Impact of the COVID-19 pandemic on HPV vaccination coverage in the general population and in PLWHs.

OBJECTIVE: On March 11, 2020, the World Health Organization (WHO) has declared the novel coronavirus (COVID-19) outbreak as a global pandemic. COVID-19 pandemic has impacted health services, including immunization programs, with a consequent reduction in vaccination coverage in those categories for which the prevention of vaccine-preventable diseases is strongly recommended. SUBJECTS AND METHODS: We conducted a retrospective cross-sectional study on the general population and on PLWHs, comparing anti-human papillomavirus (HPV) vaccination coverage data in 2019, before COVID-19 pandemic, and the 2020 data, after the announcement of the pandemic state and the lockdown and the implementation of restrictive measures to contain the contagion. RESULTS: Compared to 2019, 2020 data show a 42% reduction in HPV vaccine coverage in the general population and 36% in PLWHs. The greatest reduction in anti-HPV vaccination coverage occurred during periods of greatest restriction and mainly concerned the general population. CONCLUSIONS: The prevention of vaccine-preventable diseases remains essential. Above all, it is essential to increase and recover the anti-HPV vaccine coverage, in consideration of the data that show its preventive oncological efficacy.

Granular cell tumor of the trachea as a rare cause of dyspnea in a young woman.

Tracheal granular cell tumors are rare neurogenic neoplasms characterized by an indolent behavior. We report the case of a young woman affected by this tumor with non-specific clinical presentation. We performed a literature search in order to identify all the cases of tracheal granular cell tumor and to summarize the current state of knowledge about this rare disease.

The expanding role of endobronchial ultrasound in patients with centrally located intrapulmonary tumors.

OBJECTIVES: Tissue acquisition of lung tumors is crucial for diagnostic and treatment purposes. In patients with centrally located lung tumors without endobronchial abnormalities the yield of conventional bronchoscopy is poor. Objective of this study was to assess diagnostic yield of EBUS-TBNA in patients with lung tumors, located near or adjacent to the major airways. METHODS: International multicenter retrospective analysis (2013-2018) of linear EBUS databases in Bologna, Italy and Amsterdam, The Netherlands. Patients with a centrally-located lung tumor without endobronchial abnormalities who underwent lung tumor search with linear EBUS were included. Diagnostic yield, feasibility of EBUS guided tumor sampling, complication rate, adequacy of the aspirates for mutational analysis, and assessment of mediastinal/vascular invasion (T4) were evaluated. RESULTS AND CONCLUSION: Real-time EBUS-TBNA diagnostic yield to sample centrally located intrapulmonary tumor was 83% (136/163) and it was independent of tumor location (paratracheal, mainstem, lobar, segmental bronchus). The feasibility to sample the lung tumor was 89% (145/163). In 4 cases the tumor was not found with EBUS. In the other 14 cases, tumor sampling was not performed due to: loss of the echo window after needle insertion [n = 3], interposition of a large vessel [n = 7], switch to radial EBUS [n = 1], switch and sampling through EUS or EUS-B [n = 3]. No major complications occurred. Mutational analysis was successful in 54/63 (86%) of samples. Using surgery as reference standard, EBUS proved more reliable than CT (24/24, 100% versus 22/24, 91.7%, respectively) in the assessment of mediastinal/vascular tumor invasion (T4 status). IN CONCLUSION: Lung tumors presenting without endobronchial abnormalities and located adjacent to the major airways can be safely sampled by EBUS-TBNA resulting in high diagnostic yield irrespective of tumor location. Successful molecular profiling and reliable assessment of mediastinal/vascular invasion (T4) in patients with advanced disease provide additional value to EBUS procedures in the setting of centrally-located lung lesions.

Adenocarcinoma classification: patterns and prognosis.

Lung cancer is the most frequent human malignancy and the principal cause of cancer-related death worldwide. Adenocarcinoma is now the main histologic type, accounting for almost half of all the cases. The 2015 World Health Organization has adopted the classification recently developed by the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society. This new adenocarcinoma classification has incorporated up-to-date advances in radiological, molecular and oncological knowledge, providing univocal diagnostic criteria and terminology. For resection specimens, new entities have been defined such as adenocarcinoma in situ and minimally invasive adenocarcinoma to designate adenocarcinomas, mostly nonmucinous and ≤ 3 cm in size, with either pure lepidic growth or predominant lepidic growth with ≤ 5 mm invasion, respectively. For invasive adenocarcinoma, the new classification has introduced histological subtyping according to the predominant pattern of growth of the neoplastic cells: lepidic (formerly non mucinous brochioloalveolar adenocarcinoma), acinar, papillary, micropapillary, and solid. Of note, micropapillary pattern is a brand new histologic subtype. In addition, four variants of invasive adenocarcinoma are recognized, namely invasive mucinous (formerly mucinous brochioloalveolar adenocarcinoma), colloid, fetal, and enteric. Importantly, three variants that were considered in the previous classification have been eliminated, specifically mucinous cystadenocarcinoma, signet ring cell, and clear cell adenocarcinoma. This review presents the changes introduced by the current histological classification of lung adenocarcinoma and its prognostic implications.

Diffuse alveolar damage.

Diffuse alveolar damage (DAD) is a characteristic histopathologic pattern that has time dependent findings: intraalveolar and interstitial oedema, and hyaline membranes in the acute phase, myofibroblastic accumulation in the alveolar spaces and type II alveolar cell proliferation in the proliferative phase and fibrosis in the more advanced phases. The diagnosis of DAD is sometimes feasible on small specimens obtained by transbronchial lung biopsy or on cytological slides. Surgical lung biopsy is rarely needed.

Granulomatous lung disease.

Granulomas are a frequent challenge for pathologists, which can be identified both in histological and cytological material in a number of conditions. With regard to interstitial lung diseases, granulomas can be associated with infection (e.g. mycobacterial), immunological conditions (e.g. hypersensitivity pneumonitis), or may be idiopathic (e.g. sarcoidosis). Considering morphology, features that should be identified are the presence of necrosis, the cohesiveness and coalescence of granulomas, the presence of fibrosis and the amount and quality of the associated inflammatory infiltrate. The most interesting approach to granulomatous lung disease is indeed represented by their pattern of distribution within the secondary lobule; in fact, granulomas can be distributed along lymphatic routes (e.g. sarcoidosis), randomly (miliary infections, e.g. mycobacterial and fungal infections), or along the airways (hypersensitivity pneumonitis, hot tub lung, aspiration pneumonia and sometimes infections). We propose a combined radiological-histopathological approach for defining the morphological features and anatomic localization of granulomatous ILDs. In addition, a detailed review of their clinical features is provided, together with a description of the main procedures used to obtain respiratory samples for pathology and microbiology studies in these patients.

Insulin-like growth factor receptor 1 (IGFR-1) is significantly associated with longer survival in non-small-cell lung cancer patients treated with gefitinib.

BACKGROUND: The aim of the study was to assess whether loss of PTEN and expression of insulin-like growth factor receptor 1 (IGFR-1) could be responsible for intrinsic resistance to the tyrosine kinase inhibitor (TKI) gefitinib. PATIENTS AND METHODS: One hundred and twenty-four gefitinib-treated patients with advanced non-small-cell lung cancer (NSCLC) were analyzed for PTEN and IGFR-1 expression by immunohistochemistry. RESULTS: IGFR-1 was evaluated in 77 patients and resulted positive in 30 (39.0%). IGFR-1 expression was not significantly associated with clinical or biological characteristics. No difference in response to gefitinib treatment (16.7% versus 12.8%, P = 0.74) and time to progression (2.6 versus 3.06 months, P = 0.83) was observed between IGFR-1+ and IGFR-1-. Median survival was significantly longer in IGFR-1+ patients (17.8 versus 7.3 months, P = 0.013). PTEN expression was successfully evaluated in 93 cases. Loss of PTEN was detected in 19 tumors (20.4%) and was not associated with any clinical or biological characteristic. No difference in terms of response, time to progression and survival was observed between PTEN+ and PTEN- patients. In multivariable analysis IGFR-1 negative status was significantly associated with higher risk of death (hazard ratio 2.21, P = 0.012). CONCLUSIONS: IGFR-1 expression and loss of PTEN are not associated with intrinsic resistance to gefitinib. Clinical relevance of these two biomarkers as determinant for acquired resistance, and the prognostic role of IGFR-1 expression in patients not exposed to TKIs should be evaluated further.

HER3 genomic gain and sensitivity to gefitinib in advanced non-small-cell lung cancer patients.

In non-small-cell lung cancer (NSCLC), sensitivity to tyrosine kinase inhibitors (TKIs) is associated with activating mutations and genomic gain of the epidermal growth factor receptor (EGFR). Preclinical data suggested that HER3 overexpression increases sensitivity to TKIs. A total of 82 NSCLC patients treated with gefitinib (250 mg), and previously evaluated for EGFR and HER2 status by fluorescence in situ hybridisation (FISH) and DNA sequencing, and for Phospho-Akt status by immunohistochemistry, were investigated for HER3 genomic gain by FISH. Patients with high polysomy and gene amplification were considered as HER3 FISH positive (+). HER3 FISH+ pattern was significantly associated with female gender (P=0.02) and never smoking history (P=0.02). Patients with HER3+ tumours (26.8%) had a significantly longer time to progression (3.7 vs 2.7, P=0.04) than patients with HER3- tumours, but not a significantly better response rate or survival. Patients with EGFR+/HER3+ tumours had higher objective response rate (36.4 vs 9.9%, P=0.03) and time to progression (7.7 vs 2.7 months, P=0.03) than patients with EGFR- and/or HER3- tumours, but no significantly longer survival. No difference in response was observed according to HER3 status in patients with EGFR+ tumours. Patients with HER2+/HER3+ tumours had similar outcome as patients with HER2- and/or HER3- tumours. Significantly different clinical end points were not observed between patients with HER3+/P-Akt+ and HER3- and/or P-Akt- tumours. Genomic gain for HER3 is not a marker for response or resistance to TKI therapy in advanced NSCLC patients.

Differential diagnosis between usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP) assessed by high-resolution computed tomography (HRCT).

PURPOSE: The aim of this study was to assess the accuracy of high-resolution CT in the differential diagnosis between UIP and NSIP, and the correlations with histological and functional findings. MATERIALS AND METHODS: Patients underwent thin-collimation spiral CT (1 mm), with 10-mm interval. Pulmonary function was assessed with a pneumotacograph and body plethysmograph connected with a computer for data analysis. Three pathologists, blinded to the clinical and functional data, provided a histological diagnosis based on established criteria reported in the literature. The study group only included patients with a histological diagnosis of either UIP or NSIP. RESULTS: We achieved a correct diagnosis of NSIP in 86.6% of cases (76.4% sensitivity; 84.6% specificity), whereas UIP was correctly diagnosed in 73.3% of cases (84.6% sensitivity; 76.5% specificity). An 80% agreement was achieved between the HRCT and histological findings in the whole case series (73% sensitivity, 87% specificity, p<0.01). CONCLUSIONS: The most important finding of our study was that a ground glass appearance equal to or greater than 15% is highly suggestive of NSIP. Therefore, our results could be useful to confirm a suggested diagnosis of NSIP.

Prognostic relevance of cell proliferation in major salivary gland carcinomas.

Several proliferation markers, such as DNA ploidy, Ki67, MiB1 and proliferating cell nuclear antigen have been shown to correlate with clinical course and prognosis in several epithelial tumours and lymphomas. In the present study, the prognostic relevance of these markers was evaluated in major salivary gland carcinomas. A sample of 36 cases out of 85 patients submitted to surgery for major salivary gland carcinomas at our institution between 1987 and 1997 were studied. The sample comprised 8 adenoid-cystic carcinomas, 6 ductal carcinomas, 11 mucoepidermoid carcinomas and 11 acinic cell carcinomas. Follow-up ranged from 1 to 12 years (mean 6.2). In some patients, DNA ploidy (euploid or aneuploid) was studied by flow cytometry. In others, proliferation activity was studied by means of monoclonal antibody MiB1, identifying cells in the proliferative cycle. In some patients, both techniques were used. Follow-up was related to these indices, TNM and stage. Even if ploidy suggested a favourable outcome in diploid cancer (13 favourable vs. 2 unfavourable) and poor outcome in aneuploid cancer (4 favourable vs. 5 unfavourable), the difference was not statistically significant with p = 0.06 in Fisher's exact test. Instead, the proliferative tumour cell fraction, evaluated by MiB1, was statistically correlated with prognosis. Comparing survival curves by Log rank Test it yielded p = 0.007 using an MiB1 cut-off of 5. Applying a cut-off of 20 yielded p = 0.001. Of particular interest were MiB1 values in acinic cell carcinomas for which grading is challenging and lacks consensus. In our group of acinic cell carcinomas, survival correlated with values of MiB1 > or < 15 with p = 0.009 in Log rank test. In conclusion, despite a trend towards correlation between ploidy and prognosis, the present study yielded p = 0.06, whereas the proliferative fraction assessed by MiB1 was significantly correlated with outcomes. Indeed, "growth fraction" in acinic cell carcinomas may stratify different classes of risk.

[Etiopathogenic hypothesis on carcinoma of the gallbladder: our study]. / Un'ipotesi eziopatogenetica in tema di carcinoma della colecisti: il nostro studio.

The authors are interested in determining causes of gallbladder cancer (GBC). By this intention, they theorize a correlation between genetic modifications (which are responsible of malignant transformation of biliary epithelium) and some intestinal infections. From 1999 to 2004 they observed 15 GBC and all 15 gallbladder have been analyzed histologically and from microbiological aspect; by these means from 1999 till 2004 they have studied also 30 persons with colelithiasis. The authors noticed that bile of both groups contained, in three cases in the first and in 8 cases in the second, a germ named Escherichia Coli which normally lives in intestine, while in 10 operated gallbladders of the first group and 12 of the second there was a positive for k-ras. They are studying to confirm their theories.

[Merkel cell tumor: a case report and literature review]. / Tumore a cellule di Merkel: presentazione di un caso clinico e revisione della letteratura.

Merkel cell tumor (MCT) is extremely rare, being discovered so far about 400 cases in literature. It is classified among neuroendocrine tumors. We report a case of MCT in the subclavicular region in a 93 years old woman. We confirm the efficacy of radiotherapy associated with octreotide, which these tumours express specific receptors for.

Acute exacerbation of idiopathic pulmonary fibrosis: report of a series.

This study describes five cases presenting an acute clinical course of pulmonary fibrosis, in the absence of specific precipitating factors. A retrospective chart review of five patients with histologically proved usual interstitial pneumonia was carried out in 2001-2002. Clinical data, bronchoalveolar lavage (BAL) findings, high resolution computed tomography and histological features were reported. On admission all cases presented hypoxemia and dyspnoea, while some showed an increase of carbohydrate antigen 19.9 or laboratory tests typical of infection, although appropriate cultures were all negative. Altogether, four subjects died and only one is on follow-up. A pattern of diffuse ground-glass or alveolar opacification superimposed on reticular and linear findings was evident on lung imaging in all cases. Marked neutrophilia, together with type II reactive cells hyperplasia, was detected on BAL. Histological findings, from open lung biopsy or autopsy, showed all the aspects of usual interstitial pneumonia with superimposed features of acute lung injury, such as diffuse alveolar damage, with or without hyaline membranes, type II reactive cells hyperplasia and numerous fibroblastic foci. This study also underlines the diagnostic value of bronchoalveolar lavage versus open lung biopsy.

Acute interstitial pneumonia: report of a series.

Four cases of acute interstitial pneumonia (AIP) are described with special emphasis on clinical background, lung imaging and bronchoalveolar lavage findings. A retrospective chart review of four patients with histologically-proven AIP, diagnosed between 1998 and 2000, was carried out. Clinical data, bronchoalveolar lavage (BAL) findings, high-resolution computed tomography (HRCT) and histological features were analysed. Three patients died and only one is in follow-up. HRCT showed areas of ground glass attenuation and alveolar consolidation in all patients. Histology, documented by open lung biopsy or autopsy specimens, was consistent with the organising form of diffuse alveolar damage pattern. BAL findings were characteristic, with a huge neutrophilia associated with scattered atypical type II pneumocytes collected in clusters with extracellular amorphous material (fragments of hyaline membranes) observed in two out of three cases. In this paper, four cases of acute interstitial pneumonia are reported in detail. The poor prognosis associated with this entity has been confirmed and the possible diagnostic role of the bronchoalveolar lavage is emphasised.

Respiratory failure due to micronodular type II pneumocyte hyperplasia.

AIMS: To report the first case of respiratory failure due to micronodular type II pneumocyte hyperplasia. METHODS AND RESULTS: Biopsy, explant and autopsy material from a 16-year-old girl, a smoker, with no personal or family history of tuberous sclerosis, who died following lung transplantation necessitated by progressive respiratory failure, was evaluated histologically. Micronodular pneumocyte hyperplasia was identified histologically as the cause of the respiratory failure. Foci of hyperplastic type II pneumocytes measuring up to 4 mm were widely scattered through the lungs. The hyperplastic cells had abundant eosinophilic cytoplasm, vesicular nuclei and prominent nucleoli. Immunohistochemistry showed that they stained for cytokeratins AE1, AE3 and CAM 5.2 and for epithelial membrane antigen (EMA), but not for carcinoembryonic antigen (CEA), S100, smooth muscle actin, CD68 and HMB-45. CONCLUSIONS: Although micronodular type II pneumocyte hyperplasia is usually of no clinical significance, in our patient the process was so florid as to cause respiratory failure, which was severe enough to necessitate lung transplantation.

Acute lung injury associated with 5-fluorouracil and oxaliplatinum combined chemotherapy.

Diarrhoea, T-CD4+ lymphopenia and bilateral patchy pulmonary infiltrates developed in a male 60 yrs of age, who was treated with oxaliplatinum and 5-fluorouracil for unresectable rectum carcinoma. The findings from transbronchial lung biopsy and bronchoalveolar lavage (BAL) were consistent with an organizing diffuse alveolar damage pattern. Once extensive microbiological studies proved negative, corticosteroids were given and a complete remission of clinical and radiological abnormalities was achieved. It is concluded that the aforementioned pathological manifestations were due to chemotherapy and included a pulmonary adverse reaction, a feature never previously associated with oxaliplatinum and 5-fluorouracil regimens.