Question:

A 28-year-old man comes to the office for follow-up. Two years ago, he was diagnosed with early-stage nodular sclerosis Hodgkin lymphoma after a chest x-ray revealed a mediastinal mass. The patient underwent combination chemotherapy and radiation treatment. Follow-up imaging has revealed no evidence of disease, and he currently feels well. The patient has no other medical conditions and takes no medications. He does not use tobacco, alcohol, or illicit drugs. Vital signs and physical examination are normal. Compared to the general population, this patient is at greatest risk for which of the following?

Diabetes mellitus

Osteoporosis

Primary sclerosing cholangitis

Rheumatoid arthritis

Solid organ malignancy

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Explanation:

Patients with Hodgkin lymphoma (HL) are generally treated with combination chemotherapy and radiation therapy, which cures >75% of cases. However, these treatments are associated with serious long-term complications, including:

Secondary malignancy: Radiation exposure increases the risk of solid organ (eg, breast, lung) malignancy, and chemotherapy increases the risk of hematologic malignancy. Most cases arise >5 years after treatment. Secondary malignancies are the leading cause of death in those who have been cured of HL.
Cardiovascular disease: Risk of coronary artery disease, valve damage, peripheral vascular disease, and cardiomyopathy are increased in those who have been treated for HL. Cardiovascular disease is the leading nonmalignant cause of death in long-term HL survivors.

Other common treatment-related complications include pulmonary disease (eg, fibrosis, bronchiectasis) and hypothyroidism from chest radiation and neuropathy from chemotherapy.

(Choice A) Survivors of HL do not have an increased risk of diabetes mellitus (DM). However, patients who have concomitant DM are at increased risk for cardiovascular complications of treatment.

(Choice B) Early osteoporosis is often seen in those who take glucocorticoids, anticonvulsants, and antidepressants; risk is also increased in those who have disorders of calcium metabolism due to inflammatory bowel disease, celiac disease, hyperthyroidism, and hyperparathyroidism. It is not linked to treatment for HL.

(Choice C) Primary sclerosing cholangitis often occurs in patients with ulcerative colitis (and to a lesser extent, Crohn disease). It is not linked to treatment for HL.

(Choice D) Rheumatoid arthritis can increase the risk of developing lymphoma due to chronic immune activation and treatment with alkylating agents (eg, azathioprine, methotrexate). However, lymphoma does not increase the risk of developing rheumatoid arthritis.

Educational objective:
Hodgkin lymphoma is generally treated with combination chemotherapy and radiation therapy. Although >75% of patients are cured, treatment can lead to long-term complications, most notably secondary malignancy (eg, solid organ, hematologic) and cardiovascular disease.