Overview.
Lymphomatoid granuloma is a rare type of vasculitis and granulomatous reaction. It is characterized by vascular dystrophic and vascular destructive lesions and granulomatous reactions in various tissues with extensive atypical lymphoproliferative infiltrates, primarily involving the lungs but also other tissues outside the lungs.
Questions you may be concerned about
What is lymphomatoid granuloma?
Lymphomatoid granuloma is a lymphoproliferative disorder that occurs outside the lymph nodes and is centered on blood vessels with vascular injury.
Based on the number of a particular type of cell in the lesion and the degree of tissue necrosis, the disease can be classified as grade I, II, or III, with the higher the grade, the worse the prognosis.
Grade I lesions contain a few or no EBV-positive cells and usually lack necrosis and are considered benign; grade II lesions have scattered EBV-positive cells and the presence of focal necrotic tissue, which is not widespread, and are considered to be junctional; and grade III lesions, which have a large number of EBV-positive cells and a large amount of necrotic tissue, are classified as neoplastic.
The presentation of lymphomatoid granuloma lacks specificity and is characterized by systemic symptoms, pulmonary symptoms, neurologic damage, and skin lesions. Some patients may have hepatomegaly and liver failure. It may be complicated by respiratory distress and death due to hemoptysis, as well as complications such as partial obstruction of the lobar bronchus, aphasia, mild hemiparesis, and blindness.
If the disease is found during the examination, it is recommended to go to the hospital immediately for diagnosis and treatment so as not to miss the condition.
Etiology
The cause of the disease is unknown.
Symptoms
Systemic symptoms include fever, malaise, fatigue, weight loss, joint pain and skin lesions. Death usually occurs within 14 months of the onset of symptoms from generalized lung lesions and secondary infections. Because it primarily invades the lungs, the most common complaints are lower respiratory symptoms such as cough, hemoptysis, chest pain, and dyspnea. Some patients develop neurologic damage, which manifests as confusion, ataxia, seizures and cranial nerve dysfunction. Skin lesions are mainly infiltrative red plaques and subcutaneous or dermal nodules, and ulcerated maculopapular or erythematous lesions may also occur. They occur symmetrically on the lower limbs and buttocks, but may be generalized throughout the body. Skin lesions may precede lung damage or occur at the same time, and often accompanied by systemic symptoms, such as fever, lethargy, weight loss, myalgia and arthralgia and other extra-thoracic symptoms, commonly due to different parts of the involvement and the corresponding clinical manifestations.
1.Respiratory system
Respiratory symptoms are often the main complaint, and most of the patients have cough, sputum, dyspnea or shortness of breath, chest pain and so on. Lung involvement is the most common early manifestation of the disease, often accompanied by varying degrees of fever, emaciation, a small number of patients may only lung X-ray abnormalities without clinical symptoms. In some patients, lung involvement is present at the onset of the disease and is progressive. In others, progressive lung involvement may occur during the course of the disease, and the lesions are mainly located in the two lower lung fields, especially in the outer bands of the two lungs, while the apical regions of the lungs are seldom affected, and the lesions are almost always bilateral, with a wide range of spread, but they may also be asymmetric. Although the lung lesions are characteristic of lymphoma, bilateral hilar lymph node enlargement is rarely seen, and lymph node enlargement occurs only in other organ systems and is atypical. About 1/3 of patients with clinical conditions similar to those of lymphoma may develop pulmonary cavitation and may die from hemoptysis. Respiratory failure due to destruction of large portions of the lung parenchyma is also a major cause of death in this disease. The scope of respiratory involvement in this disease is usually small, but sometimes it is also characterized by respiratory tract lesions, manifested as obstructive bronchiolitis.
2. Nervous system
The manifestations include peripheral neuropathy, cerebral nerve palsy and various central nervous system symptoms and signs. Aphasia, headache, sensory abnormalities, hemiparesis, ataxia, confusion, convulsions, etc. may occur when the nervous system is involved. It may occur before, in the middle of, or even when the lung lesions are in remission. Peripheral neuropathy is mostly an asymmetric CNS lesion that can involve any part of the brain and spinal cord, and may present with Bell’s palsy, temporary blindness, diplopia, proptosis, vision loss, or vertigo; common symptoms include aphasia, mild hemiparesis, blindness, movement disorders, paraparesis, kinetic nerve paralysis, cerebral nerve paralysis, headache, sensory abnormalities, confusion, coma, seizures, quadriplegia, and optic nerve edema, Deafness, facial paralysis, sensory retardation, cerebral edema, meningoencephalitis. Peripheral nerve involvement presents with sensory abnormalities in the lower extremities. It may occur before the appearance of other systemic lesions.
3. Skin
The most common site of extrapulmonary involvement is the skin, which is a large infiltrative erythematous nodule, ulcer, and some patients present with the first skin lesions; skin lesions can precede lung involvement by 2 to 9 years. Because of the high incidence of skin lesions, the ease of biopsy, and the typical histologic appearance of the lesions, a careful dermatologic examination should be performed when lymphomatoid granuloma is suspected. The most common typical lesions seen are reddish-purple macules, papules, or hard, raised subcutaneous nodules (sometimes ulcerated), 1 to 4 cm in size and 2 to 3 cm in diameter, most often located on the extremities. The lesions can occur anywhere, but are commonly found on the buttocks, abdomen, thighs and femurs, and lower extremities. The repair process is often accompanied by scarring and hyperpigmentation. Other skin lesions are non-specific changes such as small blisters of extensive lichen planus, patchy alopecia, localized absence of sweating and circumscribed plaques, and subcutaneous nodules sometimes very large, which may occasionally be the main clinical manifestation. Major skin lesions may also be manifested as subcutaneous lesions that begin red and eventually turn copper-colored and hard. Skin lesions usually occur at the same time as the lung lesions, but may precede or follow the lung lesions by months to years, and the presence or absence of skin lesions is not associated with prognosis.
4. Kidney involvement
About half of the patients have histologic changes in the kidneys without clinical symptoms. Clinically significant renal involvement is rare.
5. Other
Some patients may have hepatomegaly and liver failure. A few patients have hepatomegaly such as enlarged lymph nodes, splenomegaly and ascites, which may also be an early manifestation of the disease. Due to the extensive infiltration of the liver, the disease may cause progressive liver failure and death. Most cases may have enlarged lymph nodes, and individual cases may have a giant spleen with lymphomatous granulomatous infiltration, which may lead to a decrease in white blood cell count.
Examination
1. Laboratory examination
(1) Blood count and sedimentation
A few patients have severe anemia, white blood cell count may be increased or decreased, and lymphocytes may be increased and blood sedimentation may be accelerated.
(2) Urine routine
Generally normal, sometimes with mild proteinuria and leukocytes.
(3) Biochemical examination
When the liver parenchyma is extensively invaded, transaminases may be elevated.
(4) Immunological examination
Some patients may have elevated IgG or IgM, and the cellular immunity test is mostly negative for rheumatoid factor, lupus cells, and antinuclear antibodies.
(5) Peripheral blood test
There may be anemia, decreased or increased white blood cell count, increased or decreased lymphocytes.
(6) Blood tests
Blood sedimentation may be normal or increased. Rheumatoid factor may be positive, RF is often positive, and ANA is often negative.
(7) Immunoglobulin test
Immunoglobulin IgAIgG may be mildly increased.
(8) Pathologic examination
(9) Immunophenotype
EBV positive, B cells often express CD20 and CD79a, CD15 negative; LMP1 positive. Some monoclonal cells are cytoplasmic Ig-positive, and atypical lymphocytes may be CD3-positive, with more CD4+ cells.
2. Other auxiliary examinations
(1) X-ray examination: X-ray chest radiographs vary according to the period of lesion progression. Typical cases show multiple nodular shadows in the middle and lower lobes of both lungs, varying in size from several millimeters to 10 centimeters in diameter, 1/3 of which are accompanied by the formation of thick-walled cavities, and 20% of them are unilateral lung nodular shadows only. A few showed large infiltrative shadows in the lungs, and pleural effusion was seen in 1/3 of the cases, but the hilar lymph nodes were not enlarged. Occasionally, diffuse reticular nodular and villous alveolar infiltration or multiple nodular lesions are seen in both lungs, similar to metastatic lung cancer lesions, mostly bilateral, mainly involving the two lower lung fields, especially the nodular shadows in the outer bands of both lungs may rapidly increase or decrease in size, and may even disappear completely. A few patients have mediastinal or hilar lymph node enlargement.
(2) According to the condition, clinical manifestations, symptoms and signs, electrocardiogram, ultrasound, CT, MRI and other examinations.
3. Relevant examinations
Immunoglobulin A, immunoglobulin G, immunoglobulin M, total cholesterol, antinuclear antibody, plasma cells, lymphocytes, lupus cells, rheumatoid factor, cerebrospinal fluid, immunoglobulin, blood sedimentation.
Diagnosis
1. Diagnostic criteria
(1) Age of onset and gender: the disease can be seen in all ages, and is relatively common in the elderly, with an average age of onset of 50 years and a male to female ratio of 1.7:1.
(2) Clinical manifestations: respiratory symptoms are most common, and may be accompanied by fever and emaciation. Skin lesions are also more common, manifesting as large infiltrating erythema, nodules, ulcers, etc. The central nervous system is also often involved. The central nervous system is also often involved, which may manifest as mental abnormality, ataxia, hemiparesis, convulsions; cerebral nerve involvement may present Bell’s palsy, temporary blindness, diplopia, proptosis, decreased visual acuity or vertigo; peripheral nerve involvement may present with abnormal sensation in the lower limbs. A small number of patients have liver damage, such as hepatosplenomegaly, but superficial lymph nodes are rarely involved.
2.Diagnostic steps
When the above mentioned lung lesions or accompanying skin and nervous system lesions or accompanying liver and spleen lymph node enlargement occur clinically, we should consider the possibility of this disease, and further feasible chest X-ray examination, such as the appearance of multiple nodular shadows with cavity formation is an important diagnostic clue, but it must be confirmed by the pathology in order to confirm the final diagnosis.
Differential diagnosis
It should be differentiated from lymphoma, Weil’s granulomatosis, infectious granulomatosis, obstructive bronchitis, and metastatic lung tumor.
Complications
The most common complication is dyspnea, especially in patients with enlarged lymph nodes in the mediastinum or lungs. In some patients, pulmonary cavitation may occur, and death may result from hemoptysis. Partial obstruction of the lobar bronchioles and destruction of large portions of the lung parenchyma may also occur, resulting in respiratory failure, which is also a major cause of death in this disease. Central nervous system lesions can involve any part of the brain and spinal cord, aphasia, mild hemiparesis, blindness, motor disorders, paraplegia, motor nerve palsy, cerebral nerve palsy, headache, sensory abnormality, blurred consciousness, coma, convulsions, quadriplegia, optic nerve edema, deafness, facial paralysis, sensory slowness, cerebral edema, meningoencephalitis and so on. Extensive infiltration of the liver can result in progressive hepatic failure and death.
Treatment
There is no satisfactory treatment for this disease so far. Treatment with glucocorticosteroids at the early stage of the disease course can obtain certain efficacy, and combined treatment with hormones and immunosuppressants is more effective than hormone treatment alone.
1.Drug treatment
Corticosteroid hormone is suitable for early term focal lesions, i.e. benign lymphocytic vasculitis and granulomas, the use of medium to large doses of corticosteroid hormone can alleviate the condition. Prednisone is commonly used, and immunosuppressant therapy can also be applied. Early combined application of cyclophosphamide and corticosteroids can lead to long-term remission.
2. Radiation therapy
Isolated lesions can be treated with small-dose radiation therapy.
Prognosis
The prognosis of the disease is poor, and most of the patients die 2 years after the onset of the disease. The prognosis of the disease is related to the degree of pulmonary and extrapulmonary involvement and histologic grading.
Prevention
1. Maintain environmental hygiene, strengthen physical exercise, improve autoimmune function and prevent infection.
2. Pay attention to the regularity of life, combine work and rest, be in a good mood, and avoid intense mental stimulation.
3. Strengthen nutrition, prohibit cold and greasy food, pay attention to warm tonic.
4. Avoid cold and flu, prevent secondary bacterial infection.
5. Early diagnosis and treatment.