Hodgkin Lymphoma

Question 1

What is HL?

Answer 1

Hodgkin Lymphoma (HL) first described by Thomas Hodgkins in 1832 is defined as monoclonal lymphoid neoplasm characterised by the presence of multinucleated giant cells, Reed-Sternberg and Hodgkin cells with characteristic immunophenotype and appropriate cellular background.

Question 2

Epidemiology

Answer 2

Worldwide ditribution.
One of the common malignancies of young
adults.
Constitutes about 1% of all malignancies and
about 18% of all lymphomas in the USA.
Males affected more than females.
Whites more than Africans.
Has bimodal age distribution, 1st peak in the 3rd
decade and 2nd peak >60 years of life.
Median age of occurence in Nigeria is 30 years.

Question 3

What is the etiology of HL?
Major cause in HIV?
Incubation time?

Answer 3

The etiology ofHodgkin diseaseis unknown.
Infectious agents,esp Epstein-Barr virus (EBV).
About 50% of Hodgkindisease cases are EBV-positive;
Almost 100% of HIV-associatedHodgkin
diseasecases are EBV-positive.
The averageincubation time to symptoms of
Hodgkindisease was2.9 years.

Genetic predisposition may play a role.
≈1% of ptshave a family history.
Siblings of an affected individual have a 3- to 7-fold increased risk.
This risk is higher in monozygotic twins.

Question 4

Pathogenesis?

Answer 4

The exact origin of RS cell is not known.
RS cells comprise only 1-2% of the total tumor cell mass.
Most of the cells are varieties of reactive, mixed inflammatory cells consisting of lymphocytes, plasma cells, neutrophils, eosinophils, and histiocytes.

Question 4

Classification of HL

Answer 4

1. Nodular Lymphocyte-Predominant HL (NLPHL)
2. Classical HL:
   – Nodular Sclerosis (NSHL)
   - Mixed Cellularity (MCHL)
   - Lymphocyte-rich (LRHL)
   - lymphocyte-depleted (LDHL)

Question 5

Dicuss the classification and their characteristcs

Answer 5

1. NLPHL: makes up 3–8% of cases; contain large atypical B cells and lymphocytic and histiocytic (L&H) ‘popcorn’ cells.
   These cells are CD30–, CD15–, CD20+, CD45+, CD75+, CD79a+.

2.‘Classical’ HL: large mononuclear (Hodgkin’s cells) or binucleate/multinuclear cells
RS cells make up only 1–2% of the cellularity of
the lymph node.
These cells are CD30+ and typically CD15+, CD20–, CD45–, CD75–, CD79a–.
The predominant cells are an infiltrate of
lymphocytes, plasma cells, eosinophils and
histiocytes containing scattered neoplastic cells
and a variable degree of fibrosis.

Nodular sclerosing HL (NSHL): ~80%;
prominent bands of fibrosis and nodular growth pattern;
lacunar Hodgkin’s cells;
variable numbers of RS cells.

Mixed cellularity HL (MCHL): ~17%;
mixed infiltrate of lymphocytes, eosinophils and histiocytes with classical RS cells.

Lymphocyte depleted HL (LDHL): rare
diffuse hypocellular infiltrate with necrosis, fibrosis and sheets of RS cells.

Lymphocyte rich classical HL (LRCHL):
uncommon; diffuse predominantly lymphoid infiltrate with scanty RS cells of ‘classical’ phenotype.

Question 6

What are the CLINICAL FEATURES of HL?

Answer 6

Usually present with enlarged, painless and rubbery lymph node ≈ 80% cervical, and upto 50% have mediastinal mass.
Alcohol-induced nodal pain.
Pattern of nodal spread is contiguous and usually axial.
≈ 25% have systemic symptoms
– unexplaned fever,
- drenching night sweats,
- unexplained weight loss > 10% of pre-diagnosis weight,
- fatigue, weakness, anorexia.

Intensed pruritus.
Hepatosplenomegaly.
Infiltrative lung disease + pleural involvement.
Skin infiltration – Leukemids.
Bone marrow infiltration.

Because of defect in cellular immunity, they are more susceptible to TB, fungal, protozoal and viral infections including P carinii and HZV.
Primary extranodal presentation (bone marrow, CNS, skin) is rare.

Question 7

What are the lab features, Hematological and biochemical, Radiological?

Answer 7

Diagnosis is based on finding the RS/H cells in an appropriate cellular background of reactive T cells, histiocytes, & eosinophils with varrying degrees of fibrosis from tissue biopsy.
Hematological;
FBC – Eosinophilia, Lymphocytosis, Lymphopenia,
Thrombocytopenia or Thrombocytosis,
Anemia – chronic disease, immune-mediated hemolysis
Raised ESR – index of disease progression and monitoring response
BMA/Biopsy – those with abnormal FBC or advanced-stage disease

Biochemical;
↑ serum alkaline phosphatase – index of disease activity
↑ serum lactate dehydrogenase – collerates with tumour load.
Hypercalcemia
Hyperuricemia
Impaired glucose

Radiological;
CXR
CT Scanning of chest, abdomen & pelvis
Gallium or PET scans
Bone scan
Echocardiography

Question 8

What is the DIFFERENTIAL DIAGNOSIS?

Answer 8

NHL
TB
HIV
Syphilis
Infectious Mononucleosis

Question 8

Discuss treatment

Answer 8

The primary treatment is aimed at complete
response (CR), which is defined as the
“disappearance of all evidence of disease“
Partial Response (PR) - Regression of
measurable disease and no new sites
Stable Disease (SD) - Failure to attain CR/PR or
RD
Relapsed disease - Any new lesion or
increase by 50% of Previously involved sites from nadir

Modalities includes;
Radiotherapy
Combination Chemotherapy
Salvage therapy

For early-stage disease (Ia & IIa)
combination chemotherapy (4-6 cycles) & Involved Field Radiotherapy
Advanced-stage disease –
Chemotherapy (6-8 cycles) with Radiotherapy in the presence of bulky disease.

Question 9

What is the Pretreatment Evaluation?

Answer 9

Detailed history and complete physical examination
FBC & ESR
LFT, Test of renal function, and serum uric acid
Lactate dehydrogenase
CXR, CT, MRI & Bone scan
ECG/Echocardiography
Bone Marrow Biopsy
Patient’s counselling
Adequate hydration
Prevention of hyperuricemia - TLS

Question 10

What are the Unfavourable Factors?
What are B symptoms?

Answer 10

Stage II with ≥ 4 nodes involvement/ stage III and IV
Age > 50 years
ESR > 50 mm/hr if asymptomatic or > 30mm/hr with B symptoms.
Mediastinal/thoracic ratio > 0.35

Question 11

What are the Complications of Chemotherapy?

Answer 11

Early – Nausea & vomiting
Alopecia
Myelosuppression
Infection
Late – Sterility – MOPP (Mechlorethamine, Oncovin. Procarbazine, Prednisone)
Neuropathy – Vincristine
Cardiomyopathy – Doxorubicin
Pulmonary fibrosis – Bleomycin
Secondary leukemia – Alkylating agents

Question 13

What are the Complications of RTH?

Answer 13

Early - Anorexia & Nausea
Mouth dryness, pharyngitis, cough &
dermatitis
Myelosuppression – Neutropenia
Thrombocytopenia
Late - Hypothyroidism
Pericarditis, Pneumonitis
Coronary artery disease
Secondary Neoplasms – lung, breast, stomach,
thyroid, skin, etc

Question 13

Q Differences Between NHL and HL