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OBJECTIVE: The deregulation of E-cadherin is associated with Src/FAK signaling axis and histone deacetylase (HDAC)/EZH2 activity. However, the association between EZH2 and FAK and its clinical significance in endometrial carcinoma has not been reported. METHODS: 202 archived cases of endometrial carcinoma (1996-2000) were reviewed and divided into two subtypes. TMAs were developed as per established procedures. EZH2, FAK, and pFAK immunohistochemical stains were performed and the expression was scored as negative (0), low (1) and high (2). Proper statistical analysis was used to assess the correlation between the expression profiles and the clinicopathological parameters and clinical outcome. RESULTS: A total of 141 (69.8%) type-1 tumors and 61 (30.2%) type-2 tumors were identified. EZH2 overexpression was identified in 7.6% of type-1 tumors vs. 63% of type-2 tumors (p<0.001). FAK and pFAK overexpression was only seen in 24.8% and 1.7% of Type-1 tumors as compared to 72% and 58.8% of type-2 tumors, respectively (p<0.001). A positive correlation between the expression of EZH2, FAK, pFAK and PTEN (p<0.0001) was found. The overexpression of EZH2, FAK, and pFAK were significantly associated with high histologic grade, angiolymphatic invasion, lymph node metastasis, myometrial invasion and cervical involvement (p<0.01). Kaplan-Meier analysis demonstrates that the overexpression of EZH2 (p=0.0024), FAK and pFAK (p=0.0001) was significantly associated with decreased overall survival. CONCLUSION: The overexpression of EZH2, FAK and pFAK correlates with well established pathologic risk factors and may predict a more aggressive biologic behavior in endometrial carcinoma, transforming these proteins into potential therapeutic targets for treatment of endometrial cancer.
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Neoplasias Endometriales/metabolismo , Quinasa 1 de Adhesión Focal/biosíntesis , Complejo Represivo Polycomb 2/biosíntesis , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Endometriales/enzimología , Neoplasias Endometriales/patología , Proteína Potenciadora del Homólogo Zeste 2 , Activación Enzimática , Femenino , Humanos , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Fosfohidrolasa PTEN/metabolismo , Fosforilación , Tasa de Supervivencia , Regulación hacia Arriba , Adulto JovenAsunto(s)
Anemia/complicaciones , Cuerpos de Inclusión/patología , Neutrófilos/patología , Infecciones Urinarias/complicaciones , Anciano de 80 o más Años , Anemia/sangre , Anemia/diagnóstico , Anemia/patología , Muerte , Humanos , Masculino , Pronóstico , Infecciones Urinarias/sangre , Infecciones Urinarias/diagnóstico , Infecciones Urinarias/patologíaRESUMEN
BACKGROUND: Small cell carcinoma (SMCC) is rarely diagnosed in urine specimens. Cytologically, this tumor is similar to pulmonary SMCC. However, clinicopathologic correlation may be required to differentiate between primary urinary bladder SMCC and metastatic SMCC from a remote primary or secondary bladder involvement by direct extension of the tumor from nearby organs (prostate, uterus, or ovary). A unique case of a rare pulmonary-type ovarian SMCC, the tumor cells of which were detected in a voided urine specimen, is described herein. CASE: A 79-year-old female presented to the urologic clinic with a history of metastatic SMCC of unknown primary with hematuria. The voided urine specimen examination revealed tumor cells cytomorphologically consistent with small cell neuroendocrine carcinoma. Following cytologic diagnosis, cystoscopic examination and bladder biopsy were performed. The histopathology revealed a widely invasive tumor with a morphology typical of SMCC. The overlying urothelium was unremarkable. By immunohistochemistry, tumor cells were found positive for neuroendocrine markers, EMA and WT-1. The morphologic and immunohistochemical features of the tumor were most consistent with urinary bladder involvement by pulmonary-type primary ovarian SMCC. CONCLUSION: It is justified to think that SMCC cell detection in urine specimens does not necessarily imply their origin from primary bladder malignancy. Performing additional studies may be prudent in order to exclude secondary involvement of the bladder in this tumor as the correct diagnosis has significant clinical implications.
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Carcinoma de Células Pequeñas/patología , Carcinoma de Células Pequeñas/orina , Neoplasias Ováricas/patología , Neoplasias Ováricas/orina , Orina/citología , Anciano , Carcinoma de Células Pequeñas/diagnóstico , Femenino , Humanos , Metástasis de la Neoplasia , Neoplasias Ováricas/diagnósticoRESUMEN
Diagnosis of hematologic malignancies have matured to encompass molecular as well as phenotypic characteristics. Cytogenetic abnormalities are considered common events in this regard. These abnormalities generally consist of structural chromosomal abnormalities or gene mutations, which often are integral to the pathogenesis and subsequent evolution of an individual malignancy. Improvements made in identifying and interpreting these molecular alterations have resulted in advances in the diagnosis, prognosis, monitoring, and therapy for cancer. As a consequence of the increasingly important role of molecular testing in hematologic malignancy management, this article presents an update on the importance and use of molecular tests, detailing the advantages and disadvantages of each test when applicable.
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Análisis Citogenético , Neoplasias Hematológicas/diagnóstico , Técnicas de Diagnóstico Molecular , Aberraciones Cromosómicas , Neoplasias Hematológicas/genética , HumanosRESUMEN
We report an unusual case of fully developed fetal intestinal segment(s) within a nodule on the chorionic plate of the placenta of a 27-year-old female patient at 37 weeks gestation with spontaneous vaginal delivery. Gross examination of the placenta revealed a chorionic plate nodule near the insertion of the umbilical cord, which, upon microscopic evaluation, raised the differential diagnostic possibilities of placental teratoma, vitelline/omphalomesenteric duct anomaly, and intestinal organoid differentiation. We discuss the distinguishing features, morphogenesis, and clinical significance of the aforementioned entities and review the pertinent medical literature.
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Ovarian hyperthecosis, a source of estrogen, may occur in postmenopausal women. In this study, we evaluated the possible association of ovarian hyperthecosis with endometrial polyp, endometrial hyperplasia, and endometrioid adenocarcinoma in postmenopausal women. Our study consisted of 238 postmenopausal women: 108 with endometrioid adenocarcinoma and 130 without endometrial carcinoma. The International Federation of Gynecology and Obstetrics system was used to grade endometrioid adenocarcinoma. Within the endometrioid adenocarcinoma cases, 48 (44.4%) were grade 1, 46 (42.6%) were grade 2, and 14 (13.0%) were grade 3. Among the noncancer cases, 71 (54.6%) had atrophic endometrium, 32 (24.6%) had endometrial polyp, and 27 (20.8%) had endometrial hyperplasia. The frequency of ovarian hyperthecosis in patients with endometrial polyp (46.9%), endometrial hyperplasia (55.6%), and grade 1 (43.8%), grade 2 (54.3%), and grade 3 (57.1%) endometrioid adenocarcinoma was each significantly higher than that in patients with atrophic endometrium (23.9%), supporting an association of these lesions with ovarian hyperthecosis in postmenopausal women. There was no statistically significant difference in the rate of ovarian hyperthecosis among patients with endometrial polyp, endometrial hyperplasia, and grade 1, grade 2, and grade 3 endometrioid adenocarcinoma. Our study indicates that ovarian hyperthecosis with its resultant risk factor of hyperestrinism may contribute to the pathogenesis of endometrial polyp, endometrial hyperplasia, and endometrioid adenocarcinoma in postmenopausal women. Although some studies show that grade 3 endometrioid adenocarcinoma has different genetic/molecular changes from its lower-grade counterparts, our study suggests that endometrioid adenocarcinoma of all grades may share the common risk factor of hyperestrinism.
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Carcinoma Endometrioide/patología , Hiperplasia Endometrial/patología , Neoplasias Endometriales/patología , Endometrio/patología , Ovario/patología , Pólipos/patología , Posmenopausia , Biopsia , Carcinoma Endometrioide/cirugía , Estudios de Casos y Controles , Hiperplasia Endometrial/cirugía , Neoplasias Endometriales/cirugía , Endometrio/cirugía , Femenino , Humanos , Histerectomía , Persona de Mediana Edad , Clasificación del Tumor , Pólipos/cirugíaRESUMEN
Adrenocortical carcinoma (ACC) is a rare endocrine malignancy that is usually large (>5 cm) at time of diagnosis. Delayed diagnosis significantly worsens survival. We describe adrenal gland morphology prior to ACC diagnosis and discern potential causes of delayed diagnosis. ACC patients seen at The University of Texas MD Anderson Cancer Center between 1998 and 2014 who had cross-sectional body imaging ≥3 months prior to their diagnosis. We conducted a detailed review of clinical and radiological features in these patients prior to ACC diagnosis. Of 439 patients with ACC, 25 had imaging preceding ACC diagnosis (5 with normal adrenal glands and 20 with preexisting masses). On the first available images, the median mass size was 2.8 cm (range 0-9) with median precontrast density of 36 Hounsfield units (range 17-43) and became 9 cm (range 1-18) at the time of ACC diagnosis. The median interval between first available image and ACC diagnosis was 20 months (range 3-89). In the 5 patients whose initial images showed normal adrenal glands, the time between the last normal scan and ACC diagnosis ranged from 5 to 36 months. The most common reason for delayed ACC diagnosis was the presumed benign status of the preexisting mass (n = 13, 65 %). Radiologically suspicious adrenal masses can precede ACC diagnosis and have variable growth patterns. ACC can also develop de novo within a few months in a radiologically documented normal adrenal gland. The presumed benignancy of preexisting masses based on size is the main reason for delayed ACC diagnosis.
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Neoplasias de la Corteza Suprarrenal/patología , Glándulas Suprarrenales/patología , Adrenalectomía , Carcinoma Corticosuprarrenal/patología , Adulto , Anciano , Anciano de 80 o más Años , Diagnóstico Tardío , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Sebaceous lymphadenoma (SLA) is a rare benign tumor of the salivary gland that commonly arises in the parotid gland in adults. It is rarely diagnosed correctly preoperatively. In addition, to the best of our knowledge, SLA has not been described yet in the literature in association with Cowden's syndrome (CS). We present an extremely rare case of parotid SLA that was diagnosed preoperatively by fine needle aspiration in a patient with CS.
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Hepatosplenic T-cell lymphoma (HSTL) is a rare T-cell neoplasm of the lymphoid system. This type of lymphoma is characterized by sinusoidal infiltration of spleen, liver, bone marrow and lymph nodes by neoplastic lymphocytes. Here, we discuss a patient who had a left axillary lymph node biopsy with characteristic histological and immunohistochemical features of HSTL. In addition, infiltrating neoplastic T-cells and simultaneous characteristic features of myelofibrosis (MF) were also present in the bone marrow biopsy specimen. In contrast to secondary MF, primary MF is a progressive disease and may significantly affect the prognosis of coexisting HSTL. There are few reports in the literature talking about mild bone marrow fibrosis in association with T cell lymphoma, however marked increase in bone marrow fibrosis and HSTL never being reported. This case is shedding light on HSTL and marked increase in bone marrow fibrosis.
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Cytogenetic abnormalities are considered to be common events in hematologic malignancies. These abnormalities generally consist of structural chromosomal abnormalities or gene mutations, which often are integral to the pathogenesis and subsequent evolution of an individual malignancy. Improvements made in identifying and interpreting these molecular alterations have resulted in advances in the diagnosis, prognosis, monitoring, and therapy for cancer. As a consequence of the increasingly important role of molecular testing in hematologic malignancy management, this article presents an update on the importance and use of molecular tests, detailing the advantages and disadvantages of each test when applicable.
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Neoplasias Hematológicas/diagnóstico , Técnicas de Diagnóstico Molecular , HumanosRESUMEN
INTRODUCTION: Human immunodeficiency virus-1 (HIV-1) infected monocytes are now believed to serve as a reservoir for HIV-1 infection, and to play a role in viral rebound phenomena in certain groups of patients who failed or stopped highly active antiretroviral therapy (HAART). Data characterizing the morphological changes of peripheral blood monocytes in HIV-1-infected individuals are limited. MATERIALS AND METHODS: In this study, we collected monocytes from 21 asymptomatic HIV-1-infected individuals with CD4 count more than 500 cells/mm(3) and healthy individuals. The monocytes ultrastructural morphologic changes and α-naphthyl butyrate esterase (ANBE) activity were compared between the two groups. RESULTS: In monocytes from patients infected with HIV-1, activity of α-naphthyl butyrate esterase (ANBE) was markedly increased compared with normal monocytes. In both light microscopic and ultrastructural studies, the cytoplasm of monocytes from HIV-1-infected patients contained a haphazard appearing network of thin fibrils. Cell surface expression of the activation marker HLA-DR molecule was upregulated. There were no discernible differences between the cell surface expression of CD4, CD14, and CD16 molecules comparing normal monocytes to those from HIV-1-infected patients. α-naphthyl butyrate esterase (ANBE) was markedly increased compared with normal monocytes. In both light microscopic and ultrastructural studies, the cytoplasm of monocytes from HIV-1-infected patients contained a haphazard appearing network of thin fibrils. Cell surface expression of the activation marker HLA-DR molecule was upregulated. There were no discernible differences between the cell surface expression of CD4, CD14, and CD16 molecules comparing normal monocytes to those from HIV-1-infected patients. CONCLUSIONS: Possibly, changes in the activity of ANBE along with a disrupted appearing cytoplasmic fibril network contribute to monocyte dysfunction in HIV-1-infected patients.
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Esthesioneuroblastoma (ENB) is a rare tumor derived from olfactory neuroepithelium. ENB in a site outside of where olfactory epithelium exists is exceedingly rare with only five cases of ENB isolated to the sphenoid sinuses described in the literature to date. To the best of our knowledge, a skin metastasis of ENB outside the head and neck region has not been reported. We present an unusual case of a 33-year-old male diagnosed with primary sphenoid sinus ENB, who underwent surgical resection of the tumor followed by chemoradiation. About 5 months later, the patient developed a dermal mass in the sternal region, clinically suspicious for metastasis. Fine needle aspiration (FNA) revealed a tumor with morphological features and immunophenotype consistent with the metastasis from patient's known primary sphenoid sinus ENB. Our case demonstrates that the skin may be a rare site of a metastatic ENB, and FNA is a cost-effective and reliable diagnostic method of a suspected cutaneous metastasis.
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Intravascular papillary endothelial hyperplasia (IPEH), also known as Masson's tumor, is a benign unusual vascular lesion thought to arise from an organizing thrombus. Histologically, IPEH is characterized by papillary fronds lined by proliferating endothelium that may mimic angiosarcoma, and therefore the correct diagnosis may prevent unnecessary radical procedures. Involvement of the bladder is extremely rare, with only three cases reported in the literature. We report a case of IPEH arising in the bladder of a patient with history of prostate cancer treated with radiotherapy.
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INTRODUCTION: Glucose transporter 1 (Glut-1) is a facilitative glucose transporter expressed in many cancers including breast cancer. Basal-like breast cancer (BLBC) is a high-risk disease associated with poor prognosis and lacks the benefit of targeted therapy. The aim of this study was to characterize the immunohistochemical (IHC) expression of Glut-1 in patients with BLBC compared with non-BLBC. MATERIALS AND METHODS: We identified 523 cases of invasive breast carcinoma from our database. The clinicopathologic findings and the biologic markers including estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (Her2) status were reviewed. IHC stains for cytokeratin 5/6 (CK5/6), epidermal growth factor receptor (EGFR), p53, and Glut-1 were performed on tissue microarray using standard procedures. BLBC was defined as ER-,PR-, Her2-, and CK5/6+ and/or EGFR+. RESULTS: Of informative cases, 14.7% were categorized as BLBC versus 85.3% as non-BLBC. Glut-1 was expressed in 42 (76.4%) of 55 BLBCs, whereas only 55 (23.8%) of 231 non-BLBCs showed immunostaining for Glut-1 (P < .001). Overall, Glut-1 expression was significantly associated with high histologic grade, ER negativity, PR negativity, CK5/6 positivity, EGFR expression, and high p53 expression (P < .001). However, there was no correlation between Glut-1 immunostaining and patient's outcome. CONCLUSIONS: Our results show that Glut-1 is significantly associated with BLBC and might be a potential therapeutic target for this aggressive subgroup of breast cancer, and this warrants further investigations.