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534Background: With the increasing practice of infertility treatments, concerns were raised about the long-term effects of hormonal ovarian stimulation, especially regarding the risk of breast, endometrial and ovarian cancer. We evaluated the long term cancer incidence in women enrolled into fertility programs from 1980 to 2005. Methods: This is a retrospective cohort study of consecutive women entered into fertility programs in 4 italian centers operating in areas covered by Cancer Registries. Eligibility criteria included premenopausal woman aged 20 to 41 years, who received at least 1 cycle of ovarian stimulation in the context of an Assisted Reproductive Technology (ART) treatment. The primary endpoint was breast cancer (BC) incidence; secondary endpoints were incidence of cervical, endometrial and ovarian cancer. Cancer incidence was assessed by linkage with databases of Cancer Registries. The relationship between ovarian stimulation and cancer incidence was assessed using region specific standardize...

The special types of breast cancer seem to have not only distinct morphological features but also distinct biological features. Women diagnosed with a first primary invasive breast cancer in the 2004–2005 period were identified through Tuscan Cancer Registry. Information on age, tumor size, lymph node status, histological type and grade, hormonal receptors, HER2 immunohistochemical expression were collected. Five subtypes were defined: luminal A, luminal B HER2+, luminal B HER2−, triple negative, and HER2 positive. The association between the histological type and molecular subgroups was assessed by a Fisher’s exact test, and a multinomial logistic regression model was used. Out of 1,487 patients, 34 % were luminal A subtype, 25 % luminal B HER2−, 11 % luminal B HER2+, 19 % triple negative, and 10.2 % HER2+; 58.5 % of cancers were ductal NOS types. With luminal A as reference, histological types distribution was significantly different between the subgroups. Mucinous, tubular, and cribriform histotypes were found among luminal A cancers more than in other subgroups; all medullary carcinomas were triple negative cancers. Pathological stage at diagnosis was more advanced, and histological grade was lower among subgroups other than luminal A. Significant association between breast cancer histotypes and molecular subgroups was found.

In a population-based screening program, a percentage of tumors remain undetected; these tumors comprise a heterogeneous group, and they are more likely to have adverse prognostic features. The aim of this study was to identify differences in biological characteristics of screen-detected versus interval breast cancers in a population-based screening program according to molecular subtypes.We analyzed the population-based data from a long-running screening program in the area of Florence. Data on screening history and on age, T and N status, grade, histotype, hormonal status and Ki-67 and HER2 expression were retrieved. Subtypes of breast cancer were defined on the expression of ER, PR, Ki-67 and HER2: luminal A if ER/PR+, HER2- and Ki6714 %, luminal B (HER2 negative) if ER/PR+, HER2- and Ki67 ≥14 %, luminal B (HER2 positive) if ER/PR+ and HER2+, triple negative if ER/PR-and HER2-, HER2 positive if ER/PR- and HER2+. Association between molecular subtypes and mode of detection will be evaluated by a logistic regression model adjusted for the potential confounding variables.Information about biomarkers was known for 277 cases, 211 screening-detected and 66 interval cancers. Among interval cases, the triple-negative cancers were more represented than luminal A (OR = 3.52; CI, 1.112-11.13; p = 0.0319), while the proportion of HER2+ was quite similar (OR = 1.57; p = 0.4709).Although made on a small number of cases, our results suggest a difference in distribution of molecular subtypes according to mode detection, confirming the results of earlier studies.

to evaluate the excess risk in the deaths due to suicide in a huge case-series of cancer patients and in particular in a group with recent diagnosis.observational cohort.population-based study based on 136,105 patients of the cancer registry of Tuscany Region, incident during 1985-2005, 42,321 of whom diagnosed during 2000-2005.standardised mortality ratio (SMR) of suicide by sex, age, prognosis, time since diagnosis and period of incidence.deaths due to suicide were 0.2% of all the deaths observed in the cohort of patients. Overall cases, 1985-2005, showed a SMR of 1.47 (p0.05), it was higher than expected for men (SMR =1.50), for subjects older that 54 years, especially for cancers with poor prognosis (SMR=2.27), particularly during the first year after diagnosis (SMR=2.87) but also in the following years. Cases diagnosed in 2000-2005 had a SMR=1.19 (n.s.), confirmed the high risk for the age 55-64 years (SMR=2.27), for cancers with worse prognosis (SMR=3.23) and during the first year after diagnosis (SMR=2.64). Trend analysis showed that the excess in the risk of suicide death among cancer patients decreased over time (p=0.042).although suicide is not one of the major cause of death among cancer patients, we confirmed that those patients had a higher risk than the general population. SMR higher than expected were documented for the age 55-64 years, for cancers with poor prognosis and during the first year after diagnosis. Trend analysis shows that excess in the risk of suicide death among cancer patients is decreasing over time. This may be due, among other possible explanations, to the relevant development of the palliative care system in the area based both on hospices and on home care. Although suicide deaths are rather rare, their prevention among cancer patients is still a priority, due to its likely depressive etiology and to the effects on the family and on the health system.

The aim of this study is to evaluate the prognostic values of some biological parameters in a population based series of female breast cancer patients. Through the Tuscan Cancer Registry all the invasive breast cancer cases diagnosed during the period 2004–2005 in the provinces of Florence and Prato, central Italy, were retrieved. Molecular subtypes were analyzed defined by immunohistochemical markers, by age, tumor size, lymph node status, histotype, grade of differentiation and proliferative marker. Out of 1487 patients 70.3% were luminal A subtype (ER/PR + HER2-), 15.6% luminal B (ER/PR + HER2+), 8.1% triple negative (ER/PR-HER2-), 6.0% HER2+ (ER/PR-HER2+); the 3 year survival rates were 93.3%, 89.5%, 86.3%, 82.7% respectively (p < 0.001). Analysis of survival by the Cox proportional hazards model showed an independent prognostic value of molecular classification. Our study revealed significant differences in clinicopathological characteristics among breast cancer molecular subtypes and confirmed their prognostic independent role.

The objective of this study was to evaluate the time trend of melanoma thickness in a population-based case series. All invasive (n=2862) and in-situ (n=605) cutaneous melanoma incident cases diagnosed in 1985-2004 were retrieved from the Tuscany Cancer Registry, central Italy. Standardized (European population) incidence rates were computed for four periods: 1985-1989, 1990-1994, 1995-1999, 2000-2004, and for Breslow thickness classes (or =1, 1.01-2.00,2 mm). The annual percent change (APC) of the standardized rates was computed. Thickness was evaluated on the basis of sex, age, morphology type, site and period of time. Median thickness was evaluated by means of a nonparametric K-sample test. The incidence rate of melanoma rose significantly for both invasive (APC=+5.1%) and in-situ lesions (APC=+11.1). The sex distribution of patients with invasive melanoma did not change over time (mean male/female ratio 0.95). The mean age at diagnosis did not change (57.2 years; SD=17.2 years). From 1985-1989 to 2000-2004 the median value of thickness decreased from 1.68 to 0.8 mm (P0.001). Within the Breslow categories the median value of thickness decreased significantly for thin melanomas (or =1 mm) but not for intermediate (1.01-2.00) or for thick melanomas (2 mm). Among the most common melanoma types, the median thickness decreased for superficial spreading melanomas but not for nodular melanomas. Over time, the incidence of melanoma has increased notably and the median thickness has decreased. However, median thickness has decreased only among thin melanomas, whereas it has not changed for thick melanomas, most of which are of the nodular type.

Objectives: We analysed our experience in primary malignant chest-wall tumours (PMCWTs) with an emphasis on a new reconstruction technique and on survival. Methods: From 1998 to 2008, 41 patients (23 (56%) male, mean age 48 years) with PMCWTwere operated in our unit: chondrosarcoma n = 25; osteosarcoma n = 8; Ewing’s sarcoma n = 2; other n = 6. We performed nine sternectomies and 32 lateral chest-wall resections (median number of ribs resected = 3.5). Resections were extended to the lung (n = 2), diaphragm (n = 3), vertebral body (n = 3), scapula (n = 1) and upper limb (n = 1). Stability was obtained by a prosthetic material, rigid and non-rigid and a muscular flap. As non-rigid material, we mostly used a polytetrafluoroethylene patch (n = 24). In the past 2 years, two patients (one total sternectomy and one wide anterior chest-wall resection) were reconstructed with a rigid system composed of mouldable titanium connecting bars and rib clips (Strasbourg Thoracic Osteosyntheses System — STRATOS, MedXpert GMbH, Heitersheim, Germany). A muscular flap was added in 12 patients (29.3%). Results: There was no perioperative mortality or significant morbidity and all patients were extubated within first 24 h. At a mean follow-up of 60.5 months (range 4—130 months), the overall 5- and 10-year survival was 61% and 47%, respectively. In the chondrosarcoma group, 5- and 10-year survival was 80%. Conclusions: Wide resection with tumour-free margins is necessary in PMCWT to minimise local recurrence and to contribute to longterm survival. The STRATOS system, developed for chest-wall replacement, allows a firm reconstruction, simple to handle and to fix, avoiding instability or paradoxical movement also in wide chest-wall resections. # 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

The purpose of this study was to characterize patients diagnosed with synchronous primary carcinomas of the endometrium and ovary. Between 1985 and 2002, 46 patients with synchronous primary carcinomas of the endometrium and ovary were identified. Clinical and pathological information was obtained from the database and pathological reports. Kaplan-Meier survival analysis, log rank tests of survival differences, and multivariate Cox regression analysis were performed. Median age at diagnosis was 55 years. Twenty-one patients (46%) had an endometrioid histology both of their endometrial and ovarian cancers. Patients with younger age, high uterine differentiation grade, and early-stage ovarian cancer had a more favorable prognosis than those with older age, low grade of differentiation, and advanced stage disease. The Cox proportional hazards model analysis indicates that young age and high grade of differentiation are independent prognostic factors. In this series of patients, women with synchronous primary cancer of the endometrium and ovary were young; the survival rate was greater in patients aged less than 50 years and in patients with an early stage. No significantly different survival between patients with endometrioid carcinoma and patients with non-endometrioid carcinomas was detected.

BACKGROUND. To assess the role of cytology in tumor diagnosis and to explore the potential of this technique to improve tumor registry quality, the authors investigated the role of cytology as a diagnostic tool in registry databases. METHODS. Through the Italian Network of Cancer Registry (AIRTum) archive, the authors retrieved tumors diagnosed during the years 1983–2002 from several registries, Varese, Torino, Ragusa, Ferrara, Genova, and the Tuscan Cancer Registry. The authors then analyzed the amount of morphological confirmation by topographic code, distinguishing cytological from histological diagnosis. The authors analyzed, only for the Tuscan Cancer Registry, the amount of morphological confirmation by both histological and cytological diagnosis and demonstrated the variation of cytological confirmation with stage of tumor. RESULTS. The better morphological modality for diagnosis was rarely cytology, particularly among lung and pleural tumors; when considered together with histological analysis, cytology examination was often reported in cervical uterine and breast tumors. The usefulness of cytology increases with tumor stage, particularly in sites where biopsy is performed with difficulty. CONCLUSIONS. Cytology may be useful to improve tumoral characterization in advanced stages or in sites inaccessible for histology; moreover, cytology is useful as an initial detector of pathology, prior to histology. A prospect of improvement in diagnostic cytopathology and the use of ancillary techniques, such as molecular biology, could help clinicians and could increase the accuracy of cancer registration. Cancer (Cancer Cytopathol) 2007. © 2007 American Cancer Society.

The present study evaluates the application of an automatic system for variables coding by means of strings reading in the text of the pathology reports, in the database of the Tuscany Cancer Registry. Incidence data for the years 2000 (n. 6297) and 2001 (n. 6291) for subjects for whom computerised pathology reports were available were included. The system is based on Queries (SQL language) linked to Functions (Visual Basic for Applications) that work on Windows Access. The agreement between original data inputted by the registrars and variables coded by means of automatic reading has been evaluated by means of Cohen's kappa. The following variables were analysed: cancer site (kappa = 0.87 between "manual" and automatic coding, for cases incident in the year 2001), morphology (kappa=0.75), Berg's morphology groups (kappa=0.87), behaviour (kappa=0.70), grading (kappa=0.90), Gleason (kappa=0.90), focality (kappa=0.86), lateralily (kappa=0.36), pT (kappa=0.92), pN (kappa=0.76), pM (kappa=0.28), number of lymph nodes (kappa=0.69), number of positive lymph nodes (kappa=0.70), Breslow thickness (kappa=0.94), Clark level (kappa=0.91), Dukes (kappa=0.74). The system of automatic reading of strings allows to collect a very huge amount of reliable information and its use should be implemented by the Registries.

Cyclooxygenase-2 (COX-2) is the inducible form of the enzyme involved in the first two steps of the prostaglandins and thromboxane synthesis. Up-regulation of COX-2 is demonstrated in tumors where it can modulate tumoral progression, metastasis, multidrug resistance and angiogenesis. Selective COX-2 inhibitors are seen with growing interest in the tumors treatment. This present study reviews the COX-2 expression in 32 primary oligodendrogliomas (24 WHO II; eight WHO III) and two glioblastomas with prominent oligodendroglial features (WHO IV). Immunohistochemical results were compared with survival in order to verify the COX-2 prognostic significance. COX-2 positivity was found in 44% tumors. Median survival of the patients with a COX-2 positive lesion was 37 months; median survival of the patients with a COX-2 negative lesion was 93 months (P = 0.010). Twenty-nine percent WHO grade II tumors, 87% WHO grade III, 50% WHO grade IV resulted COX-2 positive (P = 0.016). In patients affected by WHO grade II oligodendroglioma, median survival was 24 and 96 months, respectively, in COX-2 positive and negative lesions (P = 0.012). In conclusion, even if further studies on different, homogeneous and larger series in vivo are certainly necessary, it is believed that COX-2 could really have a prognostic value and can be considered as a possible therapeutic opportunity.

The vascular lesions in the placenta form a heterogeneous group of possibly interrelated alterations. Gestational age distribution is different for chorangioma, chorangiosis, and chorangiomatosis; the pathogenesis is unclear, and histological features, especially those of chorangiosis and chorangiomatosis, frequently overlap. Chorangiomatosis shows intermediate features between chorangiosis and chorangioma. In this lesion, particularly when multifocal, the presence of small capillaries is similar to chorangiosis, but the gestational age is different from both chorangiosis and chorangioma. We present three cases of chorangiosis examined during one-year routine pathological analysis of placental tissue and report the histological, histochemical, and immunohistochemical features. Furthermore, we go into the difficulty of discerning the villous capillary lesions and the utility of this division, and describe the clinical effects of these lesions on fetal outcome.

BACKGROUND Minoxidil is a K+ channel opener able to cause relaxation of vascular smooth muscles and modify cell growth and cell fate or migration. It is now widely used for its hair growth promoting effects. When locally applied, it is absorbed through the skin and may have systemic pharmacological effects. CASE A 28-year-old white pregnant woman daily applied minoxidil 2% to her scalp because of hair loss. At the 22nd gestational week, after a routine ultrasound test showing significant brain, heart, and vascular malformations of the fetus, pregnancy was interrupted. The placenta had numerous ischemic areas and a discrepancy between gestational age and villi maturation. In the villi, capillaries were increased in number, significantly enlarged, and excessively marginalized. The fetus' heart was increased in volume and had a globose shape, the aorta had a distal stenosis. The sigmoid colon was significantly increased in length and a mesentery commune was present. The brain had enlarged ventricles and abundant hemorrhages. Histological examination showed areas of demyelinization with gliosis, signs of excessive and inappropriate angiogenesis, and capillary rearrangement. CONCLUSIONS Further knowledge on minoxidil-induced fetal toxicity would be beneficial before allowing its use in pregnant women. Birth Defects Research (Part A), 2003. © 2003 Wiley-Liss, Inc.

The authors report a rare meningioma-primary cerebral B cell lymphoma association that occurred in an insulin-dependent type-I diabetic woman. The woman was initially operated on because of meningothelial meningioma of the fronto-basal region, and 2 months later showed a primitive-non-Hodgkin B cell lymphoma, localized in the same area as the meningioma. The published literature on the meningioma-primary cerebral lymphoma association is revised.

We present an unusual case of intracranial plasma cell granuloma in a 70-year-old man with a 6-month history of progressive visual disturbance. The lesion extensively involved the cranial base, extended into the frontal region, and reached the floor of the third ventricle in the suprasellar area. Microscopic examination of multiple diagnostic transsphenoidal biopsies showed an inflammatory proliferation with a predominance of cells that were immunohistochemically determined to be polyclonal plasma cells. Ultrastructural analysis confirmed the presence of numerous mature plasma cells in a mixed inflammatory proliferation. In situ hybridization for Epstein-Barr viral RNA revealed no evidence of viral expression. The patient was treated with steroid therapy and radiotherapy, without any appreciable reduction of the lesion's size. He is alive with persistent severe visual disturbance 14 months after the diagnosis. We discuss the etiopathogenetic, diagnostic, and therapeutic issues related to this entity, and review the literature.

The clinical, histopathological, and ultrastructural features of a cerebellar liponeurocytoma are reported. The tumor, a 3-cm mass localized in the right cerebellar hemisphere, was resected from a 61-year-old man clinically presenting with symptoms of intracranial hypertension. The lesion was composed of small, in some areas closely packed, medulloblastoma-like cells with prominent areas of lipidization phenomena. Moreover, mitoses, cellular atypia, and numerous vascular structures were focally observed. Glial and neuronal differentiation was immunohistochemically noted (glial fibrillary acidic protein, synaptophysin, neurofilaments, and neuron-specific enolase positivity). The p53 oncoprotein was detected in the majority of neoplastic cells and a moderate proliferation activity, evaluated by Mib-1 antibody, was focally appreciated. Ultrastructural study did not show evident neuritic processes, synapses, or dense core neuroendocrine granules. This cerebellar tumor previously called lipidized medulloblastoma and recently renamed cerebellar liponeurocytoma is considered an adult neoplasm with excellent prognosis histologically presenting prominent lipidized areas and, at the immunohistochemical and ultrastructural level, both glial and neuronal differentiation. The present study provides the first description of a less differentiated and histologically more aggressive form of this unusual tumor.

Neurocytoma is an unusual neuronal tumor especially affecting young people. It commonly arises in the ventricles and has a benign outcome. Herein, we report on a rare case of extraventricular neurocytomas (right parietal lobe) in a young girl admitted to hospital for a cranial trauma subsequent to a seizure. The tumor, radiologically well-circumscribed, cystic and enhancing, was surgically excised. The patient, who received no post surgical treatment, is alive and well after 18 months of follow-up. Pathological examination showed a well-differentiated lesion composed of uniform, round cells with perinuclear halos in a neuropil background and immunohistochemically positive for neuronal markers (synaptophysin, neuron-specific enolase, neurofilaments). The authors emphasize the role of the morphological and immunohistochemical evaluations to recognize this rare tumor.

Chordoid glioma is an uncommon low-grade brain neoplasm arising in the third ventricular region, predominantly in middle-aged women. It characteristically shows chordoma-like histologic features and glial fibrillary acidic protein immunoreactivity. We present a case of chordoid glioma in a previously healthy 56-year-old woman admitted to our hospital because of a cranial trauma subsequent to an incidental fall. Radiologic examinations revealed a well-demarcated, partially cystic, enhancing mass at the level of the lamina terminalis. The lesion was surgically removed. The patient remained alive and well 8 months after the surgery. Histologically, the tumor consisted of clusters and cords of epithelioid cells embedded in a mucinous matrix. Lymphoplasmacytic infiltrates and Russell bodies were prominent. Immunohistochemically, the tumor cells were positive for glial fibrillary acidic protein, neurofilaments, and neuron-specific enolase, suggesting a divergent neuronal and glial differentiation. The Ki-67 index was low. The clinicopathologic profile and the differential diagnosis of this tumor are discussed.

Pharyngeal brain heterotopia is a congenital and generally biologically benign lesion. In contrast to brain heterotopia in the nose, the most common site of this lesion, brain heterotopia in the pharynx is very rare. Pharyngeal heterotopic tissue can be composed of various components, i.e., astrocytes, neurons, ependyma or choroid plexus, oligodendrocytes, retina, and, occasionally, neoplastic nodules. In contrast, nasal lesions are often only composed of astrocytes. We report a case of brain heterotopia in the pharyngeal region, diagnosed in a newborn female infant, causing serious respiratory distress. The infant underwent surgical excision of the lesion, and after 1 year of follow-up, she is recurrence-free. The mass, about 3 cm in diameter and showing no connection with encephalic structures, was characterized by numerous papillary structures and areas containing stellate-like or spindle cells focally forming nodules. Moreover, there was inflammatory infiltration, whereas mitoses, hemorrhages, and necroses were absent. Immunohistochemistry revealed a choroid plexus nature of the papillary formations (S-100, cytokeratins, transthyretin and vimentin-positive) and the presence of glial and neuronal cells in the remaining areas (glial fibrillary acidic protein, neuron-specific enolase, neurofilaments, synaptophysin, and S-100 positive). This case report confirms that the presence of choroid plexus is not uncommon and that pharyngeal brain heterotopia is usually benign.