Small cell lymphomas

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The 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 (includes MALT 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)(q32;q21) IGH/BCL2[3] may transform into DLBCL very common
Mantle cell lymphoma mantle zone small CD5+, CD23-, CD43+, cyclin D1+[2] t(11;14)(q13;q32) BCL1/IGH[4] (also IGH/BCL1[5]) aggressive, poor prognosis[6] DDx: Castleman disease
Marginal zone lymphoma (includes MALT) marginal zone, spleen, GI tract small CD21+, CD11c+, CD5-, CD23-[2] t(11;18)(q21;q21) / API2‐MALT1, t(14;18)(q32;q21) / IGH‐MALT1, t(1;14)(p22;q32) / IGH‐BCL10[7] classical GI lymphoma subtypes: extranodal marginal zone lymphoma (AKA MALT lymphoma), SMZL, nodal marginal zone lymphoma
Precursor B cell lymphoblastic lymphoma/leukemia location ? small CD10+, CD5-, TdT+, CD99+[2] t(9;22), others good prognosis (?) other ?
B cell small lymphocytic lymphoma /
chronic lymphocytic leukemia 		location ? Small CD5+, CD23+, CD43+, cyclin D1- trisomy 12; deletions of 11q, 13q, 17p[8] good prognosis / indolent course 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,[9] like many other small cell lymphomas.

Microscopic

Features (lymph node):

  • Abundant abnormally-shaped 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).

Note:

  • The intrafollicular component of the lymph node is compressed - follicles are often described as "kissing", as they nearly touch.
  • In bone marrow specimens the neoplastic cells classically have a paratrabecular arrangement,[10] i.e. the lymphoma cells are found adjacent to the bone spicules.

Image:

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.[11]
  • 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:[12]

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

IHC

Features:[9]

  • 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.[9]
    • Should not be confused with t(14;18)(q32;q21)/IGH-MALT1 seen in MALT lymphomas.[7]

Mantle cell lymphoma

  • Abbreviated MCL.

General

  • Relatively aggressive - guarded prognosis.[6]

Microscopic

Features:[13]

  • 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:

Images:

IHC

  • CD5 +ve.
    • Negative in case reports.[14]
  • CD43 +ve.
  • Cyclin D1 +ve.

Others:

  • CD23 -ve.
    • Positive in CLL.

Molecular

  • t(11;14)(q13;q32) / IGH-CCND1.[16]

Marginal zone lymphoma

General

Classification

  • Comes in three different flavours:
    1. Extranodal marginal zone lymphoma.
      • If in mucosa-associated lymphoid tissue known as a MALT lymphoma, AKA MALToma.
    2. Splenic marginal zone lymphoma (SMZL).
    3. Nodal marginal zone lymphoma (NMZL).

Microscopic

Features:

  • "Lymphoepithelial lesion" - gastric crypts invaded by a monomorphous population of lymphocytes.[18]
    • 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.[19]

Images:

IHC

Features:[20]

  • 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.

Molecular

There are several associated with MALT lymphoma:[7]

  • t(11;18)(q21;q21) / API2‐MALT1[21] - most common translocation in MALT lymphoma.[22]
  • t(14;18)(q32;q21) / IGH‐MALT1.
  • t(1;14)(p22;q32) / IGH‐BCL10.

The MALT1 associated translocations can be assessed with an ISH break apart probe for MALT1.

Hairy cell leukemia

  • Abbreviated HCL.

General

  • Name comes from appearance on blood smear - cell hairy.

Clinical:[23]

  • Pancytopenia.
  • Splenic enlargement.
  • No lymphadenopathy.
  • Good prognosis (with treatment), though (likely) not curable.

Gross

Features:[17]

  • Huge beefy red spleen.
    • Red as white pulp obliterated.

Microscopic

Features:[24]

  • Small cells (10-20 micrometers) with "Fried egg"-like appearance:
    • Well-demarcated fuzzy cell borders,
    • Clear/whispy cytoplasm and,
    • Central round nucleus.
      • Peri-nuclear clearing ("water-clear rim"[25]) -- key feature.

DDx:

Images:

IHC

Features:[26]

  • CD20 +ve, CD25 +ve, CD103 +ve.
  • CD5 -ve.

Flow cytometry:

  • CD19 +ve, CD11c +ve, FMC7 +ve.

B cell small lymphocytic lymphoma/chronic lymphocytic leukemia

  • Abbreviated CLL and SLL.

General

  • 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:[27]
    • Incidence of transformation <5%.
    • Prognosis < 1 year.

Microscopic

Features in a lymph node:[28]

  • 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:

IHC

  • CD20 +ve.
  • CD5 +ve.
  • CD23 +ve -- occasionally negative.[29]
  • CD43 +ve.

Others:

  • Cyclin D1 -ve.

Molecular

Precursor B-cell lymphoblastic lymphoma/leukemia

General

  • Good prognosis.
  • Paediatric - usu. <6 years old.

Microscopic

Features:[30]

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

IHC

Features:[2]

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

Molecular

Subclassification based on molecular abnormalities (translocations, rearrangements):[31]

  • t(9;22) / BCR-ABL.
  • t(1;19) / E2A-PBX1.
  • t(12;21) / ETV-CBFalpha.
  • MLL rearrangement.

Precursor T-cell lymphoblastic lymphoma/leukemia

General

  • Prognosis poor. (???)

Microscopic

Features:

  • Small lymphoid cells. (???)

IHC

Features:[32]

  • 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. ↑ Yanai, S.; Nakamura, S.; Takeshita, M.; Fujita, K.; Hirahashi, M.; Kawasaki, K.; Kurahara, K.; Sakai, Y. et al. (Dec 2010). "Translocation t(14;18)/IGH-BCL2 in gastrointestinal follicular lymphoma: correlation with clinicopathologic features in 48 patients.". Cancer. doi:10.1002/cncr.25811. PMID 21192062.
  4. ↑ URL: http://atlasgeneticsoncology.org/Anomalies/t1114ID2021.html. Accessed on: 10 August 2010.
  5. ↑ URL: http://www.wipo.int/patentscope/search/en/WO2010059499. Accessed on: 26 May 2011.
  6. ↑ 6.0 6.1 Hankin, RC.; Hunter, SV. (Dec 1999). "Mantle cell lymphoma.". Arch Pathol Lab Med 123 (12): 1182-8. doi:10.1043/0003-9985(1999)1231182:MCL2.0.CO;2. PMID 10583923.
  7. ↑ 7.0 7.1 7.2 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. ↑ 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.
  9. ↑ 9.0 9.1 9.2 9.3 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.
  10. ↑ Iancu, D.; Hao, S.; Lin, P.; Anderson, SK.; Jorgensen, JL.; McLaughlin, P.; Medeiros, LJ. (Feb 2007). "Follicular lymphoma in staging bone marrow specimens: correlation of histologic findings with the results of flow cytometry immunophenotypic analysis.". Arch Pathol Lab Med 131 (2): 282-7. doi:10.1043/1543-2165(2007)131[282:FLISBM]2.0.CO;2. PMID 17284114.
  11. ↑ DG. 17 August 2010.
  12. ↑ 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.
  13. ↑ DG. 17 August 2010.
  14. ↑ URL: http://path.upmc.edu/cases/case308/dx.html. Accessed on: 14 January 2012.
  15. ↑ Online 'Mendelian Inheritance in Man' (OMIM) 168461
  16. ↑ URL: http://atlasgeneticsoncology.org/Anomalies/t1114ID2021.html. Accessed on: 10 August 2010.
  17. ↑ 17.0 17.1 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. 326. ISBN 978-1416054542.
  18. ↑ 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.
  19. ↑ DB. 6 August 2010.
  20. ↑ Lester, Susan Carole (2005). Manual of Surgical Pathology (2nd ed.). Saunders. pp. 95. ISBN 978-0443066450.
  21. ↑ 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. 170. ISBN 978-1416054542.
  22. ↑ Streubel, B.; Lamprecht, A.; Dierlamm, J.; Cerroni, L.; Stolte, M.; Ott, G.; Raderer, M.; Chott, A. (Mar 2003). "T(14;18)(q32;q21) involving IGH and MALT1 is a frequent chromosomal aberration in MALT lymphoma.". Blood 101 (6): 2335-9. doi:10.1182/blood-2002-09-2963. PMID 12406890.
  23. ↑ URL: http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=cmed&part=A34022. Accessed on: 20 August 2010.
  24. ↑ URL: http://emedicine.medscape.com/article/200580-diagnosis. Accessed on: 18 August 2010.
  25. ↑ URL: http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=cmed&part=A34022. Accessed on: 20 August 2010.
  26. ↑ URL: http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=cmed&part=A34022&rendertype=table&id=A34029. Accessed on: 20 August 2010.
  27. ↑ 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.
  28. ↑ DG. 17 August 2010.
  29. ↑ URL: http://path.upmc.edu/cases/case296/dx.html. Accessed on: 14 January 2012.
  30. ↑ DG. 17 August 2010.
  31. ↑ Randolph TR (2004). "Advances in acute lymphoblastic leukemia". Clin Lab Sci 17 (4): 235–45. PMID 15559730. http://findarticles.com/p/articles/mi_qa3890/is_200410/ai_n9429273/pg_2.
  32. ↑ Lester, Susan Carole (2005). Manual of Surgical Pathology (2nd ed.). Saunders. pp. 97. ISBN 978-0443066450.
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