Small cell lymphomas

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Small cell lymphomas are a collection of commonly seen lymphomas that have a near-identical histomorphologic appearance.

The group includes:

  1. Small lymphocytic lymphoma/chronic lymphocytic leukemia.
  2. Follicular lymphoma.
  3. Mantle cell lymphoma.
  4. Marginal zone lymphoma.
  5. Hairy cell leukemia.
  6. Immunoproliferative small intestinal disease (IPSID).[1]

Table of B-cell lymphoma

Small cell lymphomas:

Name Location Size of cells IHC Translocations Clinical Other
Follicular lymphoma Follicle Small, centrocytes, centroblasts CD10+, BCL6+[2] t(14,18) Clinical ? Other ?
Mantle cell lymphoma Mantle zone Small CD5+, CD23-, CD43+, cyclin D1+[2] t(11;14)(q13;q32)[3] Clinical ? Other ?
Marginal zone lymphoma (MALT) Marginal zone Small CD21+, CD11c+, CD5-, CD23-[2] Translocations Clinical Other
Precursor B cell lymphoblastic lymphoma/leukemia Location ? Small CD10+, CD5-, TdT+, CD99+[2] Translocations ? Clinical ? Other ?
B cell small lymphocytic lymphoma /
chronic lymphocytic leukemia 		Location ? Small CD5+, CD23+, CD43+, cyclin D1- Translocations ? Good prognosis Other ?

Medium and large cell lymphomas:

Name Location Size of cells IHC Translocations Clinical Other
Burkitt's lymphoma Follicle Large cells CD10, BCL6 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

Follicular lymphoma

General

  • A very common type of lymphoma.
  • Expresses BCL2,[4] like many other small cell lymphomas.

Microscopic

Features:

  • Abundant abnormal lymphoid follicles - key feature - including some of the following:
    • Non-polarized mantle zone (normal mantle zone is usu. thicker at capsular aspect).
    • Non-polarized germinal center (normal germinal center has dark & light area).
    • Loss of tingible body macrophages.
    • Sinuses effaced (lost).

Grading

  • Grade 1-2: <= 22 centroblasts / HPF; where 1 HPF ~= 0.2376 mm^2 (22 mm eye piece @ 40X objective).
  • Grade 3A: >22 centroblasts / HPF; where 1 HPF ~= 0.2376 mm^2 (22 mm eye piece @ 40X objective).
  • Grade 3B: only centroblasts (within a nodular architecture).

Notes:

  • Significant interobserver variability.[5]
  • Grade 1 & Grade 2 lumped together.
  • One should evaluate 10 HPFs.
  • Only centroblasts without a nodular architecture is Diffuse large B cell lymphoma (DLBCL).

The usual cut points mentioned by people with HPFitis are:[6]

  • Grade 1: 0-5 centroblasts / HPF.
  • Grade 2: 5-15 centroblasts / HPF.
  • Grade 3: >15 centroblasts / HPF.

IHC

Features:[4]

  • CD10 +ve.
  • BCL6 +ve.

Others:

  • 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

  • t(14;18)(q32;q21)/IGH-BCL2 in 70-95% of cases.[4]
    • Should not be confused with t(14;18)(q32;q21)/IGH-MALT1 seen in MALT lymphomas.[7]

Mantle cell lymphoma

General

  • Comes in different flavours.

Microscopic

Features:[8]

  • Small monomorphic (uniform size, shape and staining) lymphoid population.
  • Abundant mitoses.
  • Scattered epithelioid histiocytes (should not be confused with tingible-body macrophages).
  • Sclerosed blood vessels.

DDx:

  • Other small cell lymphomas, esp. marginal zone lymphoma.
  • Burkitt's lymphoma.

IHC

  • CD5 +ve.
  • CD43 +ve.
  • Cyclin D1 +ve.

Others:

  • CD23 -ve.
    • Positive in CLL.

Molecular

  • t(11;14)(q13;q32).[9]

Marginal zone lymphoma

General

  • Abbreviated as MZL.

Classification

  • Comes in three different flavours:
    • Extranodal marginal zone lymphoma (AKA MALT lymphoma = mucosa-associated lymphoid tissue lymphoma).
    • Splenic marginal zone lymphoma.
    • Nodal marginal zone lymphoma (NMZL).

Microscopic

Features:

  • "Lymphoepithelial lesion" - gastric crypts invaded by a monomorphous population of lymphocytes.[10]
    • Features:
      1. Cluster of lymphocytes - three cells or more - key feature.
        • Single lymphocytes don't count.
      2. Clearing around the lymphocyte cluster.
    • Not specific for MALT lymphoma, i.e. may be seen in other types of lymphoma.[11]

Images:

IHC

Features:[12]

  • CD20 +ve.
  • BCL2 +ve.
  • CD21 +ve.
  • CD11c +ve (flow cytometry or laser scanning cytometry - only; not available for paraffin).
  • CD43 +ve/-ve.

Others:

  • CD5 -ve.
  • CD10 -ve.
  • CD23 -ve.

Hairy cell leukemia

General

  • Name comes from appearance on blood smear - cell hairy.
  • Often associated with splenic enlargement.

Microscopic

Features:[13]

  • Small cells with:
    • Clear cytoplasm and,
    • Central round nucleus.
      • "Fried egg"-like appearance -- key feature.

Images:

B cell small lymphocytic lymphoma/chronic lymphocytic leukemia

General

  • Abbreviated CLL and SLL.
  • Very common.
  • Good prognosis.

Richter's transformation

  • CLL/SLL may under go a Richter's transformation into a high-grade non-Hodgkin's lymphoma (NHL), e.g. DLBCL:[14]
    • Incidence of transformation <5%.
    • Prognosis < 1 year.

Microscopic

Features in a lymph node:[15]

  • Mixed population of lymphoid cells with "proliferation centers" - key feature:
    1. Larger cells (~ 1.5x the size of resting lymphocyte ~ 12-15 micrometers):
      • Nucleoli.
      • Form (nodular) collections.
    2. Small dark cells (~ size of resting lymphocyte ~ 8-10 micrometers):
      • Predominant population.
      • Lack nucleolus.

Images:

Precursor B-cell lymphoblastic lymphoma/leukemia

General

  • Prognosis poor. (???)

Microscopic

Features:[16]

  • High mitotic rate.
  • "Starry sky" pattern.
  • Small nucleoli.

IHC

Features:[2]

  • CD10 +ve, TdT +ve, CD99 +ve.
  • CD5 -ve.

Precursor T-cell lymphoblastic lymphoma/leukemia

General

  • Prognosis poor. (???)

Microscopic

Features:

  • Small lymphoid cells. (???)

IHC

Features:[17]

  • TdT +ve, CD34 +ve, CD99 +ve, CD1a +ve/-ve.
  • TIA1 -ve.

See also

References

  1. ↑ Al-Saleem T, Al-Mondhiry H (March 2005). "Immunoproliferative small intestinal disease (IPSID): a model for mature B-cell neoplasms". Blood 105 (6): 2274–80. doi:10.1182/blood-2004-07-2755. PMID 15542584. http://bloodjournal.hematologylibrary.org/cgi/content/long/105/6/2274.>
  2. ↑ 2.0 2.1 2.2 2.3 2.4 Lester, Susan Carole (2005). Manual of Surgical Pathology (2nd ed.). Saunders. pp. 95. ISBN 978-0443066450.
  3. ↑ URL: http://atlasgeneticsoncology.org/Anomalies/t1114ID2021.html. Accessed on: 10 August 2010.
  4. ↑ 4.0 4.1 4.2 Vitolo U, Ferreri AJ, Montoto S (June 2008). "Follicular lymphomas". Crit. Rev. Oncol. Hematol. 66 (3): 248–61. doi:10.1016/j.critrevonc.2008.01.014. PMID 18359244.
  5. ↑ DG. 17 August 2010.
  6. ↑ Mills, Stacey E; Carter, Darryl; Greenson, Joel K; Oberman, Harold A; Reuter, Victor E (2004). Sternberg's Diagnostic Surgical Pathology (4th ed.). Lippincott Williams & Wilkins. pp. 813. ISBN 978-0781740517.
  7. ↑ Bacon CM, Du MQ, Dogan A (April 2007). "Mucosa-associated lymphoid tissue (MALT) lymphoma: a practical guide for pathologists". J. Clin. Pathol. 60 (4): 361–72. doi:10.1136/jcp.2005.031146. PMC 2001121. PMID 16950858. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2001121/.
  8. ↑ DG. 17 August 2010.
  9. ↑ URL: http://atlasgeneticsoncology.org/Anomalies/t1114ID2021.html. Accessed on: 10 August 2010.
  10. ↑ Papadaki, L.; Wotherspoon, AC.; Isaacson, PG. (Nov 1992). "The lymphoepithelial lesion of gastric low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT): an ultrastructural study.". Histopathology 21 (5): 415-21. PMID 1452124.
  11. ↑ DB. 6 August 2010.
  12. ↑ Lester, Susan Carole (2005). Manual of Surgical Pathology (2nd ed.). Saunders. pp. 95. ISBN 978-0443066450.
  13. ↑ URL: http://emedicine.medscape.com/article/200580-diagnosis. Accessed on: 18 August 2010.
  14. ↑ Tsimberidou AM, Keating MJ (April 2006). "Richter's transformation in chronic lymphocytic leukemia". Semin. Oncol. 33 (2): 250–6. doi:10.1053/j.seminoncol.2006.01.016. PMID 16616072.
  15. ↑ DG. 17 August 2010.
  16. ↑ DG. 17 August 2010.
  17. ↑ Lester, Susan Carole (2005). Manual of Surgical Pathology (2nd ed.). Saunders. pp. 97. ISBN 978-0443066450.
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