Hodgkin lymphoma in children and adolescents

1

Describe the incidence and epidemiology of Hodgkin lymphoma in children and adolescents.

There are approximately 1200 new cases of Hodgkin lymphoma (HL) diagnosed in the United States annually among children and adolescents. Among adolescents, HL is associated with a higher socioeconomic background. In contrast, the incidence of HL among young children tends to increase with increasing family size and lower socioeconomic status. The mixed cellularity histologic subtype is more common in these younger patients. In low-income countries, an early peak occurs before adolescence, where it is also associated with Epstein-Barr virus (EBV) infection, mixed cellularity histology, and male sex.

2

What is the epidemiologic relationship between HL and Epstein-Barr virus?

An infectious etiology for Hodgkin has long been suggested by its epidemiologic characteristics, and much of the data point specifically to EBV. High EBV antibody titers have been detected in young patients with HL, suggesting that enhanced activation of EBV may precede the development of HL. EBV is more often associated with HL occurring in patients with primary or secondary immunodeficiencies, such as human immunodeficiency virus (HIV) infection and after solid organ transplant.

3

Name the subtypes of HL.

The World Health Organization (WHO) histologic classification recognizes two major subtypes of HL: classical HL (cHL) and nodular lymphocyte predominant HL (nLPHL). The primary distinctions between these two are on the basis of histology and immunohistochemical staining pattern.

• A.

  cHL has four histologic subtypes:

  • Nodular sclerosis (most common): The primary histologic subtype of cHL is nodular sclerosis (up to 70% of cases). This is the most common cHL histology and often involves neck and mediastinum.

  • Mixed cellularity: The majority of the remaining cases exhibit the mixed cellularity histology. This is the second most common cHL, patients are younger than 10 years old, and EBV frequently involved. Often there is advanced disease at presentation.

  • Lymphocyte-depleted.

  • Lymphocyte-rich (least common).

• B.

  nLPHL accounts for 10% to 20% of pediatric HL, usually presents with early-stage disease (IA, IIA), and has a male predominance, indolent course, and good prognosis but can have late and occasionally multiple relapses and transformation to T-cell/histiocyte rich large B-cell lymphoma.

4

Describe the clinical presentation of HL.

• Painless lymphadenopathy

• Persistent cough, shortness of breath, or chest pain related to the presence of a mediastinal mass (in approximately two-thirds)

• Constitutional symptoms

5

Define “B” symptoms.

B symptoms describe the extent of systemic or constitutional symptoms that accompany a diagnosis of HL. Presenting with any or all of the following defines having B-symptoms.

• Unintentional weight loss of at least 10% in 6 months

• Drenching night sweats

• Unexplained fevers of at least 38°C for 3 consecutive days

6

What is included in the diagnostic workup for suspected HL?

Workup should begin with a thorough history to determine the presence or absence of B-symptoms, as well as family history, other medical conditions, and infectious history. Physical examination should focus on palpation of lymph nodes, auscultation of lungs, and palpation of the abdomen assessing for hepatosplenomegaly. The diagnosis of HL requires histologic confirmation with an excisional lymph node biopsy. Fine-needle aspiration of a lymph node should be avoided because a negative biopsy will not rule out a diagnosis of HL because of the rarity of the Hodgkin-Reed-Sternberg (HRS) cells within the lymph node. Diagnostic imaging includes a chest radiograph, both posteroanterior (PA) and lateral, and a positron emission tomography/computed tomography (PET/CT) scan is used to determine the metabolic activity of involved nodes and extralymphatic organs, including the bone and bone marrow. All involved sites should be assigned a Deauville score. Contrast-enhanced CT scan of the neck, chest, abdomen, and pelvis should be included. Bilateral bone marrow biopsy has largely been replaced by PET scan.