Pulmonary veno-occlusive disease (PVOD) and pulmonary capillary hemangiomatosis (PCH) are two unusual idiopathic disorders that almost uniformly manifest to the clinician as pulmonary arterial hypertension (PAH). Impressive clinical signs and symptoms often obscure the true underlying capillary or postcapillary disorder, thus severely compromising timely and appropriately directed therapy. The hemodynamics of PVOD and PCH are the consequence of a widespread vascular obstructive process that originates in either the alveolar capillary bed (in cases of PCH) or the pulmonary venules and small veins (in PVOD). Since the earliest descriptions of PVOD and PCH, there has been a debate as to whether these are two distinct diseases or varied expressions of a single disorder. The cause of PVOD or PCH has not yet been identified, although there are several reported associations. Without curative lung or heart-lung transplantation, patients with these conditions face inexorable clinical deterioration and death within months to a few short years of initial presentation. Surgical lung biopsy is the definitive diagnostic test, but it is a risky undertaking in such critically ill patients. The imaging manifestations of PVOD and PCH often reflect the underlying hemodynamic derangements, and these findings may assist the clinician in discerning PAH from an underlying capillary or postcapillary process with findings of septal lines, characteristic ground-glass opacities, and occasionally pleural effusion.

The aim of this study was to investigate the prevalence, predictors and radiological findings of primary Sjögren's syndrome (pSS)-associated lung involvement. This retrospective cohort study included 123 patients with demographic, clinical, laboratory and radiological data who were diagnosed with pSS. Lung involvement was defined based on the presence of pulmonary signs/symptoms and/or impaired pulmonary function tests along with alterations in high-resolution computerized tomography (HRCT). Thirty patients (24.4%) had pulmonary signs/symptoms at the initial presentation and/or during the follow-up period. Based on the criteria, 14 patients (11.4%) were defined as having pSS with lung involvement. The smoking rate, male/female ratio and the mean ages were found to be higher in patients with lung involvement (P < 0.05). Positive IgM-rheumatoid factor (RF), anti-La and anti-Ro results, the presence of hypergammaglobulinemia and lymphopenia had high specificity despite the low sensitivity rates to detect pSS-associated lung disease. A significant difference was found in forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV(1)) results between the patients with and without lung involvement. Impaired FEV(1) had high specificity and positive predictive value compared to impaired FVC, particularly in non-smoker patients. The most frequent HRCT finding was ground-glass attenuation (64.3%). Other common findings were bronchiectasis, reticular pattern and honeycombing. The lesions involved predominantly the lower lobes. In conclusion, the presence of hypergammaglobulinemia and lymphopenia, positivity for RF, anti-La and anti-Ro, and impaired (FVC) and/or FEV(1) values could be the predictive parameters with a high specificity despite the low sensitivity rates. Smoking history, male gender and age are also risk factors. These parameters may be helpful to distinguish pSS-associated lung involvement from lung disorders unrelated to pSS.

To better characterize the clinical and pathologic features of granulomatous reaction to Pneumocystis jirovecii, we reviewed 20 cases of this uncommon response. Patients included 15 males and 5 females (mean age 52 y). The most common symptom was dyspnea (5 of 14). Primary medical diagnoses included human immunodeficiency virus/acquired immunodeficiency syndrome (7 of 20), hematopoietic (6 of 20), and solid malignancies (4 of 20). Radiology findings included nodular (8 of 16) and diffuse (5 of 16) infiltrates and solitary nodules (3 of 16). Diagnostic procedures with the highest yield were open lung biopsy (13 of 20) and autopsy (5 of 20); false-negative results were most common on bronchial washings/brushings, bronchoalveolar lavage, fine needle aspiration, and transbronchial biopsy. Follow-up showed resolution of disease (6 of 13), death from disease (6 of 13), and death from unknown cause (1 of 13). Histologically, clusters of Gomori methenamine silver-positive (20 of 20) Pneumocystis organisms were identified in all cases. Organisms were identified within well (16 of 20) and poorly (4 of 20) formed necrotizing (16 of 20) and non-necrotizing (4 of 20) granulomas ranging in size from 0.1 to 2.5 cm (mean 0.5 cm); granulomas were multiple (18 of 20) or single (2 of 20). Giant cells (11 of 20), a fibrous rim (8 of 20), and eosinophils (6 of 20) were seen. Foamy eosinophilic exudates were present centrally within some granulomas (5 of 20). Cystic spaces (1 of 20) and calcification (1 of 20) were rare. Only one case demonstrated classic intra-alveolar foamy exudates containing Pneumocystis. Granulomatous P. jirovecii pneumonia occurs most commonly in males with human immunodeficiency virus/acquired immunodeficiency syndrome, hematopoietic, and solid malignancies. The diagnosis may be overlooked as conventional radiologic and pathologic features are absent. When suspected, open lung biopsy is most likely to yield diagnostic material. Attention to organism morphology avoids misdiagnosis as Histoplasma.

BackgroundDespite advances in diagnostic and treatment strategies, head and neck squamous cell cancer (HNSCC) constitutes one of the worst cancer types in terms of prognosis. PTEN is one of the tumour suppressors whose expression and/or activity have been found to be reduced in HNSCC, with rather low rates of mutations within the PTEN gene (6-8%). We reasoned that low expression levels of PTEN might be due to a transcriptional repression governed by an oncogene. Tbx2 and Tbx3, both of which are transcriptional repressors, have been found to be amplified or over-expressed in various cancer types. Thus, we hypothesize that Tbx3 may be over expressed in HNSCC and may repress PTEN, thus leading to cancer formation and/or progression.MethodsUsing immunohistochemistry and quantitative PCR (qPCR), protein and mRNA levels of PTEN and Tbx3 were identified in samples excised from cancerous and adjacent normal tissues from 33 patients who were diagnosed with HNSCC. In addition, HeLa and HEK cell lines were transfected with a Tbx3 expressing plasmid and endogenous PTEN mRNA and protein levels were determined via qPCR and flow cytometry. Transcription assays were performed to demonstrate effects of Tbx3 on PTEN promoter activity. Mann–Whitney, Spearman’s Correlation and Wilcoxon signed-rank tests were used to analyze the data.ResultsWe demonstrate that in HNSCC samples, Tbx3 mRNA levels are increased with respect to their normal tissue counterparts (p<0.001), whereas PTEN mRNA levels are significantly reduced in cancer tissues. Moreover, Tbx3 protein is also increased in HNSCC tissue sections. Over-expression of Tbx3 in HeLa and HEK cell lines causes reduction in endogenous PTEN mRNA and protein levels. In addition, transcription activity assays reveal that Tbx3 is capable of repressing both the basal and induced promoter activity of PTEN.ConclusionsWe show that Tbx3 is up-regulated in tissue samples of HNSCC patients and that Tbx3 represses PTEN transcription. Thus, our data not only reveals a new mechanism that may be important in cancer formation, but also suggests that Tbx3 can be used as a potential biomarker in cancer.

Background Langerhans cell histiocytosis (LCH) is a rare disorder of the reticuloendothelial system with unknown etiology. This report aims to present a case of LCH with diffuse involvement of the oral cavity and to raise awareness of the distinguishing features of this diagnostically challenging entity. Case ReportA 26-year-old male patient presented with complaints of teeth mobility, intense pain, and difficulty in chewing. Intraoral and radiological examinations revealed generalized gingival hyperplasia and severe teeth mobility with widespread alveolar bone loss. Periodontal therapy was performed with no significant improvement. An incisional biopsy revealed Langerhans cells and positive reaction to S-100 and CD1, and the patient was diagnosed with LCH. The patient underwent systemic chemotherapy with vinca alkaloids and corticosteroids. Regression of gingival lesions, as well as significant decrease in mobility of the remaining teeth and severity of pain, was achieved during 12 months of follow-up. ConclusionThe rarity and variable system involvement of LCH necessitate a multidisciplinary approach be carried out for accurate diagnosis, effective treatment, and an uneventful follow-up. Awareness of oral manifestations of LCH may aid clinicians greatly in reducing morbidity and mortality associated with this debilitating condition.

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Glucose transporter-1 (GLUT-1) mediates the transport of glucose across the cellular membrane. Its elevated levels and/or activation have been shown to be associated with malignancy. The aim of this study was to investigate GLUT-1 expression in pulmonary neuroendocrine carcinomas. Tissue microarray-based samples of 178 neuroendocrine carcinomas, including 48 typical carcinoids, 31 atypical carcinoids, 27 large cell neuroendocrine carcinomas and 72 small cell carcinomas from different patients, were studied immunohistochemically for GLUT-1 expression. Forty-seven percent (75/161) of pulmonary neuroendocrine carcinomas were immunoreactive with GLUT-1. GLUT-1 was observed in 7% (3/46) of typical carcinoid, 21% (6/29) of atypical carcinoid, 74% (17/23) of large cell neuroendocrine carcinoma and 78% (49/63) of small cell carcinoma. GLUT-1 expression correlated with increasing patient age (P = 0.01) and with neuroendocrine differentiation/tumor type (P < 0.001), but not with gender, tumor size or stage. GLUT-1 expression was seen in a characteristic membranous pattern of staining along the luminal borders or adjacent to necrotic areas. GLUT-1 expression was associated with an increased risk of death for neuroendocrine carcinomas as a group (risk ratio = 2.519; 95% confidence interval = 1.519–4.178; P < 0.001) and carcinoids (risk ratio = 4.262; 95% confidence interval = 1.472–12.343; P = 0.01). In conclusion, GLUT-1 is expressed in approximately half of the pulmonary neuroendocrine carcinomas and shows a strong correlation with neuroendocrine differentiation/grade, but not with other clinicopathologic variables. Further studies appear plausible to elucidate the prognostic significance of GLUT-1 expression in pulmonary carcinoids.

Ectopic breast tissue can occur anywhere along the primitive embryonic milk line and can be the site of the same pathologic processes found in the normal breast. Phyllodes tumor is an extremely rare fibroepithelial neoplasm that occurs in ectopic breast tissue of the vulva. To date, only 8 cases of phyllodes tumor in the vulva have been reported in the literature. This paper presents two additional case of benign phyllodes tumor in the vulva. The first patient was a 43-year-old woman, presenting with a lesion on the left anterior mons pubis that had increased in size in the last three months. The second patient was a 50-year-old woman, presenting with a two-month history of a mass in the right labium majus. The patients underwent excisional biopsy. The histological examination of both specimens revealed a characteristic pattern of benign phyllodes tumor. In conclusion, the pathologists need to be aware that the lesion can occur in this location. Herein, the concepts about the histogenesis of phyllodes tumor in the vulva are discussed and a brief review of the previously reported cases is given. Key Words: Vulva, Phyllodes tumor ÖZEktopik meme dokusu ilkel embriyonik sütyolu boyunca herhangi bir yerde ortaya çıkabilir ve normal memede izlenebilen aynı patolojik durumlar ektopik meme dokusunda da görülebilir. Fillods tümör vulvadaki ektopik meme dokusunda oluşan nadir bir fibroepitelyal neoplazidir. Literatürde bugüne kadar 8 olgu bildirilmiştir. Bu makalede literatüre ek olarak iki ayrı vulvar fillods tümör vakası sunulmuştur. İlk olgu, sol ön mons pubiste boyutu son üç ayda artış gösteren bir lezyon ile kliniğe başvurmuş 43 yaşında kadın hastadır. İkinci olgu 50 yaşında kadın hasta olup, iki aydır varolan sağ labium majusta kitle ile başvurmuştur. Mevcut lezyonlara eksizyonel biopsi yapılmış ve örneklerin patolojisi benign fillods tümör ile uyumlu rapor edilmiştir. Sonuç olarak, fillods tümörün vulva lokalizasyonunda da karşılaşabilecek bir antite olduğu unutulmamalıdır. Burada, vulvar fillods tümörün histogenezi ile ilgili kavramlar tartışılmış ve olgularımız daha önce bildirilen olgular eşliğinde sunulmuştur.