Hodgkin Lymphoma

General Overview and Incidence

  • Definition of Hodgkin lymphoma (HL): lymphoid neoplasm affecting lymph nodes; paucity of neoplastic cells with rich inflammatory background

  • Classic Hodgkin lymphoma (cHL) 90% to 95% of cases

  • Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) 5% to 10% of cases ,


  • 2.5 to 3 per 100,000 per year with higher incidence in men

  • In 2014, estimated 204,065 people with HL in the United States

  • In 2017, estimated 8260 new cases of HL in the United States and 1030 estimated deaths related to HL

  • Fourth most common type of lymphoma of all non-Hodgkin lymphoma (NHL)


  • Unknown

  • Epstein-Barr virus (EBV) exposure association in up to 30% of cases

  • Bimodal distribution with peaks in young adolescents and patients older than 65 years

  • Human immunodeficiency virus (HIV)/AIDS-associated and family history

Clinical Features

The most common presentation is nontender lymphadenopathy in the neck, in the supraclavicular region, or in the axillae. Mediastinal lymphadenopathy that causes chest pain, dyspnea, or cough is also frequent in these patients and may present as an incidental finding on a chest x-ray. Up to one-third of patients with HL may present with night sweats and unexplained weight loss (defined as >10% of baseline weight). Pel-Ebstein fever, an unexplained fever that remits and relapses over weeks, is characteristic ( Box 11.1 ).

Box 11.1

Clinical Signs and Symptoms

  • Constitutional: Fever >38 ° C, drenching night sweats, weight loss

  • Brain: Paraneoplastic syndromes, cerebellar degeneration, limbic encephalitis

  • Cutaneous: Inflammatory-like erythema nodosum

  • Lymph nodes: Painless lymphadenopathy, 75% cervical region, then mediastinal, axillary, para-aortic

  • Liver: Sometimes enlarged

  • Spleen: Sometimes enlarged

  • Bone marrow: Pancytopenia, 5% to 8% involved

  • Kidneys: Nephrotic syndrome

  • Blood: Thrombocytopenia

    • Hypercalcemia

    • Immune hemolytic anemia

    • Thromboembolic events at risk

In addition to the previously mentioned symptoms, unusual presentations include severe and unexplained itching and pain at an enlarged lymph node after consumption of alcohol. Patients with HIV and AIDS have an increased frequency of HL, in whom it tends to involve extranodal sites and has an aggressive clinical course with poorer prognosis.

A total of 5% to 10% of all HL cases are NLPHL. These occur predominantly in males between 30 and 50 years. Most patients present with localized early stage (stage I–II) lymphadenopathy. Splenic and bone marrow involvement is rare. This particular type of HL is slow growing compared with cHL and has frequent relapses. This subtype can transform into diffuse large B-cell lymphoma (DLBCL) in 3% to 5% of cases.

Diagnostic Studies


The Ann Arbor staging system is currently used to stage HL in patients with newly diagnosed disease. It is imperative to accurately stage the disease as it has prognostic as well as treatment implications. Positron emission tomography–computed tomography (PET-CT) scanning is the current standard test used to identify involved lymph node groups as well as the bone marrow, although bone marrow biopsy is often performed to confirm bone marrow involvement ( Table 11.1 ; Boxes 11.2–11.5 ; Figs. 11.1 and 11.2 ).

Table 11.1

Ann Arbor Staging System for Hodgkin Lymphoma

Stage Extent of Disease
I Involvement of a single lymph node region or lymphoid structure
II Involvement of ≥2 lymph node regions on one side of the diaphragm
III Involvement of ≥2 lymph node regions on both sides of diaphragm
IV Disseminated involvement of a deep, visceral organ

Box 11.2

Subtypes of Classic Hodgkin Lymphoma

  • Nodular sclerosis

  • Mixed cellularity

  • Lymphocyte-rich

  • Lymphocyte-depleted

Box 11.3

Histopathology of Classic Hodgkin Lymphoma

  • Large binucleated or mononuclear Reed-Sternberg cells (see Fig. 11.1 )

  • Cells with abundant cytoplasm, can be basophilic

  • One or two nuclei, large prominent nucleoli with perinuclear clearing

  • Less than 10% of infiltrate

  • Background: Chasm of inflammatory cells, neutrophils, plasma cells, lymphocytes, fibrosis (see Fig. 11.2 )

Box 11.4

Workup for Suspected Classic Hodgkin Lymphoma

ALCL, anaplastic large cell lymphoma; ALK1, anaplastic lymphoma kinase 1; BCL2, B-cell lymphoma-2; BOB1, B-lymphocyte-specific co-activator BOB.1/OBF.1; cHL, classic Hodgkin lymphoma; EBV , Epstein-Barr virus; EMA , epithelial membrane antigen; IHC, immunohistochemistry; LD, lymphocyte depleted; LMP1, latent membrane protein 1; MC, mixed cellularity; MUM1, MUM1/IRF4-multiple myeloma-1/interferon regulatory factor-4; NLPHL, nodular lymphocyte-predominant Hodgkin lymphoma; OCT2, octamer binding protein-2; RS, Reed-Sternberg.

Initial Workup for Suspected cHL

  • CD30 (98%)

  • CD15 (85%)

  • PAX5 (90% weak to moderate)

  • CD20 (20% variable)

  • CD3 (<5%)

  • CD45 (<45%)

  • ALK1 (<3% to rule out ALK + ALCL)

  • EBER-1 (75% MC, LD)

Additional Workup for Suspected cHL

  • MUM1 (98%)

  • Fascin (90%)

  • BCL6 (40%)

  • LMP1 (30-40%) cHL versus pediatric/adult NHL

  • CD138 (30%)

  • OCT2, BOB1, CD79a (15% +) cHL versus NLPHL

  • EMA (<5% +)

  • Cytotoxic markers, ALK1 (<5% +) cHL versus ALCL ,

  • CD43 T-cell antigens, ALK1 (<5% positive) cHL vs ALCL ,

Prognostic Morphologic and IHC Biomarkers in cHL

  • CD68/CD163 + host cells ,

  • CD20 + RS cells

  • Eosinophilia host cells ,

  • BCL2 + RS cells

  • FOXP3 low positive RS cells

  • EBV + >60 years

  • EBV + <15 years

Box 11.5

Differential Diagnosis of Classic Hodgkin Lymphoma

ALCL, anaplastic large cell lymphoma; AKL, anaplastic lymphoma kinase 1; DLBCL, diffuse large B-cell lymphoma; HIV, human immunodeficiency virus ; LPDs, lymphoproliferative disorders; NHL, non-Hodgkin lymphoma; OCT2, octamer binding protein-2; PTCL, peripheral T-cell lymphoma.

Concurrent Composite Neoplasms With cHL

  • Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL)

  • Follicular lymphoma (FL)

  • Mantle cell lymphoma (MCL)

  • Marginal zone lymphoma (MZL)

  • Large B-cell lymphoma (LBCL)

  • Discrete or intermixed

  • EBV + (MZL and DLBCL)

  • Langerhans cell proliferation

Differential Diagnostic Mimickers of cHL

  • Melanoma (S100)

  • Poorly differential carcinoma (keratins)

  • Malignant neoplasm with pleomorphic anaplastic cells

  • Germ cell tumor (OCT2, SALL4 )

  • Necrotizing granulomatous lymphadenitis

  • Immunodeficiency LPDs

  • Primary immune disorders

  • HIV

  • PTLD

  • Iatrogenic immunodeficiency LPDs

  • ALCL ALK positive or negative

  • NHL

  • Lennert PTCL

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Apr 3, 2021 | Posted by in HEMATOLOGY | Comments Off on Hodgkin Lymphoma

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