Differential expression of the semaphorin 3A pathway in prostatic cancer.

AIMS: To analyse the expression pattern of the semaphorin 3A (Sema3A) pathway, including the receptor neuropilin 1 (NRP1) and its ligands the 'antitumoral' Sema3A and the 'protumoral' vascular endothelial growth factor (VEGF)in prostatic cancer. METHODS AND RESULTS: tissues were obtained from 120 patients treated by prostatectomy for clinically localized prostatic cancer, and 31 hormone-refractory prostatic cancer (HRPC) samples. Immunohistochemistry was performed on tissue microarrays using antibodies directed against Sema3A, NRP1 and VEGF. Moreover, real-time reverse transcriptase-polymerase chain reaction was performed on frozen prostatic tissue, including normal prostate, clinically localized tumours and HPRC. Sema3A immunoreactivity of the membrane of cancer cells was closely associated with NRP1 expression in clinically localized prostatic cancer, but not in HRPC. In clinically localized cancer, Sema3A expression correlated with lower preoperative prostate-specific antigen (PSA) and pathological stage; NRP1 reactivity was associated with lower PSA and Gleason score, and VEGF reactivity with higher PSA and Gleason score. HRPC displayed higher expression of NRP1 compared with clinically localized cancer, and lower Sema3A immunoreactivity. CONCLUSIONS: These results support the hypothesis that dysregulation of the Sema3A pathway plays a key role in prostatic cancer progression, and suggest a loss of the inhibitory Sema3A autocrine loop in HRPC.

Pineocytoma and pineal parenchymal tumors of intermediate differentiation presenting cytologic pleomorphism: a multicenter study.

Cytologic pleomorphism has been described in a limited number of benign pineal tumors, namely pineocytoma (PC) and pineal parenchymal tumors (PPTs) of intermediate differentiation (PPTID). We examined the clinicopathologic features in a retrospective series of 14 cases (seven females and seven males aged from 10 to 65 years) of pleomorphic PPT. Seven cases were PC, with no mitoses and with areas of tumoral cells forming large pineocytomatous rosettes and other areas with giant cells containing hyperchromatic nuclei. The other seven were PPTID, presenting few mitoses (< or =2), a Ki67 proliferation index between 3% and 7%, and predominantly composed of small neoplastic cells and scattered giant cells, sometimes multinucleated. In the 14 tumors, the proportion of pleomorphic areas was variable. Most tumoral cells showed extensive neuronal differentiation with strong expression of neuron-specific enolase, synaptophysin and neurofilaments. Some of the neoplastic cells expressed S100 protein. The follow-up period ranged from 1.2 to 13 years and only one PC and one PPTID progressed after stereotactic biopsy or incomplete resection. The lack of invasiveness and the low proliferation index of these tumors suggest a benign clinical course despite the marked pleomorphism, the latter of which can lead to upgrading.

The use of impression cytology in the follow-up of severe ocular burns.

AIMS: To evaluate by impression cytology (IC) the expression of the MHC class II inflammatory marker HLA-DR by the conjunctival epithelium, the cytological modifications of the conjunctival surface according to the Nelson's classification, and the eventual correlation between the two after severe ocular burns. METHODS: A total of 24 patients (24 eyes) who presented with severe ocular burns underwent IC. We compared them with 18 healthy eyes. HLA-DR expression was studied by flow cytometry as well as the conjunctival histology evaluated with the Nelson's classification from 2-24 months after the onset of burns. RESULTS: There was a significant upregulation of the expression of HLA-DR in eyes with burns compared to the healthy population at 2 months (p<0.001), 6 months (p<0.001), 12 months (p = 0.019), 18 months (p = 0.0171) and 24 months (p = 0.01766). A significant difference was found between the Nelson grade in the pathological population and those of the healthy population at 2 months (p = 0.0157). HLA-DR upregulation was significantly correlated with the Nelson's grades between 2 months (r = 0.69, p<0.0001) and 6 months (r = 0.61, p = 0.0001). CONCLUSION: The IC technique can act as a useful tool for following-up ocular surface inflammation after severe ocular burns.

Prognosis and histopathologic features in papillary tumors of the pineal region: a retrospective multicenter study of 31 cases.

Papillary tumor of the pineal region (PTPR) is a recently described tumor entity thought to arise from the specialized ependyma of the subcommissural organ. Whereas histologic features of PTPR are well defined, data on the prognostic value of PTPR remain scarce. We therefore investigated clinicopathologic features, including data on progression-free survival and overall survival, in a retrospective series of 31 PTPR. The age of the 14 males and 17 females ranged from 5 to 66 years (median age, 29 years). Histologically, all tumors were characterized by an epithelial-like growth pattern in which the vessels were covered by layers of columnar or cuboidal tumor cells forming perivascular pseudorosettes. Most of the tumor cells showed strong expression of neuron-specific enolase, cytokeratins (particularly CK18), S-100 protein, and vimentin. Most PTPRs examined also expressed microtubule-associated protein-2. Expression of synaptophysin, epithelial membrane antigen, transthyretin, neural cell adhesion molecule, and nestin was encountered in some tumors. Gross total resection could be achieved in 21 of 31 cases; 15 patients received radiotherapy on resection of the primary tumor. Nevertheless, the majority of patients experienced recurrences; 5-year estimates for overall survival and progression-free survival were 73% and 27%, respectively. To conclude, the clinical course of PTPR is characterized by frequent local recurrence, and the value of radiotherapy on disease progression will need to be investigated in future prospective trials.

Sjögren's syndrome with ANCA-associated crescentic extramembranous glomerulonephritis.

A 49-year-old woman with a 1-year history of Sjögren's syndrome was diagnosed with cutaneous leukocytoclastic vasculitis and necrotizing crescentic membranous glomerulonephritis. Antineutrophil cytoplasmic antibodies targeting myeloperoxidase were found. She reported a transient episode of nephritis 4 years earlier. This pattern of kidney disease is not typical of Sjögren's syndrome. Methylprednisolone boluses followed by oral glucocorticoid therapy were given in combination with mycophenolate mofetil. Renal function stabilized after 2 months, and tests for anti-myeloperoxidase reverted to negative.

Papillary tumor of the pineal region in a child: case report and review of the literature.

CASE REPORT: A 13-year-old boy presented with a history of intracranial hypertension. Radiologic studies revealed triventricular hydrocephalus secondary to a space-occupying lesion in the pineal region. Endoscopic third ventriculostomy was performed to treat hydrocephalus, and the lesion was biopsied. Complete resection of the tumor was subsequently performed. After a period of uncertainty, the diagnosis of papillary tumor of the pineal region was established. Tumor bed radiotherapy at a dose of 50 Gy was associated. With a follow-up of 15 months, the postoperative course was satisfactory with return to school and no residual tumor on magnetic resonance imaging. CONCLUSION: Papillary tumors of the pineal region constitute a rare entity, with a difficult diagnosis, an uncertain prognosis, and a high risk of local recurrence; they must be treated by a combination of surgery and radiotherapy. The only identified prognostic factor is the complete or incomplete nature of surgical resection.

Solitary intestinal fibromatosis associated with congenital ileal atresia.

We report for the first time an association between congenital solitary intestinal fibromatosis and intestinal atresia. The spindle cell proliferation showed a high apoptotic index contrasting with a low proliferation rate, suggesting that the tumor may have undergone focal and spontaneous regression, leading to intestinal atresia.