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Haematopathology (view source)

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Understanding of '''haematopathology''' is important in [[anatomical pathology]], as '''haematologic malignancies''' are often in the (clinical) differential diagnosis and may mimic ''[[small blue round cell tumours]]'' or ''[[breast|lobular breast carcinoma]]''.
Understanding of '''haematopathology''' is important in [[anatomical pathology]], as '''haematologic malignancies''' are often in the (clinical) differential diagnosis and may mimic ''[[small blue round cell tumours]]'' or ''[[breast|lobular breast carcinoma]]''.


==Bone marrow==
The lymph node is discussed below; however, details are covered in the ''[[lymph node]]'' article and ''[[lymph node pathology]]'' article.
{{main|Bone}}
Bone marrows are important for understanding haematopathology.  They are dealt with in the ''[[bone]]'' article.


==Normal lymph node==
=Bone marrow=
===Normal (clinical)===
{{main|Bone marrow}}
*Round.
Bone marrows are important for understanding haematopathology. They are dealt with in the ''[[bone marrow|bone]]'' article.
*"Soft".
*Mobile.


===Pathologic (clinical) - associations===
=Normal lymph node=
*Rubbery = suggestive of lymphoma.
{{main|Lymph node}}
*Fixed (immobile) = suggestive of cancer.
{{main|Lymph node pathology}}
*Tender (hurts when ya touch it) = suggestive of infection.
 
===Radiologic & clinical===
*Elongated = may be cancer.
*"Large" = could be cancer or infection.
 
===Malignant - statistical associations===
Nodes with metstases tend to be:
*Hard.
*Ellipical (as opposed to circular) on section.
*"Large".
*May be immobile (fixed to a surrounding structure).
 
Note:
*"Large" depends on the location in the body.
 
===Gross pathologic exam===
Normal:
*Firm (relative to adipose tissue).
*Glissening surface when cut.
 
Pathologic:
*White lesions, espically irregular = suggestive of carcinoma.
*white, glissening, with lobulated surface - "fish flesh" = suggestive of lymphoma.


===Microscopic===
===Microscopic===
{{main|Lymph node}}
The microscopic lymph node architecture in described the ''[[lymph node]]'' article, along with B cell maturation and lymph node cell types.
The microscopic lymph node architecture in described the ''[[lymph node]]'' article, along with B cell maturation and lymph node cell types.


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**Plasma cells.
**Plasma cells.


==Heparin-induced thrombocytopenia==
=Haematologic neoplasia=
*Thrombocytopenia due to heparin.<ref>[http://emedicine.medscape.com/article/1357846-overview http://emedicine.medscape.com/article/1357846-overview]</ref>
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.


Classification:
==Myelodysplastic syndrome==
*Type 1 - in first two days of exposure - considered non-immune and considered not to be serious.
{{Main|Myelodysplastic syndrome}}
*Type 2 - in the first 4-10 days - considered serious.
At first approximation, these can be thought of as "pre-leukemia/lymphoma".


Diagnosis (simplified):
==Leukemia==
*50% decline in platelets - within 4-10 days of starting heparin.
{{Main|Leukemia}}
*HIT assay - several exist.<ref>[http://emedicine.medscape.com/article/1357846-diagnosis http://emedicine.medscape.com/article/1357846-diagnosis]</ref>
These predominantly have blood/bone marrow involvement.


==Lymphoma classification==
==Lymphoma==
Lymphomas can be divided into:
{{main|Lymphoma}}
*Hodgkin's lymphoma.
These form masses. They typically arise from lymph nodes or aggregates of lymphocytes.
*Non-Hodgkin's lymphoma (NHL).


Other categorizations:
==Plasma cell lesions==
*T cell lymphomas (rare).
{{Main|Plasma cell neoplasms}}
*B cell lymphomas (more common).


Two most common NHLs:
==Myeloproliferative neoplasms==
*Follicular lymphoma (FL).
{{main|Myeloproliferative neoplasms}}
*Diffuse large B-cell lymphoma (DLBCL).
This subset of haematopathology includes, among others, polycythemia vera. Historically, these were not classified as neoplasias.


===Lymphoma as a med student===
=Specific diagnoses=
*Acute lymphoid leukemia (ALL) - predominantly in '''smALL''' people, i.e. children.
==Hemophagocytic syndrome==
*Acute myeloid leukemia (AML).
{{main|Hemophagocytic syndrome}}
*Chronic myeloid leukemia (CML).
===General===
*Chronic lymphoid leukemia (CLL) - relatively good prognosis.
*Rare.
 
===Histology===
*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/>
 
===IHC===
*CD45+.
**AKA ''common lymphocyte antigen''.
**Useful to differentiate from carcinomas (e.g. small cell carcinoma).
*CD3 -- T cell marker (all T cells).
**CD4 -- subset of T cells.
**CD8 -- subset of T cells.
*CD20 -- B cell marker.
**CD19 -- B cell marker - used for flow cytometry.
*CD10 -- follicular cell ???
*CD30 -- Hodgkin's lymphoma (most sensitive).
 
==Hodgkin's lymphoma==
*Abbreviated ''HL''.
 
===Clinical===
Sx:<ref name=wmsp_p567>WMSP P.567.</ref>
*Fever, night sweats, weight loss.
*Infections (due to immune dysfunction).
 
Diagnosis:
*HL cannot be diagnosed with standard flow cytometry (FC) - but has been diagnosed with specialized FC.<ref>{{cite journal |author=Fromm JR, Thomas A, Wood BL |title=Flow cytometry can diagnose classical hodgkin lymphoma in lymph nodes with high sensitivity and specificity |journal=Am. J. Clin. Pathol. |volume=131 |issue=3 |pages=322–32 |year=2009 |month=March |pmid=19228638 |doi=10.1309/AJCPW3UN9DYLDSPB |url=}}</ref>
===Histology===
*Reed-Sternberg cell (by definition).
**Large binucleated cell.
**Macronucleolus - approximately the size of a RBC.
 
===HL subtypes===
Types:<ref name=wmsp_p567/>
*Classical HL (CHL) - ~95% of HL.
*Nodular lymphocyte-predominant HL (NLPHL) - ~5% of HL.
 
 
===Classical HL===
There are four CHL subtypes:<ref name=wmsp_p567/>
#Nodular sclerosis CHL - ~70% of CHL.
#*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===
*AKA ''lympho-histiocytic variant''.


===Microscopic===
Features:
Features:
*The diagnostic cells in this variant: relatively small, lobulated nucleus, small nucleoli.
*Macrophages eat RBCs, WBCs.


Image:
==Heparin-induced thrombocytopenia==
*[http://webpathology.com/image.asp?case=388&n=16 Popcorn cell (webpathology.com)].
*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>


===IHC===
Classification:
Abbreviated panel - see WMSP for details:<ref>WMSP P.568.</ref>
*Type 1 - in first two days of exposure - considered non-immune and considered not to be serious.
*CD30 Reed-Sternberg cells (RSCs) +ve ~98%
*Type 2 - in the first 4-10 days - considered serious.
*CD15 Reed-Sternberg cells +ve ~80%, stains neutrophils.
*CD45 '''often negative''' in RSCs.
*CD20 may stain RSCs.
*PAX5 +ve.<ref>APBR P.683.</ref>


Additional - for completeness:
Diagnosis (simplified):
*CD3 (T lymphocytes)
*50% decline in platelets - within 4-10 days of starting heparin.
*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>


NLPHL IHC '''differs''' from the classical HL:<ref>APBR P.683.</ref>
==Disseminated intravascular coagulation==
*LCA +ve.
*Commonly abbreviated ''DIC''.
*CD20 +ve.
===General===
*CD10 +ve.
*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>
*Bcl-6 +ve.
*EMA +ve.
*CD30 -ve
*CD15 -ve.


==Follicular lymphoma==
Clinical:
*A common type of lymphoma.
*Schistocytes (red blood cell fragmentation).


===Microscopic===
===Gross===
*Abundant abnormal lymphoid follicles.
Features:<ref>{{Ref HospAuto|209}}</ref>
 
*Pleural petechial haemorrhages.
==Diffuse large B-cell lymphoma==
*Abbreviated ''DLBCL''.


===Microscopic===
===Microscopic===
Features:<ref>PBOD P.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==
===General===
*Abbreviated ''BL''.
*Extremely high proliferative rate & rate of apoptosis.
 
===Subtypes===
*Three subtypes recognized:<ref name=pmid12610094>{{cite journal |author=Bellan C, Lazzi S, De Falco G, Nyongo A, Giordano A, Leoncini L |title=Burkitt's lymphoma: new insights into molecular pathogenesis |journal=J. Clin. Pathol. |volume=56 |issue=3 |pages=188–92 |year=2003 |month=March |pmid=12610094 |pmc=1769902 |doi= |url=http://jcp.bmj.com/cgi/pmidlookup?view=long&pmid=12610094}}</ref>
#Endemic:
#*Found in Africa.
#*EBV (Epstein-Barr virus) associated.<ref name=pmid12610094/>
#Non-endemic:
#*Typical of the BL seen in the western world; EBV negative.
#Immunodeficiency associated:
#*Associated with HIV infection.
 
===Pathophysiology===
*Origin cell: germinal centre B cells (favoured) vs. memory B cells.<ref name=pmid12610094/>
*Common translocation t(8;14).<ref name=pmid12610094/>
 
===Cytologic definition===
*t(8;14) (q24;q32) translocation + a few variants or c-myc rearrangement.<ref name=pmid12610094/>
 
===Histology===
*"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===
*Malignancy derived from the plasma cells.
*Histologic component of ''multiple myeloma''; to diagnose multiple myeloma other (non-pathology) criteria are needed.
 
===Microscopic===
*Cells with "clock face" nuclei.
*Russell bodies:
**Eosinophilic, large (10-15 micrometres), homogenous immunoglobulin-containing inclusions.
***Images: [http://www.healthsystem.virginia.edu/internet/hematology/hessimages/russell-bodies-website-arrow.jpg Russel bodies (healthsystem.virginia.edu)], [http://www.pathguy.com/lectures/russ2.jpg Russel bodies (pathguy.com)] - several in one cell.
*Dutcher bodies - intranuclear crystalline rods.
*Prominent ''perinuclear hof'' - cresent shaped lucency at the nuclear membrane (due to large Golgi apparatus).
 
Images: [http://ashimagebank.hematologylibrary.org/cgi/content/full/2004/0126/100984 http://ashimagebank.hematologylibrary.org/cgi/content/full/2004/0126/100984].
 
DDx:
*Neuroendocrine carcinoma - nucleus often has a plasmacytoid (plasma cell) look.
 
==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)].
 


==Table of B-cell lymphoma==
=Cytometry - population cell marker quantification=
{| class="wikitable"
{{main|Cytometry}}
! Name
! Location
! Size of cells
! IHC
! Translocations
! Clinical
! Other
|-
| Follicular lymphoma
| Follicle
| Small, centrocytes, centroblasts
| CD10, bcl-6
| t(14,18)
| 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
|}


==Population cell marker quantification==
===Two techniques===
Two techniques:
#[[Flow cytometry]].
*Flow cytometry.
#Laser scanning cytometry (LSC).
*Laser scanning cytometry (LSC).


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


Normal:
===Normal===
*T-cells to B-cells usually 1:1.
*T-cells to B-cells usually 1:1.
*In reactive nodes T-cell predominate.
*In reactive nodes T-cells predominate.
*Normal thymic tissue has cells that are positive for both CD4 and CD8.
*Normal thymic tissue has cells that are positive for both CD4 and CD8.
*Kappa (k) and lambda (l) are not expressed by the same cell.
*Kappa (k) and lambda (l) are not expressed by the same cell.
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GS guidelines - non-malignant is:<ref>GS. LSC Procedure. March 11, 2010.</ref>
GS guidelines - non-malignant is:<ref>GS. LSC Procedure. March 11, 2010.</ref>
*CD19 ~= CD20
*CD19 ~= CD20.
*CD5 = CD3
*CD5 = CD3.
*CD2 > CD3 and CD5
*CD2 > CD3 and CD5.
*CD4 + CD8 ~= CD3
*CD4 + CD8 ~= CD3.
*CD7 = the smalest number of T-cell
*CD7 = the smallest number of T-cell.


Abnormal:
===Abnormal===
*CD4>CD8 predominance classically seen in:
See ''[[cytometry]]''.
**Sarcoidosis.
**Hodgkin's lymphoma.
*T cell lymphoma - loss of one of the T-cell markers (CD2, CD3, CD5 or CD7).


===Sample report===
=Abnormal sign out=
B-Cell Associated Markers
<pre>
*CD10.
Lymph Node, Right Posterior Triangle of Neck, Excision:
**Germinal centre marker.
- Lymphoid tissue with abnormal architecture, predominantly small cells.
**+ve in: follicular l., Burkitt l., precursor lymphoblastic leukemia.
- Case will be sent to hematopathology for opinion.
*CD19.
</pre>
**B cell marker.
**Should be ~=CD20.
*CD20.
**B cell marker.
**Should be ~=CD20.
*CD23.
**+ve in CLL/SLL.
*FMC7
**B cell marker.
*Kappa+CD19/20+.
**B cell clonality.
*Lambda+CD19/20+
**B cell clonality.
T-Cell Associated Markers
*CD3.
**CD3 ~= CD4 + CD8.
**Usually: CD2 > CD3 > CD7.
*CD5.
**Usually: CD2 > CD5 > CD7.
*CD4.
**CD3 ~= CD4 + CD8.
*CD8.
**CD3 ~= CD4 + CD8.
*CD7.
**Usually least prevalent T cell marker; < CD2, < CD3, < CD5.
*CD2.
**Usually most prevalent T cell marker; > CD3, > CD5, > CD7.
NK-Cell Associated Markers
*CD56.
*CD16.
Miscellaneous Markers
*CD11c.
*CD14.


==See also==
=See also=
*[[Stomach]].
*[[Stomach]].
*[[Lymph nodes]].
*[[Lymph nodes]].


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


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