Lymphoma

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

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).

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

  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).

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.
  • 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 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:[2]

  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.[3]
  3. Lymphocyte-rich CHL - rare.
    • T lymphocytes only (no mix of cells).
  4. Lymphocyte-depleted CHL - rare.
    • May be associated with HIV infection.[3]

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)[4]) - 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):

Follicular lymphoma

Main article: Small cell lymphomas

Diffuse large B-cell lymphoma

Main article: Diffuse large B cell lymphoma

General

  • Abbreviated DLBCL.

Microscopic

Features:[5]

  • 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 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:[6]
    • 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).

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:

Images:

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.[8]
  • 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

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:

Name Location Size of cells IHC Translocations Clinical Other
Follicular lymphoma Follicle Small, centrocytes, centroblasts CD10+, bcl-6+[10] t(14,18) Clinical ? Other ?
Mantle cell lymphoma Mantle zone Small CD5+, CD23-, CD43+, cyclin D1+[10] t(11;14)(q13;q32)[11] Clinical ? Other ?
Marginal zone lymphoma (MALT) Marginal zone Small CD21+, CD11c+, CD5-, CD23-[10] Translocations Clinical Other
Precursor lymphoblastic lymphoma/leukemia Location ? Small CD10+, CD5-, TdT+, CD99+[10] Translocations ? Clinical ? Other ?

Medium and large cell lymphomas:

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

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. ↑ 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.
  3. ↑ 3.0 3.1 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.
  4. ↑ 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.
  5. ↑ 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.
  6. ↑ 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.
  7. ↑ URL: http://www.thefreelibrary.com/Dutcher+bodies+in+chronic+synovitis-a083551789. Accessed on: 4 August 2010.
  8. ↑ AML. Harrison's 16th Ed.
  9. ↑ AG. 8 July, 2009.
  10. ↑ 10.0 10.1 10.2 10.3 Lester, Susan Carole (2005). Manual of Surgical Pathology (2nd ed.). Saunders. pp. 95. ISBN 978-0443066450.
  11. ↑ URL: http://atlasgeneticsoncology.org/Anomalies/t1114ID2021.html. Accessed on: 10 August 2010.
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