EBUS-guided cryobiopsy in the diagnosis of thoracic disorders.

BACKGROUND: Endobronchial Ultrasound (EBUS) has emerged as a crucial tool for diagnosing intrathoracic disorders, particularly in the staging of lung cancer. However, its diagnostic capabilities in the context of benign and rare diseases remain a subject of debate. AIM: to investigate the diagnostic yield and safety of EBUS-transbronchial mediastinal cryobiopsy (EBUS-TMC) in comparison to EBUS-transbronchial needle aspiration (TBNA) for a broad spectrum of intrathoracic diseases. METHODS: a single-centre retrospective observational study conducted on 48 patients who underwent both EBUS-TBNA and endobronchial ultrasound-transbronchial mediastinal cryobiopsy (EBUS-TMC) in the same procedure between August 2021 and October 2023. RESULTS: The overall diagnostic yield of EBUS-TMC surpassed that of EBUS-TBNA (95.8% vs 54.1 %), notably excelling in the diagnosis of sarcoidosis (92.8% vs 78.5 %), rare mediastinal disorders (100% vs 0 %), hyperplastic lymphadenopathy (100% vs 0 %), and lymphoproliferative disease (100% vs 0 %). No significant differences were observed in the diagnosis of NSCLC and SCLC. Samples obtained through EBUS-TMC facilitated the acquisition of NGS and immunohistochemical analyses more readily. CONCLUSION: EBUS-TMC may contribute to the precise diagnosis and subtyping of mediastinal diseases, especially lymphomas and rare mediastinal tumors, thereby reducing the number of non-diagnostic procedures.

Diagnostic yield and safety of transbronchial lung cryobiopsy for diffuse parenchymal lung diseases diagnosis: Comparison between 1.7-mm and 1.9-mm probes.

PURPOSE OF THE RESEARCH: transbronchial lung cryobiopsy has been recently accepted as a valid and less invasive alternative to surgical lung biopsy. The purpose of this randomized controlled study was to evaluate, for the first time, the quality and safety of biopsy specimens obtained by using the new disposable 1.7-mm cryoprobe compared with the standard re-usable 1.9 mm cryoprobe in the diagnosis of diffuse parenchymal lung diseases. METHODS: 60 consecutive patients were prospectively enrolled and randomly assigned to two different groups: 1.9 mm (group A) and 1.7 mm (group B); primary endpoints were pathological and multidisciplinary diagnostic yield, sample size and complication rate. PRINCIPAL RESULTS: the pathological diagnostic yield of cryobiopsy was 100% in group A and 93.3% in group B (p = 0.718); cryobiopsy median diameter was 6.8 mm in group A and 6.7 mm in group B (p = 0,5241). Pneumothorax occurred in 9 patients in group A and 10 in group B (p = 0.951); mild-to-moderate bleeding in 7 cases and 9 cases in group A and B respectively (p = 0.559). No death or severe adverse events were observed. CONCLUSIONS: there was no statistically significant difference between the two groups, regarding diagnostic yield, adverse events and sampling adequacy.

Pulmonary vein stenosis mimicking interstitial lung disease.

Pulmonary vein stenosis (PVS) is a rare condition, often difficult to diagnose and associated with poor prognosis at advanced stages. Lung parenchymal abnormalities are indirect evidence of PVS and can manifest as multifocal opacities, nodular lesions, unilateral effusions, and interstitial septal thickening. These can lead to erroneous diagnoses of airway disease, pneumonia, malignancies or interstitial lung disease. This review summarizes the current literature about the approach to, evaluation and management of these patients. Our case report demonstrates that PVS is an under-recognized complication of cardiovascular surgery and should be considered in all patients presenting with respiratory symptoms after a cardiac procedure.

The 2015 World Health Organization Classification of lung tumors: new entities since the 2004 Classification.

In the last few years different new pulmonary neoplastic lesions have been recognised and some of them, namely NUT carcinoma, PEComatous tumors, pneumocytic adenomyoepithelioma, pulmonary myxoid sarcoma, myoepithelial tumors/carcinomas entered in the last 2015-WHO classification of lung tumors. In addition angiomatoid fibrous histiocytoma and ciliated muconodular papillary tumor have been morphologically and genetically characterized albeit not yet included in the 2015-WHO classification.In the present paper we summarised the clinical, morphological, immunohistochemical and molecular features of these new entities. The knowledge of key histologic and molecular characteristics may help pathologists in achieving a correct diagnosis thus leading to an adequate therapeutic approach.

Endobronchial-ultrasound needle aspiration and endoscopic ultrasound-fine-needle aspiration in thoracic diseases.

EBUS-TBNA and EUS-FNA are minimally invasive techniques rapidly gaining ground in the non-surgical invasive diagnostic approach to thoracic diseases due to their high accuracy and low morbidity and mortality compared to surgical techniques. Moreover, in the diagnosis and staging of lung cancer the combination of the two techniques is superior to either test alone. In this review we focus on the role of EBUS-TBNA and EUS-FNA in both malignant and non-malignant thoracic diseases.

Diffuse Neuroendocrine Hyperplasia with Obliterative Bronchiolitis and Usual Interstitial Pneumonia: An Unusual "Headcheese Pattern" with Nodules.

A 74-year-old non-smoker female presented to our attention with a history of dyspnea and cough. CT scan revealed multiple areas of patchy ground glass attenuation associated to a diffuse mosaic oligoemia. Scattered bilateral subcentimetric pulmonary nodules were also present. Patient underwent a surgical lung biopsy. Specimens showed features of diffuse neuroendocrine hyperplasia, microhoneycombing, fibroblast foci. A final diagnosis of diffuse neuroendocrine hyperplasia with obliterative bronchiolitis and UIP was rendered.

Interstitial lung disease preceding primary biliary cirrhosis in a male patient.

A 47-year-old male was admitted with subacute onset of dry cough and fever. Chest tomography demonstrated multifocal areas of consolidation and ground glass attenuation. Cytological analysis of bronchoalveolar lavage revealed lymphocytosis and eosinophilia and anatomopathological exam of transbronchial cryobiopsy showed poorly formed non-caseous granulomas associated to interstitial lympho-plasmocitary infiltrate. The diagnosis of idiopathic granulomatous lung disease (GLD) was assumed and the patient started oral prednisolone, presenting clinical, functional and radiological improvement. Two years later, the patient was diagnosed with primary biliary cirrhosis (PBC). At this time, it was possible to associate GLD with the autoimmune hepatobiliary disease. Clinical, epidemiological and pathological aspects of this uncommon case of interstitial lung disease as first presentation of PBC in a male patient are discussed.

Breast metastases from a Renal Cell Carcinoma. A case report and review of the literature.

INTRODUCTION: Metastases to the breast from extra-mammary tumors are uncommon and few sporadic cases are reported in the international literature. An accurate differential diagnosis of secondary cancer is mandatory because both prognosis and treatment differ with respect to primary breast tumors. PRESENTATION OF CASE: We present the case of a 70-year-old woman with an isolated metastasis to the breast occuring 9 years after undergoing a nephrectomy for Renal Cell Carcinoma (RCC). Clinical examination revealed a palpable and mobile mass in the right breast with an enlarged ipsilateral axillary lymph node. Mammographic findings showed a dense, well circumscribed solid mass and the breast ultrasonography findings were those of a hypoechoic homogeneous solid nodule with no posterior attenuation but with prominent peripheral vascularity. A tru-cut biopsy was conclusive for a metastatic deposit by RCC. A whole-body CT scan showed no evidence of further recurrences. The patient underwent metastasectomy and exeresis of the papable lymphnode. DISCUSSION: In patients with former surgery for RCC, a diagnosis based on a preoperative biopsy allows to indicate the proper surgical treatment: in facts, as compared to primary breast tumors treatment, the rationale to pursue wide surgical margins is pointless in cases of metastases and, similarly, the biopsy of the sentinel lymphnode is void of sense due to the lack of its physiopathological prerequisite. CONCLUSION: We suggest to consider a micro-histological biopsy of any new breast lesion appearing in a patient with a history of treatment for RCC. Prompt diagnosis is necessary to choose the right treatment.

The effect of anticoagulant therapy for idiopathic pulmonary fibrosis in real life practice.

BACKGROUND: IPF is a common form of interstitial lung disease for which there is no effective therapy and usually results in death. Two previous contradictory studies showed anticoagulant therapy  to be associated with both improved and worsened survival, respectively. OBJECTIVE: The objective of this retrospective cohort study was to evaluate the effect of anticoagulant therapy on the survival and disease progression of patients with idiopathic pulmonary fibrosis (IPF) in real clinical practice. METHODS: We compared the clinical characteristics, time to disease progression, incidence of acute exacerbation, and survival of 25 (20%) IPF patients receiving anticoagulant therapy to the remaining 97 IPF patients not receiving anticoagulant therapy. In addition we conducted a sensitivity analysis using as comparator a group of 25 patients matched by age, sex, functional impairment, cardiac comorbidities and pulmonary hypertension. RESULTS: Patients on anticoagulant therapy had a worse 1- and 3-year survival (84% and 53% versus 89% and 64% in the non-anticoagulant group, respectively), a difference that persisted after adjusting for age and comorbidities (hazard ratio 3.1 - 95% confidence interval, 1.4 to 7.0; p=0.006) and after comparison with the matched group (adjusted HR=4.8, 95% CI: 1.8-12.8; p=0.002). IPF patients on anticoagulant therapy had a shorter interval to disease progression ( 0.7 years versus 1.6 years, adjusted HR 2.2 -95% CI, 0.96 to 5.1; p=0.063) confirmed also in the analysis with matched subgroups (HR=2.7 (95% CI: 1.2-6.5); p=0.023). The incidence of acute exacerbations did not differ in the two groups (22% versus 23%). Two patients (8%) experienced anticoagulant treatment related complications and included an episode of hemorrhagic shock. CONCLUSION: In this retrospective study patients treated with anticoagulants had a worse survival and a shorter interval to disease progression. This support the recent finding that warfarin worsen the respiratory status and survival of IPF patients.

Prognostic value of 18F-FDG standard uptake value by integrated PET/CT in the staging of malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is a rare and aggressive tumor with generally disappointing results in terms of survival, however, there are occasional long-term survivors probably due to the biologic characteristics of the disease. Standard uptake value (SUV) of [(18)F] Fluorodeoxyglucose (FDG) evaluated by photon emission tomography (PET) is now widely accepted as an indicator of biologic behavior in several malignancies. The aim of this study was to verify whether SUV(max) and SUV(mean) are inversely associated with the prognosis of patients with MPM and whether there was a correlation between grading/disease stage and SUV value. Patients with histologically proven MPM underwent integrated PET and computed tomography (CT) scanning. Patients fasted and received 5.18 MBq of FDG per kilogram of body weight. Based on the maximum Chi-Square method, a SUV(max) of 4.21 (range: 2.30-14.74) and a SUV(mean) of 2.78 (range: 1.80-7.00) were used to classify patients as having a good or poor prognosis, respectively. From January 2004 to March 2010, 27 patients were analyzed: median age was 65 years (range: 54-77) and histologic MPM subtypes were epithelioid (23 patients) and biphasic (4 patients). At a median follow-up of 23 months (range: 1-52), there was no difference in median survival for either high or low SUV(max) [26 months (range: 11-not reached) vs.19 months (range: 12-not reached); p=0.811] or for high or low SUV(mean) [26 months (range: 8-not reached) vs.19 months (range: 11-not reached); p=0.831]. High SUV(max) (p=0.018) was statistically correlated with high-stage disease. There was only a trend towards statistical significance between high-grade disease and high SUV(mean) (p=0.083); no such trend was found between advanced stages and SUV(max) (p=0.268). We observed a significant correlation only between high SUV(max) and high-grade disease. No other relationships between SUV(max) and SUV(mean) with biologic and clinical parameters were found. This is probably due to the patient characteristics and to the non-routine use of 18F-FDG PET/CT to stage rare tumors such as MPM.

Prospective evaluation of drug-induced lung toxicity with high-resolution CT and transbronchial biopsy.

PURPOSE: This study compared the results of high-resolution computed tomography (HRCT) and cytohistology after transbronchial biopsy in the evaluation of drug-related interstitial lung disease (DR-ILD). MATERIALS AND METHODS: Patients with a clinical and imaging diagnosis of DR-ILD were prospectively included in a study protocol lasting 5 years. All patients were evaluated by bronchoscopy with transbronchial biopsy or bronchoalveolar lavage (BAL) following an HRCT examination that raised a suspicion of DR-ILD. Two radiologists (one senior and one junior), unaware of the diagnosis, reported the single HRCT findings, their distribution and predominant pattern. In the event of disagreement, the diagnosis was subsequently reached by consensus. Cytohistological examination was considered the gold standard in the diagnosis of DR-ILD. Patients who were unable to undergo the endoscopic procedure were excluded from the study. RESULTS: The study included 42 patients (25 men, 17 women; age range 20-84 years). Transbronchial biopsy was performed in all but four patients (one case of alveolar haemorrhage and three cases of lipoid pneumonia) in whom the diagnosis was established with BAL. Assessment of the HRCT images revealed the following patterns: noncardiogenic pulmonary oedema (n=13); organising pneumonia (OP) (n=9); hypersensitivity pneumonitis (HP) (n=2); alveolar haemorrhage (AH) (n=2); nonspecific interstitial pneumonia (NSIP) (n=5); lipoid pneumonia (LP) (n=1); sarcoid-like pattern (n=1). Cytohistological diagnosis revealed diffuse alveolar damage (DAD) in 11 patients, OP in seven, HP in three, AH in three, chronic interstitial pneumonia (CIP) in eight, LP in three and pseudosarcoidosis in one. Subdivision of the drugs into antineoplastic and nonantineoplastic agents showed that the most common patterns were CIP (n=6), DAD (n=2) and OP (n=2) in the antineoplastic group and DAD (n=9) and OP (n=5) in the nonantineoplastic group. Sensitivity and specificity of the radiological analysis was excellent, especially for patterns such as OP and DAD (sensitivity 0.86 and specificity 0.88 for OP; sensitivity 1 and specificity 0.93 for DAD). CONCLUSIONS: HRCT demonstrated excellent sensitivity and specificity. In cases in which its specificity was low, HRCT was nonetheless useful for biopsy planning and clinical-radiological monitoring after discontinuation of the drug treatment.

Idiopathic nonspecific interstitial pneumonia: an interstitial lung disease associated with autoimmune disorders?

Recent evidence suggests that idiopathic nonspecific interstitial pneumonia (iNSIP) is a distinct clinical entity amongst other idiopathic interstitial pneumonias, and some data seem to suggest a possible pathogenetic role of autoimmunity. The aim of the present study was to assess if iNSIP might represent an early lung manifestation of an autoimmune disease. After initial review of cases found in the medical records database by searching for the term "NSIP" (n = 63), 37 iNSIP cases were identified, and were re-evaluated using a dynamic integrated multidisciplinary approach. 27 cases with iNSIP were selected for the study. Mean ± sd age at first respiratory symptom was 54.2 ± 8 yrs, 70% were females, and 59% were never-smokers. At follow-up (mean ± sd 59.7 ± 29 months, range 12-138 months), autoimmune diseases occurred in 14 (52%) patients, with seven (26%) cases of autoimmune thyroiditis, six (22%) of undifferentiated connective tissue disease and three (11%) of connective tissue disease. Patients developing autoimmune diseases were older and more frequently never-smoking females. In >50% of patients diagnosed with iNSIP, evidence of autoimmune diseases develops within 2 yrs, suggesting a probable link between the clinical entity of iNSIP and autoimmune disorders.

Cathepsin-K is a sensitive immunohistochemical marker for detection of micro-granulomas in hypersensitivity pneumonitis.

UNLABELLED: Hypersensitivity Pneumonitis (HP) is an interstitial lung disease that occurs upon exposure to a variety of inhaled organic antigens. The presence of small non-caseating granulomas and isolated giant cells is not specific, but is considered a relevant histological feature for HP. The detection of granulomas is widely considered as easy on standard histological stains, but microgranuloma detection can be difficult and/or time consuming, especially in chronic HP cases. Cathepsin K (Cath-K) is a potent cysteine protease expressed at high levels in activated macrophages (osteoclasts, and epithelioid cells in granulomas), but is not expressed in resident macrophages thus representing a promising marker to rapidly detect and quantitatively evaluate microgranulomas in interstitial lung diseases. We analyzed the expression of Cath-K by immunohistochemistry in 22 subacute and chronic HP cases, using semi-quantitative scores. Control samples included normal lung tissue, and a variety of interstitial lung diseases: 3 Wegener's granulomatosis, 3 sarcoidosis, 3 tuberculosis, 1 berylliosis, 20 idiopathic pulmonary fibrosis (IPF), 2 Langerhans' cell histiocytosis, 5 nonspecific-interstitial pneumonia (NSIP), 5 cryptogenic organising-pneumonia (COP), 2 Airway-Centered Interstitial Fibrosis (ACIF), 5 desquamative interstitial pneumonia (DIP), 3 respiratory bronchiolitis interstitial lung disease (RB-ILD). Intense expression of Cath-K was demonstrated in epithelioid and giant cells in all cases containing granulomas (HP, sarcoidosis, Wegener's granulomatosis, berylliosis, tuberculosis). Among HP cases 19/22 (86.3%) contained granulomas that could be semiquantitatively evaluated. In all HP and control cases alveolar macrophages did not express Cath-K, including cases characterised by large collections of alveolar macrophages such as DIP and RB-ILD. CONCLUSIONS: Cath-K represents a sensitive and specific marker to detect and quantitate granulomatous reactions in interstitial lung diseases, and is particularly useful in chronic HP cases.

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.

The role of transbronchial lung biopsy for the diagnosis of diffuse drug-induced lung disease: a case series of 44 patients.

At present, no studies have evaluated the role of bronchoscopic transbronchial lung biopsy (TBLB) in the diagnosis of diffuse drug-induced lung disease (DILD), and there is no consensus for a definite diagnostic workup approach for this rare clinical entity. The aim of the present study was to evaluate the clinical usefulness of TBLB in diffuse DILD. This study was a retrospective analysis of patients with diffuse DILD, who underwent bronchoscopy. The role of TBLB was assessed to determine whether the histological results are useful for the final diagnosis. Over a 5-yr period, 44 patients underwent bronchoscopy, and all had a bronchoalveolar lavage (BAL). Thirty-three of the 44 patients underwent TBLB (75%), and the results of TBLB were diagnostically helpful in 25 (75.7%) of the procedures. No histopathologic abnormality was identified in 6 (18%) of the 33 patients. In 2 patients (6%) the obtained samples were not adequate, since no lung parenchyma was obtained. No severe complications related to bronchoscopic procedures occurred. In conclusion, TBLB is a safe procedure, and is diagnostically helpful in the majority of cases of patients with diffuse DILD. Histological data obtained by TBLB further corroborate clinical, laboratory, radiologic and BAL results for a definitive diagnosis of diffuse DILD.

[Benign solitary fibrous tumor of the pancreas: a rare location of extra-pleural fibrous tumor. Single case report and review of the literature]. / Tumore fibroso benigno solitario del pancreas: una rara localizzazione di tumore fibroso extrapleurico. Caso clinico e revisione della letteratura.

BACKGROUND/AIMS: Extra pleural solitary fibrous are very rare, but occasionally they appear in extraserosal soft tissues or parenchymatous organs, where their diagnosis is often a challenge. In this report we describe the case of a patient with a single primary solitary fibrous tumor of the pancreatic head with a review of the literature. METHODS/RESULTS: A 62 years old woman underwent a Traverso-Longmire procedure in November 2004. Sixteen months after resection there is no evidence of recurrence. The tumour showed immunoreactivity for CD34, CD99, bcl-2, vimentin and smooth muscle actin. MIB-1 proliferating activity was < 5%. CONCLUSIONS: Extra pleural solitary fibrous tumor are often benign lesions. In the pancreas only 2 cases have been described so far. Other mesenchymal tumours that may occur in the pancreas include leiomyosarcoma, tumours of the peripheral nerve sheath, fibrous histiocytic tumours and rare vascular tumours. The differential diagnosis is mainly based on immunohistochemistry. The surgical approach is fundamental for the treatment of solitary fibrous tumour.

[Sentinel lymph nodes in early gastric cancer: preliminary feasibility study]. / Il linfonodo sentinella nell'early gastric cancer studio preliminare di fattibilità.

From January to December 2004, 8 patients with pre-operative diagnosis of early gastric cancer (EGC) and no nodal involvement were submitted to sentinel node biopsy using the dual mapping procedure with endoscopic blue dye and 99mTc radio-colloid injection. All the patients underwent standard radical gastrectomy and D2 lymphadenectomy. The resected nodes were evaluated by routine (hematoxylin-eosin) histopathological examination; the sentinel (blue or hot) nodes in addition were evaluated with immunohistochemistry for cytokeratin. The preliminary results and perspectives for feasibility of sentinel node biopsy and its accuracy in predicting the nodal status in EGC are discussed.

Corticotrophin-releasing activity of desmopressin in Cushing's disease: lack of correlation between in vivo and in vitro responsiveness.

Desmopressin (DDAVP), an arginine vasopressin analogue, markedly stimulates ACTH secretion in patients with Cushing's disease, in contrast to its minimal effect in normal subjects. However, little is known about the mechanisms underlying this action and it appeared to be of interest to evaluate the effect of DDAVP on ACTH-secreting pituitary adenomas in vitro, in comparison with its effect in the same patients in vivo. Pituitary adenomas from 14 patients with Cushing's disease were incubated with DDAVP, corticotrophin-releasing hormone (CRH) and DDAVP together with vasopressin receptor antagonists or CRH. Incubation with DDAVP induced a modest dose-dependent increase in ACTH concentrations which appeared maximal at 10 nM. CRH stimulated ACTH to a greater extent compared with DDAVP and potentiated the effect of DDAVP alone. The DDAVP-induced ACTH increase appeared blunted by vasopressin V(2) and V(3) receptor antagonists. V(3) receptor gene expression was detected by RT-PCR in all adenoma samples except for two which were not responsive to DDAVP in vitro but responsive to the peptide in vivo. Surprisingly, no difference in the in vitro ACTH secretory response was observed between in vivo DDAVP-responsive (ACTH peak>150% baseline) and -unresponsive (ACTH peak<120% baseline) patients, suggesting that the pituitary adenoma is not the sole mediator of the ACTH-releasing effect of DDAVP. In conclusion, the marked stimulatory effect of DDAVP observed in patients with Cushing's disease appears to be mainly dependent on an extrapituitary action, possibly the inhibition of a corticotrophin release-inhibitory factor.

Role of biological markers in the clinical outcome of colon cancer.

We investigated a number of biological markers, evaluated under strict intralaboratory quality control conditions, in terms of their role in predicting clinical outcome of patients with colon cancer treated with 5-FU-containing regimens. Colon cancer tissue from 263 patients enrolled onto two randomised clinical trials were studied for their cytofluorimetrically determined DNA content and their immunohistochemically evaluated microvessel density, vascular endothelial growth factor expression, thymidylate synthase expression and tumour lymphocyte infiltration. Disease-free survival and overall survival of patients were analysed as a function of the different variables. At a median follow up of 57 months, age, gender and Dukes' stage showed an impact on disease-free survival, whereas no biological marker emerged as an indicator of better or worse disease-free survival. Only histological grade and Dukes' stage were found to influence overall survival. The different biological variables, studied with particular attention for determination reliability, proved to have no impact on the clinical outcome of patients with colon cancer. Therefore, other markers must be identified to complement clinico-pathological variables in the management of this disease.