Abstract: Pulmonary alveolar proteinosis (PAP) is a rare, heterogeneous diffuse lung disease in childhood. We report a case of an asymptomatic 13-year old girl with PAP. She had radiolographic findings suggesting the diagnosis, which was confirmed by the "milky" bronchoalveolar lavage fluid and the histology of transbronchial biopsy. Total lung lavage was performed by flexible fiberoptic bronchoscope under local anesthesia with success. This is the first reported case of a PAP in a child that was treated by being awake during bronchoscopy. After one-year of follow-up, the patient remains free of symptoms.
Abstract: A rare case of an invasive cutaneous infection by Geotrichum candidum in an 80-year-old male patient with diabetes mellitus is reported. The primary site of infection manifested after trauma as an ulcerative lesion on the distal phalanx of the midfinger and extended throughout the right hand. Histological examination showed fungal invasion in the deep dermis without vascular involvement and G. candidum was grown in cultures from the biopsy material. Angiography revealed severe obstructive disease of the right brachial artery and its branches. Treatment, after susceptibility testing of the isolated strain, consisted of sequential administration of intravenous liposomal amphotericin B with oral voriconazole followed by liposomal amphotericin B, resulting in substantial improvement of the infection.
Abstract: Although coagulatory system disorders are well recognized in patients with acute leukemia, these usually present with either hemorrhagic complications or thrombosis of small vessels. Large vessel thrombosis is a very rare clinical presentation. We present a patient with previously undiagnosed acute myeloid leukemia (M5), who was referred to our hospital with symptoms of acute ischemia of his right lower limb. Occlusion of the right external iliac artery due to a combination of leucostasis and coagulation disorders was noted and successfully treated with urgent leukapheresis, immediate chemotherapy and surgical thromboembolectomy.
Abstract: The expression of c-erbB receptors was immunohistochemically examined in paraffin embedded specimens from non-small-cell lung carcinomas. A total of 209 patients were enrolled [squamous-cell carcinomas (n=59), adenocarcinomas (n=130), large-cell carcinomas (n=15) and giant-cell carcinomas (n=5)]. The HercepTest kit scoring guidelines were used for the interpretation of positivity. C-erbB-1 was overexpressed in older patients, in squamous-cell carcinomas and in poorly-differentiated tumours, whereas c-erbB-2 overexpression with adenocarcinomas and poorly-differentiated tumours. C-erbB-4 overexpression correlated with advanced disease stage. The c-erbB-1/4 pair was the most commonly overexpressed and significantly correlated with female gender, while the c-erbB-1/2 pair with older age. Response to chemotherapy was significantly reduced in patients with tumours overexpressing c-erbB-1 receptor as well as the c-erbB-1/2 and c-erbB-3/4 receptor pairs. Patients' overall survival was significantly correlated with the co-expression of c-erbB-1 and c-erbB-4 receptors. These findings clearly suggest that specific receptors overexpression or co-overexpression is correlated with patients' disease control rate and outcome. A better understanding of the overexpression of the heterodimerized partners of c-erbB family receptors may provide a useful predictive indicator of response to molecular targeted therapies with c-erbB inhibitors.
Abstract: Idiopathic pulmonary fibrosis (IPF) is a deadly disease, largely unresponsive to treatment with corticosteroids and immunosuppressives. The aim of this randomized, prospective, open-label study was to characterize the molecular effects of IFN-gamma-1b and colchicine, on biomarkers expression associated with fibrosis (TGF-beta, CTGF) and immunomodulatory/antimicrobial activity (IFN-gamma), in the lungs of patients with IPF. Fourteen (14) patients with an established diagnosis of IPF received either 200 microg of IFN-gamma-1b subcutaneously three times per week, or 1mg of oral colchicine per day, for 24 months. Using RT-PCR assay, we evaluated the transcription levels of transforming growth factor beta1 (TGF-beta1), connective-tissue growth factor (CTGF), and interferon-gamma (IFN-gamma) genes in lung tissue before and after treatment with IFN-gamma-1b or colchicine. Marked mRNA expression of TGF-beta1 and CTGF, but complete lack of interferon-gamma was detected in fibrotic lung tissue at entry. After treatment, both groups exhibited increased expression of IFN-gamma gene at 6 months that was sustained at 24 months. The expression of CTGF and TGF-beta1 remained almost stable before and after treatment, in the IFN-gamma-1b group, while TGF-beta1 was statistically decreased after therapy, in the colchicine group (p=0.0002). Significant difference in DLCO (% pred), was found between the two treatment groups in favor of IFN-gamma-1b group (p=0.04). In addition, the IFN-gamma-1b group showed stability in arterial PO2 while the colchicine group significantly deteriorated (p=0.02). In conclusion, we report the effect of antifibrotic agents (IFN-gamma-1b and colchicine) in TGF-beta, CTGF, and endogenous IFN-gamma gene expression, in human fibrosis. However, extended studies are needed to verify the pathophysiological consequences of these findings.
Abstract: BACKGROUND: Using a goat animal model, we tested the hypothesis that angiotensin-II inhibition reduces fibrotic degeneration of both the atrial and ventricular myocardium as well as AF induction susceptibility. METHODS: We studied three groups of five goats over a 6-month period. The study animals in the first two groups were implanted with a pacemaker capable of maintaining AF with burst pacing. Additionally, in one group, goats were administered candesartan (AF+candesartan group). The third group (SR group) of animals served as control. Animals were tested for AF induction on day 0, 1, 30, 90 and 180. A "Vulnerability Index" (VI) for AF induction was calculated, defined as the ratio of total time in AF per number of bursts needed to induce sustained AF, in each session. At the end of the study, all four heart chambers were examined and fibrosis quantified. RESULTS: Both AF goat groups developed cardiomegaly due to tachy-cardiomyopathy. Although, the VI was significantly increased in AF group over time (28.8 +/- 43 to 284.7 +/- 291, p = 0.045), this was not the case for AF+candesartan group (30.3 +/- 40 to 170.8 +/- 243, p = 0.23). Histology revealed a significant increase of fibrous tissue in goats with induced AF, noticeable in all four heart chambers, compared to controls. However, the degree of fibrosis was significantly lower in AF animals on candesartan. CONCLUSIONS: Our study demonstrated a beneficial effect of angiotensin II inhibition on tachyarrhythmia-induced ventricular fibrosis. It is also consistent with previous studies indicating a reduction in burst-induced AF susceptibility in goats and confirms the favorable effects in atrial structural remodeling.
Abstract: BACKGROUND: Osteoid osteomas (OO) are small, benign osteoblastic lesions. Ethmoid bone OO has been very rarely reported so far. CASE PRESENTATION: We report a case of a 16-year-old boy suffering from persistent epiphora and a mild pain in the area of median canthus, due to a bone density mass within the right ethmoid air cells extending to the ipsilateral right orbit. The mass was removed via an external ethmoidectomy approach. Histopathologic examination of the specimen set the diagnosis of OO. One year after the operation the patient is free of symptoms, while no recurrence occurred. CONCLUSION: A case of ethmoid bone OO associated with dacryocystitis is reported. Although benign and rare, OO should be considered in differential diagnosis of the ethmoid bone osteoblastic lesions.
Abstract: BACKGROUND: Primary non-Hodgkin lymphomas (NHLs) of the sinonasal tract comprise a rare entity that constitutes 1.5% of all NHLs and 2.2% of extranodal lymphomas in the whites. Clinical diagnosis may be very challenging because of the variety and low specificity of the presenting symptoms and signs. METHODS-RESULTS: We present three cases of NHLs, initially diagnosed as benign diseases. All three cases have been eventually correctly diagnosed and treated in our hospital between January 2000 and December 2003. The patients have been under close follow-up from 11 to 36 months after the initial treatment. One of them remains without clinical or radiological evidence of recurrence, whereas the two others died 11 and 16 months after the initial diagnosis. CONCLUSION: It is important to underline that atypical or persistent symptoms of rhinosinusitis may represent the initial expression of a more serious condition such as deep fungal infection, vasculitis, lymphoma, or other malignancy.
Abstract: ABSTRACT : Oral mucosal melanomas are highly malignant tumors. The 'chameleonic' presentation of a mainly asymptomatic condition, the rarity of these lesions, the poor prognosis and the necessity of a highly specialized treatment are factors that should be seriously considered by the involved health provider. We present the case of a 75-year-old man who was referred to the Ear, Nose and Throat department. His symptoms were voice alteration and saliva drooling, progressively worsening during the last few weeks. The absence of pain was the reason for the delay of seeking medical care. The diagnosis was an oversized oral melanoma. This is an example of how the time of diagnosis and the evolution of a disease could be seriously influenced by patient's behavior. Melanomas arising from oral mucosa have poor prognosis unless they are discovered and treated early. The vigilance of the physicians is necessary to have success in this difficult task.
Abstract: Fibril-associated collagens with interrupted triple helices (FACITs) XII and XIV act as fibril organizers and assist in the maintenance of uniform fibril size. We investigated the spatial expression patterns of collagens XII and XIV in cryptogenic organizing pneumonia (COP)/organizing pneumonia (OP) and in idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia (UIP) and compared them to normal human lung. Study subjects included 10 patients with COP/OP, 10 patients with IPF/UIP, and 8 control subjects. Immunostaining for collagens XII and XIV was carried out in paraffin-embedded human lung tissue sections. Picrosirius red histochemical staining for collagen I expression and electron microcopy to evaluate fibril diameter were also performed. In normal lung, collagens XII and XIV were expressed in perivascular and subpleural connective tissue. In COP/OP, both collagens showed intense staining in perivascular connective tissue, thickened alveolar septae, and subpleural areas. In IPF/UIP, XII and XIV were expressed in perivascular connective tissue, in areas of established fibrosis, and in areas of subpleural thickening. Only collagen XII was expressed in granulation tissue plugs in COP/OP and in fibroblastic foci in IPF/UIP. Collagen type I was overexpressed in fibrotic areas. Electron micrographs revealed obvious fibril diameter alteration and fusion in the same areas. FACITs XII and XIV are expressed in normal and fibrotic lung. Unlike collagen XIV, collagen XII was expressed in granulation tissue plugs in COP/OP and in fibroblast foci in IPF/UIP. This may suggest a possible distinct role for both collagens in the modulation of the extracellular matrix during the onset of fibrotic process.
Abstract: Parotid gland is the most common location of malignant mixed tumors. Three different subtypes of these tumors exist: carcinoma ex pleomorphic adenoma, carcinosarcoma, and metastasizing mixed tumor. Carcinoma ex-pleomorphic adenoma is by far the most common subtype. Although unusual sites of these tumors have been published, we report an extremely rare case of a malignant mixed tumor located in the nasal cavity.
Abstract: BACKGROUND: The incidence of multiple primary malignant neoplasms increases with age and they are encountered more frequently nowadays than before, the phenomenon is still considered to be rare. CASE PRESENTATION: We report a case of a man in whom urinary bladder transitional cell carcinoma, metachronous prostate adenocarcinoma and small cell lung carcinoma were diagnosed within an eighteen-month period. The only known predisposing factor was that he was heavy smoker (90-100 packets per year). The literature on the phenomenon of multiple primary malignancies in a single patient is reviewed and the data is summarized. CONCLUSION: It is important for the clinicians to keep in mind the possibility of a metachronous (successive) or a synchronous (simultaneous) malignancy in a cancer patient. It is worthy mentioning this case because clustering of three primary malignancies (synchronous and metachronous) is of rare occurrence in a single patient, and, to our knowledge, this is the first report this combination of three carcinomas appearing in the same patient.
Abstract: STUDY OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) is a chronic, usually fatal lung disease of unknown etiology. A common feature is the presence of microscopic areas of epithelial cell dropout. Increased apoptosis of these cells could elucidate the speculative pathogenesis of the disease. Therefore, the aim of our study was to examine the expression of p53, p21, bcl-2, bax, and caspase-3 in association with DNA strand breaks in bronchial and alveolar epithelial cells in lung specimens from IPF patients and control subjects. PATIENTS AND METHODS: We examined by immunohistochemistry the expression of p53, p21, bax, bcl-2, and caspase-3 in association with DNA strand breaks detected by terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling (TUNEL) in bronchial and alveolar epithelial cells in lung specimens taken by biopsy in 12 IPF patients and 10 control subjects. An independent tissue evaluation by two pathologists graded semiquantatively the degree of staining present. RESULTS: TUNEL was positive in epithelial cells in all IPF patients and only in one control subject. The expression of p53, p21, bax, and caspase-3 was up-regulated in IPF patients compared to control subjects. Bcl-2 was expressed less in IPF patients than in control subjects. CONCLUSIONS: These results confirm that apoptotic hyperplastic epithelial cells are present in patients with IPF and that the expression of p53, p21, bax, and caspase-3 appears to be up-regulated and that of bcl-2 down-regulated in these cells. The increased expression of proapoptotic molecules in epithelial cells in IPF may be involved in the inadequate and delayed reepithelialization, which in turn contributes to fibroblast proliferation.
Abstract: Pulmonary toxicity, as an adverse effect of methotrexate (MTX) therapy, is uncommon in psoriatics. This report concerns a patient with psoriatic arthritis who developed fatal pneumonitis with a histopathological pattern of the organizing stage of diffuse alveolar damage and who was receiving MTX at a dose of 15 mg weekly for 1 month. The patient died despite the immediate withdrawal of MTX, the administration of corticosteroids, and adequate supportive care. Since MTX pneumonitis is a potentially fatal complication, new pulmonary symptoms, even in patients on low-dose MTX treatment, should be appropriately investigated.
Abstract: OBJECTIVE: To compare c-erbB2 (HER-2/Neu) immunohistochemical staining results obtained in 2 pathology departments and evaluate the reproducibility of staining and assessments. STUDY DESIGN: Ninety primary invasive ductal carcinoma cases constituted the material of this study. For concordant assessment, serial sections from the same tissue blocks were prepared in both Turkey and Greece and were sent to each other. Evaluation of c-erbB2 (HER-2/Neu) staining was done independently in 2 departments by experienced pathologists. Stained slides were evaluated semiquantitatively in Turkey and both semiquantitatively and automatically in Greece. RESULTS: There was complete agreement on staining density in 58 (64.4%) cases in both centers. In 15 cases there were major discordances in staining degrees, and in 17 cases there was a major discordance. Hypothetical treatment decisions based on these results showed that 82% of patients would have been handled the same way. CONCLUSION: Comparison of immunostaining patterns performed at 2 centers provided valuable data that may be used in the development of quality assurance policies. The present study showed the usefulness of multicenter comparative studies in initiating the development of guidelines.
Abstract: A case of meningioangiomatosis (MA), in a 10-year-old-girl with refractory complex partial and secondary generalized seizures, starting at the age of 8 years, is presented. MRI evaluation revealed a lesion located at the left frontal lobe; the patient underwent surgical lesionectomy. Histology revealed the lesion to have the features of MA. The patient is symptom-free a year postoperation. We report the histological, immunohistochemical and imaging findings in view of previous pertinent reports.
