Lesions of the small airway are observed in a wide variety of pulmonary conditions, most of which are due to infection, tobacco and connective tissue diseases. They are sometimes isolated or, more often, associated with involvement of other pulmonary structures such as the bronchi, the lung parenchyma and the pleura. The pathological spectrum of the bronchiolar response to injury is relatively limited. Thus, the same lesion is observed in various clinical settings. There is no correlation between the severity of the small airway involvement seen by the pathologist and the clinical and functional manifestations of bronchiolitis. The causes of bronchiolitis may be classified on a clinical basis, on aetiology or on histological appearance, yet no single classification appears to be suitable. An integrated clinical, radiological, functional and histological approach is needed. As they are seen by the pathologist microscopically, small airway lesions may be subdivided into three categories: (1) simple nonspecific lesions (bronchiolitis - cellular, follicular, granulomatous, obliterative, constrictive) that are never exclusively related to one clinical picture, (2) or displaying a more specific pattern like the respiratory bronchiolitis of the smoker or the histolgical changes of asthma, (3) bronchiolar lesions in conditions described as "interstitial", predominantly centrilobular, involving the small airways and the lung parenchyma, and visible radiologically. After recalling the normal histological appearances of the bronchioles, this review describes the diversity of the histopathological lesions of the small airways.

Crystal-storing histiocytosis (CSH) localized to the thoracic region is a rare occurrence, often secondary to lymphoproliferative or plasma cell diseases. About 10 case reports have been previously published, and 3 of these have no relationship with clonal hematologic disorders. We collected here the first series of 5 consecutive cases of CSH involving lungs (4 cases) and pleura (1 case). There were 3 women and 2 men with a mean age at diagnosis of 65 years. All cases had an underlying hematologic disorder (2 B-cell marginal-zone lymphomas, 2 monoclonal gammopathy of undetermined significance and 1 pulmonary plasmacytoma). Despite a common morphology characterized by a dense and irregular growth of large eosinophilic histiocytes with intracytoplasmic refractile crystals, 2 cases presented with cystic changes at gross and imaging examinations, calcified amyloid was found in 2 cases, and 1 case showed an interstitial lung disease with nonspecific interstitial pneumonia pattern. Histiocytes were immunoreactive for CD68 (clones PGM-1 and KP-1) but were not for CD1a and S100; the associated lymphoplasmacellular disorder had a clonal profile on molecular analysis with κ light-chain restriction. Two cases were originally misdiagnosed as cystic fibrohistiocytic tumor and carcinoid tumor, thus confirming that CSH localized to this site may result in a diagnostic challenge with a broad spectrum of differential diagnoses. The presence of intracytoplasmic crystals and a plasma cell infiltrate around a histiocytic proliferation should alert the pathologist to consider CSH and to carefully investigate the presence of clonal hematologic disease.

IgG4-related lung disease is commonly associated with autoimmune pancreatitis. Recently, isolated IgG4-related interstitial lung disease (ILD) without other organ involvement has newly been reported in two cases with clinical features of nonspecific interstitial pneumonitis (NSIP).We report the first case of an isolated IgG4-related ILD in a 78-year-old man with dry cough and dyspnea, whose clinical findings proved to be different from NSIP. Serum IgG4 levels were increased. Chest CT scan revealed bilateral consolidations especially in the lower lobes, enlarged mediastinal and hilar lymph nodes and pleural effusions. Video-assisted thoracoscopic (VATS) lung biopsy revealed a pattern similar to usual interstitial pneumonia (UIP) and an abundant IgG4-positive plasma cell infiltration. He was effectively treated by steroid therapy.Increasing recognition of IgG4 related diseases has led to a growing number of new entities. The novel concept of isolated IgG4-related ILD as a pulmonary manifestation of a systemic IgG4-related disorder should be taken into account as a possible differential diagnosis of ILD and mass-forming lesions, even when no other organ manifestation is clinically apparent at the time of diagnosis. Lung specific diagnostic criteria and algorithms are required to enhance diagnostic accuracy in cases of possible IgG4-related ILD.

The aim of this study was to describe the high-resolution CT (HRCT) scan features that characterize familial interstitial pneumonia (FIP).FIP was defined by the presence of two or more cases of probable or definite idiopathic interstitial pneumonia (IIP) in individuals related within three degrees. The cases were collected consecutively from three centers. We identified 371 individuals with potential FIP from 289 families, including 340 individuals who had HRCT scans. Two chest radiologists independently reviewed the HRCT scans, scoring the extent and distribution of HRCT scan findings, and assessed the overall radiologic diagnosis.HRCT scan abnormalities suggestive of IIP were present in 85% (289 of 340 subjects). The most frequent findings were reticular pattern (n = 238, 82%) and ground-glass opacity (GGO) associated with reticular abnormality (n = 231, 80%). Other changes included GGO in 116 (40%), honeycombing in 92 (32%), and micronodules in 65 (22%). In the 289 cases with evidence of IIP, the findings were diffusely distributed in the craniocaudal plane in 186 (64%), and the lower lung zones were predominantly involved in 89 (31%). In the axial plane, 194 (67%) had a subpleural distribution; 88 (30%) were diffuse. The imaging pattern was classified as definite or probable usual interstitial pneumonia (UIP) in only 62 subjects (22%) and definite or probable nonspecific interstitial pneumonia (NSIP) in 35 subjects (12%). In 160 subjects (55%), the imaging findings did not conform to previously described UIP or NSIP patterns.Reticulation and a mixed GGO/reticular pattern are the most common HRCT scan findings in FIP. The parenchymal abnormalities are most often diffuse in the craniocaudal dimension and have a predominantly peripheral distribution in the axial dimension. Although a radiologic UIP pattern is not uncommon, most cases do not conform to typical UIP or NSIP patterns.

Lung disease is common among wild and managed populations of bottlenose dolphins Tursiops truncatus. The purpose of the study was to apply standardized techniques to the ultrasound evaluation of dolphin lungs, and to identify normal and abnormal sonographic findings associated with pleuropulmonary diseases. During a 5 yr period (2005 to 2010), 498 non-cardiac thoracic ultrasound exams were performed on bottlenose dolphins at the Navy Marine Mammal Program in San Diego, California, USA. Exams were conducted as part of routine physical exams, diagnostic workups, and disease monitoring. In the majority of routine exams, no abnormal pleural or pulmonary findings were detected with ultrasound. Abnormal findings were typically detected during non-routine exams to identify and track disease progression or resolution; therefore, abnormal results are overrepresented in the study. In order of decreasing prevalence, abnormal sonographic findings included evidence of alveolar-interstitial syndrome, pleural effusion, pulmonary masses, and pulmonary consolidation. Of these findings, alveolar-interstitial syndrome was generally nonspecific as it represented several possible disease states. Pairing ultrasound findings with clinical signs was critical to determine relevance. Pleural effusion, pulmonary masses, and pulmonary consolidation were relatively straightforward to diagnose and interpret. Further diagnostics were performed to obtain definitive diagnoses when appropriate, specifically ultrasound-guided thoracocentesis, fine needle aspirates, and lung biopsies, as well as radiographs and computed tomography (CT) exams. Occasionally, post mortem gross necropsy and histopathology data were available to provide confirmation of diagnoses. Thoracic ultrasound was determined to be a valuable diagnostic tool for detecting pleural and pulmonary diseases in dolphins.

It has been shown that peripheral muscle dysfunction is a critical factor in determining exercise intolerance in patients with several chronic lung diseases, including idiopathic pulmonary fibrosis. We hypothesized that exercise capacity would be, at least in part, determined by peripheral muscle dysfunction in patients with fibrotic nonspecific interstitial pneumonia (f-NSIP), another major subtype of fibrotic interstitial lung disease. The aim of the current study was to elucidate the relevance of peripheral muscle dysfunction and its contribution to exercise intolerance in f-NSIP.The six-minute walk test was evaluated in 30 consecutive patients with f-NSIP along with potential determinants of exercise capacity, including respiratory muscle force and peripheral muscle force.Among 30 patients, the median age was 61 years, and 21 were female. Sixteen patients showed significantly decreased quadriceps force (QF), and 17 had significant decreases in maximum expiratory pressure. Exercise capacity and muscle power were clearly related to sex. Adjusted for sex, QF showed a significant relation to exercise capacity measured by six-minute walk distance (6MWD), whereas pulmonary function parameters such as vital capacity showed marginal correlations. In stepwise multiple regression analysis, only QF was an independent predictor of 6MWD.Quadriceps weakness is often observed in patients with f-NSIP. It seems that QF significantly contributes to exercise capacity in this population.

Pulmonary dendritic cells (DCs) are key regulators of immune responses. An increased accumulation of DCs was reported in the lungs of patients with idiopathic interstitial pneumonia (IIP).This study aimed to investigate the number of pulmonary DCs in patients with collagen vascular disease associated interstitial lung diseases (CVD-ILDs).Lung tissue samples obtained from 27 patients with IIP and 39 patients with CVD-ILD were detected using monoclonal antibodies against CD1a, CD1c, CD83, Langerin and DC-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN).No significant differences in the number or distribution of DCs were observed between patients with IIP and CVD-ILDs. When DC marker expression was analyzed according to pathological subgroup, patients with idiopathic usual interstitial pneumonia (UIP) showed increased DC-SIGN staining when compared with CVD-UIP (p < 0.05).Both mature and immature DCs accumulate in CVD-ILDs. The number of DCs expressing DC-SIGN in CVD-UIP was decreased compared with that in idiopathic UIP. The variation in accumulated DC-SIGN-positive cells might help to explain the differences in the development and maintenance of lung inflammation between idiopathic UIP and CVD-UIP.

Scleroderma is a generalized connective tissue disease characterised by inflammatory, vascular and fibrotic changes of skin and a variety of internal organs. Pulmonary disease is estimated to occur in 70% to 85% of patients with scleroderma. Lung involvement is usually seen as diffuse and bilateral basilar reticulonodular infiltrates. A 45 year old woman was admitted to the hospital because of coughing for a period one month and detected multiple, diffuse, irregular pulmonary nodules reported in chest computerised tomography. The thickening of the skin of the fingers, face and neck, sclerodactyly and the loss of substance from the finger pad were found in physical examination. No clinical or laboratory findings suggesting malignancy was found. Elevated liver function tests, antinuclear antibody, antimitochondrial antibody and anticentromer antibody were detected in blood analyse. In the bronchoalveolar lavage of the patient whose DLCO was decreased, 61% lymphocyte, 13% eosinophil was seen. The computerised tomography guided lung biopsy was reported as nonspecific interstitial pneumonia, liver biopsy was reported as portal inflammation and fibrosis. With these findings the patient was diagnosed as scleroderma and treated with cyclophosphamid and corticosteroid. At the end of the first month of the treatment nodular lesions were disappeared in the chest computerised tomography. With the unusual radiologic manifestation, scleroderma should be also considered in the etiology of multipl pulmonary nodules.

The differential diagnosis between idiopathic nonspecific interstitial pneumonia(INSIP) and idiopathic pulmonary fibrosis(IPF)/usual interstitial pneumonia(UIP)is tough in both clinicians and pathologists. In this study, we analyzed the lesions of right lung removed from a 58-year-old patient by gross and microscopy. The results showed that the pathological appearance of nonspecific interstitial pneumonia (NSIP) and UIP coexisted in his upper lobe. Besides, because of severe fibrosis in middle and lower lobes, it was hard to distinguish the lesions of NSIP fibrotic pattern (NSIP-F) or UIP. Based on clinic-radiologic-pathological data, the diagnosis of INSIP-F was made for this patient finally. Our study suggests that UIP is not always an accurate diagnosis when the NSIP and UIP coexist, and NSIP can have regions of UIP. VIRTUAL SLIDE: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2573531681608730.

To describe computed tomographic (CT) findings of anthracofibrosis involving lung parenchyma.Retrospectively reviewed CT findings of 34 patients with anthracofibrosis involving lung parenchyma, showing deposition of anthracotic pigmentation with focal fibrotic lesions on histologic examination.Types included nodules (41.2%), masses (55.9%), and fibrotic consolidation (2.9%). The mean size was 26.8 mm. The most common location was right upper lobe (n = 10). Satellite nodules were identified in 5 patients, calcification was identified in 11 patients, necrotic low attenuation was identified in 9 patients, and marginal spicule was identified in 26 patients (76.5%). The CT images showed airway manifestation of anthracofibrosis in 13 patients, nodal manifestation in 11 patients, and inactive tuberculosis in 14 patients. Initial radiologic diagnosis included tuberculosis (n = 10), lung cancer (n = 9), organized pneumonia (n = 7), nonspecific pulmonary nodule (n = 7), and anthracofibrosis (n = 1).Anthracofibrosis involving lung parenchyma appears as a nodule, mass, or fibrotic consolidation, surrounded by long spicule. It may be the spectrum of bronchial anthracofibrosis involving small airway of lung parenchyma.