Difference between revisions of "Haematopathology"

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(split-out lymphoma)
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*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>[http://emedicine.medscape.com/article/1357846-diagnosis http://emedicine.medscape.com/article/1357846-diagnosis]</ref>


==Lymphoma classification==
==Lymphoma==
Lymphomas can be divided into:
{{main|Lymphoma}}
*Hodgkin's lymphoma.
*Non-Hodgkin's lymphoma (NHL).


Other categorizations:
==Plasma cell lesions==
*T cell lymphomas (rare).
:See ''[[lymphoma]]''.
*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==
{{main|Hodgkin's lymphoma}}
===General===
*Abbreviated ''HL''.
 
===Microscopic===
By definition, HL has Reed-Sternberg cells (RSCs).
 
====Classical HL====
Features (classic HL):
*Reed-Sternberg cell.
**Large binucleated cell.
***May be multinucleated.
***May have a horseshoe-like shape.
**Macronucleolus - approximately the size of a RBC (~8 micrometers).
**Well-defined cell border.
 
Notes:
*Large mononuclear cells are common (so called "mononuclear RSCs") but not diagnostic.
 
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)].
 
=====Subtypes=====
There are four CHL subtypes:<ref name=Ref_WMSP567>{{Ref WMSP|567}}</ref>
#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.
#*May be associated with HIV infection.<ref name=pmid20138008>{{cite journal |author=Sissolak G, Sissolak D, Jacobs P |title=Human immunodeficiency and Hodgkin lymphoma |journal=Transfus. Apher. Sci. |volume=42 |issue=2 |pages=131–9 |year=2010 |month=April |pmid=20138008 |doi=10.1016/j.transci.2010.01.008 |url=}}</ref>
#Lymphocyte-rich CHL - rare.
#*T lymphocytes only (no mix of cells).
#Lymphocyte-depleted CHL - rare.
#*May be associated with HIV infection.<ref name=pmid20138008/>
 
Memory device:
*The subtypes prevalence is in reverse alphabetical order.
 
====Nodular lymphocyte-predominant HL====
Features (nodular lymphocyte-predominant Hodgkin's lymphoma):
*''Popcorn cell'' (previously known as ''Lymphocytic & histiocytic'' cell (L&H cell)<ref name=pmid9499174>{{cite journal |author=Küppers R, Rajewsky K, Braeuninger A, Hansmann ML |title=L&H cells in lymphocyte-predominant Hodgkin's disease |journal=N. Engl. J. Med. |volume=338 |issue=11 |pages=763–4; author reply 764–5 |year=1998 |month=March |pmid=9499174 |doi=10.1056/NEJM199803123381113 |url=}}</ref>) - variant of RSC:
**Cells (relatively) small (compared to classic RSCs).
**Lobulated nucleus - '''key feature'''.
**Small nucleoli.
*Subtle nodularity at low power (2.5x or 5x objective).
 
Images (NLPHL):
*[http://webpathology.com/image.asp?case=388&n=16 Popcorn cell (webpathology.com)].
*[http://commons.wikimedia.org/wiki/File:Popcorn_cell_in_nodular_lymphocyte_predominant_Hodgkin_lymphoma_-_very_high_mag_cropped.jpg Popcorn cell (WC)].
 
==Follicular lymphoma==
{{main|Small cell lymphomas}}
 
==Diffuse large B-cell lymphoma==
{{main|Diffuse large B cell lymphoma}}
===General===
*Abbreviated ''DLBCL''.
 
===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:
*Large bizarre cells can occasionally mimic Reed-Sternberg cells, seen in [[Hodgkin lymphoma]].
 
==Burkitt's lymphoma==
{{main|Burkitt lymphoma}}
===General===
*Abbreviated ''BL''.
*Subtyped by etiology.
 
===Microscopic===
Features:
*"Starry-sky pattern":
**The ''stars'' in the pattern are: tingible-body macrophages.  
***''Tingible-body macrophages'' = macrophages containing apoptotic tumour cells.
**The tumour cells are the sky.
*Tumour cells:<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>
**Medium-sized (~1.5-2x the size of a RBC) with uniform size ("monotonous") -- '''key feature'''.
**Round nucleus.
**Small nucleoli.
**Relatively abundant cytoplasm.
**Brisk mitotic rate.
 
Image: [http://en.wikipedia.org/wiki/File:Burkitt_lymphoma,_H%26E.jpg Starry-sky pattern - Ed Uthman (WC)].
 
==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:
*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>
| 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==
==Cytometry - population cell marker quantification==

Revision as of 03:46, 18 August 2010

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

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.

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.[2]

Lymphoma

Main article: Lymphoma

Plasma cell lesions

See lymphoma.

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.[3]
    • Lambda dominance is less common.

GS guidelines - non-malignant is:[4]

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

Abnormal

See cytometry.

See also

References

  1. ↑ http://emedicine.medscape.com/article/1357846-overview
  2. ↑ http://emedicine.medscape.com/article/1357846-diagnosis
  3. ↑ SB. March 10, 2010.
  4. ↑ GS. LSC Procedure. March 11, 2010.
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