LH/hCG-Receptor Expression May Have a Negative Prognostic Value in Low-Risk Endometrial Cancer.

INTRODUCTION: A 51 year-old woman was diagnosed with endometrial cancer (EC) and underwent surgical staging. Pathological evaluation showed a 2 cm × 1 cm G2 endometrioid EC with a 30% myometrial deep invasion (FIGO Stage 1A). The patient was classified as low risk of recurrence, and no adjuvant treatment was offered. Six months after surgery, the patient developed an early vescico-vaginal recurrence, and chemotherapy treatment was started. Few months later, a subsequent involvement of vaginal wall, ileum, and omentum was detected, and the patient underwent second surgery. BACKGROUND: LH/hCG-receptor (LH/hCG-R) expression has been previously reported to be associated with an invasive phenotype in EC cells. Moreover, in a preclinical mouse model of EC behaves as a prometastatic molecular device. DISCUSSION: We analyzed the expression level of LH/hCG-R in cancer specimens collected during surgeries. Molecular and immunohistochemical analyses showed a strong expression of both mRNA and protein for LH/hCG-R in all specimens. CONCLUSION: LH/hCG-R expression may be assessed together with other clinicopathological parameters in order to better predict the risk of recurrence in low-risk EC patients. Further clinical trials are warranted in order to validate LH/hCG-R as biomarker in EC.

Women With Primary Sjögren Syndrome and With Non-Sjögren Sicca Syndrome Show Similar Vulvar Histopathologic and Immunohistochemical Changes.

The goal of this study was to evaluate the characteristics and the prevalence of histopathologic and immunohistochemical changes in vulvar biopsies, in women with Primary Sjögren Syndrome (pSS) and non-Sjögren Sicca Syndrome (nS-SS). Twenty-one women with pSS and 11 with nS-SS (investigated by xerophtalmia and xerostomia tests, biopsy of minor salivary glands, gynecological history, and gynecologic symptoms score) underwent vulvar biopsies, evaluated for histopathologic and immunohistochemicalchanges, and compared with those obtained from 26 patients with lichen sclerosus. An inflammatory infiltrate was present in 31/32 biopsies (96.9%); biopsies from pSS patients showed a mild infiltrate in 10 cases and a moderate infiltrate in 11 cases; and patients with nS-SS had a mild infiltrate in 8 biopsies and moderate infiltrate in the other 2 biopsies. By immunohistochemistry, the infiltrate was composed predominantly of T lymphocytes (CD3), CD20 B cells were sparse and mean CD4:CD8 T-cell ratio was 1.5. No differences were observed between the grading of the inflammatory infiltrate in nS-SS and pSS; no correlation was shown between vulvar inflammatory infiltrate score (mild or moderate) and salivary glands inflammatory score. No differences were found in gynecologic symptoms, as well as in clinical and demographical characteristics between patients with mild and those with moderate vulvar inflammatory score. A higher prevalence of moderate inflammatory infiltrate was observed in biopsies from women with lichen sclerosus than in pSS and nS-SS patients (61.5% vs. 27.5%, P=0.02). Women with pSS and nS-SS show a high and similar prevalence of vulvar inflammatory infiltrate. A gynecologic evaluation is needed both in pSS and nS-SS to assess genital involvement and, eventually, to address a therapy targeted to genital symptoms.

Abdominal Wall Endometriosis on the Right Port Site After Laparoscopy: Case Report and Literature Review.

BACKGROUND: Endometriosis can be intrapelvic or, rarely, extrapelvic. Endometriosis involving the rectus abdominis muscle on the trocar port site is a rare event; until now, only 16 cases have been reported in the literature. The majority of cases were associated with previous abdominal surgery such as diagnostic laparoscopy, cyst excision, appendectomy, myomectomy, or cholecystectomy. We review all the reported cases of this unusual form of extrapelvic endometriosis. CASE REPORT: We report a new case of abdominal wall endometriosis at the trocar port site in the rectus abdominis muscle in a woman who had undergone 2 laparoscopies for endometriosis in the 3 years before coming to our attention. The diagnosis was made by sonography. We performed a surgical resection of the lesion with a free macroscopic margin of 5-10 mm. CONCLUSION: Endometriosis should be considered in the differential diagnosis of any abdominal swelling. In our experience, surgery is the treatment of choice.

HPV-related cervical disease and oropharyngeal cancer.

Human papillomavirus (HPV), especially HPV 16, is associated with the development of both cervical and oral cancer. We show the case of a woman affected by HPV-related cervical disease and oropharyngeal squamous cell carcinoma (OPSCC). A 41-year-old woman arrived at our Colposcopy Center following an abnormal Pap smear result (ASC-H) and a diagnosis of moderate cervical dysplasia obtained by a cervical biopsy. She underwent a colposcopy that showed a cervical abnormal transformation zone grade 2. A laser conization was performed in November 2010. Histology reported a moderate/severe dysplasia. The cone resection margins were free. Follow-up colposcopy and cytology were negative. The HPV testing showed an infection by HPV 16. In October 2012, the patient presented to the Head-Neck ER after episodes of hemoptysis; a lesion was found in the left tonsillar lodge. A biopsy was performed with a result of squamous cell carcinoma with low-grade differentiation. The HPV testing detected a high-risk HPV and the immunohistochemical analysis was positive for p16. She was treated by chemotherapy and brachytherapy. She was followed at the head-neck center with monthly visits with oral visual inspection that showed complete absence of mucosal abnormalities. HPV-related OPSCC and cervical precancerous/cancerous lesions have significant similarities in terms of pathogenesis. They are both caused largely by HPV 16, as in the present case. In conclusion, because of this association found in literature and in our case, we think that women with HPV cervical lesions should have regular surveillance for oropharyngeal cancer, whereas women with OPSCC should be encouraged to have diligent cervical screening.

Angiocentric glioma: clinical, morphological, immunohistochemical and molecular features in three pediatric cases.

Angiocentric glioma is a rare slow growing tumor. It is associated to seizures and is mainly diagnosed in children and young adults. We describe the clinical, histo-pathological and molecular (IDH1, IDH2 and BRAFV600E mutational status) features in 3 children, 2 girls (2- and 11-years old) and 1 boy (10-years old). The tumors were located at the left temporo-parietalinsular, left parieto-occipital and left subcortical paramedian region respectively. All 3 patients were operated. Two patients are well at 2 and 16 months of follow-up while the third still suffers from seizures at 7 years of follow-up. Histologically, all tumors were composed of spindle-shaped cells showing a prominent tendency to align around the blood vessels and to grow in the subpia space creating palisade-like structures. In one case the tumoral cells were embedded in a mucoid matrix and some microcalcifications were observed. In all the cases the neoplastic cells diffusely immunostained for GFAP and S-100. Punctate dot-like intracytoplasmic staining for EMA was also observed. All tumors resulted in wild type for the mutations investigated. Owing to the rarity of angiocentric glioma, we believe that each new case should be recorded to produce a better clinical, pathological and molecular characterization of this lesion.

Glioneuronal tumor with neuropil-like islands: clinical, morphologic, immunohistochemical, and molecular features of three pediatric cases.

Glioneuronal tumors with neuropil-like islands are rare. The 1st reported cases were localized in the cerebral hemispheres of adults, showed homogeneous histopathologic features (infiltrating astrocytic growth and neuropil-like islands rimmed by neuronal cells), and had an unfavorable behavior. We report 3 pediatric cases (1 boy and 2 girls, ages 4, 6, and 8 years, respectively). The boy had a cerebral tumor, and the girls had a spinal tumor. The younger girl also had multiple posterior fossa lesions. The boy and older girl underwent a gross total resection. The younger girl underwent a subtotal resection of the spinal tumor; posterior fossa lesions were not surgically treated. The boy and younger girl are in complete remission at 33 and 24 months, respectively, after surgery and subsequent high-dose chemoradiotherapy. The older girl had a recurrence that was partially resected. Afterward, she started high-dose chemoradiotherapy and had an optimal radiologic response at 4 months follow up. Microscopically, the common denominator was the presence of synaptophysin-positive neuropil-like islands. One tumor showed ependymal features (pseudorosettes and punctate epithelial membrane antigen immunopositivity). Two tumors had 1p deletion. 19q deletion, MGMT gene promoter methylation, EGFR amplifications or polysomy, and EGFR, IDH1, IDH2, and TP53 genes mutation analyses yielded negative results. In conclusion, glioneuronal tumor with neuropil-like islands can affect children, arise in the spinal cord, and show ependymal features in its glial component. A high-dose chemoradiotherapy program is effective.

Primary cerebral myxofibrosarcoma: clinical, morphologic, immunohistochemical, molecular, and ultrastructural study of an infrequent tumor in an extraordinary localization.

Herein, we describe an intracerebral primary low-grade myxofibrosarcoma occurring in a 9-year-old boy. The lesion measured 7 cm and occupied the left parieto-occipital region. A gross-total removal of the tumor was performed. Nine months later, radiologic follow-up revealed a local recurrence which was again surgically removed. The patient then underwent radiotherapy and chemotherapy. He was well and disease-free at 6 months follow-up. The tumor was composed of spindle, stellated, and multinucleated cells embedded in a myxoid background. Foci of increased cellularity, pleomorphism, and high mitotic rate were present. The tumor borders were sharply demarcated from the non-neoplastic nervous parenchyma. Immunohistochemical staining showed that the neoplastic cells were vimentine and CD34 positive. Fluorescence in-situ hybridization analyses did not show FUS and EWSR1 gene rearrangements. Primary intracranial myxofibrosarcomas are very rare (to the best of our knowledge, less than 10 published cases in the international literature). We believe each new case should be recorded to produce a better clinical, pathologic, molecular, prognostic, and therapeutic characterization of this lesion.

Lipoastrocytoma: Case report and review of the literature.

Lipoastrocytoma is an extremely rare tumor, with only six cases described. We report the case of an astrocytoma involving the upper part of the cerebellar-pontine angle and the right portion of the clivus starting from the brainstem with a diffuse lipomatous component in a 39 year-old man. The patient was admitted with headache of 1 year's duration and diplopia over the previous 3 months. MRI revealed a ponto-cerebellar lesion that showed irregular enhancement after contrast administration. Subtotal excision of the tumor was accomplished. Adjuvant chemotherapy and radiation therapy were not administered. Histologically the tumor showed the classical histology of low-grade astrocytoma and a portion of the lesion was composed of lipid-laden cells. Immunohistochemistry for glial fibrillary acid and S-100 proteins clearly demonstrated the glial nature of these cells. Ki-67/Mib-1 labeling index was low (2%). The patient remains in good neurological conditions after 10 months. Our case has a benign postoperative behavior, also after subtotal excision, with restrictions due to the short follow-up. It is important to record each new case of this rare tumor to produce a better characterization of this lesion.

Teratoid hepatoblastoma.

We present the case of a Middle Eastern child, diagnosed and treated at 8 months of age for a hepatic neuroblastoma. After surgical removal of a 7 cm mass of the left liver lobe at our institution when the child was 15 months of age, the tumor was reclassified as a teratoid hepatoblastoma. The tumor was composed of fetal and embryonal hepatic tissue, undifferentiated tissue, and a teratoid background of loose mesenchymal tissue containing osteoid, squamous, and mucinous epithelium. We speculate on the histogenesis of teratoid hepatoblastoma and discuss its association with chemotherapy.

Expression of estrogen receptor beta in colon cancer progression.

Colon cancer is the most frequent neoplasia of the intestine. This pathology is the third highest cause of death from cancer with 430,000 deaths globally per year. Estrogen has also been implicated in the development and progression of colon cancer. Also sex-specific differences have been suggested to be involved in the process. Previous studies have shown the estrogen beta receptor to be the dominant receptor type in normal colonic tissue and its down-regulation along with the progression of colorectal cancer. The presence of estrogen receptors and products of estrogen-related genes in the colon suggests that estrogens have direct effects on the colonic tissue. However, the specific effect of estrogens on a normal colon and the role in the colon carcinogenesis are far from clear. The aim of this study is to analyze by real-time polymerase chain reaction, the relative quantitative expression of the estrogen receptors beta, beta1, beta2, and beta5 in colon adenocarcinomas and to compare this expression with the respective in normal tissues. Moreover, we evaluate a possible correlation between estrogen's receptor expressions and disease stages. Normal tissues show estrogen receptor beta expression greater than pathologic tissues and the estrogen receptor beta result as most expressed in the lower disease stages.

A pilot study on ocular safety of intravitreal infliximab in a rabbit model.

PURPOSE: To determine whether infliximab may be used safely as an intraocular drug, the ocular safety of intravitreal infliximab in rabbits was studied by clinical examination, electroretinography (ERG), and histology in rabbits. METHODS: Twelve New Zealand albino rabbits were selected for this study. Different infliximab doses, namely 1.0 mg, 1.7 mg, and 3.3 mg in 0.1 mL, were injected intravitreally into one eye each of three rabbits. As a control, the vehicle solution was injected into the fellow eye of each animal. Eye clinical examination and ERG recordings were made before and 2, 6, and 12 weeks after injection. Eventually, the rabbits were humanely killed, and the retinas were examined by light microscopy. In addition, the elimination half-life of the drug in the vitreous was assessed. RESULTS: Slit lamp biomicroscopy, indirect funduscopy, and ERG evidenced no significant differences between control and infliximab-injected eyes in this rabbit model, at any of the tested doses. Histologic examination revealed no retinal abnormality in the rabbits injected with 1 mg and 1.7 mg intravitreal infliximab. In two of three eyes injected with 3.3 mg infliximab, significant edema of the nerve fibers was detected compared with the control group. The half-life of the drug was estimated to be 8.5 days. CONCLUSIONS: These results indicate that infliximab may be a safe intravitreal drug in the rabbit model at a dose of up to 1.7 mg. If proven safe and efficacious in further studies, intravitreal injection of infliximab could be considered an alternative to systemic administration in selected patients.

Surveillance for endometrial cancer in women on tamoxifen: the role of liquid-based endometrial cytology - cytohistological correlation in a population of 168 women.

AIMS: The aim of this study was to evaluate the utility of liquid-based cytology for endometrial surveillance in patients receiving tamoxifen. METHODS: One hundred and sixty-eight women scheduled for hysteroscopy were enrolled in the study. The women sequentially underwent hysteroscopy, endometrial cytology and biopsy. RESULTS: Endometrial biopsy only was inadequate in 112 (67%) patients, both endometrial biopsy and cytology were inadequate in 19 (11%) patients, endometrial cytology only was inadequate in 4 (2%) patients, and both endometrial biopsy and cytology were adequate in 33 (20%) patients. Overall, endometrial biopsy was inadequate in 131 (78%) patients and endometrial cytology in 23 (14%) patients. Endometrial cytology provided sufficient material for diagnosis more often than endometrial biopsy (p < 0.05). In the series of 33 patients (20%) in whom both endometrial cytology and biopsy were adequate, there was a 100% correlation between the endometrial cytology and biopsy results. CONCLUSIONS: For the first time, this study shows the diagnostic efficacy of liquid-based endometrial cytology in the follow-up of women receiving tamoxifen. It could be applied solely or in conjunction with ultrasonography.

A comparative analysis of lichen sclerosus of the vulva and lichen sclerosus that evolves to vulvar squamous cell carcinoma.

OBJECTIVE: The aim of this study was to determine whether the premalignant change in lichen sclerosus (LS) could be identified with immunohistochemical analyses. STUDY DESIGN: Eight cases of histologically diagnosed vulvar LS, which showed, after a period of 10 months-9 years, an evolution to carcinoma of the vulva that was histologically documented, were compared with 8 cases of vulvar LS, for which follow-up information was available for at least 9 years. The proliferative index and the expression of tumor suppressors p16 and p53 were analyzed. RESULTS: The difference of MIB1 labeling index of evolving or unchanged LS cases was significant (P = .005). The difference in the p53 of evolving or unchanged LS cases shows a trend towards association (P = .08). Both LS cases (evolving or unchanged) did not show p16 positive staining. CONCLUSION: The evaluation of MIB1 and p53 may identify those vulvar LS cases with a high likelihood of evolving into squamous cell carcinoma, which would need careful periodic checks or adjunctive biopsies. The study must be confirmed by a larger number of cases to substantiate this observation.