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Haematopathology (view source)

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The lymph node is discussed below; however, details are covered in the ''[[lymph node]]'' article and ''[[lymph node pathology]]'' article.
The lymph node is discussed below; however, details are covered in the ''[[lymph node]]'' article and ''[[lymph node pathology]]'' article.


==Bone marrow==
=Bone marrow=
{{main|Bone}}
{{main|Bone marrow}}
Bone marrows are important for understanding haematopathology.  They are dealt with in the ''[[bone]]'' article.
Bone marrows are important for understanding haematopathology.  They are dealt with in the ''[[bone marrow|bone]]'' article.


==Normal lymph node==
=Normal lymph node=
{{main|Lymph node}}
{{main|Lymph node}}
{{main|Lymph node pathology}}
{{main|Lymph node pathology}}
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**Plasma cells.
**Plasma cells.


=Haematologic neoplasia=
Historically, haematologic neoplasias were split into leukemia (disease of the bone marrow & blood) and lymphoma (disease in discrete masses -- usually lymph nodes). In the modern day, this distinction has blurred.
==Myelodysplastic syndrome==
{{Main|Myelodysplastic syndrome}}
At first approximation, these can be thought of as "pre-leukemia/lymphoma".
==Leukemia==
{{Main|Leukemia}}
These predominantly have blood/bone marrow involvement.
==Lymphoma==
{{main|Lymphoma}}
These form masses. They typically arise from lymph nodes or aggregates of lymphocytes.
==Plasma cell lesions==
{{Main|Plasma cell neoplasms}}
==Myeloproliferative neoplasms==
{{main|Myeloproliferative neoplasms}}
This subset of haematopathology includes, among others, polycythemia vera. Historically, these were not classified as neoplasias.
=Specific diagnoses=
==Hemophagocytic syndrome==
==Hemophagocytic syndrome==
{{main|Hemophagocytic syndrome}}
{{main|Hemophagocytic syndrome}}
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==Heparin-induced thrombocytopenia==
==Heparin-induced thrombocytopenia==
*Thrombocytopenia due to heparin.<ref>[http://emedicine.medscape.com/article/1357846-overview http://emedicine.medscape.com/article/1357846-overview]</ref>
*Thrombocytopenia due to heparin.<ref name=emed_hit>URL: [http://emedicine.medscape.com/article/1357846-overview http://emedicine.medscape.com/article/1357846-overview]. Accessed on: 17 May 2011.</ref>


Classification:
Classification:
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Diagnosis (simplified):
Diagnosis (simplified):
*50% decline in platelets - within 4-10 days of starting heparin.
*50% decline in platelets - within 4-10 days of starting heparin.
*HIT assay - several exist.<ref>[http://emedicine.medscape.com/article/1357846-diagnosis http://emedicine.medscape.com/article/1357846-diagnosis]</ref>
*HIT assay - several exist.<ref name=emed_hit>URL: [http://emedicine.medscape.com/article/1357846-overview http://emedicine.medscape.com/article/1357846-overview]. Accessed on: 17 May 2011.</ref>
 
==Lymphoma classification==
Lymphomas can be divided into:
*Hodgkin's lymphoma.
*Non-Hodgkin's lymphoma (NHL).
 
Other categorizations:
*T cell lymphomas (rare).
*B cell lymphomas (more common).
 
Two most common NHLs:
*Follicular lymphoma (FL).
*Diffuse large B-cell lymphoma (DLBCL).
 
===Lymphoma as a med student===
*Acute lymphoid leukemia (ALL) - predominantly in '''smALL''' people, i.e. children.
*Acute myeloid leukemia (AML).
*Chronic myeloid leukemia (CML).
*Chronic lymphoid leukemia (CLL) - relatively good prognosis.
 
===Histologic classification===
#"Size".
#Nodularity.
 
===="Size"====
*The single most important factor for classifying lymphomas.
*Not really based on size.
 
{| class="wikitable"
|
| "Large"
| "Small"
| Utility
|-
| Nucleoli
| present
| absent
| most discriminative
|-
| Size
| >2x RBC dia.
| <2x RBC dia.
| moderate
|-
| Chromatin pattern
| "open" (pale)
| "closed"
| moderate/minimal
|-
| Cytoplasm
| mold-minimal <br>basophilic cytoplasm
| scant cytoplasm
| minimal
|}
 
===Histologic terms===
*Lymphomas = cells look discohesive, may be difficult to differentiate from poor differentiated carcinoma.
*Auer rods = Acute myeloid leukemia.
**Granular cytoplasmic rod (0.5-1 x4-6 micrometres).
*Reed-Sternberg cells = Hodgkin's lymphoma.
**Large cell - very large nucleus.
***Classically binucleated.
*Russell bodies = Plasmacytoma (+others).
**Eosinophilic, large, homogenous immunoglobulin-containing inclusions.<ref name=pmid3979421>{{cite journal |author=Alanen A, Pira U, Lassila O, Roth J, Franklin RM |title=Mott cells are plasma cells defective in immunoglobulin secretion |journal=Eur. J. Immunol. |volume=15 |issue=3 |pages=235–42 |year=1985 |month=March |pmid=3979421 |doi= |url=}}</ref>
***''Mott cell'' is a cell that contains Russell bodies.<ref name=pmid3979421/>
*Effacement of nodal architecture.
*Loss of proliferation centers.
 
===IHC===
====General====
*CD45.
**AKA ''common lymphocyte antigen''.
**Useful to differentiate from carcinomas (e.g. small cell carcinoma).
====T cell markers====
*CD2 -- T cell marker (all T cells).
*CD3 -- T cell marker (all T cells).
**CD4 -- subset of T cells.
**CD8 -- subset of T cells.
*CD7 -- often lost first in T cell lymphomas.
*CD5 -- +ve in CLL & mantle cell lymphoma.
*CD43 -- +ve in mantle cell lymphoma
 
====B cell markers====
*CD20 -- B cell marker.
**CD19 -- B cell marker - used for [[flow cytometry]].
*PAX-5.
*CD79a.
 
*CD10 -- follicule center.
*BCL-6.
*BCL-2.
 
====Follicular dendritic cells====
*CD23 -- follicular dendritic cells.
*CD21 -- follicular dendritic cells.
 
====Hodgkin's lymphoma====
=====Classic=====
*CD30 -- Hodgkin's lymphoma (most sensitive).
*CD15.


==Hodgkin's lymphoma==
==Disseminated intravascular coagulation==
{{main|Hodgkin's lymphoma}}
*Commonly abbreviated ''DIC''.
===General===
===General===
*Abbreviated ''HL''.
*Usually associated with sepsis or septic shock.<ref>URL: [http://emedicine.medscape.com/article/779097-overview http://emedicine.medscape.com/article/779097-overview]. Accessed on: 23 October 2010.</ref>
 
===Microscopic===
By definition, HL has Reed-Sternberg cells (RSCs).
 
====Classical HL====
Features (classic HL):
*Reed-Sternberg cell.
**Large binucleated cell.
**Macronucleolus - approximately the size of a RBC (~8 micrometers).
**Well-defined cell border.


Images (classic HL):
Clinical:
*[http://commons.wikimedia.org/wiki/File:Hodgkin_lymphoma_cytology_large.jpg HL mixed cellularity - cytology (WC)].
*Schistocytes (red blood cell fragmentation).
*[http://commons.wikimedia.org/wiki/File:Hodgkin_lymphoma_cytology_small.jpg HL mixed cellularity - cytology (WC)].
*[http://en.wikipedia.org/wiki/File:Hodgkin_lymphoma_%281%29_mixed_cellulary_type.jpg HL mixed cellularity (WC)].


=====Subtypes=====
===Gross===
There are four CHL subtypes:<ref name=Ref_WMSP567>{{Ref WMSP|567}}</ref>
Features:<ref>{{Ref HospAuto|209}}</ref>
#Nodular sclerosis CHL - ~70% of CHL.
*Pleural petechial haemorrhages.
#*Mixed cellular background - T cell, plasma cells, eosinophils, neutrophils and histiocytes.
#*Nodular sclerosing fibrosis - thick strands fibrosis.
#Mixed cellularity CHL - ~20-25% of CHL.
#*Like nodular sclerosis - but no fibrosis.
#Lymphocyte-rich CHL - rare.
#*T lymphocytes only (no mix of cells).
#Lymphocyte-depleted CHL - rare.
#*Assoc. with HIV infection.
 
Memory device:
*The subtypes prevalence is in reverse alphabetical order.
 
====Nodular lymphocyte-predominant HL====
Features (nodular lymphocyte-predominant Hodgkin's lymphoma):
*''Lymphocytic & histiocytic'' cell (L&H cell)<ref name=pmid9499174>PMID: 9499174</ref> - variant of RSC:
**Cells (relatively) small (compared to classic RSCs).
**Lobulated nucleus - '''key feature'''.
**Small nucleoli.
 
Image (NLPHL):
*[http://webpathology.com/image.asp?case=388&n=16 Popcorn cell (webpathology.com)].
 
==Follicular lymphoma==
{{main|Small cell lymphomas}}
 
==Diffuse large B-cell lymphoma==
{{main|Diffuse large B cell lymphoma}}
===General===
*Abbreviated ''DLBCL''.


===Microscopic===
===Microscopic===
Features:<ref name=Ref_PBoD676>{{Ref PBoD|676 (???)}}</ref>
Features:<ref name=Ref_PBoD8_670>{{Ref PBoD8|670}}</ref>
*Large cells -- 4-5 times the diameter of a small lymphocytes.
*Microvascular occlusion.
*Typically have marked cell-to-cell variation in size and shape.
*Cytoplasm usu. basophilic and moderate in abundance.
*+/-Prominent nucleoli, may be peripheral and/or multiple.  


Notes:
Notes:
*Large bizarre cells can occasionally mimic Reed-Sternberg cells, seen in [[Hodgkin lymphoma]].
*Microvascular occlusion is also seen in [[thrombotic microangiopathies]].
 
==Burkitt's lymphoma==
{{main|Burkitt lymphoma}}
===General===
*Abbreviated ''BL''.
*Subtyped by etiology.
 
===Microsopic===
*"Starry-sky pattern".
**The ''stars'' in the pattern are: tingible-bodies laden macrophages.
***''[[Tingible-bodies macrophages]]'' = macrophages containing dead body of apoptotic tumor cells.
*Tumour cells:<ref name=pmid12610094/>
**Medium size.
**Round nuclei.
**Multiple nucleoli.
**Relatively abundant cytoplasm.
 
Image: [http://en.wikipedia.org/wiki/File:Burkitt_lymphoma,_H%26E.jpg Starry-sky pattern - Ed Uthman (www.wikipedia.org)].
 
==Plasmacytoma==
===General===
*[[AKA]] ''plasma cell myleoma''.
*Malignancy derived from the plasma cells.
*Histologic component of ''multiple myeloma''; to diagnose multiple myeloma other (non-pathology) criteria are needed.
*Prognosis: poor.
 
===Microscopic===
Features:
*Abundant eosinophilic cytoplasm.
*Eccentrically placed nucleus.
**Usually with "clock face" morphology.
***"Clock face" morphology = chromatin clumps around the edge of the nucleus, like the numbers on a clock face.
**May have nucleoli.
*Russell bodies:
**Eosinophilic, large (10-15 micrometres), homogenous immunoglobulin-containing inclusions.
***Images: [http://commons.wikimedia.org/wiki/File:Russell_bodies_2_high_mag_mini.jpg Russell bodies (WC)], [http://www.healthsystem.virginia.edu/internet/hematology/hessimages/russell-bodies-website-arrow.jpg Russell bodies (healthsystem.virginia.edu)], [http://www.pathguy.com/lectures/russ2.jpg Russell bodies - several in one cell (pathguy.com)].
*Dutcher bodies - intranuclear crystalline rods.
**Dutcher bodies are ''PAS stain'' +ve.<ref>URL: [http://www.thefreelibrary.com/Dutcher+bodies+in+chronic+synovitis-a083551789 http://www.thefreelibrary.com/Dutcher+bodies+in+chronic+synovitis-a083551789]. Accessed on: 4 August 2010.</ref>
**Image [http://ashimagebank.hematologylibrary.org/cgi/content/full/2003/0227/100629 Dutcher bodies (hematologylibrary.org)].
*Prominent ''perinuclear hof'' - cytoplasmic crescent shaped lucency adjacent to the nuclear membrane (due to large Golgi apparatus); nucleus has a [http://en.wikipedia.org/wiki/Bib_%28garment%29 "bib"].
 
Images:
*[http://ashimagebank.hematologylibrary.org/cgi/content/full/2004/0126/100984 Various images (hematologylibrary.org)].
*[http://commons.wikimedia.org/wiki/File:Plasmacytoma1.jpg Plasmacytoma (WC)].
 
DDx:
*Neuroendocrine carcinoma - nucleus often has a plasmacytoid (plasma cell-like) appearance.
 
==Acute myeloid leukemia==
===General===
*May afflicits young adult.
*Males>females.
 
===Complications===
*Chloroma - soft tissue mass.
*Leukostasis.
**Occurs - lungs and brain.<ref>AML. Harrison's 16th Ed.</ref>
*Hyperviscosity syndrome.
*Spontaneous bleeding with low platelet counts.
 
===Classification===
There are two classifications:
#FAB (French-American-British) - based on histologic appearance/maturation.
#WHO classification.
 
===Histology===
*Auer rods - not required to diagnose.<ref>AG. 8 July, 2009.</ref>
**Cytoplasmic granular rods in blast cells.
***Dimensions: approx. 0.5-1 x 4-6 micrometres.
**Images: [http://en.wikipedia.org/wiki/File:Auer_rods.PNG Auer rods (WP)], [http://www.healthsystem.virginia.edu/internet/hematology/HessImages/Acute-myelogenous-leukemia-M4-100x-Auer-rods-website-arrow.jpg Auer rods (virginia.edu)].
 
==Angioimmunoblastic T-cell lymphoma==
 
===Microscopic===
Features:
*Clear cytoplasm.
*"Empty" sinus; subcapsular sinuses "open".
 
===IHC===
*CD7 -ve.
*CD20 +ve.
*TIA-1 -ve.
 
==Anaplastic large cell lymphoma==
===General===
*Abbreviated '''ALCL'''.
*May look a lot like a carcinoma.
**Often subcapsular in LNs.
*Usually T-cell derived.
*Alk IHC:
** +ve = good prognosis.
** -ve = bad prognosis.


DDx:
=Cytometry - population cell marker quantification=
*Hodgkin's lymphoma.
{{main|Cytometry}}
 
===Microscopic===
Features:
*Large cells with eosinophilic cytoplasm.
*Usu. appear cohesive.
*May be subcapsular.
*Large multinucleated cell - "wreath cell" - '''key feature'''.
 
===IHC===
Features:
*Variable CD30 +ve. (???)
*CD45 +ve. (???)
 
==Table of B-cell lymphoma==
Small cell lymphomas:
{| class="wikitable"
! Name
! Location
! Size of cells
! IHC
! Translocations
! Clinical
! Other
|-
| Follicular lymphoma
| Follicle
| Small, centrocytes, centroblasts
| CD10+, bcl-6+<ref name=Ref_Lester95>{{Ref Lester|95}}</ref>
| t(14,18)
| Clinical ?
| Other ?
|-
| Mantle cell lymphoma
| Mantle zone
| Small
| CD5+, CD23-, CD43+, cyclin D1+<ref name=Ref_Lester95>{{Ref Lester|95}}</ref>
| t(11;14)(q13;q32)<ref>URL: [http://atlasgeneticsoncology.org/Anomalies/t1114ID2021.html http://atlasgeneticsoncology.org/Anomalies/t1114ID2021.html]. Accessed on: 10 August 2010.</ref>
| Clinical ?
| Other ?
|-
| Marginal zone lymphoma (MALT)
| Marginal zone
| Small
| CD21+, CD11c+, CD5-, CD23-<ref name=Ref_Lester95>{{Ref Lester|95}}</ref>
| Translocations
| Clinical
| Other
|-
| Precursor lymphoblastic lymphoma/leukemia
| Location ?
| Small
| CD10+, CD5-, TdT+, CD99+<ref name=Ref_Lester95>{{Ref Lester|95}}</ref>
| Translocations ?
| Clinical ?
| Other ?
|}
 
Medium and large cell lymphomas:
{| class="wikitable"
! Name
! Location
! Size of cells
! IHC
! Translocations
! Clinical
! Other
|-
| Burkitt's lymphoma
| Follicle
| Large cells
| CD10, bcl-6
| t(8;14) (q24;q32)
| Rapid growth
| "Starry sky"
|-
| Diffuse large B cell lymphoma
| Follicle (?)
| Large 4-5X of lymphocyte
| MIB-1 >40%
| none/like follicular l.
| Poor prognosis
| Common among lymphomas
|-
| Name
| Location
| Size of cells
| IHC
| Translocations
| Clinical
| Other
|}
 
==Cytometry - population cell marker quantification==
{{main|cytometry}}


===Two techniques===
===Two techniques===
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===Common markers===
===Common markers===
*CD3, CD4, CD8, CD5, CD7.
*CD3, CD4, CD8, [[CD5]], CD7.
*CD19, CD20, FMC7.
*CD19, [[CD20]], FMC7.
*Kappa, lambda.
*Kappa, lambda.


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See ''[[cytometry]]''.
See ''[[cytometry]]''.


==See also==
=Abnormal sign out=
<pre>
Lymph Node, Right Posterior Triangle of Neck, Excision:
- Lymphoid tissue with abnormal architecture, predominantly small cells.
- Case will be sent to hematopathology for opinion.
</pre>
 
=See also=
*[[Stomach]].
*[[Stomach]].
*[[Lymph nodes]].
*[[Lymph nodes]].


==References==
=References=
{{reflist|2}}
{{reflist|2}}


[[Category:Haematopathology]]
[[Category:Haematopathology]]
Michael
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