Background: Apoptosis has recently been proposed to contribute to the pathogenesis of emphysema. Methods: In order to establish if cell fate plays a role even in end-stage disease we studied 16 lungs (9 smoking-associated and 7 α1antitrypsin (AAT)-deficiency emphysema) from patients who had undergone lung transplantations. Six unused donor lungs served as controls. Apoptosis was evaluated by TUNEL analysis, single-stranded DNA laddering, electron microscopy and cell proliferation by an immunohistochemical method (MIB1). The role of the transforming growth factor (TGF)-β1 pathway was also investigated and correlated with epithelial cell turnover and with the severity of inflammatory cell infiltrate. Results: The apoptotic index (AI) was significantly higher in emphysematous lungs compared to the control group (p ≤ 0.01), particularly if only lungs with AAT-deficiency emphysema were considered (p ≤ 0.01 vs p = 0.09). The proliferation index was similar in patients and controls (1.9 ± 2.2 vs 1.7 ± 1.1). An increased number of T lymphocytes was observed in AAT-deficiency lungs than smoking-related cases (p ≤ 0.05). TGF-β1 expression in the alveolar wall was higher in patients with smoking-associated emphysema than in cases with AAT-deficiency emphysema (p ≤ 0.05). A positive correlation between TGF-βRII and AI was observed only in the control group (p ≤ 0.005, r² = 0.8). A negative correlation was found between the TGF-β pathway (particularly TGF-βRII) and T lymphocytes infiltrate in smoking-related cases (p ≤ 0.05, r² = 0.99) Conclusion: Our findings suggest that apoptosis of alveolar epithelial cells plays an important role even in end-stage emphysema particularly in AAT-deficiency disease. The TGFβ-1 pathway does not seem to directly influence epithelial turnover in end-stage disease. Inflammatory cytokine different from TGF-β1 may differently orchestrate cell fate in AAT and smoking-related emphysema types.

Idiopathic pulmonary hemosiderosis (IPH) is a rare disease of unknown etiology characterized by hemoptysis, diffuse pulmonary infiltration, and anemia. Diagnosis requires a detailed clinical history and transbronchial lung biopsy (TLB). A 19-year-old man developed progressive dyspnea, hemoptysis, and anemia. The chest x-rays showed bilateral opacities. IPH was diagnosed on the basis of clinical findings and TLB. The patient was treated with corticosteroidal therapy. His respiratory function worsened, and he underwent lung transplantation in 1997. The pathological examination on native lungs confirmed the previous histologic diagnosis. In 2000, the patient again developed hemoptysis, fever, and hypoxemia. A recurrence of the disease was established by TLB. This is the first report of recurring IPH. The possibility of recurrent IPH raises the question whether these patients should be disqualified from lung transplantation. This question is unanswerable because incidence of recurrence, time course, and impact on the graft function are presently unknown and unpredictable.

The aim of this study is to validate the accuracy of HER2 assessment on biopsies by comparing matched biopsy/surgical material from the same patients. HER2 status was evaluated by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) in 103 cases of gastric and gastroesophageal junction cancers in coupled biopsy and surgical material. Complete concordance between IHC and FISH results on biopsy versus surgical samples was noted in 80% and 95% of cases, respectively. At comprehensive comparison, including IHC and FISH data on biopsy and surgical samples, 89% of biopsies were predictive of HER2 status in surgical samples, whereas 11% showed variable inconsistencies. The majority of these (10 of 12 cases) showed IHC score 0/1+ on biopsy but were all IHC positive and amplified at surgery; in particular, three (3 of 35; 8.5%) IHC score 0 and four (4 of 16; 25%) IHC score 1+ cases were FISH amplified on biopsy material also, whereas the remaining three cases were FISH non-amplified on biopsy. The percentage of cases, which were FISH amplified with IHC score 1+ or 2+ on biopsies, were similar (25% and 33%, respectively) and they also shared a similar grade of amplification. These data suggest that both IHC score 1+ and 2+ on biopsy material represent "equivocal cases" that may merit further investigation. The predictive value of HER2 IHC in biopsies is high. FISH analysis should be considered for IHC score 2+ and 1+ biopsy cases. Approximately 8% of cases will not be accurately predicted by biopsy evaluation.

Successful human pregnancy needs several highly controlled steps to guarantee an oocyte’s fertilization, the embryo’s pre-implantation development, and its subsequent implantation into the uterine wall. The subsequent placenta development ensures adequate fetal nutrition and oxygenation, with the trophoblast being the first cell lineage to differentiate during this process. The placenta sustains the growth of the fetus by providing it with oxygen and nutrients and removing waste products. It is not surprising that issues with the early development of the placenta can lead to common pregnancy disorders, such as recurrent miscarriage, fetal growth restriction, pre-eclampsia, and stillbirth. Understanding the normal development of the human placenta is essential for recognizing and contextualizing any pathological aberrations that may occur. The effects of these issues may not become apparent until later in pregnancy, during the mid or advanced stages. This review discusses the process of the embryo implantation phase, the molecular mechanisms involved, and the abnormalities in those mechanisms that are thought to contribute to the development of pre-eclampsia. The review also covers the histological hallmarks of pre-eclampsia as found during the examination of placental tissue from pre-eclampsia patients.

Congenital anomalies of the tubular gastrointestinal tract are an important cause of morbidity not only in infants, but also in children and adults. The gastrointestinal (GI) tract, composed of all three primitive germ layers, develops early during embryogenesis. Two major steps in its development are the formation of the gut tube (giving rise to the foregut, the midgut and the hindgut), and the formation of individual organs with specialized cell types. Formation of an intact and functioning GI tract is under strict control from various molecular pathways. Disruption of any of these crucial mechanisms involved in the cell-fate decision along the dorsoventral, anteroposterior, left-right and radial axes, can lead to numerous congenital anomalies, most of which occur and present in infancy. However, they may run undetected during childhood. Therapy is surgical, which in some cases must be performed urgently, and prognosis depends on early diagnosis and suitable treatment. A precise pathologic macroscopic or microscopic diagnosis is important, not only for the immediate treatment and management of affected individuals, but also for future counselling of the affected individual and their family. This is even more true in cases of multiple anomalies or syndromic patterns. We discuss some of the more frequent or clinically important congenital anomalies of the tubular GI, including atresia’s, duplications, intestinal malrotation, Meckel’s diverticulum and Hirschsprung’s Disease.

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disorder with a poor prognosis. Epithelial instability is a crucial step in the development and progression of the disease, including neoplastic transformation. Few tissue markers for epithelial instability have been reported in IPF. Squamous cell carcinoma antigen (SCCA) is a serine protease inhibitor typically expressed by dysplastic and neoplastic cells of epithelial origin, more often in squamous cell tumours. At present, no information is available on its expression in IPF. Methods: SCCA and transforming growth factor β (TGFβ) expression in surgical lung biopsies from 22 patients with IPF and 20 control cases was examined. An in vitro study using A549 pneumocytes was also conducted to investigate the relationship between SCCA and TGFβ expression. SCCA and TGFβ epithelial expression was evaluated by immunohistochemistry and reverse transcription–PCR (RT-PCR). SCCA values were correlated with different pathological and clinical parameters. Time course analysis of TGFβ expression in A549 pneumocytes incubated with different SCCA concentrations was assessed by real time RT–PCR. Results: SCCA was expressed in many metaplastic alveolar epithelial cells in all IPF cases with a mean value of 24.9% while it was seen in only two control patients in up to 5% of metaplastic cells. In patients with IPF, SCCA correlated positively with extension of fibroblastic foci (r = 0.49, p = 0.02), expression of TGFβ (r = 0.78, p<0.0001) and with carbon monoxide transfer factor decline after 9 months of follow-up (r = 0.59, p = 0.01). In vitro experiments showed that incubation of cultured cells with SCCA induced TGFβ expression, with a peak at 24 h. Conclusion: Our findings provide for the first time a potential mechanism by which SCCA secreted from metaplastic epithelial cells may exert a profibrotic effect in IPF. SCCA could be an important biomarker in this incurable disease.