Difference between revisions of "Lymphoma"

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*[[Hodgkin's lymphoma]].
*[[Hodgkin's lymphoma]].
*Carcinoma.
*Carcinoma.
Images:
*[http://commons.wikimedia.org/wiki/File:Anaplastic_large_cell_lymphoma_-_very_high_mag.jpg ALCL - very high mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Anaplastic_large_cell_lymphoma_-_cropped_-_very_high_mag.jpg ALCL - cropped - very high mag. (WC)].


===IHC===
===IHC===

Revision as of 07:02, 23 November 2011

Lymphoma is almost a specialty for itself. It can be subclassified a number of ways.

This article is an introduction to lymphoma. An introduction to lymph nodes and lymph node pathology that is not lymphoma are in the articles lymph node and lymph node pathology.

A general introduction to haematopathology is in the haematopathology article.

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).

Leukemia 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

  1. "Size".
  2. Nodularity.

"Size"

  • The single most important factor for classifying lymphomas.
  • Not really based on size.
"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
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.[1]
      • Mott cell is a cell that contains Russell bodies.[1]
  • 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).

Others:

  • AE1/AE3 -- to r/o 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
  • ALK1[2] - prognostic in anaplastic large cell lymphoma (ALCL).[3]
  • TIA1 - cytotoxic T-cell.[4]
  • Granzyme B.

B cell markers

  • CD10 -- follicle center.
  • BCL6 -- follicle center.
  • BCL2 -- normally negative in germinal centers (GCs), marks T cell; +ve in small B cell lymphomas.
  • MUM1 -- -ve in follicular lymphoma, +ve in DLBCL that did not arise from follicular lymphoma.

Plasma cell

  • Kappa -- usu. slightly stronger than lambda.
  • Lambda.
  • CD56[6] -- also +ve in NK/T cell lymphomas.
  • CD57 -- +ve in T-cell large granular lymphocytic leukemia.[7].
  • CD138.

Follicular dendritic cells

  • CD23 -- follicular dendritic cells.
  • CD21 -- follicular dendritic cells.

Hodgkin's lymphoma

Classic
  • CD30 +ve -- Hodgkin's lymphoma (most sensitive).
  • CD15 +ve.
  • PAX5 +ve.
  • EMA -ve.
  • EBER +ve/-ve.

Others:

  • CD20, CD45: weak +ve or -ve.
NLPHL
  • CD20 +ve.
  • CD30 -ve, CD15 -ve.
  • EMA +ve/-ve.
  • EBER -ve.

Others

  • Myeloperoxidase - in PMNs.
  • Glycophorin C.
  • CD61 -- megakaryocytes.
  • TdT.
  • CD34.

Hodgkin's lymphoma

Main article: 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):

Subtypes

There are four CHL subtypes:[8]

  1. Nodular sclerosis CHL - ~70% of CHL.
    • Mixed cellular background - T cell, plasma cells, eosinophils, neutrophils and histiocytes.
    • Nodular sclerosing fibrosis - thick strands fibrosis.
  2. Mixed cellularity CHL - ~20-25% of CHL.
    • Like nodular sclerosis - but no fibrosis.
    • May be associated with HIV infection.[9]
  3. Lymphocyte-rich CHL - rare.
    • T lymphocytes only (no mix of cells).
  4. Lymphocyte-depleted CHL - rare.
    • May be associated with HIV infection.[9]

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)[10]) - 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):

Small cell lymphomas

Main article: Small cell lymphomas

This grouping includes:

  • Follicular lymphoma.
  • Marginal zone lymphoma.
    • Nodal marginal zone lymphoma.
    • Extranodal marginal zone lymphoma (MALT lymphoma).
    • Splenic marginal zone lymphoma.
  • Mantle zone lymphoma.
  • Small lymphocytic lymphoma (SLL) / chronic lymphocytic leukemia (CLL).
  • Hairy cell leukemia.

Diffuse large B-cell lymphoma

Main article: Diffuse large B cell lymphoma

General

  • Abbreviated DLBCL.

Microscopic

Features:[11]

  • 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.

Intravascular lymphoma

  • Rare.
  • Usually B-cell lineage (see below intravascular large B-cell lymphoma).
    • May be T-cell lineage.[12]

Intravascular large B-cell lymphoma

General

  • AKA angiotropic lymphoma, intravascular malignant lymphomatosis, malignant angioendotheliomatosis.
Clinical
  • Often a non-specific presentation.[13]
    • +/-Fever.
    • +/-Multiple infarcts.
    • +/-Non-specific skin lesions.

Microscopic

Features:

  • Abundant atypical intravascular lymphoid cells that are:
    • Large (~2-3X size of a mature lymphocyte or RBC).
    • Nucleolus prominent.

Notes:

  • It may be hard to find RBCs in the vessels.
  • Looks sorta like a DLBCL -- but is intravascular.

Images:

IHC

Features:[13]

  • CD20 +ve - key feature.
  • CD3 -ve.
  • CD34 -ve.

Burkitt's lymphoma

Main article: 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:[14]
    • 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: Starry-sky pattern - Ed Uthman (WC).

Plasma cell neoplasms

Main article: Plasma cell neoplasms
  • These arise from plasma cells.
  • AKA plasma cell myeloma, plasmacytoma.
  • Multiple myeloma (a clinical diagnosis) fits into this category.

Acute myeloid leukemia

General

  • May afflicits young adult.
  • Males>females.

Complications

  • Chloroma - soft tissue mass.
  • Leukostasis.
    • Occurs - lungs and brain.[15]
  • Hyperviscosity syndrome.
  • Spontaneous bleeding with low platelet counts.

Classification

There are two classifications:

  1. FAB (French-American-British) - based on histologic appearance/maturation.
  2. WHO classification.

Histology

Enteropathy-associated T cell lymphoma

General

  • Abbreviated EATL.
  • AKA enteropathy-type T cell lymphoma (ETTL).
  • T cell lymphoma due to celiac sprue.

Microscopic

Features:

  • Epithelium preserved.
  • Small lymphoid cells in the mucosa and submucosa.

Image: EATL (WC).

Angioimmunoblastic T-cell lymphoma

Microscopic

Features:

  • Clear cytoplasm.
  • "Empty" sinus; subcapsular sinuses "open".

IHC

  • CD7 -ve.
  • CD20 +ve.
  • TIA-1 -ve.

Primary mediastinal B-cell lymphoma

  • Abbreviated PMBL.
  • AKA primary mediastinal large B-cell lymphoma.

General

Features:[17][18]

Microscopic

Features:

Images:

Anaplastic large cell lymphoma

  • Abbreviated ALCL.

General

  • May look a lot like a carcinoma.
    • Often subcapsular in LNs.
  • Usually T-cell derived.
  • May be isolated to the skin - good prognosis.

Alk IHC (systemic form):

  • +ve = good prognosis.
  • -ve = bad prognosis.

Microscopic

Features:

  • Large cells with eosinophilic cytoplasm.
  • Usually appear cohesive.
  • May be subcapsular in a lymph node and mimic a carcinoma.
  • Hallmark cells = "horseshoe-shaped or donut-shaped nucleus + eosinophilic paranuclear region"[19][20] - key feature.
    • The donut-shaped version is also known as a "wreath cell"[21] - large (multi-nucleated) cells with (morphologically) one toroidal-shaped nucleus.

DDx:

Images:

IHC

Features:

  • CD30 +ve.
  • ALK-1 -ve/+ve; strongly supports ALCL Dx if +ve.
  • CD45 +ve.
  • CD4 +ve.
  • CD3 -ve/+ve.
  • CD7 -ve/+ve.
  • EMA +ve.

Molecular

  • t(2,5)(p23;q35)[22] - can be detected with FISH break apart probe.

Cutaneous T cell lymphoma

See Dermatologic neoplasms.

General

  • Abbreviated as CTCL.
    • Sézary syndrome is a subset of CTCL.

Microscopic

Features:[23]

  • Cerebriform nucleus (Sézary cell):[24]
    • Hyperchromatic.
    • "Convoluted" = twisted, coiled.[25]

Images:

Lymphoplasmacytic lymphoma

  • May be referred to as Waldenström macroglobulinemia, a hyperviscosity syndrome, that arises from it.

General

Features:[26]

  • B cell neoplasm.
  • Secretes monoclonal IgM.

Clinical:[26]

  • Symptoms of blood hyperviscosity (visual impairment, neurologic impairment, bleeding, cryoglobulinemia).
  • Hemolysis.

Microscopic

Features:[26]

Adult T-cell leukemia/lymphoma

General

  • Etiology: Human T-cell Lymphoma Virus 1 (HTLV-1).[27]
  • Poor prognosis ~ 1 year survival with treatment.

Microscopic

Features:[28]

  • Cloverleaf nuclei; nuclei with multiple lobulations.

Table of lymphoma

B cell lymphomas

Name Size of cells Site Histomorphology IHC Translocations Clinical Prevalence DDx
Follicular lymphoma small (centrocytes) lymph node, germinal center abundant atypical follicles (lack GC polarity, lack polar mantle zone), effaced sinuses, scattered large cells (centroblasts) CD10+, bcl-6+[29] t(14,18) usually indolent, may transform to DLBCL very common DLBCL, other small cell lymphomas
Mantle cell lymphoma small, monomorphic lymph node, mantle zone monomorphic lymphoid, abundant mitoses. +/-scattered epithelioid histiocytes, sclerosed blood vessels CD5+, CD23-, CD43+, cyclin D1+[29] t(11;14)(q13;q32)[30] indolent ??? uncommon other small cell lymphomas, PTGC, Castleman disease, Burkitt's lymphoma
Extranodal marginal zone lymphoma (MALT lymphoma) small mucosa-associated lymphoid tissue, GI tract + elsewhere +/- lymphepithelial lesion (cluster of 3+ cells in epithelium) CD21+, CD11c+, CD5-, CD23-[29] ??? indolent ??? common other small cell lymphomas, neuroendocrine tumours
Precursor B-cell lymphoblastic lymphoma/ leukemia small lymph node ???, bone marrow nuclei slightly large than resting lymphocytes, scant basophilic cytoplasm, irregular nuclear membrane, no nucleoli, stippled chromatin[31] CD10+, CD5-, TdT+, CD99+[29] +/-t(12;21)[32] aggressive ??? uncommon small cell lymphomas
Hairy cell leukemia small bone marrow, peripheral blood perinuclear clearing, clear cytoplasm, central nucleus CD25+, CD103+, CD5-[33] translocations ? splenomegaly, no lymphadenopathy, pancytopenia, good prognosis with Tx uncommon small cell leukemias/lymphomas (e.g. SMZL)
Burkitt's lymphoma medium, monomorphic lymph node, germinal center (???) tingible-body macrophages ("starry sky" appearance), round nucleus, small nucleoli, mitoses +++ CD10+, BCL6+, BCL2- t(8;14) (q24;q32) rapid growth, may be associated with EBV, HIV/AIDS uncommon DLBCL, mantle cell lymphoma
Diffuse large B cell lymphoma large cells (>2x RBC, often larger), variable size lymph node usually, germinal center sheets of large discohesive cells; if only nodular = follicular lymphoma MIB-1 >40% none / like follicular lymphoma t(14,18) / c-MYC (like Burkitt lymphoma) poor prognosis very common Burkitt lymphoma, ALCL, Hodgkin lymphoma
Primary mediastinal B-cell lymphoma large (>2x RBC, often larger), variable size mediastinum histomorphology ? IHC ? translocations ? predominantly young adults, better prognosis than DLBCL uncommon DLBCL
B cell small lymphocytic lymphoma /
chronic lymphocytic leukemia 		small lymph node (???) proliferation centres CD5+, CD23+, CD43+, cyclin D1- trisomy 12; deletions of 11q, 13q, 17p[34] good prognosis / indolent course common other small cell lymphomas

T cell lymphomas

Name Size of cells Site Histomorphology IHC Translocations Clinical Prevalence DDx
Angioimmunoblastic lymphoma size of cells ? site ? histomorphology ? IHC ? translocations ? clinical ? prevalence ? DDx ?
Enteropathy-type T cell lymphoma size of cells ? site ? histomorphology ? IHC ? translocations ? clinical ? prevalence ? DDx ?
Precursor lymphoblastic lymphoma / leukemia size of cells ? site ? histomorphology ? IHC ? translocations ? clinical ? prevalence ? DDx ?
Adult T-cell lymphoma / leukemia size of cells ? site ? cloverleaf nuclei (multilobular nuclei) IHC ? translocations ? poor prognosis ~ 1 year survival w/ Tx; d/t HTLV-1 prevalence ? DDx ?
Peripheral T cell lymphoma (NOS) size of cells ? site ? histomorphology ? TIA-1+ translocations ? clinical ? prevalence ? DDx ?
Anaplastic large cell lymphoma large deep & subcapsular sinuses of LN eosinophilic cytoplasm, nucleoli, often cohesive, wreath cell (C-shaped nucleus) CD30+/-, Alk+/-, CD4+, CD3- t(2,5)(p23;q35)[22] clinical ? uncommon carcinoma
Extranodal NK / T cell lymphoma nasal type size of cells ? site ? histomorphology ? EBER+, CD16+, CD56+, CD57-, TIA-1+, Granzyme B+ translocations ? clinical ? prevalence ? DDx ?
Blastic NK cell lymphoma size of cells ? site ? histomorphology ? IHC ? translocations ? clinical ? prevalence ? DDx ?

See also

References

  1. ↑ 1.0 1.1 Alanen A, Pira U, Lassila O, Roth J, Franklin RM (March 1985). "Mott cells are plasma cells defective in immunoglobulin secretion". Eur. J. Immunol. 15 (3): 235–42. PMID 3979421.
  2. ↑ URL: http://www.ncbi.nlm.nih.gov/omim/601284. Accessed on: 31 August 2010.
  3. ↑ Pittaluga S, Wlodarska I, Pulford K, et al. (August 1997). "The monoclonal antibody ALK1 identifies a distinct morphological subtype of anaplastic large cell lymphoma associated with 2p23/ALK rearrangements". Am. J. Pathol. 151 (2): 343–51. PMC 1858018. PMID 9250148. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1858018/.
  4. ↑ URL: http://www.ncbi.nlm.nih.gov/omim/603518. Accessed on: 18 August 2010.
  5. ↑ URL: http://www.ncbi.nlm.nih.gov/omim/167414. Accessed on: 18 August 2010.
  6. ↑ URL: http://www.ncbi.nlm.nih.gov/omim/116930. Accessed on: 31 August 2010.
  7. ↑ URL: http://www.nature.com/bmt/journal/v33/n1/full/1704298a.html. Accessed on: 31 August 2010.
  8. ↑ Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 567. ISBN 978-0781765275.
  9. ↑ 9.0 9.1 Sissolak G, Sissolak D, Jacobs P (April 2010). "Human immunodeficiency and Hodgkin lymphoma". Transfus. Apher. Sci. 42 (2): 131–9. doi:10.1016/j.transci.2010.01.008. PMID 20138008.
  10. ↑ Küppers R, Rajewsky K, Braeuninger A, Hansmann ML (March 1998). "L&H cells in lymphocyte-predominant Hodgkin's disease". N. Engl. J. Med. 338 (11): 763–4; author reply 764–5. doi:10.1056/NEJM199803123381113. PMID 9499174.
  11. ↑ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 676 (???). ISBN 0-7216-0187-1.
  12. ↑ Wang L, Li C, Gao T (March 2010). "Cutaneous intravascular anaplastic large cell lymphoma". J Cutan Pathol. doi:10.1111/j.1600-0560.2010.01538.x. PMID 20337769.
  13. ↑ 13.0 13.1 13.2 Lapkuviene O, Forchetti D, Roepke JE (October 2001). "Unusual sites of involvement by hematologic malignancies. Case 1. Intravascular large B-cell lymphoma presenting with CNS symptoms". J. Clin. Oncol. 19 (19): 3988–91. PMID 11579120. http://jco.ascopubs.org/content/19/19/3988.full.
  14. ↑ Bellan C, Lazzi S, De Falco G, Nyongo A, Giordano A, Leoncini L (March 2003). "Burkitt's lymphoma: new insights into molecular pathogenesis". J. Clin. Pathol. 56 (3): 188–92. PMC 1769902. PMID 12610094. http://jcp.bmj.com/cgi/pmidlookup?view=long&pmid=12610094.
  15. ↑ AML. Harrison's 16th Ed.
  16. ↑ AG. 8 July, 2009.
  17. ↑ Johnson, PW.; Davies, AJ. (2008). "Primary mediastinal B-cell lymphoma.". Hematology Am Soc Hematol Educ Program: 349-58. doi:10.1182/asheducation-2008.1.349. PMID 19074109.
  18. ↑ Coso, D.; Rey, J.; Bouabdallah, R. (Feb 2010). "[Primary mediastinal B-cell lymphoma]". Rev Pneumol Clin 66 (1): 32-5. doi:10.1016/j.pneumo.2009.12.007. PMID 20207294.
  19. ↑ Rapkiewicz, A.; Wen, H.; Sen, F.; Das, K. (Dec 2007). "Cytomorphologic examination of anaplastic large cell lymphoma by fine-needle aspiration cytology.". Cancer 111 (6): 499-507. doi:10.1002/cncr.23120. PMID 17941004. http://onlinelibrary.wiley.com/doi/10.1002/cncr.23120/full.
  20. ↑ Ponzoni, M.; Terreni, MR.; Ciceri, F.; Ferreri, AJ.; Gerevini, S.; Anzalone, N.; Valle, M.; Pizzolito, S. et al. (Nov 2002). "Primary brain CD30+ ALK1+ anaplastic large cell lymphoma ('ALKoma'): the first case with a combination of 'not common' variants.". Ann Oncol 13 (11): 1827-32. PMID 12419758.
  21. ↑ Amin, HM.; Lai, R. (Oct 2007). "Pathobiology of ALK+ anaplastic large-cell lymphoma.". Blood 110 (7): 2259-67. doi:10.1182/blood-2007-04-060715. PMID 17519389. http://bloodjournal.hematologylibrary.org/content/110/7/2259.full.html.
  22. ↑ 22.0 22.1 Lamant L, Meggetto F, al Saati T, et al. (January 1996). "High incidence of the t(2;5)(p23;q35) translocation in anaplastic large cell lymphoma and its lack of detection in Hodgkin's disease. Comparison of cytogenetic analysis, reverse transcriptase-polymerase chain reaction, and P-80 immunostaining". Blood 87 (1): 284–91. PMID 8547653.
  23. ↑ URL: http://emedicine.medscape.com/article/209091-overview. Accessed on: 19 August 2010.
  24. ↑ URL: http://emedicine.medscape.com/article/204529-diagnosis. Accessed on: 19 August 2010.
  25. ↑ URL: http://dictionary.reference.com/browse/convoluted. Accessed on: 19 August 2010.
  26. ↑ 26.0 26.1 26.2 Mitchell, Richard; Kumar, Vinay; Fausto, Nelson; Abbas, Abul K.; Aster, Jon (2011). Pocket Companion to Robbins & Cotran Pathologic Basis of Disease (8th ed.). Elsevier Saunders. pp. 325. ISBN 978-1416054542.
  27. ↑ Mitchell, Richard; Kumar, Vinay; Fausto, Nelson; Abbas, Abul K.; Aster, Jon (2011). Pocket Companion to Robbins & Cotran Pathologic Basis of Disease (8th ed.). Elsevier Saunders. pp. 327. ISBN 978-1416054542.
  28. ↑ Mitchell, Richard; Kumar, Vinay; Fausto, Nelson; Abbas, Abul K.; Aster, Jon (2011). Pocket Companion to Robbins & Cotran Pathologic Basis of Disease (8th ed.). Elsevier Saunders. pp. 328. ISBN 978-1416054542.
  29. ↑ 29.0 29.1 29.2 29.3 Lester, Susan Carole (2005). Manual of Surgical Pathology (2nd ed.). Saunders. pp. 95. ISBN 978-0443066450.
  30. ↑ URL: http://atlasgeneticsoncology.org/Anomalies/t1114ID2021.html. Accessed on: 10 August 2010.
  31. ↑ Mitchell, Richard; Kumar, Vinay; Fausto, Nelson; Abbas, Abul K.; Aster, Jon (2011). Pocket Companion to Robbins & Cotran Pathologic Basis of Disease (8th ed.). Elsevier Saunders. pp. 315. ISBN 978-1416054542.
  32. ↑ Mitchell, Richard; Kumar, Vinay; Fausto, Nelson; Abbas, Abul K.; Aster, Jon (2011). Pocket Companion to Robbins & Cotran Pathologic Basis of Disease (8th ed.). Elsevier Saunders. pp. 317. ISBN 978-1416054542.
  33. ↑ URL: http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=cmed&part=A34022&rendertype=table&id=A34029. Accessed on: 20 August 2010.
  34. ↑ Mitchell, Richard; Kumar, Vinay; Fausto, Nelson; Abbas, Abul K.; Aster, Jon (2011). Pocket Companion to Robbins & Cotran Pathologic Basis of Disease (8th ed.). Elsevier Saunders. pp. 318. ISBN 978-1416054542.
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