There could be two carcinogenetic pathways for lung adenocarcinoma (LADC): the nonsmokers’ pathway and the smokers’ pathway. This review article describes the two pathways with special reference to ...potential relationships between histological subtypes, malignant grades, and driver mutations. The lung is composed of two different tissue units, the terminal respiratory unit (TRU) and the central airway compartment (CAC). In the nonsmokers’ pathway, LADCs develop from the TRU, and their histological appearances change from lepidic to micropapillary during the progression process. In the smokers’ pathway, LADCs develop from either the TRU or the CAC, and their histological appearances vary among cases in the middle of the progression process, but they are likely converged to acinar/solid at the end. On a molecular genetic level, the nonsmokers’ pathway is mostly driven by EGFR mutations, whereas in the smokers’ pathway, approximately one‐quarter of LADCs have KRAS mutations, but the other three‐quarters have no known driver mutations. p53 mutations are an important factor triggering the progression of both pathways, with unique molecular alterations associated with each, such as MUC21 expression and chromosome 12p13‐21 amplification in the nonsmokers’ pathway, and HNF4α expression and TTF1 mutations in the smokers’ pathway. However, investigation into the relationship between histological progression and genetic alterations is in its infancy. Tight cooperation between traditional histopathological examinations and recent molecular genetics can provide valuable insight to better understand the nature of LADCs.
It has been supposed there could be two carcinogenetic pathways for lung adenocarcinoma (LADC): the nonsmokers’ pathway and the smokers’ pathway. This review article describes the two pathways with special reference to potential relationships between histological subtypes, malignant grades, and driver mutations
A Japanese case of COVID‐19: An autopsy report Okudela, Koji; Hayashi, Hiroyuki; Yoshimura, Yukihiro ...
Pathology international,
October 2020, Letnik:
70, Številka:
10
Journal Article
Recenzirano
Odprti dostop
A 93‐year‐old woman was admitted with a 10‐day history of cough and prostration. Thoracic computed tomography revealed extensive ground‐glass opacities in both the lungs. The polymerase chain ...reaction test of sputum for severe acute respiratory syndrome‐coronavirus‐2 (SARS‐CoV‐2) was positive. She was treated with antiviral agents and steroid pulse therapy. However, her oxygen saturation gradually declined, and she died 10 days after hospitalization. The most important autopsy finding was fuzzily segmented diffuse alveolar damage (DAD) that expanded from the subpleural to the medial area. No remarkable changes were observed in organs other than the lungs. Therefore, pneumocytes were suggested as the primary target for SARS‐CoV‐2, which might explain why coronavirus infectious disease‐19 is a serious condition. Thus, early treatment is essential to prevent viral replication from reaching a level that triggers DAD.
Objective Interstitial lung disease (ILD) is the most critical manifestation in patients with rheumatoid arthritis (RA). In some cases, ILD may appear before the RA onset. Some patients with an ...initial diagnosis of idiopathic interstitial pneumonia (IIPs) develop RA; however, few studies have reported on its features, and the details remain unknown. In the present study, the clinical, radiological, and pathological features were evaluated in patients with ILD preceding RA. Methods The clinical, radiological, and pathological features of patients with ILD preceding RA were retrospectively reviewed using the medical records. Patients Ten patients with ILD preceding RA out of 883 IIP patients who underwent a surgical lung biopsy at our hospital from 2004 to 2018 were retrospectively examined. Results The median patient age was 59 (range 50-76) years old, and 7 of the patients were women. The median time from the ILD diagnosis to the RA onset was 50 (range 33-65) months. Regarding the high-resolution computed tomography pattern, the "indeterminate for UIP" pattern was the most popular, and cysts were seen in all cases. Attenuation around the cyst was prominent. Pathological findings showed plasma cell infiltration, bronchus-associated lymphoid tissue (BALT), and bronchiolitis in the lobules. Cellular and destructive bronchiolitis was noticeable in many patients with ILD preceding RA and contributed to the destruction and dilation of the bronchiole. Conclusion In ILD patients with IIP, radiological and pathological findings with increased attenuation around the cysts, prominent inflammatory cell infiltration (especially in plasma cells), an increase in the BALT number, and cellular and destructive bronchiolitis might serve as helpful RA development indicators.
Nuclear atypia is one of the most important morphological features used to diagnose malignant neoplasms. The potential molecular alteration that causes nuclear atypia remains unknown. P53 and ...p16INK4A play crucial roles in cell cycle checkpoints and repairing DNA damage to maintain integrity of the genome. Thus, inactivation of p53 and p16INK4A has been hypothesized to alter the chromatin structure and result in nuclear atypia. This study examined 201 primary lung cancers for the immunohistochemical expression of p53 and p16INK4A, and analyzed potential associations with the essential elements of nuclear atypia, such as nuclear size, circularity of the outline, and the density and granularity of chromatin. Tumors that expressed high levels of p53 had larger nuclei with higher chromatin density and distorted nuclear outlines. Tumors that expressed low levels of p16INK4 had larger nuclei with distorted nuclear outlines. Thus, alterations in p53 and p16INK4A may be the potential cause of nuclear atypia in neoplastic cells.
A 61-year-old patient with cystic bronchiectasis and bronchial artery hyperplasia in the left lung was diagnosed with polymyositis-related interstitial lung disease. After nine months of ...immunosuppressive therapy, he developed unilateral autoimmune pulmonary alveolar proteinosis (APAP) in the right lung with respiratory failure. After bronchial artery embolization to prevent massive hemoptysis, whole-lung lavage was performed using veno-venous extracorporeal membrane oxygenation. His respiratory condition improved, and he was discharged from the hospital with supplemental oxygen. Three reported cases of APAP with polymyositis-related interstitial lung disease, including the present case, were all positive for anti-glycyl tRNA synthetase antibody and were under immunosuppressive treatment.
BACKGROUND Pleuroparenchymal fibroelastosis (PPFE) is a rare form of interstitial pneumonia and sometimes coexists with a histologic usual interstitial pneumonia (UIP) pattern. This study aimed to ...describe the distinct clinical features of PPFE with UIP pattern compared with idiopathic pulmonary fibrosis (IPF). METHODS We conducted a retrospective review of the medical records of 110 consecutive patients with IPF with a histologic UIP pattern on surgical lung biopsy specimen. Patients meeting radiologic criteria for the diagnosis of PPFE based on high-resolution CT scan and with a histologic UIP pattern were included. RESULTS Nine of eleven patients meeting radiologic criteria for the diagnosis of PPFE were histologically confirmed as having PPFE with UIP pattern. The PPFE with UIP pattern group showed a significantly higher residual volume (1.8 L vs 1.3 L, P < .01), higher Paco2 (44.6 mm Hg vs 41.7 mm Hg, P = .04), and higher complication rate of pneumothorax and pneumomediastinum than the 99 patients with IPF/UIP. The ratio of anteroposterior to transthoracic diameter in patients with PPFE with UIP pattern was significantly lower than that in patients with IPF/UIP ( P = .04). Survival time tended to be shorter in patients with PPFE with UIP pattern. CONCLUSIONS The results support the view that PPFE with UIP pattern is a disease entity distinct from IPF/UIP and may well be classified as PPFE.
A new classification of adenocarcinoma (ADC) was proposed by the International Association for the Study of Lung Cancer, the American Thoracic Society, and the European Respiratory Society ...(IASLC/ATS/ERS) in 2011. The present study evaluates its prognostic value in stage I disease of Japanese cases. One‐hundred‐and‐seventy‐nine cases with pathological stage I ADC were classified according to the new classification system and their association with disease recurrence was analyzed. Eighteen (10.1%) and 24 (13.4%) cases were adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA), respectively. One‐hundred‐and‐thirty‐seven cases (76.5%) were invasive adenocarcinoma (IVA), in which 43 (24.0%) were lepidic (LEP), 59 (33.0%) were acinar (ACN), 16 (8.9%) were papillary (PAP), 1 (0.6%) was micropapillary (MPAP), 12 (6.7%) were solid predominant subtypes (SOL), and 6 (3.4%) were invasive mucinous adenocarcinoma (MUC). The5‐year disease‐free survivals (DFS) of patients with AIS and MIA were 100%. Those of LEP, ACN, PAP, SOL and MUC were 93.5%, 83.7%, 75.0%, 44.4% and 62.5%, respectively. Multivariate analysis showed that high‐histological grade (SOL, MPAP, MUC) had an independent prognostic value to predict post‐operative recurrence (HR 3.661, 95% CI 1.421–9.437, P = 0.007). In conclusion, the present study demonstrates a prognostic value of the 2011 IASLC/ATS/ERS classification of ADC in Japanese cases.
This report describes two cases of granulomatous lung inflammation following coronavirus disease 2019 (COVID-19), presenting as a sarcoidosis-like reaction with granuloma formation in airspaces and ...interstitium. Clinical and pathological findings in both cases were similar to but still distinct from sarcoidosis. In the first case, the chest CT of a 55-year-old male with a history of polymerase chain reaction (PCR)-confirmed COVID-19 showed well-defined multiple nodules in the bilateral lung fields. He underwent video-assisted thoracic surgery for diagnostic purposes. The pathological specimen showed loose non-caseous granulomas with mild lymphoplasmacytic infiltration and early fibroblastic proliferation in alveolar spaces. In the second case, a 68-year-old male, who presented with consolidation in the anterior segment of the right upper lobe, underwent bronchoscopy and transbronchial lung biopsy showed non-caseous granulomas with mild lymphoplasmacytic infiltration in the peribronchiolar interstitium. The opacities improved spontaneously in both cases. Further studies are needed to determine whether COVID-19 could cause granulomatous lung inflammation distinct from sarcoidosis.
Objective Rapidly progressive interstitial lung disease (RP-ILD) with anti-melanoma differentiation-associated protein 5 (MDA5) antibody potentially presents with a fatal clinical course and requires ...early intensive treatment. Recently, perilobular opacity was reported to pathologically correspond to the acute phase of diffuse alveolar damage in RP-ILD with anti-MDA5 antibody. We aimed to investigate whether or not perilobular opacity was a common radiological finding in RP-ILD patients with anti-MDA5 antibody. Methods We conducted a retrospective review of the medical records of eight consecutive patients with RP-ILD with anti-MDA5 antibody. The clinical features and radiological findings of follow-up computed tomography (CT) during the course of their disease were evaluated. Results Among eight RP-ILD patients with anti-MDA-5 antibody, six showed perilobular opacity in the lower lobes, and the remaining two had only consolidation on high-resolution CT. Of note, the perilobular opacity in all six patients thickened and progressed to consolidation with a loss of lung volume in a short period. Despite intensive treatment, 6 patients (75%) died within 100 days after the first visit. Notably, the two patients with consolidation presented with a very rapid clinical course and died in 13 days each. In the two survivors, the perilobular opacity and consolidation recovered with improvement in the loss of lung volume. Conclusion Rapidly progressive perilobular opacity that thickens and progresses to consolidation is characteristic of RP-ILD with anti-MDA5 antibody. Chest physicians should immediately check the status of anti-MDA-5 antibody in order to initiate early aggressive therapy in RP-ILD patients with rapidly progressive perilobular opacity.
Immunohistochemical analysis of formalin-fixed paraffin-embedded (FFPE) tissue blocks is routinely used to identify virus-infected cells. However, detecting virus particles in FFPE sections using ...light microscopy is difficult because of the light diffraction resolution limitations of an optical microscope. In this study, light microscopy and field emission scanning electron microscopy were performed to observe 3-dimensional virus particles in FFPE sections in a nondestructive manner using NanoSuit or osmium conductive treatment methods. The virus particles in FFPE sections were immunostained with specific antibodies against the surface antigens of the viral particles and stained with 3,3'-diaminobenzidine. A metal solution (0.2% gold chloride or 2% osmium tetroxide) was applied to enhance the 3,3'-diaminobenzidine-stained area. This procedure is nondestructive for FFPE sections and is a simpler method than transmission electron microscopy. To validate the applicability of this technique, we performed 3-dimensional imaging of the virus particles of different sizes, such as human papillomavirus, cytomegalovirus, and varicella-zoster virus. Furthermore, ultrathin sections from the FFPE sections that were observed to harbor viral particles using field emission scanning electron microscopy were prepared and assessed using transmission electron microscopy. In the correlative areas, transmission electron microscopy confirmed the presence of large numbers of virus particles. These results indicated that the combination of marking viral particles with 3,3'-diaminobenzidine/metal staining and conductive treatment can identify active progeny virus particles in FFPE sections using scanning electron microscopy. This easy correlative imaging of field emission scanning electron microscopy of the identical area of FFPE in light microscopy may help elucidate new pathological mechanisms of virus-related diseases.
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