Hodgkin lymphoma

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Hodgkin lymphoma, abbreviated HL, is a malignancy that afflicts people in the prime of their life. Fortunately, it usually has a good prognosis.

Pathologists say "... it is both the easiest and hardest diagnosis to make." The reason for this is: the diagnosis depends on finding Reed-Sternberg cells; if they are obvious the diagnosis is easy... if you can't find 'em and an alternative diagnosis is not apparent -- you wonder whether you're missing them.

Clinical

Symptoms:[1]

  • "B symptoms":[2] fever, night sweats, weight loss.
  • Infections (due to immune dysfunction).

Diagnosis:

  • HL cannot be diagnosed with standard flow cytometry (FC) - but has been diagnosed with specialized FC.[3]

Prognosis:

  • Usu. good.
  • Unlike non-Hodgkin lymphomas, it spreads in a predictable pattern; thus, staging plays an important role in determining the therapy.[4]

Hodgkin lymphoma subtypes

Types:[1]

  • Classical HL (CHL) - ~95% of HL.
  • Nodular lymphocyte-predominant HL (NLPHL) - ~5% of HL.

Classic HL

  • Four types of classic HL (see below).

NLPHL

  • AKA lympho-histiocytic variant.
  • Abbreviated NLPHL.
  • Different IHC and morphologic appearance than classic HL.
  • Significant risk for transformation into diffuse large B cell lymphoma (DLBCL); 10-year cumulative transformation rate (to DLBCL) in one study was 12%.[5]

Microscopic

By definition, HL has Reed-Sternberg cells (RSCs).

Classical HL

Features (classic HL):

  • Reed-Sternberg cell.
    • Large binucleated cell (>= 45 micrometres).[6]
      • May be multinucleated.
      • May have a horseshoe-like shape.
    • Macronucleolus - approximately the size of a RBC (~8 micrometers).
    • Well-defined cell border.
    • Abundant cytoplasm.

Notes:

  • Large mononuclear cells are common (so called "mononuclear RSCs") but not diagnostic.

Images (classic HL):

Subtypes of classic HL

There are four CHL subtypes:[1]

  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.[7]
  3. Lymphocyte-rich CHL - rare.
    • T lymphocytes only (no mix of cells).
  4. Lymphocyte-depleted CHL - rare.
    • May be associated with HIV infection.[7]

Memory device:

  • The subtypes prevalence is in reverse alphabetical order.

Nodular lymphocyte predominant Hodgkin lymphoma

Features (nodular lymphocyte-predominant Hodgkin's lymphoma):

  • Popcorn cell (previously known as Lymphocytic & histiocytic cell (L&H cell)[8]) - 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):

DDx both CHL & NLPHL

IHC

Abbreviated panel:[10]

  • CD30 Reed-Sternberg cells (RSCs) +ve ~98%
  • CD15 Reed-Sternberg cells +ve ~80%, stains neutrophils.
  • CD45 often negative in RSCs.
  • CD20 may stain RSCs.
  • PAX5 +ve.[11]

Additional - for completeness:

  • CD3 (T lymphocytes)

NLPHL IHC differs from the classical HL:[11]

  • LCA +ve.
  • CD20 +ve.
  • CD10 +ve.
  • Bcl-6 +ve.
  • EMA +ve.
  • CD30 -ve
  • CD15 -ve.

"UHN panel"

Antibody NLPHL CHL
CD45 +ve -ve
CD20 +ve -ve
BCL6
MUM1[12] -ve
CD30 -ve +ve (most sensitive).
CD15 -ve +ve
CD21 networks present no networks
CD23 networks present no networks
OCT-2 +ve -ve
PAX5 +ve +ve (proves B cell linage)
CD3 usu. < benign B cell usu. > benign B cell component
CD57 rosettes around malign. cells -
EBER -ve +ve/-ve
EMA +ve/-ve -ve
4 unstained

See also

References

  1. ↑ 1.0 1.1 1.2 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.
  2. ↑ URL: http://lymphoma.about.com/od/symptoms/f/bsymptoms.htm. Accessed on: 11 August 2010.
  3. ↑ Fromm JR, Thomas A, Wood BL (March 2009). "Flow cytometry can diagnose classical hodgkin lymphoma in lymph nodes with high sensitivity and specificity". Am. J. Clin. Pathol. 131 (3): 322–32. doi:10.1309/AJCPW3UN9DYLDSPB. PMID 19228638.
  4. ↑ 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.
  5. ↑ Biasoli I, Stamatoullas A, Meignin V, et al. (February 2010). "Nodular, lymphocyte-predominant Hodgkin lymphoma: a long-term study and analysis of transformation to diffuse large B-cell lymphoma in a cohort of 164 patients from the Adult Lymphoma Study Group". Cancer 116 (3): 631–9. doi:10.1002/cncr.24819. PMID 20029973.
  6. ↑ 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. 329. ISBN 978-1416054542.
  7. ↑ 7.0 7.1 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.
  8. ↑ 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.
  9. ↑ Gualco, G.; Natkunam, Y.; Bacchi, CE. (Jan 2012). "The spectrum of B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma: a description of 10 cases.". Mod Pathol. doi:10.1038/modpathol.2011.200. PMID 22222636.
  10. ↑ Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 568. ISBN 978-0781765275.
  11. ↑ 11.0 11.1 Lefkowitch, Jay H. (2006). Anatomic Pathology Board Review (1st ed.). Saunders. pp. 683. ISBN 978-1416025887.
  12. ↑ URL: http://www.ncbi.nlm.nih.gov/omim/601900. Accessed on: 10 August 2010.
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