Morphological and morphometric analysis of cutaneous squamous cell carcinoma in patients with recessive dystrophic epidermolysis bullosa: a retrospective study.

BACKGROUND: Recessive dystrophic epidermolysis bullosa is a highly disabling genodermatosis characterized by skin and mucosal fragility and blistering. Cutaneous squamous cell carcinoma (cSCC) is one of the most devastating complications, having a high morbidity and mortality rate. Patients with recessive dystrophic epidermolysis bullosa were reported to have up to a 70-fold higher risk of developing cSCC than unaffected individuals. Immune cells play a role in cancer evolution. OBJECTIVE: The aim of our study was to evaluate immunohistological differences between cSCC in patients with and without recessive dystrophic epidermolysis bullosa. METHODS: A retrospective study of 25 consecutive cases was performed; five were biopsies of cSCC taken from five patients with recessive dystrophic epidermolysis bullosa; as controls we analysed 10 cSCC in subjects without recessive dystrophic epidermolysis bullosa (5 primitive, 3 postburns and 2 postradiotherapy), 5 cSCC in renal transplant recipients and 5 cutaneous pseudoepitheliomatous hyperplasia in patients with recessive dystrophic epidermolysis bullosa. RESULTS: A significant reduction of CD3+, CD4+ and CD68+ between the cSCC in patients with recessive dystrophic epidermolysis bullosa compared to primary cSCC and a significant reduction of CD3+, CD4+, CD8+ and CD20+ were observed in cSCC in patients with recessive dystrophic epidermolysis bullosa compared to secondary cSCC. On the contrary, there was no difference in CD3+, CD8+, CD20+ and CD68+ expression when comparing cSCC in patients with recessive dystrophic epidermolysis bullosa to cSCC in renal transplant recipients. No significant difference was found in size, histopathology, grading, number of mitoses and EGFR expression between the different groups. CONCLUSIONS: Our data show a reduction in immune cell peritumoral infiltration. Considering the well-known evolution of cSCC in patients with recessive dystrophic epidermolysis bullosa, as well as the younger age at diagnosis, it can be assumed that immune dysfunction might contribute to the cSCC aggressiveness in these patients.

Metastatic melanoma of the gallbladder: report of two cases and a review of the literature.

Melanoma is one of the most aggressive and highly metastatic cancers. The most common sites of distant metastases are soft tissues, lung, liver, skin and brain, whereas only few patients develop gastrointestinal metastases. Metastatic involvement of the gallbladder is rare and more often part of a widespread disease than a solitary lesion. The "gold-standard" treatment of metastatic melanoma of the gallbladder remains unclear. We report two cases of patients with past history of cutaneous melanoma who developed visceral metastases. The first patient was asymptomatic and had a widespread disease with metastatic involvement of both the spleen and the gallbladder. The second patient had an isolated metastasis of the gallbladder and complained of upper abdominal pain. The chosen treatment was open cholecystectomy (and splenectomy) in the first case and laparoscopic cholecystectomy in the second. A review of the literature is provided.

"Intestinal-type" mucinous adenocarcinoma of the vulva: a report of two cases.

BACKGROUND: "Intestinal-type" mucinous carcinoma of the vulva is extremely rare with very few cases reported in the literature. CASE REPORT: The authors report two patients who had diagnosis of intestinal-type mucinous adenocarcinoma of the vulva after excisional biopsy. In both cases, restaging was perfomed with total body computed tomography (CT) scan, gastroscopy, and colonoscopy that showed no other site of disease. A radical vulvectomy with bilateral systematic inguinal lymphadenectomy was performed, and in both cases no residual disease was found. A patient developed metastatic (liver, bone marrow) colonic cancer 36 months after primary surgery, received multiple lines of chemotherapy, and died of disseminated disease 18 months after diagnosis. The other patient was found to have dysplastic polyp in the sigmoid colon, and is alive without disease at 39 months after primary diagnosis. CONCLUSION: Intestinal-type mucinous carcinoma of the vulva has a poor prognosis. Strict endoscopic follow-up of the colon is mandatory in such cases, considering the high propensity of associated gastrointestinal (GI) tumors.

Decreased expression of the augmenter of liver regeneration results in increased apoptosis and oxidative damage in human-derived glioma cells.

The mammalian growth factor erv1-like (GFER) gene encodes a sulfhydryl oxidase enzyme, named Augmenter of Liver Regeneration (ALR). Recently it has been demonstrated that ALR supports cell proliferation acting as an anti-apoptotic factor. This effect is determined by ALR ability to support the anti-apoptotic gene expression and to preserve cellular normoxic conditions. We recently demonstrated that the addition of recombinant ALR (rALR) in the culture medium of H(2)O(2)-treated neuroblastoma cells reduces the lethal effects induced by the hydrogen peroxide. Similar data have been reported in the regenerating liver tissue from partially hepatectomized rats treated with rALR. The purpose of the present study was to evaluate the effect of the GFER inhibition, via the degradation of the complementary mRNA by the specific siRNA, on the behaviour of the apoptosis (apoptotic gene and caspase expression and apoptotic cell number) and of the oxidative stress-induced parameters (reactive oxygen species (ROS), clusterin expression and mitochondrial integrity) in T98G glioma cells. The results revealed a reduction of (i) ALR, (ii) clusterin and (iii) bcl-2 and an increase of (iv) caspase-9, activated caspase-3, ROS, apoptotic cell number and mitochondrial degeneration. These data confirm the anti-apoptotic role of ALR and its anti-oxidative properties, and shed some light on the molecular pathways through which ALR modulates its biological effects.

Morphometric and ultrastructural features of the mare oviduct epithelium during oestrus.

Morphometric, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) investigations have displayed regional differences in the mare oviductal epithelium. The entire mucosa of the oviduct was lined with a pseudostratified epithelium, which consisted of two distinct cell types, ciliated and non-ciliated. Ciliated cells were predominant in the three different segments of the oviduct and their percentage increased from fimbriae to ampulla and significantly decreased in the isthmus. SEM revealed in the infundibulum finger-like mucosal folds, some of them interconnected, in the ampulla numerous and elaborated branched folds of the mucosa, whereas the isthmus displayed a narrow lumen, short and non-branched mucosal folds. In the ampulla and isthmus the majority of non-ciliated cells showed apical blebs provided or not of short microvilli. TEM displayed different ultrastructural features of ciliated and non-ciliated cells along the oviduct. Isthmus ciliated cells presented a more electron-dense cytoplasm than in infundibulum and ampulla cells and its cilia were enclosed in an amorphous matrix. The non-ciliated cells of infundibulum did not contain secretory granules but some apical endocytic vesicles and microvilli coated by a well developed glycocalyx. Non-ciliated cells of ampulla and isthmus contained secretory granules. Apical protrusions of ampulla displayed two types of secretory granules as well as occasional electron-lucent vesicles. Isthmus non-ciliated cells showed either electron-lucent or electron-dense cytoplasm and not all contained apical protrusions. The electron-dense non-ciliated cells displayed microvilli coated with a well developed glycocalyx. Three types of granules were observed in the isthmus non-ciliated cells. The regional differences observed along the epithelium lining the mare oviduct suggest that the epithelium of the each segment is involved in the production of a distinctive microenvironment with a unique biochemical milieu related to its functional role.

Liquid-based endometrial cytology: the Florence and Bari experience.

Several diagnostic procedures are available to investigate the endometrium, i.e. sonography, hysteroscopy, biopsy, endometrial curettage and cytology. Among these, endometrial cytology is less commonly utilized. Although the use of cytology in the diagnosis of endometrial adenocarcinoma has already been proposed due to its low cost and simple execution, a general consensus has not been reached. The improvement of the diagnostic capacity of endometrial cytology following the introduction of a liquid-based method suggests that this test should be routinely used in endometrial diagnosis. The main advantages of this method are the reduction in confounding factors, the distribution of cells on a thin layer and the possibility to obtain more slides from the same sample. The aim of this article is to focus on the methodological procedures and diagnostic criteria in liquid-based endometrial cytology based on the experience in two Italian centres: Department of Pathology, University of Bari and Department of Human Pathology and Oncology, University of Florence. The sampling method used by the Bari authors consists in the collection of liquid for uterine distension during hysteroscopy, while the Florence group used an endometrial brush. The sensitivity and specificity at Bari were 75% and 83%, respectively, and were 94-100% and 95-100% at Florence, respectively. Endometrial cytology provided sufficient diagnostic material significantly more often than biopsy. We thus propose that endometrial cytology can be used in routine diagnosis either alone or in association with other diagnostic procedures in order to improve diagnostic accuracy.

The post-cesarean section symptomatic bladder flap hematoma: a modern reappraisal.

The bladder-flap hematoma (BFH) is an unusual complication of the cesarean section (CS) performed by Misgaw Ladach method or Stark CS (performed without peritoneal closure) and it is an usual event after the visceral peritoneal closure performed during the traditional method. A BFH is generally thought of as a blood collection located in a space placed between the bladder and lower uterine segment (LUS), called vescico-uterine space. If, during a Stark CS, pathological fluid collections arise in this space by uterine suture bleeding, these decant into the large peritoneal cavity causing a hemoperitoneum. This last complication can be easily and accurately detectable by ultrasonography, which can be utilised by non-invasive monitoring as a guide for the clinical follow-up. In the authors' experience, the CS by Stark method is associated with a lower febrile and infective morbidity and it is possible also to perform a successful conservative laparoscopy for the BFH management. Laparoscopical treatment of BFH offers to patients the potential clinical benefits of the minimally invasive endoscopical treatments, but it should be reserved for surgeons trained in extensive laparoscopic procedures.

Prognostic implications of NUMB immunoreactivity in salivary gland carcinomas.

The gene numb encodes for a protein (Numb) involved in cell fate decisions in Drosophila, with proposed endocytic and developmental functions in mammalians. The distribution pattern of Numb in human tissues however, has not been fully characterized. We set out to explore the immunohistochemical expression of Numb in normal and neoplastic (28 adenoid cystic and 34 mucoepidermoid carcinomas) salivary glands, and correlated the results with the clinico-pathologic features of the neoplasms. Intense Numb immunoreactivity was detected in normal ductal cells and in a subset of acinar cells. In salivary carcinomas, we detected diffuse and intense Numb immunostaining in 5 adenoid cystic and 8 mucoepidermoid carcinomas. By contrast, the majority of adenoid cystic and mucoepidermoid cancers showed only moderate (14 and 5 cases) or focal staining (9 and 21 cases), respectively. The corresponding expression of Numb mRNA was documented in normal parotid gland and adenoid cystic carcinoma. Numb immunoreactivity was inversely correlated with the histological grade and Ki-67 immunoreactivity of both adenoid cystic and mucoepidermoid carcinomas. In addition, while tumor grade, stage, Ki-67 and Numb immunoreactivity were associated with disease-free survival in univariate analysis, only Numb and Ki-67 immunoreactivities retained independent prognostic significance in multivariate analysis. These data suggest that loss of Numb is implicated in aberrant differentiation programs of salivary gland carcinomas and may serve as a prognostic indicator in patients treated for these neoplasms.

A rare case of choroidal metastasis presented after conservative management of endometrial cancer.

Hematogenous dissemination from endometrial cancer is quite rare. We report a 31-year-old woman who developed choroidal metastasis following conservative management of early-stage endometrial carcinoma. She had received kidney transplantation and was taking steroids and cyclosporine. Three years after hysterectomy for persistent endometrial carcinoma, she developed multiple metastatic disease (to both lungs and right pelvis), and while on treatment with paclitaxel and carboplatin, she complained of a rapid visual deterioration. Ophthalmologic evaluation revealed a metastatic choroidal tumor associated with multiple central nervous system metastases. The patient refused further treatment and died 1 month after diagnosis of choroidal involvement. In conclusion, this is the first reported case of choroidal metastasis from endometrial cancer and highlights the need to consider immunosuppressive treatment as an absolute contraindication to conservative fertility-sparing treatment in gynecological malignancies.

[Embryo and fetal pathology in routine diagnostics: what has changed and what needs to be changed]. / L'embrio-patologia e la patologia feto-perinatale nella diagnostica anatomo-patologica: cosa e cambiato e cosa e necessario cambiare.

The Authors have focused on the most important feto-neonatal and placental diseases in order to develop modern diagnostic tools which can meet the needs of clinicians (obstetricians, gynecologists, and neonatologists) for the best possible management of both the mother and the newborn. Although far from being operational instructions, it should be intended as a programmatic document providing a guideline on the issues that have cropped up in eight years of work of the APEFA group, as well as during several residential and practical classes. First of all, a synopsis is provided of the main issues concerning placental diagnosis in the newborn, as well as in case of fetal loss. A reasoned review is then provided of the main diagnostic criteria in placental pathology, in the light of therapeutical measures toward the mother (monitoring of future pregnancies) and the newborn (management of newborns at risk or with infectious disease). Legal issues in case of fetal distress at the end of pregnancy, neonatal damage and peripartum death have also been discussed with particular attention. Early and late miscarriages have also been separately examined, as well as fetal deaths. For each of these categories, a critical analysis is presented of current issues, followed by some considerations on the development of diagnostic methods and technology, and a modern diagnostic process is then outlined. Reference tables are also provided for diagnostic, auxological parameters, as well as on essential procedures. Issues concerning legal abortions and terminations of pregnancies have also been considered, with particular reference to tests and supplemental genetic and ultrasound examinations, diagnostic questions about malformations and forensic medicine assessments that are often involved with these specific categories. Malformations, fetal distress and growth retardation, sudden fetal and neonatal death, as well as embryo-pathology are all briefly dealt with also with synoptic tables. Diagnostic criteria are thus optimized and specially aimed at solving "human reproduction pathology" issues.

A case of Sertoli-Leydig cell tumor in a postmenopausal woman.

Sertoli-Leydig cell tumor belongs to the group of sex cord-stromal tumors of the ovary. These neoplasms account for less than 0.5% of all ovarian tumors and are more often encountered in young women between the ages of 20 and 30 years who usually become virilized. We described an unusual case of Sertoli-Leydig cell tumor in a postmenopausal women who presented with a solid right pelvic mass, a large amount of ascites, and laboratory tests revealing an elevated CA125, all suggesting a pelvic malignancy. Although five similar cases of postmenopausal women with Sertoli-Leydig cell tumor of ovary have been reported in the literature, we believe that this is an useful addition to the literature.

[Varix of the extra-hepatic portion of the fetal intra-abdominal umbilical vein: pathogenesis, prenatal sonographic diagnosis, and perinatal outcome]. / La varice del tratto intra-addominale extra-epatico della vena ombelicale fetale: patogenesi, diagnosi ecografica prenatale ed outcome perinatale.

AIM: Aim of the study was to investigate pathogenesis, diagnosis, and prognosis of the fetal intra-abdominal umbilical vein varix (FIUVV). METHODS: We reviewed all cases of FIUVV diagnosed in our hospital from August 1999 to December 2002. The umbilical vein was considered dilated when the measurement was above 2 standard deviation of the mean for gestational age. In all cases prenatal echocardiography and post-natal karyotype were performed. Our cases were also considered in the light of all the cases of FIUVV reported in literature. RESULTS: FIUVV was diagnosed in 5 cases between 22 and 37 weeks' gestation, among an unselected population of pregnant woman. Karyotype was normal in all cases; an apparently isolated septal ventricular defect was present in one patient. No obstetrical complications due to the presence of FIUVV (i.e. thrombosis) were associated. CONCLUSIONS: In our case series no obstetrical complications, and only one mild fetal anomaly were present. In literature an high association has been reported between the presence of FIUVV and fetal anomalies and/or obstetrical complications. Fetal echocardiography and detailed US study of fetal anatomy is needed to exclude associated anomalies. Karyotype should be offered only when other fetal anomalies are present. In presence of FIUVV, a close fetal monitoring by serial color Doppler and ultrasonographic examinations should be performed.

Confocal laser scanning microscope study of terminal villi vessels in normal term and pre-eclamptic placentas.

The aim of this study was to compare immunocytochemical confocal scanning laser microscopy measures of villus capillarization in control placentas with pre-eclamptic ones. Accordingly, placentas from normal term pregnancies (n=3) and cases of late-onset pre-eclampsia without intrauterine growth retardation (IUGR) featuring normal uterine artery Doppler (n=3) were analyzed by confocal scanning laser microscopy (CSLM), which is a powerful technique for obtaining three-dimensional reconstructions of any kind of blood vessels (arteries, veins, capillaries). A laser light beam is used in order to detect CD34 antibody-related immunofluorescence, which is a marker of endothelial cells. Villus capillarization was assessed by estimating the following parameters: number of pixels, mean, maximum and minimum immunofluorescence amplitude. Our results show a significant hyper-ramification of the capillary loop in pre-eclamptic placentas, featuring irregular profile and narrow lumina. Such findings support the hypothesis that several agents causing angiogenesis and vasoconstriction affect villus vessels in pre-eclamptic placentas, thus promoting a lasting condition of fetal hypoxia by decreasing endothelial surface and materno-fetal exchanges.

[Unusual presentation of metastatic osteosarcoma as a giant duodenal polyp. A case report]. / Osteosarcoma metastatico polipoide del duodeno. descrizione di un caso ad insolita presentazione.

INTRODUCTION: Osteosarcoma is a malignant bone neoplasm with an usually high metastatic potential. Besides the common metastatic sites such as lungs, bone, and pleura, metastases to unusual sites such as liver, brain and regional lymph nodes have also been reported with increasing frequency; among them, gastrointestinal metastases represent an extraordinarily rare event in the natural history of this neoplasia. MATERIALS AND METHODS: We describe a case of a 27 year old man, who was diagnosed with a grade IV osteoblastic osteosarcoma of the left tibia and submitted to 5 courses of pre-surgical chemotherapy; later he underwent tibial resection with implantation of a prosthesis, followed by 2 further courses of adjuvant chemotherapy. Five years after the patient presented with melena and acute anemia; during endoscopic examination, a large bleeding duodenal polyp was found, so a surgical resection of the gastric antrum, duodenum, head of the pancreas, main bile ducts and gallbladder was performed. The surgical specimen was formalin fixed and paraffin embedded, and sections obtained by the blocks were stained with haematoxylin-eosin; immunohistochemical and ultrastructural analysis were performed. RESULTS: Microscopically, the tumor mass showed a mostly fasciculated architecture, composed of spindle and epithelioid cells in a scarce fibromyxoid stroma, featuring large areas of coagulative necrosis and small foci of sclerohyalinosis. Tumor cells featured large vesciculous nuclei, with a few prominent nucleoli; no foci of osteoid matrix were detectable. The ultrastructural analysis revealed small calcified electron-dense depots both in the perinuclear cytoplasm and in the extracellular collagen matrix compatible with an "early osteoid formation". Due to alteration of the natural history of the tumor induced by multiagent chemotherapy, the rate of metastases of osteosarcoma to unusual sites has been increasing. We report the 9th case of a gastrointestinal metastasis of osteosarcoma reported thus far, and only the second one arising in the duodenum. Both the histological features and the immunohistochemical findings were not suggestive for osteosarcoma metastases because the tumor appeared dedifferentiated; in our case the combination of electron microscopy and clinical history played a pivotal role to establish the final diagnosis.

Neoadjuvant chemotherapy in advanced ovarian cancer: a case-control study.

The aim of this study was to compare the outcome of patients with advanced ovarian carcinoma treated with neoadjuvant chemotherapy (NACT) with those treated conventionally with primary debulking surgery. From 1994 to 2003, all consecutive cases of advanced-stage epithelial ovarian carcinoma treated with NACT at the University of Bari were identified. A well-balanced group of women who underwent primary debulking surgery followed by platinum-based chemotherapy was selected as controls. Kaplan-Meier and Cox proportional hazards analyses were used to determine the predictors for survival. Thirty women with advanced-stage epithelial ovarian carcinoma were treated with NACT and compared to 30 patients who underwent primary debulking surgery. Patients in the NACT were significantly older and had a poorer performance status compared to the controls. However, no statistical difference was observed in overall disease-specific survival (P= 0.66) and disease-free survival (P= 0.25) between the two groups. Although patients in the NACT group are significantly older and have a poorer performance status, this treatment modality does not compromise survival. Prospective randomized trials comparing NACT to conventional treatment to determine the quality of life and cost/benefit outcomes are now appropriate for women presenting advanced epithelial ovarian cancer.

[Morphometric and histological evaluation of uterine leiomyomas treated with GnRH agonists or progestational agents]. / Valutazione istologica e morfometrica di leiomiomi dell'utero trattati con analoghi del GnRH o progestinici.

Both gonadotropin-releasing hormone (GnRH agonists) and progestational agents are commonly used in order to reduce the size of uterine leiomyomas before surgery. So far, little is known about the histologic changes underlying such shrinkage mechanism. Probably the conflicting data on this subject are due to the qualitative and subjective methods used by most previous reports. In this study we analyzed 42 leiomyomas from patients treated with GnRH agonists (14 different patient samples), patients treated with progestational agents (14 different patient samples) and age-matched control patients (14 different patient samples), using qualitative (light microscope analysis) and quantitative (morphometric analysis by a specific software) methods. We assessed the following parameters: areas of necrosis, areas of hyalinization, vasal density, vasal thrombi, thickness of vasal walls, size of vasal lumina, cell density, maximum nuclear diameter, maximum cytoplasmic diameter, mitotic index on each sample. The analysis showed that leiomyomas from women treated with GnRH agonist exhibited broader areas of necrosis, greater cell density, and wider vasal lumina, while those from women treated with progestational agents exhibited thicker vasal walls than the other two groups, respectively. In conclusion, our results suggest that vasal wall changes are the basis of leiomyomas shrinkage after GnRH agonist therapy.