A case of lymphomatoid granulomatosis with multiple thin-walled cavities]

We report a case of rapidly progressive lymphomatoid granulomatosis. A 48-year-old man was admitted because of hemoptysis and high fever. A chest radiograph and chest computed tomograms revealed multiple nodules, thin-walled cavities in the lungs, some containing ball-like masses. After admission, clinical studies, including percutaneous and transbronchial biopsies failed to provide sufficient evidence for proper diagnosis. Fluoro-deoxyglucose positron emission tomography (FDG-PET) showed strong accumulations of abnormal shadows in the lesions. A VATS biopsy was performed to make possible an exact diagnosis. The histological findings showed angiocentric lesions with infiltration of polymorphous cells, and were compatible with lymphomatoid granulomatosis (LYG). The respiratory failure progressed as the reticular shadows in the chest radiograph increased, so treatment with methylprednisolone pulse therapy (1,000 mg/day for 3 days) was started, and followed with prednisolone therapy (60 mg/day for 3 weeks). Initially, the symptoms improved, but gradually deteriorated, and the pulmonary nodules became enlarged. The patient finally died of progressive respiratory failure in addition to uncontrollable empyema with an MRSA infection. We attributed the cavity formation and ball-like masses in the cavities to the occlusion of small pulmonary arteries and tissue necrosis along the drainage bronchus.     

发热、肺部肿块、关节酸痛、浅表淋巴结肿大

A 69-year-old man with fever,pulmonary nodules,joint pain and superficial lymphadenopathy was admitted to our hospital.The patient had a history of ten year hypertension.She smoked a pack of cigarettes daily for forty years and quitted for fifteen years.Family history of coronary heart disease,diabetes,cancer or other diseases was negative.Chest CT showed a nodule in the left lung lower lobe.Percutaneous lung biopsy revealed a large number of atypical B cell proliferation and infiltration which involved the vessel wall.The atypical B-cell phenotype and genotype was EBERs (+),CD20 (+),CD30 (+),CD15 (-).The patient was diagnosed as pulmonary lymphomatoid granulomatosis (LYG),an angiodestructive and angioinvasive lymphoproliferative disorder which is an Epstein-Barr virus associated B cell disorder with reactive T lymphocytes.The patient received six courses of chemotherapy.In this rare case,misdiagnosis of LYG often occurred due to the complex clinical presentation and non-specific imaging.Percutaneous or open lung biopsy is the main choice in the diagnosis of LYG.     

Failure of CHOP with rituximab for lymphomatoid granulomatosis

We present a 66-year-old male patient with pulmonary lymphomatoid granulomatosis. The patient had progressive disease after three courses of CHoP and rituximab and, therefore, treatment with interferon-alpha 2b 5 x 10(6) IE three times a week was started. This resulted in stable disease for five months. subsequently, progression occurred and the patient died 12 months after initial presentation. lymphomatoid granulomatosis is a rare, poor-risk, Epstein-Barr virus related, B cell lymphoproliferative disease. There is no standard treatment but promising results have been reported with rituximab, either as monotherapy or in combination with chemotherapy. This case demonstrates that lymphomatoid granulomatosis is still a chemotherapy-resistant disease in some patients despite addition of rituximab. A review of the literature regarding aetiology, clinical features, diagnosis and treatment options is presented.     

Phenotypic characterization of skin-infiltrating T cells in cutaneous T- cell lymphoma: comparison with benign cutaneous T-cell infiltrates

Using a panel of monoclonal antibodies, we have studied cell surface antigens of infiltrating mononuclear cells in skin biopsies from patients with cutaneous T-cell lymphoma (CTCL) and compared them with the T-cell surface phenotype seen in benign cutaneous T-cell infiltrations (e.g., contact dermatitis, delayed hypersensitivity skin tests, granuloma annulare) and in dermal infiltrates of lymphomatoid granulomatosis patients. We found that unlike circulating CTCL (Sezary) cells, CTCL cells infiltrating skin epidermis frequently expressed the T-cell antigen 3A1. Cutaneous infiltrates in 10 patients with mycosis fungoides (MF) and 1 patient with Sezary syndrome were OKT4 (inducer T cell), OKT8 (suppressor/cytotoxic T cell); 2 patients with MF were OKT4- , OKT8; and one MF patients's skin T cell were OKT4-, OKT8+. Similar to CTCL infiltrating cells, most of the benign skin T-cell infiltrates were usually 3A1+. OKT4+, and OKT8-. Our study shows the complex nature of T-cell antigen patterns in inflammatory and malignant skin T-cell infiltrations. We demonstrated that the CTCL the skin epidermal infiltrating T-cell phenotype is not invariate, and in many cases, is similar to the phenotype of clinically benign cutaneous T-cell infiltrations.     

Lymphomatoid granulomatosis and diffuse alveolar damage associated with methotrexate therapy in a patient with rheumatoid arthritis

We report on a patient of rheumatoid arthritis (RA) who sequentially developed an axillary mass and a fatal interstitial pneumonia during a 2-year course of methotrexate (MTX) therapy. Autopsy revealed a systemic lymph node involvement and the diagnosis of Epstein–Barr virus (EBV)-related lymphoproliferative disease (LPD) with the features of lymphomatoid granulomatosis was made. The lung tissue specimens revealed a typical diffuse alveolar damage (DAD), and small nodules consisting of atypical B lymphocytes showing positive staining for EBV were sparsely recognized only in basal lungs. This is the first report of a RA patient receiving MTX therapy sequentially developing MTX-associated lymphomatoid granulomatosis and DAD.     

Treatment of refractory retrobulbar granuloma with rituximab in a patient with ANCA-negative Wegener’s granulomatosis: a case report

Abstract

Retrobulbar granuloma is one of the serious complications in Wegener’s granulomatosis and often shows resistance to conventional therapy during long-term treatment. The outcome of this complication includes visual loss, orbital and facial deformity, fistula formation, as well as infection. There has been increasing evidence that shows the efficacy of rituximab, a chimeric anti-B cell mAb, for the treatment of autoimmune diseases including Wegener’s granulomatosis. We present a 22-year-old Japanese woman who was diagnosed with Wegener’s granulomatosis complicated by refractory retrobulbar granuloma. She was admitted to our hospital with pain of the right eye and right proptosis during treatment with monthly IVCY for Wegener’s granulomatosis. We diagnosed refractory retrobulbar granuloma by computed tomography (CT) scan and biopsy. She showed a refractory growth of retrobulbar granuloma in spite of negative ANCA. She was also complicated with pulmonary granulomatous lesions in bilateral apices. After approval by an institutional ethical committee and informed consent of this patient, rituximab 375 mg/m² was intravenously administered weekly four times. Concomitant prednisolone 0.5 mg/kg was also administered for 2 weeks and gradually tapered. Treatment of rituximab resulted in prompt relief of symptoms in this case and the reduction of the granuloma. BVAS score also improved from 6 to 0 at 3 months and was kept in remission for 12 months. Circulating CD19-positive cells were kept less than 0.1% during the follow-up. There were no serious adverse events. This case suggests that rituximab is effective for refractory retrobulbar granuloma complicated in Wegener’s granulomatosis even when ANCA titers are negative.     

Treatment of refractory retrobulbar granuloma with rituximab in a patient with ANCA-negative Wegener’s granulomatosis: a case report

Retrobulbar granuloma is one of the serious complications in Wegener’s granulomatosis and often shows resistance to conventional therapy during long-term treatment. The outcome of this complication includes visual loss, orbital and facial deformity, fistula formation, as well as infection. There has been increasing evidence that shows the efficacy of rituximab, a chimeric anti-B cell mAb, for the treatment of autoimmune diseases including Wegener’s granulomatosis. We present a 22-year-old Japanese woman who was diagnosed with Wegener’s granulomatosis complicated by refractory retrobulbar granuloma. She was admitted to our hospital with pain of the right eye and right proptosis during treatment with monthly IVCY for Wegener’s granulomatosis. We diagnosed refractory retrobulbar granuloma by computed tomography (CT) scan and biopsy. She showed a refractory growth of retrobulbar granuloma in spite of negative ANCA. She was also complicated with pulmonary granulomatous lesions in bilateral apices. After approval by an institutional ethical committee and informed consent of this patient, rituximab 375 mg/m² was intravenously administered weekly four times. Concomitant prednisolone 0.5 mg/kg was also administered for 2 weeks and gradually tapered. Treatment of rituximab resulted in prompt relief of symptoms in this case and the reduction of the granuloma. BVAS score also improved from 6 to 0 at 3 months and was kept in remission for 12 months. Circulating CD19-positive cells were kept less than 0.1% during the follow-up. There were no serious adverse events. This case suggests that rituximab is effective for refractory retrobulbar granuloma complicated in Wegener’s granulomatosis even when ANCA titers are negative.     

Pulmonary hyalinizing granuloma with massive infiltration of lymphocytes]

A 39-year-old man was admitted to our hospital for examination of multiple nodules and infiltrates on a chest radiograph. His chest HRCT revealed multiple nodules with or without thick- or thin-walled cavities. Specimens obtained by video-assisted thoracoscopic biopsy showed bundles of hyalinized collagen fibers, some of which contained accumulated plasma cells in the center. The nodules were surrounded by massive lymphoid cells which formed germinal centers. These findings are compatible with pulmonary hyalinizing granuloma. The lymphoid cells looked uniform in some areas and had infiltrated along the bronchioles and small vessels and into the intralobular septa in a manner resembling pulmonary lymphoma or pseudolymphoma. The findings suggested that pulmonary hyalinizing granuloma may overlap pulmonary lymphoma. The disease has shown no progression for four years although no treatment has been given.     

Isolated Primary Lymphomatoid Granulomatosis of Central Nervous System

Lymphomatoid granulomatosis (LG) is an infrequent extranodal Epstein-Barr virus (EBV)-associated B-cell lymphoproliferative disorder characterized by angiocentric and angiodestructive polymorphic lymphoid infiltration. CNS is involved in one of every 4 patients, but isolated CNS involvement at presentation is rare. A 67-year-old man was admitted to our hospital because of visual impairment. Magnetic resonance imaging (MRI) revealed a suprasellar mass lesion isointense to gray matter on T1 and T2-weighted images. The hypotalamic/chiazmatic mass was resected through a transsphenoidal approach. Pathological examination of the biopsy specimen revealed large atypical, CD20-positive B-lymphocytes within a background containing numerous CD3-positive small T-lymphocytes and scattered admixed plasma cells and histiocytes. Necrotic areas and vascular infiltration by a mixed mononuclear cell infiltrate with scattered large atypical lymphoid cells was present. In situ hybridization for EBV showed few large cells both around blood vessels and adjacent to the necrotic zone. This morphologic and immunophenotypic features was diagnostic for lymphomatoid granulomatosis. The patient was successfully treated with steroids, high-dose methotrexate and radiotherapy.     

Wegener's granulomatosis responding to antituberculous drugs

We present a case of Wegener's granulomatosis (WG) that responded to antituberculous drugs. A 44-year-old woman with multiple nodules on chest radiograph received a diagnosis of pulmonary tuberculosis because open-lung biopsy specimens showed caseous granulomas. Her chest shadows underwent repeated resolution after the start of antituberculous treatment, and relapse after the cessation of the drugs. Antineutrophil cytoplasmic antibody was positive (14 enzyme-linked immunosorbent assay units), and the second lung biopsy specimens showed necrotizing granulomas and vasculitis without pathogenic organisms. Thus, the patient received a diagnosis of WG and was successfully treated with trimethoprim/sulfamethoxazole 10 years after her initial evaluation. Antituberculous drugs were effective in this case of WG.     

Pulmonary lymphomatoid granulomatosis radiologically mimicking interstitial pneumonia]

We report a rare case of pulmonary lymphomatoid granulomatosis radiologically mimicking interstitial pneumonia. A 57-year-old man was admitted to our hospital because of chest bilateral reticular shadow with sustained cough and breathlessness for 10 years. Chest CT scans showed multiple ground-glass opacities, traction bronchiectasis and cystic change in both lungs, in addition to hilar and mediastinal lymphadenopathy. A histopathologically diagnosis of pulmonary lymphomatoid granulomatosis (angiocentric immunoproliferative lesion, grade 1) was made by thoracoscopic lung biopsy. In this case, serological and immunohistochemical analyses did not show Epstein-Barr virus infection. No clinical or radiological deterioration has been observed thereafter despite no medication.     

Case report of limited form of Wegener's granulomatosis detected by a health examination with no subjective symptoms]

A 60-year-old woman with no subjective symptoms was admitted to our hospital because of chest radiograph abnormality detected by a health examination. A computed tomographic scan of the thorax showed multiple nodules in both lungs without cavitation. Other organ lesions were not detected. Specimens from transbronchial lung biopsy revealed non-specific granuloma with necrosis. Antituberculous therapy was not effective, and serum PR 3-ANCA revealed to be positive. So we performed an excisional biopsy of the lung by video-assisted thoracoscopic surgery. The specimens showed necrotizing vasculitides, and granulomata which consisted of mainly lymphocytes, epithelioid cells and Langhans' giant cells. We here report a rare case of a patient with a limited form of Wegener's granulomatosis suffering from no subjective symptoms detected by a health examination.     

Wegener’s granulomatosis detected initially by integrated 18F-fluorodeoxyglucose positron emission tomography/computed tomography

Early diagnosis is crucial for effective treatment of Wegener’s granulomatosis, although this disease shows only atypical symptoms in the primary stage. This report describes a patient suspected of having a malignancy based on integrated 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT), which showed increased uptake in pulmonary nodules and nasopharyngeal mucosa. Integrated PET/CT is therefore considered to be useful to confirm the distribution and determine the optimal site for biopsy.     

Síndrome autoinmune/inflamatorio inducido por adyuvante que debuta con manifestaciones pulmonares y articulares

A 59 year-old female with a history of injection of an oily material in the buttocks 11 years ago. She developed symmetric aditive polyarthritis as well as superior and inferior airways involvement. There was no evidence of granulomatosis with polyangiitis (Wegener). She had several serum autoantibodies and a skin biopsy showed a foreign body granuloma. The diagnosis of adjuvant induced autoimmune/inflammatory syndrome was made. The pulmonary involvement was an atypical manifestation at the onset of disease.     

Lymphomatoid granulomatosis. A report of 2 cases

Two patients with lymphomatoid granulomatosis were diagnosed by postmortem autopsy or exploratory thoracotomy. The lung, skin, spleen, renal and lymph nodes were involved. The most common presenting complaints are fever, cough, expectoration shortness of breath. The radiographic manifestations are multiple, bilateral nodular shadows. The histologic features is a unique form of pulmonary angiitis and granulomatosis, which is a necrotizing angiocentric and angio-destructive infiltrative process composed of small lymphocytes and atypical lymphoreticular cells.     

Pulmonary lymphoma of large B-cell type mimicking Wegener's granulomatosis

A 27-year-old man with a primary pulmonary lymphoma of large B-cell type is described. Symptoms involved both the upper and lower respiratory tract. A chest roentgenogram showed a dense mass with cavitation. Transbronchial biopsy specimens revealed no atypical cells, rather they demonstrated granulomatous infiltration and vasculitis consistent with but not conclusively diagnostic of Wegener's granulomatosis. The pulmonary mass became smaller after sulfamethoxazole-trimethoprim therapy. These features suggested Wegener's granulomatosis. However, an open biopsy specimen was diagnostic for diffuse lymphoma of large B-cell type. High-grade pulmonary lymphoma should be considered in the differential diagnosis of patients with clinical and pathologic features suggesting Wegener's granulomatosis.     

Lymphomatoid granulomatosis: Report of a case and review of the literature

A 24 year old man had a nonproductive cough and chest pain. Chest roentgenogram showed a diffuse infiltrate, and pulmonary function studies showed restrictive lung disease. Extremity weakness, deteriorating mental status and neuropathy progressed as pulmonary findings diminished on corticosteroid therapy. Lung biopsy showed lymphomatoid granulomatosis. The neurologic status deteriorated despite treatment with Cytoxan^®, intrathecal metnotrexate and brain irradiation. Autopsy showed mass lesions of lymphomatoid granulomatosis in the brain and healed lesions in the lungs. A review of the neurologic and pulmonary findings in reported cases show that diminution of pulmonary disease with progression of neurologic disease manifest by mass lesion is unusual. Since the etiology, prognosis and prevalence of this disease remains undefined, all patients with this disease should be reported on.     

Wegener's granulomatosis: pitfalls in the management of pulmonary disease: A case of Wegener's granulomatosis with a hilar mass

Wegener's granulomatosis (WG) is a systemic, granulomatous vasculitis that typically affects the upper airways, lungs, and, in most cases, the kidneys. Lung involvement occurs in 85% of patients. A classic feature of WG is multiple pulmonary nodules, which frequently cavitate. Hilar adenopathy or mediastinal masses are rare. These atypical pulmonary findings should raise suspicion of diseases other than WG and lead to biopsy with cultures, even when the diagnosis of WG appears to be certain. These guidelines proved to be reliable in a patient with WG in whom a hilar mass was associated with tuberculosis.     

Intense 18F-fluorodeoxyglucose uptake caused by pulmonary Mycobacterium intracellulare infection]

A 70-year-old woman was admitted to our hospital for the evaluation of a pulmonary nodule in the left S5 segment. On 18F-fluorodeoxyglucose positron emission tomography (18FDG-PET), the nodule showed substantial uptake of 18F-fluorodeoxyglucose. Bronchoscopy was performed, but the cytology was negative. For a pathological diagnosis, a lung biopsy was carried out using video-associated thoracoscopy. The biopsy specimen showed granuloma formation with multinuclear giant cells. An acid-fast bacteria culture of the specimen was positive for Mycobacterium intracellulare. An atypical mycobacterium infection should be considered as a possibility when the 18FDG-PET of patients with pulmonary nodules is interpreted.     

Pulmonary malignancy associated with granulomatous vasculitis in the maxillary sinus

Summary A 63-year-old man presented with pulmonary infiltrates and maxillary sinusal opacities. Although necrotizing vasculitis and granulomatous inflammation were present in nasal mucosa, pulmonary biopsy revealed adenocarcinoma. Simultaneous appearance of granulomatosis in the maxillary sinus and necrotic lung nodule does not necessarily mean that the lung abnormalities are also granuloma. This case report suggests that differential diagnosis between Wegener's granulomatosis and lung carcinoma may be difficult.