Honeycomb Lesions Research Articles

Prevalence and Characteristics of Sleep Apnea in Intensive Care Unit Survivors After SARS-CoV-2 Pneumonia.

Sleep apnea (SA) was reported as possibly exacerbating symptoms of COVID-19, a disease induced by SARS-CoV-2 virus. The same comorbidities are common with both pathologies. This study aimed to estimate the prevalence, characteristics of SA and variation in AHI three months after severe COVID-19 requiring intensive care unit (ICU) admission. A prospective cohort of patients admitted to ICU for severe COVID-19 underwent an overnight home polygraphy 3 months after onset of symptoms, as part of a comprehensive follow-up program (pulmonary function tests, 6-minute walk tests and chest CT-scan). Patients with an apnea hypopnea index (AHI) ≥5 were considered as having SA. We performed a comparative descriptive analysis of 2 subgroups according to the existence, severity of SA and indication for effective SA treatment: patients with absent or mild SA (AHI <15) vs patients with moderate to severe SA (AHI ≥15). Among 68 patients included, 62 (91%) had known comorbidities (34 hypertension, 21 obesity, 20 dyslipidemia, 16 type 2 diabetes). It has been observed a preexisting SA for 13 patients (19.1%). At 3 months, 62 patients (91%) had SA with 85.5% of obstructive events. Twenty-four patients had no or a mild SA (AHI <15) and 44 had moderate to severe SA (AHI ≥15). Ischemic heart disease exclusively affected the moderate to severe SA group. Except for thoracic CT-scan which revealed less honeycomb lesions, COVID-19 symptoms were more severe in the group with moderate to severe SA, requiring a longer curarization, more prone position sessions and more frequent tracheotomy. SA involved 91% of patients in our population at 3 months of severe COVID-19 and was mainly obstructive type. Although SA might be a risk factor as well as consequences of ICU care in severe COVID-19 infection, our results underline the importance of sleep explorations after an ICU stay for this disease.

Significant accumulation of KRAS mutations in bronchiolar metaplasia-associated honeycomb lesions of interstitial pneumonia.

Interstitial pneumonia (IP) is a major risk factor for lung adenocarcinoma (LADC). IP-related LADC predominantly develops in the bronchiolar metaplasia lining in honeycomb lesions. Kirsten rat sarcoma virus (KRAS) is the most common oncogene mutated in IP-related LADC. The present study examined the metaplastic epithelia in honeycomb lesions for KRAS mutations using digital droplet polymerase chain reaction (ddPCR), a sensitive method used to detect infrequent mutations. Significantly higher KRAS mutation variant allele frequencies (VAFs) were detected in the metaplastic lung epithelia from 13 patients with IP compared with those in 46 non-lesioned lung samples from patients without IP (G12V, P=0.0004, G12C, P=0.0181, and G12A, P=0.0234; Mann Whitney U test). Multivariate analyses revealed that higher KRAS G12V (logistic regression model; P=0.0133, odds ratio=7.11) and G12C (P=0.0191, odds ratio=5.81) VAFs in patients with IP were independent of confounding variables, such as smoking and age. In patients with IP, metaplastic epithelia exhibited significantly higher KRAS G12V and G12C VAFs compared with the non-lesioned counterparts (paired t-test; G12V, P=0.0158, G12C, P=0.0465). These results suggested that IP could increase KRAS mutations and supported the hypothesis that bronchiolar metaplasia could be a precursor for IP-related LADC.

Accuracy and complications of percutaneous transthoracic needle lung biopsy for the diagnosis of malignancy in patients with idiopathic pulmonary fibrosis.

To determine the accuracy of CT-guided percutaneous transthoracic needle lung biopsy (PTNB) for the diagnosis of malignancy and the associated complication rates in patients with idiopathic pulmonary fibrosis (IPF). This retrospective study included 91 CT-guided PTNBs performed in 80 patients with IPF from April 2003 through December 2016. Data regarding patients, target lesions, procedures, complications, and pathological reports were collected, and the final diagnosis was made. The diagnostic accuracy, sensitivity, specificity, percentage of nondiagnostic results, and complication rates were determined. Multivariable logistic regression analyses were performed to identify risk factors for nondiagnostic results and major complications. Three biopsies (technical failure [n = 2] and undetermined final diagnosis [n = 1]) were excluded from the diagnostic accuracy calculation. The diagnostic accuracy, sensitivity, and specificity were 89% (78/88), 90% (62/69), and 84% (16/19), respectively. The percentage of nondiagnostic results was 34% (30/88). Lesion size ≤ 3 cm (odds ratio [OR], 8.8; 95% confidence interval [CI], 2.5-31.2; p = 0.001) and needle tip placement outside the target lesion (OR, 13.7; 95% CI, 1.4-132.2; p = 0.02) were risk factors for nondiagnostic results. The overall and major complication rates were 51% (46/91) and 12% (11/91), respectively. The presence of honeycombing along the path of the needle (OR, 11.2; 95% CI, 1.4-89.1; p = 0.02) was an independent risk factor for major complications. CT-guided PTNB shows a relatively reasonable accuracy in diagnosing malignancy in patients with IPF. The complication rate may be high, especially when the needle passes through honeycomb lesions. • In patients with idiopathic pulmonary fibrosis (IPF), CT-guided percutaneous transthoracic needle lung biopsy (PTNB) showed a relativelyreasonable accuracy for the diagnosis of malignancy. • Target lesion size ≤ 3 cm and biopsy needle tip placement outside the target lesion were risk factors for nondiagnostic results of CT-guided PTNB. • The complication rate may be high, especially in cases where the biopsy needle passes through honeycomb lesions.

Three-Dimensional Quantitative Analysis of Chronic Obstructive Pulmonary Lesions on CT Images

In this paper, the three-dimensional segmentation of pulmonary honeycomb lesions and the function of image biomarkers are integrated into a quantitative analysis module of the lung, and integrated into the PACS image diagnosis workstation for the quantitative analysis of doctors. It is difficult to segment honeycomb lesions in lung CT images because of its diffuse and blurred edges, but it has good texture characteristics. Based on this feature, this paper converts honeycomb lesions into a texture classification problem. Firstly, the lung parenchyma is extracted by automatic threshold segmentation and region growing method, and then the lung parenchyma is divided into several small regions according to the texture by watershed method. Then, according to the texture characteristics of each small area, the trained support vector machine is used to classify. Finally, the correlation between gray level and spatial position of slice data is used to correct the classification results, so as to reduce false positive areas. In order to expand the study of imaging biomarkers of chronic lung diseases to more extensive major diseases, a sample database was established for a wide range of multiple lesions. Through feature extraction and feature analysis of multiple lesions in database, potential feature differences can be excavated, which lays a solid foundation for further study of image biomarkers of multiple lesions.

Evaluation of poor prognostic factors of respiratory related death in microscopic polyangiitis complicated by interstitial lung disease

The prognosis of microscopic polyangiitis (MPA) with interstitial lung disease (ILD) is significantly worse than that of MPA without ILD. However, the clinical characteristics in MPA-ILD, especially poor prognostic factors, are not elucidated. We evaluated demographic, clinical, laboratory, and radiological findings, treatments, and outcomes of 80 patients with MPA, and investigated prognostic factors of respiratory-related death in patients with myeloperoxidase (MPO)-anti-neutrophil cytoplasmic antibody (ANCA) positive MPA-ILD. Ground-glass opacity and fibrosis were evaluated as scores on high-resolution computed tomography (HRCT). The presence of ILD was consistent with a high risk of respiratory-related death (hazard ratio, 4.8; P = 0.04). Multivariable logistic regression analyses using propensity scoring showed right or left lower lobe fibrosis score to be significantly associated with respiratory-related death (P = 0.0005 and 0.0045, respectively). A right or left lower lobe fibrosis score ≥ 2, indicating the presence of honeycombing at 1 cm above the diaphragm, was determined to be the best cut-off value indicating a poor prognosis. The 5-year survival rate was significantly lower in patients with right or left lower lobe fibrosis score ≥ 2 (survival rates: 37% and 19%, respectively) than those with a score < 2 (71% and 68%, respectively) (P = 0.002 and 0.0007, respectively). These findings suggest that the presence of honeycomb lesions in bilateral lower lobes on chest HRCT was associated with respiratory-related death in patients with MPO-ANCA positive MPA-ILD.

Diagnostic value of Endothelin 1 as a marker for diagnosis of pulmonary parenchyma involvement in patients with systemic sclerosis

Background Systemic sclerosis (SSc) is a connective tissue disease and one of the manifestations associated with this disease is pulmonary involvement. Studies showed that endothelin 1 (ET-1) plays a role in pulmonary dysfunction due to SSc. The aim of this study was to determine the level of ET-1 in SSc patients and to evaluate its association with the early stages of pulmonary fibrosis. Methods In this cross-sectional study, 48 patients with SSc were enrolled in the study. The stiffness of the skin was evaluated based on the modified Rodnan skin score. CT records, lung function tests and echocardiography were done. The samples were divided into two groups of patients with and without pulmonary parenchymal involvement. Blood sample was taken to measure the serum levels of ET-1 by ELISA method. ANOVA and Tukey HSD tests were used for statistical analysis. Results According to pulmonary CT scan, 68.2% of patients had pulmonary involvement. There was no significant difference in the presence of honeycomb lesions and fibrosis in lung CT scan of the patients in case of gender (P = 0.819 and P = 0.356, respectively). There was no statistical difference between the results of spirometry in patients with anti-Scl-70 and anti-centromere test. The mean serum level of ET-1 in the studied population was 0.55 ± 0.232 pg/mL, in the men was 0.47 ± 0.14 pg/mL and in the women was 0.55 ± 0.24 pg/mL. There was no significant difference between the two groups in the case of gender and type of the disease (P = 0.475 and P = 0.150, respectively). The ROC diagram of serum level of ET1 in patients based on the type of the disease shows that the serum level of ET-1 of 55% has 50% sensitivity and 52.2% specificity. Conclusion Serum level of ET-1 could not be used for screening of pulmonary involvement in SSc because its sensitivity and specificity is related to pulmonary fibrosis, honeycomb lesions and disease form. Anti Scl-70 with low levels, DLCO, FVC, FEV1, TLC can be used to assess the possibility of pulmonary involvement and response to treatment.

Development and Validation of a Comprehensive Multiparameter-Based Scoring System to Assess Pulmonary Fibrosis Severity

Background: An assessment method that can accurately assess the severity and prognosis of pulmonary fibrosis, including idiopathic pulmonary fibrosis (IPF), is currently lacking. This study aimed to develop a new multiparameter-based method, which can be easily used to accurately assess pulmonary fibrosis severity. Method: 1. Development of a HRCT combined pulmonary function & physiological parameter (CTPF) assessment method: Parameters that can be easily collected in clinical practice and have been proven by literature to have a good prognostic value were used to develop the new assessment method. The method included two parts. 1) CT-based fibrosis staging: a four-section honeycomb lung method. Four representative lung CT sections were selected (the aortic arch section, the tracheal bifurcation section, the section of basal (dorsal) segment of the tracheal bifurcation at the inferior lobes, and the section below the right lung apex) and evenly divided into 100 small areas. The percentage of honeycomb lesion area in the entire lung was determined semi-quantitatively and used to determine fibrosis stage (I-V) (CT-based fibrosis stage). 2) Five representative lung function and physiological parameters including FVC%pred, DLco%pred, SpO2%, age, and gender were used to assess IPF severity grade (PF-based severity grade). The 5 parameters were scored, and the total scores were used to determine PF-based severity grade, which included score 0-3 for mild (a), score 4-6 for moderate (b), and score 7-10 for severe (c). The two parts were combined to determine a CTPF stage. For example, CTPF stage II a represents fibrosis stage II and severity grade a (mild). 2. Validation of the new method: The CTPF method was used to assess 192 patients with IPF, who were diagnosed in Shanghai Pulmonary Hospital and had complete medical records. Two radiologists used the CT-based fibrosis staging method to evaluate patients' HRCT and determined the fibrosis stage. Pulmonologist determined the PF-based severity grade and combined both assessments to determine the final CTPF stage. 3. Statistical analyses: Intra-group correlation coefficient was calculated to estimate the consistency between the CT scores from the two radiologists. Spearman correlation coefficient was calculated to evaluate the correlation between CT scores and lung function parameters: FVC%pred, DLco%pred, SpO2%, and composite physiologic index (CPI). Death was the study endpoint. Lung transplantation was considered a competitive risk. The competitive risk Fine-Gray model was used to analyze the relationship between CT-based stage/PF-based grade and prognosis (accumulative death). CT-based stage, PF-based grade, and gender, age, and physiologic (GAP) stage were used as predictors to establish Fine-Gray regression prediction models. Nomogram was prepared to illustrate the prediction models. The predictive effectiveness of the models on predicting death risk was verified by cross-validation method. Results: 1. The intra-group correlation coefficient of the CT scores of the two radiologists was 0.95, P<0.05. 2. The CT scores negatively correlated with FVC%pred/DLco%pred/SpO2% and positively with CPI index. 3. The CTPF comprehensive model, which combined CT stage and PF grade, predicted that the AUC index of one-, two-, and three-year death risk was 78.6 (95% CI: 58.6-93.0), 77.8 (95% CI: 58.8- 83.4), and 73.4 (95% CI: 57.5- 85.1), respectively. 4.The CTPF model showed higher predictive accuracy than the GAP model. Conclusion: We combined CT-based staging and PF-based grading methods to develop a new comprehensive CTPF assessment method. The new method is simple, can be adopted easily in clinical practice, and can more accurately assess IPF severity and predict death risk than existing assessment methods. Funding Statement: This study was funded by grants from the National Science Foundation of China (Grant No: 81730002, 81670055, 81670056, 91442103, 81500052, and 81570057), Ministry of Science and Technology of the People’s Republic of China (2016YFC1100200 and 2016YFC1100204) and Shanghai Family Planning Commission Health Industry Clinical Research Project (20184Y0084). Declaration of Interests: The authors confirm that there are no conflicts of interest. Ethics Approval Statement: The study was approved by the Institutional Ethics Committee of Shanghai Pulmonary Hospital (No. K17-006).

Relationship between non-TRU lung adenocarcinomas and bronchiolar metaplasia - potential implication in their histogenesis.

Lung adenocarcinomas (ADCs) have been roughly divided into two groups: the terminal respiratory unit (TRU) type and non-TRU type. These ADCs appear to develop through exclusive carcinogenetic pathways because of differences in their cellular morphologies and the profiles of protein expression and genetic alterations. The TRU type develops from atypical adenomatous hyperplasia as a precursor. On the other hand, the histogenesis of the non-TRU type has not yet been defined in detail. We herein investigated histopathological changes in the non-tumor lung tissues of patients with non-TRU-type ADCs in order to define their potential histogenesis. The non-TRU type preferentially occurs in patients with interstitial pneumonia, in whom tumors are located in honeycomb lesions and are associated with bronchiolar metaplasia (BM). Among patients without interstitial pneumonia, non-tumor lung tissues from non-TRU-type ADCs were often affected by multiple BM. In these cases, tumors often were associated with BM. Metaplastic cells adjacent to non-TRU-type ADCs ectopically expressed HNF-4α, a marker for non-TRU-type ADCs. These results suggest that the non-TRU type develops through distinct histogenesis, in which BM is implicated.

The pathological features of idiopathic interstitial pneumonia-associated pulmonary adenocarcinomas.

To investigate the pathological features of idiopathic interstitial pneumonia (IIP)-associated pulmonary adenocarcinoma. Surgically resected adenocarcinomas associated with IIP (the IIP group) and adenocarcinomas without IIP (the non-IIP group) were subjected to analysis. Adenocarcinomas in the IIP group were subdivided into two groups: one group included tumours connected to bronchiolar metaplasia in honeycomb lesions (the H-IIP group), and the other included tumours unrelated to honeycomb lesions (the NH-IIP group). Histomorphological appearance and immunohistochemical expression were compared among the H-IIP group, the NH-IIP group, and the non-IIP group. Most of the tumour cells in the H-IIP group had a tall, columnar shape that showed similar features to proximal bronchial epithelium, whereas tumour cells in the NH-IIP group and the non-IIP group had a club-like shape that showed similar features to respiratory bronchiolar/alveolar epithelium. Adenocarcinomas in the H-IIP group tended to be negative for thyroid transcription factor-1 (TTF-1) and positive for hepatocyte nuclear factor-4α (HNF-4α). The frequency of EGFR mutations was significantly lower in adenocarcinomas in the H-IIP group, although the frequencies of KRAS and ALK mutations did not differ among the three groups. Idiopathic interstitial pneumonia-associated pulmonary adenocarcinomas, especially those arising from honeycomb lesions, have distinct pathological features.

Phenotype of regenerative epithelium in idiopathic interstitial pneumonias.

The epithelial alteration in interstitial pneumonias is one of the repair processes at the sites of disease activity. Regenerative epithelial cells may participate in remodeling of the lung. To determine the phenotype of regenerative epithelial cells in usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP), the expression of Clara cell 10KD protein (CC10), cytokeratin (CK) 14 and 17, surfactant apoprotein (SP)-A, KL-6/MUC1, transforming growth factor (TGF) beta2 were examined in 25 patients with UIP, 9 patients with NSIP and normal lung tissues from 10 patients with lung cancer. In honeycomb lesions of UIP, non-ciliated columnar cells mainly expressed CC10, cuboidal cells expressed CC10, CK17, CK14 and SP-A in descending order. Fibroblastic foci are covered by CK17, CK14, CC10, and a few SP-A positive flattened or cuboidal cells. Regenerative epithelium in NSIP mainly comprised cuboidal cells expressing SP-A, CC10 and CK17. KL-6 was more remarkably expressed in cuboidal and non-ciliated columnar cells both in UIP and NSIP. Expression of TGFbeta2 was observed in cuboidal and flattened epithelium. In severe fibrotic areas, CC10 expressing cells were more prominent, while SP-A positive cells were more prominent in less fibrotic areas. Regenerative epithelial cells in remodeling area in UIP may be derived from bronchiolar basal cells and Clara cells, while most of those in NSIP may be derived from type II pneumocytes. The different origin of regenerative epithelium may reflect the severity and extent of the injury and the degree of consequent fibrosis in UIP and NSIP.

Nonspecific interstitial pneumonia and usual interstitial pneumonia: comparison of the clinicopathologic features and prognosis.

Nonspecific interstitial pneumonia (NSIP) has recently been proposed as a histologic type of idiopathic interstitial pneumonia (IIP), but its broad spectrum of clinicopathologic findings and variable prognosis are poorly understood. It is particularly unclear how NSIP and usual interstitial pneumonia (UIP) are related. The present study investigated the clinicopathologic features and prognosis of NSIP, and its differential diagnosis from UIP. The clinicopathologic findings and prognosis in 21 NSIP and 18 UIP patients who underwent surgical or video-assisted thoracoscopic lung biopsy were reviewed. NSIP was more frequent in women and showed nonspecific clinical manifestations. High-resolution computed tomography (HRCT) demonstrated ground-glass, net-like, and patchy attenuation in both lungs. Semiquantitative HRCT showed a median fibrosis score of 3 (range, 0 to 7) in NSIP patients and 5 (range, 2 to 7) in UIP patients (P<0.01). On histopathologic examination, NSIP cases were heterogeneous and the findings could be categorized into cellular and fibrosing patterns. The mean age of the NSIP and UIP patients was 48 and 60 years, respectively. The frequencies of fibroblast foci, myogelosis, honeycomb lesions, and pulmonary structural destruction in NSIP and UIP patients were 16.7% and 100% (P<0.001), 22.2% and 85.7% (P<0.05), 16.7% and 92.9% (P<0.001), and 27.8% and 100% (P<0.05), respectively. The responses to glucocorticoid treatment and the prognosis were significantly greater in NSIP than those in UIP. NSIP was difficult to be differentiated from UIP by general clinical manifestations, but HRCT can be helpful for this purpose. Definitive diagnosis depends on the results of surgical lung biopsy.

Cone-beam CT features of ameloblastomas

To summarize and analyze the cone-beam CT (CBCT) imaging features of ameloblastomas for clinical preoperative diagnosis. Thirty-seven cases with complete data proven by pathology were retrospectively studied for distinct CBCT features. Of the 37 cases, 31 were primary and 6 were recurrent. On CBCT images, the 37 cases were composed of 36 cases (97.3%) of intraosseous lesions (17 cases of multilocular lesions, 17 cases of unilocular lesions, and 2 cases of honeycomb lesion) and 1 case (2.7%) of extraosseous lesion (soft tissue lesion). Of the 17 multilocular cases, 15 (88.2%) showed tongue-shaped crests in lesions. Thirty-four cases (94.4%) showed apparent expansible change toward lip/buccal and (or) palatal/lingual sides ofjaw, with partialcortical erosion. CBCT imaging yields accurate three-dimensional images of lesion shape and structure. Therefore, CBCT can be usedfor the clinical diagnosis and surgical assessment of ameloblastoma.

Case report of pancreatic dermoid cyst: can fine needle aspiration make the diagnosis?

Pancreatic dermoid cysts are rare, benign, germ cell tumors and part of the differential diagnosis for cystic neoplasms of the pancreas.A 35-year-old man presented with an incidentally discovered, 2 cm cystic pancreatic neoplasm of the pancreatic tail identified on CT scan. Endoscopic ultrasound (EUS) revealed a complex, honeycomb lesion. Fine needle aspiration (FNA) yielded a sample of whitish, necrotic material containing histiocytes, benign epithelial cells, and lymphocytes. After distal pancreatectomy and splenectomy was performed, histology revealed a cyst lined by stratified squamous epithelium with benign sebaceous units consistent with a pancreatic dermoid cysts.Although axial imaging reliably detects cystic neoplasms of the pancreas, diagnostic criteria for rare lesions are lacking; therefore alternative modalities such as EUS/FNA can be utilized. This case report highlights the EUS and FNA findings associated with pancreatic dermoid cysts.

Hypertrophic (Verrucous) Cutaneous Lupus Erythematosus of the Lip and Oral Cavity: A Series of 4 Cases

So-called “hypertrophic cutaneous lupus erythematosus (LE)” (also termed “verrucous cutaneous LE”) is a dis-tinct and rare clinical variant of chronic cutaneous LE that is characterized by intense tissue hyperplasia and hyperkeratosis. Hypertrophic LE causes marked disfigu-rement and is usually resistant to therapy (1, 2). Lesions occur more commonly on the face and upper limbs, with no specific mention in the literature of lesions occurring on the lips or oral mucosa. We describe here a series of 4 cases with a diagnosis of LE who presented with hypertrophic lesions on the skin and oral mucosa. Clinical and laboratory data are presented, together with detailed characterization of the mucosal involvement.CaSE REpoRtSClinical data for the 4 patients are shown in table SI (available from http://www.medicaljournals.se/acta/content/?doi=10.2340/00015555-1433). all patients presented hypertrophic cutaneous LE of longstanding duration. only patient 1 had multiple active cutaneous LE lesions at the time of examination (Fig. 1A, B). Skin lesions in patients 2 and 4 were mainly residual, with intense scarring. The lesion in patent 3 was confined to the lip area (Fig. 1C–F). Histopathology of biopsied oral lesions revealed marked hyperkeratosis, presence of a granular layer, focal hydropic degeneration of the basal layer, necro-tic basal keratinocytes, and melanophages of variable intensity (Fig. 1G, H). There were no signs of kerati-nocytic atypia. Dermal components included dilated papillary vessels, mucin, and scarce inflammatory in-filtrate, except for case 2, in which inflammatory cells were abundant in a superficial and deep pattern. Direct immunofluorescence findings were non-diagnostic.In patients 1, 2 and 3, LE activity was more pronoun -ced on the tegument. In addition to skin lesions, patient 4 had a several year history of lupus arthritis.DISCuSSIonthere are few published case series of oral compromise in LE. of these, some uniformity can be observed in the clinical picture, despite the great variety of descriptive terms employed (“oral discoid lesion”, “chronic pla-que”, “lupus cheilitis”, “acute ulcer”, “erythematous ulcer”, “ulcerated plaque”, “pebbly red areas”, “ho-neycomb lesions”, “keratotic white lesion”, “purpuric lesion”, and “diffuse palatal petechial erythema”, among others); a clinical characterization based on established dermatological criteria would be useful. Our group has proposed a method that simply compares mucosal LE lesions with their cutaneous counterparts (acute, subacute and chronic mucosal LE in analogy to acute, subacute and chronic cutaneous LE) in order to better understand those lesions (3).We describe here 4 patients with what is known as hypertrophic/verrucous LE (a subtype of chronic cuta -

Suppression of plasminogen activator inhibitor-1 by RNA interference attenuates pulmonary fibrosis

Background and aimThere is a growing body of evidence demonstrating that plasminogen activator inhibitor-1 (PAI-1) is involved in the progression of pulmonary fibrosis. In fact, PAI-1 knockout mice are protected...

Histopathologic Analysis of Sixteen Autopsy Cases of Chronic Hypersensitivity Pneumonitis and Comparison With Idiopathic Pulmonary Fibrosis/Usual Interstitial Pneumonia

Hypersensitivity pneumonitis (HP) is an interstitial lung disease caused by the inhalation of organic substances and certain inorganic chemicals. The histopathologic features of chronic HP (CHP) have not been studied extensively. We examined the pathologic characteristics of 16 autopsy cases of clinically confirmed CHP and compared them with 11 cases of idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP). To clarify the exact intralobular location of the fibrotic lesions, we conducted 3-dimensional reconstruction of fibrosis of CHP and IPF/UIP. Granuloma was not detected in any CHP case. Similar to IPF/UIP, honeycombing lesions were found dominantly in the lower lobes in most CHP cases; upper lobe dominance and asymmetrical distribution of honeycomb lesions were more frequent in CHP than in IPF/UIP. In all lungs affected by CHP, centrilobular fibrosis was outstanding, often connecting to the perilobular areas in the appearance of "bridging fibrosis," which was clearly demonstrated by 3-dimensional imaging. Centrilobular and bridging fibrosis were significantly more conspicuous in CHP than IPF/UIP; however, considerable overlap was found. It is important to thoroughly explore the possibility of antigen exposure in cases of lungs with UIP with centrilobular fibrosis to discriminate CHP from IPF/UIP.

AKR1B10 in usual interstitial pneumonia: Expression in squamous metaplasia in association with smoking and lung cancer

The incidence of lung cancer (LC) is markedly increased among patients with usual interstitial pneumonia (UIP), and tobacco smoking is its superimposed risk factor. AKR1B10 (aldo-keto reductase 1B10) is frequently overexpressed in pulmonary squamous cell carcinoma and adenocarcinoma in smokers. To investigate the role of AKR1B10 in the pulmonary carcinogenesis in UIP with correlation to tobacco smoking, we examined 13 UIP cases with LC, 13 UIP cases without LC, and 30 cases of non-UIP LC using AKR1B10 immunohistochemistry. AKR1B10 immunoreactivity was confined to squamous metaplasia in honeycomb lesions of UIP and neoplastic cells of LC. Squamous metaplastic foci showed AKR1B10 immunoreactivity more frequently in UIP with LC (24/36 foci, 67%) than in UIP without LC (16/44 foci, 37%) ( P<0.01). AKR1B10 expression in UIP was also more frequent in squamous metaplastic foci in smokers (38/67 foci, 57%) than in non-smokers (2/13 foci, 15%) ( P<0.01). AKR1B10 expression was frequently observed in both UIP-associated LC (10/13 foci, 77%) and non-UIP LC (18/30 foci, 60%). Ki-67 labeling index was significantly higher in AKR1B10-positive squamous metaplasia of UIP than in AKR1B10-negative squamous metaplasia of UIP. Our results demonstrate that AKR1B10 is involved in the development of LC in UIP in association with smoking. AKR1B10 might be useful as a new marker for identification of high LC risk patients in UIP.

OP17.08: Sonographic based triage for symptomatic deep infiltrating endometriosis treated with a levonorgestrel‐releasing intrauterine system

To report three cases of severely symptomatic deep infiltrating endometriosis managed by transvaginal sonography (TVS) and by a levonorgestrel-releasing intrauterine system (LNG-IUS). A 34 years-old woman was admitted for severe dysmenorrhea and dyspareunia, menorrhagia and severe anemia. The patient was previously unsuccessfully treated with tranexamic acid, progestins, danazol, GnRH analogues and endometrial resection. TVS showed an enlarged uterus, with inhomogeneous and thickened posterior myometrium, with focal honeycomb lesions highly and irregularly vascularized, typical for deep adenomyosis. A LNG-IUS was inserted. At 48 months follow-up, the patient was free of symptoms. A 38-year-old woman presented with cyclic worsening dysmenorrhea, deep dyspareunia and dyschezia during the last year. TVS showed normal uterus and ovaries, and on the left, an inhomogeneous hypoechoic lesion which infiltrate the antimesenteric sigmoid wall, painful at push-and-pull maneuvers, highly suspicious for sigmoid endometriosis. Barium enema confirmed the TVS image. By the imaging diagnosis of endometriosis, a LNG-IUS was placed. At 21 months follow-up, the patients referred dramatically improvement of symptoms with pain only evoked by deep pelvic exam. A 41 years-old woman was referred with a recent history of severe dysmenorrhea and dysuria. TVS showed an inhomogeneous polypoid 3 cm lesion involving the vesical base and vesicouterine septum. Cystoscopy confirmed a polypoid extramucosal lesion close to uretero-vesical junction. A LNG-IUS was inserted. At 8 months follow-up, the patient persisted free of symptoms. Accurate diagnosis by TVS of deep infiltrating endometriosis may permit a conservative medical treatment based on LNG-IUS.

Hyperplastic epithelial foci in honeycomb lesions in idiopathic pulmonary fibrosis.

Seventy-two cases of idiopathic pulmonary fibrosis (IPF) were examined from 2856 consecutive autopsy cases at the Japanese Red Cross Medical Center in Tokyo from 1973-1996. Primary lung cancer had arisen in 31 of 72 cases of IPF (43%), significantly higher than the incidence in cases without IPF (8.1%) and in the cases with non-IPF chronic lung diseases (11.9%). Hyperplastic epithelial foci in the honeycomb lesions of IPF cases were significantly more prominent in the lower than in the upper lobe, in cases with or without lung cancer, and they were more prominent in the lower lobe of IPF with than in those without cancer. The length of hyperplastic epithelial foci in the lower lobe of IPF cases was longer than that in interstitial pneumonia-associated with collagen vascular diseases. There was a higher PCNA labeling index of hyperplastic epithelial foci in IPF cases than in cases of interstitial pneumonia-associated with collagen vascular diseases. The PCNA labeling index was almost the same between smokers and nonsmokers with IPF. Overexpression of p53 was observed in hyperplastic epithelial foci in honeycomb lesion of IPF. DNA ploidy analysis of hyperplastic epithelial foci in the paraffin sections of 12 IPF cases revealed aneuploidy patterns in eight cases. These results strongly suggest that accelerated cell proliferation occurs in the honeycomb lesion of IPF, and that regenerative epithelia becomes susceptible to carcinogenic agents in addition to the smoking effect.

Immunohistochemical localization of surfactant apoproteins in usual interstitial pneumonia associated with pulmonary carcinoma.

Surfactant apoproteins A and B (SP-A and SP-B) are antigenic determinants of pulmonary surfactant complexes. The role and functional significance of these proteins are largely unknown and the pattern of expression is probably related to the functional maturation of type II pneumocytes. Differential expression of SP-A and SP-B was reported in the developing human lung but little is known of their expression in the chronic injury. We studied 5 surgical cases of usual interstitial pneumonia (UIP) associated with carcinoma to evaluate the expression of pulmonary surfactant apoproteins. These cases were immunohistochemically examined by the streptavidin-biotin complex method using monoclonal antibodies HS-1 and HS-2 against pulmonary surfactant apoprotein A (SP-A) and B (SP-B), respectively. In UIP, SP-B was expressed strongly in type II pneumocytes and Clara cells but bronchiolar epithelium and metaplastic squamous cell lines in the honeycomb lesion were non-reactive. SP-A showed a similar pattern but much weaker reactivity when compared to that of SP-B. Type II pneumocytes in normal lung tissue exhibited weak immunoreactivity and no difference in the intensity of staining between SP-A and SP-B. Neither carcinomatous area nor metaplastic lining cells at honeycomb lesion show immunoreactivity to SP-A and SP-B. These results suggest that type II pneumocytes in the UIP are functionally immature in their expression of the apoprotein types and the metaplastic squamous cells or neoplastic transformed cells do not have molecular characteristics of type II pneumocytes.