Lung hypoplasia and severe pulmonary hypertension in an infant with double heterozygosity for spondyloepiphyseal dysplasia congenita and achondroplasia

A rare instance of double heterozygosity for spondyloepiphyseal dysplasia congenita and achondroplasia is presented. Despite midface hypoplasia, thorax deformity and lung hypoplasia, the child survived the neonatal period. Severe pulmonary hypertension, already present at birth, led to right heart failure and death at the age of 1 year.     

Bronchioalveolar stem cells in lung repair,regeneration and disease

Bronchioalveolar stem cells (BASCs) are a lung resident stem cell population located at bronchioalveolar duct junctions that contribute to the maintenance of bronchiolar club cells and alveolar epithelial cells of the distal lung. Their transformed counterparts are considered to be likely progenitors of lung adenocarcinomas, which has been a major area of research in relation to BASCs. A critical limitation in addressing the function of BASCs in vivo has been the lack of a unique BASC marker, which has prevented specific targeting of BASCs in animal models of respiratory conditions. Recently, there have been several studies describing genetically modified mice that allow in vivo quantification, tracing, and functional analysis of BASCs to address this long-standing issue. These cutting-edge experimental tools will likely have significant implications for future experimental studies involving BASCs and the elucidation of their role in various lung diseases. To date, this has been largely explored in models of lung injury including naphthalene-induced airway injury, bleomycin-induced alveolar injury, hyperoxia-induced models of bronchopulmonary dysplasia, and influenza virus infection. These novel experimental mouse tools will facilitate the assessment of the impact of BASC loss on additional respiratory conditions including infection-induced severe asthma and chronic obstructive pulmonary disease, as well as respiratory bacterial infections, both in early life and adulthood. These future studies may shed light on the potential broad applicability of targeting BASCs for a diverse range of respiratory conditions during lung development and in promoting effective regeneration and repair of the lung in respiratory diseases. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Type I and III collagen protein precursors and mRNA in the developing human lung

Extracellular matrix proteins have a prominent role in both ontogenesis and fibrogenesis in the human lung. The aim of this study was to analyse the expression of newly formed precursor proteins and mRNA of collagen types I and III in developing human lung tissues from 12 to 40 weeks of gestation, and also in neonatal disorders such as respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD). Lung tissues were obtained at autopsy from 60 non-malformed cases. All tissues were analysed by immunohistochemistry and 24 were also investigated by mRNA in situ hybridization. The precursor proteins and mRNA of both collagens were expressed in abundance in pulmonary arteries and veins during all developmental periods. In RDS and BPD, precursor proteins and mRNAs of both collagen types were increased within alveolar walls. The cells in these locations showed alpha-smooth muscle actin, vimentin, and variable desmin immunoreactivity. Collagen I and III precursor proteins and mRNA were also observed in pleura, bronchi, bronchioles, and around chondrocytes during all developmental periods and in diseased lung. In conclusion, collagens I and III were expressed in a similar way in and around various cell types in the developing lung and their expression was increased within alveolar walls in RDS and BPD. Myofibroblast-type cells appeared to produce mRNA for both types of collagen in alveoli.     

Rhabdomyomatosis of the newborn lung unassociated with other malformations

 

Aims:

To describe a case of rhabdomyomatosis of the lung unassociated with other external or visceral malformations in a newborn infant.  

Methods and results:

A 26 weeks' gestation newborn male with no relevant medical or family history presented a well-circumscribed solid area in the posterior mediastinum occupying the upper lobe of the right lung. The possibility of neuroblastoma or an extralobar pulmonary sequestration were excluded after laboratory and arteriographic studies. No visceral anomalies were found. At the age of 9 months the patient underwent a partial lobectomy, and he is free of disease 39 months after surgery. Histological examination demonstrated the presence of numerous bundles of striated fibres arranged haphazardly in the pulmonary interstitium in a background of a type-II congenital cystic adenomatoid malformation-like morphology of the resected lung.  

Conclusion:

The presence of striated muscle fibres in the lung not necessarily represents a lethal congenital malformation. As this case shows, rhabdomyomatosis of the lung can affect a single pulmonary lobe, and resection of the affected lung parenchyma may be curative. It is important for pathologists to be aware of this entity, although it is exceptional, and to include it in the differential diagnosis of pulmonary masses in the newborn lung.     

Early postnatal lung development in the eastern quoll (Dasyurus viverrinus)

Early postnatal lung development (1–25 days) in the eastern quoll (Dasyurus viverrinus) was investigated to assess the morphofunctional status of one of the most immature marsupial neonates. Lung volume, surface density, surface area, and parenchymal and nonparenchymal volume proportions were determined using light microscopic morphometry. The lungs of the neonate were at the canalicular stage and consisted of two “balloon-like” airways with few septal ridges. The absolute volume of the lung was only 0.0009 cm³ with an air space surface density of 108.83 cm⁻¹ and a surface area of 0.082 cm². The increase in lung volume in the first three postnatal days was mainly due to airspace expansion. The rapid postnatal development of the lung was indicated by an increase in the septal proportion of the parenchyma around day 4, which was reflected by an increase in the airspace surface density and surface area. By day 5, the lung entered the saccular stage of development with a reduction in septal thickness, expansion of the tubules into saccules and development of a double capillary system. The subsequent saccular period was characterized by repetitive septation steps, which increased the number of airway generations. The lungs of the newborn Dasyurus viverrinus must be considered as structurally and quantitatively insufficient to meet the respiratory requirements at birth. Hence, cutaneous gas exchange might be crucial for the first three postnatal days. The lung has to mature rapidly in the early postnatal period to support the increased metabolic requirements of the developing young.     

Pathology of seven mucous cell adenomas of the bronchial glands with particular reference to ultrastructure

The pathology, including ultrastructure, of seven mucous cell adenomas of the bronchial glands is described. They occurred as polypoid intraluminal lesions in both male and female patients between the ages of 7 and 55 years (mean 26 years). Histologically they were all benign and consisted of predominantly mucus-secreting cells arranged in acini or ducts or in solid groups. A little squamous differentiation was evident in four cases, insufficient in our opinion, to justify the term mucoepidermoid tumour. By electron microscopy, many tumour cells resembled mucous cells of the bronchial glands, containing typical large mucous granules of finely granular, reticular or fibrillated material, and sometimes small electron-dense bodies. In four cases some cells showed both secretory granules and features of squamous differentiation such as numerous tonofilaments and desmosomes. Oncocytic differentiation was seen occasionally.     

Acid-base regulation during embryonic development in amniotes, with particular reference to birds

During avian embryonic development, the carbon dioxide tension inside the egg increases as the shell restricts gas exchange with the environment. Acid-base regulation of the avian embryo is a complex process, not only due to the non-function of the lungs and limited functionality of the kidneys but also because the embryo is affected by the inflow of bicarbonates from the shell, when calcium is reabsorbed for calcification. Moreover, interaction occurs between the embryo and the extraembryonic compartments. It has been shown that carbonic anhydrase plays a crucial role in the formation of sub-embryonic fluid and in the chorioallantoic membrane and kidney. This review provides a detailed overview of the acid-base status of the extraembryonic compartments inside chicken eggs, and their interaction in keeping the acid-base status of the embryo balanced. Secondly, experimental acid-base disturbances are summarized. The last part of the review briefly compares embryos of birds and other amniotes (mammals and reptiles) with regard to acid-base regulation.     

Changes in sialic acid expression in the lung during intrauterine development of the human fetus

Sialic acid is a component of glycoproteins that influences enzymatic and receptor functions of cells. During proliferation and differentiation of tissues, sialic acid can serve as a recognition determinant in intercellular communication and interactions of cells with the extracellular matrix. In the present study, sialic acid expression in relation to developmental maturity of the lung has been studied. We analyzed 12 necroptic lung specimens from foetuses of different gestational ages from the 15th week to the neonate. Sections were stained histochemically using 3 lectins specific for sialic acid: Tritrichomonas mobilensis lectin (TML), specific for sialic acid without linkage preference, Sambucus nigra agglutinin (SNA), specific for alpha2,6-linked sialic acid, and Maackia amurensis leucoagglutinin (MAL), specific for alpha2,3-linked sialic acid. MAL positivity dominated over SNA positivity showing prevalence of alpha2,3-linked sialic acids to be homogeneously distributed in the lung at the canalicular stage of development. In more mature lungs, well-differentiated bronchial epithelium showed strong sialic acid expression of both linkages. Sialic acid with alpha2,6 linkage dominated in vascular endothelium. Our results showed a slight decrease in sialic acid expression in lungs with gestational age to a relative minimum before birth. Lectin staining of mature lung tissue showed intense sialic acid expression in alveolar epithelial type II cells. Changes in expression of specific sialic acids during differentiation of the lungs may be useful as marker of the degree of maturity of the foetus.     

Current and emerging treatment options for interstitial lung disease in patients with rheumatic disease

The management of connective tissue disease-associated interstitial lung disease (CTD-ILD) is complex and this arena offers many challenges to the practicing clinician. Unfortunately, treatment strategies and recommendations are often based on experience rather than evidence, and there are few effective therapeutic options. Pharmacologic intervention with immunosuppression is usually the mainstay of therapy and is reserved for those with clinically significant and/or progressive ILD. There is a desperate need for controlled trials across the spectrum of CTD-ILD and a number of potentially promising novel therapies warrant further study. It is important to address co-morbid conditions or aggravating factors (e.g., gastroesophageal reflux, aspiration, bone health, pulmonary hypertension, Pneumocystis jiroveci prophylaxis) and to institute non-pharmacologic management strategies (e.g., supplemental oxygen and cardiopulmonary rehabilitation) as part of a comprehensive treatment plan in CTD-ILD.     

Pulmonary involvement in type 1 Gaucher disease: functional and exercise findings in patients with and without clinical interstitial lung disease

Pulmonary disease is a well-known complication of Type 1 Gaucher disease (GD), although its incidence is not well established and its severity varies. The purpose of this study was to determine the frequency and extent of pulmonary involvement in patients with GD. Pulmonary involvement was assessed by history, physical examination and chest radiograph in 150 consecutive patients with Type 1 GD presenting at a specialized center for genetic diseases. Five patients were noted to have clinical evidence of pulmonary involvement. Full pulmonary function tests were performed in these five patients and in an additional 13 patients randomly selected from the remaining 145. Many of the 18 patients also underwent radionuclide body imaging with 67 Gallium citrate and 111Indium-tagged leucocyte scans, as well as incremental cardiorespiratory exercise tests. Lung biopsies were available in two patients with lung disease, and a second examination of lung tissue was performed in one of these two patients post-mortem. Clinical lung disease was detected in five patients. All five had dyspnea, diffuse infiltrates, restrictive impairment and low single breath CO diffusing capacity (DLCOSB). Two of these patients underwent exercise testing and showed abnormalities consistent with lung disease (ventilatory limitation, excessive ventilation and increased dead space) as well as decreased VO2 max. and anaerobic threshold (AT). In contrast, in the other 13 patients, physical examination, chest radiographs and pulmonary function were normal (except for a low DLCOSB in one patient). Responses on exercise testing (performed in six of the 13 patients) were consistent with a circulatory impairment (decreased VO2 max. and AT). Our study found that <5% of patients with Type 1 GD have clinical interstitial lung disease. In addition, we found that some patients, without evident lung involvement, may experience limitations in physical exertion and are easily fatigued; this is attributable to impaired circulation.     

青年人和老年人肺癌临床病理特征比较

目的　比较青年人和老年人肺癌的临床病理特征。方法　对 83例 30岁以下青年人肺癌 (青年组 )和 89例 70岁以上老年人肺癌 (老年组 )的临床资料和组织病理进行回顾性分析。结果　①青年组肺癌占同期肺癌总数的 4 18% ,老年组占4 4 8%。②青年组和老年组肺癌的男女性别比分别为 2 19∶1和 11 7∶1(P <0 0 5 ) ;青年组女性发病比率为 31 3% ,老年组为7 9% (P <0 0 1)。③青年组和老年组吸烟者各占 36 1%和 6 9 7% (P <0 0 1)。④青年组和老年组各型肺癌所占比率分别为鳞癌 31 3% / 5 9 6 %、腺癌 37 3% / 2 5 8%、小细胞癌 2 1 7% / 12 4 % ;青年组腺癌和小细胞癌明显高于老年组 (P <0 0 5和P <0 0 1) ,而青年组鳞癌则明显低于老年组 (P <0 0 1)。⑤青年组和老年组的低分化癌比率分别占 6 3 9%和 4 3 8% (P <0 0 1)。结论　青年人肺癌以女性、肺腺癌和小细胞癌发病比例高为特征 ,且以低分化癌占多数 ;而老年人肺癌则以男性和鳞癌占优势 ,可能与老年男性吸烟群体增加有关     

Supramaximal test results of male and female speed skaters with particular reference to methodological problems

Summary Six male and six female elite speed skaters were tested during two bicycle ergometer tests: a 30 s sprint test and a 2.5 min supra maximal test. During the 2.5 min test oxygen consumption was measured every 30 s. The males showed 30–31% higher mean power output values both during the sprint test (1103 versus 769 Watt) and during the 2.5 min test (570 versus 390 Watt). Maximal oxygen consumption was 31% higher for the males than for the females (5.10 versus 3.50 l · min^–1). However, when expressed per kilogram lean body weight (LBM), power output and oxygen consumption was equal for both sexes. Differences between present and previous results are most likely due to methodological problems with the estimation of load during the supra maximal test. Subjects appear to experience difficulties in distributing their power output over the 2.5 min if they are tested for the first time. For experienced skaters and cyclists, fixed levels of 19 W · kgLBM^–1 as initial load setting for the sprint test and 8 W · kg LBM^–1 for the 2.5 min test are recommended.     

Pathology of pulmonary tuberculosis and non-tuberculous mycobacterial lung disease: Facts,misconceptions, and practical tips for pathologists

Most pathologists are familiar with the microscopic features of tuberculosis and the need to examine special stains for acid-fast bacteria (AFB) in cases of granulomatous lung disease. However, misconceptions do exist, including the concept that finding AFB in “caseating granulomas” confirms the diagnosis of tuberculosis. This dogma is attributable to the high prevalence of tuberculosis in many countries, as well as unfamiliarity with the microscopic spectrum of non-tuberculous mycobacterial lung disease. This review aims to provide surgical pathologists with practical tips to identify AFB, illustrate the histologic overlap between pulmonary tuberculosis and non-tuberculous mycobacterial lung disease, and highlight the importance of cultures in this setting. M. tuberculosis and non-tuberculous mycobacteria cannot be reliably differentiated either on the basis of the tissue reaction or by bacterial morphology on acid-fast stains. Although a presumptive clinical diagnosis of tuberculosis can be made without culture-confirmation, the only definitive means to determine the true identity of AFB is by cultures or molecular methods. Making this distinction is most critical when AFB are found in incidentally detected lung nodules in geographic locations where the incidence of tuberculosis is low, because in such settings AFB in necrotizing granulomas of the lung are more likely to be non-tuberculous mycobacteria than M. tuberculosis.     

角化生长因子在慢性肺疾病早产大鼠的表达

目的探讨高氧致CLD早产大鼠KGF表达的变化规律.方法 60只新生早产大鼠随机分为2组,每组30只:A组-对照组;B组-高氧组(吸入95%O2).分别采用Western Blotting及RT-PCR检测肺组织KGF及其mRNA表达.结果高氧组肺内KGF及其mRNA表达高于对照组.结论高氧引起新生早产大鼠肺内KGF及其mRNA的表达随时间发生变化.     

Heterozygous CTNNB1 and TBX4 variants in a patient with abnormal lung growth,pulmonary hypertension,microcephaly, and spasticity

The canonical wingless (Wnt) and fibroblast growth factor (FGF) signaling pathways involving CTNNB1 and TBX4, respectively, are crucial for the regulation of human development. Perturbations of these pathways and disruptions from biological homeostasis have been associated with abnormal morphogenesis of multiple organs, including the lung. The aim of this study was to identify the underlying genetic cause of abnormal lung growth, pulmonary hypertension (PAH), severe microcephaly, and muscle spasticity in a full-term newborn, who died at 4 months of age due to progressively worsening PAH and respiratory failure. Family trio exome sequencing showed a de novo heterozygous nonsense c.1603C>T (p.Arg535*) variant in CTNNB1 and a paternally inherited heterozygous missense c.1198G>A (p.Glu400Lys) variant in TBX4, both predicted to be likely deleterious. We expand the phenotypic spectrum associated with CTNNB1 and TBX4 variants and indicate that they could act synergistically to produce a distinct more severe phenotype. Our findings further support a recently proposed complex compound inheritance model in lethal lung developmental diseases and the contention that dual molecular diagnoses can parsimoniously explain blended phenotypes.     

右肺肺段间平面在肺段切除术中的意义

目的：为右肺肺段切除术寻找肺段段间平面提供解剖学基础。方法：在48个成人右肺标本上，切开肺段间各表面形态处的脏胸膜，以寻找、分离其“自然分裂线”的方法，寻找段间平面。结果：（1）上叶尖前切迹、第1肋压迹和裂间嵴的出现率分别为91.7％，77.1％和93.8％，尖前切迹能被分离的占64.6％；（2）中叶“中副裂”的出现率为72.9％，能分离的占62.5％。结论：尖前切迹、“中副裂”、“底前副裂”能分离出段间平面，是肺段分界的表面标志，可作为肺段切除术的手术入路。