A case of esophageal tuberculosis which developed during the treatment for tuberculous lymphadenitis

A 23-year-old man was admitted to the other hospital complaining of fever and lymph node swelling in the left neck. Computed tomography showed swollen mediastinal lymph nodes without intrapulmonary lesions. Mycobacterium tuberculosis were identified by sputum culture and cervical lymph node biopsy and the case was diagnosed as tuberculous lymphadenitis. Three weeks after starting treatment with four anti-tuberculous drugs, he complained chest pain while eating and chest X-ray showed a new infiltrative shadow in the right cardiophrenic angle, then he was admitted to our hospital. Esophagoscopy revealed a deep ulceration with fistulas at 30 cm from the incisor and he was diagnosed as esophageal tuberculosis by histological examination of the biopsy specimen showing remarkable leukocytes infiltration and epithelioid cell granulomas with a few multinucleated giant cells. After antituberculous chemotherapy for six months, the mediastinal and cervical lymphadenopathy were reduced in size and the esophageal ulceration almost disappeared. Although esophageal tuberculosis is rare, the disease might develop during or after mediastinal or periesophageal tuberculous lymphadenitis.     

An adult case of cervico-mediastinal lymph nodes tuberculosis followed by the development of pulmonary lesions during the treatment with antituberculous drugs

A 27-year-old man was admitted to our hospital due to a painful mass in the right neck and fever. Cervical and superior mediastinal computed tomography showed an enlargement of right supraclavicular lymph node and multiple swollen mediastinal lymph nodes, including low-density areas and contrast medium-enhanced septa and margins. Smears of the pus obtained from right supraclavicular lymph node showed acidfast bacilli identified as Mycobacterium tuberculosis by PCR method. He was treated with antituberculous drugs with INH, RFP, EB, and PZA. PZA was given for initial two months. Six months later, productive cough developed and chest X-ray films showed infiltrative shadow in the right upper lung field. One month after the onset of cough, bronchoscopy revealed a polypoid lesion with a white coating in the right main bronchus. Microscopic examination of the specimen obtained by transbrochial biopsy revealed many epithelioid cell granulomas, consistent with tuberculosis. From these findings, pulmonary lesion was suggested to be due to invasion of the mediastinal lymph node into the bronchus. After one year of antituberculous chemotherapy, the swelling of the cervical-mediastinal lymph nodes was reduced and the abnormal chest X-ray shadows disappeared.     

Sarcoid-like granulomatosis in patients treated with anti-TNFα factors. A case report and review of the literature

This report describes a 56-year-old woman who developed granulomatous lesions consistent with sarcoidosis during adalimumab therapy for rheumatoid arthritis. Cervical and axillary lymphadenopathy developed approximately 21 months after adalimumab administration. Non-caseating epithelioid cell granulomas consistent with sarcoidosis were detected both in an axillary lymph node specimen and in the bone marrow. Diseases showing similar histologic changes, especially tuberculosis, were excluded, and a diagnosis of sarcoidosis was made. Adalimumab was discontinued, and recovery was observed. The current case is, to our knowledge, the first to describe adalimumab-induced non-caseating granulomas in lymph nodes and bone marrow without pulmonary involvement in a patient treated for rheumatoid arthritis.     

Carcinoma in villous adenoma of ascending colon associated with sarcoid reaction in the regional lymph nodes.

A 79-year-old woman was admitted to our hospital due to continuous anal bleeding. Colonoscopy showed a huge villous tumor on the middle area of the ascending colon. A typical right colectomy and lymph node dissection were performed. The resected specimen showed a villous type tumor located on the ascending colon. The histopathologic investigation demonstrated a moderately differentiated adenocarcinoma arising in a tubulovillous adenoma and extending to the submucosa. Although there was no evidence of metastatic carcinoma in the dissected lymph nodes, epithelioid cell granulomas with multinucleated giant cells lacking in the central caseous necrosis suggested sarcoid reaction.     

A rare case of sarcoidosis with bilateral leg lymphedema as an initial symptom

A 55-year-old man was admitted to our hospital because of bilateral leg lymphedema. He also showed subcutaneous nodules and CT scan disclosed multiple enlarged lymph nodes at thoracic, abdominal, and inguinal areas. Biopsy of the inguinal lymph node and the subcutaneous nodule revealed noncaseating epithelioid cell granuloma, a finding consistent with sarcoidosis. Lymphedema was attributed to the blockade of lymph flow by the systemic lymph node involvement of the disease. Within 1 week after the initiation of steroid therapy, his leg edema disappeared. Lymphedema could be the initial symptom of systemic sarcoidosis.     

Case of pulmonary coccidioidomycosis presented with multiple infiltrative opacities]

A 54-year-old man was admitted to our hospital to be operated on for inguinal hernia, but complained of dry cough and cervical lymph nodes swelling after traveling to California in the United States. The chest X-ray films taken on admission showed consolidations in both lungs. The laboratory data revealed an increase in white blood cell counts with eosinophilia, and elevated ESR, IgE and beta-D-glucan. The biopsied lung specimen by VATS showed epithelioid granulomas consisting of giant cells and eosinophils. In addition, spherulitic forms filled with endopores were detected in the specimen. A diagnosis of primary pulmonary coccidioidomycosis was made. Eosinophilia and elevated in IgE and beta-D-glucan were closely related to the severity of the disease gravity after the treatment with fluconazole.     

Vertebral and Rib Sarcoidosis: Long-Term Clinical Remission with Methotrexate

We describe a patient with bilateral hilar lymphadenopathy shown on a chest radiograph and supraclavicular lymphadenopathy. Biopsy of a supraclavicular lymph node showed non-caseating granulomas. A diagnosis of sarcoidosis was made and no treatment was given. One year later she complained of cervical and lumbar pain and decreasing strength of the right hand. Magnetic resonance imaging of the spine showed multiple lesions within the vertebral bodies of six vertebrae, and thoracic computed tomography showed partial destruction of the first right rib. A biopsy of the second lumbar vertebra demonstrated non-caseating granulomas. Corticosteroid treatment was unsuccessful and long-term remission of the symptoms was achieved with a weekly low dose of methotrexate. Received: 26 November 1998 / Accepted: 26 April 1999     

Tuberculous pleurisy diagnosed by medical thoracoscopy in an adalimumab-treated rheumatoid arthritis patient after treatment of latent tuberculosis infection

A 28-year-old rheumatoid arthritis woman treated with adalimumab was admitted with fever, cough, and right chest pain. X-ray showed right pleural effusion. By medical thoracoscopy, diffuse white nodules were observed, and biopsy specimen demonstrated epithelioid cell granulomas with necrosis and auramine-stained organisms, which suggested a diagnosis of tuberculous pleurisy. Medical thoracoscopy can be a potent diagnostic method when tuberculous pleurisy is suspected. Notably, despite latent tuberculosis treatment, active tuberculosis was not prevented.     

A case of diffuse endobronchial infiltration in a patient with non-Hodgkin's lymphoma]

A 38-year-old man with diffuse endobronchial infiltration with non-Hodgkin's lymphoma (NHL) is reported. He was admitted to our hospital on November 1990 because of lymph node swelling. Physical examination on admission revealed left axillary, bilateral cervical and inguinal lymph node swelling. Chest and abdominal CT scan showed para-aorta lymph node swelling, mild splenomegaly and heterogeneous density of the liver, although hilar and mediastinal lymphadenopathy were not found. Microscopic examination of the biopsy specimen obtained from the right inguinal lymph node and liver revealed NHL (B cell lymphoma, diffuse, mixed type). After two courses of chemotherapy, a chest roentgenogram showed bilateral hilar lymphadenopathy and reticular shadows. CT scan demonstrated a thickening of the left main bronchus. Bronchoscopic examination revealed a small submucosal nodule in the left main bronchus on February 1991, from which the biopsy specimen revealed NHL infiltration similar to that of the lymph node. At follow-up bronchoscopic examination, in spite of chemotherapy, scattered NHL infiltration was found in the submucosal space of the left vocal cord, carina and the bifurcation between left upper and lower bronchi. In patients with NHL, endobronchial involvement is rare. In this case, diffuse endobronchial infiltration was not thought to be direct invasion from the lymph node but hematogenous or lymphatic spread to the bronchi.     

A case of diffuse large B-cell lymphoma transformed from immunoglobulin A-producing marginal zone B-cell lymphoma

We present a rare case of diffuse large B-cell lymphoma transformed from immunoglobulin (Ig) A-secreting marginal zone B-cell lymphoma. A 62-year-old woman was admitted to our hospital for examination of a disseminated pulmonary shadow. Gradual swelling of bilateral axilla and right inguinal lymph nodes were noted after admission. Histological examination of the lymph node biopsy specimen revealed the appearance of marginal zone B-cell lymphoma. The surface Ig of lymphoma cells was IgA-kappa, which coincided with the class of monoclonal Ig found in the patient's serum. The lymph node swelling and pulmonary shadow subsided, and the serum IgA level was normalized by 3 courses of systemic chemotherapy. However, after 4 courses of treatment, new tumor lesions at the right chest wall and left arm progressively became apparent. The biopsy specimen of the tumor showed a feature of diffuse large B-cell lymphoma. Despite intensive chemotherapy, the patient died of spreading tumor burden into the central nervous system.     

A case of primary lung cancer with cervical tuberculous lymphadenitis]

A 66-year-old woman was admitted due to right cervical lymphadenopathy and an abnormal chest radiograph. Acid-fast bacilli smear of fine needle aspiration from a right cervical lymph node was positive. Histopathological examination of the specimen obtained by percutaneous right cervical lymph node biopsy showed necrotizing epithelioid granulomas and no malignant cells. Therefore, right cervical tuberculous lymphadenitis was diagnosed. Partial lung resection of the right S4 was carried out by video-assisted thoracoscopic surgery and primary lung cancer was diagnosed. To our knowledge, there has been no previous report of both primary lung cancer and cervical tuberculous lymphadenitis being present at the time of the first examination. We report this very rare case.     

Anti-Kveim monoclonal antibody. New monoclonal antibody reacting to epithelioid cells in sarcoid granulomas

A monoclonal antibody to the sarcoid granulomagenic agent contained in Kveim suspension was prepared by immunizing mice with Kveim suspension. One monoclonal antibody (IHY-1) that reacted with the epithelioid cells in sarcoid granulomas on immunoperoxidase technique was selected. The immunoperoxidase technique was used to compare this monoclonal antibody's binding to sarcoidosis- or tuberculosis-affected lymph nodes. IHY-1 is a monoclonal antibody of IgM class. This antibody did not react to erythrocytes, lymphocytes, monocytes, alveolar macrophages, or the macrophage-derived cell lines such as U-973 and KG-1. It reacted to granuloma epithelioid cells of sarcoidosis-affected lymph nodes. The monoclonal antibody also reacted positively to epithelioid cells in tuberculous granulomas although the reaction was not as strong. Since IHY-1 was found to bind to both types of granulomas, this suggests that the epithelioid cells in sarcoidosis have antigenicity common to the epithelioid cells in tuberculosis.     

A case of small liver cancer presenting as a huge mediastinal mass]

A 61-year-old male was admitted because of hemoptysis. He had a 9 year history of liver cirrhosis associated with HB viral chronic hepatitis. Physical examination revealed no abnormalities. Laboratory investigations revealed positive HBs antigen with normal alpha-fetoprotein. Chest X-ray film showed large mediastinal lymph nodes and an endobronchial polypoid mass in the distal end of the right main bronchus. The right main PA was narrowed due to compression by the mediastinal mass. Bronchoscopic examination revealed a polypoid mass in the right main bronchus. The biopsy specimen was histologically diagnosed as undifferentiated large cell carcinoma. The patient developed respiratory failure, and died 3 weeks after admission. Autopsy revealed a small liver cancer of 1.3 cm diameter within the cirrhotic liver, associated with a small abdominal lymph node metastasis and large mediastinal lymph node swellings. Thromboembolism in the bilateral main pulmonary arteries was concluded to be the cause of death. The mediastinal mass which directly invaded into the right main bronchus had a close histological similarity with the liver cancer, showing undifferentiated carcinoma cells with bizarre nuclei and abundant cytoplasm. An immunohistological study revealed cells positive for alpha-fetoprotein in the mediastinal lymph nodes. The patient was diagnosed as having small liver cancer with mediastinal lymph node metastases. A survey of the literature revealed only a few cases of advanced hepatoma associated with prominent mediastinal metastases. This is the first reported case of small liver cancer presenting with large mediastinal lymph node metastases.     

A case of pulmonary sarcoidosis with calcification in the lung

A 35 year-old male farmer presented with complaints of productive cough and sputum. The chest X-ray films showed reticulonodular shadows bilaterally in the upper and middle lung fields, segmental infiltration in the right lung, and no BHL. Tuberculin reaction was negative. Serum angiotensin converting enzyme level was 26.5 IU/ml. Precipitating antibodies for Thermophilic actinomycetes and M.f. were negative. BAL showed moderate lymphocytosis (24.3%), and CD 4/8 was 1.67. A biopsy specimen of right scalene lymph node showed epithelioid cell granulomas and TBLB epithelioid cell granulomas and spot-like calcification. Pulmonary sarcoidosis with calcification in the lung is very rare.     

An adult case of cervico-mediastinal tuberculous lymphadenitis]

We reported a case of cervico-mediastinal tuberculous lymphadenitis followed by the development of pulmonary lesions and recurrent laryngeal nerve palsy. A 48-year-old man was admitted to our hospital due to fever, dry cough, and loss of body weight. He had no medical history of tuberculosis or other significant diseases. On admission, a right cervical tumor was palpable and chest X-ray films revealed widened superior mediastinum. Chest computed tomography showed multiple swollen mediastinal lymph nodes, including multiple low-density areas and contrast medium-enhanced septa and margins. Gallium-67 scintigraphy demonstrated abnormal uptake in the right cervix and mediastinum. A PPD skin test was strongly positive and ribosomal RNA of tubercle bacilli was detected in aspirated gastric juice. Although anti-tuberculous chemotherapy was initiated, fever and cough persisted, and hoarseness due to left recurrent laryngeal nerve palsy developed. One month later, chest X-ray films showed abnormal infiltration in the left upper lung field. The patient was sero-negative for HIV. To confirm the diagnosis, right supraclavicular lymph node biopsy was performed. Microscopic examination of the biopsy specimen revealed acid-fast bacilli and granuloma with central caseous necrosis surrounded by Langhans' giant cells and epithelioid cells. After 9 months of extended anti-tuberculous chemotherapy, the cervical and mediastinal masses receded and the abnormal chest X-ray shadows disappeared. Because the incidence of tuberculosis in Japan is gradually increasing among young people as well as the elderly, the differential diagnosis of this disease will become more necessary.     

Pulmonary Mycobacterium avium complex disease showing nodular bronchiectasis--: pathological findings in two cases

Histopathological examinations were carried out on 2 cases of Mycobacterium avium complex (MAC) disease of nodular bronchiectasis (NB) type on radiograms. The removed lung specimens revealed histological findings of granulomatous bronchiolopneumonia, consisting of epithelioid cell granulomas with lymphocytic infiltrations without exudation in the alveolar areas surrounding the respiratory bronchiole. The central bronchiolar walls were also affected by epithelioid cell granulomas with lymphocytic infiltration, occasionally showing polypoid protrusion into the bronchiolar lumen accompanying emphysema in the peripheral alveolar area. Bronchial lesions seemed to progress from peripheral to central airway with consequent atrophy and disappearance of intramural smooth muscles, resulted in bronchioloectasis. These histological findings well correspond to radiographical 'nodular bronchiectasis'. Large histiocytic granulomas without caseous necrosis developed in some area, which are not usually found in tuberculosis lesions. Epithelioid cell granulomas were occasionally found in the hilar lymph nodes as well as in the walls of lymphatic vessel in the pulmonary interlobular tissues, indicating intrapulmonary lymphatic spread of the mycobacteria.     

Does tumour necrosis factor‐α inhibitor infliximab induce histological resolution of pulmonary sarcoid granulomas?

Background: Sarcoid granuloma formation involves the orchestration of cytokines and chemokines, which modulate the host's immune response to the antigen stimulus. The release of cytokines enhances expression of the pro‐inflammatory cytokine tumour necrosis factor‐α (TNF), which plays a crucial role in the formation of sarcoid granuloma, being released from T‐lymphocytes and alveolar macrophages. Objective: The aim of this study was to evaluate the effect of infliximab in a case of pulmonary sarcoidosis using a histological approach. Materials and Methods: A 44‐year‐old man with biopsy verified chronic pulmonary sarcoidosis being resistant to treatment with corticosteroids and cell cycle inhibitors. Persisting disease activity was confirmed by declining lung function tests and a positive fluorine‐18‐fluorodeoxyglucose–positron emission tomography scan. The patient was treated with a single course of infliximab 3‐mg/kg body weight; 11 days later, a single lung transplantation was performed. Immunohistological staining with the macrophage marker CD68 was performed on lung tissue and mediastinal lymph node tissue from both the initial diagnostic evaluation (prior to infliximab) as well as from the explanted lung (after infliximab). Results: Biopsy specimens from lung and mediastinal lymph nodes prior to infliximab demonstrated sarcoid granulomas, and staining with CD68 showed dense infiltration by macrophages (epithelioid cells) in the central part of the granulomas. In contrast, biopsies from the explanted lung after infliximab demonstrated acellular sarcoid granulomas with central amorphous masses, and staining with CD68 showed complete absence of macrophages. Conclusions: In this patient, the TNF inhibitor infliximab appeared to induce resolution of sarcoid granulomas starting with disappearance of macrophages probably caused by cell lysis or apoptosis. Please cite this paper as: Milman N, Andersen CB, Baslund B, Loft A and Iversen M. Does tumour necrosis factor‐α inhibitor infliximab induce histological resolution of pulmonary sarcoid granulomas? The Clinical Respiratory Journal 2007; 1:106–113.     

An autopsy case of sudden death in a patient with giant cell myocarditis

We present a case of a 28-year-old male weight lifter who died suddenly while driving a bicycle. Forensic autopsy and histopathological examinations revealed granulomatous lesions in the myocardium and hilar lymph nodes. The latter had massive caseation necrosis, epithelioid granulomas and Langhans' giant cells suggestive of tuberculosis. However, the myocardium showed predominantly multinucleated foreign body and myogenic giant cells, lymphocytes, plasma cells, macrophages, eosinophils. Staining for acid-fast bacilli was negative. The present case highlights the difficulty in establishing whether the granulomatous lesions in the hilar lymph nodes and the myocardium are incidental findings or whether they are related by the same pathogenetic mechanisms.     

Antisynthetase syndrome associated with sarcoidosis

A 30-year-old man complained of polyarthralgia and fatigue. The clinical findings and laboratory data included myositis, polyarthritis, interstitial pneumonia, Raynaud's phenomenon, mechanic's hand, and anti PL-7 antibody (threonyl-tRNA synthetase antibody). All of these signs were consistent with antisynthetase syndrome. His chest radiograph revealed bilateral hilar lymphadenopathy. Biopsy specimens from his mediastinal lymph node and muscle showed noncaseating epithelioid cell granulomas. Lung histology revealed nonspecific interstitial pneumonia. Antisynthetase syndrome associated with sarcoidosis was diagnosed. Interstitial pneumonia in this patient responded well to high-dose corticosteroid therapy.     

Enlarged cervical lymph nodes and elevated liver chemistry tests: a therapeutic dilemma

We describe the case of a 36-years-old male patient, originating from India, who presented with enlarged cervical lymph nodes and elevated liver chemistry tests. Histologically necrosing granulomas were observed in the lymph nodes, and PCR revealed DNA from mycobacterium tuberculosis. However, in the liver biopsy granulomatous hepatitis without central necrosis was seen. With a positive PCR for mycobacteria from liver tissue and no evidence for other hepatic diseases we started drug treatment with standard quadruple regimen consisting of isoniazid, rifampicin, ethambutol, and pyrazinamide. Five days after onset of therapy, liver chemistry tests rose 10-fold, forcing us to interrupt treatment. Gradual step-wise re-exposition with the same medication after return of liver chemistry tests to baseline was well tolerated without any further side effects. Liver involvement of tuberculosis can have many facets and may be treated by gradual dosing of standard drugs.