Lingual Osseous Choristoma: Case report and literature review of this rare entity.

Intraoral osseous choristoma represents a benign lesion of growing ectopic bone in the soft tissues of the oral cavity. It is considered as rare entity while fewer than 100 cases have ever been reported worldwide. Nevertheless, the pathogenetic mechanism that drives this abnormal ossification still remains controversial. In the present study a case of lingual osseous choristoma in a 50-year old male is presented. The patient was treated with surgical excision and no recurrence was observed. In addition epidemiology, clinical presentation, and pathogenesis are reviewed, serving as a reminder of this rare pathology. Key words:Osseous choristoma, osteoma, tongue.

Condylomata acuminata, Bowenoid papulosis, and squamous cell carcinoma, all positive for human papillomavirus type 16/18 DNA, coexisting in the genital area: a case report.

In an attempt to raise awareness among physicians of the importance of early diagnosis and treatment of penile cancer and its precursor lesions, we report the unique case of a male patient with condylomata acuminata, Bowenoid papulosis, and squamous cell carcinoma, all HPV 16/18-positive, coexisting in his genital area.

In contrast to melanocytes, keratinocytes of normal human adult interfollicular epidermis do not express galectin-1.

INTRODUCTION: Galectins constitute a phylogenetically conserved family of proteins that specifically bind to glycoconjugates bearing ß-galactoside residues. Although galectin-1 (Gal 1), the first identified member of the galectin family, is involved in highly important biological processes at the molecular and cellular level in human skin, its expression in keratinocytes of normal human adult interfollicular epidermis (NHAIE) remains in dispute, whereas that in epidermal melanocytes has drawn very little attention so far. This prompted us to investigate the expression of Gal 1 in the keratinocytes and melanocytes of NHAIE. METHODS: Biopsy specimens obtained from the buttock skin of 23 healthy adult volunteers of both sexes were processed for single and double immunohistochemical staining using antibodies against Gal 1 and Melan-A. RESULTS: In contrast to epidermal melanocytes, which revealed a distinct Gal 1 immunoreactivity, keratinocytes of NHAIE were completely devoid of any expression of this galectin. CONCLUSIONS: This article simultaneously assesses Gal 1 immunoreactivity of keratinocytes and melanocytes in NHAIE for the first time. Our findings may contribute to a better understanding of alterations in Gal 1 expression in various benign and malignant cutaneous disorders and may be of importance for the future design of targeted therapies.

Erythema nodosum induced by oral isotretinoin in a patient with condylomata acuminata.

Erythema nodosum (EN) is a form of septal panniculitis, which is believed to represent a delayed hypersensitivity reaction activated by infectious agents, drugs, granulomatous and autoimmune diseases, pregnancy, and malignancies. There are only four reported cases of EN during oral isotretinoin therapy to our knowledge, all of them occurring in patients with severe acne. Since acne itself can trigger EN, the question as to whether there is indeed a causative relationship between isotretinoin and EN in the reported cases remains to be elucidated. We present herein a 20-year-old woman with multiple vulvar condylomata acuminata who developed EN two weeks after onset of oral isotretinoin therapy. To the best of our knowledge, this is the first report of EN occurring during isotretinoin treatment in a patient without acne and strongly indicates that the pathogenesis of EN can be directly related to the biological actions of isotretinoin. Erythema nodosum should be regarded as a rare side effect of oral isotretinoin therapy, regardless of the underlying disease. Physicians should be aware of this rare side effect.

Extensive and recalcitrant common warts in an immunocompetent patient: rapid and complete remission after oral isotretinoin monotherapy.

An immunocompetent patient with extensive and recalcitrant common warts that was orally treated with isotretinoin (1 mg/kg/day) is reported. His lesions revealed a complete remission after 6 weeks of treatment, which was well tolerated. The patient has presently completed a 23-month follow-up and shows no evidence of relapse of his skin lesions. In view of these remarkable therapeutic results, further randomized controlled clinical studies in large numbers of patients are now warranted, which will definitely determine whether monotherapy with oral isotretinoin at a dose of 1 mg/kg/day may be regarded as a highly effective and well-tolerated therapeutic modality for extensive and recalcitrant common warts in both immunocompetent and immunocompromised patients.

Pemphigus vulgaris possibly associated with application of a tissue expander in a patient with Crohn's disease and primary sclerosing cholangitis.

Pemphigus vulgaris (PV) is an autoimmune disease of the skin and mucous membranes characterized by suprabasal acantholysis and formation of blisters and erosions due to generation of IgG autoantibodies directed against desmosomal proteins. Tissue expanders are devices that, through controlled mechanical overstretch, are capable of generating new skin that is used to cover wounds or extended surgical defects. We report the case of a 13-year-old girl suffering from Crohn's disease (CD) and primary sclerosing cholangitis (PSC) who developed PV after application of a tissue expander for surgical removal of a giant congenital melanocytic nevus (GCMN). To the best of our knowledge, the case presented here is the first report of PV possibly associated with the application of a tissue expander and also the first report of coexistence of PV with either PSC or with PSC and CD in the same patient. Triggering or acute exacerbation of PV may be considered a possible side-effect of tissue expander application, especially in patients with a genetic predisposition for pemphigus and/or other autoimmune diseases. In view of the increasing use of tissue expanders in clinical practice, physicians should be aware of this rare side-effect in order to promptly diagnose it.

Golimumab-associated persistent erythema multiforme in a patient with ulcerative colitis in full remission.

Erythema multiforme is an immune-mediated cutaneous disorder that is thought to represent a hypersensitivity reaction to infections, drugs, vaccines, malignancies, autoimmune diseases, radiation, and menstruation. Golimumab is a human IgG1-kappa anti-TNF antibody that has been approved for the treatment of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and ulcerative colitis. We report herein a 41-year-old woman with persistent erythema multiforme, that occurred 18 months after onset of golimumab treatment of her ulcerative colitis; the latter remains in full remission over a period of 36 months.

Classic form of eosinophilic pustular folliculitis in an immunocompetent girl: rapid and complete resolution after low-dose oral indomethacin treatment.

Eosinophilic pustular folliculitis (EPF) is a rare noninfectious pruritic dermatosis, first described by Ise and Ofuji in 1965. We report the case of a 15-year oldimmunocompetent girl that presented with a widespread papulopustular eruption four days after her arrival in Japan. The clinical diagnosis of the classicform of EPF was confirmed by histological examination of the lesional skin that revealed an intense, mainly eosinophilic, dermal infiltrate within and aroundpilosebaceous units. Oral administration of lowdose indomethacin (25 mg/day) led to a complete resolution of the eruption within 6 weeks without causing any side effects. The patient is presently completing a 15-month follow-up and remains free ofrelapses. To the best of our knowledge, it is the first time that low-dose oral indomethacin is reported to be capable of causing a rapid and complete resolutionof the classic form of EPF.

Gamma-irradiation induces HER-2/neu overexpression in breast cancer cell lines and sensitivity to treatment with trastuzumab.

PURPOSE: Overexpression of human epidermal growth factor receptor-2 (HER-2/neu) in breast cancer patients is a prerequisite for treatment with trastuzumab. In the present study, we demonstrate by fluorescence in situ hybridization (FISH) analysis that HER-2/neu gene amplification and chromosome 17 (CEP17) polysomy can be induced by irradiation in human breast cancer cell lines with low basal level of HER-2/neu. MATERIALS AND METHODS: The irradiation-induced HER-2/neu gene amplification and CEP17 polysomy enhanced HER-2/neu at the protein level in both human MDA-MB-231 and MDA-MB-435 breast cancer cell lines which was determined by immunohistochemistry and fluorescence analysis and was correlated with mRNA levels. RESULTS: Irradiation affected to a high degree the responsiveness of both cell lines to in vitro treatment with trastuzumab. The direct antiproliferative effect of trastuzumab, as well as its capacity to induce natural killer (NK) cell-mediated antibody-dependent cell-mediated cytotoxicity (ADCC), was considerably higher in the irradiated tumor cells compared to their non-irradiated counterparts. CONCLUSION: Our data demonstrate that irradiation induces HER-2/neu gene amplification and CEP17 polysomy thereby enhancing expression of this protein in breast cancer cell lines rendering them susceptible to treatment with trastuzumab. They also suggest that patients with HER-2/neu negative inoperable tumors undergoing local radiation therapy may benefit from treatment with trastuzumab.

Inverted papilloma of the ureter: study of a rare case with emphasis on clinicopathologic implications.

A 62-year old male patient presented complaining of intermittent macroscopic hematuria. The ultrasonographic investigation revealed a hydronephrosis of remarkable degree with indiscrete renal parenchyma. The abdominal computed tomography scan identified a ureteral lesion with proximal dilatation, hydronephrosis and a functionless ipsilateral renal unit. The retrograde urography showed a 4-cm lesion with multiple filling defects and a smooth contour. The endoscopic examination showed an exophytic lesion, highly suspicious for malignancy. Urine cytology revealed atypia. Right nephroureterectomy was performed and the pathology revealed a ureteral inverted papilloma (UIP). Polymerase chain reaction examination for the presence of human papilloma virus, using GP5+/6+ consensus primers, was negative. The presence UIP should be considered in patients with urotheleal lesions in the ureter when the diagnostic workup for malignancy is inconclusive. The clinical course of the disease seems to be favorable.

Detection of herpes simplex virus in first trimester pregnancy loss using molecular techniques.

BACKGROUND: The etiology of early pregnancy loss is multifactorial and may include viral pathogens. The aim of this study was to investigate the presence of herpes simplex virus (HSV) in gestational tissues of first trimester pregnancy loss using molecular techniques. PATIENTS AND METHODS: Gestational tissue from 95 women with first trimester pregnancy loss and 36 women with elective termination of pregnancy was investigated by nested polymerase chain reaction (PCR) and in situ hybridization techniques. RESULTS: HSV was detected by the nested PCR technique in 41 out of the 95 (43.2%) cases of early pregnancy loss and in 6 out of the 36 (16.7%) cases of elective pregnancy termination (p=0.03). The HSV-positive cases in the early pregnancy loss group were observed between the 6th and the 12th gestational week and mostly in the 9th, 8th and 6th week. The in situ hybridization technique was successful in 18 out of 25 PCR-positive cases (72%) and revealed that the hybridization signal was mostly localized in the nuclei of the decidual and intermediate trophoblastic cells and less commonly in the chorionic villous trophoblastic cells. CONCLUSION: HSV seems to play a significant role in first trimester pregnancy loss and its detection by sensitive and accurate molecular techniques would permit prompt antiviral therapy for a successful future pregnancy.

Epstein-Barr virus associated primary intracranial leiomyoma in organ transplant recipient: case report and review of the literature.

INTRODUCTION: A 45 year old female renal transplant recipient presented with headaches of 3 months duration. Clinical and radiological evaluation revealed an approximately 4x4 cm rounded, enhancing mass at the left temporal pole. At surgery, the mass had dural attachment and clinically, radiographically, and macroscopically resembled a meningioma. Histopathological analysis revealed a leiomyoma. Epstein-Barr virus (EBV) DNA was demonstrated within the tumour cell nuclei by the in situ hybridisation technique. DISCUSSION: This is the first documentation of an EBV-associated primary intracranial leiomyoma in an organ transplant recipient and provides additional evidence of a possible relation between EBV infection and development of smooth-muscle tumours (SMT). CONCLUSION: With increasing numbers of individuals being on long-term immuno-suppression, EBV-associated SMTs may be encountered more frequently in the future.

Numerical aberrations of chromosomes 1 and 7 by fluorescent in situ hybridization and DNA ploidy analysis in breast cancer.

The goals of this study were to detect the numerical alterations of chromosomes 1 and 7 in breast cancer and to correlate the findings with DNA ploidy status as well as with parameters of prognostic significance. Fluorescence in situ hybridization (FISH) with centromeric probes for chromosomes 1 and 7 and cellular DNA content measurement by image analysis-based cytophotometry were applied on interface nuclei from fresh tissue imprints of 59 breast ductal carcinomas. Immunohistochemical stainings for estrogen receptor (ER), progesterone receptor (PR), HER-2, p53, and Ki67 were performed on paraffin tumor sections. The correlation between DNA ploidy and chromosomal aberrations revealed a significant association between aneuploidy and aneusomy for both chromosomes 1 (p=0.002) and 7 (p=0.00001), however, a number of diploid tumors were found to be aneusomic, especially for chromosome 1. Chromosome 7 polysomy was significantly associated with a higher incidence of axillary lymph node metastasis (p=0.05), poorly differentiated (grade III) tumors (p=0.03), negative ER and PR status (p=0.02 and 0.001, respectively), as well as p53 protein expression (p=0.05) and a higher Ki67 labeling index (p=0.004). Chromosome 1 aneusomy was only related with HER-2 protein overexpression (p=0.05). No association between chromosome alterations and tumor size was detected. In conclusion, the results of our study indicate that the detection of numerical aberrations of chromosomes 1 and 7 by FISH seems to be more sensitive than DNA ploidy status for the evaluation of abnormal cellular DNA and chromosome 7 aneusomy characterizes tumors with aggressive features and therefore might be a useful predictor of unfavorable biological behavior in breast cancer.

Evaluation of HER2 gene status in breast cancer by chromogenic in situ hybridization: comparison with immunohistochemistry.

BACKGROUND: The purpose of this study was to evaluate HER2 gene status in relation to chromosome 17 polysomy with the chromogenic in situ hybridization (CISH) technique and to compare the results with those of immunohistochemistry (IHC). METHODS AND RESULTS: Sixty six cases of breast carcinoma with an immunohistochemical HER2 protein score of 1+, 2+ 3+ (HercepTest) were investigated. HER2 gene status was evaluated on paraffin sections with the CISH technique using a digoxigenin-labeled DNA probe. In HER2 positive cases with low level amplification (LLA), the copy number of chromosome 17 was determined. Thirty four tumors (51.5%) were negative and 32 (48.5%) were positive for HER2 gene amplification. Of these 10 tumors (15%) showed LLA and 22 tumors (33.5%) high level amplification (HLA). Nine of ten tumors with LLA had an equal or greater than two ratio of HER2 to chromosome 17 signals. The correlation of the results obtained by CISH and IHC showed that the concordance of the two methods was highest in the 3+ group (100%) and lower in 1+ group (89%), whereas a high degree of discordance was found in the 2+ group (69%). CONCLUSIONS: CISH is an accurate and practical technique for the evaluation of both HER2 gene and chromosome 17 status and its application is considered necessary especially for the clarification of the 2+ results of IHC.

Herpes simplex virus as a determinant risk factor for coronary artery atherosclerosis and myocardial infarction.

BACKGROUND: Viruses have been detected in atherosclerotic and non-atherosclerotic vascular tissues and may be involved in the mechanisms of atherogenesis. In the present study, we investigated the role of herpes simplex virus (HSV) in the early and late stages of coronary artery atherosclerosis. METHODS AND RESULTS: HSV prevalence was investigated in coronary artery samples from 42 autopsy cases, in which death was related to myocardial infarction (MI), and 28 young age autopsy cases without heart disease, who had died from fatal injuries (young victim group), using nested polymerase chain reaction (nPCR) and the highly sensitive in situ hybridization with tyramide signal amplification (ISH-TSA). HSV was detected by nPCR in 18 out of 42 (43%) myocardial infarction cases and in 7 out of 28 (25%) young victim group cases, respectively. Using ISH-TSA, HSV DNA was detected in the coronary arteries of the MI group in 16 out of 42 (38%) of the cases; the hybridization signal was localized in the nuclei of endothelial cells, the nuclei of smooth muscle cells, the macrophages around the atheroma, and in the lymphocytes infiltrating the vascular wall. In the young victim group, HSV DNA was detected by ISH-TSA in 7 out of 28 (25%) autopsy cases; the signal was localized in the endothelial and the intimal spindle cells of the coronary arteries. CONCLUSION: The findings of this study suggest that HSV seems to play a significant role in the initiation and progression of coronary atherosclerosis, and may open new perspectives in preventing the development of vascular damage via an appropriate antiviral treatment.

Morphology, molecular regulation and significance of apoptosis in pituitary adenomas.

Apoptosis represents energy-requiring spontaneous single cell death, with specific morphologic and biochemical features. It is a rapidly processed sequence of events resulting in elimination of damaged cells. Apoptosis occurs in physiological remodeling and proliferative conditions, and also in neoplastic lesions. Several molecules and molecular systems such as bcl-2/bax, Fas/FasL and caspases regulate the apoptotic process. Apoptosis is characterized by a stereotypic pattern of morphologic features, which can be illustrated mostly by electron microscopy. DNA and biochemical assays, based on the specific pattern of nucleosomal fragmentation can detect apoptosis. The in situ labeling techniques are currently used to demonstrate apoptosis in paraffin sections. Several studies of pituitary animal models, cell lines and human pituitaries have been performed during the last 6 years. By electron microscopy, pituitary adenoma cells undergoing apoptosis exhibit a common prototypical pathway of changes. Although the results by the situ labeling techniques are not uniform, apoptosis occurs with low frequency in a subset of pituitary adenomas, in carcinomas and in pituitary hyperplasia. Alternative techniques based on remodeling of cytoskeleton by caspase activity can identify early apoptotic stages. This review presents the principles of apoptosis and summarizes the morphologic and functional changes of apoptosis in pituitary.

Detection of herpes simplex virus, cytomegalovirus, and Epstein-Barr virus in the semen of men attending an infertility clinic.

OBJECTIVE: To investigate the prevalence of herpes simplex virus (HSV), cytomegalovirus (CMV), and Epstein-Barr virus (EBV) in the semen of men with fertility problems. DESIGN: A descriptive clinical study. SETTINGS: Outpatient infertility clinic of a private hospital. PATIENT(S): One hundred thirteen men attending an infertility clinic in Athens. INTERVENTION(S): Semen samples were collected by masturbation. MAIN OUTCOME MEASURE(S): Detection of HSV, CMV, and EBV in semen by a nested polymerase chain reaction technique. Complete spermogram including sperm count, motility, pH, viscosity, and morphology. RESULT(S): Viral DNA was detected by the nested polymerase chain reaction technique in 64 (56.6%) of 113 semen samples. Specifically, HSV DNA was detected in 56 (49.5%) semen samples, EBV DNA in 19 (16.8%) semen samples, and CMV DNA in 8 (7.1%) semen samples. HSV was significantly related to low sperm count and poor motility. In contrast, CMV and EBV did not show any association with sperm concentration and motility. CONCLUSION(S): Herpes simplex virus seems to play a significant role in male infertility, and its early detection by the nested polymerase chain reaction technique will permit successful antiviral therapy to increase the possibility for fertility restoration and long-term protection of the sperm quality. Finally, the detection of herpes viruses within semen will allow better control of the transmission of these viruses.

A fatal case of postinfantile giant cell hepatitis in a patient with chronic lymphocytic leukaemia.

Postinfantile giant cell hepatitis has been associated with various aetiologies, including drug taking, autoimmune diseases and viral infections. We present a fatal case of giant cell hepatitis in a patient with chronic lymphocytic leukaemia. No liver biopsy was available ante-mortem. The patient was treated with corticosteroids and aciclovir for suspected autoimmune hepatitis and reactivation of Epstein-Barr virus in the context of his haematological malignancy. Post-mortem liver biopsy showed severe giant cell hepatitis while the study of liver tissue by electron microscopy revealed paramyxo-like viral particles in the cytoplasm of the affected hepatocytes similar to those observed in previous reports of giant cell hepatitis. This case illustrates that the diagnosis of the underlying cause of giant cell hepatitis may be complicated because a heterogeneous group of different aetiologies needs to be investigated. The identification of the causative agent is essential before commencing any kind of therapy. A few sporadic case reports of paramyxo-like virus related, postinfantile giant cell hepatitis have shown that ribavirin was quite effective treatment but further clinical evaluation is needed.