classical Hodgkin lymphoma

Digital cases

 HPC:188 (HPC:188) : classical Hodgkin lymphoma
 HPC:234 : classical Hodgkin lymphoma
 HPC:292 : classical Hodgkin lymphoma, mixed cellularity type
 HPC:337 : classical Hodgkin lymphoma, mixed cellularity type
 HPC:351 : classical Hodgkin lymphoma, scleronodular type
 JRC:7378 : classical Hodgkin lymphoma, in bone marrow.
 JRC:7415 : classical Hodgkin lymphoma.
 JRC:7424 : classical Hodgkin lymphoma (nodular sclerosing).

Subtypes

 nodular sclerosing Hodgkin lymphoma
 mixed cellularity Hodgkin lymphoma
 lymphocyte rich classical Hodgkin lymphoma
 lymphocytic depleted Hodgkin lymphoma (lymphocyte depletion)

• diffuse fibrose variant
• reticular variant

Microscopical synopsis

 heterogenous population
 Sternberg cells
 Hodgkin cells

Variants

 interfollicular Hodgkin lymphoma (6859389)

Associations

 mantle cell lymphoma (14576485, 14657719)

Differential diagnosis

 nodular lymphocyte predominant Hodgkin lymphoma
 reactive lymphadenitis (3366442)

Cytogenetics

 t(l4;18)
 t(2;5)
 del(lp)
 dup(lq)
 del(6q)
 del(7q)
 Chr.4 rearrangments

• 4q25-28 rearrangements

CGH

 Copy number alterations are found in more than 20% of cases included gains of 2p, 9p, 12p, 16p, 17p, 17q, 19p, 19q, 20q, 21q and losses of 1p, 6q, 7q, 8p, 11q, and 13q. (20339089)

 high-resolution recurrent changes defining minimally gained and lost regions harboring genes involved in NFkappaB signaling such as REL, IKBKB, CD40, and MAP3K14. (20339089)

 Gains of chromosome 16p11.2-13.3 are significantly more frequent in pretreatment and relapse biopsies of patients failing treatment and were associated with shortened disease-specific survival (p=0.028). (20339089)

 In the therapy-resistant HL cell line KMH2, genomic gains and overexpression of the multidrug resistance gene ABCC1 mapping to cytoband 16p13.11. (20339089)

 doxorubicin exposure to KMH2 induces ABCC1 expression and that siRNA silencing of ABCC1 sensitizes KMH2 cells to doxorubicin toxicity in-vitro, suggesting that overexpression of ABCC1 contributes to the drug resistance phenotype found in KMH2. (20339089)

Susceptibility loci

 2p16.1 (REL) (21037568)
 8q24.21 (21037568)
 10p14 (GATA3) (21037568)

See also

 Hodgkin lymphomas

• nodular lymphocyte predominant Hodgkin lymphoma

References

 A genome-wide association study of Hodgkin’s lymphoma identifies new susceptibility loci at 2p16.1 (REL), 8q24.21 and 10p14 (GATA3). Enciso-Mora V, Broderick P, Ma Y, Jarrett RF, Hjalgrim H, Hemminki K, van den Berg A, Olver B, Lloyd A, Dobbins SE, Lightfoot T, van Leeuwen FE, Försti A, Diepstra A, Broeks A, Vijayakrishnan J, Shield L, Lake A, Montgomery D, Roman E, Engert A, von Strandmann EP, Reiners KS, Nolte IM, Smedby KE, Adami HO, Russell NS, Glimelius B, Hamilton-Dutoit S, de Bruin M, Ryder LP, Molin D, Sorensen KM, Chang ET, Taylor M, Cooke R, Hofstra R, Westers H, van Wezel T, van Eijk R, Ashworth A, Rostgaard K, Melbye M, Swerdlow AJ, Houlston RS. Nat Genet. 2010 Dec;42(12):1126-30. PMID: 21037568

 Genome-wide copy number analysis of Hodgkin Reed-Sternberg cells identifies recurrent imbalances with correlations to treatment outcome. Steidl C, Telenius A, Shah SP, Farinha P, Barclay L, Boyle M, Connors JM, Horsman DE, Gascoyne RD. Blood. 2010 Mar 25. PMID: 20339089

 Hammerschmidt W, Sugden B. Epstein-Barr virus sustains Burkitt’s lymphomas and Hodgkin’s disease. Trends Mol Med. 2004 Jul;10(7):331-6. PMID: 15242681