Hodgkin's%20lymphoma Diagnosis

Diagnosis

Physical Examination

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

Laboratory Tests

Complete blood count, with differential and platelet count
Erythrocyte sedimentation rate (ESR)
Liver, renal, and bone function tests
Metabolic panel, including lactate dehydrogenase (LDH) levels and serum beta-2-microglobulin
Testing for hepatitis B and C, and 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
Excisional lymph node biopsy is preferred to conclude diagnosis of Hodgkin's lymphoma (HL) but excisional lymph node biopsy may also be used
Bone marrow biopsy from at least 1 site of patients with stage III-IV HL or stage II with anemia is considered if positron emission tomography–computed tomography (PET-CT) scan is not available

Immunohistochemistry

Classic Hodgkin Lymphoma (CHL)

Typical immunophenotype includes CD15+, CD30+, PAX-5+, CD20-, CD3-, CD45- and CD79a-
CD15 and CD30 are expressed by Reed-Sternberg cells and are characteristic of CHL

Nodular Lymphocyte-Predominant Hodgkin Lymphoma (NLPHL)

Immunophenotypes identified with NLPHL include CD15-, CD20+, CD30-, CD45+, CD79a+, CD3-, BCL6+, and PAX-5+

Imaging

Chest Radiography

Suggested for patients with large mediastinal mass

Computed Tomography (CT)

CT scan with contrast of the neck, chest, abdomen and 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 and treatment evaluation
Fluorodeoxyglucose positron emission tomography (FDG-PET) scanning is used to improve staging in CHL, with better detection for lesions compared to CT scan

Classification

Classification According to Histology

Based on the classification by the World Health Organization (WHO)

Classic Hodgkin Lymphoma (CHL)

Accounts for 95% of Hodgkin's lymphoma (HL) cases
Morphologic feature: Presence of Reed-Sternberg cells
Subtypes of CHL:
- Nodular sclerosis
  - Most common CHL subtype (60%)
  - Presents in a partially nodular pattern with fibrous/sclerotic bands separating nodules, lacunar cells, diffuse areas, and necrosis
- Mixed cellularity
  - Makes up 20-25% of diagnosed HL patients, commonly affects older men
  - Often Ebstein-Barr virus (EBV)-positive, with diffuse infiltrates, fine interstitial fibrosis, Hodgkin and Reed-Sternberg (HRS) cells, and without band-forming sclerosis
- Lymphocyte-depleted
  - Most commonly seen in the human immunodeficiency virus (HIV)-positive patients
  - With diffuse infiltrates, diffuse fibrosis and necrosis, numerous HRS cells, and occasional bizarre sarcomatous variants and inflammatory cells; EBV also present
- Lymphocyte-rich
  - Presents as nodular or diffuse, with HRS cells uncommon, with infrequent eosinophils or plasma cells

A mediastinal mass with a maximum width ≥1/3 of the internal transverse diameter of the thorax at the T5/T6 level or >10 cm maximum nodal mass dimension is classified as bulky disease

Nodular Lymphocyte-Predominant Hodgkin Lymphoma (NLPHL)

Accounts for 5% of HL 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 Disease Stage (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 ≥2 lymph node regions or structures on the same side of the diaphragm^1,2
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) and 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 CHL According to Prognosis

Favorable and unfavorable stages are classified based on the German Hodgkin Study Group (GHSG), European Organization for the Research and Treatment of Cancer (EORTC), and 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 and II HL and ≥1 risk factor
Criteria for inclusion:

GHSG	EORTC
Extranodal disease absent	Age <50 years
Large mediastinal adenopathies absent	Large mediastinal adenopathies absent
ESR <50 without B symptoms	ESR <50 without B symptoms
ESR <30 with B symptoms	ESR <30 with B symptoms
1-2 sites of involvement	1-3 sites of involvement

Early Stage Unfavorable Hodgkin's Lymphoma

Patients with stages I and II HL and >1 risk factor
Criteria for inclusion:

GHSG	EORTC	NCCN
Extranodal involvement present	Age ≥50 years	Bulky disease >10 cm
Bulky mediastinal involvement present	Bulky mediastinal involvement present	Bulky mediastinal involvement present
ESR >50 without B symptoms	ESR >50 without B symptoms	ESR ≥50 or any B symptoms
ESR >30 with B symptoms	ESR >30 with B symptoms
>2 sites of involvement	>3 sites of involvement	>3 sites of involvement

Advanced Stage Hodgkin's Lymphoma

Patients with stages III and IV
Criteria for inclusion:
- Hemoglobin (Hgb) <10.5 g/dL
- White blood cells (WBC) >15,000/mm³
- Lymphocytes <600/mm³ or <8% of WBC
- Albumin <4 g/dL
- Stage IV disease
- Male gender
- Age ≥45 years

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