Brenner tumour of the ovary--an incidental histological finding.

Brenner tumours of the ovary are uncommon neoplasms and mostly benign. There is general agreement that Brenner tumors are derived from the surface epithelium of the ovary or the pelvic mesothelium through transitional cell metaplasia. It is essential to categorise these tumours as benign, borderline or malignant type as the biologic behaviour and choice of surgery differs in all of the three categories. The authors report a case of Brenner tumour that had only a single area with a beginning indistinct stroma vessel invasion. However the presence of characteristic epithelial nests, fibromatous stroma, and marked cytological metaplasia without atypia provided important clues to the correct diagnosis--proof of a benign tumour.

Presentation of a patient with in situ amelanotic melanoma of the vulva.

Amelanotic malignant melanoma of the vulva is extremely rare. The authors describe here a case of amelanotic malignant melanoma of the vulva, occurring in a 71-year-old woman without any clinical symptoms. The woman had a small nodular lesion in the left labia majora. Local excision was performed. Histological examination revealed an in situ malignant melanoma without any evidence of invasive disease. All suspicious lesions in the vulva region, even if there are no clinical symptoms, should be biopsied, and if an in-situ melanoma is identified, partial or total vulvectomy should be considered.

Lactate dehydrogenase 5 isoenzyme overexpression defines resistance of prostate cancer to radiotherapy.

BACKGROUND: Radiotherapy provides high-cure rates in prostate cancer. Despite its overall slow clinical growth, high proliferation rates documented in a subset of tumours relate to poor radiotherapy outcome. This study examines the role of anaerobic metabolism in prostate cancer growth and resistance to radiotherapy. METHODS: Biopsy samples from 83 patients with prostate cancer undergoing radical hypofractionated and accelerated radiotherapy were analysed for MIB1 proliferation index and for lactate dehydrogenase isoenzyme LDH5, a marker of tumour anaerobic metabolism. Ninety-five surgical samples were in parallel analysed. Correlation with histopathological variables, PSA and radiotherapy outcome was assessed. Dose-response experiments were performed in PC3 and DU145 cancer cell lines. RESULTS: High MIB1 index (noted in 25% of cases) was directly related to Gleason score (P<0.0001), T3-stage (P=0.0008) and PSA levels (P=0.03). High LDH5 (noted in 65% of cases) was directly related to MIB1 index (P<0.0001), Gleason score (P=0.02) and T3-stage (P=0.001). High Gleason score, MIB1, LDH5 and PSA levels were significantly related to poor BRFS (P=0.007, 0.01, 0.03 and 0.01, respectively). High Gleason score (P=0.04), LDH5 (P=0.01) and PSA levels (P=0.003) were significantly related to local recurrence. MIB1 and T-stage did not affect local control. Silencing of LDHA gene in both prostate cancer cell lines resulted in significant radiosensitisation. CONCLUSIONS: LDH5 overexpression is significantly linked to highly proliferating prostate carcinomas and with biochemical failure and local relapse following radiotherapy. Hypoxia and LDHA targeting agents may prove useful to overcome radioresistance in a subgroup of prostate carcinomas with anaerobic metabolic predilection.

Immunohistochemical studies of wound healing after monopolar electrocautery and ultrasound submucosal inferior nasal turbinate reduction in sheep.

BACKGROUND: Extracellular matrix (ECM) proteins such as fibronectin and collagen III, enzymes such as matrix metalloproteinases and macrophages have been demonstrated to intervene in nasal and paranasal sinuses wound healing. AIM OF THE STUDY: To compare concentration of ECM proteins, enzymes and the recruitment of macrophages during wound repair after monopolar electrocautery in contrast with ultrasound submucosal surgical tissue reduction of inferior nasal turbinate (INT) tested in sheep. MATERIALS AND METHODS: Prospective controlled study in sheep. Immunostaining for collagen III, fibronectin, CD68 and matrix metalloproteinase-9 (MMP9) was applied in tissue specimens of INT mucosa after monopolar electrocoagulation (MEC) and ultrasound tissue reduction (UTR). Twelve INTs were studied 1, 3 and 8 weeks post-operatively in each interventional group (MEC and UTR) and 5 INTs were studied in animals of the control group (without surgery). The immunoreactivity was quantitatively graded between 0% to 100% immunoreactivity by a blinded senior pathologist. RESULTS: At the end of the study period collagen III, fibronectin and MMP9 were increased in both groups compared to the levels of the control group. When compared to control group, CD68 immunoreactivity was found higher in MEC group but not in UTR group. Fibronectin subepithelial immunoreactivity exhibited a substantial negative correlation with mucosal epithelial cell necrosis, a substantial positive correlation with fibrosis in MEC-treated specimens and a significant positive correlation with sinusoid engorgement in UTR-treated specimens. Collagen III tissue immunoreactivity showed a particularly significant negative correlation with sinusoid engorgement in MEC-treated specimens. CONCLUSION: Correlation of fibronectin and collagen III immunoreactivity to histopathologic findings suggests different ECM repair processes between MEC and UTR turbinate tissue reduction. The use of CD68 and MMP9 provides additional clues to the mode of actions of these techniques and to the molecular and cellular events of the nasal mucosa wound healing process.

Autophagy and hypoxia in colonic adenomas related to aggressive features.

AIM: The study investigated whether autophagic activity and hypoxia parallel the adenoma-carcinoma sequence. METHOD: The study comprised 120 tubular adenomas with high-grade dysplasia, including 22 with questionable evidence of invasion, 37 with definite stromal invasion and 29 with severely dysplastic adenoma, 10 traditional serrated adenomas and 22 classical tubular adenomas lacking aggressive features. The samples were stained immunohistochemically for autophagy (LC3A and Beclin-1) and hypoxia-inducible factor1-alpha (HIF1α) markers. RESULTS: LC3A was detected as diffuse cytoplasmic staining and as dense "stone-like" structures (SLS) within cytoplasmic vacuoles. Beclin-1 reactivity was purely cytoplasmic, whereas that of HIF1α was both cytoplasmic and nuclear. SLS counts in noninvasive, nontransformed areas of tubular adenomas were consistently low (median SLS = 0.5; 200× magnification), whereas a progressive increase was noted from areas of equivocal invasion (median SLS = 1.3; 200× magnification) and intramucosal carcinoma (median SLS = 1.4; 200× magnification) to unequivocal invasive foci (median SLS = 2.1; 200× magnification) (P < 0.0001). A similar association was shown for Beclin-1 and HIF1α expression (P < 0.05). Traditional serrated adenomas yielded low SLS counts and weak HIF1α reactivity, but high cytoplasmic LC3A and Beclin-1 expression (P < 0.01). CONCLUSION: A hypoxia-driven autophagy in adenomatous polyps, when particularly intense and localized, is commonly associated with early invasion or severely dysplastic adenoma.

Vascular density analysis in colorectal cancer patients treated with vatalanib (PTK787/ZK222584) in the randomised CONFIRM trials.

BACKGROUND: Pharmacological inhibitors of vascular endothelial growth factor (VEGF) receptors, like vatalanib, have been tested in randomised trials (CONFIRM (Colorectal Oral Novel therapy For the Inhibition of Angiogenesis and Retarding of Metastases) 1 and 2) in colorectal cancer showing activity in a subgroup of patients with high serum LDH expression. In the current study, we assessed the predictive role of vascular density (VD) in patients treated in the above trials. METHODS: Paraffin-embedded materials from 141 patients were analysed with immunohistochemistry for the expression of the CD31 (pan-endothelial cell marker) and of phosphorylated pVEGFR2/KDR on endothelial cells. The VD was correlated with response to therapy and with progression-free (PFS) and overall survival (OS). RESULTS: A significant association of pVEGFR2/KDR+ VD with poor response in the placebo group was noted (response rates (RRs) 15% (3/20) when high VD vs 52% (26/50) when low VD; P=0.006). The RR increased from 15 (3/20) to 50% (11/22) in tumours with high VD when vatalanib was added to chemotherapy (P=0.02). A significantly improved PFS was noted in patients with high pVEGFR2/KDR+ VD when treated with vatalanib (P=0.002). A similar effect was also noted in patients with high CD31+ VD (P=0.07). Overall survival was marginally improved (P=0.07). CONCLUSION: Assessment of the activated vessel density may allow the stratification of patients recruited in randomised trials with VEGFR-targeting anti-angiogenic agents, unmasking their therapeutic potential and enabling their introduction in the clinical practice for the benefit of specific patient subgroups, at the same time reducing the cost of therapy.

Cancer stem cell phenotype relates to radio-chemotherapy outcome in locally advanced squamous cell head-neck cancer.

BACKGROUND: Cancer stem cells (CSCs) tend to repopulate malignant tumours during radiotherapy and, therefore, prolongation of the overall treatment time may result in radiotherapy failure. Thus, an estimate of the number of CSCs in tumour biopsies may prove most useful in predicting resistance to radiotherapy and a guide for development therapies aimed to eradicate a cancer cell population with effects on radiotherapy-related cancer regrowth. METHODS: The CSC population was investigated semi-quantitatively in 74 locally advanced squamous cell head-neck cancers (HNSCC) from an equal number of patients, treated with accelerated platinum-based radiotherapy. A standard immunohistochemical technique and the CSC markers CD44, CD24, Oct4, integrin-ß1 and aldehyde dehydrogenase isoform 1A1 (ALDHA1) was used, in parallel with the proliferation marker MIB-1. The results were correlated with the site of the tumour, the MIB-1 index, the tumour grade and stage, and prognosis. RESULTS: The expression of CD44, CD24 and Oct4 were significantly associated with the MIB-1 proliferation index. In addition, the CD44 was linked with the better differentiated HNSCC. The CD44, Oct4 and integrin-ß1 were all associated with poor prognosis but, in a multivariate analysis, the integrin-ß1 had an independent statistical significance in terms of local relapse, distant metastases and overall survival. Interestingly, ALDH1 was associated with favourable prognosis. CONCLUSION: CSC markers are linked with poor radiotherapy outcome in HNSCC, with integrin-ß1 being the strongest and independent prognostic factor. Targeting CSC molecules with monoclonal antibodies or pharmaceutical agents may prove important for the treatment of HNSCC.

Rectal endometriosis causing colonic obstruction and concurrent endometriosis of the appendix: a case report.

INTRODUCTION: Endometriosis is a clinical entity which presents with functioning endometrial tissue at sites outside the uterus. Bowel endometriosis is usually asymptomatic, but it may show non-specific symptoms. The presence and/or association of appendiceal endometriosis, concomitant with rectal endometriosis, is possible. CASE PRESENTATION: A 36-year-old Greek woman was admitted to the emergency room of our hospital with signs of acute abdomen. On physical examination, our patient had a painful distended abdomen. Digital examination revealed an empty rectum and bowel obstruction was diagnosed. Our patient underwent exploratory laparotomy and rectum stenosis (almost complete obstruction) was observed. The bowel stenosis was resected, and temporary colostomy and appendectomy were performed. The pathology report showed endometriosis of the colon and the appendix, and our patient received medical treatment for endometriosis. Six months after this operation our patient had another surgery for restoration of large bowel continuity. No endometriosis was found. Our patient was doing well at the one-year follow up. CONCLUSION: Endometriosis of the bowel is a disease that may cause large bowel obstruction. In women of reproductive age, the surgeon should consider endometriosis as a differential diagnosis in case of various gastrointestinal symptoms.

Intestinal-type metaplasia in the original squamous epithelium of the cervix.

There have been a number of reports on cervical carcinomas, both invasive and intraepithelial (CIN III), indicating the presence of intracellular mucins in the absence of glandular differentiation. Yet, the expression of such cells in the normal/original squamous epithelium of the cervix remains unexplored. We investigated the presence of mucin-distended goblet cells at this site, after examining retrospectively normal cervices from 250 hysterectomy specimens. Goblet cells were detected in 3.2% (8/250) of the cervices examined using haematoxylin and eosin stained sections and confirmed by mucin histochemistry: alcian blue (AB) pH 2.5, periodic acid-Schiff reaction with and without diastase digestion (PAS-d, PAS) and the combined AB/PAS. Additional sections were stained with Diazo and Masson-Fontana for argentaffin granules and Grimelius for argyrophil cells, but were all negative and no other cell types were identified. It is believed that this incomplete type of intestinal metaplasia is an acquired change in the cervix, derived from multi-potential stem cells of Müllerian duct origin.

Leiomyomas of spermatic cord and testis presenting as hernia--chromosomal analysis.

We report a rare case of three leiomyomas of the permatic cord and testis in a 73-year-old man. Indirect, large, painful, non-reducible inguinal hernia was diagnosed at admission. During surgery, the hernia was revealed. Furthermore, two tumors were found, both attached on the spermatic cord, and a third tumor close to the testis. All the tumors were carefully removed and no orchidectomy was performed. Hernia repair was performed and the removed tumors were sent to the Pathology Department. All tumors were benign. At the first follow up, chromosomal analysis was also performed. Chromosomal lymphocyte analysis revealed increased fragility at site 4q31. Two years after surgery, the patient was admitted again with a new similar tumor, and underwent a new surgical treatment. In the case of large non-reducible inguinal hernias, surgeons have to consider tumors in the inguinal area in their differential diagnosis.

Myxoid leiomyosarcoma of the uterus: a diagnostic challenge.

Myxoid leiomyosarcoma is an extremely rare variant of leiomyosarcoma, masquerading almost to perfection as a benign lesion. For, indeed, the tumor lacks the defining features of high mitotic activity, cellular atypia or necrosis, and the microscopic picture is dominated by abundant myxoid stroma containing sparse spindle cells. We report here such a case occurring in the uterus and discuss the differential diagnosis. The relevant literature is reviewed.

Beclin 1 over- and underexpression in colorectal cancer: distinct patterns relate to prognosis and tumour hypoxia.

INTRODUCTION: Autophagy enables cells to recycle long-lived proteins or damaged organelles. Beclin 1, the mammalian orthologue of the yeast Apg6/Vps30 gene, functions as a scaffold for the formation of autophagosomes. MATERIALS AND METHOD: The immunohistochemical patterns of Beclin 1 expression and their prognostic relevance were studied in formalin-fixed tissues from 155 patients with colorectal adenocarcinoma treated with surgery alone. RESULTS: Using the weak homogeneous expression of Beclin 1 in normal colonic tissues as a basis for assessing tumours, the following grouping/staining patterns were recognised in colorectal carcinomas: a normal-like pattern in 62 of 155 (40%) cases, an underexpression pattern in 24 of 155 (15.5%) cases, extensive overexpression of Beclin 1 in 33 of 155 (21.3%) tumours and limited overexpression of the protein in 36 of 155 (23.2%) tumours. Extensive overexpression of Beclin 1 was significantly linked with overexpression of HIF1α and LDH5, as well as with high histological grade, vascular invasion and nodal involvement. Furthermore, patients with extensive over- or underexpression of Beclin 1 had a significantly poorer overall survival compared with the other two groups (P<0.0001). Beclin 1 had an independent prognostic relevance in multivariate analysis. CONCLUSIONS: Beclin 1 has an important role in growth and metastasis of colorectal cancer. Loss of Beclin 1 expression (allelic loss or microRNA regulatory activity, as suggested in the literature) defines poor prognosis presumably by promoting anti-apoptotic pathways, while overexpression of the protein, being linked with tumour hypoxia and acidity, also defines subgroups of tumours with aggressive clinical behaviour.

Angiogenesis and angiogenic factor expression in thyroid cancer.

PURPOSE: Increased expression of angiogenic factors and high vascular density characterize tumors with increased invasive and metastatic capability. Anti-vascular endothelial growth factor (VEGF) therapies have shown an important potentiation of chemotherapy and radiotherapy in experimental and clinical studies. The purpose of this study was to investigate whether it could be possible to identify a subgroup of thyroid cancer patients with high angiogenic activity. METHODS: Formalin-fixed paraffin-embedded tissues from 25 papillary and 18 follicular thyroid carcinomas were assessed immunohistochemically for angiogenic activity, i.e. vascular density (VD) and expression of VEGF and basic fibroblast growth factor (bFGF). RESULTS: VD was significantly higher in follicular tumors (p=0.05). Tumors > 4 cm had a significantly higher VD (p=0.001). High VEGF expression was significantly related to high VD (p=0.05). There was no association of bFGF with histological characteristics. CONCLUSIONS: Increased angiogenic activity is a common feature of thyroid carcinomas, particularly in follicular tumors and larger carcinomas. These results support the testing of anti-VEGF therapies in combination with radiotherapy and chemotherapy in advanced thyroid tumors.

Prognostic and predictive factors of invasive ductal breast carcinomas.

PURPOSE: To investigate the significance of certain immunohistochemical markers, namely estrogen (ER) and progesterone receptors (PgR), c-erbB-2 oncogene, p53 tumor suppressor gene and E-cadherin adhesion molecule, in invasive ductal breast carcinomas. METHODS: A series of 102 primary breast carcinomas of the ductal type and a standard immunohistochemical technique was used to detect the aforementioned biological markers. The findings were related to various clinical and pathological tumor characteristics, including lymph node metastases. RESULTS: ER and E-cadherin were expressed more commonly in tumors of low histological grade and small number (< or =3) of metastatic lymph nodes, whereas c-erbB-2 and the p53 gene were usually expressed in breast tumors of high histological grade and increased number (>3) of metastatic lymph nodes. PgR, on the other hand, was detected frequently in patients with early menarche and metastases in <3 lymph nodes, but this tendency was not statistically significant. CONCLUSION: The use of these biomarkers, preferably in combination, may provide additional prognostic and therapeutic information which may be proved useful in planning breast cancer treatment.

Vascular leiomyoma of the nasal vestibule. Case report and literature review.

OBJECTIVES: Vascular leiomyoma (angioleiomyoma) of the nasal cavity is an extremely rare tumour. Following a thorough review of relevant literature, we found that such tumours are more common in females. Only 4 of 30 reported cases have been found in male patients. Moreover, considering the site of the lesion within the nasal cavity, only 3 of these 30 cases originated from the nasal vestibule. Hereby, we present a case of vascular leiomyoma arising specifically from the floor of the nasal vestibule in a 68-year-old man, which is unique because it combines the specific tumour localization with the patient's gender. CASE REPORT: The patient was treated surgically. The tumour was completely removed through an intraoral incision. CONCLUSIONS: This is the first reported case of vascular leiomyoma arising from the floor of the nasal vestibule affecting a male patient.

Carcinoid tumor of the appendix during pregnancy. A rare case and a review of the literature.

We present a rare case of a carcinoid tumor of the appendix that was diagnosed during pregnancy in a 24-year-old female. The patient was admitted to our department for acute abdominal pain localized on the right half of the abdomen, mimicking acute appendicitis. Open appendectomy was carried out and at the histological examination carcinoid was found in the surgical specimen. Only few similar cases were found in the literature reporting appendiceal carcinoid tumor during pregnancy.

Irregular dental structures in a benign ovarian cystic teratoma (dermoid cyst): case report.

Mature cystic teratomas, often referred to as dermoid cysts, are the most common germ cell tumors of the ovary in women of reproductive age. The gross pathologic appearance of a dermoid cysts is characteristic. Hair follicles, skin glands, muscle, and other tissues lie within the cyst wall. We present a case of a dermoid cyst ovarian tumor in a 24-your-old patient with a tooth lying on each wall. The mass was laparoscopically removed by ovarian cystectomy.

Cytogenetic study in cultured human lymphocytes treated with three commonly used preservatives.

Potassium sorbate, sodium benzoate and potassium nitrate have been tested for their genotoxic, cytostatic and cytotoxic potential in human peripheral blood cells in vitro. Potassium nitrate has shown no activity in the test system. When potassium sorbate and sodium benzoate were used at concentrations of 2.0, 0.2 and 0.02 mM no cytostatic activity was detected. However, concentrations of 4 and 8 mM have shown a weak cytostaticity. Additionally, a genotoxic activity using the SCE methodology has been observed at 8 mM of sodium benzoate and at 4 and 8 mM of potassium sorbate. No cytotoxic activity has been induced by the three preservatives. Data demonstrate that the preservatives at low concentrations can be considered as non genotoxic under conditions tested.