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NORD is very grateful to Elaine S. Jaffe, MD, Chief, Hematopathology Section, Lab of Pathology, National Cancer Institute, and Wyndham H. Wilson, M.D, Ph.D, Senior Investigator, Metabolism Branch, National Cancer Institute, for assistance in the preparation of this report.
Lymphomatoid granulomatosis is a rare disorder characterized by overproduction (proliferation) of white blood cells called lymphocytes (lymphoproliferative disorder). The abnormal cells infiltrate and accumulate (form lesions or nodules) within tissues. The lesions or nodules damage or destroy the blood vessels within these tissues. The lungs are most commonly affected in lymphomatoid granulomatosis. Symptoms often include cough, shortness of breath (dyspnea) and chest tightness. Other areas of the body such as the skin, kidneys or central nervous system are also frequently affected.
The abnormal cells in lymphomatoid granulomatosis are B-cells (B lymphocytes) containing the Epstein-Barr virus. There are two main types of lymphocytes: B-lymphocytes, which may produce specific antibodies to "neutralize" certain invading microorganisms, and T-lymphocytes, which may directly destroy microorganisms or assist in the activities of other lymphocytes. Because lymphomatoid granulomatosis is caused by the overproduction of abnormal B-cells, affected individuals may eventually develop B-cell lymphoma, a form of non-Hodgkin lymphoma. Lymphoma is a general term for cancer of the lymphatic system.
The symptoms and progression of lymphomatoid granulomatosis vary greatly from case to case. The disorder may occasionally resolve without treatment (spontaneous remission) in some affected individuals or more commonly it will progress and cause life-threatening complications. Occasionally, it is an incidental and asymptomatic finding on chest radiographs (less than 5 percent).
In almost all cases, lymphomatoid granulomatosis affects the lungs and often causes a cough, shortness of breath (dyspnea) and chest tightness. In most patients, the cough is non-productive and is rarely associated with blood (hemoptysis). Systemic symptoms are not uncommon and may include fever, a general feeling of poor health (malaise), weight loss, and fatigue. Affected individuals may occasionally develop numbeness and tingling and/or weakness of their lower extremities.
Approximately 40-50 percent of affect individuals will develop skin lesions such as a patchy reddish (erythematous) rash consisting of flat discolored lesions (macules), small, elevated bumps (papules) or, more rarely, solid, raised, flat-topped lesions (plaques). Small bumps or growths (nodules) just below the surface of the skin (subcutaneous) may also develop. Larger nodules may become open sores (ulcerated).
In approximately 30 percent of cases, the central nervous may be involved potentially resulting in mental status changes, headaches, seizures, paralysis of one side of the body (hemiparesis), or loss of the ability to coordinate voluntary movements (ataxia).
Less commonly, the kidneys or liver may be involved, although this rarely leads to the development of symptoms. In some cases the liver may become enlarged (hepatomegaly). In some extremely rare cases, lymphomatoid granulomatosis may only affect the skin or only the central nervous system (isolated lymphomatoid granulomatosis).
Lymphomatoid granulomatosis may eventually progress to a form of large B-cell lymphoma.
The exact cause of lymphomatoid granulomatosis is unknown. Lymphomatoid granulomatosis occurs with greater frequency in individuals with some form of immune system dysfunction including individuals with Sjogren syndrome, rheumatoid arthritis or chronic viral hepatitis.
It is likely that some combination of immunodeficiency, genetic and familial factors all play a role in the development of lymphomatoid granulomatosis. The therapy used varies, but is generally directed against eliminating the EBV-infected B-cells or boosting the immune system.
The classification of lymphomatoid granulomatosis has been difficult. Originally, the disorder was viewed as a benign process with the potential to progress to malignant lymphoma. Researchers believed that defective cells were T-cells. Scientific advances in technology have allowed researchers to determine that the abnormal cells in lymphomatoid granulomatosis are B-cells infected by the Epstein-Barr virus. However, most of the cells within the tissues are T-cells, reacting against the abnormal T-cells. The Epstein-Barr virus is common among the general population and is relatively well-known because it is the cause of infectious mononucleosis (IM), usually with no long-lasting effects.
Lymphomatoid granulomatosis affects males twice as often as females. It is most common in adults after the fifth decade, but can occur at any age and has been reported in children. The prevalence of lymphomatoid granulomatosis is unknown.
The disorder was first described in the medical literature in 1972.
Churg-Strauss syndrome is a rare disorder that may affect multiple organ systems, especially the lungs. The disorder is characterized by the abnormal clustering of certain white blood cells (hypereosinophilia) in the blood and tissues, inflammation of blood vessels (vasculitis), and the development of inflammatory nodular lesions called granulomas (granulomatosis). Most affected individuals have a history of allergy. In addition, asthma and other associated lung (pulmonary) abnormalities (i.e., pulmonary infiltrates) often precede the development of the generalized (systemic) symptoms and findings seen in Churg-Strauss syndrome by as little as six months or as much as two decades. Asthma, a chronic respiratory disorder, is characterized by inflammation and narrowing of the lungs' airways, causing difficulties breathing (dyspnea), coughing, the production of a high-pitched whistling sound while breathing (wheezing), and/or other symptoms and findings. Nonspecific findings associated with Churg-Strauss syndrome typically include flu-like symptoms, such as fever, a general feeling of weakness and fatigue (malaise), loss of appetite (anorexia), weight loss, and muscle pain (myalgia). Additional symptoms and findings may vary depending upon the specific organ systems involved. The nerves outside the central nervous system (peripheral nerves), kidneys, or gastrointestinal tract are often involved. Without appropriate treatment, serious organ damage and potentially life-threatening complications may result. Although the exact cause of Churg-Strauss syndrome is unknown, many researchers indicate that abnormal functioning of the immune system plays an important role. (For more information, choose "Churg Strauss" as a search term in the Rare Disease Database.)
Wegener's granulomatosis is an uncommon disorder characterized by inflammation of blood vessels (vasculitis) that results in damage to various organ systems of the body, most often the respiratory tract and kidneys. Symptoms may include ulcerations of the mucous membranes in the nose with secondary bacterial infection, a persistent runny nose, sinus pain, and chronic middle ear infection (otitis media) potentially resulting in hearing loss. In some cases, kidney abnormalities may progress to kidney failure, a serious complication. If the lungs are affected, a cough, expectoration of blood (hemoptysis), and inflammation of the thin membrane lining the outside of the lungs and the inside of the lung may be present. The exact cause of Wegener's granulomatosis is not known. (For more information on this disorder, choose "Wegener's granulomatosis" as your search term in the Rare Disease Database.)
Lymphoma is a general term for other cancers of the lymphatic system. Lymphomas result from errors in the production of a white blood cell (lymphocyte) or transformation of a lymphocyte into a malignant cell. Abnormal, uncontrolled growth and multiplication (proliferation) of malignant lymphocytes may lead to enlargement of a specific lymph node region or regions; involvement of other lymphatic tissues, such as the spleen and bone marrow; and spread to other bodily tissues and organs, potentially resulting in life-threatening complications. The specific symptoms and physical findings may vary from case to case, depending upon the extent and region(s) of involvement and other factors.
Sarcoidosis is a multisystem disorder that most often affects individuals between 20 and 40 years of age. Females appear to be affected more frequently than males. Sarcoidosis is characterized by the abnormal formation of inflammatory masses or nodules (granulomas) consisting of certain granular white blood cells (modified macrophages or epithelioid cells) in certain organs of the body. The granulomas that are formed are thought to alter the normal structure of and, potentially, the normal functions of, the affected organ(s), causing symptoms associated with the particular body system(s) in question. In individuals with sarcoidosis, such granuloma formation most commonly affects the lungs. However, in many cases, the upper respiratory system, lymph nodes, skin, and/or eyes may be involved. In addition, in some cases, other organs may be affected, including the liver, bone marrow, spleen, musculoskeletal system, heart, salivary glands, and/or nervous system (i.e., central or peripheral nervous system). The range and severity of symptoms associated with sarcoidosis vary greatly, depending upon the specific organ(s) involved and the degree of such involvement. The exact cause of sarcoidosis is not known. However, possible infectious, environmental, genetic, and immunological factors are under investigation as potential causes of the disorder. (For more information on this disorder, choose "Sarcoidosis" as your search term in the Rare Disease Database.)
A diagnosis of lymphomatoid granulomatosis is made based upon a detailed patient history, a thorough clinical evaluation, and a variety of specialized tests such as the surgical removal and microscopic examination (biopsy) of tissue samples taken from an affect organ such as the lungs. A skin biopsy is not reliable because the characteristic abnormal cells may be missing.
Certain x-ray studies (e.g., CT scans) may be able to aid in diagnosis. A CT scan of the lungs or another affected organ can help determine the extent of lymphomatoid granulomatosis. Magnetic resonance imaging (MRI) of the brain may be performed to rule out involvement of the central nervous system.
The most effective therapy for individuals with lymphomatoid granulomatosis is unknown. For individuals with minimal disease, observation may be recommended since long-term survival without treatment has occurred as well as spontaneous remission. In most cases, however, treatment is recommended. Treatment recommendations are mostly based on the grade of disease. Lymphomatoid granulomatosis is pathologically divided into three grades (I, II, III), which are determined by the number of EBV+ B-cells and the extend of necrosis. In patients with grade I/II disease, interferon alfa-2b has been shown to be highly effective in most patients, and leads to longterm remissions and potential cures. In patients with grade III disease, interferon alfa-2b is not effective, and combination chemothearpy with rituximab should be used. However, there is a frequent rate of recurrence with grade I/II disease following chemotherpy-rituximab in grade III disease.
Corticosteroids alone are only recommended as a temporizing measure and should not be used for long term control of lymphomatoid granulomatosis. Similarly, rituximab alone is seldom effective for long term control. Neither of these agents effectively eradicates and abnormal EBV clones and corticosteroids can increase immusuppression and ultimately disease progression.
If patients develop lymphomatoid granulomatosis on immune suppressive agents, they should be stopped if possible and the patient observed. If the disease is progressive or advanced, then treatment as outlined above should be institutued.
Patients with grade I/II disease in the central nervous system (CNS) frequently respond to interferon alpha-2b and do not require intrathecal or high dose systemic chemothearpy. Rarely patients with CNS invovlement require brain radiation.
Researchers at the Division of Clinical Sciences of the National Cancer Institute seek additional patients for a study of treatment of Lymphomatoid Granulomatosis with interferon alfa-2b for grade I/II and EPOCH-Rituximab /Alpha-Interferon for Grade III. To participate, patients must be diagnosed with LYG, 12 or older, and not pregnant or nursing.
For information, contact:
Patient Recruitment and Public Liaison Office
CC, Building 61, 10 Cloister Court
Bethesda, MD 20892-4754
Phone: (800) 411-1222
Fax: (301) 480-9793
Refer to Protocol Number 94-C-0074
Potential participants may also contact Dr. Wyndham H. Wilson, the principal investigator, at (301) 435-2415 or visit the study's Web site at: http://bethesdatrials.cancer.gov/clinical-research/search_detail.aspx?ProtocolID=NCI-94-C-0074
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
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Patsalides AD, Atac G, Hedge U, et al. Lymphomatoid granulomatosis: abnormalities of the brain at MR imaging. Radiology. 2005;237:265-273.
McCloskey M, Catherwood M, McManus G, et al. A case of lymphomatoid granulomatosis masquerading as a lung abscess. Thorax. 2004;59:818-819.
Brown JR, Skarin AT. Clinical mimics of lymphoma. Oncologist. 2004;9:406-416.
Guven A, Baskin D. Lymphomatoid granulomatosis in a boy with long-term follow-up. Ped Hem Onc. 2001;18:377-382.
Moertel CL, Carlson-Green B, Watterson BA, Simonton SC. Lymphomatoid granulomatosis after childhood acute lymphoblastic leukemia: report of effective therapy. Pediatrics. 2001;107:e82.
Beaty MW, Toro J, Sorbara L, et al. Cutaneous lymphomatoid granulomatosis: correlation of clinical and biological features. Am J Surg Pathol. 2001;25:1111-1120.
Petrella TM, Walker IR, Jones GW, Leber B. Radiotherapy to control CNS lymphomatoid granulomatosis: a case report and review of the literature. Am J Hematol. 1999;62:239-241.
Jaffe ES, Wilson WH. Lymphomatoid granulomatosis: pathogenesis, pathology and clinical implications. Cancer Surv. 1997;30:233-48.
Wilson WH, Kingma DW, Raffeld M, Wittes RE, Jaffe ES. Association of lymphomatoid granulomatosis with Epstein-Barr viral infection of B lymphocytes and response to interferon-alpha 2b. Blood. 1996;87:4531-4537.
Kamangar N. Lymphomatoid Granulomatosis. Emedicine. http://emedicine.medscape.com/article/299751-overview. Updated January 18, 2012. Accessed February 23, 2012.
Report last updated: 2012/03/15 00:00:00 GMT+0