hodgkin's%20lymphoma
HODGKIN'S LYMPHOMA

Hodgkin's lymphoma is a malignancy that arises from germinal center B cell.

Histologically, there is a presence of multinucleated giant cells in a mixed inflammatory background.

It is also known as Hodgkin's disease, Hodgkin lymphoma or Hodgkin disease.

It commonly affects individuals ages 15-30 years old and those 55 years old and above.

The key morphologic characteristics include presence of Reed-Sternberg cells and lymphocyte-predominant cells.

Diagnosis

Physical Examination

  • Node-bearing areas (eg cervical, anterior mediastinal, supraclavicular, & axillary areas)
  • Spleen & liver size measurement is advised
  • Extranodal involvement commonly occurs in the lungs, bone, liver & bone marrow

Laboratory Tests

  • Complete blood count, with differential & platelet count
  • Erythrocyte sedimentation rate (ESR)
  • Liver, renal, & bone function tests
  • Metabolic panel, including lactate dehydrogenase (LDH) levels & serum beta-2-microglobulin
  • Testing for hepatitis B & C, & human immunodeficiency virus (HIV) is also suggested
  • Testing for pregnancy should be done prior to initiation of treatment

Biopsy

  • Preferred study that provides adequate tissues for different examinations
  • Core needle biopsy is preferred to conclude diagnosis of Hodgkin's lymphoma but excisional lymph node biopsy may also be used
  • Bone marrow biopsy from at least 1 site of patients with stage III-IV Hodgkin's lymphoma or stage II with anemia is considered if positron emission tomography–computed tomography (PET-CT) scan is not available

Immunohistochemistry

Classical Hodgkin’s Lymphoma

  • Typical immunophenotype includes CD15+, CD30+, PAX-5+, CD20-, CD3-, CD45- & CD79a-
  • CD15 & CD30 are expressed by Reed-Sternberg cells & is diagnostic of classic Hodgkin's lymphoma (CHL)

Nodular Lymphocyte-Predominant Hodgkin’s Lymphoma

  • Immunophenotypes identified with nodular lymphocyte-predominant Hodgkin's lymphoma (NLPHL) include CD15-, CD20+, CD30-, CD45+, CD79a+, CD3-, BCL6+, & PAX-5+

Imaging

Chest Radiography

  • Suggested for patients with large mediastinal mass

Computed Tomography (CT)

  • Computed tomography (CT) scan with contrast of the neck, chest, abdomen & pelvis
  • Contrast-enhancement is required for findings to be conclusive

Positron Emission Tomography - CT (PET-CT) Scan

  • Gold standard for clinical staging of Hodgkin's lymphoma, both during initial diagnosis & treatment evaluation
  • Used to identify the Deauville score in patients with classic Hodgkin's lymphoma (CHL)
  • Fluorodeoxyglucose positron emission tomography (FDG-PET) scanning is used to improve staging in classic Hodgkin's lymphoma (CHL), with better detection for lesions compared to computed tomography (CT) scan

Classification

Classification According to Histology

  • Based on the World Health Organization (WHO) modification of the Revised European-American Lymphoma (REAL) classification

Classic Hodgkin Lymphoma (CHL)

  • Accounts for 95% of Hodgkin's lymphoma cases
  • Morphologic feature: presence of Reed-Sternberg cells
  • Subtypes of classic Hodgkin's lymphoma (CHL):
    • Nodular sclerosis
      • Most common classic Hodgkin's lymphoma (CHL) subtype (60%)
      • Most commonly afflicts young women
      • Presents in a partially nodular pattern with fibrous/sclerotic bands separating nodules, lacunar cells, diffuse areas, & necrosis
    • Mixed cellularity
      • Makes up 20-25% of diagnosed Hodgkin's lymphoma patients, commonly affects older men
      • Often Ebstein-Barr virus (EBV)-positive, with diffuse infiltrates, fine interstitial fibrosis, Hodgkin & Reed-Sternberg (HRS) cells, & without band-forming sclerosis
    • Lymphocyte-depleted
      • Most commonly seen in the elderly & human immunodeficiency virus (HIV)-positive patients
      • With diffuse infiltrates, diffuse fibrosis & necrosis, numerous Hodgkin & Reed-Sternberg (HRS) cells, & occasional bizarre sarcomatous variants & inflammatory cells; Ebstein-Barr virus (EBV) also present
    • Lymphocyte-rich
      • Presents as nodular or diffuse, with Hodgkin & Reed-Sternberg (HRS) cells uncommon, with infrequent eosinophils or plasma cells
  • A mediastinal mass with a max width >1/3 of the internal transverse diameter of the thorax at the T5/T6 level or >10 cm max nodal mass dimension is classified as bulky disease

Nodular Lymphocyte-Predominant Hodgkin Lymphoma (NLPHL)

  • Accounts for 5% of Hodgkin's lymphoma cases
  • Morphologic feature: numerous large “popcorn”/lymphocyte predominant cells, tightly packed nodular growth pattern, with or without diffuse areas, absent Reed-Sternberg cells

Classification According to Staging (Cotswold Staging Classification for Hodgkin’s Lymphoma)

  • Developed by the American Joint Committee on Cancer: Cotswold modifications of the Ann Arbor Staging System

  • Stage Features
    I Involvement of a single lymph node region (eg cervical, axillary, inguinal, mediastinal) or lymphoid structure (eg spleen, thymus, Waldeyer's ring)
    II Involvement of two or more lymph node regions or structures on the same side of the diaphragm1,2
    III Involvement of lymph regions or structures on both sides of the diaphragm3
    IV Diffuse or disseminated node involvement of one or more extranodal organs/tissue beyond designated extranodal contiguous extension4
    1Lateralized hilar nodes are defined as nodes involving both sides and should be considered as Stage II disease
    2All nodal disease within the mediastinum is considered to be a single lymph node region; another site should be added for any hilar involvement, with anatomic regions written in subscript
    3May be subdivided into stage III-1 (spleen or splenic hilar/celiac/portal node involvement) & stage III-2 (paraaortic/iliac/inguinal/mesenteric node involvement)
    4Extranodal contiguous extension involves disease that can be encompassed within an irradiation field appropriate for nodal disease of the same anatomic extent

Classification of Classic Hodgkin's Lymphoma (CHL) According to Prognosis

  • Favorable & unfavorable stages are classified based on the German Hodgkin Study Group (GHSG), European Organization for Research and Treatment of Cancer (EORTC), & the National Cancer Institute of Canada (NCIC)
  • Advanced stages (III-IV) are classified based on the Hasenclever International Prognostic Score (IPS)

Early Stage Favorable Hodgkin's lymphoma

  • Patients with stages I & II Hodgkin's lymphoma & ≥1 risk factor
  • Criteria for inclusion:
    • No nodal extension
    • Large mediastinal adenopathies absent
    • Erythrocyte sedimentation rate (ESR) <50 mm/hour & no B symptoms (unexplained fever >38oC, night sweats, significant weight loss >10% within 6 months)
    • Limited to 1-2 sites of involvement
    • Age ≤50 years old

Early Stage Unfavorable Hodgkin's Lymphoma

  • Patients with stages I & II Hodgkin's lymphoma & >1 risk factor
  • Criteria for inclusion:
    • Large mediastinal adenopathies present
    • >3 involved sites
    • Erythrocyte sedimentation rate (ESR) >30 mm/hour with B symptoms
    • Erythrocyte sedimentation rate (ESR) >50 mm/hour without B symptoms
    • Extranodal extension present
    • Age >50 years old
    • Presence of a bulky mediastinal mass

Advanced Stage Hodgkin's Lymphoma

  • Patients with stages IIB, III & IV
  • Criteria for inclusion:
    • Diffuse or disseminated node involvement of one or more extranodal organs/tissue beyond designated extranodal contiguous extension
    • Hemoglobin (Hgb) <10.5 g/dL
    • White blood cells (WBC) >15,000/mL
    • Lymphocytes <600/mL or <8% of white blood cells (WBC)
    • Albumin <4 g/dL
    • Male
    • Age >45 years old
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