Hodgkin lymphoma

What every physician needs to know:

Hodgkin lymphoma (HL) is divided into two subgroups, including classical HL (CHL) and nodular lymphocyte predominant Hodgkin lymphoma (NLPHL). While classical HL is divided into four distinct entities: nodular sclerosis, mixed cellularity, lymphocyte-rich, and lymphocyte-depleted, the subtypes have little prognostic significance with current therapies. However, differentiating between CHL and NLPHL is critical, as these diseases have distinct natural histories and treatment options are different. Staging is based on the Ann Arbor system as detailed in Table I.

Table I.
I Involvement of a single lymph node region (I) or a single extralymphatic organ or site (IE)
II Involvement of two or more lymph node regions on the same side of the diaphragm (II) or localized involvement of an extralymphatic organ or site (IIE)
III Involvement of lymph node regions on both sides of the diaphragm (III) or localized involvement of an extralymphatic organ or site (IIIE) or spleen (IIIS) or both (IIISE)
IV Diffuse or disseminated involvement of one or more extralymphatic organs, with or without associated lymph node involvement

Several features at presentation (for example, stage, presence of bulky disease, and specific laboratory findings) dictate treatment and can predict outcome, highlighting the importance of an appropriate work-up. Overall, outcomes are favorable with approximately 80% of patients achieving durable remissions with chemotherapy ± radiotherapy.

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Survivorship is a major focus for oncologists caring for patients with HL. Efforts are underway to balance therapy such that toxicities are minimized for the vast majority of patients who will be cured, and treatment is maximized for the smaller subset predicted to fail standard therapy. Ongoing national studies are evaluating the role of early interim positron emission tomography/computed tomography (PET/CT) following two cycles of chemotherapy to guide treatment decisions. (See Table I)

Are you sure your patient has Hodgkin lymphoma? What should you expect to find?

Most patients with classical HL present with painless cervical and/or supraclavicular lymphadenopathy. Lymph node involvement is frequently contiguous. Systemic symptoms, or “B” symptoms (fevers [with temperatures greater than 38° C], drenching night sweats, or weight loss [greater than 10% baseline body weight]) occur in approximately 10% of patients with early stage disease, and in 30 to 40% of patients with advanced stage disease. Chest pain, cough, dyspnea, and superior vena cava (SVC) syndrome are rare, even in patients with bulky mediastinal involvement.

NLPHL frequently presents with solitary cervical, axillary, or inguinal lymphadenopathy with no consistent pattern of spread, in contrast to classical HL. Presence of any other symptoms related to the disease, including B symptoms, is unusual. Most patients present with early stage disease, and mediastinal involvement is rare.

Beware of other conditions that can mimic Hodgkin lymphoma:

Other lymphoma subtypes can mimic classical HL. The most common histologies are nodular lymphocyte predominant Hodgkin lymphoma (NLPHL), primary mediastinal B-cell lymphoma, anaplastic large cell lymphoma, and T-cell rich large B-cell lymphoma.

Non-malignant conditions are frequently in the differential diagnosis as well, including rheumatologic and infectious diseases, such as fever of unknown origin (FUO), acute HIV infection, infectious mononucleosis, and sarcoid.

Which individuals are most at risk for developing Hodgkin lymphoma:

Approximately 8,500 cases of HL (55% men) are diagnosed annually in the United States.

Patients with NLPHL are frequently male and most frequently in the 30 to 50 year age group. In developed countries, classical HL has a bimodal age distribution with the first peak in the third decade of life and the second after the age of 50. The highest rates in the United States occur among Caucasians, followed by African Americans, Hispanics, and Asians. Interestingly, an increasing incidence seen among Chinese immigrants suggests an association with westernization and an environmental risk factor.

Documentation of multiply affected family members and twin studies point to genetic factors as well, though familial HL accounts for only a minority of cases, and no consistent mechanism of inheritance has been identified. The noted association between HL and factors that decrease exposure to infectious agents at an early age (for example, early birth order, decreased number of siblings, advanced maternal education, and single family dwellings) suggest a common virus at a late age of onset.

A history of infectious mononucleosis increases the risk of HL two to three-fold, and points toward Epstein-Barr virus (EBV) as an etiologic agent. EBV latent genes are expressed in the neoplastic Hodgkin/Reed-Sternberg (HRS) cells in approximately 30 to 50% of classical HL cases, with the mixed cellularity (MC) subtype expressing EBV DNA in up to 70% of cases. Several epidemiologic studies support evidence of a 10-fold higher risk of HL among HIV-infected persons compared with HIV-negative persons. This excess risk is most pronounced in individuals with moderate immunosuppression, which is in sharp contrast to the pattern demonstrated in HIV-associated non-Hodgkin’s lymphoma. Clonal EBV genomes have been demonstrated in 80 to 100% of HIV associated HL tissues.

What laboratory studies should you order to help make the diagnosis and how should you interpret the results?

An excisional lymph node biopsy is usually required to obtain the diagnosis of HL, rarely an extranodal site of involvement is biopsied for definitive diagnosis. With rare exceptions, needle biopsies should not be used as the sole means of diagnosis. The presence of Hodgkin/Reed-Sternberg cells (HRS) admixed in a background of inflammatory cells is required for a diagnosis of classical HL.

HRS cells are positive for CD30 in nearly all cases, CD15+ in 75 to 85% of cases, and usually negative for CD45. CD20 is variably expressed and frequently only present in a minority of the cells. NLPHL is characterized by the presence of large neoplastic cells, called popcorn or lymphocyte predominant (LP) cells, intermingled among a diffuse infiltrate predominantly of small lymphocytes and histiocytes.

Immunohistochemistry can distinguish classical HL from NLPHL when morphology is unclear, as LP cells express CD20 and lack CD15 and CD30 in most instances. Bilateral bone marrow biopsies are recommended for patients with stage III/IV disease, and for any patient with presence of B symptoms. This test is optional in patients with early stage disease, due to the low incidence of bone marrow involvement.

Necessary laboratory tests include a complete blood count (CBC) with differential, comprehensive metabolic panel with particular attention paid to the alkaline phosphatase, albumin and calcium levels, and an erythrocyte sedimentation rate (ESR). Knowing the white blood cell (WBC) count, absolute lymphocyte count, hemoglobin, albumin, and ESR in advance of initiating treatment, is important for predicting response to therapy. Elevated alkaline phosphatase, while common, does not necessarily predict liver or bone involvement. Testing for HIV is indicated in patients with known risk factors and in patients with unusual disease presentations.

What imaging studies (if any) will be helpful in making or excluding the diagnosis of Hodgkin lymphoma?

Imaging studies are helpful in suspected cases of HL, though never make or exclude the diagnosis. Classical HL almost always causes mass lesions in the centriaxial lymph nodes and usually spreads in a contiguous pattern. Most often the involvement is in the supradiaphragmatic nodes (90%). When extranodal involvement occurs, it most commonly involves the liver, bone, lungs, and bone marrow. In patients with extensive mediastinal involvement, direct extension to the chest wall, pericardium, or pleura is often present. Spread to distant organs is almost always preceded by splenic involvement.

Imaging studies are essential for staging patients once a diagnosis of HL is established. Chest radiographs (CXR), previously relied upon for assessing mediastinal bulk, have now been replaced by chest computed tomography (CT) and/or positron emission tomography (PET)/CT. The differences in the ability to measure mediastinal disease between a CXR and CT are negligible, and CT is typically considered sufficient. Bulky mediastinal disease on chest CT is defined as the thoracic ratio of the maximum transverse mass diameter, greater than or equal to 0.35 of the internal transverse thoracic diameter, or a mass measuring greater than or equal to 10 cm .

CT has been largely supplanted by PET/CT for staging patients, though frequently CT is the first test obtained in the work-up of a patient. PET/CT has proven quite useful in monitoring response to therapy, and having a baseline scan is helpful in this regard. In the rare cases when CT alone is obtained, scanning the chest, abdomen, and pelvis is required to fully stage the patient. A CT of the neck likely adds little to a thorough physical examination and is usually only necessary if radiation is planned.

If you decide the patient has Hodgkin lymphoma, what therapies should you initiate immediately?

Oncologic emergencies rarely occur in HL and usually there is adequate time to complete a thorough work-up of the patient. For those who present with symptomatic mediastinal disease, SVC syndrome, large pleural or pericardial effusions, or spinal cord compression, prompt initiation of therapy is indicated. In nearly all circumstances, the optimal treatment is with chemotherapy, rather than radiotherapy. Chemotherapy typically works faster and treats the entire disease burden, in contrast to radiation.

For patients with known cardiac or pulmonary disease, measurement of the ejection fraction and the diffusing capacity of the lung for carbon monoxide (DLCO) is indicated, respectively. The likelihood of cardiac and pulmonary complications without risk factors is otherwise low.

Fertility discussions should be initiated prior to starting treatment. When feasible, sperm cryopreservation for interested males should be arranged. Typically, a sexually transmitted infection work-up (for example, HIV, hepatitis B/C, and syphilis) is required prior to acceptance of cryopreserved samples. Ovarian tissue or oocyte cryopreservation for interested females can be discussed, though is frequently not feasible given the lack of insurance coverage and the significant delay required prior to starting definitive treatment. Adriamycin/bleomycin/vinblastine/dacarbazine (ABVD) chemotherapy is associated with a low risk of infertility (less than 3 to 4%); therefore, these approaches will be unnecessary in the majority of patients with HL, especially those with early stage, favorable disease.

More definitive therapies?

Treatment of HL is largely dictated by the patient’s stage and risk factors at the time of presentation.

Refer to Table II for the most commonly used chemotherapy regimens.

Table II.
Chemotherapeutic Regimens

Early stage favorable

In the United States, “favorable” HL is defined as the absence of bulky disease. The German Hodgkin Study Group (GHSG) and European Organization for Research and Treatment of Cancer (EORTC) have unique definitions for favorable and unfavorable early stage HL, as outlined in Table III.

Table III.
Early stage Hodgkin lymphoma prognostic groups

Current treatment strategies are aimed at minimizing toxicities in patients with favorable, early stage HL. Combined modality therapy with four cycles of Adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) and involved field radiotherapy (IFRT) has been the standard approach for patients with early stage HL. More recently, two cycles of chemotherapy, followed by reduced IFRT (20 Gy) has been demonstrated to cure greater than 90% of patients with favorable early stage HL, as defined by the GHSG. Studies are ongoing to determine whether IFRT can be eliminated entirely.

Early stage unfavorable

In the United States, unfavorable HL is defined by the presence of bulky disease (Table I). At least 75% of patients with early stage unfavorable HL are cured with combined modality therapy with 4 to 6 cycles of ABVD followed by 30 Gy IFRT. In a GHSG trial, superior results were demonstrated with 2 cycles of escalated BEACOPP (bleomycin/etoposide/doxorubicin/cyclophosphamide/vincristine/procarbazine/prednisone) followed by 2 cycles of ABVD and 30 Gy IFRT compared with 4 cycles of ABVD and 30 Gy IFRT. The estimated 4 year freedom from treatment failure was 95% compared with 89%, with no difference in overall survival.

While the study arm was more toxic, no difference in treatment related deaths or secondary neoplasia rates were demonstrated between the treatment arms. A United States cooperative group study evaluated whether IFRT can be safely eliminated in patients who obtain a complete response on PET/CT following the first 2 cycles of ABVD. Preliminary results show that more than 90% of these patients will remain without progression for 3 years.

Advanced stage

The current standard of care for advanced stage HL is with 6 cycles of ABVD, which will cure approximately 70% of patients. Escalated BEACOPP will cure nearly 85% of patients but at the cost of nearly uniform sterility and a 3 to 4% incidence of secondary leukemias. Current approaches under investigation include switching from ABVD to escalated BEACOPP in patients who do not achieve a complete response based on early interim PET/CT, following 2 cycles of ABVD.

Brentuximab vedotin (BV), an antibody-drug conjugate targeting CD30, was FDA (Food and Drug Administration) approved in 2011 for patients failing either two prior regimens or an ASCT. Seventy five percent of patients treated with BV on a phase II study responded (including 34% complete responses), and the median duration of response was over 6 months. A phase I study of BV + ABVD or AVD in previously untreated patient with advanced stage HL has been completed. Excess pulmonary toxicity was seen in the bleomycin-containing arm. The CR rate was 95% in both arms and 46 of 48 patients had negative PET/CT scans after 2 cycles of therapy. Based on these findings, an international, phase III randomized study is underway comparing ABVD versus BV+AVD.

Second line

The standard therapy for relapsed HL is with high dose chemotherapy, followed by autologous stem cell transplant (ASCT). Approximately 40 to 50% of patients will be cured with an ASCT. Salvage regimens, such as ICE (ifosfamide, carboplatin, and etoposide) or ESHAP (etoposide, solumedrol, high dose cytarabine, and cisplatin) are administered to reduce tumor burden prior to ASCT.

ASCT is most effective in patients with chemosensitive disease, highlighting the importance of achieving a response to the salvage chemotherapy. A phase III study demonstrated an improvement in progression free survival for BV for maintenance compared with placebo following ASCT for patients with high-risk disease defined as a relapse within 12 months or in extranodal sites.

Patients who experience disease progression on salvage chemotherapy should be treated with alternative non-cross resistant regimens, single agent drugs, or clinical trials. Patients with relapsed disease after an ASCT can often survive for months or even years, especially in those whose initial remission was greater than 12 months. A subset of patients who fail an ASCT may be cured with a reduced intensity allogeneic transplant.

Several recent important studies using PD-1 (programmed death ligand -1) inhibitors in HL have been published. HL is ideally suited to this approach as the Hodgkin Reed Sternberg cell harbors near uniform upregulation of chromosome 9p24 which encodes PDL-1 and PDL-2 (programmed death ligands 1 and 2). In patients with relapsed/refractory disease who failed brentuximab and the majority of whom progressed after autologous transplant, the overall response rate for both nivolumab and pembrolizumab was approximately 65%. Nivolumab has been FDA approved in this setting. Multiple on-going studies are evaluating the use of these agents in combination in both the upfront and relapsed settings.

Management of NLPHL

Patients with early stage NLPHL are often treated with IFRT alone. For the rare patient with advanced stage disease, treatment with rituximab and combination chemotherapy is indicated. Options include CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), CVP (cyclophosphamide, vincristine, and prednisone), and ABVD. Relapses tend to occur at distant sites from the original regions of involvement at presentation, and repeat treatment with IFRT is generally feasible. NLPHL is associated with a small risk (less than 3%) of transformation to non-Hodgkin’s lymphoma.

What other therapies are helpful for reducing complications?

ABVD should be administered at full dose on schedule regardless of the absolute neutrophil count (ANC). Outcomes are negatively impacted by dose reductions and delays, highlighting the importance of maintaining dose intensity and dose duration. Typically, WBC stimulating growth factors are unnecessary with standard ABVD, except in immunosuppressed patients (for example, post-transplant lymphoproliferative disorders and HIV-associated HL). The incidence of febrile neutropenia is very low with standard ABVD chemotherapy.

Symptom management is of utmost importance to ensure optimal quality of life. Notable achievements have been made in the prevention and treatment of chemotherapy-induced nausea and vomiting. ABVD is considered to be a moderate to highly emetogenic regimen. Patients should be pre-medicated with a serotonin (5-HT3) antagonist and a steroid, and consideration should be given for a neurokinin 1 antagonist, especially in those patients who are predisposed to nausea (for example, young women, history of motion sickness, history of morning sickness with pregnancies). Patients are provided with prescriptions for antiemetics, such as prochlorperazine and lorazepam, to take as needed at home.

Treatment with vinblastine can lead to autonomic and peripheral neuropathy. Constipation is a common side effect from vinblastine which can be prevented with an aggressive bowel regimen. The severity of peripheral neuropathy can be curtailed by diligent monitoring. The dose should not be decreased, unless a patient develops grade 2 or greater motor neuropathy. The neuropathy is typically transient and neuropathic pain can be effectively treated with gabapentin or pregabalin.

Bleomycin pulmonary toxicity has been well-described in patients treated with ABVD. It frequently presents as a pneumonitis and rarely progresses to a fibrosis, which can be fatal. Suggested risk factors for the development of bleomycin pulmonary toxicity include advanced age, smoking history, bleomycin dose, underlying lung disease, and granulocyte colony-stimulating factors. Treatment includes discontinuation of bleomycin and administration of corticosteroids. Assessing for pulmonary symptoms prior to every cycle of chemotherapy and withholding bleomycin until a CXR is obtained to evaluate for bilateral interstitial infiltrates if symptoms develop, are crucial steps to prevent development.

HL survivors, particularly those patients who receive radiation, are at increased risk for various health problems, including heart disease, thyroid dysfunction, impaired immunity, and second cancers, underscoring the need for continued medical management with particular emphasis on prevention and screening. Cardiovascular disease is the most common non-malignant cause of death among long-term survivors. Most of the increased risk is accounted for by patients who have one or more known cardiac risk factors, such as hypertension, hypercholesterolemia, or smoking history.

Current guidelines focus on management of the cardiac risk factors and recommend annual blood pressure, serum glucose, and lipid panels. Obtaining a baseline stress test/echocardiogram at 10 years after treatment is also appropriate. Up to 50% of patients treated with radiation therapy may develop hypothyroidism, with approximately half of cases occurring within 5 years. Annual evaluation of thyroid stimulating hormone (TSH) is recommended to detect subclinical hypothyroidism and if the TSH is elevated, then a full panel should be obtained to determine the degree of compensation.

Patients with HL have impaired immunity and should receive annual influenza vaccinations. Women treated with chest radiation before the age of 25 have an estimated cumulative absolute risk for developing breast cancer of 30% by age 55. Annual mammography and breast MRI is recommended starting 8 to 10 years following mediastinal radiation in women treated between 10 and 30 years of age. Patients with HL are at increased risk for lung cancer, particularly older patients (greater than 40 years old) and smokers who were treated with alkylating agents or chest radiation. Consideration should be given to annual screening after 5 years, with low dose spiral chest CT.

What should you tell the patient and the family about prognosis?

Nearly 80% of patients will be cured of HL. From the onset, the goal of therapy is always cure, even for patients with advanced stage disease and poor prognostic features. The response rates and mortality rates are largely influenced by stage, the number of favorable or unfavorable (poor risk) features that a patient has at the time of diagnosis, as well as the response to the initial treatment.

See Table IV for the International Prognostic Score (IPS) for advanced stage disease. In a recent evaluation of the IPS, the 5 year freedom from progression rates, are 66 to 86% depending on the number of risk factors. The vast majority of relapses (80 to 90%) occur within the first two years after diagnosis. HL survivors still have a five-fold higher incidence of mortality, compared with normal controls, largely secondary to the increased risk of secondary cancers and cardiovascular disease, which are mostly linked to latent effects from radiation. After 15 years, the actuarial risk of death from other causes surpasses deaths due to HL. This has serious implications for both attempting to limit these toxicities and for monitoring for late complications of therapy.

Table IV.
The International Prognostic Score for Hodgkin Lymphoma

In contrast to CHL, NLPHL is associated with a continuous rate of relapse even beyond 10 years, with 5 and 10 year progression-free survival rates of 75% and 60%, respectively. However the prognosis of patients with NLPHL is typically better than that of patients with CHL. This is likely related to the distribution of disease stage, since most patients present with early stage disease and lack poor prognostic features. Overall survival at 5 and 10 years is approximately 95 and 90%, respectively. Of those who die, most die from complications of therapy or development of non-Hodgkin lymphoma (NHL), underscoring the need for long-term follow-up.

What if scenarios.

The vast majority of patients with HL are cured with standard treatment approaches, though 20% of patients ultimately succumb to the disease and a similar percentage of patients are overtreated. One of the greatest challenges is identifying prognostic markers that will allow for tailoring of therapy such that treatment can be maximized in those with a high risk of failure, and reduced in the most favorable subsets.

If from the onset, one could predict who would fail standard ABVD, then the tradeoff of switching to a more toxic but effective regimen, such as escalated BEACOPP, would be valuable. Likewise, if one could predict who would not benefit from radiation, then sparing the long-term toxicities, while recognizing that the failure rate may be slightly increased, would similarly be justified. Whether an early-interim PET, following two cycles of chemotherapy will be predictive in this regard is still under investigation. The high negative predictive value appears quite consistent across several studies, which are mostly retrospective, though the positive predictive value has been less reliable, with 2 year progression free survival rates ranging from 10 to 60% for advanced-stage patients with a positive scan following two cycles of ABVD.

Prospective studies of risk-adapted approaches utilizing the results of early interim PET, are currently being explored in the United States, Canada, and Europe. Results are anxiously anticipated to help guide these challenging decisions.

Common management problems
  • A patient presents for cycle 2, day 1 of ABVD with an ANC of 400

Treatment should proceed on time regardless of the ANC. The incidence of febrile neutropenia with ABVD is low (less than 3%). Studies have demonstrated that dose intensity can be maintained without the use of WBC stimulating factors.

  • A patient presents for cycle 3 of ABVD complaining of a one week history of a dry cough

New onset of a cough in a patient receiving ABVD is concerning for the development of bleomycin associated pulmonary toxicity. Treatment with bleomycin should be held until a CXR is obtained to rule out presence of interstitial infiltrates. Obtaining pulmonary function tests (PFTs) may be useful as well. As long as the CXR is clear, treatment can proceed and the patient’s symptoms should be followed closely. CXR can be normal in the setting of significant changes on DLCO. If the CXR reveals findings concerning for bleomycin toxicity, or if the DLCO has decreased substantially (less than 60%) , the bleomycin should be discontinued for all subsequent cycles. Steroids should be initiated for the management of the pneumonitis. If the cough persists for greater than 2 weeks despite a negative CXR, consider evaluation with a thin section chest CT and/or pulmonary function tests (PFTs), or consider empiric discontinuation of bleomycin.

  • A patient presents for cycle 2 of ABVD with complaints of severe arm pain, but a negative physical examination

This complaint is usually related to a chemical phlebitis from dacarbazine (DTIC). Consideration should be made for placing an indwelling central venous catheter. The discussion should emphasize the increased risk of catheter-associated venous thromboses and infections associated with portacath placement. The likelihood of recurrent phlebitis is actually quite low. In the majority of our patients undergoing ABVD chemotherapy, we favor using peripheral IV access.

  • A patient with bulky stage II disease has a positive PET/CT at the completion of six cycles of ABVD

Typically, a biopsy is recommended to confirm the presence of refractory disease. In this patient with bulky disease, there is a role for involved field radiotherapy, but whether this should be administered as the next treatment versus as consolidation following ASCT, is less clear.


HL is a monoclonal B cell disorder. Clonal immunoglobulin gene rearrangements are present in the HRS cells of CHL and the LP cells of NLPHL. The HRS cells compose only a minority of the cellular makeup in HL, with the vast majority of the cellular population consisting of reactive cells, such as lymphocytes, macrophages, stromal cells, eosinophils, and mast cells. The most abundant cells are CD4+ T cells.

It has become increasingly evident that the microenvironment plays a key role in the proliferation of HRS cells. Soluble factors, including cytokines and chemokines, facilitate crosstalk between the HRS cells and the microenvironment, thereby controlling the cellular milieu and the replication and antiapoptotic phenotype of HRS cells. HRS cells also appear to use their microenvironment to escape from host immune surveillance.

Learning about the microenvironment has provided insight into biologic prognostic factors in HL. To date, none of the biomarkers have been incorporated into clinical practice, largely because of a lack of reproducibility. More recently, gene expression profiling has identified signatures, including cytotoxic T lymphocytes, background reactive B lymphocytes, and tumor associated macrophages, associated with treatment outcome, that have since been validated by immunohistochemistry (IHC). High expression of CD68, a macrophage marker that can be assessed by IHC, correlates with reduced progression-free and overall survival. Knowledge of the microenvironment and the altered immune surveillance, along with the dysregulated pathways involved, will continue to provide insight into biologic targets and therapies in HL.

What other clinical manifestations may help me to diagnose Hodgkin lymphoma?

Uncommonly, HL can present with unusual symptoms. Atypical presentations occur more frequently in the elderly and in patients with HIV infection. Inquiring about HIV risk factors is important when obtaining a medical history. Bone marrow biopsy and/or liver biopsy should be considered in older patients with recurrent fevers and negative CT scans, as “occult CHL” may occur in these sites.

If the disease is localized in the mediastinum, a patient may not seek medical attention until chest pain or a cough develops. Similarly disease confined to the retroperitoneum, as is occasionally seen in older patients with HL, may present with abdominal or back pain. B symptoms occur in approximately 35% of patients, and are present more frequently in older patients and in those with HIV. Pruritus occurs infrequently (less than 5%) and has no prognostic significance. Alcohol-related pain in the sites of involvement is rare, with an incidence of less than 2%.

The most common presentation is with cervical or supraclavicular lymphadenopathy. Patients with extensive disease may have multiple nodal chains involved, along with splenomegaly. A small percentage of patients will present with an excoriated rash secondary to pruritus. Rarely patients will present with SVC syndrome, pericardial tamponade, neurologic complaints secondary to spinal cord compression, or unusual symptoms associated with paraneoplastic syndromes.

What other additional laboratory studies may be ordered?

During the course of treatment, a CBC, comprehensive metabolic panel, and ESR are frequently obtained to monitor for response and for any side-effects of the chemotherapy.