Contrast sensitivity in patients with Beta-thalassemia major and sickle cell disease under regular transfusions and treatment with desferrioxamine.

PURPOSE: Evaluation of contrast sensitivity in patients with beta-thalassemia major and sickle cell disease which undergo regular transfusions and chelation therapy with desferrioxamine (DFX). MATERIALS AND METHODS: We studied contrast sensitivity in 48 eyes (24 patients) with beta-thalassemia major (group A) and in 42 eyes (21 patients) with sickle cell disease (group B), compared to 60 eyes of 30 healthy individuals (control group). Contrast sensitivity was measured using B-VAT II-SG Mentor Video Aquity Tester. RESULTS: We found no statistically significant difference between group A and group B in any spatial frequency, while we found statistically significant differences between group B and control group in all spatial frequencies studied. Between group A and control group we found statistically significant differences in spatial frequencies of 2.3, and 6 cyc/deg. CONCLUSION: DFX causes retinal alterations that may explain reductions in contrast sensitivity function and justifies regular evaluations that may allow early detection of visual function deterioration.

Juvenile idiopathic arthritis-associated uveitis: Data from a region in western Greece.

OBJECTIVE: To evaluate the characteristics and visual prognosis of juvenile idiopathic arthritis-associated uveitis (JIA). METHODS: A retrospective review was performed on 56 patients who met the criteria for JIA to identify those with uveitis and related complications. Patients were referred to and were examined in the Pediatric Department of the University Hospital of Ioannina, between 1995 and 2007. RESULTS: The prevalence of JIA-associated uveitis was high. Despite this and the related complications, the final visual outcome was satisfactory in the majority of the cases. Authors did not observe any correlation between prognosis and sex, age at the onset of uveitis or arthritis, pattern of arthritis, or positivity for antinuclear antibodies (ANA). CONCLUSION: We found a remarkably high prevalence of uveitis and related ocular complications in 7 (28%) of the patients, and the rate of poor visual outcome was 12%.

Orbital cavernous hemangioma in an infant with intracranial lesions: a case report.

INTRODUCTION: Cavernous hemangiomas of the orbit are benign vascular malformations, commonly encountered in adults. Although they are infrequent in pediatric population their diagnosis and course are of a great significance, mainly because they can cause visual disturbances such as amblyopia that can ensue, and secondarily due to their cosmetic and psychological effect. Special attention is required in follow up and treatment. Additionally, a systemic evaluation is necessary in order to discover asymptomatic lesions elsewhere in the body carrying a risk of complications. CASE PRESENTATION: The authors describe the clinical course, diagnosis, therapeutic approach and prognosis of an infant with an orbital cavernous hemangioma accompanying intracranial lesions. A female infant 18 months of age, presented with a mass in the left upper eyelid, causing blepharoptosis. Preoperative magnetic resonance imaging and angiography of the brain and the orbits showed a hemangioma of the left upper eyelid and intracranial lesions to the left temporal fossa and the pons. At the age of 2 years and 8 months she was admitted again due to severe eyelid swelling, intense strong pain, exophthalmos and collateral ophthalmoplegia. Two operations were performed to remove the orbit mass. Histological examination, showed characteristics of cavernous hemangioma. CONCLUSION: The atypical presentation of cavernous orbital hemangioma with early infantile onset, merits attention.

Mucinous breast carcinoma presenting as Paget's disease of the nipple in a man: a case report.

INTRODUCTION: Male breast cancer is rare compared to its female counterpart representing less than 1% of cancer in men. Moreover, mucinous carcinoma of the male breast is an extremely rare histological subtype of malignancy. Paget's disease of the nipple is rarely observed in males. CASE REPORT: Herein, we describe a unique case of an 86 years old man with mucinous breast cancer presenting as Paget's disease of the nipple. According to the immunohistochemical evaluation the neoplastic cells were positive for estrogen (ER) and progesterone receptors (PR). CONCLUSION: To our best knowledge this is the first case of mucinous male breast cancer presenting as Paget's disease of the nipple.

The E-cadherin adhesion molecule and colorectal cancer. A global literature approach.

The E-cadherin-catenin complex plays a crucial role in epithelial cell cell adhesion and in the maintenance of tissue architecture. Down-regulation of E-cadherin expression correlates with a strong invasive potential, resulting in poor prognosis in human carcinomas. Progress has been made in understanding the interaction between the different components of this protein complex and how this cell-cell adhesion complex is modulated in cancer cells. The present study is an update of the role of E-cadherin in human colorectal cancer. It emphasizes new features and the possible role of the complex in clinical practice, discussed in the light of references obtained from the Medline database from 1987 to 2007. In colorectal carcinomas, changes in E-cadherin expression have been correlated with tumour size, histopathology and differentiation, but results are still inconsistent. Further studies may yield greater insight into the early molecular interactions critical to the interaction between adhesion molecules and tumour initiation and progression. This should aid the development of novel strategies for both prevention and treatment of cancer.

Findings of an experimental study in a rabbit model on posterior capsule opacification after implantation of hydrophobic acrylic and hydrophilic acrylic intraocular lenses.

PURPOSE: Study on cell growth on the posterior capsule after implantation of hydrophobic acrylic (Acrysof SA 60 AT) and hydrophilic acrylic (Akreos Disc) intraocular lenses (IOL) in a rabbit model and comparison of posterior capsule opacification (PCO). METHODS: Phacoemulsification was performed in 22 rabbit eyes, and two different IOL types (Acrysof SA60 AT and Akreos Disc) were implanted. These IOLs had the same optic geometry (square edged) but different material and design. Central PCO (CPCO), peripheral PCO (PPCO), Sommering's ring (SR) formation, type of growth, extension of PCO, cell type, inhibition, and fibrosis were evaluated three weeks after surgery. Histological sections of each globe were prepared to document the evaluation of PCO. RESULTS: No statistically significant difference was observed between a hydrophobic acrylic IOL and a hydrophilic acrylic IOL in relation to the CPCO, PPCO, type of growth, extension, cell type, inhibition, and fibrosis. Statistically significant difference was observed in relation to the formation of SR with Acrysof SA 60 AT group presenting more SR than Akreos Disc group. CONCLUSION: PCO was not influenced by the material of the IOL or the design of the haptics of the IOLs we studied.

Orbital metastasis from verrucous carcinoma of the oral cavity: case report and review of the literature.

A rare case of metastatic verrucous carcinoma (VC) of the oral cavity is presented. The patient was referred to the Ophthalmology Department due to diplopia. The patient reported history of diagnosis of verrucous squamous carcinoma in the oral cavity occuring 6 years earlier that although excised presented several recurrences. The lesion metastasized to local lymph nodes and after being characterized as inoperable the patient underwent thirty-seven sessions of radiation therapy. Two months after completion of radiation therapy, the patient underwent an orbital CT scan that revealed a mass with morphological features consistent with secondary involvement of the orbit from the known VC. Although treated with chemotherapy, the patient died 5 months later. No other case of this entity, which usually presents as a slow-growing lesion enlarging with direct extension rather than frank invasion, metastasizing to the orbit has been reported in relevant literature.

Alterations of the p53, Rb and p27 tumor suppressor pathways in diffuse large B-cell lymphomas.

Diffuse large B-cell lymphomas (DLBCL) display defects in cell cycle and apoptosis regulation. Therefore, the immunohistochemical expression patterns of the proteins p14, p21, Hdm2 and cyclin D2 were analyzed in relation to the previously reported expression of other major cell cycle proteins (p53, Rb, p16, p27, Ki-67 and cyclins A, B1, D2, D3 and E), apoptosis-associated proteins (bcl2, bcl-xl, bax, bak, bad and bid) and the B-cell differentiation immunophenotypes. Expression of the proteins p14, p21, Hdm2 and cyclin D2 was observed in 62/71 (87%), 22/76 (29%), 35/74 (47%) and 11/77 (14%) cases, respectively. Immunohistochemical alterations of the p53 (p53-Hdm2-p21-p14), Rb (Rb-p16-cyclin D [D2 or D3]) and p27 (p27-cyclin E) pathways were found in 56/77 (73%), 53/79 (67%) and 54/79 (68%) cases, respectively. Concomitant alterations of the p53-Rb, p53-p27 and Rb-p27 pathways were found in 40/77 (52%), 38/77 (50%) and 36/79 (46%) cases, respectively. Three concomitant alterations of the p53-Rb-p27 pathways were found in 28/79 (35%) cases. The main findings of the present study were the following: alterations of the p27 pathway were associated with higher expression of Ki-67 (p = 0.023); concomitant alterations of the p53Rb pathways and the p53-p27 pathways were associated with higher expression of cyclin A (p = 0.015 and p = 0.021, respectively) and concomitant alterations of the p53, Rb and p27 pathways were associated with higher expression of cyclin A (p = 0.013). Since cyclin A supports DNA replication, centrosome duplication and mitosis, these findings indicate that concomitant alterations of the p53, Rb and p27 pathways in DLBCL may have cooperative effects resulting in increased neoplastic cell proliferation. This might explain, at least partially, the association between concurrent aberrations of the p53, Rb and p27 pathways and aggressive clinical behavior in DLBCL.

Primary mantle cell lymphoma of the conjunctiva: a case report.

Primary non-Hodgkin's lymphomas of the conjunctiva are uncommon. They are almost exclusively extranodal marginal zone B-cell lymphomas/mucosa-associated lymphoid tissue lymphomas. In this study, we report an extremely rare case of conjunctival mantle cell lymphoma in a 78-year-old man, presenting as a unilateral epibulbar mass.

Mucosa-associated lymphoid tissue lymphoma of the lacrimal gland--a case report.

MALT lymphoma of the ocular adnexa, an indolent B-cell lymphoma, rarely affects the lacrimal gland. The case of a 73-year-old man with ptosis and edema of the left upper eyelid, due to lacrimal gland swelling, is presented. Clinical evaluation and imaging examination led to excision biopsy. The mass histopathology, presenting organized lymphoid tissue, composed mainly of small B-cells, accompanied by immunophenotypic characteristics, was compatible with MALT lymphoma. Treatment with monoclonal antibody against CD-20 achieved a successful long-term disease control (4 years). The diagnostic approach is described and the pathological features and clinical signs of this rare entity are discussed, based on recent literature. The indolent clinical course of this lymphoma, either remaining localized or disseminating to other mucosal sites, is a distinct characteristic affecting prognosis.

Matrix metalloproteinases in carcinoma of unknown primary.

BACKGROUND: The purpose was to study proteolysis-related molecules, matrix metalloproteinase-2 (MMP-2) and MMP-9 and tissue inhibitor of metalloproteinases-1 (TIMP-1), in carcinoma of unknown primary (CUP). METHODS: Paraffin-embedded tumor material from 75 patients diagnosed with CUP was used. Tumor histologies were adenocarcinoma (77%), undifferentiated carcinoma (19%), and squamous cell carcinoma (4%) and patients were categorized into favorable (62%) and unfavorable (38%) subsets. The tissue expression of MMP-2, MMP-9, and TIMP-1 was assessed by use of specific monoclonal antibodies and evaluated by means of a visual staining score. The expression of molecules studied was analyzed against clinicopathological data. RESULTS: MMP-2 was found expressed in 69% (strong expression in 49%), MMP-9 in 49% (strong in 36%), and TIMP-1 in 79% (strong in 44%) of studied cases. The expression of MMP-2 correlated positively with MMP-9. TIMP-1 was significantly higher in unfavorable compared with favorable tumors and was associated with a shorter survival of patients (7.5 vs. 12 mos). No other associations were detected. CONCLUSIONS: MMP-2, MMP-9, and TIMP-1 are widely expressed in CUP, suggesting an essential role of proteolysis in these tumors. TIMP-1 may be considered a possible marker of poor prognosis in CUP patients.

Angiogenesis in cancer of unknown primary: clinicopathological study of CD34, VEGF and TSP-1.

BACKGROUND: Cancer of unknown primary remains a mallignancy of elusive biology and grim prognosis that lacks effective therapeutic options. We investigated angiogenesis in cancer of unknown primary to expand our knowledge on the biology of these tumors and identify potential therapeutic targets. METHODS: Paraffin embedded archival material from 81 patients diagnosed with CUP was used. Tumor histology was adenocarcinoma (77%), undifferentiated carcinoma (18%) and squamous cell carcinoma (5%). The tissue expression of CD34, VEGF and TSP-1 was assessed immunohistochemically by use of specific monoclonal antibodies and was analyzed against clinicopathological data. RESULTS: VEGF expression was detected in all cases and was strong in 83%. Stromal expression of TSP-1 was seen in 80% of cases and was strong in 20%. The expression of both proteins was not associated with any clinical or pathological parameters. Tumor MVD was higher in tumors classified as unfavorable compared to more favorable and was positively associated with VEGF and negatively with TSP-1. CONCLUSION: Angiogenesis is very active and expression of VEGF is almost universal in cancers of unknown primary. These findings support the clinical investigation of VEGF targeted therapy in this clinical setting.

A rare case of primary malignant melanoma of the scrotum diagnosed by fine-needle aspiration.

We report a case of a 55-yr-old man with malignant melanoma of scrotum. He was referred to our Hospital with a complaint of gradual focal enlargement of the scrotum in a period of 3 yr. On physical examination, a pigmented, poorly marginated mass, with central necrosis was observed. A fine-needle aspiration (FNA) of the lesion was performed. Cytological examination revealed highly cellular smears, containing malignant cells, dispersed or arranged in loose aggregates. Cellular morphology and characteristics were identical to those of malignant melanoma arising elsewhere in the skin. The immunocytochemical study revealed positivity of neoplastic cells for anti-melanoma monoclonal antibody (HMB-45) antigen. Histological confirmation finally was provided after wide excision of the lesion. We emphasize the difficulties in differential diagnosis considerations and diagnostic pitfalls of scrotal lesions.

Proliferation profile of classical Hodgkin's lymphomas. Increased expression of the protein cyclin D2 in Hodgkin's and Reed-Sternberg cells.

There is accumulating evidence that Hodgkin's and Reed-Sternberg cells of classical Hodgkin's lymphomas (cHL) display multiple and concurrent alterations in different pathways and checkpoints of the cell cycle. However, the expression of cyclin D2 and its relation to other major cell cycle proteins has not been analyzed in cHL. The aim of the present study was to assess expression of cyclin D2, Ki67, cyclin A, cyclin B1, cyclin D1, cyclin D3, cyclin E, p53, Rb, p16 and p27 proteins in order to gain further insight into the proliferation profile of cHL. Overexpression of cyclin D2 in Hodgkin's and Reed-Sternberg cells was detected in 64/89 (72%) cases of cHL. This finding, in view of recent in vitro data showing that constitutive activation of nuclear factor (NF)-kB could upregulate cyclin D2 expression in part via signal transducer and activator of transcription (STAT)-5a, suggests that induction of cyclin D2 expression may support the proliferation of Hodgkin's and Reed-Sternberg cells. In addition, the present study showed that (1) increased p27 expression status was significantly correlated with higher levels of cyclin A expression (P=0.048) and (2) increased p53 expression status was significantly correlated with higher levels of cyclin A (P<0.001) and cyclin B1 (P=0.040) expression. The association between increased p27 and p53 expression status and higher expression levels of G2/M cyclins suggests that the impairment of the growth inhibitory activity of the p27 and p53 tumor suppressor pathways may promote the proliferation of Hodgkin's and Reed-Sternberg cells.

Diffuse large B-cell lymphomas with germinal center B-cell-like differentiation immunophenotypic profile are associated with high apoptotic index, high expression of the proapoptotic proteins bax, bak and bid and low expression of the antiapoptotic protein bcl-xl.

The aim of this study was to analyze the relations between differentiation immunophenotypes and the status of apoptosis and proliferation in diffuse large B-cell lymphomas. Therefore, the bcl6/CD10/MUM1/CD138 differentiation immunophenotypic profiles were studied in relation to (a) the apoptotic index, (b) the apoptosis-associated bcl2 family proteins bcl2, bcl-xl, bax, bak, bad and bid, (c) the proliferation index (Ki67) and (d) the cell cycle proteins cyclin A, cyclin B1, cyclin D3, cyclin E, p53, Rb, p16 and p27 in 79 cases of diffuse large B-cell lymphomas. Two major differentiation immunophenotypic profiles were distinguished: the germinal center B-cell-like profile; 31 cases (bcl6+/CD10+/-/MUM1-/CD138-: 29 cases and bcl6-/CD10+/MUM1-/CD138-: two cases) and the nongerminal center B-cell-like profile (bcl6+/-/CD10-/MUM1+/CD138-); 48 cases. The expression of bax, bak and bid and the apoptotic index were significantly higher in the germinal center B-cell-like profile than in the nongerminal center B-cell-like profile (P=0.045, 0.018, 0.003 and 0.034, respectively). In contrast, the expression of bcl-xl was significantly lower in the germinal center B-cell-like profile than in the nongerminal center B-cell-like profile (P=0.026). The expression of bcl6 and CD10 showed significant positive correlation with the expression of bax (r=0.659, P<0.001 and r=0.240, P=0.033, respectively), bak (r=0.391, P<0.001 and r=0.233, P=0.039, respectively) and bid (r=0.652, P<0.001 and r=0.238, P=0.035, respectively) and significant negative correlation with the expression of bcl-xl (r=-0.536, P<0.001 and r=-0.250, P=0.029, respectively). The expression of MUM1 showed significant negative correlation with the expression of bax (r=-0.276, P=0.014) and bid (r=-0.266, P=0.018) and significant positive correlation with the expression of bcl-xl (r=0.238, P=0.037). The above findings indicate that diffuse large B-cell lymphomas with germinal center B-cell-like immunophenotypic profile are associated with increased apoptosis status, high expression of the proapoptotic proteins bax, bak and bid and low expression of the antiapoptotic protein bcl-xl.

Fine-needle aspiration of secondary malignancies of the penis: a report of three cases.

Metastatic malignancy to the penis is an uncommon clinicopathologic entity, with only 300 cases reported since 1870. Of the reported cases, 75% were secondary to genitourinary primary tumors. Priapism is the most frequent symptom, although dysuria, ulceration, and node formation have also been described. We report three cases of penile metastatic involvement from primary tumors in the urinary bladder (two cases) and prostate (one case), respectively. Fine-needle aspiration (FNA) cytology from the penile nodules was performed in each case. The smears in all cases were highly cellular, and atypical neoplastic cells were observed singly, in clusters, or in papillary formations. The cells were pleomorphic with hyperchromatic nuclei and prominent nucleoli. Immunocytochemistry was performed for keratin 8 and 18 and prostatic-specific antigen (PSA). In conclusion, although it has rarely been used as a diagnostic tool, FNA of the penis can be proved effective and safe in diagnosing a suspected secondary malignancy.