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Mucinous ovarian carcinoma (MOC) represents a distinct entity within ovarian malignancies, characterized by diagnostic challenges due to its rarity and the potential overlap with other tumor types. The determination of tumor origin is important for precise postsurgical treatment. This article highlights the accurate diagnosis and management of MOC, including the use of imaging modalities, serological tumor markers, immunohistochemistry, and genomic analyses. Transabdominal and transvaginal ultrasonography, complemented by MRI and CT, plays a pivotal role in differentiating MOC from other mucinous tumors and in surgical planning, particularly for fertility preservation. Serological markers like CA19-9, CA-125, and CEA, though not definitive, provide valuable preoperative insights. Immunohistochemistry aids in distinguishing primary MOC from metastatic mucinous carcinomas, while genomic profiling offers the potential for precision medicine through the identification of specific molecular signatures and treatment susceptibilities. Despite advancements in diagnostic techniques, no single method conclusively differentiates between primary and metastatic tumors intraoperatively. The paper reviews the origins, diagnosis, and differential diagnosis of primary mucinous ovarian carcinoma highlights the need for a multimodal diagnostic approach and advocates for the inclusion of MOC patients in clinical trials for personalized therapies, recognizing the heterogeneity of the disease at the molecular level.
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Metastases to the breast from extramammary sources are extremely rare, with the ovary, primarily high-grade serous carcinoma, being the most common origin. We report a case of breast metastases from advanced stage ovarian mucinous carcinoma in a 48-year-old female- a case hitherto unreported in the literature. The case is noteworthy for its atypical presentation marked by an areolar rash, clinically suggestive of Paget disease of the nipple. This unique clinical scenario, coupled with histopathological examination revealing in-situ-like carcinoma component, posed a diagnostic challenge in discerning the tumour origin. We emphasize the need for heightened awareness among pathologists to avoid misdiagnosing metastatic carcinomas as primary breast tumours, a potential pitfall with significant clinical implications.
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OBJECTIVE: To investigate the clinical and magnetic resonance imaging (MRI) features for preoperatively discriminating primary ovarian mucinous malignant tumors (POMTs) and metastatic mucinous carcinomas involving the ovary (MOMCs). METHODS: This retrospective multicenter study enrolled 61 patients with 22 POMTs and 49 MOMCs, which were pathologically proved between November 2014 to Jane 2023. The clinical and MRI features were evaluated and compared between POMTs and MOMCs. Univariate and multivariate analyses were performed to identify the significant variables between the two groups, which were then incorporated into a predictive nomogram, and ROC curve analysis was subsequently carried out to evaluate diagnostic performance. RESULTS: 35.9% patients with MOMCs were discovered synchronously with the primary carcinomas; 25.6% patients with MOMCs were bilateral, and all of the patients with POMTs were unilateral. The biomarker CEA was significantly different between the two groups (p = 0.002). There were significant differences in the following MRI features: tumor size, configuration, enhanced pattern, the number of cysts, honeycomb sign, stained-glass appearance, ascites, size diversity ratio, signal diversity ratio. The locular size diversity ratio (p = 0.005, OR = 1.31), and signal intensity diversity ratio (p = 0.10, OR = 4.01) were independent predictors for MOMCs. The combination of above independent criteria yielded the largest area under curve of 0.922 with a sensitivity of 82.3% and specificity of 88.9%. CONCLUSIONS: Patients with MOMCs were more commonly bilaterally and having higher levels of CEA, but did not always had a malignant tumor history. For ovarian mucin-producing tumors, the uniform locular sizes and signal intensities were more predict MOMCs.
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Adenocarcinoma Mucinoso , Neoplasias Ováricas , Femenino , Humanos , Neoplasias Ováricas/diagnóstico por imagen , Neoplasias Ováricas/cirugía , Carcinoma Epitelial de Ovario/diagnóstico , Adenocarcinoma Mucinoso/diagnóstico por imagen , Adenocarcinoma Mucinoso/cirugía , Mucinas , Diagnóstico DiferencialRESUMEN
Tumor heterogeneity remains an ongoing challenge in the field of cancer therapy. Intratumor heterogeneity significantly complicates the diagnosis of cancer and presents challenging clinical problems due to resistance to drug therapy. This study aimed to elucidate the genetic changes histologically (mucinous cystadenoma (MCA), mucinous borderline tumor (MBT), and mucinous ovarian carcinoma (MOC)) in a portion of mucinous ovarian tumors within the same sample. Seven tumor samples obtained from different patients were used to evaluate the genetic mutations in each component. Intratumor genetic heterogeneity was observed in all patients; among them, BRAF (V600E) and p53 (T118I, P142S, T150I, and T170M) point mutations were observed in the MBT component, while KRAS (G12D and G13D) and PIK3CA (E545K) mutations were found in the MOC component. The current findings suggest that diverse genetic alterations occur in mucinous tumors, according to tumor histology. Tumor heterogeneity and genetic diversity in mucinous ovarian tumors might be the cause of treatment failure. Knowledge of intertumor heterogeneity may lead to an increased understanding of the tumor response to treatment.
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Adenocarcinoma Mucinoso , Neoplasias Ováricas , Femenino , Humanos , Proyectos Piloto , Carcinoma Epitelial de Ovario , Adenocarcinoma Mucinoso/genética , Adenocarcinoma Mucinoso/patología , Neoplasias Ováricas/diagnóstico , MutaciónRESUMEN
BACKGROUND: Mucinous carcinoma (MC) is a histological subtype of ovarian cancer that has a worse prognosis at advanced stages than the most prevalent histological subtype, high-grade serous carcinomas. Invasive patterns have been recognized as prognostic factors for MCs. MCs with infiltrative invasion were more aggressive than those with expansile invasion. MC with an expansile pattern exhibited behavior similar to mucinous borderline tumors (MBT). However, genomic analysis of invasive patterns is insufficient. This study aimed to compare genetic information between groups with MC and infiltrative invasion (Group A) and those with MC with expansile invasion or MBT (Group B). METHODS: Ten cases each of MC with infiltrative invasion, MC with expansile invasion, and MBT between 2005 and 2020 were identified. Deoxyribonucleic acid (DNA) extraction from formalin-fixed paraffin-embedded tissues was performed, and cases with DNA fragmentation or the possibility of DNA fragmentation were excluded. Mutant base candidates and tumor mutation burden (TMB) values (mutations/megabase) were calculated. RESULTS: After assessing the quality of purified DNA, seven cases of MC with infiltrative invasion, five cases of MC with expansile invasion, and three cases of MBT were included. More patients in group A experienced recurrence or progression (p < 0.01) and died of disease (p = 0.03). Moreover, the TMB value was statistically higher in group A than in group B (p = 0.049). There were no statistical differences in the incidence of the mutations of KRAS, TP53, and CREBBP. KRAS, TP53, and CREBBP mutations were discovered in 8/15 (53.3%), 6/15 (40.0%), and 5/15 (33.3%) cases, respectively. CONCLUSIONS: Genetic analysis revealed that Group A had higher TMB than Group B. Therefore, this result might be useful for future treatment.
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Adenocarcinoma Mucinoso , Neoplasias Quísticas, Mucinosas y Serosas , Neoplasias Ováricas , Femenino , Humanos , Estudios Retrospectivos , Proteínas Proto-Oncogénicas p21(ras)/genética , Estadificación de Neoplasias , Adenocarcinoma Mucinoso/genética , Adenocarcinoma Mucinoso/patología , Neoplasias Quísticas, Mucinosas y Serosas/patología , Neoplasias Ováricas/patología , Carcinoma Epitelial de Ovario/patología , ADNRESUMEN
BACKGROUND: The vast majority of ovarian mucinous carcinomas are metastatic tumours derived from nonovarian primary cancers, typically gastrointestinal neoplasms. Therapy targeting claudin18.2 might be used in gastric, gastroesophageal junction and pancreatic cancers with high expression of claudin18.2. In this study, we aimed to profile the expression of claudin18.2 in primary ovarian mucinous carcinoma (POMC) and metastatic gastrointestinal mucinous carcinoma (MGMC). METHODS: Immunohistochemistry was used to detect claudin 18.2 expression in whole tissue sections of ovarian mucinous carcinomas, including 32 POMCs and 44 MGMCs, 23 of which were derived from upper gastrointestinal primary tumours and 21 of which were derived from lower gastrointestinal primary tumours. Immunohistochemical studies for claudin18.2, SATB2, PAX8, CK7 and CK20 were performed in all 76 cases. RESULTS: Among 76 primary and metastatic mucinous carcinomas, claudin18.2 was expressed in 56.6% (43/76) of cases. MGMCs from the upper gastrointestinal tract, including 22 derived from primary stomach tumours and one derived from a pancreas tumour, were positive for claudin 18.2 in 69.5% (16/23) of cases. MGMCs from the lower gastrointestinal tract, including 10 derived from primary appendiceal cancer and 11 derived from colorectal cancers, showed no claudin18.2 expression (0/21). The expression rate of claudin18.2 in primary ovarian mucinous neoplasms, including 22 primary ovarian mucinous carcinomas and 10 primary ovarian borderline mucinous tumours, was 84.4% (27/32). The common immunophenotypic characteristics of POMCs, upper gastrointestinal tract-derived MGMCs, and lower gastrointestinal tract-derived MGMCs were claudin18.2 + /PAX8 + /SATB2- (17/32), claudin18.2 + /PAX8-/SATB2- (16/23) and claudin18.2-/PAX8-/SATB2 + (19/21), respectively. CONCLUSION: Claudin18.2 is highly expressed in POMCs and MGMCs derived from upper gastrointestinal tract primary tumours; therefore, claudin18.2-targeted therapy might serve as a potential therapeutic strategy for POMCs and MGMCs from the upper gastrointestinal tract.
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Adenocarcinoma Mucinoso , Claudinas , Neoplasias Gastrointestinales , Neoplasias Ováricas , Neoplasias Pancreáticas , Femenino , Humanos , Adenocarcinoma Mucinoso/metabolismo , Biomarcadores de Tumor/metabolismo , Carcinoma Epitelial de Ovario/diagnóstico , Diagnóstico Diferencial , Neoplasias Gastrointestinales/patología , Neoplasias Ováricas/metabolismo , Neoplasias Pancreáticas/diagnóstico , Estómago/patología , Factores de Transcripción/metabolismo , Claudinas/metabolismoRESUMEN
The most common subtype of ovarian carcinoma associated with somatically derived yolk sac tumor (YST) is endometrioid carcinoma. Only two cases of ovarian mucinous carcinomas associated with YST have been reported; herein, we present three additional patients, along with a review of previous literature and our pathology archives to analyze the tumor prognosis. The patients' ages ranged from 38 to 53 years. Two patients had FIGO stage 1 tumors, and one patient had a stage 3 tumor. Two patients died of the disease within a year, and one patient survived with distant metastasis (32 months after surgery). In all three tumors, the YST-like component comprised less than 5% of the total tumor area. Together with the two previously reported mucinous carcinomas with a YST-like component, the prognosis of the five mucinous carcinomas with a YST-like component were compared with that of 19 conventional mucinous carcinomas resected at our hospital. The survival curves were estimated using the Kaplan-Meier method. As a result, the overall survival rate of patients with mucinous carcinomas with a YST-like component was significantly lower than that of patients with conventional mucinous carcinomas (P = .0014). Our study indicates that the presence of a YST-like component in mucinous carcinomas would be a strong prognostic indicator.
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Adenocarcinoma Mucinoso , Carcinoma Endometrioide , Tumor del Seno Endodérmico , Neoplasias Ováricas , Femenino , Humanos , Adulto , Persona de Mediana Edad , Pronóstico , Tumor del Seno Endodérmico/diagnóstico , Tumor del Seno Endodérmico/cirugía , Inmunohistoquímica , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/cirugía , Neoplasias Ováricas/patología , Carcinoma Endometrioide/patología , Carcinoma Epitelial de Ovario , Adenocarcinoma Mucinoso/diagnóstico , Adenocarcinoma Mucinoso/cirugíaRESUMEN
OBJECTIVES: The aim of the study was to explore the rate of upstaging after complete surgical staging among patients with apparent FIGO stage I ovarian mucinous carcinoma. METHODS: Ovarian mucinous carcinoma patients with surgical treatment at the Peking Union Medical College Hospital between October 2020 and January 1994 were retrospectively reviewed. RESULTS: In total, 163 patients were included in this study. Surgical restaging was performed in 89 patients after initial incomplete surgical staging, and one-step complete surgical staging was performed in 74 patients. Among these initially incompletely staged patients, residual tumors were found in 16 patients (16/89, 17.9%). Among the 19 patients with apparent FIGO stage IA, no patient was found to have residual tumors after incomplete staging surgery, according to the final pathology result of restaging surgery. Ovarian cystectomy (OR=4.932, 95% CI= 1.347-18.058, P=0.016) was an independent risk factor for residual tumors after incomplete staging surgery. Among all 163 patients, upstaging occurred in 15 patients (15/163, 9.2%). Among 44 apparent FIGO stage IA patients, no patient was upstaged to FIGO II-IVB. Moreover, both a history of ovarian mucinous tumor (OR=4.745, 95% CI= 1.132-19.886, P=0.033) and bilateral ovary involvement (OR=9.739, 95% CI= 2.016-47.056, P=0.005) were independent risk factors for upstaging to FIGO stage II-IVB. CONCLUSIONS: For patients with apparent FIGO stage IA disease, the possibility of residual tumors and upstaging is relatively low. For patients with cystectomy, bilateral mucinous carcinomas, or a history of ovarian mucinous tumors, complete staging surgery maintains greater significance.
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Adenocarcinoma Mucinoso , Neoplasias Ováricas , Adenocarcinoma Mucinoso/patología , Adenocarcinoma Mucinoso/cirugía , Carcinoma Epitelial de Ovario/patología , Femenino , Humanos , Estadificación de Neoplasias , Neoplasia Residual/patología , Neoplasias Ováricas/patología , Neoplasias Ováricas/cirugía , Estudios RetrospectivosRESUMEN
BACKGROUND: The aim of this study was to evaluate the clinicopathological factors and prognosis of mucinous carcinoma (MC) with infiltrative invasion, MC with expansile invasion, and high-grade serous carcinoma (HGSC). METHODS: Cases of MC and HGSC between 1984 and 2019 were identified. The clinicopathological factors and prognosis of MC with infiltrative invasion or expansile invasion and HGSC were retrospectively compared. Although our present study included cases in our previous studies, we extended observational period when analysis was performed. Accordingly, our study added increased cases and survival analysis was newly conducted. RESULTS: After pathological review, 27 cases of MC with infiltrative invasion, 25 cases of MC with expansile invasion, and 219 cases of HGSC were included. MC had a better prognosis in terms of progression-free survival (PFS, p < 0.01) and overall survival (OS, p < 0.01) than HGSC for all International Federation of Gynecology and Obstetrics (FIGO) stages; however, multivariate analysis did not show statistical differences in PFS and OS. There were no statistically significant differences in PFS and OS for all FIGO stages between MC with infiltrative invasion and HGSC. However, in cases with FIGO stages II to IV, MC with infiltrative invasion had worse PFS (p < 0.01) and OS (p < 0.01) than HGSC. In univariate analysis, MC with infiltrative invasion was a worse prognostic factor for PFS (hazard ratio [HR] 2.83, p < 0.01) and OS (HR 3.83, p < 0.01) than HGSC. Compared with HGSC, MC with expansile invasion had better PFS (p < 0.01) and OS (p < 0.01). Multivariate analysis demonstrated that MC with expansile invasion was a better prognostic factor for PFS (HR 0.17, p < 0.01) and OS (HR 0.18, p = 0.03) than HGSC. CONCLUSIONS: Compared to the prognosis of HGSC, that of MC was different according to the invasive pattern and FIGO stage. Therefore, future study may be needed to consider this association.
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Adenocarcinoma Mucinoso , Cistadenocarcinoma Seroso , Neoplasias Ováricas , Adenocarcinoma Mucinoso/patología , Carcinoma Epitelial de Ovario/patología , Cistadenocarcinoma Seroso/patología , Femenino , Humanos , Estadificación de Neoplasias , Neoplasias Ováricas/patología , Embarazo , Pronóstico , Estudios RetrospectivosRESUMEN
BACKGROUND: Ovarian metastases (OM) of pancreatic adenocarcinoma (PA) (OM-PA) can mimic primary ovarian mucinous carcinoma (POMC) on imaging and histology. These metastases are often symptomatic and not highly chemosensitive, so that oophorectomy may be considered. AIMS: The aims of this study were to compare the characteristics of OM-PA and POMC, and discuss the role of surgery. PATIENTS AND METHODS: Clinical, imaging, and histological data of patients with OM-PA and POMC (2000-2017) in three tertiary centers were reviewed. Twenty-six genes were analyzed by next generation sequencing (NGS) on both primary PA and OM-PA. RESULTS: Twenty-two women with OM-PA (n = 13, 11 with surgical resection) or POMC (n = 9) were selected. OM-PA were smaller than POMC (p = 0.02); imaging, histological, and immunohistochemistry data did not clearly differentiate OM-PA from POMC in 12 of 22 cases (54%). Seven PA/OM-PA pairs were analyzed, and a concordant KRAS mutation was identified in all cases. In four OM-PA, concordant mutations were also found in TP53 (n = 3), SMAD4 (n = 1), MET (n = 1), and PDGFRA (n = 1) genes. The aim of oophorectomy in 11 OM-PA was for antalgic (n = 6) or curative (n = 5) intent. Pain improved in 4/6 of the former patients, but 2/6 had significant morbidity, and 2/6 died of rapid tumor progression. After oophorectomy, median progression-free and overall survivals were 6 (0-11) and 8 months (1-131), respectively. CONCLUSION: Analysis of mutation profiles in both primary PA and ovarian tumors, especially KRAS, can help to determine the pancreatic origin of OM-PA. Surgical resection of OM-AP in highly selected patients may improve pelvic symptoms but may also cause significant morbidity. The benefit to survival requires further studies.
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BACKGROUND: In ovarian mucinous carcinoma, invasive pattern is the important factor but there were less reposts to investigate it. The aim of this study was to examine the association between prognosis and invasive patterns of ovarian mucinous carcinoma and to investigate the biomarkers of the diagnosis and prognosis immunochemically. Patients with ovarian mucinous carcinoma at our institution between 1984 and 2018 were identified. A pathological review was conducted using the 2020 World Health Organization criteria. The prognosis of infiltrative invasion and expansile invasion of ovarian mucinous carcinoma were retrospectively compared. In addition, immunohistochemical staining was conducted for all cases, and the immunohistochemical differences between the two invasive patterns were compared. RESULTS: After the pathological review, 25 cases with infiltrative invasion and 24 cases with expansile invasion were included. Ovarian mucinous carcinoma with infiltrative invasion showed significantly worse progression-free survival (PFS, p < 0.01) and overall survival (OS, p < 0.01) than those with expansile invasion. Multivariate analysis demonstrated that the pattern of infiltrative invasion was a worse prognostic factor for PFS (hazard ratio 9.01, p < 0.01) and OS (hazard ratio 17.56, p < 0.01). Immunohistochemically, cytokeratin (CK) 5/6 (p = 0.01), cluster of differentiation (CD) 24 (p = 0.02), and epithelial growth factor receptor (EGFR) (p < 0.01) were statistically related to infiltrative invasion. The PFS (p = 0.04) and OS (p = 0.02) of cases with EGFR-positive OMC were worse than those with negative OMC. CONCLUSIONS: Infiltrative invasion was observed to be a prognostic factor showing worse outcomes for ovarian mucinous carcinoma compared to expansile infiltration. CK5/6, CD24, and EGFR might be biomarkers of the diagnosis.
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Adenocarcinoma Mucinoso/metabolismo , Antígeno CD24/metabolismo , Carcinoma Epitelial de Ovario/metabolismo , Queratina-5/metabolismo , Queratina-6/metabolismo , Neoplasias Ováricas/metabolismo , Adenocarcinoma Mucinoso/patología , Adenocarcinoma Mucinoso/terapia , Biomarcadores de Tumor/metabolismo , Carcinoma Epitelial de Ovario/patología , Carcinoma Epitelial de Ovario/terapia , Quimioterapia Adyuvante , Procedimientos Quirúrgicos de Citorreducción , Receptores ErbB/metabolismo , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Análisis Multivariante , Invasividad Neoplásica , Neoplasia Residual , Neoplasias Ováricas/patología , Neoplasias Ováricas/terapia , Pronóstico , Supervivencia sin Progresión , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
AIMS: Grading of primary ovarian mucinous carcinoma (OMC) is inconsistent among practices. The International Collaboration on Cancer Reporting recommends grading OMC using the International Federation of Gynecology and Obstetrics (FIGO) system for endometrial endometrioid carcinoma, when needed. The growth pattern (expansile versus infiltrative), a known prognostic variable in OMC, is not considered in any grading system. We herein analysed the prognostic value of various grading methods in a well-annotated cohort of OMC. METHODS AND RESULTS: Institutional OMCs underwent review and grading by the Silverberg and FIGO schemes and a novel system, growth-based grading (GBG), defined as G1 (expansile growth or infiltrative invasion in ≤10%) and G2 (infiltrative growth >10% of tumour). Of 46 OMCs included, 80% were FIGO stage I, 11% stage II and 9% stage III. On follow-up (mean = 52 months, range = 1-190), five patients (11%) had adverse events (three recurrences and four deaths). On univariate analysis, stage (P = 0.01, Cox proportional analysis), Silverberg grade (P = 0.01), GBG grade (P = 0.001) and percentage of infiltrative growth (P < 0.001), but not FIGO grade, correlated with disease-free survival. Log-rank analysis showed increased survival in patients with Silverberg grade 1 versus 2 (P < 0.001) and those with GBG G1 versus G2 (P < 0.001). None of the parameters evaluated was significant on multivariate analysis (restricted due to the low number of adverse events). CONCLUSIONS: Silverberg and the new GBG system appear to be prognostically significant in OMC. Pattern-based grading allows for a binary stratification into low- and high-grade categories, which may be more appropriate for patient risk stratification. Despite current practices and recommendations to utilise FIGO grading in OMC, our study shows no prognostic significance of this system and we advise against its use.
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Adenocarcinoma Mucinoso/patología , Carcinoma Epitelial de Ovario/patología , Clasificación del Tumor/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Persona de Mediana Edad , Adulto JovenRESUMEN
Pseudomyxoma peritonei (PMP), also referred to as gelatinous ascites, is a rare disorder, described for the first time by R. Wyerth in 1884. It is characterized by diffuse peritoneal involvement, composed of mucinous ascites and multifocal mucinous epithelial implants. This disease mainly affects women. Its incidence is estimated at 2 cases per one million inhabitants. Pseudomyxoma peritonei can be asymptomatic, discovered during a laparotomy. The most common symptom is abdominal distension associated with diffuse abdominal pain. Abdominal CT scan is the most specific diagnostic tool. It shows pathognomonic signs of gelatinous ascites. Mucinous neoplasms of the appendix are the most frequent cause of pseudomyxoma peritonei accounting for 90% of cases. Pseudomyxoma peritonei of ovarian origin is very rare. There are essentially two types of treatment: multiple debulking surgery and cytoreductive surgery with perioperative intraperitoneal chemotherapy consisting of hyperthermic intraperitoneal chemotherapy with or without immediate postoperative intraperitoneal chemotherapy. We report a case of pseudomyxoma peritonei secondary to mucinous carcinoma of the left ovary.
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Adenocarcinoma Mucinoso/diagnóstico , Neoplasias Ováricas/diagnóstico , Seudomixoma Peritoneal/etiología , Dolor Abdominal/etiología , Adenocarcinoma Mucinoso/patología , Femenino , Humanos , Laparotomía/métodos , Persona de Mediana Edad , Neoplasias Ováricas/patología , Seudomixoma Peritoneal/diagnósticoRESUMEN
Leptomeningeal carcinomatosis, leptomeningeal meningitis, or, as referred here, leptomeningeal metastasis (LM), is a rare but frequently fatal complication seen in advanced stage of cancer either locally advanced or after a metastasis of a known primary cancer. We present a rare and uncommon case of leptomeningeal metastases from carcinoma of unknown primary. A 32-year-old female was diagnosed with LM; however, no known primary carcinoma was identified after 2 separate biopsies. The first biopsy of the right pre-tracheal lymph node showed poorly differentiated pan-keratin (AE1 and AE3) and placental alkaline phosphatase with the possibility of germ cell origin. Second cytology of cervical lymphadenopathy was remarkable for cytokeratin 7 and 20, placental alkaline phosphatase, and CDX2 suggestive of germ line tumor with both mucinous ovarian and gastrointestinal carcinomas. Unfortunately, the LM progressed rapidly despite multiple cycles of germ cell origin directed systemic and intrathecal chemotherapy, and the patient opted for hospice care without getting a chance to identify the primary source.
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Carcinomatosis Meníngea/secundario , Neoplasias Primarias Desconocidas , Adulto , Femenino , Humanos , Carcinomatosis Meníngea/diagnóstico , Carcinomatosis Meníngea/diagnóstico por imagen , Carcinomatosis Meníngea/patología , Neoplasias Primarias Desconocidas/diagnóstico , Neoplasias Primarias Desconocidas/patología , Neuroimagen , Tomografía Computarizada por Rayos X , UltrasonografíaRESUMEN
BACKGROUND: Epithelial ovarian cancer development before menarche is extremely rare. CASE: We report a prepubertal girl who developed ovarian mucinous carcinoma with mural carcinosarcomatous components. SUMMARY AND CONCLUSION: Magnetic resonance imaging showed a polycystic mass with solid components. The left adnexa was removed. Histological analysis revealed a mucinous tumor with mural carcinosarcomatous components. Three weeks later, ascites and peritoneal metastasis were detected. The patient received a combination therapy of paclitaxel with carboplatin. After 4 chemotherapy cycles the right adnexa, uterus, partial omentum, and pelvic peritoneum were removed. Four additional paclitaxel/carboplatin therapy cycles were administered. She remains free from recurrence after 29 months. To our knowledge, this is the first report of ovarian mucinous carcinoma with mural carcinosarcomatous components in a prepubertal girl.
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Adenocarcinoma Mucinoso/patología , Carcinoma Epitelial de Ovario/patología , Neoplasias Ováricas/patología , Adenocarcinoma Mucinoso/diagnóstico por imagen , Adenocarcinoma Mucinoso/terapia , Adolescente , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carboplatino/uso terapéutico , Carcinoma Epitelial de Ovario/diagnóstico por imagen , Terapia Combinada , Femenino , Humanos , Imagen por Resonancia Magnética , Neoplasias Ováricas/diagnóstico por imagen , Neoplasias Ováricas/terapia , Paclitaxel/uso terapéuticoRESUMEN
BACKGROUND: The presence of anaplastic and sarcomatoid components in ovarian mucinous carcinoma is extremely rare. CASE: A 64-year-old woman underwent radical surgery for right ovarian cancer. Pathological examination showed mucinous adenocarcinoma with a focal mural nodule of anaplastic and sarcomatoid carcinoma (FIGO stage IIB). She underwent adjuvant chemotherapy but developed severe respiratory failure and died after 9 months. Autopsy showed that the bilateral pulmonary parenchyma was filled with a multinodular hemorrhagic mass, and the cardiac wall had a massive invasive lesion. Histopathological examination of the lung and myocardium revealed diffuse invasion of the anaplastic carcinoma component with infiltrating osteoclastic giant cells. CONCLUSION: This case is very rare, and the clinical management of anaplastic carcinoma arising in mucinous neoplasms remains challenging.
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Adenocarcinoma Mucinoso/patología , Carcinoma/secundario , Neoplasias Cardíacas/secundario , Neoplasias Pulmonares/secundario , Neoplasias Primarias Múltiples/patología , Neoplasias Ováricas/patología , Adenocarcinoma Mucinoso/cirugía , Anaplasia , Apendicectomía , Autopsia , Carcinoma/diagnóstico por imagen , Carcinoma/patología , Quimioterapia Adyuvante , Resultado Fatal , Femenino , Neoplasias Cardíacas/diagnóstico por imagen , Neoplasias Cardíacas/patología , Humanos , Histerectomía , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Escisión del Ganglio Linfático , Persona de Mediana Edad , Neoplasias Primarias Múltiples/diagnóstico por imagen , Neoplasias Primarias Múltiples/secundario , Neoplasias Primarias Múltiples/cirugía , Neoplasias Ováricas/cirugía , Salpingooforectomía , Tomografía Computarizada por Rayos XRESUMEN
AIM: To determine whether CD44, which is associated with tumor growth and metastasis, is related to carcinogenesis and prognosis in ovarian mucinous carcinomas (MACs). MATERIALS AND METHODS: Tissue blocks from 71 patients with benign mucinous ovarian tumors were used in the study: 35 were from patients with borderline mucinous ovarian tumors, and 60 from patients with MACs. Immunochemical analysis was performed to evaluate the expression of CD44 and examine its association with tumorigenesis and survival. RESULTS: Compared to benign tumors, borderline tumors had high CD44 expression levels (p=0.047). Conversely, MACs had lower expression than borderline tumors (p=0.032). Progression-free and overall survival of patients with MAC with low CD44 expression were worse than those of patients with high expression (p=0.04 and p=0.02, respectively). CONCLUSION: Malignant transformation of mucinous tumors is associated with changes in CD44 expression, with low expression level being a prognostic factor in MAC.
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Adenocarcinoma Mucinoso/metabolismo , Adenocarcinoma Mucinoso/mortalidad , Receptores de Hialuranos/metabolismo , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/mortalidad , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/metabolismo , Femenino , Humanos , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Adulto JovenRESUMEN
The aim of this study was to clarify the synergistic effects of dual inhibition of the PI3K/mTOR and MAPK pathways in ovarian mucinous carcinoma (OMC) cells, using fluorescence resonance energy transfer (FRET) imaging. We exposed 6 OMC cell lines to a PI3K/mTOR inhibitor (voxtalisib, SAR245409) and/or a MEK inhibitor (pimasertib), and evaluated synergistic effects using the Chou-Talalay method. Then, S6K (PI3K pathway) and ERK (MAPK pathway) kinase activities, and their individual proliferative or cytotoxic effects were calculated by time-lapse FRET imaging. In combination with SAR245409, pimasertib (30 nM) synergistically inhibited cell growth (combination indexes: 0.03-0.5) and induced apoptosis in all 6 OMC cell lines. FRET-imaging results demonstrated that ERK inhibition induced both anti-proliferation and apoptosis in a dose-dependent manner in both MCAS and OAW42 cells. However, S6K inhibition suppressed proliferation in a threshold manner in both cell lines, although apoptosis was only induced in OAW42 cells. These results demonstrated that combined PI3K/mTOR and MEK inhibition exhibited synergistic antitumor effects in OMC cells and that FRET imaging is useful for analyzing kinase activities in live cells and elucidating their cytostatic and cytotoxic effects.
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Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Cistadenocarcinoma Mucinoso , Ensayos de Selección de Medicamentos Antitumorales/métodos , Transferencia Resonante de Energía de Fluorescencia/métodos , Neoplasias Ováricas , Línea Celular Tumoral , Sinergismo Farmacológico , Femenino , Humanos , Quinasas Quinasa Quinasa PAM/antagonistas & inhibidores , Modelos Teóricos , Niacinamida/análogos & derivados , Niacinamida/farmacología , Inhibidores de las Quinasa Fosfoinosítidos-3 , Quinoxalinas/farmacología , Sulfonamidas/farmacología , Serina-Treonina Quinasas TOR/antagonistas & inhibidoresRESUMEN
OBJECTIVE: To compare clinicopathological characteristics and survival rates between patients with primary ovarian mucinous carcinoma and those with primary ovarian serous carcinoma. METHODS: This retrospective study reviewed archival tumour specimens, originally diagnosed as primary ovarian mucinous carcinoma, using refined histological criteria. All patients were contacted to establish survival status. Clinicopathological characteristics and patient survival data were compared with a group of control patients with primary ovarian serous carcinoma. RESULTS: Of the 33 patients originally diagnosed with primary ovarian mucinous carcinoma, this diagnosis was only confirmed in 18. Primary ovarian mucinous carcinoma was more commonly associated with early International Federation of Gynecology and Obstetrics tumour stages and low-grade histology than primary ovarian serous carcinoma. Patients with primary ovarian mucinous carcinoma had a significantly higher overall 5-year survival rate than those with primary ovarian serous carcinoma (12/12 [100%] versus 14/24 [58%]). Kaplan-Meier survival plots demonstrated that patients with primary ovarian mucinous carcinoma had a survival advantage over patients with primary ovarian serous carcinoma. CONCLUSIONS: Primary ovarian mucinous carcinomas are frequently low-grade, stage I tumours and have an excellent prognosis.
Asunto(s)
Adenocarcinoma Mucinoso/diagnóstico , Cistadenocarcinoma Seroso/diagnóstico , Neoplasias Ováricas/diagnóstico , Adenocarcinoma Mucinoso/mortalidad , Adenocarcinoma Mucinoso/patología , Adenocarcinoma Mucinoso/cirugía , Adulto , Anciano , Cistadenocarcinoma Seroso/mortalidad , Cistadenocarcinoma Seroso/patología , Cistadenocarcinoma Seroso/cirugía , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/patología , Neoplasias Ováricas/cirugía , Pronóstico , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
Hypoxia-inducible factor-1 (HIF-1) is one of the most promising pharmacological targets for all types of cancer, including ovarian cancer. Ovarian clear cell carcinoma (OCCC) has poor prognosis because of its insensitivity to chemotherapy. To elucidate the characteristics of this troublesome cancer, we examined HIF-1α expression under normoxia or hypoxia in various ovarian cancer cell lines. HIF-1α was highly expressed under normoxia only in RMG-1, an OCCC cell line. To examine whether HIF-1 is involved in the tumorigenesis of RMG-1 cells, we established HIF-1α-silenced cells, RMG-1HKD. The proliferation rate of RMG-1HKD cells was faster than that of RMG-1 cells. Furthermore, the activity of MEK/ERK in the Ras pathway increased in RMG-1HKD cells, whereas that of mTOR in the PI3K pathway did not change. Activation of the Ras pathway was attributable to the increase in phosphorylated MEK via PP2A inactivation. To confirm the crosstalk between the PI3K and Ras pathways in vivo, RMG-1 or RMG-1HKD cells were transplanted into the skin of nude mice with rapamycin (an inhibitor of mTOR), PD98059 (an inhibitor of MEK), or both. RMG-1HKD cells showed higher sensitivity to PD98059 than that observed in RMD-1 cells, whereas the combination therapy resulted in synergistic inhibition of both cells. These findings suggest that inhibition of HIF-1, a downstream target of mTOR in the PI3K pathway, activates the Ras pathway on account of the increase in MEK phosphorylation via PP2A inactivation, and the crosstalk between the 2 pathways could be applied in the combination therapy for HIF-1-overexpressing cancers such as OCCC.