Lymphoma,  Hodgkin

HL may occur at any age but is generally a disease of young adults. Although it can be seen across the age spectrum, the median age is 39, and it is most frequently seen in the group 20-34 years of age. Incidence rate have stayed flat for several decades, but fortunately, mortality rates have steadily declined, from 1.3 cases per 100,000 in 1975 to 0.3 cases per 100,000 in 2014. Over this period, the 5-year survival has improved from 70% to 85%.

In HL, the cancer cells form only a small fraction of the tumor, surrounded by a reactive inflammatory background consisting of lymphocytes, eosinophils, neutrophils, histiocytes, and plasma cells. The malignant cells are multinucleate giant cells or large mononuclear cells and are referred to as Hodgkin and Reed-Sternberg (HRS) cells. It is the pattern of the lymphocytic infiltrate that determines the classic subtypes of HL. HL is subdivided into classical and nodular lymphocyte-predominant HL, with the latter having a more indolent biology. Classical HL is further subdivided into four histologic subtypes based on morphology, the abundance of HRS cells, and the background infiltrate (Table 47–7).

The cause of HL is not well understood; however, epidemiologic studies have revealed certain patterns of disease clustering. The incidence appears to be higher with a lower number of siblings, early birth order, siblings with HL, a decreased number of playmates, certain HLAs, single-family dwellings, and patients who have undergone tonsillectomy. The incidence is increased also in persons with immunodeficiencies and autoimmune disorders. This pattern suggests that an oncogenic virus may cause HL. Epstein-Barr virus (EBV) is detected in HRS cells in a majority of HL specimens from the developing world; however, this is less frequent in North America and Western Europe.

Most patients present with enlarging but painless lymph nodes, often in the lower neck or supraclavicular region. Mediastinal involvement is common; however, these nodes can grow quite large before a diagnosis is made, either secondary to symptoms (cough or dyspnea) or routine chest x-ray. About 25% of patients will have systemic symptoms, called B symptoms, including weight loss, fever, and drenching night sweats. Both bulky mediastinal disease (> 10 cm) and B symptoms are associated with a poorer prognosis. Some patients will present with pruritis without obvious skin pathology and resistant to topical agents. This can sometimes be a clue to clinically occult HL.

Staging

For many years, the Ann Arbor staging system had been used to stage HL; however, this was based on interventions such as bone marrow biopsy or staging laparotomy (splenectomy, wedge liver biopsy, and dissection of the para-aortic, iliac, splenic hilar, and hepatic portal lymph nodes) that were commonly used. Today, with the advent of fluorodeoxyglucose (FDG) positron emission tomography (PET)- CT, the staging system has changed accordingly. The Deauville scale established a consensus on simple, reproducible criteria for PET interpretation. The most modern staging system for both HL and NHL today is the Lugano classification (Table 47–8). This classifies patients as having limited or advanced disease based on histology and other prognostic factors.

Treatment

HL has changed from a uniformly fatal disease to one that is curable in the majority of patients with the advent of combination chemotherapy and radiation. Today, the 5-year relative survival for patients under 19 years of age is 96.4%, and for patients between 20 and 64 years, it is 89.9%.

Treatment is guided by both the stage of disease as well as stratification into favorable and unfavorable prognostic factors. Because many patients were more likely to die from long-term complications of the treatment than the lymphoma itself, the focus has been to minimize the risks of therapy while maintaining the excellent outcomes. For early-stage classical HL, chemotherapy consists of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) and involved-field radiation. Increasingly, select patients with an excellent response on PET after chemotherapy may be spared the radiation. Patients with early classical HL with unfavorable prognostic features may require additional cycles of ABVD in combination with either involved-field radiotherapy or extended-field radiotherapy.

Although ABVD remains the standard regimen for advanced classical HL, an intensified seven-drug combination of escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) is also an option. A multivariate analysis comparing escalated BEACOPP versus ABVD showed a significant benefit to progression-free survival and a small but significant overall survival benefit with BEACOPP, but with greatly increased toxicity. The response rates, toxicity, and patient comorbidities must be weighed when deciding on a regimen, and ABVD remains the most commonly used regimen in the United States.

Although most patients with classical HL are cured with first-line therapy, significant percentages of patients either fail to respond (refractory disease) or relapse. In this case, salvage therapy typically involves an alternate chemotherapy regimen. High-dose chemotherapy and autologous hematopoietic cell transplantation (HCT) should be considered for patients with early relapse (within 12 months), second relapse, or a generalized systemic relapse, even after 12 months. For patients who fail this approach or are not candidates for high-dose chemotherapy with HCT, there are unfortunately few good treatment options. These patients should consider clinical trials of newer approaches, such as antibody-drug conjugates or immunotherapy.

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• Study Questions

 

 

The patient in this image has which of the following conditions?

A

An infection with cytomegalovirus

B

An infection with herpes simplex virus

C

The nodular sclerosis variant of Hodgkin lymphoma

D

Burkitt lymphoma

The correct answer is C.

Explanation:

In the center of the image is a Reed-Sternberg cell, which is characteristic of Hodgkin lymphoma.