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Categorizing breast neoplasia as ductal or lobular is a daily exercise that relies on a combination of histologic and immunohistochemical tools. The historically robust link between loss of the E-cadherin molecule and lobular neoplasia has rendered staining for E-cadherin by immunohistochemistry a staple of this diagnostic process. Unfortunately, discordances between E-cadherin expression and histomorphology, and variations in E-cadherin staining patterns and intensities abound in clinical practice, but are often neglected in favour of a binary interpretation of the E-cadherin result. In this article, we highlight the complexities of E-cadherin expression through a review of the E-cadherin protein and its associated gene (CDH1), the mechanisms leading to aberrant/absent E-cadherin expression, and the implications of these factors on the reliability of the E-cadherin immunohistochemical stain in the classification of ductal versus lobular mammary neoplasia.
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BACKGROUND: Extra-gastrointestinal stromal tumor is a rare subtype of soft tissue sarcomas with significantly variable presentation, management, and prognosis. This makes it crucial to report the different institutional experiences of encountering extra-gastrointestinal stromal tumors (EGIST). CASE PRESENTATION: We report 3 cases of EGIST diagnosis at American University of Beirut Medical Center for 2 males and 1 female in the 5th, 6th, and 7th decades of life, respectively. For the first case, the tumor was initially suspected to be ovarian cancer, but biopsy revealed a diagnosis of EGIST, and the patient was started on neoadjuvant therapy. In the second case, the tumor was retro-gastric and prelim diagnosis was gastric cancer but again biopsy revealed an EGIST histopathology, and the patient underwent surgery and adjuvant treatment. For the third case, a previous history of testicular cancer prompted an initial suspicion of recurrence with metastasis but biopsy and immunohistochemistry staining revealed EGIST with related markers. The patient underwent treatment at a different institution in his home country. CONCLUSION: This report sheds light on the importance of keeping EGIST amongst any differential list for abdominal and pelvic tumors. It also shows that EGIST-focused studies are needed to assess the effectiveness of the different treatment modalities available when utilized specifically for EGIST. This would allow for better oncological outcomes and improved quality of life.
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Tumores del Estroma Gastrointestinal , Neoplasias Pélvicas , Neoplasias Testiculares , Masculino , Humanos , Femenino , Tumores del Estroma Gastrointestinal/diagnóstico , Tumores del Estroma Gastrointestinal/terapia , Tumores del Estroma Gastrointestinal/patología , Calidad de Vida , PronósticoRESUMEN
Sclerosing epithelioid fibrosarcoma (SEF) is a rare but aggressive sarcoma. We report the first case of hepatic SEF in pediatric patient, which is also the second case in literature. A 17-year-old previously healthy female presented with a liver mass measuring 13.7 cm in greatest dimension and mild elevation of liver enzymes and cancer antigen 19-9. Needle biopsy revealed multiple cores of liver parenchyma mostly replaced by densely hyalinized fibrotic tissue and areas of small-to-medium sized epithelioid cells with eosinophilic and clear cytoplasm. Immunohistochemistry (IHC) demonstrated diffuse strong cytoplasmic staining of MUC4, suggesting a working diagnosis of sclerosing epithelioid fibrosarcoma (SEF)/low-grade fibromyxoid sarcoma (LGFMS). Liver explant demonstrated a well-circumscribed, nodular mass with firm, gray-white cut surface, and similar histopathology as seen in needle biopsy with no convincing evidence suggesting LGFMS. Sequencing panel revealed EWSR1::CREB3L1 gene fusion and confirmed the diagnosis of SEF. Post-operative cancer antigen 19-9 normalized 3 months after transplant; follow-up 3 and 6 months post-transplant imaging at that time showed no concern for disease recurrence.
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Fibrosarcoma , Sarcoma , Neoplasias de los Tejidos Blandos , Humanos , Femenino , Niño , Adolescente , Recurrencia Local de Neoplasia , Fibrosarcoma/diagnóstico , Fibrosarcoma/genética , Fibrosarcoma/patología , Sarcoma/genética , Neoplasias de los Tejidos Blandos/patología , Hígado/patologíaRESUMEN
PURPOSE: The angular vein extends between the supraorbital and supratrochlear veins superiorly and the facial vein inferiorly. Rarely, this vessel can be involved by infections, vascular malformations, or benign tumors. In this study, we report both our experience and the published literature on angular vein disorders. METHODS: A retrospective study was performed on patients seen between 2008 and 2022. The medical literature was searched for reports of conditions affecting the angular vein. RESULTS: During the study period, we encountered 5 patients with angular vein disorders. Information from these patients was combined with 18 published cases. Among the 23 patients, the diagnosis was confused with lacrimal drainage abnormalities in 52%, and 57% underwent imaging. "Swelling" or a palpable, moveable mass were frequent findings. Pain or tenderness was experienced by 43.5% of patients. Five patients were observed, and 2 infections were treated with antibiotics. The remaining 16 lesions were successfully treated with excision (n = 15) or cauterization (n = 1), without complications. Final diagnosis included 14 vascular malformations (isolated varix: 7, thrombosis: 6, cavernous venous malformation: 1), 7 vascular tumors (intravenous pyogenic granulomas: 6, intravascular papillary endothelial hyperplasia: 1) and thrombophlebitis (n = 2). CONCLUSIONS: Disorders of the angular vein are uncommon and frequently misdiagnosed as lacrimal abnormalities. While these lesions can frequently be identified on clinical findings, imaging can be helpful in some cases. Patients with suspected thrombophlebitis require urgent antibiotic therapy. Minimally symptomatic angular vein lesions can be observed. Surgical excision is effective in treating the different vascular malformations and tumors affecting this structure.
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Aparato Lagrimal , Tromboflebitis , Várices , Malformaciones Vasculares , Humanos , Estudios RetrospectivosRESUMEN
Rhabdomyosarcoma (RMS) is an aggressive childhood soft-tissue tumor, with propensity for local invasion and distant metastasis. Exosomes are secreted vesicles that mediate paracrine signaling by delivering functional proteins and miRNA to recipient cells. The transmembrane protein CD147, also known as Basigin or EMMPRIN, is enriched in various tumor cells, as well as in tumor-derived exosomes, and has been correlated with poor prognosis in several types of cancer, but has not been previously investigated in RMS. We investigated the effects of CD147 on RMS cell biology and paracrine signaling, specifically its contribution to invasion and metastatic phenotype. CD147 downregulation diminishes RMS cell invasion and inhibits anchorage-independent growth in vitro. While treatment of normal fibroblasts with RMS-derived exosomes results in a significant increase in proliferation, migration, and invasion, these effects are reversed when using exosomes from CD147-downregulated RMS cells. In human RMS tissue, CD147 was expressed exclusively in metastatic tumors. Altogether, our results demonstrate that CD147 contributes to RMS tumor cell aggressiveness, and is involved in modulating the microenvironment through RMS-secreted exosomes. Targeted inhibition of CD147 reduces its expression levels within the isolated exosomes and reduces the capacity of these exosomes to enhance cellular invasive properties.
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Basigina , Exosomas , Rabdomiosarcoma , Basigina/genética , Carcinogénesis , Transformación Celular Neoplásica , Exosomas/metabolismo , Humanos , Rabdomiosarcoma/metabolismo , Transducción de Señal , Microambiente TumoralRESUMEN
AIMS: Clear cell stromal tumour of the lung (CCST-L) is a rare, recently recognised neoplasm which has been found to express TFE3 and harbour YAP1::TFE3 fusions. Initial data suggested a benign process; however, a single reported case gave rise to distant metastases. We sought to describe the clinicopathological and molecular features of additional cases of CCST-L. METHODS AND RESULTS: Pathology and molecular archives were searched for cases of CCST-L or tumours with YAP1::TFE3 fusions. Clinical features were noted. Available slides, including immunohistochemical studies, were re-reviewed for diagnosis confirmation and assessment of pathological features. Results of molecular studies were also recorded. Four tumours were identified, all occurring in women (median age = 61 years, range = 24-69). Median tumour size was 4.4 cm (range = 1-9.5 cm); three tumours were unifocal and one was multifocal. Tumours were composed of epithelioid to spindled cells with eosinophilic to clear cytoplasm and grew in sheets, vague nests and short fascicles. Nuclear atypia was predominately mild; however, two cases showed scattered atypical cells. Mitotic activity was generally low, although one case showed a mitotic count of 6/2 mm2 . All tumours expressed TFE3 and harboured YAP1::TFE3 fusions. One case was unresectable and was treated with chemotherapy, and two underwent complete resection. One patient died of disease 7 months following diagnosis, while a second patient was alive with no evidence of disease after 43 months. Follow-up was not available for two cases. CONCLUSION: CCST-L expresses TFE3, harbours YAP1::TFE3 fusions and at least rare cases behave in an aggressive manner.
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Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice , Neoplasias Pulmonares , Adulto , Anciano , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/genética , Femenino , Fusión Génica , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Neoplasias Pulmonares/genética , Persona de Mediana Edad , Proteínas Señalizadoras YAP , Adulto JovenRESUMEN
Herpes simplex virus and Cytomegalovirus co-infection has been reported to occur in a variety of sites in immunocompromised patients. To our knowledge, few cases of such co-infection have been reported to occur in the esophagus. We report a case of a 60-year-old woman who was maintained on immunosuppressive therapy for a presumed diagnosis of pemphigus vulgaris, who presented with odynophagia. Investigations revealed ulcerative esophagitis caused by both HSV and CMV. The patient was treated with valganciclovir with full recovery. We also present the results of various studies on patients with similar presentation particularly those caused by HSV and CMV co-infection.
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Multiple randomized studies have shown that combination of chemotherapy and immune checkpoint inhibitors (ICIs) leads to better response rates and survival as compared to chemotherapy alone in the advanced stage of NSCLC. Data suggesting a benefit to using ICIs in the neoadjuvant therapy of patients with early stage NSCLC are emerging. Eligible subjects were treatment naïve patients with stage IB, II, and resectable IIIA NSCLC. Patients received three cycles of neoadjuvant chemotherapy with four doses of avelumab every 2 weeks. Patients with squamous cell cancer received cisplatin or carboplatin on day 1 and gemcitabine on days 1 and 8 of each cycle of chemotherapy. Patients with nonsquamous histology received cisplatin or carboplatin with pemetrexed on day 1 of each cycle. Patients then proceeded to their planned surgery. Out of 15 patients accrued as part of stage 1 of the study, four had a radiologic response (1 complete response), lower than the minimum of six responses needed to continue to phase 2 of the study. The study was therefore terminated. Majority had adenocarcinoma histology and stage IIIA disease. The treatment was well tolerated with no unexpected side effects. Four patients (26.7%) had grade III/IV CTCAE toxicity. This study confirms that the preoperative administration of chemotherapy and avelumab is safe. There was no indication of increased surgical complications. The benefit of adding immunotherapy to chemotherapy did not appear to enhance the overall response rate of patients in the neoadjuvant setting in patients with resectable NSCLC because this study failed to meet its primary endpoint.
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Adenocarcinoma del Pulmón/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Terapia Neoadyuvante , Neumonectomía , Adenocarcinoma del Pulmón/mortalidad , Adenocarcinoma del Pulmón/patología , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Humanos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante/efectos adversos , Terapia Neoadyuvante/mortalidad , Estadificación de Neoplasias , Neumonectomía/efectos adversos , Neumonectomía/mortalidad , Supervivencia sin Progresión , Factores de TiempoRESUMEN
BACKGROUND: Intracystic/encapsulated papillary carcinoma remains a poorly understood disease of the breast with a little amount of reports that describe it. It shares features with DCIS and IDC and predominantly affects postmenopausal women. This study aims to evaluate the clinical presentation, treatment, and outcomes in IPC patients managed at our institution. METHODS: We retrospectively pooled twenty-eight IPC patients' medical records at our institution. Descriptive analysis of clinicopathological characteristics, approach, and outcomes was done along with a quantitative statistical analysis. RESULTS: Cases were divided into three groups: isolated IPC, IPC associated with DCIS, and IPC associated with Invasive Carcinoma. Treatment modalities varied according to the IPC type and its associated components. All patients presented with a palpable mass. Immunohistochemical staining revealed that all isolated IPCs were ER and PR positive and HER2 negative. Lymph node dissection proved necessary only in IPC associated invasive carcinoma. Irregular borders and lobulations, among others, were found on non-invasive core biopsies that turned out to be associated with invasion on surgical pathology. All patients were alive after a median follow-up time of 23 months when the study was over with no reports of recurrence. CONCLUSION: IPC cases and treatment approaches at our institution appear similar to the available literature and confirm the excellent prognosis among IPC. Even more, further studies into the key features such as BMI, family history, and radiological findings are necessary for a potential algorithm that could assess for risk of finding invasion in surgical pathology and subsequently the need for axillary/sentinel lymph node biopsy.
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Neoplasias de la Mama/diagnóstico , Carcinoma Intraductal no Infiltrante/diagnóstico , Carcinoma Papilar/diagnóstico , Glándulas Mamarias Humanas/patología , Adulto , Anciano , Anciano de 80 o más Años , Axila , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Carcinoma Intraductal no Infiltrante/epidemiología , Carcinoma Intraductal no Infiltrante/patología , Carcinoma Intraductal no Infiltrante/terapia , Carcinoma Papilar/epidemiología , Carcinoma Papilar/patología , Carcinoma Papilar/terapia , Quimioterapia Adyuvante , Femenino , Estudios de Seguimiento , Humanos , Glándulas Mamarias Humanas/cirugía , Mastectomía , Anamnesis , Persona de Mediana Edad , Invasividad Neoplásica/diagnóstico , Invasividad Neoplásica/patología , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/prevención & control , Pronóstico , Estudios Retrospectivos , Ganglio Linfático Centinela/patología , Biopsia del Ganglio Linfático Centinela , Resultado del TratamientoRESUMEN
OBJECTIVE: Meningioma is the most common intracranial primary brain tumor. Risk factors such as age and exposure to radiation as well as prognostic factors such as grade, location, and extent of surgical resection have been reported in the literature worldwide; however, to our knowledge, data from the Middle East is still warranted. In this study, we aim to identify the characteristics, risk factors and outcomes of meningioma patients treated at a multidisciplinary regional referral center in the Middle East. PATIENTS AND METHODS: This is a retrospective chart review with a prospective follow up of outcomes. It included patients diagnosed with meningioma between January 2005 and December 2015 at the American University of Beirut Medical Center. Patient's demographics, risk factors and outcomes were first retrospectively collected. Then, we conducted phone calls to all included alive patients to update their disease status and outcomes. RESULTS: One-hundred and ninety-five patients were included. 69 % had grade I tumors and around 31 % with grades II and III meningiomas. The means of the overall survival and progression free survival (PFS) were 198 and 126 months, respectively. The residence area (city vs. countryside), occupation, alcohol use, oral contraceptive use, family history of meningioma, previous head trauma, radiation exposure for head/brain imaging, cell phone use, and finally, the tumor Ki-67 protein level did not correlate with the survival outcomes. The meningioma grade and extent of resection were significant predictors of the PFS on the univariate analysis, whereas, in the multivariate analysis only previous radiotherapy was significant in prolonging PFS. CONCLUSION: In our study cohort, that included around 30 % grades II and III tumors, previous radiotherapy use was the only significant prognostic factor for longer PFS in patients diagnosed with meningioma. Future prospective studies should be conducted to evaluate genetic and molecular factors that could possibly be linked to meningioma grade and prognosis in our population of Middle Eastern patients.
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Neoplasias Meníngeas/epidemiología , Meningioma/epidemiología , Adulto , Anciano , Femenino , Humanos , Líbano , Masculino , Neoplasias Meníngeas/patología , Neoplasias Meníngeas/terapia , Meningioma/patología , Meningioma/terapia , Persona de Mediana Edad , Supervivencia sin Progresión , Estudios Retrospectivos , Centros de Atención Terciaria , Resultado del TratamientoRESUMEN
Lymphoid follicles/aggregates in gastric biopsies have been traditionally linked to Helicobacter pylori gastritis, and less commonly to other inflammatory and neoplastic conditions. The frequency of such aggregates in normal stomachs has yet to be adequately evaluated. This is especially relevant when it comes to diagnosing non-specific chronic gastritis in biopsy specimens with chronic inflammation but no evidence of H pylori infection. Sleeve gastrectomies represent an opportunity to study adequately preserved gastric mucosa in patients who are otherwise asymptomatic and lack a history of gastric disease.To study sleeve gastrectomy specimens to quantify the amount of lymphoid follicles/aggregates and lymphocytic infiltration in normal stomachs.Sixty-eight bariatric sleeve gastrectomies and 13 control specimens from Whipple resections were examined for multiple histologic features including type, quantity, and distribution of chronic inflammation and lymphoid follicles/aggregates. Presence of H pylori was documented by both Hematoxylin and eosin-stained (H&E) and immunohistochemistry (IHC). Clinical information including age, sex, medication intake, prior endoscopy, and/or H pylori infection was recorded. The patient population was divided in 2 groups, H pylori negative versus H pylori positive, and statistical analysis was performed by a biostatistician.Two hundred sixty three fundic sections from 68 bariatric patients were examined. Fifty three patients were found to be H pylori-negative, compared with 15 who were positive for H pylori. Among the H pylori-negative group, the average number of lymphoid aggregates was 3.33, compared with an average of 6.26 in the H pylori positive group (the difference was statistically significant with a P-value of .008). The average number of plasma cells per high power field was 2.15 in the H pylori negative group, compared and average of 5.07 in the H pylori positive group (the difference was also statistically significant with a P-value <.001). Clinically, 10 of the 53 H pylori-negative patients had esophagogastroduodenoscopy (EGD) that showed endoscopic mild non-erosive gastric erythema. The remaining had no documentation of symptoms or medication intake, including Non-steroidal anti-inflammatory drugs (NSAIDs) and Proton Pump Inhibitors (PPI).Our results suggest that the presence of lymphoid aggregates and plasma cells infiltration can be a normal finding in otherwise normal gastric mucosa, though more pronounced in H pylori infected patients.
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Mucosa Gástrica/patología , Gastritis/patología , Infecciones por Helicobacter/patología , Helicobacter pylori/aislamiento & purificación , Tejido Linfoide/citología , Células Plasmáticas/citología , Estudios de Casos y Controles , Femenino , Gastrectomía , Gastritis/diagnóstico , Humanos , MasculinoRESUMEN
BACKGROUND: Ultrasound, along with ultrasound-guided fine needle aspiration, is currently used for the axillary evaluation of breast cancer patients in order to identify candidates for axillary lymph node dissection. The aim of this study is to evaluate the accuracy of this tool in correctly identifying patients who may or may not benefit from axillary clearance in light of the ACOSOG Z0011 trial recommendations. METHODS: One hundred one patients (65 with positive US-FNA with corresponding axillary lymph node dissection (ALND), and 36 with negative US-FNA with corresponding ALND/sentinel lymph node biopsy) were studied for the number of involved axillary lymph nodes, tumor clinicopathologic features, and axillary radiologic findings. RESULTS: From the positive US-FNA group, 43% of patients had two or fewer positive lymph nodes upon ALND pathologic examination. In the US-FNA negative group, the negative predictive value for detecting axillary disease was 72.7%. With both groups combined, the sensitivity, specificity, PPV, and NPV of US-FNA for selecting patients based on axillary disease burden were 86%, 51.7%, 57%, and 83.3%, respectively. CONCLUSION: Based on Z0011 guidelines, US-FNA is not a reliable tool in triaging patients in need for ALND and leads to overtreatment of 43% patients when positive, while depriving a small but significant percentage of patients from necessary therapy, when negative.
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Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/patología , Carcinoma Intraductal no Infiltrante/patología , Carcinoma Lobular/patología , Biopsia Guiada por Imagen/métodos , Ganglios Linfáticos/patología , Ultrasonografía/métodos , Axila , Biopsia con Aguja Fina , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/cirugía , Carcinoma Ductal de Mama/diagnóstico por imagen , Carcinoma Ductal de Mama/cirugía , Carcinoma Intraductal no Infiltrante/diagnóstico por imagen , Carcinoma Intraductal no Infiltrante/cirugía , Carcinoma Lobular/diagnóstico por imagen , Carcinoma Lobular/cirugía , Manejo de la Enfermedad , Reacciones Falso Positivas , Femenino , Estudios de Seguimiento , Humanos , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/cirugía , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Biopsia del Ganglio Linfático CentinelaRESUMEN
CD30 is a member of the tumor necrosis factor family of cell surface receptors normally expressed in lymphocytes, as well as some lymphomas, but has been described in other malignancies. Anaplastic lymphoma kinase (ALK) is a tyrosine kinase receptor that belongs to the insulin receptor superfamily, and is normally expressed in neural cells, but has been detected in several malignancies. There is conflicting data in the literature that describes the expression of these receptors in breast cancer, and the aim of this study is to test the expression of CD30 and ALK in a cohort of Middle Eastern patients with breast carcinoma.Cases of invasive breast cancer from the archives of AUBMC were reviewed over a period of 9 years, and the blocks that were used for immunohistochemical staining for ER, PR, Her-2/neu were selected. Immunohistochemical staining for CD30 (JCM182) and ALK (5A4 and D5F3) was performed.Two hundred eighty-four cases were identified (2 cases were male), with a mean age of 55â±â12. CD30 and ALK expression was not seen in any of the cases.Our cohort showed complete negativity to both CD30 and ALK, adding to the conflicting data available in the literature, and more studies are needed to reliably identify a trend of expression of CD30 and ALK in breast carcinoma, especially in the Middle East.
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Quinasa de Linfoma Anaplásico/metabolismo , Neoplasias de la Mama/metabolismo , Antígeno Ki-1/metabolismo , Adulto , Anciano , Neoplasias de la Mama/patología , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
PURPOSE: The most significant adverse risk factor for neuroblastoma (NB) is MYCN gene amplification, which strongly associates with high-risk disease. Fluorescent in situ hybridization (FISH) is considered the best method to evaluate MYCN gene status. However, it requires a laboratory that can perform highly complex testing, specialized personnel, and costly reagents. Herein, we aimed to investigate the feasibility of using immunohistochemistry (IHC) to detect MYCN protein expression in lieu of FISH, a strategy potentially useful in areas with limited resources. METHODS: A pilot cohort of 78 patients with NB, including 34 of Middle Eastern descent (MED) who had a higher prevalence of MYCN gene amplification (44.11%) and 44 of North American descent (NAD), nine (20.45%) of whom had MYCN amplification, was evaluated with IHC for MYCN protein. Correlations of FISH results and protein expression are presented. RESULTS: A positive correlation between MYCN gene amplification and protein expression by IHC was seen in 22 (91.66%) of the 24 MYCN-amplified NB cases-14 (93.33%) of 15 patients of MED and eight (88.88%) of nine patients of NAD. Agreement between negative FISH and negative IHC results was noted in 18 (94.73%) patients of MED and 34 (97.14%) patients of NAD. Two cases had weak protein expression but no gene amplification (MED: n = 1; 5.0%; NAD: n = 1; 2.9%). CONCLUSION: An excellent overall correlation between MYCN gene status by FISH and MYCN protein expression by IHC was confirmed. MYCN IHC in NB with reflexing to FISH in equivocal cases is potentially useful in a limited-resource setting. Evaluation of effectiveness using a larger cohort and optimization to perform MYCN IHC manually is needed.
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Proteína Proto-Oncogénica N-Myc/genética , Proteína Proto-Oncogénica N-Myc/metabolismo , Neuroblastoma/diagnóstico , Adolescente , Niño , Preescolar , Estudios de Factibilidad , Femenino , Amplificación de Genes , Humanos , Hibridación Fluorescente in Situ , Lactante , Recién Nacido , Masculino , Neuroblastoma/genética , Neuroblastoma/metabolismo , Proyectos PilotoRESUMEN
INTRODUCTION: Although normal epithelial cells do not show human epidermal growth factor receptor-2 (HER2) gene amplification and should lack membrane staining by HER2 immunohistochemistry (IHC), HER2 staining in benign breast epithelium is occasionally encountered. The significance of this occurrence has not yet been adequately studied, and its associated American Society of Clinical Oncology/College of American Pathologists recommendations are vague. Our objective is to assess the correlation between HER2 IHC 3+ breast cancer cases with normal epithelium staining (NES) and their corresponding fluorescence in situ hybridization (FISH) results, and to suggest recommendations for interpretation. MATERIALS AND METHODS: A total of 154 breast cancer cases with HER2 IHC 3+ were reviewed. NES, along with other clinicopathologic characteristics, were recorded. NES was scored as present or absent. All study cases were sent for FISH testing. All cases, and particularly those that showed false positivity for IHC (positive IHC, negative FISH) were examined for NES. RESULTS: Of the 154 cases, 146 cases were FISH-positive (94.8%) and 2 failed FISH testing (1.3%). Conversely, 22% (34/154) of the cases showed NES for HER2. Of these 34 cases, 23 (67%) were FISH-amplified, 9 (26%) were FISH not amplified, and 2 failed FISH testing. Notably, all of the false-positive (FISH-negative) breast cancer cases showed some degree of positivity in normal breast epithelium. CONCLUSIONS: Our findings, though descriptive, show a very strong association between NES and false-positive HER2 IHC. This confirms the need to carefully evaluate IHC-positive breast cancers for NES, and to have a low threshold for confirmatory testing by FISH.
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Biomarcadores de Tumor/análisis , Neoplasias de la Mama/patología , Mama/patología , Inmunohistoquímica/métodos , Hibridación Fluorescente in Situ/métodos , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Mama/metabolismo , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Femenino , Estudios de Seguimiento , Amplificación de Genes , Humanos , Persona de Mediana Edad , PronósticoRESUMEN
OBJECTIVES: To determine the prevalence and prognostic value of MGMT promoter methylation and IDH1 mutation in glioblastoma multiforme (GBM) patients from the Middle East. PATIENTS AND METHODS: Records of patients diagnosed between 2003 and 2015 were reviewed. MGMT promoter methylation was measured using methylation-specific polymerase chain reaction and IDH-1 mutation was reported. The primary endpoint was overall survival (OS). RESULTS: A total of 110 patients were included. The median age was 51 years and 71 patients (64.5%) were males. The median diameter of GBM was 4.6 cm and 29 patients (26.4%) had multifocal disease. Gross total resection was achieved in 38 patients (24.9%). All patients received adjuvant radiation therapy, and 96 patients (91.4%) received concomitant temozolomide. At a median follow up of 13.6 months, the median OS was 17.2 months, and the OS at 1 and 2 years were 71.6% and 34.8%, respectively. On multivariate analysis, age at diagnosis (HR 1.019; P = 0.044) and multifocality (HR 2.373; P = 0.001) were the only independent prognostic variables. MGMT promoter methylation was found in 28.2% of patients but did not significantly correlate with survival (HR 1.160; P = 0.635). IDH-1 mutation was found in 10% of patients was associated with a non-significant trend for survival improvement (HR 0.502; P = 0.151). CONCLUSION: Patients with GBM from the Middle East have adequate survival outcomes when given the optimal treatment. In our patient population, MGMT promoter methylation did not seem to correlate with outcomes, but patients with IDH1 mutation had numerically higher survival outcomes.
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Neoplasias Encefálicas/genética , Metilasas de Modificación del ADN/genética , Glioblastoma/genética , Isocitrato Deshidrogenasa/genética , O(6)-Metilguanina-ADN Metiltransferasa/genética , Adulto , Biomarcadores de Tumor/genética , Neoplasias Encefálicas/cirugía , Metilación de ADN/genética , Enzimas Reparadoras del ADN/genética , Femenino , Glioblastoma/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Regiones Promotoras Genéticas/genéticaRESUMEN
PURPOSE: Outcomes in pediatric osteosarcoma have dramatically improved over the past few decades, with overall survival rates of 70% and 30% for patients with localized and metastatic disease, respectively. PATIENTS AND METHODS: We retrospectively reviewed clinical characteristics and outcomes of 38 patients treated between 2001 and 2012 at a single institution in Lebanon. All patients received a uniform three-drug chemotherapy regimen consisting of cisplatin, doxorubicin, and methotrexate. Ifosfamide and etoposide were added to the adjuvant treatment regimen in case of metastatic disease and/or poor degree of tumor necrosis (< 90%). RESULTS: After a median follow-up of 61 months (range, 8 to 142 months), patients with localized disease had 5-year overall and event-free survival rates of approximately 81% and 68%, respectively, whereas for metastatic disease, they were approximately 42%. The most common primary site was the long bones around the knee (n = 34; 89.5%). Six patients (15.8%) had metastatic disease to lungs, and three (7.9%) had synchronous multifocal bone disease with lung metastases. Adverse prognostic factors included nonlower extremity sites, metastasis, poor degree of necrosis, and delay of more than 4 weeks in local control. In bivariable analysis, only degree of necrosis was a prognostic predictor for survival and disease recurrence. CONCLUSION: Treatment of pediatric osteosarcoma in a multidisciplinary cancer center in Lebanon resulted in survival similar to that in developed countries. Delay in local control was associated with worse outcome. The only statistically significant inferior outcome predictor was poor degree of necrosis at the time of local control.