Radiological-pathological correlation of negative CT biopsy results enables high negative predictive value for thoracic malignancy.

AIM: To evaluate multidisciplinary team (MDT) practice of radiological-pathological correlation of non-malignant biopsy results to examine the additive effect on the predictive values of computed tomography (CT) biopsy for malignancy and their subsequent management and outcomes. MATERIALS AND METHODS: A service evaluation of the MDT management of non-malignant lung biopsy results (May 2014- May 2017) was undertaken. RESULTS: Sixty patients had a non-malignant diagnosis on initial CT biopsy. Five patients were lost to follow-up leaving 55 in the final cohort. Forty-eight of the 55 patients had biopsy results classified as potentially non-specific, of which 26 were classified as concordant with radiology (e.g., organising pneumonia with compatible CT features), and 22 were classified as discordant (e.g., non-specific inflammation and yet sufficiently suspicious CT features). Patients with concordant negative pathology showed resolution (n=19) or stability (n=6) on imaging follow-up. One lesion demonstrated growth and was proven malignant on surgical resection. Discordant lesions were managed with repeat biopsy (n=8) or surgical resection (n=13), with 12 final benign diagnoses and nine malignancies. The negative predictive value of CT biopsy alone was 44/55 (80%), following repeat biopsy was 44/50 (88%), and following radiological-pathological assessment was 32/33 (97%). No patients underwent a shift in stage from time of biopsy to resection. CONCLUSION: Combining radiological-pathological interpretation of negative biopsy results offers superior negative predictive value for lung malignancy without delayed diagnosis of lung cancer.

PGAM5 expression and macrophage signatures in non-small cell lung cancer associated with chronic obstructive pulmonary disease (COPD).

BACKGROUND: COPD patients are at increased risk of developing non-small cell lung carcinoma that has a worse prognosis. Oxidative stress contributes to carcinogenesis and is increased in COPD patients due to mitochondrial dysfunction. We determined whether mitochondrial dysfunction is a contributing factor to the reduced survival of COPD patients with non-small cell lung carcinoma (NSCLC). METHODS: Using a transcriptomic database and outcome data of 3553 NSCLC samples, we selected mitochondrial-related genes whose levels in the tumour correlated with patient mortality. We further selected those genes showing a ≥ 2 fold expression in cancer compared to normal tissue. Cell-type specific expression of these proteins in lung tissue from NSCLC patients who were non-smokers or smokers with or without COPD (healthy smokers) was determined by immunohistochemistry. Gene set variation analysis was used in additional NSCLC datasets to determine the relative expression of specific macrophage transcriptomic signatures within lung cancer tissue. RESULTS: The expression of 14 mitochondrial-related genes was correlated with patient mortality and these were differentially expressed between cancer and normal lung tissue. We studied further the expression of one of these genes, PGAM5 which is a regulator of mitochondrial degradation by mitophagy. In background lung tissue, PGAM5 was only expressed in alveolar macrophages, with the highest expression in smokers with COPD compared to healthy smokers and non-smokers. In cancerous tissue, only the malignant epithelial cells and associated macrophages at the periphery of the cancer expressed PGAM5. Pre-neoplastic epithelium also showed the expression of PGAM5. There was no difference in expression in cancer tissue between COPD, healthy smoker and non-smoker groups. Macrophages at the edge of the cancer from COPD patients showed a trend towards higher expression of PGAM5 compared to those from the other groups. There was a significant correlation between PGAM5 expression in cancer tissue and the level of expression of 9 out of 49 previously-defined macrophage transcriptomic signatures with a particular one associated with patient mortality (p < 0.05). CONCLUSION: PGAM5 is expressed in pre-neoplastic tissue and NSCLC, but not in normal epithelium. The association between PGAM5 expression and patient mortality may be mediated through the induction of specific macrophage phenotypes.

Pulmonary light-chain deposition disease: CT and pathology findings in nine patients.

AIM: To review the clinical features of nine patients with pulmonary light-chain deposition disease (LCDD) and record their high-resolution CT (HRCT) and histopathological findings. MATERIALS AND METHODS: Patients with a diagnosis of LCDD on lung biopsy specimen were retrospectively identified. The HRCT characteristics of nodules, cysts, and ancillary findings; change at follow-up; and histopathological findings were documented. RESULTS: Features common to all nine cases were thin-walled cysts. In seven cases, vessels traversing the cysts were identified. The majority of patients (8/9) had at least one pulmonary nodule. There was no zonal predominance of either cysts or nodules. The disease appeared stable in the majority of cases with no serial change in HRCT appearances (5/6 cases with follow-up data, mean duration 29 months). CONCLUSION: To the authors' knowledge, this is the largest series of pulmonary LCDD patients in the literature, and the first systematic assessment of HRCT findings. Pulmonary cysts are a unifying feature, usually with pulmonary nodules, and serial change on HRCT is unusual.

Congenital diaphragmatic hernia.

Infants with congenital diaphragmatic hernia (CDH) have significant mortality and long-term morbidity. Only 60-70% survive and usually those in high-volume centres. The current Task Force, therefore, has convened experts to evaluate the current literature and make recommendations on both the antenatal and post-natal management of CDH. The incidence of CDH varies from 1.7 to 5.7 per 10,000 live-born infants depending on the study population. Antenatal ultrasound scanning is routine and increasingly complemented by the use of magnetic resonance imaging. For isolated CDH, antenatal interventions should be considered, but the techniques need vigorous evaluation. After birth, management protocols are often used and have improved outcome in nonrandomised studies, but immediate intubation at birth and gentle ventilation are important. Pulmonary hypertension is common and its optimal management is crucial as its severity predicts the outcome. Usually, surgery is delayed to allow optimal medical stabilisation. The role of minimal invasive post-natal surgery remains to be further defined. There are differences in opinion about whether extracorporeal membrane oxygenation improves outcome. Survivors of CDH can have a high incidence of comorbidities; thus, multidisciplinary follow-up is recommended. Multicentre international trials are necessary to optimise the antenatal and post-natal management of CDH patients.

Significance of connective tissue disease features in idiopathic interstitial pneumonia.

In idiopathic interstitial pneumonia (IIP), the significance of connective tissue disease (CTD) features in the absence of a specific CTD diagnosis remains unclear. We studied the clinical and prognostic utility of a diagnosis of undifferentiated CTD (UCTD) in patients with biopsy-proven IIP. IIP patients undergoing surgical lung biopsy (1979-2005) were studied (nonspecific interstitial pneumonia (NSIP), n = 45; idiopathic pulmonary fibrosis, n = 56). UCTD was considered present when serum autoantibodies were present and symptoms or signs suggested CTD. The relationship between UCTD and NSIP histology was evaluated. A clinical algorithm that best predicted NSIP histology was constructed using a priori variables. The prognostic utility of UCTD, and of this algorithm, was evaluated. UCTD was present in 14 (31%) NSIP and seven (13%) IPF patients. UCTD was not associated with a survival benefit. The algorithm predictive of NSIP (OR 10.4, 95% CI 3.21-33.67; p<0.0001) consisted of the absence of typical high-resolution computed tomography (HRCT) features for IPF and 1) a compatible demographic profile (females aged <50 yrs) or 2) Raynaud's phenomenon. In patients with an HRCT scan not typical for IPF, this algorithm predicted improved survival (hazard ratio 0.35, 95% CI 0.14-0.85; p = 0.02) independent of IIP severity. UCTD is associated with NSIP histology. However, the diagnostic and prognostic significance of UCTD in IIP patients remains unclear.

Expression of muscarinic receptors by human macrophages.

Macrophages increase in number and are highly activated in chronic obstructive pulmonary disease (COPD). Muscarinic receptor antagonists inhibit acetylcholine-stimulated release of neutrophilic chemoattractants, suggesting that acetylcholine may regulate macrophage responses. Therefore, expression and function of components of the non-neuronal cholinergic system in monocyte-macrophage cells was investigated. RNA was isolated from monocytes, monocyte-derived macrophages (MDMs), lung and alveolar macrophages from nonsmokers, smokers and COPD patients, and expression of the high-affinity choline transporter, choline acetyltransferase, vesicular acetylcholine transporter and muscarinic receptors (M(1)-M(5)) ascertained using real-time PCR. M(2) and M(3) receptor expression was confirmed using immunocytochemistry. Release of interleukin (IL)-8, IL-6 and leukotriene (LT)B(4) were measured by ELISA or EIA. All monocyte-macrophage cells expressed mRNA for components of the non-neuronal cholinergic system. Lung macrophages expressed significantly more M(1) mRNA compared with monocytes, and both lung macrophages and alveolar macrophages expressed the highest levels of M(3) mRNA. Expression of M(2) and M(3) protein was confirmed in MDMs and lung macrophages. Carbachol stimulated release of LTB(4) from lung macrophages (buffer 222.3 ± 75.1 versus carbachol 1,118 ± 622.4 pg · mL(-1); n = 15, p<0.05) but not IL-6 or IL-8. LTB(4) release was attenuated by the M(3) antagonist, 1,1-dimethyl-4-diphenylacetoxypiperidinium iodide (4-DAMP; half maximal effective concentration 5.2 ± 2.2 nM; n = 9). Stimulation of macrophage M(3) receptors promotes release of LTB(4), suggesting that anti-muscarinic agents may be anti-inflammatory.

Elevated nocturnal desaturation index predicts mortality in interstitial lung disease.

BACKGROUND: Nocturnal desaturation may contribute to long-term pulmonary vascular stress in interstitial lung disease (ILD). We study the prevalence, severity and prognostic utility of nocturnal desaturation across ILD. METHODS: ILD patients with overnight oximetry (June 2006-August 2008) were reviewed (n = 134). Significant nocturnal desaturation was considered as > 10% of sleep with SpO2 < 90%. Desaturation index (DI) was defined as the number of desaturation events > 4%/hr. Covariates, including indices of nocturnal desaturation, were evaluated against mortality. RESULTS: Nocturnal desaturation was present in 49 (37%) patients. 31% of patients had pulmonary hypertension (PH) on echocardiography. Increased DI was associated with higher mortality independent of age, gender and BMI (HR 1.04; 95% CI 1.00, 1.06; p = 0.009). In separate models, DI and a) elevated brain natriuretic peptide (BNP; HR 1.04; 95% CI 1.00, 1.08; p = 0.04); b) moderate-severe PH on echocardiography (HR 3.15; 95% CI 1.24, 8.00; p = 0.02); and c) daytime resting SpO2 (HR 0.92; 95% CI 0.85, 0.99; p = 0.04) independently predicted mortality following adjustment for age, gender and BMI. CONCLUSION: Nocturnal desaturation is common and may be severe in ILD. Elevated nocturnal DI predicts higher mortality across ILD, independent of other vascular parameters. This finding may have important implications for the pathogenesis of PH in IPF.

Antenatal and postnatal management of congenital cystic adenomatoid malformation.

Congenital thoracic malformations (CTMs) are a heterogeneous group of rare disorders that may involve the airways or lung parenchyma. The authors have focused on the condition that causes the most controversy, namely, congenital cystic adenomatoid malformation (CCAM). The reported incidence is 3.5 and 0.94 per 10,000 live births for CTMs and CCAMs respectively. Ultrasound is the antenatal imaging modality of choice for screening for CCAMs whilst magnetic resonance imaging is complimentary for morphological and volumetric evaluation of the foetal lung. Most CCAMs are detected antenatally with only a small proportion presenting postnatally. Only a few CCAMs cause foetal problems, with foetal hydrops being the best predictor of death. Although many CCAMs regress during pregnancy, most remain detectable postnatally by CT scans. Surgical excision of symptomatic lesions is relatively straightforward, but management of asymptomatic lesions is controversial. Some surgeons adopt a "wait and see" approach operating only on those patients who develop symptoms, but others operate on asymptomatic patients usually within the first year of life. Due to the potential of malignant transformation, children should have long term follow up. There is an urgent need to delineate the natural history of antenatally detected CCAMs to guide future management.

Marginal decline in forced vital capacity is associated with a poor outcome in idiopathic pulmonary fibrosis.

In therapeutic studies in idiopathic pulmonary fibrosis (IPF), the low prevalence of significant change in pulmonary functional tests (PFTs) has been a major constraint. The prognostic value of "marginal" changes in PFTs in IPF and fibrotic non-specific interstitial pneumonia (NSIP) was evaluated. In patients with biopsy-proven IPF (n = 84) and NSIP (n = 72), forced vital capacity (FVC) and diffusing capacity of the lung for carbon monoxide (D( L,CO)) trends at 6 months were categorised as "significant" (FVC >10%; D(L,CO) >15%) or "marginal" (FVC 5-10%; D(L,CO) 7.5-15%). Proportional hazards analysis and time-dependent receiver operating characteristic methodology were used to examine PFT trends against mortality. In IPF, reductions in FVC were significant in 22 cases (26%) and marginal in 19 cases (23%). Mortality was higher in patients with a significant decline in FVC (hazard ratio (HR) 2.80, 95% CI 1.54-5.06; p<0.001) and those with a marginal decline in FVC (HR 2.31, 95% CI 1.19-4.50; p = 0.01) than in those with stable disease. Progression-free survival was lower when the decline in FVC was marginal than in stable disease (HR 2.34, 95% CI 1.19-4.60; p = 0.01). Marginal changes in D(L,CO) in IPF and marginal changes in FVC and D (L,CO) in fibrotic NSIP did not provide useful prognostic information. Marginal change in FVC in IPF denotes a poor outcome. These findings are applicable to clinical practice and to the selection of patients with more progressive disease for therapeutic studies.

A20 deletion is associated with copy number gain at the TNFA/B/C locus and occurs preferentially in translocation-negative MALT lymphoma of the ocular adnexa and salivary glands.

The genetic basis of MALT lymphoma is largely unknown. Characteristic chromosomal translocations are frequently associated with gastric and pulmonary cases, but are rare at other sites. We compared the genetic profiles of 33 ocular adnexal and 25 pulmonary MALT lymphomas by 1 Mb array-comparative genomic hybridization (CGH) and revealed recurrent 6q23 losses and 6p21.2-6p22.1 gains exclusive to ocular cases. High-resolution chromosome 6 tile-path array-CGH identified NF-kappaB inhibitor A20 as the target of 6q23.3 deletion and TNFA/B/C locus as a putative target of 6p21.2-22.1 gain. Interphase fluorescence in situ hybridization showed that A20 deletion occurred in MALT lymphoma of the ocular adnexa (8/42=19%), salivary gland (2/24=8%), thyroid (1/9=11%) and liver (1/2), but not in the lung (26), stomach (45) and skin (13). Homozygous deletion was observed in three cases. A20 deletion and TNFA/B/C gain were significantly associated (p<0.001) and exclusively found in cases without characteristic translocation. In ocular cases, A20 deletion was associated with concurrent involvement of different adnexal tissues or extraocular sites at diagnosis (p=0.007), a higher proportion of relapse (67% versus 37%) and a shorter relapse-free survival (p=0.033). A20 deletion and gain at TNFA/B/C locus may thus play an important role in the development of translocation-negative MALT lymphoma.

Leukotriene B4 release by human lung macrophages via receptor- not voltage-operated Ca2+ channels.

Increased numbers of macrophages and neutrophils in the lung is a key feature of chronic obstructive pulmonary disease (COPD). The major neutrophil chemotactic agent in the airways of COPD patients is leukotriene (LT)B(4) and is released by macrophages. The present study examines the role and mechanism of Ca(2+) in platelet-activating factor (PAF)-stimulated LTB(4) release from human lung macrophages. Macrophages were isolated from lung tissue of subjects undergoing lung resection surgery and monocyte-derived macrophages (MDM) were obtained from nonsmokers, smokers without obstruction and COPD patients. Cells were stimulated with PAF and LTB(4) release and [Ca(2+)](i) was measured. Lung macrophages and MDM released LTB(4) following stimulation with PAF (mean effective concentration: 0.08+/-0.06 microM (n = 5) versus 0.17+/-0.12 microM (n = 17), respectively). Compared with MDM, lung macrophages released approximately eight-fold more LTB(4). Neither smoking nor COPD altered MDM responses. PAF-stimulated LTB(4) release was abrogated by ethylene glycol tetraacetic acid suggesting a role for extracellular Ca(2+). This was substantiated by using store-operated channel blockers econazole, SK&F96365 and Gd(3+). However, econazole and SK&F96365 were more effective in MDM than lung macrophages. Neither LOE908 nor nifedipine could attenuate this response. These data suggest that platelet-activating factor-stimulated leukotriene B(4) release from human lung macrophages is mediated, in part, by Ca(2+) influx through receptor- but not voltage-operated Ca(2+) channels.

Corticosteroid responsiveness and clinical characteristics in childhood difficult asthma.

This study describes the clinical characteristics and corticosteroid responsiveness of children with difficult asthma (DA). We hypothesised that complete corticosteroid responsiveness (defined as improved symptoms, normal spirometry, normal exhaled nitric oxide fraction (F(eNO)) and no bronchodilator responsiveness (BDR <12%)) is uncommon in paediatric DA. We report on 102 children, mean+/-sd age 11.6+/-2.8 yrs, with DA in a cross-sectional study. 89 children underwent spirometry, BDR and F(eNO) before and after 2 weeks of systemic corticosteroids (corticosteroid response study). Bronchoscopy was performed after the corticosteroid trial. Of the 102 patients in the cross-sectional study, 88 (86%) were atopic, 60 (59%) were male and 52 (51%) had additional or alternative diagnoses. Out of the 81 patients in the corticosteroid response study, nine (11%) were complete responders. Of the 75 patients with symptom data available, 37 (49%) responded symptomatically, which was less likely if there were smokers in the home (OR 0.31, 95% CI 0.02-0.82). Of the 75 patients with available spirometry data, 35 (46%) had normal spirometry, with associations being BAL eosinophilia (OR 5.43, 95% CI 1.13-26.07) and high baseline forced expiratory volume in 1 s (FEV(1)) (OR 1.08, 95% CI 1.02-1.12). Of these 75 patients, BDR data were available in 64, of whom 36 (56%) had <12% BDR. F(eNO) data was available in 70 patients, of whom 53 (75%) had normal F(eNO). Airflow limitation data was available in 75 patients, of whom 17 (26%) had persistent airflow limitation, which was associated with low baseline FEV(1) (OR 0.93, 95% CI 0.90-0.97). Only 11% of DA children exhibited complete corticosteroid responsiveness. The rarity of complete corticosteroid responsiveness suggests alternative therapies are needed for children with DA.

Clinical course and lung function change of idiopathic nonspecific interstitial pneumonia.

Most studies of idiopathic nonspecific interstitial pneumonia (NSIP) have primarily studied mortality. In order to clarify the detailed outcome and prognostic markers in idiopathic NSIP, the clinical course with initial radiological and clinical features was analysed. The clinical course of 83 patients who were classified with idiopathic NSIP (72 fibrotic, 11 cellular; 27 males and 56 females; mean+/-sd age 54.4+/-10.1 yrs) was retrospectively analysed. In fibrotic NSIP, 16 (22%) patients died of NSIP-related causes with a median (range) follow-up of 53 (0.3-181) months. Despite the favourable survival (5-yr 74%), patients with fibrotic NSIP were frequently hospitalised with recurrence rate of 36%. Reduced forced vital capacity at 12 months was a predictor of mortality. On follow-up, lung function was improved or stable in approximately 80% of the patients. The extent of consolidation and ground-glass opacity on initial high-resolution computed tomography correlated significantly with serial changes of lung function, and the presence of honeycombing was a predictor of poor prognosis. During follow-up, eight (10%) patients developed collagen vascular disease. In conclusion, the overall prognosis of fibrotic nonspecific interstitial pneumonia was good; however, there were significant recurrences despite initial improvement and a subset of the patients did not respond to therapy. Some patients developed collagen vascular diseases at a later date.

Use of intravenous cyclophosphamide in known or suspected, advanced non-specific interstitial pneumonia.

BACKGROUND: In severe, progressive interstitial lung disease (ILD), specific diagnosis is often difficult, and treatment therefore empirical. An effective, rapidly acting, well-tolerated therapy is desirable. This study reviews the tolerability and efficacy of i.v. cyclophosphamide in known or suspected non-specific interstitial pneumonia (NSIP) following the introduction of an i.v. cyclophosphamide protocol. METHODS: Records of 54 patients with biopsy-proven (n = 7) or suspected NSIP, based on clinico-radiological consensus (n = 47), receiving i.v. cyclophosphamide over 2004-6 were reviewed (excluding systemic sclerosis). Lung-function trends over six months were evaluated, and comparative analysis of paired pulmonary-function before and after the start of therapy was performed. RESULTS: IV cyclophosphamide was well tolerated, with two withdrawals from therapy, and four deaths, not directly related to treatment. IV cyclophosphamide was associated with disease stability at six-months. Despite having severe, progressive disease, patients receiving i.v. cyclophosphamide had stable lung function at six months. A greater therapeutic response was associated with coexistent HRCT abnormalities indicative of organizing pneumonia. In 22 patients with paired pulmonary-function tests, pulmonary function trends were significantly improved (p = 0.03) and change in DLco differed significantly (p < 0.0001), following cyclophosphamide treatment. CONCLUSION: In the empirical treatment of advanced, rapidly progressive known or suspected NSIP, i.v. cyclophosphamide is a well tolerated, rapidly acting immunosuppressant, associated with improvement or stability in most cases.

Pulmonary veno-occlusive disease presenting with recurrent pulmonary oedema and the use of nitric oxide to predict response to sildenafil.

Pulmonary veno-occlusive disease (PVOD) is a disorder which causes progressive pulmonary hypertension, usually presenting with worsening dyspnoea and right heart failure. Pulmonary oedema induced by pulmonary vasodilator therapy to reduce pulmonary arterial pressure has been well described in PVOD, but here we describe a case of PVOD presenting with recurrent episodes of acute non-cardiogenic pulmonary oedema, in the absence of significant pulmonary hypertension. Concern over the risk of precipitating pulmonary oedema led us to use inhaled nitric oxide to predict the safety and efficacy of sildenafil.

Multidisciplinary interobserver agreement in the diagnosis of idiopathic pulmonary fibrosis.

The purpose of the present study was to evaluate the accuracy of the diagnosis of idiopathic pulmonary fibrosis (IPF) by respiratory physicians in six European countries, and to calculate the interobserver agreement between high-resolution computed tomography reviewers and histology reviewers in IPF diagnosis. The diagnosis of usual interstitial pneumonia (UIP) was assessed by a local investigator, following the American Thoracic Society/European Respiratory Society consensus statement, and confirmed when a minimum of two out of three expert reviewers from each expert panel agreed with the diagnosis. The level of agreement between readers within each expert panel was calculated by weighted kappa. The diagnosis of UIP was confirmed by the expert panels in 87.2% of cases. A total of 179 thoracic high-resolution computed tomography scans were independently reviewed, and an interobserver agreement of 0.40 was found. Open or thoracoscopic lung biopsy was performed in 97 patients, 82 of whom could be reviewed by the expert committee. The weighted kappa between histology readers was 0.30. It is concluded that, although the level of agreement between the readers within each panel was only fair to moderate, the overall accuracy of a clinical diagnosis of idiopathic pulmonary fibrosis in expert centres is good (87.2%).

Capillary apposition and density in the diagnosis of alveolar capillary dysplasia.

AIM: Alveolar capillary dysplasia (ACD) is a rare disorder, typically presenting with persistent pulmonary hypertension of the newborn. The aim was to characterise further the histological features of patients suspected of having ACD and to correlate histopathological features with outcome. METHODS AND RESULTS: Three pathologists retrospectively reviewed 21 surgical lung biopsy specimens (SLBx) where ACD entered the differential diagnosis. Semi-quantitative assessment showed that there was a spectrum of muscular arterial hypertrophy, capillary apposition to epithelium and capillary density within the interstitium, with the latter being more disordered in ACD. Misalignment of pulmonary vessels was also frequently seen. Four of 19 patients survived beyond the neonatal period, these having higher degrees of capillary apposition and density. Associated extrapulmonary abnormalities were common, most frequently with ACD. CONCLUSION: Poor capillary apposition and density, allied with medial arterial hypertrophy and misalignment of pulmonary vessels are the strongest diagnostic features of ACD. Of the four patients alive, all had high capillary apposition and density, suggesting that these features may be of prognostic value. SLBx remains useful in such cases as it may help predict patients who survive the neonatal period and also identify patients with disorders that are not primarily vascular anomalies.

Interobserver variation in the classification of thymic tumours--a multicentre study using the WHO classification system.

AIMS: To test the reproducibility of the current World Health Organization (WHO) classification of thymic epithelial tumours and to determine the level of interobserver variation within a group of pathologists, all with experience and expertise in thoracic pathology. METHODS AND RESULTS: Ninety-five thymic tumours were circulated to a group of 17 pathologists in the UK and The Netherlands over a 1-year period. Participants were asked to classify them according to WHO criteria. The diagnoses were subjected to statistical analysis and kappa values calculated. The overall level of agreement was moderate (kappa 0.45). When the categories were reduced in number by creating two groups, (A + AB + B1 + B2 and B3 + C), the level of agreement increased to 0.62. An alternative grouping (A + AB + B1 and B2 + B3 + C) increased it slightly further. The best agreement was in tumour types A and AB. Difficulties arose in distinguishing B1 tumours from B2 tumours and B2 tumours from B3 tumours. CONCLUSIONS: Although the WHO system describes a number of well-defined tumour types with clear diagnostic criteria, the overall level of agreement was moderate and improved if some groups were amalgamated.

CT and histopathological correlation of congenital cystic pulmonary lesions: a common pathogenesis?

AIM: To determine whether similarities exist in both the imaging and histopathological features of congenital cystic lung lesions and whether a more appropriate classification would be to adopt the theory of "malinosculation". MATERIAL AND METHODS: From the histopathology and computed tomography (CT) database, 24 patients (16 male, median age 3 years) with congenital cystic lung lesions were identified. CT studies were reviewed for site and characteristics of the lesions, parenchymal features, bronchial anatomy, and the presence of a feeding systemic vessel. Individual histopathological parameters were also correlated with CT data. RESULTS: There were five type 1 congenital cystic adenomatoid malformations (CCAMs), six type 2 CCAMs, one type 4 CCAM, one bronchial atresia, four pleuropulmonary blastomas (PPBs), and seven sequestrations. CCAMs (types 1, 2 and 4), sequestrations and PPBs appeared as cystic lesions, with cyst size less than 2 cm in type 2 CCAMs. Sequestrations were distinguished radiologically from CCAMs by systemic vessels. Reduced pulmonary attenuation was seen in bronchial atresia, type 2 CCAMs and in sequestrations. Histopathology showed an overlap in entities with sequestrations demonstrating CCAM type 2 histology and segmental atresia noted in both type 2 CCAMs and sequestrations. PPBs showed histological and imaging overlap with type 4 CCAMs and were distinguished on histology by the presence of blastematous proliferation. CONCLUSIONS: This study demonstrates overlap in the CT appearances of congenital cystic lesions. The similarity in CT and histopathology findings across the spectrum of developmental lesions supports the hypothesis of a common aetiology.