Carcinoma of the lung and diffuse interstitial pulmonary fibrosis

The clinical and histopathological findings are presented in two cases of diffuse interstitial pulmonary fibrosis in which carcinoma of the lung developed. In one case with rheumatoid arthritis and diffuse interstitial pulmonary fibrosis there was ;malignant pulmonary adenomatosis', an association which does not appear to have been reported before. In the second case idiopathic diffuse interstitial pulmonary fibrosis was complicated by large cell anaplastic carcinoma of the lung.It is suggested that in both cases the development of carcinoma of the lung was a complication of the epithelial hyperplasia and scarring that occurs in diffuse interstitial pulmonary fibrosis.It is also suggested that carcinoma found in the main bronchi in patients with diffuse interstitial pulmonary fibrosis should not be regarded as coincidental unless careful search has excluded a carcinomatous change in the periphery of the scarred lungs.     

Misalignment of lung vessels: diagnostic role of conventional histology and immunohistochemistry

Misalignment of lung vessels represents a rare congenital anomaly that may cause respiratory failure in the newborn. It is characterized by abnormal position of pulmonary veins and venules that lie adjacent to arteries and bronchi, and it is usually associated with a decreased number of alveolar capillaries (i.e., alveolar capillary dysplasia), although these two conditions have been separately described. Awareness of this anomaly is required by pathologists because it can be easily overlooked on lung biopsy or autopsy, and because definite diagnosis relies on histology. We report the case of a newborn male baby who developed respiratory distress 18 h after an uncomplicated delivery. The patient died on the 7th day, after high frequency oscillatory ventilation, nitric oxide inhalation and extracorporeal membrane oxygenation were unsuccessful. On autopsy, histology and immunohistochemistry demonstrated diffuse changes, fulfilling diagnostic criteria of misalignment of lung vessels and of alveolar capillary dysplasia in both lungs, with muscularization of very peripheral pulmonary arteries and a prominent interstitial and periadventitial fibrosis. Diffuse distribution of vessel misalignment could explain the rapid onset of respiratory failure, and the presence of diffuse fibrosis might have contributed to irreversible respiratory dysfunction by impairment of lung parenchyma extensibility.     

Hypersensitivity peumonitis in a patient with rheumatoid arthritis]

We report a case with rheumatoid arthritis and hypersensitivity pneumonitis. A 66-year-old female was admitted to our hospital because of fever, cough, and progressive dyspnea on October 10, 1997. She had a history of rheumatoid arthritis from 1987 and was treated with cyclophosphamide when she developed pulmonary symptoms in September 1997. On admission arthritis was subsided. Fine crackles on ausculation of lung, hypoxia, ground-glass appearance on chest X-ray were detected. The computed tomography of the chest disclosed diffuse interstitial shadow with patchy destruction of alveolar structures. Bronchoalveolar lavage demonstrated an increase in lymphocytes with predominance of suppressor-cytotoxic T cell subset (CD 8+). The histopathological examination of transbronchial lung biopsy showed interstitial inflammation with marked predominance of lymphocyte with intraalveolar exudate. Her condition got better and she discharged without definitive diagnosis and treatment for her respiratory symptoms. Eight hours after she went back home, she suddenly presented high fever and cough and gradually developed dyspnea. She was readmitted 5 days after the previous discharge. Although no specific precipitin antibody against various microorganisms was detected in her sera, the diagnosis of hypersensitivity pneumonitis was made. Thirty mg per day of prednisolone was resolved her symptoms promptly. There was no reported case with hypersensitivity pneumonitis and rheumatoid arthritis of other collagen diseases. The clinical course that arthritis and pulmonary symptoms appeared alternatively is of considerable interest to investigate for the pathogenesis of these two immune disorders.     

Asbestosis: demonstration of distinctive interstitial fibroelastosis: A pilot study

Asbestosis has long been defined as a diffuse interstitial “fibrotic” process, in similarity to other chronic interstitial pulmonary diseases. To address the hypothesis (which was based on morphological nuances) that the interstitial connective tissue response in asbestosis may be fibroelastotic rather than fibrotic, a comparative characterization of the connective response in cases of asbestosis and other forms of interstitial lung disease was performed. Archival open lung biopsies or autopsy specimens of pulmonary diseases featuring interstitial connective tissue abnormalities (15 of asbestosis, 21 of organizing pneumonia, 15 usual interstitial pneumonitis/idiopathic pulmonary fibrosis [IPF], 9 organizing diffuse alveolar damage, 9 “nonspecific” interstitial pneumonitis, 4 sarcoidosis, 3 each of desquamative interstitial pneumonia and chronic amiodarone toxicity, 2 cryptogenic organizing pneumonias, and 1 each of chronic hypersensitivity pneumonitis and chronic eosinophilic pneumonitis [85 total]) were stained histochemically with hematoxylin and eosin, Perl's method, Gomori's trichrome procedure, and the Verhoeff-van Gieson technique. Representative subsets of the cases (n = 20) were also studied immunohistologically using an antibody to elastin. Fibroelastosis in each of the samples was assessed for the degree of response and its location using a 3-tiered scale. The degree of fibroelastosis in the 15 cases of asbestosis was variable, with the pattern being peribronchial and perivascular in all instances; at least 2 asbestos bodies were identified in fibroelastotic foci in each of the 15 cases as highlighted with Perl's stain. Forty-seven cases of nonasbestotic lung disease (71%) showed interstitial fibrosis with a variable (usually modest) amount of admixed elastic tissue; when present, elastic fibers were distributed in a diffuse interstitial pattern, with or without perivascular accentuation. All cases of IPF also showed areas of fibroelastosis, but those foci were confined to regions of overt “honeycomb” change. No asbestos bodies were seen in any disease except asbestosis, and a predominantly peribronchial pattern of fibroelastosis was not identified in any nonasbestotic interstitial lung disease in this study. The authors conclude that the types and patterns of pulmonary connective tissue response in interstitial lung diseases may provide additional diagnostic clues to the presence of asbestosis.     

CEMENTED TUNGSTEN CARBIDE PNEUMOCONIOSIS

An autopsy case of cemented tungsten carbide pneumoconiosis, the first lethal case in our country, is presented. A 28-year-old woman, who had been engaged in grinding presintered metallic matrix for four years, developed respiratory symptoms. X-ray examinations were indicative of interstitial pulmonary fibrosis. Corticosteroid therapy revealed only little effect. She expired five years after the onset of the symptoms. Postmortem examination showed nonspecific interstitial pneumonitis resulting in marked lung fibrosis. Ultrastructurally, crystals were observed in cytoplasm of presumable macrophages in the fibrotic lung tissue. Electron probe microanalysis of the lung tissue showed the presence of tungsten and other constituents of tungsten carbide except for cobalt. Metal analysis demonstrated a large amount of tungsten in the lung. Cobalt was detected tenfold of the normal value in the bone. In pathogenesis of the pneumoconiosis in the cemented tungsten carbide workers, toxicity of cobalt is most suspectable, and in addition, individual susceptibility may be also important.     

Bronchiolitis interstitial pneumonitis: a pathologic study of 31 lung biopsies with features intermediate between bronchiolitis obliterans organizing pneumonia and usual interstitial pneumonitis, with clinical correlation

Bronchiolitis combined with interstitial pneumonitis generally has been equated with bronchiolitis obliterans organizing pneumonia (BOOP). We describe our experience with lung biopsies that had both bronchiolar and interstitial diseases. We studied 31 patients who had respiratory difficulty leading to open lung biopsy, which showed a combination of both prominent bronchiolitis and prominent interstitial pneumonitis. We compared these cases clinically and pathologically with 6 other pulmonary diseases, namely, bronchiolitis obliterans, BOOP, nonspecific interstitial pneumonitis, usual interstitial pneumonitis, airway-centered interstitial fibrosis, and idiopathic bronchiolocentric interstitial pneumonia, and with 10 cases of cystic fibrosis, an unrelated disease with both bronchiolar and interstitial pathology. The commonality of our cases was a combination of bronchiolitis and interstitial inflammation and fibrosis but little or no intra-alveolar organizing pneumonia. Bronchiolitis obliterans with organizing pneumonia involved less area than the interstitial pneumonitis in each case. All 19 patients for whom we had follow-up received corticosteroids for their pulmonary diseases. Seven patients had improvement in symptoms and pulmonary function test results and radiographic findings, 5 patients experienced subjective improvement with unchanged results of pulmonary function tests or chest x-ray, 1 patient's condition was unchanged, 6 patients' disease worsened, and 4 of these 6 died. The natural history of these cases, which we have designated bronchiolitis interstitial pneumonitis, seems more sanguine than usual interstitial pneumonitis and worse than BOOP at least in the short term. On the one hand, response to corticosteroids was not as frequent as generally accepted for BOOP. On the other hand, disease did not progress in most patients on corticosteroids.     

Pulmonary cytoplasmic hyalin resembling Mallory's alcoholic hyalin in the liver

Sixty-three consecutive autopsy cases of interstitial fibrosis of the lung, 6 cases of organizing pneumonia, 14 of pneumocystis pneumonia, and 20 of acute bacterial pneumonia complicating as a terminal illness listed in our Department of Pathology during a period from 1978 to 1983 were surveyed for Mallory body-like cytoplasmic hyalins in the alveolar cells. We found the hyalins in 10 of 63 cases (15.9%) with interstitial fibrosis of the lung and one of 6 cases with organizing pneumonia. Seven of the former 10 had an associated malignancy; 3 esophageal cancers, 2 lung cancers, and 2 leukemias. Five of the seven patients received an irradiation for treatment of their malignancies, subsequently developed interstitial fibrosis of the lung. Among the remaining 3 of the 10, one showed diffuse interstitial fibrosis associated with rheumatoid arthritis and two had an idiopathic type of diffuse pulmonary fibrosis. There was only one case in which the pulmonary hyalins were found in the absence of extensive interstitial fibrosis within small organizing foci of peribronchial and subpleural location. Pulmonary hyalins showed the same conventional staining properties and ultrastructural features as Mallory's alcoholic hyalins found in the liver, but did not reveal a simultaneous association with the hepatic hyalins. Pulmonary hyalins frequently stained positively with monoclonal anti-cytokeratin antibodies, more strongly at their periphery. Pulmonary hyalins were considered to be a non-specific reaction of alveolar cells to injuries, mostly in association with the pulmonary fibrosis of any etiology but not the hepatic hyalins.     

PULMONARY CYTOPLASMIC HYALIN RESEMBLING MALLORY'S ALCOHOLIC HYALIN IN THE LIVER

Sixty-three consecutive autopsy cases of interstitial fibrosis of the lung, 6 cases of organizing pneumonia, 14 of pneumocystis pneumonia, and 20 of acute bacterial pneumonia complicating as a terminal illness listed in our Department of Pathology during a period from 1978 to 1983 were surveyed for Mallory body-like cytoplasmic hyalins in the alveolar cells. We found the hyalins in 10 of 63 cases (15.9%) with interstitial fibrosis of the lung and one of 6 cases with organizing pneumonia. Seven of the former 10 had an associated malignancy; 3 esophageal cancers, 2 lung cancers, and 2 leukemias. Five of the seven patients received an irradiation for treatment of their malignancies, subsequently developed interstitial fibrosis of the lung. Among the remaining 3 of the 10, one showed diffuse interstitial fibrosis associated with rheumatoid arthritis and two had an idiopathic type of diffuse pulmonary fibrosis. There was only one case in which the pulmonary hyalins were found in the absence of extensive interstitial fibrosis within small organizing foci of peribronchial and subpleural location. Pulmonary hyalins showed the same conventional staining properties and ultrastructural features as Mallory's alcoholic hyalins found in the liver, but did not reveal a simultaneous association with the hepatic hyalins. Pulmonary hyalins frequently stained positively with monoclonal anti-cytokeratin antibodies, more strongly at their periphery. Pulmonary hyalins were considered to be a non-specific reaction of alveolar cells to injuries, mostly in association with the pulmonary fibrosis of any etiology but not the hepatic hyalins.     

Expression of immunoreactive activin A protein in remodeling lesions associated with interstitial pulmonary fibrosis.

The expression of activin A, one of the transforming growth factor-beta supergene family, was studied in various pulmonary conditions associated with interstitial pulmonary fibrosis (3 cases with diffuse alveolar damage, 6 cases with idiopathic pulmonary fibrosis, and 1 case with pulmonary fibrosis associated with rheumatoid arthritis) using immunohistochemical techniques on paraffin-embedded sections. Controls consisted of 10 cases with normal pulmonary parenchyma, and 2 cases with primary pulmonary hypertension and 1 case with secondary pulmonary hypertension were also studied. The lung specimens from normal parenchyma weakly expressed immunoreactive activin A on the bronchiolar epithelium. In marked contrast, all of the specimens from cases with diffuse alveolar damage and interstitial pulmonary fibrosis demonstrated strong expression of activin A on metaplastic epithelium, hyperplastic smooth muscle cells, desquamated cells, and alveolar macrophages. Pulmonary arteries from patients with primary or secondary pulmonary hypertension showed abundant immunoreactive activin A on smooth muscle cells. These findings suggest a potential role for this growth factor, activin A, in the pathogenesis of pulmonary tissue remodeling associated with interstitial pulmonary fibrosis.     

Diffuse pulmonary ossifications with mortal consequences. A case report

Dendriform pulmonary ossification (DPO) represents a relatively frequent form of diffuse pulmonary and mostly clinically inapparent bone formation of unknown etiology. An association with other pulmonary diseases, particularly pulmonary interstitial fibrosis, has been suggested. Here we report a female patient with a 15-year history of DPO whereby at the age of 48 an X-ray of the thorax first revealed findings suggestive of pulmonary fibrosis. For 9 years the patient suffered from chronic progressive ventilation disorder and after a further 3 years open lung biopsy revealed DPO in conjunction with interstitial fibrosis. After a history of progressive respiratory failure the patient suddenly died of cardiac arrhythmia along with deteriorated cor pulmonale at the age of 71. Autopsy revealed an almost complete ossification of the lungs with an increasing gradient from apex to base. In contrast to previous reports, the DPO of our patient was life-limiting.     

Fibrosis with emphysema

Wright J L, Tazelaar H D & Churg A (2011) Histopathology  58 , 517–524
Fibrosis with emphysema The concept of fibrosis with emphysema is confused by the existence of two very different clinical/pathological scenarios: first, cases in which a diffuse fibrosing interstitial pneumonia, most commonly usual interstitial pneumonia (UIP), occurs in a patient with emphysema. This combination is largely of clinical interest because of its effects on pulmonary function and pulmonary hypertension, but can produce unusual appearances in surgical lung biopsies when the fibrotic areas are wrapped around emphysematous spaces. However, the underlying morphology of emphysema and UIP or other interstitial lung disease remains unchanged. Radiological consultation is often helpful to show that the patient has both lesions; secondly, cases in which there is localized fibrosis that is part of emphysema, or related to respiratory bronchiolitis, or both. These lesions have been called ‘respiratory bronchiolitis’ (RB), ‘respiratory bronchiolitis–interstitial lung disease’ (RB‐ILD), ‘airspace enlargement with fibrosis’, ‘RB‐ILD with fibrosis’ and ‘clinically occult interstitial fibrosis in smokers’, but are probably all the same entity. Such changes are associated only rarely with the physiological or radiological features of an interstitial lung disease. Care should be taken when describing these lesions in biopsies so as not to give the impression that a diffuse interstitial lung disease is present.     

Quantitation of cytomegalovirus DNA in lung tissue of bone marrow transplant recipients.

Five bone marrow transplant recipients who died of respiratory failure were retrospectively analyzed with polymerase chain reaction (PCR) assay for pulmonary cytomegalovirus (CMV) infection. Two patients had CMV interstitial pneumonitis according to the virus isolation and the histologic and immunofluorescent examinations of the lungs, while the other three patients had non-CMV diseases (ie, idiopathic interstitial pneumonitis, pulmonary aspergillosis, or Streptococcus mitis septicemia). Cytomegalovirus DNA was amplified from the postmortem lung tissue with PCR. The PCR assay showed apparent PCR signals specific to CMV DNA in the two patients with CMV pneumonitis. In contrast, CMV DNA was hardly detectable or undetectable in the three patients without CMV disease. With quantitative PCR assay the initial CMV copy number in the lung tissue of the two patients with CMV pneumonitis was more than 10(4) copies/micrograms DNA and was over 1,000-fold more than that of the three patients without CMV pneumonitis. These results show that quantitative PCR assay could be useful as a diagnostic measure for pulmonary CMV infection.     

Pulmonary fibrosis in a steel mill worker

We report a case of pulmonary fibrosis in a 32-year-old man, who had worked at a steel mill and who died of respiratory failure due to interstitial fibrosis despite vigorous treatment. He showed SLE-associated symptoms, such as pleural effusion, malar rashes, discoid rashes, arthritis, leukopenia, and positive antinuclear antibody and anti-histone antibody. However, he did not present anti-DNA antibody. A thoracoscopic lung biopsy showed interstitial fibrosis, chronic inflammation and a small non-caseating granuloma in lung tissues, which could be induced by external agents such as metals. The manganese concentration in the lung tissue was 4.64 microg/g compared to 0.42-0.7 microg/g in the controls. The levels of other metals, such as iron, nickel, cobalt and zinc in patient's lung tissue were higher than those in the controls. The patient was probably exposed to Si and various metal dusts, and the lung fibrosis was related to these exposures. Exposure to Si and metal dusts should be sought in the history of any patient with SLE, especially in a male with pulmonary signs, and if present, exposure should be stopped. In the meantime, steps should be taken to ensure that workers exposure to Si and metal dusts in all environments have adequate protection.     

Rheumatoid arthritis complicated by pachy- and leptomeningeal rheumatoid nodule-tike granulomas and systemic vasculitis

Rheumatoid nodule is a frequent and characteristic extra-articular manifestation of rheumatoid arthritis (RA). Its involvement of central nervous system is a rare occurrence with only a few reported cases. A 78-year-old man with severe arthritis showing the formation of rheumatoid nodule-like granulomas in the dura and subarachnoid space along with the spleen is presented. The characteristic morphological finding of the granulomas was the presence of neutrophlls and the absence of definite fibrinoid necrosis, which differed from the typical features of rheumatoid nodules previously described. The diagnosis should be based on the exclusion of diseases that may cause similar granulomatous reactions including infectious diseases. Additionally, there was systemic necrotizing vasculitis in the dura and multiple cerebral Infarcts, although the association between vasculitis and cerebral infarcts was not clear.     

The pathology of asbestosis

The term asbestosis refers to diffuse interstitial pulmonary fibrosis consequent to the excess inhalation of asbestos fibres. It is a disease associated with heavy cumulative asbestos dose and the latent period, from initial exposure to disease manifestation, is long usually 20 years or more, with an inverse correlation with dose. Because heavy industrial exposures have diminished the incidence of asbestosis has decreased. Asbestosis is a divisible disease with the frequency and severity of disease correlating with cumulative asbestos dose. Disease severity also correlates with asbestos fibre type (amphiboles more potent than commercial chrysotile), immune and genetic factors. Pathologically, there are two components to the diagnostic criteria which must be met: first, the presence of diffuse interstitial lung fibrosis of an appropriate pattern; and second, some tissue marker of excess asbestos inhalation either requisite numbers of asbestos bodies (as determined by light microscopy) or elevated asbestos fibres (as determined by mineral analysis). The clinical picture is not specific although in contrast to idiopathic pulmonary fibrosis, which is the most frequent diagnostic problem, asbestosis has a slowly progressive course over decades. Lung cancer occurs at cumulative asbestos doses similar to that necessary to cause lung fibrosis (asbestosis). The main differential diagnoses with asbestosis are idiopathic pulmonary fibrosis, pulmonary fibrosis associated with connective tissue disorders, chronic phase hypersensitivity pneumonitis and silicate (mica, talc, kaolin) pneumoconiosis.     

人感染高致病性禽流感病毒H5N1的病理学观察

目的 观察人感染高致病性禽流感病毒H5N1后各主要脏器的病理改变.方法 按传染病尸体解剖要求对2例死亡病例系统解剖,并获得心、肝、脾、肺和肾等主要脏器,对1例重症患者行肺大泡切除术,组织常规HE和免疫组织化学染色,光学显微镜下观察.结果 2例肺组织主要呈弥漫性肺泡损伤改变.早期呈渗出性改变,肺泡上皮坏死脱落,肺泡腔内见大量均匀粉染渗出液伴广泛透明膜形成.中晚期主要呈增生性和纤维化性改变,肺泡上皮和支气管上皮增生,肺泡腔内渗出物和肺间质纤维化.1例在慢性支气管扩张症基础上伴弥漫性肺泡损伤和肺间质纤维化.免疫器官改变:全身淋巴组织萎缩伴活跃的噬血现象.其他脏器病变:1例心脏有间质性心肌炎;1例肾脏有急性肾小管坏死;1例有脑水肿伴脑实质内神经细胞嗜酸性变,轴突肿胀,粗细不均.脑室旁见灶状坏死.1例孕妇胎盘内多灶状滋养叶细胞坏死伴营养不良性钙化,有急性坏死性蜕膜炎.胚胎肺脏有肺水肿和肺炎改变.结论 人感染高致病性禽流感病毒H5N1后首先出现呼吸系统症状,广泛弥漫性肺泡损伤致低氧血症是病理学基础,患者最终因多器官功能衰竭致呼吸、循环衰竭死亡.     

Intraluminal fibrosis in interstitial lung disorders.

The histopathologic and ultrastructural features of intraluminal organizing and fibrotic changes were studied in open lung biopsies and autopsy specimens from 373 patients with interstitial lung disorders, including hypersensitivity pneumonitis (n = 44), idiopathic pulmonary fibrosis (n = 92), collagen-vascular diseases (n = 20), chronic eosinophilic pneumonia (n = 10), pulmonary histiocytosis X (n-90), pulmonary sarcoidosis (n = 62), pneumoconioses (n = 25), Legionnaire's disease (n = 5), drug- and toxin-induced pneumonitis (n = 4), radiation-induced pneumonitis (n = 2), lymphangioleiomyomatosis (n = 11), and chronic organizing pneumonia of unknown cause (n = 8). Three patterns of intraluminal organization and fibrosis were recognized: 1) intraluminal buds, which partially filled the alveoli, alveolar ducts and/or distal bronchioles; 2) obliterative changes, in which loose connective tissue masses obliterated the lumens of alveoli, alveolar ducts or distal bronchioles, and 3) mural incorporation of previously intraluminal connective tissue masses, which fused with alveolar, alveolar ductal, or bronchiolar structures and frequently became reepithelialized. All three patterns had common morphologic features, suggesting that, regardless of their severity, they resulted from a common pathogenetic mechanism, ie, the migration of activated connective tissue cells, through defects in the epithelial lining and its basement membrane, from the interstitial into the intraluminal compartment. Intraluminal buds were observed most frequently in hypersensitivity pneumonitis, chronic eosinophilic pneumonia, and organizing pneumonia of unknown cause. Mural incorporation and, to a lesser extent, obliterative changes were observed in most interstitial disorders and were very prominent in idiopathic pulmonary fibrosis. Mural incorporation and obliterative changes play an important role in pulmonary remodeling, especially when several adjacent alveoli and/or other air spaces are involved. Under these circumstances, intraluminal organization can mediate the fusion of adjacent alveolar structures by intraluminal connective tissue.     

Arthritis and pneumonitis produced by the same T cell clones from mice with spontaneous autoimmune arthritis

SKG mice, a newly established model of rheumatoid arthritis (RA), spontaneously develop autoimmune arthritis accompanying extra-articular manifestations, such as interstitial pneumonitis. To examine possible roles of T cells for mediating this systemic autoimmunity, we generated T cell clones from arthritic joints of SKG mice. Two distinct CD8(+) clones were established and both showed in vitro autoreactivity by killing syngeneic synovial cells and a variety of MHC-matched cell lines. Transfer of each clone to histocompatible athymic nude mice elicited joint swelling and histologically evident synovitis accompanying the destruction of adjacent cartilage and bone. Notably, the transfer also produced diffuse severe interstitial pneumonitis. Clone-specific TCR gene messages in the inflamed joints and lungs of the recipients gradually diminished, becoming hardly detectable in 6-11 months; yet, arthritis and pneumonitis continued to progress. Thus, the same CD8(+) T cell clones from arthritic lesions of SKG mice can elicit both synovitis and pneumonitis, which chronically progress and apparently become less T cell dependent in a later phase. The results provide clues to our understanding of how self-reactive T cells cause both articular and extra-articular lesions in RA as a systemic autoimmune disease.     

Mycobacterium kansasii diffuse pulmonary infection in a patient with acquired immune deficiency syndrome. Successful therapy with an antituberculous regimen

Mycobacterium kansasii is a rare cause of disseminated mycobacterial infection in patients with the acquired immune deficiency syndrome (AIDS). It occurs as the index AIDS diagnosis in only 0.2% of AIDS cases. Previously reported cases of AIDS-associated M. kansasii infection have manifested as diffuse interstitial pneumonitis and diffuse small bowel inflammation and have been refractory to antimycobacterial therapy. The authors now report success in treating a hypoxemic patient with AIDS-associated M. kansasii diffuse granulomatous interstitial pneumonitis that was diagnosed by open lung biopsy. The patient has no evidence of mycobacterial disease after 12 months of therapy with isoniazid, rifampin, and ethambutol.     

Pulmonary pathology of Erdheim-Chester disease.

Erdheim-Chester disease (ECD) is a rare non-Langerhans' cell histiocytosis that may present with pulmonary symptoms. The condition seems to be nonfamilial and typically affects middle-aged adults. Radiographic and pathologic changes in the long bones are diagnostic, but patients often present with extraskeletal manifestations. Advanced pulmonary lesions are associated with extensive fibrosis that may lead to cardiorespiratory failure. The clinical, radiologic, and pathologic features of six patients with ECD with lung involvement are presented. The patients were three men and three women (mean age, 57). Five presented with progressive dyspnea, and one presented with diabetes insipidus. Open-lung biopsies showed histiocytic infiltrates in a lymphangitic pattern with associated fibrosis and lymphoplasmacytic inflammatory infiltrates. The histiocytes did not stain with periodic acid-Schiff. Immunoperoxidase studies performed on specimens from five of six patients showed that the histiocytes were positive for CD68 and Factor XIIIa and negative for CD1a. Specimens from two patients exhibited immunoreactivity for S-100 protein. Electron microscopy studies performed on specimens from two patients showed phagocytic lysosomes but no Birbeck granules. Clinical follow-up of up to 16 years was available. At the end of that time, five patients were dead of complications related to their disease; one patient remains alive 4 years after diagnosis but with severe respiratory compromise. ECD is a rare non-Langerhans' cell histiocytosis that may present as interstitial lung disease and resemble other pulmonary conditions, particularly usual interstitial pneumonitis and pulmonary Langerhans' cell histiocytosis. Recognition of this entity will allow better assessment of its true incidence, therapeutic options, and prognosis.