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BACKGROUND: We aim to investigate any possible associations between chemokine receptor expression and responses to neoadjuvant chemotherapy (NAC) along with outcomes in patients with triple-negative breast cancer (TNBC) with locally advanced disease. METHOD: Expressions of chemokine receptors were examined immunohistochemically after staining archival tissue of surgical specimens (n = 63) using specific antibodies for CCR5, CCR7, CXCR4, and CXCR5. RESULTS: Patients with high CCR5, CCR7, CXCR4, and CXCR5 expression on tumors and high CXCR4 expression on tumor-infiltrating lymphocytes (TILs) were less likely to have a pathological complete response (pCR) or Class 0-I RCB-Index compared to others. Patients with residual lymph node metastases (ypN-positive), high CCR5TM(tumor), and high CXCR4TM expressions had an increased hazard ratio (HR) compared to others (DFS: HR = 2.655 [1.029-6.852]; DSS: HR = 2.763 [1.008-7.574]), (DFS: HR = 2.036 [0.805-5.148]; DSS: HR = 2.689 [1.020-7.090]), and (DFS: HR = 2.908 [1.080-7.829]; DSS: HR = 2.132 (0.778-5.846)), respectively. However, patients without CXCR5TIL expression had an increased HR compared to those with CXCR5TIL (DFS: 2.838 [1.266-6.362]; DSS: 4.211 [1.770-10.016]). CONCLUSIONS: High expression of CXCR4TM and CCR5TM was found to be associated with poor prognosis, and CXCR5TM was associated with poor chemotherapy response in the present cohort with locally advanced TNBC. Our results suggest that patients with TNBC could benefit from a chemokine receptor inhibitor therapy containing neoadjuvant chemotherapy protocols.
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Metaplastic breast carcinoma (MBC) -rare but fatal subtype of invasive breast carcinomas- provides limited benefit from conventional triple-negative breast carcinoma chemotherapy. We aimed to determine the immune density of this tumor and to evaluate of programmed death-ligand 1 (PD-L1) and chemokine receptor type 4 (CXCR4) expressions to determine whether it would benefit from immunotherapy. Clinicopathological characteristics of 85 patients diagnosed as MBC between 1997 and 2017 were retrospectively assessed. We evaluated the immunohistochemical expression of PD-L1 and CXCR4, and the extent of tumour infiltrating lymphocytes (TILs), with survival data. TILs groups were statistically significantly associated with lymph node status, histological subtype, squamous component, local recurrence and/or systemic metastasis, and disease-related deaths (p < 0.05). PD-L1 positivity in immune cells (ICs) has a statistically significant relationship with the presence of squamous component (p = 0.011) and HER2 positivity (p = 0.031). PD-L1 positivity in tumor cells (TCs) was found to be significantly more frequent in high-TILs density (p = 0.003). PD-L1 combined positive score was significantly associated with the tumors containing high-TILs density (p = 0.012) and squamous component (p = 0.035). Disease-free and disease-specific survival rates were found to be longer for the cases displaying PD-L1 positivity in ICs; and also PD-L1 positivity in ICs was found to be an independent prognostic factor. When the expression of CXCR4 was compared with clinicopathological and survival parameters, no statistically significant association was found (p > 0.05). Based on the results of this retrospective study, PD-L1 and TILs appear to be prognostic. This study provides rationale for further studies to determine whether a subset of patients with metaplastic breast cancer could derive a meaningful benefit from immune-targeting therapies.
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Carcinoma de Células Escamosas , Neoplasias de la Mama Triple Negativas , Humanos , Estudios Retrospectivos , Antígeno B7-H1/metabolismo , Pronóstico , Neoplasias de la Mama Triple Negativas/metabolismo , Carcinoma de Células Escamosas/patología , Inmunoterapia , Linfocitos Infiltrantes de Tumor , Biomarcadores de Tumor/metabolismo , Receptores CXCR4RESUMEN
Hereditary leiomyomatosis and renal cell carcinoma is caused by germline mutations in the fumarate hydratase (FH) gene and is associated with an increased incidence of leiomyomas and a potentially aggressive variant of renal cell carcinoma. Pathologic evaluation of uterine leiomyoma can provide an opportunity for early recognition of the syndrome. We reviewed all archived slides of the cases to identify the characteristic morphologic features described for FH-deficient leiomyomas. We performed immunohistochemistry on whole sections of patients with uterine leiomyoma to evaluate for both FH and 2-succinocysteine (2SC) expression. Of the 106 cases, 19 showed the characteristic eosinophilic nucleoli with perinuclear halos, and 24 revealed a characteristic eosinophilic cytoplasmic inclusion consisting of pink globules present within the cytoplasm. Both of these morphologic findings were present together in 15 cases, and hemangiopericytomatous vessels were detected in 23 cases. The loss of FH protein expression was detected in 14 out of 106 cases (13%), and 13 out of 106 cases (12%) were positive for 2SC. We detected 10 cases with both 2SC-positive and FH expression loss. The presence of eosinophilic nucleoli with perinuclear halos and eosinophilic cytoplasmic inclusion was associated with both loss of FH protein expression and 2SC positivity ( P < 0.001). These findings underscore the importance of hematoxylin and eosin-based predictive morphology in FH-deficient uterine leiomyomas. Therefore, morphologic assessment of uterine leiomyomas for features of FH deficiency can serve as a screening tool for hereditary leiomyomatosis and renal cell carcinoma syndrome, allowing patients to be divided according to their hereditary risk assessment.
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Carcinoma de Células Renales , Neoplasias Renales , Leiomiomatosis , Neoplasias Cutáneas , Neoplasias Uterinas , Femenino , Humanos , Carcinoma de Células Renales/metabolismo , Fumarato Hidratasa/genética , Fumarato Hidratasa/metabolismo , Neoplasias Renales/patología , Leiomiomatosis/diagnóstico , Leiomiomatosis/genética , Leiomiomatosis/patología , Neoplasias Cutáneas/patología , Neoplasias Uterinas/diagnósticoRESUMEN
We present two cases of ductal carcinoma in situ (DCIS) that arose in axillary lymph nodes excised as the sentinel lymph node from two patients with breast carcinoma. The patient ages were 72 and 36 years and both patients underwent mastectomy and axillary lymph node dissection. In addition to DCIS in the sentinel lymph node, the first patient had a wide DCIS and microinvasion in the ipsilateral breast and a micrometastasis in another sentinel lymph node. The second patient was operated on after neoadjuvant chemotherapy and had DCIS and a small focus of invasion, in addition to invasive and in situ ductal carcinoma in the lymph node having signs of chemotherapy-induced regression. The presence of DCIS was confirmed by use of the immunohistochemical method with antibodies against myoepithelial cells. As a potential source of cellular origin, DCIS was accompanied by benign epithelial cell clusters in the lymph node in both cases. Morphologic and immunohistochemical features were similar in breast and lymph node neoplasms. We conclude that DCIS may rarely develop from benign epithelial inclusions in the axillary lymph node and is a potential diagnostic pitfall in cases having ipsilateral breast carcinoma.
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Background: Immune checkpoint inhibition, combined with novel biomarkers, may provide alternative pathways for treating chemotherapy-resistant triple-negative breast cancer (TNBC). This study investigates the expression of new immune checkpoint receptors, including CD155 and CD73, which play a role in T and natural killer (NK) cell activities, in patients with residual TNBC after neoadjuvant chemotherapy (NAC). Methods: The expression of biomarkers was immunohistochemically examined by staining archival tissue from surgical specimens (n = 53) using specific monoclonal antibodies for PD-L1, CD155, and CD73. Results: Of those, 59.2% (29/49) were found to be positive (>1%) for PD-L1 on the tumour and tumour-infiltrating lymphocytes (TILs), while CD155 (30/53, 56.6%) and CD73 (24/53, 45.3%) were detected on tumours. Tumour expressions of CD155 and CD73 significantly correlated with PD-L1 expression on the tumour (p = 0.004 for CD155, p = 0.001 for CD73). Patients with CD155 positivity ≥10% were more likely to have a poor chemotherapy response, as evidenced by higher MDACC Residual Cancer Burden Index scores and Class II/III than those without CD155 expression (100% vs 82.6%, p = 0.03). At a median follow-up time of 80 months (range, 24-239), patients with high CD73 expression showed improved 10-year disease-free survival (DFS) and disease-specific survival (DSS) rates compared to those with low CD73 expression. In contrast, patients with CD155 (≥10%) expression exhibited a decreasing trend in 10-year DFS and DSS compared to cases with lower expression, although statistical significance was not reached. However, patients with coexpression of CD155 (≥10%) and low CD73 were significantly more likely to have decreased 10-year DFS and DSS rates compared to others (p = 0.005). Conclusion: These results demonstrate high expression of CD73 and CD155 in patients with residual tumours following NAC. CD155 expression was associated with a poor response to NAC and poor prognosis in this chemotherapy-resistant TNBC cohort, supporting the use of additional immune checkpoint receptor inhibitor therapy. Interestingly, the interaction between CD155 and CD73 at lower levels resulted in a worse outcome than either marker alone, which calls for further investigation in future studies.
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Aim: This study investigated the effect of neoadjuvant chemotherapy (NAC) on stromal tumor-infiltrating lymphocytes (sTILs) and their treatment response. Materials & methods: 115 patients with pre-NAC core biopsies and post-NAC surgical resection specimens were reviewed. Results: There was no significant change between pre- and post-treatment sTILs. Both pre- and post-NAC sTILs were significantly lower in patients with luminal A subtype. An increase in sTILs was observed in 21 (25.9%) patients after NAC, a decrease in 29 (35.8%) and no change in 31 (38.3%; p = 0.07). Pretreatment sTIL density was independent predictor of pathological complete response in multivariate analyses (odds ratio: 1.025, 95% CI: 1.003-1.047; p = 0.023). Conclusion: High sTIL density in core biopsies was independently related to pathological complete response. In addition, ER appears to be the most crucial factor determining the rate of sTIL.
New studies have shown that the tumor microenvironment is critical in tumor behavior. Immune cells surrounding tumor cells are the main components of the tumor microenvironment. Our study aimed to investigate the change in immune cells before and after chemotherapy in breast cancer patients. Our study included 115 patients. All patients underwent chemotherapy before surgery to shrink the tumor. Tru-cut biopsy pieces and the breast tissue obtained after surgery were examined. The presence of estrogen or progesterone receptors on tumor cells decreased the number of immune cells surrounding the tumor cells. The number of immune cells did not decrease after chemotherapy. Another finding was that the greater the number of immune cells around the tumor, the more likely that the tumor would disappear after chemotherapy.
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Neoplasias de la Mama , Terapia Neoadyuvante , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Femenino , Humanos , Linfocitos Infiltrantes de Tumor/patología , PronósticoRESUMEN
OBJECTIVES: This study aims to investigate the efficacy of abbreviated breast magnetic resonance imaging (MRI) in neoadjuvant chemotherapy (NAC) response evaluation. METHODS: MR images of 50 locally advanced breast cancer patients who underwent standard protocol (SP) breast MRI before and after NAC were re-evaluated retrospectively. Abbreviated protocol (AP) was obtained by extracting images from SP and then evaluating them in a separate session. Protocols were compared with the histological findings after surgery as the reference standard. RESULTS: A statistically significant difference was found between the two protocols in response evaluation by the McNemar test (p=0.018). However, the Kappa value was 0.62 (p<0.001), which indicates substantial agreement. No statistically significant differences were found between the two protocols (AP and SP) and pathological results in the McNemar test (p=0.12, p=0.60, respectively). Kappa values were 0.48 (p<0.001) and 0.60 (p<0.001), respectively, which indicates moderate agreement for both protocols with higher values by SP evaluation. The residual maximum median diameters were smaller than the pathology, with both protocols (p<0.001). CONCLUSION: Despite the statistical differences, there was a significant correlation in response evaluation between the two protocols. The pathological results were moderately correlated with both protocols, with SP slightly higher. However, the residual maximum median diameters were smaller than the pathology with both protocols. These results may limit the use of AP in evaluating the local extent of the tumor, especially in patients who will undergo breast-conserving surgery.
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Neoplasias de la Mama , Terapia Neoadyuvante , Mama/diagnóstico por imagen , Mama/patología , Mama/cirugía , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/cirugía , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Terapia Neoadyuvante/métodos , Estudios RetrospectivosRESUMEN
The assessment of immune infiltrate in invasive breast carcinomas (IBCs), most commonly referred to as tumor infiltrating lymphocytes (TILs), is gaining importance in the current quest for optimal biomarker selection and prediction of prognosis. In this study, the impact of intensity of TILs and expressions of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death-1 (PD-1), and lymphocyte activation gene 3 (LAG-3) in a group of breast carcinomas with regards to the prognosis and conventional pathologic parameters was scrutinized. For this purpose, 238 patients with IBCs containing different proportions of TILs were included in the study. IBCs with higher proportion of TILs were usually grade III carcinomas and correlated with poor prognostic features like receptor negativity, nonluminal intrinsic subtype (P<0.001). Similarly, PD-1 and LAG-3 positivity in immune cells (IC) were more likely to be positive in grade III IBC cases (P=0.004). In addition, PD-1 positivity in IC was more frequent in estrogen receptor-negative tumors (P=0.011) whereas LAG-3 positivity increased in large sized, estrogen receptor and progesterone receptor-negative tumors (P=0.050, 0.023, 0.04, respectively). CTLA-4 positivity in IC was more frequent in large-sized tumors (P=0.040). These 3 markers were also significantly associated with one another and also with the amount of TILs. In survival analysis, cases with prominent-TILs especially displaying CTLA-4, PD-1, and LAG-3 positivity appeared to have longer disease-free and overall survival (CTLA-4: P=0.027, P=0.024; PD-1: P=0.030, P=0.026; LAG-3: P=0.006, P=0.012, respectively). We conclude that the high proportion of TILs and as well as high expression of CTLA-4, PD-1, and LAG-3 in TILs have positively contributed to the outcome despite their correlation with poor conventional pathologic features. We suggest that these 3 immune markers can be used for the determination of proper treatment as well as prediction of prognosis in IBCs with TILs.
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Antígenos CD/metabolismo , Neoplasias de la Mama , Receptor de Muerte Celular Programada 1 , Antígeno B7-H1/metabolismo , Neoplasias de la Mama/metabolismo , Antígeno CTLA-4/metabolismo , Femenino , Humanos , Linfocitos Infiltrantes de Tumor/patología , Pronóstico , Receptor de Muerte Celular Programada 1/metabolismo , Receptores de Estrógenos/metabolismo , Proteína del Gen 3 de Activación de LinfocitosRESUMEN
BACKGROUND: Studies on PD-L1 expression in breast cancer have gained importance in recent years, especially in triple-negative breast cancer (TNBC). Our aim was to analyze the differential expression of PD-L1 to explore its correlation with response to neoadjuvant chemotherapy (NACT) and patient survival. METHODS: PD-L1 expression was evaluated immunohistochemically (Ventana SP263 clone kit) by staining tumor specimen. PD-L1 positivity was defined as membranous staining > 1%, > 5%, > 10%, and > 20% on either tumor cell (TC) and /or immune cell (IC). RESULTS: Fifty patients with locally advanced TNBC, who had a partial response to NACT, were included in the study. PD-L1 staining was observed in TCs in 25 patients (50%) and in ICs in 23 patients (46%) when PD-L1 > 1% was considered positive. Patients with PD-L1 positivity on ICs were more likely to respond to chemotherapy as measured by "MD Anderson Cancer Center Residual Cancer Burden Index" (14/22, 63.6% vs. 10/27, 37%, p = 0.064). The 5-year disease-free survival (DFS) and disease-specific survival (DSS) rates were 46.3% and 51.4%, respectively. A high (> 20%) tumoral PD-L1 positivity was associated with a better DFS and DSS. CONCLUSIONS: Studies in the literature mostly focused on PD-L1 expression in inflammatory cells. However, our results suggest that patients with a high PD-L1 expression on TCs were more likely to have a better outcome. Since patients with residual tumor burden who express PD-L1 on TILs were more likely to respond to NACT, an immune checkpoint inhibitor therapy in addition to NACT would be an important option for TNBC with locally advanced disease.
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Antígeno B7-H1 , Neoplasias de la Mama Triple Negativas , Antígeno B7-H1/metabolismo , Humanos , Linfocitos Infiltrantes de Tumor , Terapia Neoadyuvante , Neoplasia Residual , Pronóstico , Neoplasias de la Mama Triple Negativas/tratamiento farmacológicoRESUMEN
BACKGROUND: The expression of immune checkpoint receptors (ICRs) on tumor-infiltrating lymphocytes (TILs) is associated with better response to immunotherapies via immune checkpoint inhibitors. Therefore, we investigated various ICR expressions on TILs in patients with locally advanced triple-negative breast cancer (TNBC) after neoadjuvant chemotherapy (NAC). METHODS: Expressions of ICRs were examined immunohistochemically in surgical specimens (n = 61) using monoclonal antibodies for PDL-1, PD-1, TIM-3, LAG-3, and CTLA-4. Positivity was defined as staining > 1% on TILs. RESULTS: The median age was 49 (24-76) years. The majority of patients were clinically T3-4 (n = 31, 50.8%) and clinically N1-3 (n = 58, 95.1%) before NAC. Of those, 82% were found to have CTLA-4 positivity, whereas PD1, PDL-1, LAG3, and TIM-3 expressions on TILs were 62.3, 50.9, 26.2, and 68.9%. A high expression of CTLA-4 was found to be associated with a better chemotherapy response (OR = 7.94, 95% CI: 0.9-70.12, p = 0.06), whereas TIM-3 positivity was contrarily associated with a worse chemotherapy response (OR = 0.253, 95% CI: 0.066-0.974, p = 0.047) as measured by the MDACC Residual Cancer Burden Index. At a 47-month follow-up, ypN0 (DFS; HR = 0.31, 95% CI: 0.12-0.83, p = 0.02 and DSS; HR = 0.21, 95% CI: 0.07-0.62, p = 0.005) and CTLA-4 high expression on TILs (DFS; HR = 0.38, 95% CI: 0.17-0.85, p = 0.019 and DSS; HR = 0.34, 95% CI: 0.15-0.78, p = 0.01) were found to be associated with improved survival. CONCLUSIONS: These findings demonstrate that CTLA-4, PD-1, PDL-1, and TIM-3 were highly expressed in TNBC. Based on these high expression patterns, further studies directed towards combined therapies are warranted in advanced TNBC in future.
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Receptor 2 Celular del Virus de la Hepatitis A/metabolismo , Linfocitos Infiltrantes de Tumor/inmunología , Terapia Neoadyuvante/métodos , Neoplasias de la Mama Triple Negativas/genética , Adulto , Anciano , Femenino , Humanos , Persona de Mediana Edad , Adulto JovenRESUMEN
Sex cord tumor with annular tubules (SCTAT) is a highly rare type of ovarian sex cord-stromal tumor (SCST), the diagnosis of which remains to be challenging. The aim of this study was to scrutinize the utility of three immunohistochemical markers including Forkhead box protein 2 (FOXL2), SOX9, and ß-catenin and DICER1 mutation status in distinguishing SCTATs from other ovarian SCSTs. Nine cases of SCTAT, 10 Sertoli-Leydig cell tumor (SCLT), 10 adult-type granulosa cell tumor (AGCT), and 8 juvenile-type granulosa cell tumor (JGCT) were included in the study. SCTATs were characterized by diffuse and strong expression of SOX9, focal and weak expression of FOXL2, and the absence of DICER1 mutation. However, AGCTs and JGCTs displayed strong and diffuse expression of FOXL2, focal/no immunoreaction for SOX9. SLCTs generally showed moderate intensity of FOXL2 and SOX9 expression. Nuclear ß-catenin expression was observed in none of SLCT, 1/9 of SCTAT, 6/8 JGCT, and 4/10 AGCT cases, respectively. DICER1 hotspot mutation was detected in only 3 cases of SLCT and 2 cases of JGCT. We conclude that in addition to strong and diffuse SOX9 expression, weak/absent expression of FOXL2 is suggestive for the diagnosis of SCTAT. Hence, we suggest that inclusion of these two markers, SOX-9 and FOXL2, to the immunohistochemical panel helps in differentiation of SCTAT from other SCSTs in addition to morphologic findings. We also conclude that SCTATs of the ovary do not harbor DICER1 hotspot mutation.
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Biomarcadores de Tumor , ARN Helicasas DEAD-box/genética , Proteína Forkhead Box L2/análisis , Mutación , Neoplasias Ováricas , Ribonucleasa III/genética , Factor de Transcripción SOX9/análisis , Tumores de los Cordones Sexuales y Estroma de las Gónadas , beta Catenina/análisis , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Estudios de Casos y Controles , Análisis Mutacional de ADN , Diagnóstico Diferencial , Femenino , Tumor de Células de la Granulosa/química , Tumor de Células de la Granulosa/genética , Tumor de Células de la Granulosa/patología , Humanos , Inmunohistoquímica , Neoplasias Ováricas/química , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Valor Predictivo de las Pruebas , Tumor de Células de Sertoli-Leydig/química , Tumor de Células de Sertoli-Leydig/genética , Tumor de Células de Sertoli-Leydig/patología , Tumores de los Cordones Sexuales y Estroma de las Gónadas/química , Tumores de los Cordones Sexuales y Estroma de las Gónadas/genética , Tumores de los Cordones Sexuales y Estroma de las Gónadas/patologíaRESUMEN
PURPOSE: To investigate whether CD73 had a role in the pathogenesis of polypoid endometriosis. METHODS: Our study included 15 cases of polypoid endometriosis, which were diagnosed between 2005 and 2019. Clinical findings were gathered from archive files of relevant clinics and pathology reports. All glass slides were re-examined for confirmation of the diagnosis and the detection of additional microscopic findings. An immunohistochemical examination was performed using anti CD73 antibodies in 15 cases of polypoid endometriosis, and also in a control group that contained 9 cases of endometrial polyps and 9 cases of ovarian conventional endometriosis. RESULTS: In addition to standard gynecologic operations, major non-gynecologic procedures had to be performed in 7 cases. In two cases, the surgical team comprised only general surgeons, and a misdiagnosis of carcinoma was made during the frozen section in one case. The majority of the cases displayed gross polypoid lesions that measured 0.7-13 cm. The most common sites were the ovary and rectosigmoid colon. Microscopically, all lesions exhibited a fibrovascular stroma reminiscent of endometrial stroma, whereas glandular features varied. Immunohistochemical examinations revealed a significant loss of CD73 expression in the stroma of polypoid endometriosis in contrast to the control cases, which retained stromal CD73 expression (p < 0.0001). CONCLUSION: Both pathologists and surgeons performing abdominal surgeries should be aware of polypoid endometriosis because it mimics malignancy with its clinical, gross, and microscopic features. We also conclude that loss of stromal CD73 expression, due to its effect on the extracellular ATP/adenosine balance, may contribute to the pathogenesis of this rare form of endometriosis.
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5'-Nucleotidasa/metabolismo , Endometriosis , Pólipos , Endometriosis/diagnóstico , Endometriosis/patología , Endometrio/patología , Femenino , Proteínas Ligadas a GPI/metabolismo , Humanos , Neoplasias Ováricas/patología , Pólipos/patología , Neoplasias Uterinas/patologíaRESUMEN
BACKGROUND: Germline DICER1 mutations increase the risk of developing a wide variety of generally uncommon tumors. We describe a case of DICER1-related embryonal rhabdomyosarcoma (ERMS) of the uterine corpus in a prepubertal girl. CASE: A 10-year-old- girl with a history of cystic nephroma presented with a 3-week history of vaginal bleeding. A 3-cm mass filling the uterine cavity was detected, and histopathologic examination of hysteroscopy-guided biopsy samples revealed ERMS. Molecular genetic sequencing of the tumor sample revealed a DICER1 mutation. SUMMARY AND CONCLUSION: This report highlights the importance of screening for DICER1 mutations in the presence of the early-onset features of this syndrome, and extends the spectrum of DICER1-related tumors by showing the mutation in a case of ERMS of the uterine corpus.
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Rabdomiosarcoma Embrionario/genética , Neoplasias Uterinas/genética , Quimioterapia Adyuvante/métodos , Niño , ARN Helicasas DEAD-box , Femenino , Mutación de Línea Germinal , Humanos , Histerectomía , Rabdomiosarcoma Embrionario/diagnóstico , Rabdomiosarcoma Embrionario/patología , Rabdomiosarcoma Embrionario/terapia , Ribonucleasa III , Hemorragia Uterina/etiología , Neoplasias Uterinas/diagnóstico por imagen , Neoplasias Uterinas/patología , Neoplasias Uterinas/terapiaRESUMEN
INTRODUCTION: Giant vulvar condyloma is usually associated with the HPV subtypes 6 and 11 and is characterized by excessive growth of verrucous lesions on the genitals and/or perianal region. It may be observed in sexually inactive as well as sexually active women. Immunosuppression plays an important role in the development of the disease. PATIENTS AND METHODS: We report two cases of giant vulvar condyloma together with the review of the literature. RESULTS: One case was a 21-year old sexually inactive woman with a history of Type 1 Diabetes. Second case was a 20-year-old sexually active woman with a rapidly progressing disease and cervical dysplasia. Both cases were operated; all the condylomatous structures were resected with preservation of the anatomy and clitoral innervation and blood flow. Skin and subcuticular dehiscence was the only complication encountered in the first case. CONCLUSION: Main treatment of giant vulvar condyloma is surgical resection with maintenance of the vulvar anatomy. Preservation of especially the clitoral innervation as much as possible is very important.
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In this article, we present a case of anastomosing hemangioma that shows cystic change. The tumor was a unilocular cystic lesion consisting of 2 distinct layers. The inner layer was composed of a proliferation of capillary-sized blood vessels resembling red pulp of the spleen. The outer layer was composed of stromal cells that resembled Leydig or steroid cell tumor of the ovary. An immunohistochemical examination confirmed endothelial and stromal characteristics of the layers, respectively. An ultrastructural analysis revealed absence of Reinke crystalloids in the stromal cells. We conclude that anastomosing hemangioma may rarely arise from the ovary as a cystic tumor and may be accompanied with luteinization of stromal cells.
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Hemangioma/diagnóstico , Quistes Ováricos/diagnóstico , Neoplasias Ováricas/diagnóstico , Ovario/patología , Biomarcadores de Tumor/análisis , Diagnóstico Diferencial , Femenino , Hemangioma/patología , Hemangioma/cirugía , Humanos , Hallazgos Incidentales , Tumor de Células de Leydig/diagnóstico , Tumor de Células de Leydig/patología , Microscopía Electrónica , Persona de Mediana Edad , Quistes Ováricos/patología , Quistes Ováricos/cirugía , Neoplasias Ováricas/patología , Neoplasias Ováricas/cirugía , Ovario/diagnóstico por imagen , Ovario/cirugía , Ovario/ultraestructura , UltrasonografíaRESUMEN
This study was conducted to determine the demographic and clinicopathologic characteristics and evaluate the prognostic value of various factors, such as the extensiveness of surgery, related to the tumour itself and the clinical features in the recurrence of borderline ovarian tumours (BOT). We retrospectively evaluated the data of 103 patients with a borderline ovarian tumours treated at our institution between the years 2000 and 2012. The median age was 37 (16-79) years and the majority of the patients were premenopausal (76.7%). During the follow-up, 16 recurrences were observed (15.5%). The multivariate analysis showed that the micropapillary architecture and fertility sparing surgery were the only significant independent predictors for the development of a recurrence amongst all of the demographic and clinicopathological features. In our study group, we identified that the micropapillary architecture itself and the fertility sparing surgery had a significant impact on the development of a BOT recurrence. The patients who possess these features should be followed up more closely for a long time period. Impact statement What is already known on this subject? A borderline ovarian tumour is known as a recurrent disease. The recurrence rate varies between 5 and 20%. It is well known in the literature that patients treated by an oophorectomy have a relatively lower risk of development of a recurrence compared to the patients treated by cystectomy. What do the results of this study add? Although some of the clinicopathological features are shown to be risk factors for the development of a recurrence in many studies, some of the pathological-clinical and the demographic features have not been described as yet, or have been considered to be equivocal regarding the development of a recurrence. In this study, we investigate all possible demographic, pathological, and clinical factors associated with a recurrence. Not only the well-known pathological characteristics but also the new pathological parameters and clinical approaches have been investigated. For instance, microinvasion architecture and lymphadenectomy speculated in the literature as the risk factors for the development of a recurrence, have not been identified as risk factors in our study. On the other hand, our statistical analyses have revealed that micropapillary architecture should be described as a risk factor for the development of a recurrence. What are the implications of these findings for clinical practice and/or further research? We hope our study becomes influential in the literature on the field of a micropapillary architecture and the development of a recurrence. The patients carrying this feature have to be followed up very closely and carefully. Furthermore, our findings have indicated no significant relation between the performing of a lymphadenectomy and the rate of a recurrence. This result might be encouraging for the gynaecological surgeons to refrain from a lymphadenectomy for the borderline ovarian tumours.
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Cistadenocarcinoma/patología , Recurrencia Local de Neoplasia/etiología , Neoplasias Ováricas/patología , Ovario/patología , Adolescente , Adulto , Anciano , Cistadenocarcinoma/cirugía , Femenino , Humanos , Escisión del Ganglio Linfático , Persona de Mediana Edad , Tratamientos Conservadores del Órgano , Neoplasias Ováricas/cirugía , Estudios Retrospectivos , Adulto JovenRESUMEN
OBJECTIVE: To elucidate the immunohistochemical (IHC) differences of endometrioma tissues that may have the potential to progress to ovarian clear cell carcinoma (OCCC) by using KRAS, HNF1ß, PIK3CA, PPP2R1A, and ARID1A as biomarkers. STUDY DESIGN: This is a retrospective clinical study, which was conducted in an university hospital. The groups comprised 14 patients with endometrioma resection who later developed OCCC (non-healthy endometrioma-case group) and 66 patients with endometrioma resection who did not develop ovarian cancer in subsequent follow-ups (healthy endometrium-control group). IHC staining with KRAS, HNF1ß, PIK3CA, PPP2R1A, and ARID1A antibodies was performed in paraffin blocks of endometriomas obtained in both groups. For KRAS, PIK3CA, PPP2R1A, and ARID1A, cell staining intensity on a scale from 0 (negative) to 3 (strongly positive), and for HNF1ß, the percentage of stained cells (0-5) and the intensity of staining (0-3) were scored. RESULTS: KRAS, HNF1ß, PIK3CA, PPP2R1A, and ARID1A were overexpressed in the case group samples compared with the endometrioma samples in the epithelial cells, and ARID1A and KRAS in the stroma were overexpressed in the case group samples compared with the matched control samples. CONCLUSIONS: KRAS, HNF1ß, PIK3CA, PPP2R1A, and ARID1A immunostaining scores in endometriomas previous to OCCC were significantly different than in endometriomas with no malignancy occurring in subsequent follow-ups, and were single predictors of OCCC. Hence, immunostaining with these biomarkers may be a method of identifying patients with endometrioma who have the potential to develop OCCC.
Asunto(s)
Adenocarcinoma de Células Claras/patología , Endometriosis/patología , Neoplasias Ováricas/patología , Adenocarcinoma de Células Claras/genética , Adulto , Biomarcadores/metabolismo , Estudios de Casos y Controles , Fosfatidilinositol 3-Quinasa Clase I/metabolismo , Proteínas de Unión al ADN , Progresión de la Enfermedad , Endometriosis/complicaciones , Endometriosis/genética , Endometrio/metabolismo , Endometrio/patología , Femenino , Estudios de Seguimiento , Factor Nuclear 1-beta del Hepatocito/metabolismo , Humanos , Inmunohistoquímica/métodos , Proteínas Nucleares/metabolismo , Neoplasias Ováricas/genética , Proteína Fosfatasa 2/metabolismo , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , Estudios Retrospectivos , Coloración y Etiquetado/métodos , Factores de Transcripción/metabolismo , Adulto JovenRESUMEN
OBJECTIVE: As patients with increased human epidermal growth factor receptor (HER2) overexpression are more likely to benefit from trastuzumab treatment, the accuracy of HER2 receptor status in breast cancer patients is significant for appropriate disease management. However, this assessment is not harmonized and results may be highly variable between centers. The aim of this study was to investigate the degree of interlaboratory variability in the results of HER2 expression reported by 5 participating centers and to assess the concordance between these centers and a reference laboratory.Materials and Methods: A total of 30 breast cancer samples were tested and scored for HER2 expression using immunohistochemical method in 5 centers from Turkey and in a reference laboratory from Netherlands (Academic Medical Center, Amsterdam). All the participating centers had an experience of more than 10 years regarding the HER2 testing. The results were compared both among the centers and with the reference laboratory. RESULTS: When the concordance of participating centers and the reference laboratory was evaluated regarding negative (0-1+), equivocal 2(+) and positive 3(+) classification of HER2 immunostaining, the highest concordance was found in Center-A, and the lowest in Center-C (Kendall's tau-b concordance coefficient 0.911 and 0.724, respectively). The concordance of the centers with reference laboratory was 80.0% both in equivocal and positive samples, while it increased up to 91.8% in negative samples. CONCLUSIONS: This study showed that in general there is sufficiently good agreement between the reference laboratory and the participating centers for immunohistochemical HER2 assessment.
RESUMEN
BACKGROUND We compared pathological prognostic stage (PPS) with anatomic stage (AS) groups according to the updated version of breast cancer staging of the American Joint Committee on Cancer (AJCC) 8th Edition. MATERIAL AND METHODS We evaluated 353 breast cancer patients initially treated with surgery. AS and PPS were performed by evaluating the pathological data of the patients according to the AJCC 8th Edition breast cancer updated version. Stages and survival rates between the 2 staging systems were evaluated and compared. Disease-free survival (DFS) and disease-specific survival (DSS) were calculated according to both staging systems using Kaplan-Meier test. After the PPS change was made in each AS group, 10-year DFS and 10-year DSS of the changed groups were compared using the chi-square test. RESULTS The median follow-up was 114 months and the median age was 48 years. In 192 (54.4%) patients the stage change. The most significant change was 1-level downstaging in 70 (22.4%) patients, and 2-levels downstaging in 78 (22.1%) patients. Five-year DFS, 10-year DFS, 5-year DSS rate, and 10-year DSS were 86.3%, 80.3%, 93.8%, and 84.1%, respectively. The PPS system was found to provide better prognostic information when the patients with AS IIB and IIIA groups were compared according to the PPS. CONCLUSIONS According to the updated version of the AJCC 8th Edition, half of our patients had stage change when they were evaluated according to AS and PPS system. PPS gives better information about prognosis than does AS.