HER2/neu Immunostaining in Invasive Breast Cancer: Analysis of False Positive Factors

Objectives: HER2/neu gene amplification by Fluorescent in situ hybridization and protein expression by immunohistochemistry have been used for prognosis and guidance for the treatment of invasive ductal carcinoma of the breast with Trastuzumab. False positive results are a significant problem where immunohistochemistry is exclusively used to test HER2/neu protein over expression. A minority of cases of breast cancer scoring HER2 (3+) by immunohistochemistry using Hercep test may not be associated with amplification of the HER2/neu gene by FISH, a test which is a more specific and sensitive than immunohistochemistry. This study aims to examine the factors contributing to false positive results by immunohistochemistry and subsequently not showing HER2/neu gene amplification by FISH analysis.Methods: A retrospective analysis of 18 cases (3+) by immunohistochemistry in the pathology laboratory not associated with HER2/neu gene amplification was performed. The histological review of these cases was done, the technical error (i.e staining of blood vessels or benign ducts) and the interpretation errors were evaluated.Results: Polysomy 17 was absent in all the cases studied by FISH analysis. By immunohistochemistry, five of the 18 cases were purely interpretation errors and the remaining were a combination of technical and interpretational errors.Conclusion: False positive results related to technical and interpretational errors can be prevented by properly educating the technologist and pathologist to perform high quality immunostains and to render an accurate diagnosis respectively. This issue is of utmost importance as it may have deleterious effects on the selection of therapeutic arsenal in invasive ductal carcinoma of the breast

Dendritic Fibromyxolipoma of the Pyriform Sinus: A Case Report and Review of the Literature

Dendritic fibromyxolipoma is a rare and distinctive soft tissue neoplasm that is considered by many authors as a variant of spindle cell lipoma and characterized by the presence of dendritic cytoplasmic processes, plexiform vascular pattern, and keloidal collagen. It has never been reported in the larynx and hypopharynx. Its rarity and the potential to mistake it as a more clinically aggressive myxoid soft tissue neoplasm highlight the importance of its recognition. Here, a case of a dendritic fibromyxolipoma of the pyriform sinus in a 38-year-old male who presented with dysphagia, change of voice, and stridor is reported. A review of the literature, including histopathologic features and differential diagnosis, is also included

Malignant Gastric Glomus Tumor: A Case Report and Literature Review of a Rare Entity

A glomus tumor is a mesenchymal neoplasm that usually develops in the peripheral soft tissue, especially in the distal part of the extremities. The subungual zones of the fingers and toes are the most frequent sites of observation. The majority of glomus tumors are entirely benign, and the malignant counterparts are very rare, especially those arising in the visceral organs. We report a case of an extremely rare malignant glomus tumor arising in the stomach of a 53-year-old female admitted to the King Khalid University Hospital, Saudi Arabia. The patient reported a four-month history of pain and fullness in the left hypochondrium. She underwent laparotomy and resection of the gastric mass. The mass was analysed by histopathology. Based on the pathological findings of large tumor size, nuclear atypia, increased mitotic rate, atypical mitosis, the presence of necrosis, and characteristic immunohistochemistry the diagnosis of malignant glomus tumor was rendered. Ultrastructural study confirmed the diagnosis. The patient is well and continues regular follow-up

Mucinous tubular and spindle cell carcinoma of the kidney with sarcomatoid transformation

Mucinous tubular and spindle cell carcinoma (MTSCC) of the kidney is a recently described entity in the World Health Organization (WHO) 2004 classification and has a rela-tively indolent behavior. Sarcomatoid differentiation has been well documented in most histologic variants of renal cell carcinoma and its presence is known to have a worse prognosis. Its occurrence in an otherwise benign MTSCC is extremely rare. Here, we report a unique case of MTSCC in a 64-year-old patient with multiple areas of high-grade spindle cells and large areas of necrosis in it. The patient had a rapidly fatal clinical outcome

Poorly differentiated monophasic synovial sarcoma of the mediastinum

Poorly differentiated synovial sarcoma is a diagnostically challenging neoplasm. Most commonly they occur in the soft tissue of the extremities and are rare in the mediastinum. They can be indistinguishable from other "round cell tumors" based on the morphology alone or at times by immunohistochemical studies. Here in, we report an extremely rare case of metastatic poorly differentiated monophasic synovial sarcoma of the mediastinum without a known primary in a 30-year-old man. The imaging studies on admission showed 10 × 9.5 cm anterior mediastinal mass with multiple nodules in the lung and pleura along with multiple enlarged mediastinal and axillary lymph nodes. Histopathologic and immunohistochemical analysis supported the diagnosis of poorly differentiated synovial sarcoma, which was further confirmed by molecular genetic analysis

Catechin combined with vitamins C and E ameliorates insulin resistance (IR) and atherosclerotic changes in aged rats with chronic renal failure (CRF)

Author: Korish, Aida A., From the Department of Physiology (29), Faculty of Medicine, Author: Arafah, Maha M., From the Department of Pathology, Faculty of Medicine, King Saud University, PO Box 2925, Riyadh 11461, Saudi ArabiaAging is an inevitable biological process associated with increased oxidative stress and accumulation of asymmetric dimethylarginine (ADMA) a known endogenous inhibitor of nitric oxide synthase. Atherosclerosis and IR constitute major risk factors for cardiovascular mortality in elderly with chronic kidney disease (CKD). We investigated the impact of catechin, vitamins E and C supplementation on insulin sensitivity, redox state, ADMA, nitrate and nitrite (NO2 / NO3 ) levels and histological picture of heart and large blood vessels of aged rats with CRF. Findings of the present study revealed that aging in rats is associated with hyperinsulinemia, hyperlipidemia, IR indicated by higher homeostasis model assessment (HOMA)-index, increased lipid peroxidation product malondialdehyde (MDA), ADMA, and blood pressure (BP), but decreased antioxidant capacity and NO2 /NO3 levels. CRF exaggerated all these findings and caused thickened intima of carotid arteries and myocardial hypertrophy. Treatment with catechin, vitamins E and C increases the antioxidant capacity and NO2 /NO3 production but, decreases MDA, ADMA and BP levels. Also it keeps insulin sensitivity and normal intima/media thickness of carotid arteries. We conclude that decreased nitric oxide (NO) vailability due to ADMA accumulation may be responsible for IR and associated atherosclerotic hanges in aged rats with CRF. Catechin, vitamins E and C supplementation may moderate oxidative s tress of renal

HER2/neu Immunostaining in Invasive Breast Cancer: Analysis of False Positive Factors

Fluorescent in situ hybridization (FISH). 9 It has been suggested that some of these IHC "false positive" results may be in part due to increased copy number of chromosome 17, 14 False positive results are a significant problem where IHC is exclusively used to test for HER2/neu protein over expression. These are mostly confined to the group of 2+ by IHC using Hercep test and these patients are found not responding to the targeted therapy. 15 In contrast, there is usually a high level of correlation between IHC 3+ staining and amplification detected by FISH analysis. 16,17 The purpose of this study is to evaluate the factors contributing to false positive 3+ results by Hercep test kit IHC and subsequently not amplified for the HER-2/neu gene by Fluorescence in situ hybridization (FISH). Methods In a retrospective five year study, out of the consecutive 164 cases of invasive breast cancers, all the 58 cases which were reported as 3+ for HER2 immunostaining by Hercep test at King Khalid University Hospital were reviewed by two pathologists. Among these, 26 equivocal cases were assorted and sent for FISH analysis for confirmation of HER2/neu gene amplification. 18 cases were Abstract Objectives: HER2/neu gene amplification by Fluorescent in situ hybridization and protein expression by immunohistochemistry have been used for prognosis and guidance for the treatment of invasive ductal carcinoma of the breast with Trastuzumab. False positive results are a significant problem where immunohistochemistry is exclusively used to test HER2/neu protein over expression. A minority of cases of breast cancer scoring HER2 (3+) by immunohistochemistry using Hercep test may not be associated with amplification of the HER2/neu gene by FISH, a test which is a more specific and sensitive than immunohistochemistry. This study aims to examine the factors contributing to false positive results by immunohistochemistry and subsequently not showing HER2/neu gene amplification by FISH analysis. Methods: A retrospective analysis of 18 cases (3+) by immunohistochemistry in the pathology laboratory not associated with HER2/neu gene amplification was performed. The histological review of these cases was done, the technical error (i.e staining of blood vessels or benign ducts) and the interpretation errors were evaluated. Results: Polysomy 17 was absent in all the cases studied by FISH analysis. By immunohistochemistry, five of the 18 cases were purely interpretation errors and the remaining were a combination of technical and interpretational errors. Conclusion: False positive results related to technical and interpretational errors can be prevented by properly educating the technologist and pathologist to perform high quality immunostains and to render an accurate diagnosis respectively. This issue is of utmost importance as it may have deleterious effects on the selection of therapeutic arsenal in invasive ductal carcinoma of the breast

Cardiotoxic effects of arsenic trioxide/imatinib mesilate combination in rats

Authors: Saad, Sherif Y. and Alkharfy, Khalid M., From the Department of Clinical Pharmacy, College of Pharmacy and Author: Arafah, Maha M., From the Department of Pathology, College of Medicine, King Saud University, Riyadh, Saudi ArabiaCardiotoxicity is an important consideration in the evaluation of cancer chemotherapy, because chemotherapy-induced myocardial damage might be irreversible and lethal. This in-vivo study investigated the cardiotoxicity of either arsenic trioxide or imatinib mesilate, or a combination of both drugs, following repeated administration in male Wistar rats. Both arsenic trioxide and imatinib mesilate were administered daily at a dose of 5mgkg 1 intraperitoneally and 30mgkg 1 orally for 10 days, respectively. Cardiotoxicity was evaluated by biochemical and histopathological examination 48 h after the last dose. Treatment with either arsenic or imatinib, or both, resulted in significant increases in serum creatine kinase isoenzyme (CK-MB), glutathione peroxidase (GPx), lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) activity levels. Cardiac tissue of rats treated with arsenic showed significant increases in levels of reduced glutathione (GSH) content, GPx activity, malondialdehyde (MDA) and total nitrate/nitrite (NOx), whereas imatinib treatment significantly increased cardiac GSH content and MDA production level and decreased GPX activity level and NOx content. A combination of arsenic and imatinib produced significant increases in cardiac GSH content, GPx activity and MDA production levels, in addition to a reduction in NOx content. Combination arsenic/imatinib treatment extensively increased GPX activity and MDA production levels compared with imatinib treatment alone. Moreover, rats treated with arsenic or imatinib, or both, showed a significant increase in serum bilirubin, creatinine and urea levels. Histopathological examination of cardiac tissue of the combination-treated group revealed fibroblastic proliferation, myocardial disorganization and myocardial necrosis. Liver’s peroxidative alterations revealed that treatment with either arsenic or imatinib, or the two combined, increased levels of reduced-GSH and MDA production levels. However, imatinib treatment depleted liver’s GPx activity level contrary to treatment with the combination. Rats treated with arsenic alone or arsenic/imatinib combination showed significant elevation in liver NOx. In conclusion, both arsenic trioxide and imatinib mesilate might have significant cardiotoxicity and cardiac function should be monitored during treatment with them alone or in combination, as well as in the presence of preexisting cardiac dysfunction