Juvenile-onset recurrent respiratory papillomatosis with pulmonary involvement and carcinomatous transformation

Papilloma associated with recurrent respiratory papillomatosis (RRP), caused by human papilloma virus (HPV) infection types 6 and 11, is the most common benign neoplasm of the larynx. The clinical features of RRP vary widely from mild to aggressive forms. RRP in children is known as juvenile-onset recurrent respiratory papillomatosis (JORRP). Its outcome may be poor or even fatal due to the high rate of recurrence and eventual spread to the entire respiratory tract. Pulmonary invasion is reported to occur in 3.3% of patients with RRP, and malignant transformation in 0.5% of patients. We report the case of a 39-year-old female patient with a diagnosis of JORRP from the age of 3 years, with extensive bilateral pulmonary involvement and malignant transformation. Analysis of the papilloma and carcinomatous tissues revealed the presence of HPV type 11, which is associated with rapid and aggressive progression. We discussed the case on the basis of a literature review on pulmonary invasion, malignant transformation, and HPV 11 aggressiveness

Juvenile-onset recurrent respiratory papillomatosis with pulmonary involvement and carcinomatous transformation

Papilloma associated with recurrent respiratory papillomatosis (RRP), caused by human papilloma virus (HPV) infection types 6 and 11, is the most common benign neoplasm of the larynx. The clinical features of RRP vary widely from mild to aggressive forms. RRP in children is known as juvenile-onset recurrent respiratory papillomatosis (JORRP). Its outcome may be poor or even fatal due to the high rate of recurrence and eventual spread to the entire respiratory tract. Pulmonary invasion is reported to occur in 3.3% of patients with RRP, and malignant transformation in 0.5% of patients. We report the case of a 39-year-old female patient with a diagnosis of JORRP from the age of 3 years, with extensive bilateral pulmonary involvement and malignant transformation. Analysis of the papilloma and carcinomatous tissues revealed the presence of HPV type 11, which is associated with rapid and aggressive progression. We discussed the case on the basis of a literature review on pulmonary invasion, malignant transformation, and HPV 11 aggressiveness

Lung cancer biopsy: Can diagnosis be changed after immunohistochemistry when the H&E-Based morphology corresponds to a specific tumor subtype?

OBJECTIVES: Advancements in non-small cell lung cancer treatment based on targeted therapies have made the differentiation between adenocarcinoma and squamous cell carcinoma increasingly important. Pathologists are challenged to make the correct diagnosis in small specimens. We studied the accuracy of an immunohistochemical panel in subclassifying non-small cell lung cancer in routine small biopsies and compared the results with the diagnosis from resected lung specimens, autopsy samples or biopsied/resected metastases. METHODS: In total, 340 lung cancer biopsies were investigated for the expression of CK5, TTF1, p63 and surfactant. RESULTS: We characterized 166 adenocarcinomas and 124 squamous cell carcinomas. Overall, 85% of cases displayed binary staining (TTF1 positive/p63 negative, and vice versa). The diagnoses of ten cases with a morphology that indicated a specific tumor subtype were changed after immunohistochemistry (IHC). A second specimen was available for 71 patients, and the first diagnosis at biopsy was confirmed in 95% of these cases. Most non-small cell lung cancer cases present a binary immunohistochemical profile in small biopsies, contributing to good diagnostic accuracy with routine markers. In a small proportion of cases, the diagnosis can be changed after IHC even when the morphological aspects indicate one specific tumor subtype. CONCLUSIONS: We recommend that routine small biopsies of lung cancer without classic morphology should be subjected to a minimum immunohistochemical panel to differentiate adenocarcinoma from squamous cell carcinoma

The Expression of Water and Ion Channels in Diffuse Alveolar Damage Is Not Dependent on DAD Etiology

<div><p>Introduction</p><p>Aquaporins and ion channels are membrane proteins that facilitate the rapid movement of water and solutes across biological membranes. Experimental and in vitro studies reported that the function of these channels and pulmonary edema resolution are impaired in acute lung injury (ALI). Although current evidence indicates that alveolar fluid clearance is impaired in patients with ALI/diffuse alveolar damage (DAD), few human studies have addressed the alterations in pulmonary channels in this clinical condition. Additionally, it is not known whether the primary cause of DAD is a relevant variable for the channel dysfunction.</p><p>Methods</p><p>Autopsied lungs of 43 patients with acute respiratory failure (ARF) due to DAD of three different etiologies, non-pulmonary sepsis, H1N1 viral infection and leptospirosis, were compared to 18 normal lungs. We quantified the expression of aquaporin (AQP) 1, AQP3, AQP5, epithelial Na⁺ channel (ENaC) and sodium potassium ATPase (Na-K-ATPase) in the alveolar septum using immunohistochemistry and image analysis.</p><p>Results</p><p>The DAD group presented with increased expression of AQP3, AQP5 and Na-K-ATPase and decreased expression of ENaC compared to controls. However, there was no difference in protein expression within the DAD groups of different etiologies.</p><p>Conclusion</p><p>Water and ion channels are altered in patients with ARF due to DAD. The cause of DAD does not seem to influence the level of impairment of these channels.</p></div

Immune receptors and adhesion molecules in human pulmonary leptospirosis

Pulmonary involvement in leptospirosis has been increasingly reported in the last 20 years, being related to the severity and mortality of the disease. The pathogenesis of pulmonary hemorrhage in leptospirosis is not understood. Lung endothelial cells have been proposed as targets in the pathogenesis of lung involvement in leptospirosis through the activation of Toll-like receptor 2 or the complement system, which stimulates the release of cytokines that lead to the activation of adhesion molecules. The aim of this study was to investigate the involvement of immune pathways and of the intercellular and vascular cell adhesion molecules (intercellular adhesion molecule and vascular cell adhesion molecule, respectively) in the lungs of patients with pulmonary involvement of leptospirosis. We studied the lungs of 18 patients who died of leptospirosis and compared them with 2 groups of controls: normal and noninfectious hemorrhagic lungs. Using immunohistochemistry and image analysis, we quantified the expression of the C3a anaphylatoxin receptor, intercellular adhesion molecule, vascular cell adhesion molecule, and Toll-like receptor 2 in small pulmonary vessels and in the alveolar septa. There was an increased expression of intercellular adhesion molecule (P &lt;.03) and C3a anaphylatoxin receptor (P &lt;.008) in alveolar septa in the leptospirosis group compared with the normal and hemorrhagic controls. In the vessels of the leptospirosis group, there was an increased expression of intercellular adhesion molecule (P=.004), vascular cell adhesion molecule (P=.030), and Toll-like receptor 2 (P=.042) compared with the normal group. Vascular cell adhesion molecule expression in vessels was higher in the leptospirosis group compared with the hemorrhagic group (P=.015). Our results indicate that immune receptors and adhesion molecules participate in the phenomena leading to pulmonary hemorrhage in leptospirosis. (C) 2012 Elsevier Inc. All rights reserved.Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq

Demographic and Clinical Data.

<p>Demographic and Clinical Data.</p

Immunohistochemistry localization of aquaporins, Na-K-ATPase channel and ENaC channel.

<p>A: AQP1 in alveolar (short arrow) and arteriolar (long arrow) endothelial cells. Double staining for AQP1 (red) and PII cels (TTF-1, brown, red arrowhead). B: AQP1 in vascular endothelial cells (arrow). C: AQP3 in PII cells (arrows). Double staining for AQP3 (red) and PII cels (TTF1, brown). D: AQP3 in epithelial bronchiolar cells (arrow). E: AQP5 in PI cells lining the alveolar septum (arrow). Double staining for AQP5 (red) and PII cels (TTF1, brown, red arrowhead). F: AQP5 in epithelial bronchiolar cells (long arrow) and submucosal glands (short arrow). G: Na-K-ATPase channel in PI (arrow) and PII (red arrowhead) cells. Double staining for Na-K-ATPase channel (red) and PII cels (TTF1, brown). H: ENaC channel in PI cells lining the alveolar septum (arrow) and PII cells (red arrowhead). I: ENaC channel in epithelial bronchiolar cells (long arrow) and vascular endotelial cells (short arrow).</p

Aquaporin and ion channels expression in the alveolar septum of control and DAD groups.

<p>Aquaporin and ion channels expression in the alveolar septum of control and DAD groups.</p

Representative histological images of each group.

<p>H&E staining. A: control group; B: DAD group (sepsis); C: DAD group (H1N1); D: DAD group (leptospirosis). Note the hemorrhage present in the leptospirosis group. Arrows: Hyaline membrane. Bars = 100 μm.</p