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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=
===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).
*Glistening surface when cut.
 
Pathologic:
*White lesions, espically irregular = suggestive of carcinoma.
*White, glistening, with lobulated surface - "fish flesh" = suggestive of lymphoma.
**Subtle lobulation (~1 mm) on section suggestive of ''follicular lymphoma''.<ref>DB. 5 August 2010.</ref>


===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:
*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:
*T cell lymphomas (rare).
*B cell lymphomas (more common).


Two most common NHLs:
==Myelodysplastic syndrome==
*Follicular lymphoma (FL).
{{Main|Myelodysplastic syndrome}}
*Diffuse large B-cell lymphoma (DLBCL).
At first approximation, these can be thought of as "pre-leukemia/lymphoma".


===Lymphoma as a med student===
==Leukemia==
*Acute lymphoid leukemia (ALL) - predominantly in '''smALL''' people, i.e. children.
{{Main|Leukemia}}
*Acute myeloid leukemia (AML).
These predominantly have blood/bone marrow involvement.
*Chronic myeloid leukemia (CML).
*Chronic lymphoid leukemia (CLL) - relatively good prognosis.


===Histology===
==Lymphoma==
*Lymphomas = cells look discohesive, may be difficult to differentiate from poor differentiated carcinoma.
{{main|Lymphoma}}
*Auer rods = Acute myeloid leukemia.
These form masses. They typically arise from lymph nodes or aggregates of lymphocytes.
**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===
==Plasma cell lesions==
====General====
{{Main|Plasma cell neoplasms}}
*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====
==Myeloproliferative neoplasms==
*CD20 -- B cell marker.
{{main|Myeloproliferative neoplasms}}
**CD19 -- B cell marker - used for [[flow cytometry]].
This subset of haematopathology includes, among others, polycythemia vera. Historically, these were not classified as neoplasias.
*PAX-5.
*CD79a.


*CD10 -- follicule center.
=Specific diagnoses=
*BCL-6.
==Hemophagocytic syndrome==
*BCL-2.
{{main|Hemophagocytic syndrome}}
 
====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==
{{main|Hodgkin's lymphoma}}
===General===
===General===
*Abbreviated ''HL''.
*Rare.


===Microscopic===
===Microscopic===
By definition, HL has Reed-Sternberg cells (RSCs).
Features:
*Macrophages eat RBCs, WBCs.


====Classical HL====
==Heparin-induced thrombocytopenia==
Features (classic HL):
*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>
*Reed-Sternberg cell.
**Large binucleated cell.
**Macronucleolus - approximately the size of a RBC (~8 micrometers).
**Well-defined cell border.


Images (classic HL):
Classification:
*[http://commons.wikimedia.org/wiki/File:Hodgkin_lymphoma_cytology_large.jpg HL mixed cellularity - cytology (WC)].
*Type 1 - in first two days of exposure - considered non-immune and considered not to be serious.
*[http://commons.wikimedia.org/wiki/File:Hodgkin_lymphoma_cytology_small.jpg HL mixed cellularity - cytology (WC)].
*Type 2 - in the first 4-10 days - considered serious.
*[http://en.wikipedia.org/wiki/File:Hodgkin_lymphoma_%281%29_mixed_cellulary_type.jpg HL mixed cellularity (WC)].


=====Subtypes=====
Diagnosis (simplified):
There are four CHL subtypes:<ref name=Ref_WMSP567>{{Ref WMSP|567}}</ref>
*50% decline in platelets - within 4-10 days of starting heparin.
#Nodular sclerosis CHL - ~70% of CHL.
*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>
#*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==
==Disseminated intravascular coagulation==
*Commonly abbreviated ''DIC''.
===General===
===General===
*A very common type of lymphoma.
*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>
*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===
Features:
*Abundant abnormal lymphoid follicles.
 
===IHC===
Features:<ref name=pmid18359244/>
*CD10 +ve/-ve.
*CD5 -ve.
**+ve in mantle cell lymphoma.
*CD23 -ve/+ve.
**+ve in CLL.
*CD43 -ve.
**+ve in mantle cell lymphoma, marginal zone lymphoma.
*CD11c -ve -- flow cytometry only.


===Molecular===
Clinical:
*t(14;18)(q32;q21)/IGH-BCL2 in 70-95% of cases.<ref name=pmid18359244/>
*Schistocytes (red blood cell fragmentation).
**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>


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


===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==
===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===
*[[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).
 
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:
*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.
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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 smallest 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).
**CD7 is usually the first to be lost.


===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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