cells (membrane).
*Unstained x4.
*Unstained x4.
==Molecular==
*Rearrangements of BCL6.<ref>{{OMIM|109565}}</ref>
**Can be assessed with an [[ISH]] break apart probe.
*Translocation typical of [[follicular lymphoma]]: t(14;18)(q32;q21)/IGH-BCL2.<ref name=pmid18359244>{{cite journal |author=Vitolo U, Ferreri AJ, Montoto S |title=Follicular lymphomas |journal=Crit. Rev. Oncol. Hematol. |volume=66 |issue=3 |pages=248–61 |year=2008 |month=June |pmid=18359244 |doi=10.1016/j.critrevonc.2008.01.014 |url=}}</ref>
==Sign out==
<pre>
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.
</pre>
<pre>
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.
</pre>
===Preliminary===
<pre>
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.
</pre>


==See also==
==See also==
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[[Category:Haematopathology]]
[[Category:Haematopathology]]
[[Category:Diagnosis]]
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