Patient information: Features and diagnosis of Hodgkin's disease INTRODUCTION — Hodgkin's disease (HD), also known as Hodgkin's lymphoma, is a form of malignant lymphoma, a type of cancer of the body's lymphatic system. It is a disease in which tumors typically arise in the tissue of the lymph nodes and then spread in an orderly fashion to other lymph nodes, the spleen, liver, and bone marrow. Few risk factors have been convincingly identified, other than those related to exposure to certain viruses and abnormalities of immune function. The incidence, age and sex distribution, and form and structure of HD vary in different populations according to geographic location, socioeconomic status, and immunologic status. Age — Hodgkin's disease is more common in persons during in their 20s and those over age 50. The majority of patients are young adults. Approximately 7500 new cases of HD, and about 1500 deaths due to HD occur in the United States annually. Younger patients have better rates of survival at five years than older patients: 88 percent for patients younger than 45 at diagnosis, 77 percent for those 45 to 54, 67 percent for those 65 to 74, and 38 percent for those 75 and older. Geography and socioeconomic status — There are subtypes of HD that occur in different parts of the world with varying levels of socioeconomic status; these subtypes reflect the different settings in which the tumor cells grow. One of these, the nodular sclerosis (NS) subtype, is the predominant subtype in developed countries, and occurs in children and in middle and older adulthood. In developing countries, HD is most common during childhood for boys and also in older adults; there are relatively low rates in young adults. The subtype of HD that occurs most often in developing countries is mixed cellularity (MC). Role of infectious agents — It is thought that infectious agents, such as viruses, may have a role in triggering the development of Hodgkin's disease. In fact, the association of socioeconomic status with the risk of HD is believed to reflect exposure to a common virus. In other words, people who live in the same area are exposed to the same viruses and will have a similar risk of developing HD from these agents. It is unclear which specific viruses cause HD, but a number of studies have suggested that the Epstein-Barr virus (EBV), the virus that causes infectious mononucleosis ("mono"), may play a role. The highest risk period for developing HD seems to be 5 to 9 years after the diagnosis of mononucleosis. Tumor cells are infected by EBV in 40 to 50 percent of cases of classical HD. Causes other than EBV may also be responsible for Hodgkin's disease in young adults. Genetic factors — Overall, the increased risk of HD in close relatives of patients with HD is about three- to five-fold the expected rate, possibly because of genetic susceptibility and environmental exposure. There is a seven-fold increased risk among siblings of younger adults with HD and the risk in identical twins is increased about 100-fold. Increased risks are not seen in the families of older adults with HD. DIAGNOSIS — The diagnosis of HD is based upon a patient's history and physical examination, a tissue biopsy, laboratory studies, and imaging studies. The initial evaluation provides important information about prognosis, staging, and the selection of treatment. History and physical examination — The healthcare provider will ask about symptoms associated with HD, such as unexplained fever, sweating (particularly at night), weight loss, itchiness, and alcohol-induced pain. Other important points to discuss include a history of previous cancer (including other lymphomas), prior treatment with chemotherapy or radiotherapy, immune system status (eg, organ transplant or AIDS), and a family history of Hodgkin's disease or other lymphoproliferative, myeloproliferative, or tissue malignancies. A careful and complete physical examination must be performed by a physician experienced in the management of patients with Hodgkin's disease. Special attention will be directed to the areas in which lymph-node enlargement commonly occurs and the number of sites involved should be noted. Most patients diagnosed with HD have enlarged lymph node or a mass on chest x-ray. The size of the liver and spleen will also be noted. Tissue biopsy — If the history and physical exam suggests HD, most providers recommend removal and examination of an enlarged lymph node. Lymph nodes in the groin region are avoided if suspicious nodes are present elsewhere. When the diagnosis of HD is made from biopsy of a site other than a lymph node, the physician will sometimes confirm the diagnosis by performing a lymph node biopsy. Bone marrow biopsy — Patients with malignant cells in the bone marrow is often associated with an advanced stage of HD; it occurs in less than 1 percent of patients with early stage disease. Testing is done with a bone marrow biopsy. However, bone marrow biopsy usually does not affect therapy, especially among patients with advanced disease. Bone marrow biopsy is recommended for patients with newly diagnosed HD if they have one or more of the following characteristics:
Laboratory studies — Once the diagnosis of Hodgkin's disease is established by biopsy, further studies should be performed:
Although the results of these tests may not contribute directly to determining the staging of the disease, they may influence the choice of therapy and guide further investigations to other potential sites of disease. Imaging studies — Following the diagnosis of HD, additional radiologic inquiries include chest X-rays and computed tomography (CT) of the thorax, abdomen, and pelvis. Imaging of the neck is becoming more common. In addition to the CT scan, a gallium or positron emission tomographic (PET) scan is also recommended. Chest — Chest radiography with back and side views should be performed on all patients. In the past, CT scanning was performed only when chest X-rays were normal in order to detect small nodes that might not be seen in an X-ray. However, CT scanning of the chest is now recommended in all new patients because it can more accurately detect abnormalities, reduces false positive findings, and more frequently alters the subsequent therapy of patients. Abdomen — CT scanning has largely replaced bipedal lymphangiography, an X-ray technique that uses a special dye injected into the feet to make the lymph nodes and vessels show up on the X-ray film. CT scanning is now employed for the detection of disease within the abdomen, because it is easier to use and more convenient for the patient. However, bipedal lymphangiography might still be used in patients who present with Hodgkin's disease below the diaphragm and are being considered for treatment with radiotherapy, because it may permit more precise protection of normal tissues. Spleen — Although the CT scan provides detailed information about the liver and spleen, it is still difficult to reliably diagnose HD in the spleen. Isotope scanning and magnetic resonance imaging (MRI) also cannot reliably and accurately detect splenic involvement. For these reasons, staging laparotomy is performed in cases where treatment might be altered depending on the presence or absence of splenic involvement. In some cases the PET scan will detect involvement of the spleen not seen on other studies. Liver — Liver involvement occurs in approximately 5 percent of cases of HD. Involvement usually consists of microscopic areas of disease, making diagnosis difficult. Liver involvement is almost never seen without splenic involvement. Current guidelines recommend that the radiologic diagnosis of HD in the liver requires the demonstration of multiple cancerous areas using at least two imaging techniques. Bone — It is uncommon to find bone disease when diagnosing HD, but it does occur at some time in the course of the disease in up to 20 percent of patients. Bone scans should be performed in patients with bone or joint pain, specific laboratory findings, or suspected areas of bone disease on CT scan or routine X-ray examination. Gastrointestinal tract — HD is rarely seen in the gastrointestinal tract. If gastrointestinal involvement is suspected, barium contrast studies followed by endoscopy and biopsy will be used to confirm the diagnosis. Central nervous system — Central nervous system involvement with Hodgkin's disease is rare. It can present either with brain disease or with spinal deposits. If suspected, the diagnosis will be confirmed with plain radiography, CT scanning, or MRI, and examination of the cerebrospinal fluid. |