Pediatric Hodgkin Lymphoma Workup

Updated: Jun 02, 2021
  • Author: Pedro A de Alarcon, MD; Chief Editor: Vikramjit S Kanwar, MBBS, MBA, MRCP(UK)  more...
  • Print

Approach Considerations

The evaluation of the patient with Hodgkin lymphoma includes physical examination of all lymph node regions, chest radiography, CT scan of the chest/abdomen/pelvis, and nuclear imaging with gallium scan or, preferably, positive emission tomography (PET). In the past, patients with bone pain and elevated alkaline phosphatase or extensive disease also received bone scans. Nowadays PET detects more disease sites when combined with CT scans. Also, bilateral bone marrow biopsies were common practice for the staging of Hodgkin disease. Their use now is restricted to patients with advanced disease and or B symptoms. The need for bone marrow biopsies for staging is controversial, considering that a PET-CT scan can detect bone marrow involvement; however, additional studies are needed to confirm this.

Hematological and blood chemistry evaluation may reveal nonspecific findings in patients with Hodgkin lymphoma. Some usual findings include the presence of neutrophilia or eosinophilia. Some patients may have hypoalbuminemia. Some patients may have marked anemia or thrombocytopenia, and, occasionally, those may be related to an autoimmune dysregulation caused by a paraneoplastic related disorder. However, several of these findings have been used as prognostic factors.

Lymph node biopsy is mandatory to make the definitive diagnosis of Hodgkin lymphoma. Staging laparotomy is no longer advocated in pediatric Hodgkin lymphoma.



After a tissue diagnosis is made, Hodgkin lymphoma (HL) is staged by using imaging studies, evaluating the bone marrow, and assessing for B symptoms.

The most widely used staging system is the Ann Arbor staging system, as follows:

  • Stage I - Single lymph node region or single extranodal site

  • Stage II - Two or more lymph node regions on the same side of the diaphragm

  • Stage III - Lymph node regions on both sides of the diaphragm

  • Stage IV - Diffuse or disseminated involvement of one or more extralymphatic organs (liver, bone marrow, lung) or tissues with or without associated lymph node involvement (The spleen is considered a nodal site.)

A or B designations are also used. B includes the presence of at least one of the following symptoms:

  • Drenching night sweats

  • Unexplained fevers with temperature more than 38°C for 3 consecutive days

  • More than 10% loss of body weight in the past 6 months

The A designation involves the absence of symptoms described above. The E designation is extension or contiguous involvement of extranodal sites by large mediastinal masses that are not considered metastatic or stage IV.

Bulky disease defined as a 10 cm or larger mass (=6-cm mass for many pediatric trials) or large mediastinal adenopathy (mass greater than one third maximum thoracic diameter by chest radiography) is an adverse outcome factor.

In addition to the staging for pediatric patient with Hodgkin lymphoma, patients tend to be grouped according to their risk for relapse.

Table 1. Risk According to Stage (Open Table in a new window)

Risk Groups

Children’s Oncology Group

German Multicenter Studies

Stanford/Dana Farber/St. Jude

Low risk

I A no bulk or E II A no bulk or E


I A II A no bulk

Intermediate risk

I A with bulk or E, I B II A with bulk or E II B III A IV A E


I A bulk I B II A with bulk IIB III IV

High risk


II B – E III A / B - E IV A / B



The risk assignment allows the intensification of treatment according to the risk for relapse in such a way that low stages required less therapy than those with advanced stages. Risk assignment varies among the pediatric cancer cooperative groups, and, therefore, assignment of treatment varies. The risk stratification in one cooperative should not be mixed with therapy regimen of another cooperative group. The cooperative cancer groups strive to improve the outcome of children with Hodgkin lymphoma; however, the risk assignment may change with newer regimens.


CBC Count, Chemistry Panel, and Other Tests

The CBC count may reveal the following:

  • Hemolytic anemia (Coombs positive), anemia of chronic disease, or anemia secondary to involvement of the bone marrow

  • Leukocytosis, lymphopenia, eosinophilia, monocytosis

  • Thrombocytopenia due to marrow infiltration or idiopathic thrombocytopenia purpura

Assessment of acute-phase reactants may show elevations in the erythrocyte sedimentation rate (ESR) and C-reactive protein, serum copper, and ferritin levels.

A full serum chemistry panel may aid in evaluating levels of serum electrolytes; lactate dehydrogenase (LDH) levels, which reflect bulk of disease; alkaline phosphatase, which indicates bony metastasis; and liver and kidney function.

Urinalysis may reveal proteinuria. Nephrotic syndrome may be associated with Hodgkin lymphoma.


Radiography and Other Imaging Studies

Chest radiography is performed with anteroposterior and lateral projections to assess the bulk of the mediastinal mass. Mediastinal mass with a thoracic ratio of 33% or greater is of prognostic importance.

CT or MRI of the neck, chest, abdomen, and/or pelvis is indicated to assess sites of disease (nodal and extranodal), as well as to assess liver and spleen involvement. Ultrasonography can be used to assess the abdominal and pelvic structures in centers with limited resources in which CT scanning or MRI is not available. The minimal feasible amount of ionizing radiation should be used for diagnostic imaging in order to limit the future incidence of secondary malignancy.


Positron Emission Tomography

On (PET) scanning, uptake of the radioactive glucose analog 2-[18F] fluoro-2-deoxy-D-glucose (FDG) is correlated with proliferative activity in tumors undergoing anaerobic glycolysis. PET scanning is used with increasing frequency to identify the extent of disease at diagnosis and for follow-up. After 2 cycles of therapy with doxorubicin (Adriamycin), bleomycin, vinblastine, and dacarbazine (ABVD), a positive PET scan finding may be predictive of poor outcome. However, confirmation of its utility with other regimens is pending.

PET scanning is becoming an important modality to guide involved-field radiation therapy in adult Hodgkin lymphoma, [9] and its role in guiding involved-field radiation therapy in pediatrics is being explored.

Gallium scanning is rarely used and has been replaced by PET scanning. Bone scanning has been used when bony metastases are suspected because of an elevated alkaline phosphatase level, but the same information may be obtained with PET scanning.



Histological diagnosis of Hodgkin lymphoma is always required. Ideally, the largest abnormal lymph node should be excised intact (excisional biopsy). Appropriate tissue handling is of essence to allow adequate evaluation of tissue architecture. When a formal lymph node excisional biopsy specinmen cannot be obtained, particularly from sites not easily accessible to the surgeon, such as the mediastinum fine-needle aspiration biopsy may be used. Although the diagnosis of HL can be made with very small samples by expert pathologists, a definitive diagnosis may be challenging for the less experienced specialist. Fine-needle aspiration biopsies are more reliable in the diagnosis of recurrent Hodgkin lymphoma.

Fine-needle aspiration is not recommended due to the lack of stromal tissue and the difficulty of classifying Hodgkin lymphoma into one of the classic subtypes versus nodular lymphocyte–predominant (NLP) subtype.

Bone marrow biopsy previously was common practice for the staging of Hodgkin lymphoma. Its use is now restricted to patients with advance disease (stage III and IV) or any other stage with B symptoms. Some controversy exists with regard to the need for bone marrow biopsy for staging, as it is thought that the PET scanning can detect bone marrow involvement. However, additional studies are needed to confirm these findings.

Histopathologic studies consist of hematoxylin and eosin staining and special immuno histochemical staining for surface markers such as CD15, CD20, CD30, and CD45. Consider other immuno histochemical staining to ensure that they are negative and to rule out non-Hodgkin lymphoma, such as CD3 and anaplastic lymphoma kinase (ALK).[#Workup Histologic Findings]


Histologic Findings

Hodgkin lymphoma (HL) is a unique malignant neoplasm in which the malignant cell represents only a small proportion of the cells making up the tumor. The majority of the cells are small lymphocytes, histiocytes, neutrophils, plasma cells, and fibroblasts in different proportions depending on the histological subtypes.

Hodgkin lymphoma is the Reed-Sternberg cells (RSCs). The RSCs generally are binucleated or multinucleated giant cells. The typical RSC has a bilobed nucleus with 2 large nucleoli that produces the characteristic "owl’s eye" appearance. The typical RSC is characterized by CD30 positivity, absence of J chains, and frequent expression of CD15, which is consistent with classic Hodgkin lymphoma. [10] . A variant of the RSC is the so called "popcorn cell" and is formally known as the lymphocyte and histiocytic (L&H) cell, typical of nodular lymphocyte-predominant Hodgkin lymphoma. L&H cells are small with a very lobulated nucleolus and small nucleoli. Their immunophenotype is characterized by CD20 positivity, J-chain rearrangements, and, in general, CD30 and CD15 negativity.


It has been recognized that Hodgkin lymphoma can be subdivided in 2 clinical, pathological, and biologic disease entities: classic Hodgkin lymphoma and nodular lymphocyte-predominant Hodgkin Lymphoma. The 1999 World Health Organization classification is presented below: [11]

  • Nodular lymphocyte-predominant Hodgkin Lymphoma (NLPHL)

  • Classical Hodgkin lymphoma

    • Nodular sclerosis

    • Mixed cellularity

    • Lymphocyte depleted

    • Lymphocyte rich

Nodular sclerosing Hodgkin lymphoma is notable for fibrous bands that result in a nodular pattern and lacunar-type RSCs, wherein the cytoplasm in formalin-fixed specimens retracts, forming a lacuna around the nucleus. This is the most common type in all age groups (77% of adolescents and 72% of adults), although it affects only 44% of younger children.

Mixed-cellularity Hodgkin lymphoma may have interstitial fibrosis, but fibrous bands are not observed. RSCs are classic in appearance or mononuclear. Lymphocytes may predominate in the cellular background (see the image below). This subtype is more common in young children (33%) than in adolescents (11%) or adults (17%).

Mixed cellularity Hodgkin lymphoma showing both mo Mixed cellularity Hodgkin lymphoma showing both mononucleate and binucleate Reed-Sternberg cells in a background of inflammatory cells (hematoxylin and eosin, original magnification X200).

Lymphocyte-rich Hodgkin lymphoma has classic or lacunar-type H-RSC with rare or absent eosinophils on a cellular background. This type is extremely rare.

Lymphocyte-depleted Hodgkin lymphoma has large numbers of RSCs with sarcomatous variants and a hypocellular background because of fibrosis and necrosis. This type is also extremely rare.

Nodular lymphocyte-predominant Hodgkin lymphoma may be nodular, but fibrosis is unusual. The RSC variants are known as L&H cells (popcorn cells, because their nuclei resemble an exploded kernel of corn). The nuclei are multilobed and vesicular with small nucleoli. The characteristic halo of the classic RSC is absent. The background consists of histiocytes and lymphocytes with a B-cell predominance, in contrast to the cellular background in classic Hodgkin lymphoma, which has T-cell predominance.

Nodular sclerosis Hodgkin lymphoma is the most common type in developed countries, whereas in some developing countries, mixed-cellularity Hodgkin lymphoma is the most common histologic type.