C-KIT Expression in Orbital Cavernous Venous Hemangiomas.

Orbital (slow flow) cavernous venous hemangiomas (OCVH) are the most common benign orbital tumors in adults. The c-KIT is a tyrosine kinase receptor, which is expressed on several types of cells, is thought to play a key role in tumor pathogenesis. The purpose of this study was to evaluate the presence of the receptor c-KIT in OCVH. Our retrospective study examined 16 orbital cavernous venous hemangiomas from 16 cases operated on between 2006-2016 at Emek Medical Center. The mean tumor size was 18.4 mm. Symptoms appeared between 6 months and 22 years before operation. All specimens were analyzed for the c-KIT receptor through immunohistochemistry. The c-KIT was expressed by the endothelium in all 16 preparates. Staining was strong in two cases, moderate in six, and weak in eight cases, with no statistically significant correlation between staining and tumor size (p = 0.69) or the symptom duration (p = 0.15). We conclude that c-KIT may play an important role in the pathogenesis of OCVH. This pilot study is significant in that tumor-targeted therapy such as Imatinib Mesylate and Sunitinib may have a role in treating surgically complicated cases located in the orbital apex. A large multicenter collaborative study is necessary to examine the role of c-KIT in OCVH.

Role of oncogenic viruses in the development ocular surface squamous neoplasia.

PURPOSE: The pathogenesis of ocular surface squamous neoplasia is not fully understood. Therefore, we evaluated the role of oncogenic viruses in the pathogenesis of ocular surface squamous neoplasia in Israel. METHODS: Patients with ocular surface squamous neoplasia were enrolled in this retrospective study. The specimens were taken during 2004-2015 from two big centers: Emek Medical Center, Afula and the Hadassah Medical Center, Jerusalem. All the specimens (totally 26) were analyzed by immunohistochemistry for evidence of oncogenic viruses that included Human Papilloma virus, Herpes Simplex virus and Cytomegalovirus infection and 14 samples were examined by polymerase chain reaction. In addition, all the samples were examined for Epstein Barr virus infection by immunohistochemistry and Epstein Barr encoding region test. RESULTS: Twenty-six patients were included with a mean age of 61.81 [Formula: see text] 3.83 years (mean [Formula: see text]. Immunohistochemistry staining and Epstein Barr encoding region test did not detect any of the oncogenic viruses in the 26 samples. Human Papilloma virus-16 and -18, and Herpes Simplex virus were detected by polymerase chain reaction in 14.2%, 7% and 7%, respectively. CONCLUSION: We conclude from our study that oncogenic viruses may play a role in the pathogenesis of ocular surface squamous neoplasia in Israel.

Indolent T-cell lymphoproliferative disease of the gastrointestinal tract after treatment with adalimumab in resistant Crohn's colitis.

We report a case of intestinal indolent T-cell lymphoproliferative disease (TCLPD) occurring after the initiation of tumor necrosis factor-α (TNF-α) inhibitor therapy for resistant Crohn's disease. A prominent T-cell infiltrate positive for CD8, TIA-1, and T-cell receptor-ßF1 was associated with the foci of active inflammation. T-cell receptor gene clonality studies (BIOMED-2) demonstrated monoclonality. After the TNF-α inhibitor treatment was withdrawn, the T-cell infiltrates regressed, but 2 years later, the same monoclonal T-cell infiltrate reappeared at the only site of active inflammation. To the best of our knowledge, this report is the first to show a link between active inflammation and the TCLPD. In addition, it suggests a possible influence of the TNF-α inhibitor treatment on the evolution of the TCLPD. A high degree of suspicion is required in the presence of any unusual lymphoid infiltrate in inflammatory bowel disease to avoid overlooking an indolent TCLPD or misdiagnose an aggressive lymphoma.

Identification of human papillomavirus in pterygium.

PURPOSE: The purpose of this study was to evaluate the involvement of human papillomavirus in the pathogenesis of primary and recurrent pterygium in northern Israel. METHODS: A retrospective study examined 100 randomly chosen pterygium specimens with solar elastosis, from 100 patients who underwent pterygium surgery during 2012-2013 at the Emek Medical Center. All the specimens were analysed for evidence of human papillomavirus infection by immunohistochemistry. RESULTS: Human papillomavirus was not detected in any of the 100 pterygia samples by immunohistochemistry. These used samples were taken from 100 patients with mean age of 51.5 years and a primary: recurrent ratio of 8.09:1. CONCLUSION: We conclude from our study that human papillomavirus infection does not appear to be an important pathogenic factor of pterygium in Israel.

Distribution of estrogen and progesterone receptors isoforms in endometrial cancer.

BACKGROUND: 70-80% of sporadic endometrial carcinomas are defined as endometrioid carcinoma (EC). Early-stage, well differentiated endometrial carcinomas usually retain expression of estrogen and progesterone receptors (ER and PR, respectively), as advanced stage, poorly differentiated tumors often lack one or both of these receptors. Well-described EC prognosis includes tumor characteristics, such as depth of myometrial invasion. Therefore, in the current study, we evaluated the expression profile of ER and PR isoforms, including ER-α, PR-A and PR-B, in correlation to EC tumor histological depth. METHODS: Using immunohistochemistry and image analysis software, the expression of ER-α, PR-A, PR-B and Ki67 was assessed in endometrial stroma and epithelial glands of superficial, deep and extra-tumoral sections of 15 paraffin embedded EC specimens, and compared to 5 biopsies of non-malignant endometrium. RESULTS: Expression of PR-A and ER-α was found to be lower in EC compared to nonmalignant tissue, as the stromal expression was dramatically reduced compared to epithelial cells. Expression ratios of both receptors were significantly high in superficial and deep portions of EC; in non-tumoral portion of EC were close to the ratios of nonmalignant endometrium. PR-B expression was low in epithelial glands of EC superficial and deep portions, and high in the extra-tumoral region. Elevated PR-B expression was found in stroma of EC, as well. CONCLUSIONS: The ratio of ER-α and PR-A expression in the epithelial glands and the stroma of EC biopsies may serve as an additional parameter in the histological evaluation of EC tumor. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1155060506119016.

Primary effusion lymphoma-like lymphoma in a patient with inflammatory bowel disease.

A 77-year-old man with inflammatory bowel disease (IBD) and who was treated with anti-tumor necrosis factor (TNF), 6-mercaptopurine and corticosteroids, presented with primary effusion lymphoma-like lymphoma (PEL-like lymphoma) with massive ascites. The patient's clinical course was complicated by acute renal insufficiency and hypotension, which led to death within 2 wk. In general, patients with IBD may have an increased risk for development of lymphoma, which is frequently associated with immunosuppressive and/or anti-TNF antibody therapies. PEL is a rare subset of lymphoma localized to serous body cavities, lacks tumor mass or nodal involvement, and is associated with infection by human herpes virus 8 (HHV-8). Primary neoplastic effusion may also be present in patients with large B-cell lymphoma without evidence of human immunodeficiency virus or HHV-8 infections. This type of lymphoma is classified as PEL-like lymphoma. Both PEL and PEL-like lymphoma types have been reported in patients undergoing immunosuppressive therapy, but to the best of our knowledge, the case described herein represents the first PEL-like lymphoma occurring in a patient with IBD.

Patients' perceptions of radical prostatectomy for localized prostate cancer: a qualitative study.

BACKGROUND: Radical prostatectomy is one option for treating localized prostate cancer, but it can cause functional impairment of the urogenital system. OBJECTIVES: To describe the outcomes of radical prostatectomy as perceived by the patients, and their ways of coping with them. METHODS: We conducted a qualitative study of 22 men with localized prostatic cancer 1 year after surgery. The key questions related to the effect of the disease and the surgery on their lives and their view on the value of the surgery. RESULTS: The surgery was perceived as a necessary solution for the diagnosed cancer. All the participants suffered from varying degrees of urinary incontinence and erectile dysfunction. Urinary incontinence caused severe suffering. The impaired sexual ability affected relations with partners and led to feelings of shame and guilt and a decreased sense of self-esteem. In retrospect, the participants still viewed the surgery as a life-saving procedure. Faith in the surgeon contributed to their affirmation of the decision to undergo surgery despite the difficulties. CONCLUSIONS: Patients were prepared to suffer the inevitable physical and psychological sequelae of radical prostatectomy because they believed the surgery to be a definitive solution for cancer. Surgeons advising patients with localized prostatic cancer on treatment options should address these difficult issues and provide psychological support, either themselves or in collaboration with professionals.

Minimal Invasive Follicular Thyroid Carcinoma Developed in Dyshormonogenetic Multinodular Goiter Due to Thyroid Peroxidase Gene Mutation.

Background: The occurrence of thyroid carcinoma in patients with congenital hypothyroidism (CH) caused by dyshormonogenesis is very rare, and has been reported in only one patient harboring mutations in the thyroid peroxidase (TPO) gene. Patient findings: We report on a 29-year follow-up of two consanguineous siblings with CH due to total iodide organification defect who also had sensorineural hearing loss. Molecular analysis revealed a novel biallelic mutation of the TPO gene in which phenylalanine substitutes serine at codon 292 (c.875C>T, p.S292F) in exon 8. Despite early initiation, adequate doses of L-thyroxine treatment and consequently normal TSH levels, the proposita developed a huge multinodular goiter (MNG) and underwent total thyroidectomy due to tracheal compression. Pathological examination revealed a unifocal follicular thyroid carcinoma without vascular invasion in the left lobe of the thyroid gland. Summary: Our finding of follicular thyroid carcinoma arising from dyshormonogenetic MNG in a patient without elevated serum TSH levels indicates that genetic and environmental factors other than TSH level might be involved in the development of thyroid carcinoma in dyshormonogenetic MNG. Conclusions: Despite the rare occurrence of thyroid carcinoma in dyshormonogenetic MNG, we recommend long-term follow-up and regular neck ultrasound imaging to prevent delayed diagnosis of thyroid carcinoma.

Meta-analysis of unexpected findings in routine histopathology during total joint replacement.

BACKGROUND: Routine histopathological analysis of bone extracted during total joint replacement is controversial. OBJECTIVES: To evaluate the utility of routine histopathological analysis in total joint replacement. METHODS: We calculated the risk for discrepant diagnosis between the pre- and postoperative histopathological results by performing a meta-analysis of 11 studies (including our data). We also calculated the risk for significant discrepancies. RESULTS: The discrepant diagnoses analysis showed a random effect of 3% discrepancies (95% confidence interval 1.2-3.7%). Funnel plot indicates a publication bias; consequently, the conclusions from this analysis should be interpreted with caution. Regarding the significant discrepancy in diagnosis, we performed a meta-analysis of nine studies. Fixed-effects analysis of all the studies resulted in 0.16% significant discrepancies (95% CI 0.02-0.30%) with no heterogeneity (Q = 3.93, degrees of freedom = 9, P = 0.14, /2 = 49.2%), and appropriate fixed-effects models. CONCLUSIONS: We recommend no further routine histological examination, reserving this tool for cases with a controversial primary diagnosis and unexpected findings during the operation.

Cytokeratin-17 as a potential marker for squamous cell carcinoma of the larynx.

To assess cytokeratin-17 (CK17) as an immunohistochemical marker for squamous cell carcinoma of the larynx, we stained 63 tissue samples from 63 consecutive patients who were believed or suspected to have squamous cell carcinoma of the larynx for CK17 and analyzed them by computerized histomorphometry. The mean staining intensity for CK17 was significantly stronger (p < .01) in cancerous cells, dysplasia, and normal epithelium proximal to the tumor than in distal normal epithelium and polyps. The percentage of stained area, within samples taken from a single patient, was significantly higher in malignancy and dysplasia as compared to distal normal epithelium and in malignancy as compared to dysplasia and proximal normal epithelium (p < .001). The integrated optical density was significantly higher in the malignant epithelium, dysplasia, polyps, and proximal normal epithelium than in distal normal epithelium (p < .0001). We conclude that CK17 is a highly sensitive and specific immunohistochemical marker for premalignant and malignant transformation in the larynx. Further investigation is warranted in order to assess the role of CK17 in determining safe resection borders.

Classification of fungal sinusitis in immunocompetent patients.

OBJECTIVE: The objective of this study was to review the subgroup classification of fungal sinusitis in immunocompetent patients. METHODS: The study design included 19 immunocompetent patients with fungal sinusitis who were operated on between 1993 and 1998. RESULTS: Ten of 19 patients showed a fungus ball. They underwent a limited surgical endoscopic procedure, and no further treatment was needed. Four patients had allergic fungal sinusitis and were treated postoperatively with irrigation, topical steroids, and oral steroids in 2 patients as well. Five patients had chronic sinusitis with significant bone erosion. All 5 underwent an extensive endoscopic procedure and were treated postoperatively by repeated irrigation, endoscopic cleaning, and no antifungal preparation. Two patients of this group are reported broadly. CONCLUSIONS: Fungal sinusitis in immunocompetent patients is not a rare condition and can be divided into 3 categories: 1) fungus ball, 2) chronic erosive (noninvasive) fungal sinusitis, and 3) allergic fungal sinusitis. The symptomatology, treatment, and prognosis varied significantly among the 3 different categories.

Detection of cytokeratins in normal and malignant laryngeal epithelia by means of reverse transcriptase-polymerase chain reaction.

Cytokeratins (CKs) are a subgroup of intermediate filament proteins that take part in forming the cytoskeleton. The epithelial cells in different organs express distinct CKs, and this expression may be modified during malignant transformation. Here we describe the use of reverse transcriptase-polymerase chain reaction followed by Southern blotting to determine the profile of expression of CKs in both normal and malignant laryngeal samples. Thirty-six samples were subjected to histologic examination and classified as 17 squamous cell carcinomas, 3 dysplastic lesions, and 16 normal samples. CK8 and CK19 were expressed in almost all samples, both cancerous and normal, and were therefore used to verify the integrity of RNA. Expression of CK2, CK9, and CK20 was not detected in any of the samples, normal or cancerous. CK15 and CK18 showed low sensitivity for detection of cancer (36.4% and 45.5%, respectively). CK10 showed relatively high sensitivity (91%), but only moderate specificity (69.2%). Only CK17 showed both high sensitivity and specificity (91% and 92.3%, respectively; positive predictive value, 91%). We propose that CK17 may be considered a promising candidate to use as a molecular marker for malignant transformation in laryngeal squamous cell carcinoma.

Clodronate in myelofibrosis: a case report.

A 59-year-old man had well-documented agnogenic myeloid metaplasia (AMM) with pancytopenia. Frequent blood transfusions were required over a 10-month period. Androgen therapy was not beneficial and treatment with interferon resulted in severe thrombocytopenia with no decrease in transfusion requirements. Treatment with clodronate at a daily oral dose of 30 mg/kg resulted in a marked decrease in bone marrow fibrosis, and gradual normalization of blood counts over an 8-month period. He has been transfusion independent for the last 33 months. We support the findings of a previous case report that oral bisphosphonate therapy may be of value in patients with AMM.