Antoine Nobile

Epithelial sodium channel-mediated sodium transport is not dependent on the membrane-bound serine protease CAP2/Tmprss4

The membrane-bound serine protease CAP2/Tmprss4 has been previously identified in vitro as a positive regulator of the epithelial sodium channel (ENaC). To study its in vivo implication in ENaC-mediated sodium absorption, we generated a knockout mouse model for CAP2/Tmprss4. Mice deficient in CAP2/Tmprss4 were viable, fertile, and did not show any obvious histological abnormalities. Unexpectedly, when challenged with sodium-deficient diet, these mice did not develop any impairment in renal sodium handling as evidenced by normal plasma and urinary sodium and potassium electrolytes, as well as normal aldosterone levels. Despite minor alterations in ENaC mRNA expression, we found no evidence for altered proteolytic cleavage of ENaC subunits. In consequence, ENaC activity, as monitored by the amiloride-sensitive rectal potential difference (ΔPD), was not altered even under dietary sodium restriction. In summary, ENaC-mediated sodium balance is not affected by lack of CAP2/Tmprss4 expression and thus, does not seem to directly control ENaC expression and activity in vivo.

Altered Prostasin (CAP1/Prss8) Expression Favors Inflammation and Tissue Remodeling in DSS-induced Colitis.

Background:Inflammatory bowel diseases (IBD) including ulcerative colitis and Crohns disease are diseases with impaired epithelial barrier function. We aimed to investigate whether mutated prostasin and thus, reduced colonic epithelial sodium channel activity predisposes to develop an experimentally dextran sodium sulfate (DSS)–induced colitis. Methods:Wildtype, heterozygous (frCR/+), and homozygous (frCR/frCR) prostasin-mutant rats were treated 7 days with DSS followed by 7 days of recovery and analyzed with respect to histology, clinicopathological parameters, inflammatory marker mRNA transcript expression, and sodium transporter protein expression. Results:In this study, a more detailed analysis on rat frCR/frCR colons revealed reduced numbers of crypt and goblet cells, and local angiodysplasia, as compared with heterozygous (frCR/+) and wildtype littermates. Following 2% DSS treatment for 7 days followed by 7 days recovery, frCR/frCR animals lost body weight, and reached maximal diarrhea score and highest disease activity after only 3 days, and strongly increased cytokine levels. The histology score significantly increased in all groups, but frCR/frCR colons further displayed pronounced histological alterations with near absence of goblet cells, rearrangement of the lamina propria, and presence of neutrophils, eosinophils, and macrophages. Additionally, frCR/frCR colons showed ulcerations and edemas that were absent in frCR/+ and wildtype littermates. Following recovery, frCR/frCR rats reached, although significantly delayed, near-normal diarrhea score and disease activity, but exhibited severe architectural remodeling, despite unchanged sodium transporter protein expression. Conclusions:In summary, our results demonstrate a protective role of colonic prostasin expression against experimental colitis, and thus represent a susceptibility gene in the development of inflammatory bowel disease.

Diagnostic Value of the CD103+CD4+/CD4+ Ratio to Differentiate Sarcoidosis from Other Causes of Lymphocytic Alveolitis

Background: The CD103 integrin is present on CD4+ lymphocytes of the bronchial mucosa, but not on peripheral blood CD4+ lymphocytes. It has been hypothesized that CD4+ lymphocytes in pulmonary sarcoidosis originate from redistribution from the peripheral blood to the lung, and therefore do not bear the CD103 integrin. Some data suggest that a low CD103+ percentage among bronchoalveolar lavage fluid (BALF) CD4+ lymphocytes discriminates between sarcoidosis and other diagnoses. Objective: To determine the diagnostic value of BALF CD103+ to identify sarcoidosis among other causes of alveolar lymphocytosis in a large retrospective case series. Methods: Among 391 consecutive bronchoalveolar lavages performed at our institution and analyzed by flow cytometry, we identified 207 cases, which were grouped into nine diagnostic categories: sarcoidosis, tuberculosis, non-tuberculous infections, hypersensitivity pneumonitis, non-specific interstitial pneumonia, organizing pneumonia, drug-induced lung diseases, other interstitial lung diseases (ILDs), and other diagnoses. To assess the discriminative value of the CD103+CD4+/CD4+ ratio to distinguish sarcoidosis from other entities, areas under ROC curves (AUC) were calculated. Results: Sarcoidosis patients (n = 53) had significantly lower CD103+CD4+/CD4+ ratios than patients in other diagnostic categories. The AUC was 62% for sarcoidosis compared to all other diagnoses, and 69% for sarcoidosis compared to other ILDs. When combining CD103+CD4+/CD4+ and CD4+/CD8+ ratios, the AUC increased to 76 and 78%, respectively. When applying previously published cut-offs to our population, the AUC varied between 54 and 73%. Conclusions: The CD103+CD4+/CD4+ ratio does not accurately discriminate between sarcoidosis and other causes of lymphocytic alveolitis, neither alone nor in combination with the CD4+/CD8+ ratio, and is not a powerful marker for the diagnosis of sarcoidosis.

Granulomatous Reaction to Pneumocystis jirovecii Diagnosed in a Bronchoalveolar Lavage: A Case Report

Background: Granulomatous reaction to Pneumocystis jirovecii is a rare but well-known pathological finding encountered in the setting of immunosuppression, HIV infection being the most common cause. It can also potentially complicate the treatment of hematological malignancies, typically when drugs lowering the count and function of lymphocytes are used. Lung biopsy is considered the gold standard for the diagnosis of granulomatous P. jirovecii pneumonia, whereas the diffuse alveolar form is usually detected cytologically in bronchoalveolar lavage (BAL). Case: A female patient pursuing R-CHOP chemotherapy for the treatment of multiple hematological malignancies developed a rapidly progressing dyspnea. Chest CT scans revealed a worsening of a known infiltrative lung disease thought to be secondary to her chemotherapy. Alterations compatible with a drug-induced interstitial lung disease and well-formed focally necrotizing granulomas were observed on an open lung biopsy, but no microorganism was identified with special stains. Eventually, a granulomatous reaction to P. jirovecii was found in a BAL and allowed appropriate treatment with rapid improvement of the dyspnea. Conclusion: Because granulomas are tissue-bound structures, they are rarely described in BAL. This article describes the first reported cytological diagnosis of a granulomatous reaction to P. jirovecii and the potential diagnostic interest of such a peculiar finding.

Hazardous cross-reaction in a thyroid fine needle aspiration

Thyroid fine-needle aspiration cytology (FNAC) is one of the most performed medical procedures worldwide.1 It is used as a diagnostic test to separate benign thyroid nodules (colloidal and hyperplastic nodules) from thyroid malignancies, either primary (papillary thyroid carcinoma (PTC), medullary thyroid carcinoma (MTC), poorly differentiated thyroid carcinoma (PDTC), anaplastic thyroid carcinoma (ATC)) or less often metastatic.2 The negative and positive predictive values (NPV and PPV) of this procedure in The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) are respectively 97% and 98% for the benign and malignant categories. This article is protected by copyright. All rights reserved.

Reticular Perineurioma of the Hand: Diagnosis and Treatment of a Rare Case of Hand Mass

Reticular perineurioma is a rare and recently delineated morphologic variant of benign perineurioma of skin and soft tissues. Because of its nonspecific gross appearance, varying histologic patterns, and potential range of cellularity, perineurioma of the hand is likely to be confused with more commonly encountered tumor or tumor-like conditions such as schwannoma, neurofibroma, fibromyxoid tumors, and giant tumor of tendon sheath. We report the case of a 20-year-old woman who presented with a slowly growing mass of the hand, which was eventually identified as a reticular perineurioma.

Contents Vol. 91, 2016

414 Joint Annual Meeting of the Schweizerische Gesellschaft für Kardiologie / Société Suisse de Cardiologie Schweizerische Gesellschaft für Herzund thorakale Gefässchirurgie / Société Suisse de Chirurgie Cardiaque et Vasculaire Thoracique Schweizerische Gesellschaft für Pneumologie / Société Suisse de Pneumologie June 15–17, 2016, Lausanne

Malignant Mucous Cells in a Thyroid Aspirate: Looking for a Source

A 56-year-old man with no previous relevant clinical history presented to his family doctor with dysphonia and a large, palpable partly infrasternal cervical mass. He was then referred to our center for further investigations. A cervical ultrasound (US) was performed, followed by fine-needle aspiration (FNA) of the mass (Fig. 1a). Ancillary studies were performed on destained slides (Fig. 1b and Fig. 4, done in a second time). To complete the diagnostic work up, an F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDGPET/CT) (Fig. 2), a biopsy of the mass (Fig. 3), and laboratory tests were performed. What Is Your Diagnosis?

Cytological Diagnosis of Pancreatic Neuroendocrine Neoplasms

The main cytological features of neuroendocrine pancreatic neoplasm are described along with a discussion about the difficulties in classification/grading and the new reporting system for reporting pancreatic cytopathology. An overview about the ancillary techniques and the differential diagnosis is also given.