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OBJECTIVE: This multicenter study aimed to evaluate the accuracy of the one-step nucleic acid amplification (OSNA) assay in diagnosing lymph node metastasis (LNM) in patients with cervical and endometrial cancers. METHODS: Surgically removed LNs from patients with cervical and endometrial cancer were sectioned at 2-mm intervals along the short axis direction and alternately examined using the OSNA assay and conventional histopathological examination. Ultrastaging (200-µm LN sections) was performed for metastatic LNs using hematoxylin and eosin staining and immunostaining with an anti-CK19 antibody in cases where the OSNA assay and histopathological examination (performed using 2-mm LN sections) results showed discordance. RESULTS: A total of 437 LNs from 133 patients were included; 61 patients (14%) showed metastasis by histopathological examination, with a concordance rate of 0.979 (95% confidence interval [CI]: 0.961-0.991) with the OSNA assay. The sensitivity and specificity of the OSNA assay were 0.918 (95% CI: 0.819-0.973) and 0.989 (95% CI: 0.973-0.997), respectively. Discordance between the two methods was observed in nine LNs (2.1%), and allocation bias of metastatic foci was identified as the major cause of discordance. CONCLUSIONS: The OSNA assay showed equally accurate detection of LN metastasis as the histopathological examination. We suggest that the OSNA assay may be a useful tool for the rapid intraoperative diagnosis of LN metastasis in patients with cervical and endometrial cancers.
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Neoplasias de la Mama , Neoplasias Endometriales , Ácidos Nucleicos , Humanos , Femenino , Metástasis Linfática/patología , Estudios Prospectivos , Técnicas de Amplificación de Ácido Nucleico/métodos , Neoplasias Endometriales/patología , Ganglios Linfáticos/patología , Biopsia del Ganglio Linfático Centinela , Queratina-19/genética , Neoplasias de la Mama/patologíaRESUMEN
BACKGROUND: Malignant peripheral nerve sheath tumor (MPNST) is a rare soft tissue sarcoma mainly treated via surgical resection. Herein, we report a case of MPNST wherein a massive tumor thrombus extended to the major veins and heart. CASE PRESENTATION: A 39-year-old female with a history of neurofibromatosis type 1 developed MPNST from the right radial nerve. In addition to adjuvant chemotherapy, she underwent wide tumor resection and concomitant radial nerve resection, followed by postoperative radiotherapy. Histological evaluation revealed marked venous invasion. The 2-year follow-up CT revealed an asymptomatic recurrent tumor thrombus extending from the right subclavian vein to the heart. An urgent life-saving operation was performed to ligate the base of the right subclavian vein and remove the entire intravenous thrombus that extended to the right ventricle. The remaining tumor in the right subclavian vein increased in size 3 months after thrombectomy. After confirming the absence of any metastatic lesions, the patient underwent extended forequarter amputation to achieve surgical remission. One year later, a new metastasis to the right diaphragm was safely resected. The patient remains alive without any evidence of disease 2 years after the extended forequarter amputation. CONCLUSIONS: In cases of a previous history of microscopic venous invasion, recurrence can occur as a massive tumor thrombus that extends to the great vessels.
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Neurofibromatosis 1 , Neurofibrosarcoma , Neoplasias de los Tejidos Blandos , Trombosis , Adulto , Femenino , Humanos , Recurrencia Local de Neoplasia/cirugía , Trombosis/etiología , Trombosis/cirugíaRESUMEN
A 40-year-old man visited our hospital with rectal submucosal tumors measuring 5 mm and the 7 mm as detected by colonoscopy, following which an endoscopic submucosal resection was performed. Pathological examination revealed that the tumors was neuroendocrine tumor(NET); the tumor measuring 5 mm was NET G1 without lymphatic and venous invasion, while the 7 mm size was NET G2 with venous invasion but without lymphatic invasion. Lymph node and distant metastasis were not observed by computed tomography. Informed consent was obtained and he agreed to undergo additional rectal resection. Laparoscopic low anterior resection was performed and pathological examination enabled a diagnosis of rectal neuroendocrine tumor with regional lymph node metastases(T1a, N1, M0, Stage â ¢B[Union for International Cancer Control 8th edition]). Post-surgery, he was followed up for 3 years, without recurrence. This report suggests that the determination of treatment plan for rectal neuroendocrine tumor measuring less than 1 cm in diameter should be done carefully.
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Tumores Neuroendocrinos , Neoplasias del Recto , Masculino , Humanos , Adulto , Metástasis Linfática , Tumores Neuroendocrinos/secundario , Neoplasias del Recto/cirugía , Neoplasias del Recto/patología , ColonoscopíaRESUMEN
OBJECTIVES: ARID1A mutation is frequently found in clear cell ovarian cancer (CCC) and endometrioid ovarian cancer (EC). Anti-PD-1 monotherapy has been found to have limited efficacy in epithelial ovarian cancer; however, anti-PD-1 therapy showed significant clinical benefit in some CCC. We sought to define the relationship of ARID1A mutation/ARID1A expression to the immunogenic profile of different histologic subtypes of ovarian cancer. METHODS: We performed next-generation sequencing of 160 cancer-related genes. Also, we analyzed the immunohistochemical status of ARID1A, PD-L1, and CD8 with survival in different histologic subtypes of ovarian cancer in a total of 103 cases. RESULTS: ARID1A mutation was found in 0% of the high-grade serous ovarian cancer (HGSC) (n = 36), 41.5% of the CCC (n = 41), 45.0% of the EC (n = 20), and 33.3% of the mucinous ovarian cancer (MC) (n = 6) cases. ARID1A loss was found in 19.4% of the HGSC, 75.6% of the CCC, 60.0% of the EC and 0% of the MC cases. ARID1A mutation was found to be associated with high PD-L1 (p < 0.001) or CD8 levels (p < 0.001) in CCC but not in other histologic subtypes. Meanwhile, ARID1A loss was associated with high PD-L1 or CD8 levels in CCC (p < 0.001) and HGSC (p < 0.001) but not in EC and MC. In addition, ARID1A mutation was associated with high tumor mutation burden in CCC (p = 0.006). CONCLUSIONS: ARID1A mutation/ARID1A expression is associated with immune microenvironmental factors in CCC but not in EC. ARID1A status can be a biomarker for selecting candidates for immune checkpoint blockade in CCC.
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Carcinoma Epitelial de Ovario/genética , Cistadenocarcinoma Seroso/genética , Proteínas de Unión al ADN/metabolismo , Neoplasias Quísticas, Mucinosas y Serosas/genética , Neoplasias Ováricas/genética , Factores de Transcripción/metabolismo , Biomarcadores de Tumor/genética , Carcinoma Epitelial de Ovario/inmunología , Cistadenocarcinoma Seroso/inmunología , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Mutación , Neoplasias Quísticas, Mucinosas y Serosas/inmunología , Neoplasias Ováricas/inmunologíaRESUMEN
BACKGROUND: Risk-reducing salpingo-oophorectomy is performed for the primary prevention of ovarian cancer in patients with hereditary breast-ovarian cancer syndrome. We performed risk-reducing salpingo-oophorectomy for the first time in Japan in 2008, and we experienced 20 cases of risk-reducing salpingo-oophorectomy through 2019. In the past, the use of risk-reducing salpingo-oophorectomy in Japan was restricted because it was not covered by a Japanese National Health Insurance. Since April 2020, risk-reducing salpingo-oophorectomy has been covered by insurance for patients with breast-ovarian cancer syndrome and pre-existing breast cancer, and this surgery is expected to become more widely implemented in Japan. METHODS: To contribute to the widespread use of risk-reducing salpingo-oophorectomy in the future, we retrospectively reviewed 20 cases of risk-reducing salpingo-oophorectomy at our hospital cohort study to clarify the issues in its implementation. RESULTS: The variant genes for which risk-reducing salpingo-oophorectomy was indicated were BRCA1 and BRCA2 in 13 (65%) and 7 patients (35%), respectively. The median age at which risk-reducing salpingo-oophorectomy was performed was 49 years (range, 38-58), 13 patients (65%) had gone through menopause, and 16 patients (80%) had a history of breast cancer. Of the five patients (25%) with vasomotor symptoms, four received Chinese medicine, and only one received hormone replacement therapy. Occult cancer was detected in the removed ovaries in two patients (10%), although no postoperative peritoneal carcinogenesis has been observed to date. CONCLUSIONS: Women who paid for risk-reducing salpingo-oophorectomy out of pocket were older than the recommended age at which the procedure should be performed, and this may explain the higher rate of occult cancers than previously reported. We need to perform risk-reducing salpingo-oophorectomy at the recommended age to ensure that the procedure is effective for primary prevention.
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Proteína BRCA1/genética , Proteína BRCA2/genética , Predisposición Genética a la Enfermedad , Mutación/genética , Salpingooforectomía , Adulto , Neoplasias de la Mama/genética , Femenino , Heterocigoto , Humanos , Persona de Mediana Edad , Neoplasias Ováricas/genética , Ovario/patología , Estudios Retrospectivos , Factores de RiesgoRESUMEN
STUDY OBJECTIVE: To examine the diagnostic accuracy of hysteroscopic photodynamic diagnosis (PDD) using 5-aminolevulinic acid (5ALA) in patients with endometrial cancer and premalignant atypical endometrial hyperplasia. DESIGN: A single-center, open-label, exploratory intervention study. SETTING: University Hospital in Japan. PATIENTS: Thirty-four patients who underwent hysteroscopic resection in the Department of Obstetrics and Gynecology at Keio University Hospital. INTERVENTIONS: Patients were given 5ALA orally approximately 3 hours before surgery and underwent observation of the uterine cavity and endometrial biopsy using 5ALA-PDD during hysteroscopic resection. Specimens were diagnosed histopathologically and the diagnostic sensitivity and specificity of hysteroscopic 5ALA-PDD for malignancy in the uterine cavity was determined. Red (R), blue (B), and green (G) intensity values were determined from PDD images, and the relationships of histopathological diagnosis with these values were used to develop a model for objective diagnosis of uterine malignancy. MEASUREMENTS AND MAIN RESULTS: Three patients were excluded from the study because of failure of the endoscope system. A total of 113 specimens were collected endoscopically. The sensitivity and specificity of 5ALA-PDD for diagnosis of malignancy in the uterine cavity were 93.8% and 51.9%, respectively. The R/B ratio in imaging analysis was highest in malignant lesions, followed by benign lesions and normal uterine tissue, with significant differences among these groups (p <.05). The R/B and G/B ratios were used in a formula for prediction of malignancy based on logistic regression and the area under the receiver operating characteristic curve for this formula was 0.838. At a formula cutoff value of 0.220, the sensitivity and specificity for diagnosis of malignant disease were 90.6% and 65.4%, respectively. CONCLUSION: To our knowledge, this is the first study of the diagnostic accuracy of 5ALA-PDD for malignancies in the uterine cavity. Hysteroscopic 5ALA-PDD had higher sensitivity and identifiability of lesions. These findings suggest that hysteroscopic 5ALA-PDD may be useful for diagnosis of minute lesions.
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Técnicas de Diagnóstico Obstétrico y Ginecológico , Histeroscopía/métodos , Ácidos Levulínicos , Mediciones Luminiscentes/métodos , Neoplasias Uterinas/diagnóstico , Adulto , Hiperplasia Endometrial/diagnóstico , Hiperplasia Endometrial/metabolismo , Hiperplasia Endometrial/patología , Neoplasias Endometriales/diagnóstico , Neoplasias Endometriales/metabolismo , Endometrio/diagnóstico por imagen , Endometrio/patología , Femenino , Humanos , Japón , Ácidos Levulínicos/química , Ácidos Levulínicos/farmacocinética , Persona de Mediana Edad , Lesiones Precancerosas/diagnóstico , Lesiones Precancerosas/metabolismo , Lesiones Precancerosas/patología , Embarazo , Sensibilidad y Especificidad , Enfermedades Uterinas/diagnóstico , Enfermedades Uterinas/metabolismo , Enfermedades Uterinas/patología , Neoplasias Uterinas/metabolismo , Neoplasias Uterinas/patología , Ácido AminolevulínicoRESUMEN
BACKGROUND: Oesophageal cancer has a high metastatic potential and poor prognosis, with a significant risk of recurrence after radical resection. However, resected pancreatic metastasis from oesophageal cancer is rare. CASE PRESENTATION: Eleven years prior, a seventy-year-old woman had been treated with transthoracic radical oesophagectomy for oesophageal squamous cell carcinoma. Four years prior, she had undergone chemotherapy for lymph node recurrence at the splenic hilum and achieved a partial response. She had also received chemoradiotherapy for lymph node recurrence at the splenic hilum 3 years prior; a complete response was achieved. However, routine follow-up with abdominal computed tomography recently revealed a tumour at the pancreatic tail and swollen lymph nodes. The patient underwent distal pancreatectomy on the basis of a pre-operative diagnosis of primary pancreatic cancer, although a histological examination of the surgical specimen revealed metastatic squamous cell carcinoma that was compatible with metachronous pancreatic metastasis from oesophageal squamous cell carcinoma. The patient has been undergoing clinical follow-up without adjuvant therapy and has been disease-free for 24 months after resection of the pancreatic metastasis. CONCLUSIONS: Resection of pancreatic metastasis may improve prognosis and should be considered when treating patients with solitary metastasis from oesophageal squamous cell carcinoma.
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Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/terapia , Recurrencia Local de Neoplasia/terapia , Neoplasias Pancreáticas/terapia , Anciano de 80 o más Años , Quimioradioterapia Adyuvante , Endosonografía , Neoplasias Esofágicas/diagnóstico por imagen , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas de Esófago/diagnóstico por imagen , Carcinoma de Células Escamosas de Esófago/secundario , Esofagectomía , Femenino , Humanos , Escisión del Ganglio Linfático , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/patología , Ganglios Linfáticos/cirugía , Metástasis Linfática/diagnóstico por imagen , Metástasis Linfática/patología , Recurrencia Local de Neoplasia/diagnóstico por imagen , Recurrencia Local de Neoplasia/patología , Páncreas/diagnóstico por imagen , Páncreas/patología , Páncreas/cirugía , Pancreatectomía , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/secundario , Esplenectomía , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
Glypican-3 (GPC3) is expressed in most hepatocellular carcinomas (HCCs). To investigate the significance of various GPC3 staining patterns in HCC, we classified 134 HCC patients into three groups: those with diffuse GPC3 staining, canalicular GPC3 staining, and others (including negative staining). HCCs with diffuse staining were correlated with poor differentiation, high Ki-67 indices, high serum α-fetoprotein (AFP) levels, and early recurrence. In contrast, HCCs with canalicular staining were well differentiated with lower AFP levels. Overall survival in this group was better than that of the other two groups. Comparative analysis of GPC3 staining patterns with markers for HCC subclassification showed that diffuse staining was correlated with the expression of biliary/stem cell markers, whereas canalicular staining was correlated with expression of the markers of WNT-activated HCCs. Induction of leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5), known as a target of the WNT signaling pathway, in HCC cells resulted in reduced GPC3 expression in vitro. The LGR5-induced cells formed tumors with canaliculus-like structures in mice and showed canalicular GPC3 staining. The current findings showed the significance of recognizing distinct GPC3 staining patterns, i.e., diffuse and canalicular, which may reflect different carcinogenetic mechanisms and indicate the level of malignancy of HCC.
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Biomarcadores de Tumor/análisis , Carcinoma Hepatocelular/patología , Glipicanos/metabolismo , Neoplasias Hepáticas/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Inmunohistoquímica/métodos , Masculino , Persona de Mediana Edad , Coloración y Etiquetado/métodosRESUMEN
Growing evidence suggests a relationship between antibody-mediated rejection (AMR) and early graft failure due to a previously unknown etiology in liver transplantation (LTx). We herein report a 3-year-old boy who developed rapid graft failure due to de novo donor-specific antibody (DSA)-driven AMR a week after living donor LTx, requiring a second transplant on the 10th day after the first LTx. The pathology of the first graft showed massive necrosis in zone 3 along with positive C4d and inflammatory cell infiltrates in portal areas. The mean fluorescence intensity against human leukocyte antigen (HLA)-DR15, which was possessed by both the first and the second donor, peaked at 12 945 on the day before the second LTx. Antithymocyte globulin, plasma exchange along with i.v. immunoglobulin, rituximab, and the local infusion of prostaglandin E1, steroids, and Mesilate gabexate through a portal catheter were provided to save the second graft. To our knowledge, this is the first report to show a clear association between de novo DSA and acute AMR within 7 days of a LTx. Furthermore, we successfully rescued the recipient with a second graft despite possessing the same targeted HLA. The rapid decision to carry out retransplantation and specific strategies overcoming AMR were crucial to achieving success in this case of immunologically high-risk LTx.
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Multistep hepatocarcinogenesis progresses from dysplastic nodules to early hepatocellular carcinoma (eHCC) and to advanced HCC. The aim of the present study was to investigate the detailed histopathological features of eHCC. We investigated 66 small vaguely nodular lesions resected from 40 patients. The degree of cellular and structural atypia and stromal invasion were assessed. The immunohistochemical expression of HCC-related markers adenylate cyclase-associated protein 2 (CAP2), heat shock protein 70 (HSP70), Bmi-1, CD34 and h-caldesmon were evaluated. Of the 66 nodules, 10 were diagnosed as low-grade dysplastic nodules (LGDN), 10 as high-grade dysplastic nodules (HGDN) and 46 as eHCC. Among the 46 eHCC, 18 nodules (39.1%) showed marked stromal invasion and/or the presence of the scirrhous component and were subclassified as high-grade eHCC (HGeHCC). The remaining 28 eHCC, which lacked these features, were subclassified as low-grade eHCC (LGeHCC) and were examined further. HGeHCC showed high levels of cellular and structural atypia and large tumor size. The immunohistochemical expression of CAP2 and the area of sinusoidal vascularization showed increases from LGDN to HGeHCC. The density of arterial tumor vessels was high in HGeHCC compared with other nodule types. Cluster analysis of these parameters subclassified 65 nodules into HGeHCC-dominant, LGeHCC and HGDN-dominant, and LGDN-dominant groups. These results indicate the increased malignant potential of HGeHCC and suggest that it is already a transitional stage to advanced HCC. We consider that our grading classification system may be valuable for considering treatment strategies for eHCC around 2 cm in diameter.
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Carcinogénesis/genética , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Proteínas de Neoplasias/biosíntesis , Proteínas Adaptadoras Transductoras de Señales/biosíntesis , Proteínas Adaptadoras Transductoras de Señales/genética , Anciano , Antígenos CD34/biosíntesis , Biomarcadores de Tumor/biosíntesis , Biomarcadores de Tumor/genética , Proteínas de Unión a Calmodulina/biosíntesis , Carcinoma Hepatocelular/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Proteínas HSP70 de Choque Térmico/biosíntesis , Humanos , Neoplasias Hepáticas/genética , Masculino , Proteínas de la Membrana/biosíntesis , Proteínas de la Membrana/genética , Persona de Mediana Edad , Proteína Quinasa 7 Activada por Mitógenos/biosíntesis , Invasividad Neoplásica , Proteínas de Neoplasias/genética , Estadificación de NeoplasiasRESUMEN
Timothy syndrome (TS) is a congenital long QT syndrome that is associated with syndactyly and mutations in CACNA1C, encoding an L-type voltage-dependent calcium channel, Cav1.2. Recently, TS has been associated with autism and other psychological disorders. This case indicated bradycardia by prenatal screening and was diagnosed as TS by the occurrence of syndactyly and QT prolongation at birth. Despite therapy with anti-arrhythmia reagents and a pacemaker, the patient died 2 months after birth and was autopsied. The heart showed mild dilation and mild hypertrophy with a focal disarray pattern, which may be inconsistent with typical cardiomyopathy. Unexpectedly, bilateral adrenal glands showed marked shrinkage and severe fibrosis of the medulla with a small number of single-strand DNA positive medullary cells and accumulation of hemosiderin-containing macrophages. This finding suggests that CACNA1C mutation may induce drop-out of medulla cells via apoptosis. This may be due to increased concentration of calcium ions consistent with Cav1.2 expression in adrenal glands as well as in the brain and the heart. This is the first report describing a systemic autopsy of TS with adrenal medullary dystrophy.
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Enfermedades de las Glándulas Suprarrenales/patología , Médula Suprarrenal/patología , Trastorno Autístico/patología , Síndrome de QT Prolongado/patología , Sindactilia/patología , Enfermedades de las Glándulas Suprarrenales/genética , Trastorno Autístico/complicaciones , Autopsia , Femenino , Humanos , Recién Nacido , Síndrome de QT Prolongado/complicaciones , Sindactilia/complicacionesRESUMEN
BACKGROUND: This study evaluated our new strategy for treating suspected T2 gallbladder carcinoma (GBC) using a laparoscopic approach. METHODS: We examined 19 patients with suspected T2 GBC who were treated laparoscopically (LS group) between December 2007 and December 2013; these patients were compared with 14 patients who underwent open surgery (OS group). Laparoscopic staging was initially performed to exclude factors making the patients ineligible for curative resection. Intraoperative pathological examination of the surgical margin of the cystic duct was performed prior to laparoscopic gallbladder bed resection, and pathological examination was again performed to confirm the presence of carcinoma and the depth of tumor invasion. Surgery was completed when the pathological findings indicated that the patient was cancer free. Lymph node dissection was performed according to the depth of tumor invasion. RESULTS: None of the patients required conversion to laparotomy. For three patients with benign lesions, only gallbladder bed resection was required. Additional regional lymph node dissection was performed in 16 patients in the LS group. The mean operative time (309 vs. 324 min, p = 0.755) and mean number of dissected lymph nodes (12.6 vs. 10.2, p = 0.361) were not significantly different between the LS and OS groups. The intraoperative blood loss was significantly lower (104 vs. 584 mL, p = 0.002) and the postoperative hospital stay was significantly shorter (9.1 vs. 21.6 days, p = 0.002) for LS patients than for those in the OS group. In the LS group, one patient developed postoperative pneumonia, but all patients survived without recurrence after a mean follow-up of 37 months. CONCLUSION: Our strategy for suspected T2 gallbladder GBC is safe and useful, avoids unnecessary procedures, and is associated with similar oncologic outcomes as the open method.
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Colecistectomía Laparoscópica/normas , Neoplasias de la Vesícula Biliar/cirugía , Estadificación de Neoplasias , Guías de Práctica Clínica como Asunto , Anciano , Colecistectomía Laparoscópica/métodos , Femenino , Neoplasias de la Vesícula Biliar/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Tempo Operativo , Estudios RetrospectivosAsunto(s)
Alveolitis Alérgica Extrínseca/diagnóstico por imagen , Alveolitis Alérgica Extrínseca/complicaciones , Alveolitis Alérgica Extrínseca/patología , Femenino , Fluorodesoxiglucosa F18 , Humanos , Persona de Mediana Edad , Tomografía Computarizada por Tomografía de Emisión de Positrones , RadiofármacosRESUMEN
Olfactory neuroblastomas rarely secrete adrenocorticotropic hormone, leading to ectopic adrenocorticotropic hormone syndrome. However, the prevalence, timing, and triggers of ectopic adrenocorticotropic hormone syndrome in patients with olfactory neuroblastomas remain unclear. This study aimed to investigate these factors and conduct a literature review. Fifteen patients with olfactory neuroblastomas who underwent surgery at our institution were included. The prevalence of ectopic adrenocorticotropic hormone syndrome development was assessed by evaluating adrenocorticotropic hormone expression using immunohistochemistry. Furthermore, 26 patients with olfactory neuroblastomas who developed ectopic adrenocorticotropic hormone syndrome from previous reports were reviewed. Among the 15 patients, three (20%) showed adrenocorticotropic hormone-positive tumor cells at the time of initial surgery, and two (13%) developed ectopic adrenocorticotropic hormone syndrome. The timing of developing ectopic adrenocorticotropic hormone syndrome was 2.5 and 10 years following the initial treatment of olfactory neuroblastoma. Based on the literature review, nine patients with recurrent and metastatic olfactory neuroblastoma developed ectopic adrenocorticotropic hormone syndrome after the initial surgery, of whom, three had confirmed disease after developing ectopic adrenocorticotropic hormone syndrome, three developed during disease progression, two developed after receiving chemotherapy, and one developed after undergoing a biopsy. The timing of ectopic adrenocorticotropic hormone syndrome was 2.5-15 years after initial treatment. Our study revealed that acknowledging olfactory neuroblastomas can manifest as ectopic adrenocorticotropic hormone syndrome with a certain low prevalence is crucial. Moreover, our study speculated that tumor stimulation, such as biopsy or chemotherapy, as well as disease progression, could trigger ectopic adrenocorticotropic hormone syndrome onset. Thus, olfactory neuroblastomas can develop into ectopic adrenocorticotropic hormone syndrome, even long after the initial treatment.
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Síndrome de ACTH Ectópico , Estesioneuroblastoma Olfatorio , Neoplasias Nasales , Humanos , Estesioneuroblastoma Olfatorio/metabolismo , Estesioneuroblastoma Olfatorio/patología , Masculino , Femenino , Adulto , Neoplasias Nasales/metabolismo , Neoplasias Nasales/patología , Persona de Mediana Edad , Cavidad Nasal/patología , Cavidad Nasal/metabolismo , Anciano , Adulto Joven , Hormona Adrenocorticotrópica/metabolismo , Adolescente , Estudios RetrospectivosRESUMEN
The preferential response to PARP inhibitors (PARPis) in BRCA-deficient and Schlafen 11 (SLFN11)-expressing ovarian cancers has been documented, yet the underlying molecular mechanisms remain unclear. As the accumulation of single-strand DNA (ssDNA) gaps behind replication forks is key for the lethality effect of PARPis, we investigated the combined effects of SLFN11 expression and BRCA deficiency on PARPi sensitivity and ssDNA gap formation in human cancer cells. PARPis increased chromatin-bound RPA2 and ssDNA gaps in SLFN11-expressing cells and even more in cells with BRCA1 or BRCA2 deficiency. SLFN11 was co-localized with chromatin-bound RPA2 under PARPis treatment, with enhanced recruitment in BRCA2-deficient cells. Notably, the chromatin-bound SLFN11 under PARPis did not block replication, contrary to its function under replication stress. SLFN11 recruitment was attenuated by the inactivation of MRE11. Hence, under PARPi treatment, MRE11 expression and BRCA deficiency lead to ssDNA gaps behind replication forks, where SLFN11 binds and increases their accumulation. As ovarian cancer patients who responded (progression-free survival >2 years) to olaparib maintenance therapy had a significantly higher SLFN11-positivity than short-responders (<6 months), our findings provide a mechanistic understanding of the favorable responses to PARPis in SLFN11-expressing and BRCA-deficient tumors. It highlight the clinical implications of SLFN11.
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Proteína BRCA1 , Proteína BRCA2 , Replicación del ADN , ADN de Cadena Simple , Proteína Homóloga de MRE11 , Neoplasias Ováricas , Inhibidores de Poli(ADP-Ribosa) Polimerasas , Humanos , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Replicación del ADN/efectos de los fármacos , ADN de Cadena Simple/genética , ADN de Cadena Simple/metabolismo , Femenino , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Neoplasias Ováricas/metabolismo , Proteína BRCA2/genética , Proteína BRCA2/metabolismo , Proteína Homóloga de MRE11/metabolismo , Proteína Homóloga de MRE11/genética , Proteína BRCA1/genética , Proteína BRCA1/metabolismo , Línea Celular Tumoral , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Proteína de Replicación A/metabolismo , Proteína de Replicación A/genética , Cromatina/metabolismo , Ftalazinas/farmacologíaRESUMEN
Background/Aims: Poorly differentiated adenocarcinoma, signet-ring cell carcinoma, and mucinous adenocarcinoma (por/sig/muc), which are considered to be histologic subtypes with a poor prognosis, occur more frequently with colitis-associated cancer than with sporadic tumors. However, their invasiveness and manifestations are unclear. This study aimed to determine the prevalence of the por/sig/muc component in ulcerative colitis-associated neoplasms (UCANs) and its association with invasiveness and to clarify its clinicohistologic and endoscopic features. Methods: This retrospective observational study included patients diagnosed with ulcerative colitis-associated high-grade dysplasia or adenocarcinoma from 1997 to 2022 who were divided according to the presence or absence of a por/sig/muc component. Results: Thirty-five patients had UCAN with a por/sig/muc component and 66 had UCAN without this component. The 5-year survival rate was significantly lower in the por/sig/muc group than in the tub group (67% vs. 96%, P= 0.001), which was attributed to disease above stage III and depth to below the subserosa. Biopsy-based diagnosis before resection detected a por/sig/muc component in only 40% of lesions (14/35). Lesions with a por/sig/muc component were prevalent even in the early stages: stage 0 (4/36, 11%), I (8/20, 40%), II (7/12, 58%), III (10/14, 71%), and IV (6/8, 75%). Conclusions: This is the first investigation that shows UCANs with a por/sig/muc component tended to be deeply invasive and were often not recognized preoperatively. Endoscopists should be aware that UCAN often has a por/sig/muc component that is not always recognized on biopsy, and the optimal treatment strategy needs to be carefully considered.
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OBJECTIVE: To evaluate the accuracy of preoperative endometrial biopsy and magnetic resonance imaging (MRI) of endometrial cancer compared with that of intraoperative frozen section. METHODS: This retrospective study included 264 patients who underwent surgery with intraoperative frozen section for endometrial cancer at our institution between 2014 and 2018. Diagnosis was determined by histologic type, grade, and myometrial invasion. Concordance rate, sensitivity, and specificity of preoperative diagnosis and intraoperative frozen diagnosis were calculated, in comparison to the final pathologic diagnosis. RESULTS: Preoperative and intraoperative diagnoses showed no statistically significant difference in determining histologic type and grade (P = 0.152). Intraoperative diagnosis showed higher sensitivity for endometrioid carcinoma grade 3 and other types, and higher specificity for grade 1. For myometrial invasion, intraoperative diagnosis showed significantly higher concordance rate than preoperative MRI findings (P < 0.01). Intraoperative diagnosis showed higher sensitivity and specificity in patients with and without myometrial invasion, respectively. CONCLUSION: Higher agreement between intraoperative and final diagnoses, especially in myometrial invasion, suggests that intraoperative frozen section is a good indicator for appropriate surgical procedure decision making.
Asunto(s)
Neoplasias Endometriales , Secciones por Congelación , Femenino , Humanos , Estudios Retrospectivos , Miometrio/diagnóstico por imagen , Miometrio/cirugía , Miometrio/patología , Invasividad Neoplásica/patología , Neoplasias Endometriales/diagnóstico por imagen , Neoplasias Endometriales/cirugía , Imagen por Resonancia Magnética , Estadificación de NeoplasiasRESUMEN
Metastatic pancreatic cancer is a rare condition and cases of pancreatic metastasis from cervical cancer are infrequently reported. Furthermore, the incidence rates of pancreatic tumors as the cause of pancreatitis and of pancreatitis in patients with pancreatic tumors are similarly low. Pancreatitis may occur when a tumor obstructs the pancreatic duct. This condition may be difficult to manage and significantly reduces the quality of life because of severe abdominal pain. Here, we present a rare case of obstructive pancreatitis caused by pancreatic metastasis from cervical squamous-cell carcinoma, pathologically confirmed using endoscopic ultrasonography-guided fine-needle biopsy and treated with palliative irradiation to achieve rapid therapeutic relief. It is important to obtain appropriate tissue samples, confirm the pathological diagnosis, and compare the pathological findings with those of the primary tumor to select the appropriate treatment for obstructive pancreatitis caused by a metastatic pancreatic tumor.
Asunto(s)
Carcinoma de Células Escamosas , Neoplasias Pancreáticas , Pancreatitis Crónica , Neoplasias del Cuello Uterino , Femenino , Humanos , Neoplasias del Cuello Uterino/radioterapia , Neoplasias del Cuello Uterino/patología , Calidad de Vida , Páncreas/patología , Neoplasias Pancreáticas/patología , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/patologíaRESUMEN
The precise manipulation of immune tolerance is the holy grail of immunotherapies for both autoimmunity and cancer immunity. Thymomas are well known to be associated with autoimmune diseases. The exact mechanism by which autoreactivity is induced after thymectomy remains to be elucidated. We herein present the case of a 50-year-old lady with concurrent de novo type 1 autoimmune hepatitis (AIH) and pure red cell aplasia (PRCA), 1 month after undergoing a successful total thymectomy for combined squamous cell carcinoma and thymoma (Masaoka stage II). Corticosteroids yielded short-term effects for both AIH and PRCA. Literature on thymoma-associated AIH, an extremely rare immune-related comorbidity, was also reviewed.
Asunto(s)
Hepatitis Autoinmune , Aplasia Pura de Células Rojas , Timoma , Neoplasias del Timo , Femenino , Humanos , Persona de Mediana Edad , Timoma/complicaciones , Timoma/cirugía , Timectomía/efectos adversos , Hepatitis Autoinmune/complicaciones , Neoplasias del Timo/complicaciones , Neoplasias del Timo/cirugía , Aplasia Pura de Células Rojas/complicaciones , AutoanticuerposRESUMEN
OBJECTIVE: The histological grade of parotid gland carcinoma (PGC) is an important prognostic factor; however, the diagnosis prior to treatment has been challenging to make. This study aimed to investigate whether the pretreatment clinical findings, including hematological inflammatory, nutritional, and immune markers, could predict the histological grade of PGC. STUDY DESIGN: Retrospective study. METHODS: We retrospectively enrolled 111 patients with PGC and evaluated the correlation between histological grade and pretreatment clinical findings such as age, sex, tumor staging, facial nerve paralysis, pain or tenderness, adhesion to the surrounding tissues or tumor immobility, and hematological markers. RESULTS: Sixty patients (54%) were diagnosed with histological high-grade PGC. Univariate analysis revealed that age, T classification, N classification, TNM stage, facial nerve paralysis, adhesion/immobility, C-reactive protein (CRP), and CRP-to-albumin ratio (CAR) were significant predictors of PGC histological grade. On multivariate analysis, high T classification (T3, 4), high N classification (≥1), and elevated CRP (≥0.22 mg/dL) were independent predictors of high-grade PGC. CONCLUSIONS: Pretreatment T classification, N classification, and CRP are significant predictors of the histological grading of PGC. Our results are useful for treatment planning and obtaining appropriate informed consent from the patients before treatment. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:96-102, 2022.