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Hodgkin's disease

Hodgkin's lymphoma, formerly known as Hodgkin's disease, is a type of lymphoma described by Thomas Hodgkin in 1832, and characterized by the presence of Reed-Sternberg cells. more...

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Epidemiology

Unlike other lymphomas, whose incidence increases with age, Hodgkin's lymphoma has a bimodal incidence curve: that is, it occurs more frequently in two separate age groups, the first being young adulthood (age 15-35), the second being in those over 50 years old. Overall, it is more common in males, except for the nodular sclerosis variant (see below) of Hodgkin disease, which is more common in women.

The incidence of Hodgkin's disease is about 4/100,000 people/year, and accounts for a bit less than 1% of all cancers worldwide.

Symptoms

Swollen, but non-painful, lymph nodes are the most common sign of Hodgkin's lymphoma, often occurring in the neck. The lymph nodes of the chest are often affected and these may be noticed on a chest X-ray.

Splenomegaly, or enlargement of the spleen, occurs in about 30% of people with Hodgkin's lymphoma. The enlargement, however, is seldom massive. The liver may also be enlarged due to liver involvment in the disease in about 5% of cases.

About one-third of people with Hodgkin's disease may also notice some systemic symptoms, such as low-grade fever, night sweats, weight loss, itchy skin (pruritis), or fatigue. Systemic symptoms such as fever and weight loss are known as B symptoms.

Diagnosis

Hodgkin's lymphoma must be distinguished from non-cancerous causes of lymph node swelling (such as various infections) and from other types of cancer. Definitive diagnosis is by lymph node biopsy (removal of a lymph node for pathological examination). Blood tests are also performed to assess function of major organs, to detect lymphoma deposits or to assess safety for chemotherapy. Positron emission tomography is used to detect small deposits that do not show on CT scanning.

Pathology

Macroscopy

Affected lymph nodes (most often, laterocervical lymph nodes) are enlarged, but their shape is preserved because the capsule is not invaded. Usually, the cut surface is white-grey and uniform; in some histological subtypes (e.g. nodular sclerosis) may appear a nodular aspect.

Microscopy

Microscopic examination of the lymph node biopsy reveals complete or partial effacement of the lymph node architecture by scattered large malignant cells known as Reed-Sternberg cells (typical and variants) admixed within a reactive cell infiltrate composed of variable proportions of lymphocytes, histiocytes, eosinophils, and plasma cells. The Reed-Sternberg cells are identified as large often binucleated cells with prominent nucleoli and an unusual CD45-, CD30+, CD15+/- immunophenotype. In approximately 50% of cases, the Reed-Sternberg cells are infected by the Epstein-Barr virus.

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Thyroid nodules and survivors of Hodgkin's disease - Letter to the Editor
From American Family Physician, 9/15/03 by Kevin C. Oeffinger

TO THE EDITOR: The article, "Thyroid Nodules," (1) was well written and concise. However, the list of "red flags" for thyroid cancer listed in Table 2 needs to be expanded to include an additional risk group. The item, "history of radiation to the head or neck" also should include chest or mantle radiation. At particular risk for this radiation exposure are survivors of Hodgkin's disease.

Hodgkin's disease is the most common cancer diagnosed in persons 15 to 19 years of age, and is the third most common cancer for all pediatric ages, zero to 19 years. (2) Radiation therapy involving the chest or mantle area has been used in the treatment of Hodgkin's disease for decades. Standardized anatomic treatment fields, combined with the establishment of a curative dose range, produced the first cures in patients with Hodgkin's disease. Radiation treatment regimens used through the 1980s primarily prescribed doses of 35 to 44 Gy to extended fields for localized disease (stage I or IIA).

Concerns about growth impairment led to clinical trials designed to specifically address the needs of children with Hodgkin's disease. These protocols evaluated lower radiation doses (15 to 25.5 Gy) to reduced treatment fields combined with multi-agent chemotherapy. Many reports implicating radiation as a causative factor for excess cardiovascular disease and subsequent malignancy risk in long-term survivors of childhood Hodgkin's disease motivated further therapeutic refinements in the 1990s. The use of standard-dose, extended-field radiation in mature adolescents with localized Hodgkin's disease has been abandoned at most centers, because this treatment approach predisposes patients to a greater risk of cardiovascular disease and secondary solid tumor carcinogenesis. Contemporary risk-adapted treatment protocols have focused on further limiting radiation exposure of uninvolved tissues, especially the breast, and identifying patients for whom the addition of radiation optimizes disease-free survival.

The Childhood Cancer Survivor Study, (3) a 26-institution retrospective cohort study following almost 14,000 long-term survivors of childhood cancer diagnosed between 1970 and 1986, highlighted the risk of thyroid cancer following treatment for Hodgkin's disease. A cohort of 1,791 long-term survivors of Hodgkin's disease, diagnosed before the age of 21 years, were analyzed. The median age at diagnosis was 14 years and was 30 years at follow-up. From this relatively young population, 20 patients were diagnosed with thyroid cancer. Fifteen had received previous radiation therapy for their Hodgkin's disease, one had not, and treatment records were unavailable for the remaining four. The relative risk for thyroid cancer was 18.3 for all Hodgkin's survivors. Since that report, the number of new cases of thyroid cancer in the study's cohort has increased. A nested case-control study of 72 survivors with thyroid cancer as a second malignancy, including 30 Hodgkin's survivors, is underway to determine the attributable excess risk related to radiation.

As risk-adapted therapy for Hodgkin's disease continues to evolve, it is important that clinicians recognize the significant increase in risk of thyroid cancer following mantle radiation. Annual examination and palpation of the neck and thyroid gland are recommended for all survivors of Hodgkin's disease who were treated with mantle or chest radiation, regardless of the dose amount. (3)

REFERENCES

(1.) Welker MJ, Orlov D. Thyroid nodules. Am Fam Physician 2003;67:559-66.

(2.) SEER Program (National Cancer Institute [U.S.]). Cancer incidence and survival among children and adolescents: United States SEER Program, 1975-1995. Bethesda, Md.: National Cancer Insitute, 1999; NIH Publication No. 99-4649.

(3.) Sklar C, Whitton J, Mertens A, Stovall M, Green D, Marina N, et al. Abnormalities of the thyroid in survivors of Hodgkin's disease: data from the Childhood Cancer Survivor Study. J Clin Endocrinol Metab 2000;85:3227-32.

EDITOR'S NOTE: This letter was sent to the authors of "Thyroid Nodules," who declined to reply.

KEVIN C. OEFFINGER, M.D.

The University of Texas Southwestern Medical Center at Dallas

6263 Harry Hines Blvd.

Dallas, TX 75390-9067

CHARLES A. SKLAR, M.D.

1275 York Ave.

Memorial Sloan-Kettering Cancer Center

New York, NY 10021

MELISSA M. HUDSON

332 N. Lauderdale

St. Jude's Children's Research Hospital

Memphis, TN 38105

COPYRIGHT 2003 American Academy of Family Physicians
COPYRIGHT 2003 Gale Group

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