Difference between revisions of "Haematopathology"

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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=
===Normal (clinical)===
{{main|Lymph node}}
*Round.
{{main|Lymph node pathology}}
*"Soft".
*Mobile.
 
===Pathologic (clinical) - associations===
*Rubbery = suggestive of lymphoma.
*Fixed (immobile) = suggestive of cancer.
*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.


Line 60: Line 29:
**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:
*Type 1 - in first two days of exposure - considered non-immune and considered not to be serious.
*Type 2 - in the first 4-10 days - considered serious.
 
Diagnosis (simplified):
*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>
 
==Lymphoma classification==
Lymphomas can be divided into:
*Hodgkin's lymphoma.
*Non-Hodgkin's lymphoma (NHL).


Other categorizations:
==Myelodysplastic syndrome==
*T cell lymphomas (rare).
{{Main|Myelodysplastic syndrome}}
*B cell lymphomas (more common).
At first approximation, these can be thought of as "pre-leukemia/lymphoma".


Two most common NHLs:
==Leukemia==
*Follicular lymphoma (FL).
{{Main|Leukemia}}
*Diffuse large B-cell lymphoma (DLBCL).
These predominantly have blood/bone marrow involvement.


===Lymphoma as a med student===
==Lymphoma==
*Acute lymphoid leukemia (ALL) - predominantly in '''smALL''' people, i.e. children.
{{main|Lymphoma}}
*Acute myeloid leukemia (AML).
These form masses. They typically arise from lymph nodes or aggregates of lymphocytes.
*Chronic myeloid leukemia (CML).
*Chronic lymphoid leukemia (CLL) - relatively good prognosis.


===Histology===
==Plasma cell lesions==
*Lymphomas = cells look discohesive, may be difficult to differentiate from poor differentiated carcinoma.
{{Main|Plasma cell neoplasms}}
*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===
==Myeloproliferative neoplasms==
*CD45+.
{{main|Myeloproliferative neoplasms}}
**AKA ''common lymphocyte antigen''.
This subset of haematopathology includes, among others, polycythemia vera. Historically, these were not classified as neoplasias.
**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 -- follicule center.
*CD30 -- Hodgkin's lymphoma (most sensitive).
*CD23 -- follicular dendritic cells.
*CD21 -- follicular dendritic cells.


==Hodgkin's lymphoma==
=Specific diagnoses=
{{main|Hodgkin's lymphoma}}
==Hemophagocytic syndrome==
{{main|Hemophagocytic syndrome}}
===General===
===General===
*Abbreviated ''HL''.
*Rare.
 
===Microscopic===
By definition, HL has Reed-Sternberg cells (RSCs).
 
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):
*[http://commons.wikimedia.org/wiki/File:Hodgkin_lymphoma_cytology_large.jpg HL mixed cellularity - cytology (WC)].
*[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)].
 
Features (Nodular lymphocyte-predominant Hodgkin's lymphoma):
*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==
*A very common type of lymphoma.
*Express Bcl-2.<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>


===Microscopic===
===Microscopic===
Features:
Features:
*Abundant abnormal lymphoid follicles.
*Macrophages eat RBCs, WBCs.


===IHC===
==Heparin-induced thrombocytopenia==
Features:<ref name=pmid18359244/>
*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>
*CD10+/-.
*CD5-.
*CD23-/+.
*CD43-.
*CD11c-.


===Molecular===
Classification:
*t(14;18)(q32;q21)/IGH-BCL2 in 70-95% of cases.<ref name=pmid18359244/>
*Type 1 - in first two days of exposure - considered non-immune and considered not to be serious.
**Should not be confused with t(14;18)(q32;q21)/IGH-MALT1 seen in MALT lymphomas.<ref name=pmid16950858>{{cite journal |author=Bacon CM, Du MQ, Dogan A |title=Mucosa-associated lymphoid tissue (MALT) lymphoma: a practical guide for pathologists |journal=J. Clin. Pathol. |volume=60 |issue=4 |pages=361–72 |year=2007 |month=April |pmid=16950858 |pmc=2001121 |doi=10.1136/jcp.2005.031146 |url=}}</ref>
*Type 2 - in the first 4-10 days - considered serious.


==Diffuse large B-cell lymphoma==
Diagnosis (simplified):
*Abbreviated ''DLBCL''.
*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>
===Microscopic===
Features:<ref name=Ref_PBoD676>{{Ref PBoD|676 (???)}}</ref>
*Large cells -- 4-5 times the diameter of a small lymphocytes.
*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:
==Disseminated intravascular coagulation==
*Large bizarre cells can occasionally mimic Reed-Sternberg cells, seen in Hodgkin lymphoma.
*Commonly abbreviated ''DIC''.
 
==Burkitt's lymphoma==
===General===
===General===
*Abbreviated ''BL''.
*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>
*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)].
Clinical:
*Schistocytes (red blood cell fragmentation).


==Plasmacytoma==
===Gross===
===General===
Features:<ref>{{Ref HospAuto|209}}</ref>
*Malignancy derived from the plasma cells.
*Pleural petechial haemorrhages.
*Histologic component of ''multiple myeloma''; to diagnose multiple myeloma other (non-pathology) criteria are needed.
*Prognosis: poor.


===Microscopic===
===Microscopic===
*Cells with "clock face" nuclei.
Features:<ref name=Ref_PBoD8_670>{{Ref PBoD8|670}}</ref>
*Russell bodies:
*Microvascular occlusion.
**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'' - cresent shaped lucency at the nuclear membrane (due to large Golgi apparatus).


Images: [http://ashimagebank.hematologylibrary.org/cgi/content/full/2004/0126/100984 Various images (hematologylibrary.org)].
Notes:
 
*Microvascular occlusion is also seen in [[thrombotic microangiopathies]].
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)].
 
==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:
*Hodgkin's lymphoma.
 
===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>
| Translocations ?
| 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:
=Cytometry - population cell marker quantification=
{| class="wikitable"
{{main|Cytometry}}
! 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
|}


==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.
Line 376: Line 112:


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]]

Latest revision as of 15:44, 5 March 2017

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 lobular breast carcinoma.

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

Bone marrow

Main article: Bone marrow

Bone marrows are important for understanding haematopathology. They are dealt with in the bone article.

Normal lymph node

Main article: Lymph node
Main article: Lymph node pathology

Microscopic

The microscopic lymph node architecture in described the lymph node article, along with B cell maturation and lymph node cell types.

The cells of the lymph node:

  • Germinal center:
    • Centrocytes - cleaved nucleus.
    • Centroblasts - large dark, mitotically active, medullary aspect of germinal center.
    • Tingible body macrophages.
    • Follicular dendritic cells.
  • Paracortex:
    • T lymphocytes.
    • Interdigitating dendritic cells.
  • Mantle zone:
    • Immunoblasts (Memory B cells) - small lymphocytes.
  • Medulla:
    • B lymphocytes.
    • 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 article: Myelodysplastic syndrome

At first approximation, these can be thought of as "pre-leukemia/lymphoma".

Leukemia

Main article: Leukemia

These predominantly have blood/bone marrow involvement.

Lymphoma

Main article: Lymphoma

These form masses. They typically arise from lymph nodes or aggregates of lymphocytes.

Plasma cell lesions

Main article: Plasma cell neoplasms

Myeloproliferative neoplasms

Main article: Myeloproliferative neoplasms

This subset of haematopathology includes, among others, polycythemia vera. Historically, these were not classified as neoplasias.

Specific diagnoses

Hemophagocytic syndrome

Main article: Hemophagocytic syndrome

General

  • Rare.

Microscopic

Features:

  • Macrophages eat RBCs, WBCs.

Heparin-induced thrombocytopenia

  • Thrombocytopenia due to heparin.[1]

Classification:

  • Type 1 - in first two days of exposure - considered non-immune and considered not to be serious.
  • Type 2 - in the first 4-10 days - considered serious.

Diagnosis (simplified):

  • 50% decline in platelets - within 4-10 days of starting heparin.
  • HIT assay - several exist.[1]

Disseminated intravascular coagulation

  • Commonly abbreviated DIC.

General

  • Usually associated with sepsis or septic shock.[2]

Clinical:

  • Schistocytes (red blood cell fragmentation).

Gross

Features:[3]

  • Pleural petechial haemorrhages.

Microscopic

Features:[4]

  • Microvascular occlusion.

Notes:

Cytometry - population cell marker quantification

Main article: Cytometry

Two techniques

  1. Flow cytometry.
  2. Laser scanning cytometry (LSC).

Common markers

  • CD3, CD4, CD8, CD5, CD7.
  • CD19, CD20, FMC7.
  • Kappa, lambda.

Normal

  • T-cells to B-cells usually 1:1.
  • In reactive nodes T-cells predominate.
  • 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.
  • Rule-of-thumb for normal k:l range is: <6:1 and 1:<3.[5]
    • Lambda dominance is less common.

GS guidelines - non-malignant is:[6]

  • CD19 ~= CD20.
  • CD5 = CD3.
  • CD2 > CD3 and CD5.
  • CD4 + CD8 ~= CD3.
  • CD7 = the smallest number of T-cell.

Abnormal

See cytometry.

Abnormal sign out

Lymph Node, Right Posterior Triangle of Neck, Excision:
- Lymphoid tissue with abnormal architecture, predominantly small cells.
- Case will be sent to hematopathology for opinion.

See also

References

  1. ↑ 1.0 1.1 URL: http://emedicine.medscape.com/article/1357846-overview. Accessed on: 17 May 2011.
  2. ↑ URL: http://emedicine.medscape.com/article/779097-overview. Accessed on: 23 October 2010.
  3. ↑ Burton, Julian L.; Rutty, Guy N. (2010). The Hospital Autopsy A Manual of Fundamental Autopsy Practice (3rd ed.). Oxford University Press. pp. 209. ISBN 978-0340965146.
  4. ↑ Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson; Aster, Jon (2009). Robbins and Cotran pathologic basis of disease (8th ed.). Elsevier Saunders. pp. 670. ISBN 978-1416031215.
  5. ↑ SB. March 10, 2010.
  6. ↑ GS. LSC Procedure. March 11, 2010.
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