Immunhistochemical analysis of Nuclear Factor Kappa Beta expression in etiopathogenesis of ovarian tumors1.

PURPOSE: To investigate the place of the transcription factor nuclear kappa B (NF-kB), which is a marker of chronic inflammation, in the etiology of the ovarian carcinoma. METHODS: NFkB analysis with the immunohistochemical method has been performed. To evaluate immunohistochemical NF-kB expression in the ovarian tissue, the H-score method. H-score = ∑ Pi (i+1), where ''Pi'' is the percentage of stained cells in each intensity category (0-100%) and ''i'' is the intensity indicating weak (i=1), moderate (i=2) or strong staining (i=3). RESULTS: It has been seen that, the mean H score is statistically significantly higher in the patient group with serous and musinous adenocarcinoma diagnosis than the two other patient groups (p<0.005). CONCLUSIONS: Factor nuclear kappa B is an important mediator that acts in the chronic inflammation. The highest expression rates are determined by the immunohistochemical method in the ovarian cancer group.

Immunhistochemical analysis of Nuclear Factor Kappa Beta expression in etiopathogenesis of ovarian tumors

Abstract Purpose: To investigate the place of the transcription factor nuclear kappa B (NF-kB), which is a marker of chronic inflammation, in the etiology of the ovarian carcinoma. Methods: NFkB analysis with the immunohistochemical method has been performed. To evaluate immunohistochemical NF-kB expression in the ovarian tissue, the H-score method. H-score = ∑ Pi (i+1), where ''Pi'' is the percentage of stained cells in each intensity category (0-100%) and ''i'' is the intensity indicating weak (i=1), moderate (i=2) or strong staining (i=3). Results: It has been seen that, the mean H score is statistically significantly higher in the patient group with serous and musinous adenocarcinoma diagnosis than the two other patient groups (p<0.005). Conclusions: Factor nuclear kappa B is an important mediator that acts in the chronic inflammation. The highest expression rates are determined by the immunohistochemical method in the ovarian cancer group.

Glucagonoma syndrome with serous oligocystic adenoma: A rare case report.

RATIONALE: Glucagonoma and pancreatic serous oligocystic adenoma (SOA) are rare neuroendocrine and exocrine tumors of the pancreas, respectively. The coexistence of glucagonoma syndrome (GS) and SOA is a rare clinical condition and has not yet been reported. Additionally, necrolytic migratory erythema (NME), a hallmark clinical sign of GS, is often misdiagnosed as other skin lesions by clinicians due to their lack of related knowledge, which delays diagnosis of GS and thus exacerbates the prognosis. PATIENT CONCERNS: A 50-year-old male patient was admitted to our department because he presented with diabetes mellitus and a recurrent ulcerated skin rash. Prior to the accurate diagnosis, the skin manifestation was considered to be diabetic dermopathy. DIAGNOSES: The patient's fasting serum glucagon level was up to 871.5 pg/mL. A biopsy of the pancreatic tumor revealed a pancreatic neuroendocrine tumor, and immunoperoxidase staining revealed glucagon-positive cells. In addition, the histological examination of the pancreatic cystic lesions showed typical features of SOA. INTERVENTIONS: The patient received a pancreaticoduodenal resection and radiofrequency ablation for the hepatic nodular lesion. OUTCOMES: One week after surgery, the glucagon concentration decreased to near normal levels. The cutaneous lesions spontaneously resolved within 4 weeks after surgery. LESSONS: Because almost all glucagonomas are malignant or have malignant potential, their early recognition and correct diagnosis are very important for a better prognosis, especially in cases with NME as the only manifestation during the development of glucagonomas. It is therefore imperative that clinicians recognize NME early to make an accurate diagnosis.

Pancreatic mixed serous neuroendocrine neoplasm with clear cells leading to diagnosis of von Hippel Lindau disease.

Mixed serous neuroendocrine neoplasms are extremely rare tumors that are usually seen in female patients and are often associated with von Hippel Lindau (VHL) disease. We describe the case of a 38-year-old male who presented with complaints of anorexia, weight loss, and abdominal pain. CT abdomen showed a mass in the head of the pancreas, multiple small nodules in the body of pancreas, and bilateral adrenal masses. Fine needle aspiration cytology (FNAC) from the mass showed features of a neuroendocrine tumor, with many of the cells demonstrating abundant clear cytoplasm. Histopathological examination of the pancreaticoduodenectomy specimen showed a mixed serous neuroendocrine neoplasm with two components viz. serous cystadenoma and neuroendocrine tumor (NET) World Health Organization (WHO) grade 2. In addition, he was diagnosed to have bilateral pheochromocytomas and a paraganglioma. The synchronicity of these tumors suggested the possibility of VHL disease. Thus, identification of a NET with clear cells or of a mixed serous neuroendocrine neoplasm should raise suspicion of VHL disease. In a mixed tumor, FNAC may identify only one of the two components. Thorough processing of all pancreatic serous tumors for pathological examination is recommended, as NET may occur as a small nodule within the serous cystadenoma.

Serous microcystic adenoma of the pancreas associated with malrotation and Hirschsprung's disease in an infant.

Serous microcystic adenoma of the pancreas is an uncommon tumor in adults, and reported in pediatric patients only a handful of times. The authors present a case of a 6 month patient with incidental finding of a large cystic mass on the tail of the pancreas during an operation for Hirschsprung's disease. Final pathology was consistent with serous microcystic adenoma. This is the second case report describing this lesion in an infant, and the first time it has been associated with Hirschsprung's disease.

Risk for malignant and borderline ovarian neoplasms following basic preoperative evaluation by ultrasonography, ca125 level and age.

OBJECTIVE: To verify the basic preoperative evaluation in the discrimination between benign and malignant adnexal masses in our clinical practice. MATERIALS AND METHODS: Data were collected on the records of 636 women with adnexal masses who had undergone surgery either by open or endoscopic approaches. Those with obvious signs of malignancy, any history of cancer, emergency surgeries without basic evaluation were excluded. The preoperative features by age, ultrasound and serum Ca125 level were compared with final histopathological diagnosis at the four departments of the institution. These are the general gynecology (Group 1: exploratory laparotomy), the gynecologic endoscopy (Group 2: laparoscopy and adnexectomy), the gynecological oncology (Group 3: staging laparotomy) and the gynecologic endocrinology and infertility (Group 4: laparoscopy and cystectomy). RESULTS: There were simple and complex cyst rates of 22.3% and 77.2%, respectively. There were 86.3% benign, 4.1% (n:20) borderline ovarian tumor (BOT) and 6.4% (n:48) malignant lesions. There were 3 BOT and 9 ovarian cancers in Group 1 and one BOT and two ovarian cancer in the Group 2. During the surgery, 15 BOT (75%) and 37 ovarian cancer (77%) were detected in the Group 3, only one BOT was encountered in the Group 4. The risk of rate of unsuspected borderline or focally invasive ovarian cancer significantly increased by age, size, complex morphology and Ca125 (95% CI, OR=2.72, OR=6.60, OR=6.66 and OR=4.69, respectively). CONCLUSIONS: Basic preoperative evaluation by comprehensive ultrasound imaging combined with age and Ca125 level has proved highly accurate for prediction of unexpected malignancies. Neither novel markers nor new imaging techniques provide better information that allow clinicians to assess the feasibility of the planned surgery; consequently, the risk of inadvertent cyst rupture during laparoscopy may be significantly decreased in selected cases.

Tu-be or not tu-be: that is the question about serous ovarian carcinogenesis.

Our understanding of the early natural history of epithelial ovarian carcinoma is limited by the access to early lesions as the disease is very often diagnosed at advanced stages. The incessant ovulation theory from the last century that indicated the ovary as the site for the initiation of high-grade serous cancers is contrary to the newly emerging idea that ovarian cancer could arise from the distal fallopian tube. In view of the recent pathological and molecular studies, we propose to discuss the genesis of high-grade serous ovarian cancer.

Pancreatic lesions in von Hippel-Lindau disease? A systematic review and meta-synthesis of the literature.

BACKGROUND: von Hippel-Lindau (vHL) disease is a rare condition that leads to characteristic lesions within many different body systems. Pancreatic manifestations of vHL cover a wide spectrum of pathologies, and thus, accurate characterization and management is critical. METHODS: A comprehensive and systematic text word and MeSH search of the medical literature was performed to identify studies where information regarding the prevalence, clinical characteristics, and management recommendations could be extracted. RESULTS: Eleven studies were identified but 2 studies utilized the same data set. Of the 10 remaining studies, a total of 1,442 patients with vHL were available for analysis. Four hundred and twenty patients were examined for any type of pancreatic lesion, 362 for simple cysts or serous cystadenomas (SCAs), and 1,442 for neuroendocrine tumors (NETs). Of the 420 assessed for any pancreatic manifestation of vHL, 252 (60%) had a pancreatic lesion identified. Simple cysts that present as the sole manifestation of pancreatic disease were common and found in 169 of 362 (47%) patients. These are usually asymptomatic and do not normally require intervention. SCAs were reported in 39 of 362 (11%) patients and followed a similar benign course; resection is acceptable in symptomatic patients. NETs were identified in 211 of 1,442 (15%) patients, and 27 of 1,442 (2%) lesions behaved malignantly. Management of NETs depends on size, doubling time, and underlying genetics. Renal cell carcinoma is a characteristic in vHL, but there were no cases of pancreatic metastases identified from the included studies. Adenocarcinomas of the pancreas are not pathogenically linked to vHL. CONCLUSIONS: This review highlights the wide spectrum and high prevalence of pancreatic lesions in vHL. Simple cysts and SCAs are benign, but NETs require careful observation due to their malignant potential.

Comparison of risk of malignancy index (RMI), CA125, CA 19-9, ultrasound score, and menopausal status in borderline ovarian tumor.

OBJECTIVE: The aim of this study was to assess the prognostic values of risk of malignancy index (RMI IV), ultrasound score, menopausal status, and serum CA125 and CA19-9 level in patients with borderline ovarian tumor (BOT). METHODS: Fifty women having borderline ovarian tumor (BOT) and 5O individuals with benign adnexal mass were enrolled in this retrospective study. The sensitivity, specificity, positive predictive values, negative predictive values and diagnostic accuracy of preoperative serum levels of the CA125 and CA19-9, ultrasound findings and menopausal status, and RMI IV were calculated for prediction of discrimination between BOTs and benign adnexal masses and the results were compared. RESULTS: The RMI IV was the best method for discrimination between BOTs and benign adnexal masses and was more accurate than the other parameters. When Receiver Operator Characteristic area under the curves for menopausal status was analyzed, serum CA 125 and CA19-9 level, ultrasound score, RMI IV(CA125), and RMI IV(CA19-9) were, 0.580, 0.625, 0.548, 0.694, 0.734 and 0.711, respectively. The best RMI IV cut-off was found to be 200 for discrimination of benign and BOT lesions. In the RMI formulation, replacing CA125 with CA19-9 didn't affect RMI IV sensitivity and specificity for discrimination. CONCLUSION: Compared to ultrasound, menopausal status, CA-125, CA19-9, the RMI IV was found to be the best predictive method for differentiation of BOTs from benign adnexal masses. RMI IV cut-off value of 200 is suitable for differentiation of benign and BOT's.

[Borderline ovarian tumors and global radiation in relation with climate change impact]. / Tumorile ovariene cu potential malign scazut si radiatia globala.

UNLABELLED: There is limited information on borderline ovarian tumor detected intra-surgically and its most favorable treatment in relation with global radiation and climate changes. AIM: To study the pre-surgery and intra-surgery differentiation criteria of borderline ovarian tumors from invasive carcinoma, and to make a very complex analysis of the frequency, distribution, and variation in time of global radiation, temperature, and precipitation in North-East Romania. MATERIAL AND METHOD: The 54 patients (age range 20-78 years, mean age 46 years) included in this study had borderline ovarian tumors surgically treated during the last 22 years (January 1988 - December 2009) at the 4th Gynecological Clinic at Iasi, and representing 4.87% of the total 1107 ovarian tumors detected and treated during this interval. The histological types were: serous (18 cases), mucinous (27 cases), mixed (8 cases), and Brenner tumor (1 case). In order to analyze the impact of climate changes on borderline ovarian tumors a thorough study on the frequency of global radiation in relation with climate changes based on data recorded in the last 55 years was also carried out. RESULTS: The distribution of these cases depending on when surgery was performed was analyzed. In our study the frequency of ovarian borderline tumors (4.87%) is lower than in similar reports in the literature being due, in our opinion, to the influence of global radiation in relation with climate changes. CONCLUSIONS: In our study global radiation is probably responsible for a progression to invasive carcinoma in 0.7% of the borderline ovarian tumors.

A rare cause of hemosuccus pancreaticus: primary splenic artery aneurysm ruptured into pancreatic serous cystadenoma.

Hemosuccus pancreaticus is a rare clinical condition defined as bleeding into the pancreatic duct from a peripancreatic artery. We present here a 57-year-old woman admitted to our clinic with abdominal pain, tar-colored stool and confusion. Further investigations were done because of severe anemia. Abdominal computerized tomography revealed intraabdominal hematoma. Laparotomy was performed, which confirmed that intraabdominal haemorrhagia had occurred with the rupture of a splenic artery aneurysm into a pancreatic serous cystadenoma, which ruptured into the abdomen because of high pressure. This is an interesting case diagnosed with multidisciplinary approaches.

Pancreatic involvement in Von Hippel-Lindau disease.

BACKGROUND: Involvement of the pancreas in Von Hippel-Lindau disease that is a tumor predisposing syndrome mentioned in literature with some morbid and mortal progression. AIMS: For evaluation the faith of the pancreatic involvement in VHL disease we analysed our patient population with VHL disease. MATERIALS AND METHODS: 12 of the 56 patients that were evaluated in our institute with the diagnosis of Von Hippel-Lindau disease had pancreatic involvement. They are periodically examined for 5 years follow up period. Their retrospective analysis was accomplished. RESULTS AND CONCLUSIONS: Pancreatic involvement in our patient population disclosed lesions that were multicysts or serous cystadenomas. During follow up period, we did not observe significant morbidity related to pancreatic involvement. Repeated radiological examination of pancreatic lesions disclosed insignificant modifications such as slight increase or decrease in size. Whereas we considered morbidity and mortality related to renal and central nervous system pathologies in VHL disease. Shortly, even pancreatic involvement in VHL disease requires close clinical follow up, morbidity and mortality in this case is not severe as in renal and the central nervous system involvement.

Esophagogastric varices due to arterioportal shunt in a serous cystadenoma of the pancreas in von Hippel-Lindau disease.

Von Hippel-Lindau (VHL) disease is an autosomal dominant inherited disorder characterized by extensively vascularized tumors and cysts in specific organs. Angiogenesis is a striking future of VHL disease with its characteristic cysts and well-vascularized tumors. The hypervascular nature of VHL lesions has been linked to the overproduciton of vascular endothelial growth factor (VEGF) through increased expression of hypoxia inducible factor-1alpha (HIF-1alpha). Here we describe a rare case of VHL disease with esophageal and gastric varices due to arterioportal shunt in a serous cystadenoma of the pancreas, which, upon immunohistochemical examination, exhibited HIF-1alpha and VEGF expression. Rupture of esophageal varices was successfully treated with endoscopic injection sclerotherapy.

Obligate roles for p16(Ink4a) and p19(Arf)-p53 in the suppression of murine pancreatic neoplasia.

Epithelial tumors of the pancreas exhibit a wide spectrum of histologies with varying propensities for metastasis and tissue invasion. The histogenic relationship among these tumor types is not well established; moreover, the specific role of genetic lesions in the progression of these malignancies is largely undefined. Transgenic mice with ectopic expression of transforming growth factor alpha (TGF-alpha) in the pancreatic acinar cells develop tubular metaplasia, a potential premalignant lesion of the pancreatic ductal epithelium. To evaluate the cooperative interactions between TGF-alpha and signature mutations in pancreatic tumor genesis and progression, TGFalpha transgenic mice were crossed onto Ink4a/Arf and/or p53 mutant backgrounds. These compound mutant mice developed a novel pancreatic neoplasm, serous cystadenoma (SCA), presenting as large epithelial tumors bearing conspicuous gross and histological resemblances to their human counterpart. TGFalpha animals heterozygous for both the Ink4a/Arf and the p53 mutation showed a dramatically increased incidence of SCA, indicating synergistic interaction of these alleles. Inactivation of p16(Ink4a) by loss of heterozygosity, intragenic mutation, or promoter hypermethylation was a common feature in these SCAs, and correspondingly, none of the tumors expressed wild-type p16(Ink4a). All tumors sustained loss of p53 or Arf, generally in a mutually exclusive fashion. The tumor incidence data and molecular profiles establish a pathogenic role for the dual inactivation of p16(Ink4a) and p19(Arf)-p53 in the development of SCA in mice, demonstrating that p16(Ink4a) is a murine tumor suppressor. This genetically defined model provides insights into the molecular pathogenesis of SCA and serves as a platform for dissection of cell-specific programs of epithelial tumor suppression.

Clear cell endocrine pancreatic tumor mimicking renal cell carcinoma: a distinctive neoplasm of von Hippel-Lindau disease.

The dominantly inherited von Hippel-Lindau disease is characterized by clear cell neoplasms in various organs including the kidney and pancreas. Determination of primary versus metastatic lesion in this setting can be a diagnostic dilemma. The authors present five cases of clear cell endocrine pancreatic tumor (EPT) closely mimicking renal cell carcinomas in five patients with a family history or histologic evidence of von Hippel-Lindau disease. In fact, two of these tumors were confused with metastatic renal cell carcinoma by fine-needle aspiration. All five tumors had a component of clear cells arranged in nests, cords, and tubules with central hemorrhage separated by thin-wall vessels resembling renal cell carcinoma. However, these tumors also exhibited cords and festoons and a gyriform pattern suggestive of an endocrine neoplasm, and expressed chromogranin and synaptophysin. Vascular invasion was identified in four tumors, one of which metastasized. The concurrent primary renal cell carcinomas and the multicentric microcystic adenomas found in three patients did not show reactivity for the neuroendocrine markers. Focal clear cell change was noted in only one of 29 endocrine pancreatic tumors arising in patients without von Hippel-Lindau disease. Eleven metastatic renal cell carcinomas in the pancreas did not show immunoreactivity with the endocrine markers. Clear cell EPTs closely mimicking renal cell carcinoma are distinctive neoplasms of von Hippel-Lindau disease. In contrast to clear cell EPT, metastatic renal cell carcinoma does not express neuroendocrine markers and lacks neurosecretory granules by electron microscopy. Von Hippel-Lindau disease should be strongly suspected in patients with renal cell carcinoma, clear cell EPT, and multifocal microcystic serous adenomas.

[Variety of pancreatic lesions observed in von Hippel-Lindau disease. Apropos of 8 cases]. / Variété des lésions pancréatiques observées au cours de la maladie de von Hippel-Lindau. Présentation de 8 cas.

Von Hippel-Lindau's disease is a rare genetic disease, with an autosomal dominant mode of inheritance, characterised by the development of several tumours, such as haemangioblastoma of the central nervous system and retina, renal cysts or carcinoma and pheochromocytoma. Several pancreatic lesions, mainly represented by multiple cysts, are also encountered. We report here 8 cases of pancreatic involvement in patients affected with von Hippel-Lindau's disease. It consisted of multiple cysts (3 cases), serous cystadenoma (2 cases), endocrine tumour (1 case), haemangioblastoma (1 case) and ductal adenocarcinoma (1 case). Diagnosis of a rare lesion of the pancreas (multiple cysts, serous cystadenoma or vascularized tumour) in a young patient may lead to search the other lesions of von Hippel-Lindau's disease and to undergo a familial inquiry in order to propose a multidisciplinary approach for patients affected by the disease.

Two cases of ovarian tumours in women who had undergone multiple ovarian stimulation attempts.

Concerns have been raised recently about the possible association between superovulation and ovarian cancer. In order to contribute to the limited literature on this important issue, two cases of ovarian tumours in women who had undergone multiple ovulation inductions are presented. In the first case, the patient had secondary anovulatory infertility. She was treated with human menopausal gonadotrophin (HMG) alone and in combination with clomiphene citrate or buserelin for six cycles. She then underwent ovarian stimulation with buserelin/HMG in the long protocol for in-vitro fertilization (IVF) and embryo transfer. In preparation for a new IVF/embryo transfer attempt, 8 months later, the screening ultrasound revealed a cystic formation of the left ovary and an enlargement of the right. During laparotomy, both ovaries were found to bear large tumours (approximately 6 x 5 x 4 cm) which were removed. Histological examination showed that they were epithelial tumours (serous-papillary cystadenomas) of borderline malignancy. The patient conceived spontaneously 1.5 years after the operation. In the second case, the patient presented with secondary anovulatory infertility. She underwent ovulation induction with clomiphene/HMG and with buserelin/HMG in the long protocol, and intra-uterine insemination with husband's spermatozoa and conceived (singleton pregnancy). She was delivered by Caesarean section, during which a cystic tumour of the left ovary was removed. Histological examination revealed a benign mucous cystadenoma of the ovary.(ABSTRACT TRUNCATED AT 250 WORDS)

Well-differentiated serous neoplasms of the ovary.

Serous neoplasms of the ovary, which constitute the largest subgroup of the surface epithelial tumors, cluster into three distinctly clinicopathologic groups: benign neoplasms, which are architecturally noncomplex, confined to the ovary, and composed of cytologically bland cells; carcinomatous neoplasms, which have spread beyond the ovary and are cytologically malignant; and an intermediate group, which raises serious problems in taxonomy, differential diagnosis, and prognosis. This chapter focuses on differential diagnosis, emphasizing the authors' experience as well as reports from other investigators.