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Summary: Background Telomere length is correlated with cellular ageing and immortalization processes. In some human cancers telomere length measurement has proved to be of diagnostic and prognostic value. Results comparable with the traditional terminal restriction fragment length determination by Southern blotting have been obtained in metaphase and interphase cells in some studies by fluorescence in situ hybridization (FISH) analysis; FISH additionally allows for the quantification of telomeres at the cellular level.:Objectives In this study, 32 melanocytic lesions were analysed by FISH, aiming at investigating possible telomere differences among various benign and malignant lesions and correlation with telomerase activity (TA) level.:Methods FISH was performed on paraffin sections from six common naevi, eight Spitz naevi, 12 melanomas, six melanoma metastases and nine control samples of normal skin. Telomere mean maximum diameter (Feret max), area and number per nuclear area were calculated by image analysis on fluorescent images elaborated through KS400 and in situ imaging system (ISIS) for FISH analysis programs. Mean TA level was also calculated in all lesions and correlated with telomere parameters.:Results Telomere number per nuclear area was significantly lower in melanomas and metastases than in benign common and Spitz naevi and in control skin (7·24 ± 3·3; 6·11 ± 3 vs. 14·46 ± 5·6; 16·92 ± 7·8; and 12·59 ± 3·4, respectively; P < 0·001). No significant differences were found for the other telomere parameters. In common and Spitz naevi, telomere number was positively correlated with Feret max (P = 0·046 and P < 0·0001, respectively). TA was significantly higher in melanomas and metastases than in the other groups (70·18 ± 25·2; 105·07 ± 30 vs. 2·16 ± 2·4; 2·99 ± 2·1; 2 ± 1·2, respectively; P &#x2264... [ABSTRACT FROM AUTHOR]

Vascular Endothelial Growth Factor (VEGF)-D is a member of the VEGF family of angiogenic growth factors that activate the Vascular Endothelial Growth Factor Receptor (VEGFR)-2 and VEGFR-3, which are mainly expressed in blood and lymphatic vessels. Here we have analyzed by using monoclonal antibodies, the expression of VEGF-D and its cognate receptor VEGFR-3 in normal and pathologic bone marrow and lymph node biopsies. This analysis revealed that VEGF-D is expressed in B cells of the germinal centers, scattered B and T blasts, myeloid progenitors, acute leukemia, several types of non Hodgkin lymphoma, and classical Hodgkin's lymphoma. In normal tissues VEGFR-3 was only expressed in fenestrated capillaries of bone marrow and in lymphatic vessels of lymph nodes, while in VEGF-D expressing tumors newly formed vessels, but not malignant cells, showed high VEGFR-3 expression. These data suggest that VEGF-D could contribute to leukemia and lymphoma growth via the induction of angiogenesis in bone marrow and lymphoid tissues.

Mature cystic teratoma (dermoid cyst) is the most common benign germ cell tumor of the ovary, accounting for approximately 30% of all ovarian tumors. Malignant transformation is rare; the most frequent transformation reported is to squamous-cell carcinoma in 80% of cases, whereas transformation to adenocarcinoma is described in about 7% of cases. We report a case of malignant transformation to mucinous adenocarcinoma arising from respiratory-like epithelium in a mature teratoma of the ovary.

CDK9 is a member of the CDC2-like family of kinases. Its cyclin partners are members of the CYCLIN T family (T1, T2a, and T2b) and CYCLIN K. The CDK9/CYCLIN T1 complex is very important in the differentiation programme of several cell types, controlling specific differentiation pathways. Limited data are available regarding the expression of CDK9/CYCLIN T1 in haematopoietic and lymphoid tissues. The aim of this study was to analyse the expression of the CDK9/CYCLIN T1 complex in lymphoid tissue, in order to assess its role in B- and T-cell differentiation and lymphomagenesis. CDK9/CYCLIN T1 expression was found by immunohistochemistry in precursor B and T cells. In peripheral lymphoid tissues, germinal centre cells and scattered B- and T-cell blasts in interfollicular areas expressed CDK9/CYCLIN T1, while mantle cells, plasma cells, and small resting T-lymphocytes displayed no expression of either molecule. CDK9/CYCLIN T1 expression therefore appears to be related to particular stages of lymphoid differentiation/activation. CDK9 and CYCLIN T1 were highly expressed in lymphomas derived from precursor B and T cells, from germinal centre cells, such as follicular lymphomas, and from activated T cells (ie anaplastic large cell lymphomas). Hodgkin and Reed-Sternberg cells of classical Hodgkin's lymphoma also showed strong nuclear staining. Diffuse large B-cell, Burkitt's lymphomas, and peripheral T-cell lymphomas, among T-cell lymphoproliferative disorders, showed a wide range of values. No expression of CDK9 or CYCLIN T1 was detected in mantle cell and marginal zone lymphomas. However, at the mRNA level, an imbalance in the CDK9/CYCLIN T1 ratio was found in follicular lymphoma and diffuse large B-cell lymphomas with germinal centre phenotype, and in the cell lines of classical Hodgkin's lymphomas, Burkitt's lymphomas, and anaplastic large cell lymphoma, in comparison with reactive lymph nodes. These results suggest that the CDK9/CYCLIN T1 complex may affect the activation and differentiation programme of lymphoid cells. The molecular mechanism through which the CDK9/CYCLIN T1 complex is altered in malignant transformation needs to be elucidated., (Copyright 2004 Pathological Society of Great Britain and Ireland)

Background: Solitary fibrous tumor (SFT) is a rare spindle cell tumor that arises most often in the visceral pleura; however, a review of the literature shows at least 31 cases occurring in the orbit., Methods: A retrospective case series of three patients with orbital SFT: a 50-year-old man, observed in 1997, with an angioma-like lesion in the upper half of the orbit causing osteolysis of the orbital roof; a 24-year-old man, observed in 1992, with a superotemporal mass in the right orbit occupying the lacrimal gland region, firstly diagnosed as schwannoma, recurring 4 years after dacryoadenectomy; a 70-year-old man, with a retrobulbar mass diagnosed on a biopsy as hemangiopericytoma, recurring and infiltrating the orbital roof 4 years after surgery., Results: A review of the literature and presentation of three cases of SFT which showed infiltration of the orbital roof and/or recurrence., Conclusions: Our cases provide evidence of how orbital SFT can behave aggressively and mimic other orbital tumors, thus making mandatory the consideration of this relatively new entity in common clinical practice as well as careful follow-up. Their aggressive growth is unusual, described in only 6 of the 31 cases so far reported in the literature. Immunohistochemistry is of importance for the diagnosis, since CD34 immunoreactivity is peculiar to SFT.

Objective: To test CD-34 immunoreactivity in stromal cornea cells in normal and pathologic samples obtained from penetrating keratoplasty., Design: Prospective, consecutive histopathologic human tissue study., Participants and Controls: One hundred two cornea buttons from patients with different diseases, submitted for cornea transplant, were examined. Controls were expired corneas from healthy donor patients who died (n = 4), and globes enucleated for primitive intraocular neoplasias, that is, retinoblastomas (n = 8), and malignant choroidal melanomas (n = 2)., Methods: The expression of CD-34 in stromal cornea cells was examined by immunohistochemistry analysis. Other immunohistochemical stains included an endothelial cell marker (CD-31), common leukocyte antigen, and alpha-smooth muscle actin., Main Outcome Measures: Different diseases that may cause blindness and require penetrating keratoplasty have been tested for CD-34 immunoreactivity., Results: In control corneas, keratocytes present strong and consistent CD-34 immunoreactivity. Diseases leading to the loss of transparency and penetrating keratoplasty, such as keratoconus, herpes keratitis, trauma, and heredofamilial dystrophies, are associated with focal or diffuse loss of CD-34 expression, whereas pseudophakic bullous keratopathy and Fuchs' endothelial dystrophy show normal CD-34 immunoreactivity in most cases and patchy unstained stromal areas in a few cases., Conclusions: Scar tissue formation in the cornea, as in herpes keratitis and trauma, is always associated with loss of CD-34 immunoreactivity, which may otherwise be a primary event in keratoconus and heredofamilial dystrophies. Both in the pseudophakic bullous keratopathy and Fuchs' endothelial dystrophy, CD-34 immunoreactivity may be normal or lost, hence these two diseases may be considered as one and part of the same group with regard to CD-34 expression, as revealed by immunohistochemistry analysis.

Cyclooxygenase-2 (COX-2) is known to be expressed in rat brain and up-regulated by ischemia. The administration of COX inhibitors before as well as soon after the ischemic insult reduces the extension of cerebral damage in rats. Overexpression of COX-2 has also been shown in the ischemic brain of adult human patients, while no information concerning COX-2 expression in neonatal ischemia is available. Intrapartum asphyxia and perinatal brain injury may result in cerebral palsy, mental retardation or epilepsy. COX-2 expression in the brain of neonates delivered after severe birth asphyxia was investigated using immunohistochemistry. Meningeal vessel walls of term and preterm babies widely expressed COX-2 immunoreactivity, as did periventricular large vessels in preterms. A number of brain cells (mature and immature cortical, periventricular and basal ganglia neurons, and oligodendrocytes of the cerebral white matter in brains from term neonates) also expressed COX-2. The present findings suggest that COX-2 may take part in enhancing neonatal brain damage via different mechanisms, such as those involving excitotoxicity and production of reactive oxygen species.

The aim of this study was to analyse the morphological, kinetic and molecular characteristics of low-grade (LGD) and high-grade dysplasias (HDG) in comparison with intestinal metaplasia type III (IM III) and normal mucosa (NM) as well as with early gastric cancer of the intestinal type (EGC). Based on this it was verified whether these categories are distinct, progressive proliferative steps from IM III to LGD, HGD and EGC, according to Correa's sequence of events. The morphology, mitotic index (MI), and the apoptotic index (AI) were assessed. The E-cadherin expression (E-Cad), matrix-metalloproteinase activity (MMP2), and the number of microvessels (NV) were also evaluated. Among the categories, MI increases from NM to IM III and LGD, and from LGD to HGD and EGC, while AI continues to increase also from HGD to EGC. E-cad decreases from NM to EGC, although not significantly from LGD to HGD; MMP2 is significantly more expressed only in EGC. Three groups are obtained by means of cluster analysis. The first group includes all the NMs and IM IIIs, all except 1 LGD, about half of HGDs, and 1 EGC. E-Cad is highly expressed, MMP2 and angiogenesis are low, the proliferative activity is low and mitoses are partly balanced by apoptoses. The second group includes some EGCs and HGDs and is characterised by a very high proliferative activity and cell death; there is an initial loss of cell adhesion, an increase of MMP2 and NV. The third group includes the majority of EGCs, but also 1 HGD: it has intermediate MI and AI, the lowest expression of E-Cad, the highest expression of MMP2 and the most numerous microvessels. These results underscore the necessity of evaluating each case individually within the same singular category of Correa's sequence. The use of kinetic and molecular parameters in addition to the morphological analysis may give important information on the behaviour of the various lesions.

Solitary fibrous tumors (SFTs) are infrequent soft tissue neoplasms which are usually benign and surgically curable. However, their behavior is not always predictable, although several clinical and pathological criteria of malignancy have been established. In many cancers, including some soft tissue tumors, telomerase activity (TA) has been shown to be a new reliable pathological marker of malignancy. Overexpression of some cyclins is associated with higher degrees of malignancy and predictive of the clinical course. In this study, we evaluated TA, mitotic and apoptotic indices (MI, AI), and the expression of Ki-67, cyclins D1 and A in five typical and two clinicopathologically atypical SFTs, the latter two of which had also recurred. High TA was demonstrated in the two atypical cases, which also showed a higher labeling index to Ki-67, as well as higher cyclin D1 and A expression, and either none or very few apoptoses. We suggest that TA, Ki-67, cyclin expression, and AI be evaluated in SFTs as possible adjunctive pathological criteria of behavior.

Chorioamnionitis represents the leading cause of preterm birth and related pathologic conditions as well as of fetal death and frequently occurs in symptom-free mothers. Recent radiologic findings have indicated that thymus size is significantly reduced in preterm infants born to mothers with subclinical, histologically proven chorioamnionitis. However, an accurate morphologic description of the thymus gland in fetuses and neonates with chorioamnionitis is lacking, although it is known that infection and other stress processes may cause lymphocyte depletion in the thymuses of infants and older babies (acute stress involution). We describe morphologic modifications in the thymus of fetuses with histologically proven chorioamnionitis and newborn infants with chorioamnionitis and proven sepsis. The main findings included (1) decreased organ volume (ANOVA, P < .0024); (2) reduced corticomedullary ratio (P < 10(-6)); (3) significant changes in the relationship between thymic parenchyma and thymic interstitial tissue with resulting increased organ complexity (P = .03); (4) severe reduction of thymocytes; and (5) other degenerative processes such as monocyte/macrophage infiltration of Hassall's bodies. These results indicate that chorioamnionitis, with or without sepsis, is associated with significant morphologic modifications in the thymus. We wish to note that the described thymic pathology is only one aspect of the fetal systemic inflammatory response syndrome with which chorioamnionitis is associated.