RESUMEN
Pancreatic cancer (PC) is the seventh leading cause of cancer death worldwide, and remains one of our most recalcitrant and dismal diseases. In contrast to many other malignancies, there has not been a significant improvement in patient survival over the past decade. Despite advances in our understanding of the genetic alterations associated with this disease, an incomplete understanding of the underlying biology and lack of suitable animal models have hampered efforts to develop more effective therapies. LKB1 is a tumor suppressor that functions as a primary upstream kinase of adenine monophosphate-activated protein kinase (AMPK), which is an important mediator in the regulation of cell growth and epithelial polarity pathways. LKB1 is mutated in a significant number of Peutz-Jeghers syndrome (PJS) patients and in a small proportion of sporadic cancers, including PC; however, little is known about how LKB1 loss contributes to PC development. Here, we report that a reduction in Wnt/ß-catenin activity is associated with LKB1 tumor-suppressive properties in PC. Remarkably, in vivo functional analyses of ß-catenin in the Pdx-1-Cre LKB1L/L ß-cateninL/L mouse model compared to LKB1 loss-driven cystadenoma demonstrate that the loss of ß-catenin impairs cystadenoma development in the pancreas of Pdx-1Cre LKB1L/L mice and dramatically restores the normal development and functions of the pancreas. This study further determined the in vivo and in vitro therapeutic efficacy of the ß-catenin inhibitor FH535 in suppressing LKB1 loss-driven cystadenoma and reducing PC progression that delineates the potential roles of Wnt/ß-catenin signaling in PC harboring LKB1 deficiency.
Asunto(s)
Cistoadenoma Mucinoso/metabolismo , Neoplasias Pancreáticas/metabolismo , Proteínas Serina-Treonina Quinasas/deficiencia , Sulfonamidas/farmacología , beta Catenina/antagonistas & inhibidores , Quinasas de la Proteína-Quinasa Activada por el AMP , Proteínas Quinasas Activadas por AMP/metabolismo , Animales , Línea Celular Tumoral , Cistoadenoma Mucinoso/etiología , Cistoadenoma Mucinoso/prevención & control , Femenino , Humanos , Masculino , Ratones , Ratones de la Cepa 129 , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Mutación , Neoplasias Experimentales/genética , Neoplasias Experimentales/metabolismo , Páncreas/efectos de los fármacos , Páncreas/metabolismo , Páncreas/patología , Neoplasias Pancreáticas/etiología , Neoplasias Pancreáticas/prevención & control , Síndrome de Peutz-Jeghers/genética , Síndrome de Peutz-Jeghers/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Vía de Señalización Wnt/efectos de los fármacos , beta Catenina/genéticaRESUMEN
We report MR imaging findings of a rare case of endocervical mucinous borderline tumor (MBT) involving the cul-de-sac and left fallopian tube arising from extensive pelvic endometriosis with pathologic correlation in a 35-year-old woman presented with vague pelvic pain. Endocervical MBT is a type of endometriosis-associated carcinoma. Imaging findings of endocervical MBT are unilocular or oligolocular cystic lesions with enhancing mural nodules, which are different from those of the more common intestinal type MBT.
Asunto(s)
Cistoadenoma Mucinoso/diagnóstico , Endometriosis/diagnóstico , Imagen por Resonancia Magnética/métodos , Neoplasias Ováricas/diagnóstico , Lesiones Precancerosas/diagnóstico , Adulto , Cistoadenoma Mucinoso/etiología , Diagnóstico Diferencial , Endometriosis/complicaciones , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Ováricas/etiología , Pelvis , Lesiones Precancerosas/etiologíaRESUMEN
UNLABELLED: There is limited information on borderline ovarian tumor detected intra-surgically and its most favorable treatment in relation with global radiation and climate changes. AIM: To study the pre-surgery and intra-surgery differentiation criteria of borderline ovarian tumors from invasive carcinoma, and to make a very complex analysis of the frequency, distribution, and variation in time of global radiation, temperature, and precipitation in North-East Romania. MATERIAL AND METHOD: The 54 patients (age range 20-78 years, mean age 46 years) included in this study had borderline ovarian tumors surgically treated during the last 22 years (January 1988 - December 2009) at the 4th Gynecological Clinic at Iasi, and representing 4.87% of the total 1107 ovarian tumors detected and treated during this interval. The histological types were: serous (18 cases), mucinous (27 cases), mixed (8 cases), and Brenner tumor (1 case). In order to analyze the impact of climate changes on borderline ovarian tumors a thorough study on the frequency of global radiation in relation with climate changes based on data recorded in the last 55 years was also carried out. RESULTS: The distribution of these cases depending on when surgery was performed was analyzed. In our study the frequency of ovarian borderline tumors (4.87%) is lower than in similar reports in the literature being due, in our opinion, to the influence of global radiation in relation with climate changes. CONCLUSIONS: In our study global radiation is probably responsible for a progression to invasive carcinoma in 0.7% of the borderline ovarian tumors.
Asunto(s)
Tumor de Brenner/etiología , Cambio Climático , Radiación Cósmica/efectos adversos , Cistoadenoma Mucinoso/etiología , Cistadenoma Seroso/etiología , Neoplasias Ováricas/etiología , Adulto , Anciano , Tumor de Brenner/epidemiología , Tumor de Brenner/patología , Tumor de Brenner/cirugía , Transformación Celular Neoplásica , Cistoadenoma Mucinoso/epidemiología , Cistoadenoma Mucinoso/patología , Cistoadenoma Mucinoso/cirugía , Cistadenoma Seroso/epidemiología , Cistadenoma Seroso/patología , Cistadenoma Seroso/cirugía , Diagnóstico Diferencial , Progresión de la Enfermedad , Femenino , Calentamiento Global , Humanos , Persona de Mediana Edad , Invasividad Neoplásica , Neoplasias Ováricas/epidemiología , Neoplasias Ováricas/patología , Neoplasias Ováricas/cirugía , Pronóstico , Estudios Retrospectivos , Rumanía/epidemiología , Resultado del TratamientoRESUMEN
Cystic fibrosis (CF) is the most frequent genetic disease in the Caucasian population. It seems to be associated with an increased risk of digestive cancer but only few cases of pancreatic tumors have been reported. As pancreatic lesions of the pancreas in CF patients are not rare, their etiological diagnosis is substantial. We report herein a case of a mucinous cystadenoma in a patient with CF. Diagnosis and management of pancreatic cystic tumors in patients at high risk of operative morbidity are challenging. When the potential malignancy of a pancreatic cystic mass cannot be well established in a CF patient, partly because of frequent chronic pancreatitis lesions, we suggest that surgical management should be undertaken instead of radiological surveillance.
Asunto(s)
Cistoadenoma Mucinoso/etiología , Fibrosis Quística/complicaciones , Neoplasias Pancreáticas/etiología , Cistoadenoma Mucinoso/diagnóstico , Femenino , Humanos , Neoplasias Pancreáticas/diagnóstico , Adulto JovenRESUMEN
There is an increased incidence of tumors among renal transplant patients, which are associated with immunosuppression. Carcinoids are rare neuroendocrine tumors that arise from the enterochromaffin cells. Although appendiceal carcinoid tumors are the commonest malignant neoplasms affecting the appendix, and mucinous cystadenoma is the commonest benign appendiceal neoplasm, they have not been reported in immunosuppressed patients. We present two renal transplant recipients who developed combined appendiceal carcinoid and mucinous cystadenoma.
Asunto(s)
Neoplasias del Apéndice/etiología , Cistoadenoma Mucinoso/etiología , Trasplante de Riñón/efectos adversos , Adulto , Neoplasias del Apéndice/patología , Cistoadenoma Mucinoso/patología , Cistoadenoma Mucinoso/cirugía , Femenino , Humanos , Fallo Renal Crónico/cirugía , Imagen por Resonancia Magnética , Masculino , Neoplasias/epidemiología , Neoplasias/etiología , Neoplasias/patología , Neoplasias/cirugía , Neoplasias Ováricas/patología , Neoplasias Ováricas/cirugíaRESUMEN
BACKGROUND: Mucinous cystic neoplasms arise in the ovary and various extra-ovarian sites. While their pathogenesis remains conjectural, their similarities suggest a common pathway of development. There have been rare reports involving the mesentery as a primary tumour site. CASE PRESENTATION: A cystic mass of uncertain origin was demonstrated radiologically in a 22 year old female with chronic abdominal pain. At laparotomy, the mass was fixed within the colonic mesentery. Histology demonstrated a benign mucinous cystadenoma. METHODS AND RESULTS: We review the literature on mucinous cystic neoplasms of the mesentery and report on the pathogenesis, biologic behavior, diagnosis and treatment of similar extra-ovarian tumors. We propose an updated classification of mesenteric cysts and cystic tumors. CONCLUSION: Mucinous cystic neoplasms of the mesentery present almost exclusively in women and must be considered in the differential diagnosis of mesenteric tumors. Only full histological examination of a mucinous cystic neoplasm can exclude a borderline or malignant component. An updated classification of mesenteric cysts and cystic tumors is proposed.
Asunto(s)
Cistoadenoma Mucinoso/patología , Quiste Mesentérico/patología , Adulto , Cistoadenoma Mucinoso/diagnóstico , Cistoadenoma Mucinoso/etiología , Cistoadenoma Mucinoso/terapia , Femenino , Humanos , Quiste Mesentérico/diagnóstico , Quiste Mesentérico/etiología , Quiste Mesentérico/terapiaRESUMEN
BACKGROUND: IBD is a risk factor for development of colorectal neoplasia. Although IBD frequently involves the appendix microscopically, it is uncertain whether it also predisposes to appendiceal neoplasia. METHODS: We performed a retrospective case-control study of incidental appendiceal neoplasms in colectomy specimens of adults with and without IBD (cases and controls, respectively) based on surgical pathology records spanning 54 months. To minimize referral bias, patients were excluded if they had preoperative clinical evidence or a principal pathologic diagnosis of appendiceal disease. The pathologic diagnoses were confirmed retrospectively. RESULTS: Eleven appendiceal cystadenomas and 6 appendiceal carcinoid tumors were identified among 705 IBD cases (377 ulcerative colitis, 317 Crohn's disease, 11 indeterminate colitis) and 498 non-IBD controls meeting our inclusion criteria. There was no significant difference in prevalence of cyst adenomas between the cases and controls (9/705 [1.3%] versus 2/498 [0.4%], respectively, OR 3.2 [95% CI 0.7-14.9]). However, cyst adenomas were 15-fold more prevalent among cases with synchronous colorectal neoplasia compared with controls (4/69 [5.8%] versus 2/498 [0.4%], OR 15.3 [95% CI 2.7-85]) and 8-fold higher compared with cases without synchronous neoplasia (4/69 [5.8%] versus 5/636 [0.8%], OR 7.8 [95% CI 2.0-29.6]). Appendiceal carcinoids were equally prevalent in cases and controls (4/705 [0.6%] versus 2/498 [0.4%], OR 1.4 [95% CI 0.3-7.8]), cases with synchronous neoplasia and controls (1/69 [1.4%] versus 2/498 [0.4%], OR 3.6 [95% CI 0.3-40.8]), and cases with and without synchronous colorectal neoplasia (1/69 [1.4%] versus 3/636 [0.5%], OR 3.1 [95% CI 0.3-30.2]). CONCLUSIONS: IBD with synchronous colorectal dysplasia or cancer is a risk factor for development of appendiceal cystadenomas, implicating this tumor as a neoplastic complication of IBD. IBD does not predispose to the development of appendiceal carcinoids.
Asunto(s)
Neoplasias del Apéndice/etiología , Cistoadenoma Mucinoso/etiología , Enfermedades Inflamatorias del Intestino/complicaciones , Adulto , Anciano , Apendicectomía , Neoplasias del Apéndice/patología , Neoplasias del Apéndice/cirugía , Colectomía , Colonoscopía , Cistoadenoma Mucinoso/patología , Cistoadenoma Mucinoso/cirugía , Femenino , Estudios de Seguimiento , Humanos , Enfermedades Inflamatorias del Intestino/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Retrospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
A mucinous cystadenoma of the paratestis arising from an unequivocal oviduct-like structure in an 18-year-old man is reported. Mucinous cystadenomas of the testis and paratestis are extremely rare benign tumors of controversial origin. The diagnosis may be challenging and is of clinical importance because these lesions may mimic a teratoma, and teratomas in postpubertal males carry a malignant potential regardless of the degree of maturation. A few case reports and reviews of testicular and paratesticular mucinous neoplasms resembling ovarian tumors have suggested the possibility of a müllerian origin of these tumors. However, no histologic evidence has been found to support such a histogenesis. The current case demonstrates a clear transition from müllerian-type tubal epithelium to intestinal-type mucinous epithelium. This finding, in conjunction with immunophenotypic studies, strongly supports a derivation from a paratesticular müllerian remnant. To our knowledge this represents the first substantial evidence that, in at least some cases, mucinous cystadenomas of the testis and paratestis are of müllerian derivation.
Asunto(s)
Cistoadenoma Mucinoso/etiología , Cistoadenoma Mucinoso/patología , Conductos Paramesonéfricos/patología , Neoplasias Testiculares/etiología , Neoplasias Testiculares/patología , Adolescente , Cistoadenoma Mucinoso/química , Diagnóstico Diferencial , Humanos , Inmunohistoquímica , Inmunofenotipificación , Mucosa Intestinal/patología , Masculino , Neoplasias Testiculares/químicaRESUMEN
Endometriosis is a well-known precursor lesion of ovarian malignancies, particularly those of endometrioid and clear-cell types and rarely of serous or mucinous types. The association of endometriosis with mucinous borderline tumors also varies. This case is of a 60 year old female, who had a long history of more than thirty years of endometriosis and developed recurrent endocervical-like mucinous borderline tumor (ELMBT) in endometriotic foci. This case highlights challenges in the management of such complications associated with endometriosis and emphasizes the importance of long-term follow-up in cases of endometriosis.
Asunto(s)
Cistoadenoma Mucinoso/patología , Neoplasias Ováricas/patología , Cistoadenoma Mucinoso/etiología , Endometriosis/complicaciones , Endometriosis/patología , Femenino , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Neoplasias Ováricas/etiología , Lesiones Precancerosas/etiología , Lesiones Precancerosas/patologíaRESUMEN
Appendiceal tumours are rare and often discovered unexpectedly in an acute situation in which decision-making is difficult. We report the spectrum of appendiuar tumours seen in our institution over a period of more than 10 years, and discuss the clinicopathological behaviour, investigations, surgical procedures and outcomes in these patients. We have also reviewed the literature with regard to appendiceal tumours. Appendicular tumours were identified from the database of 1646 appendictomies (18% in children) performed in single centre and case notes were reviewed. Clinical presentation, investigations, histopathology, surgical procedures and outcome were analysed. Twelve patients with appendiceal tumours were identified (0.72%): 8 carcinoid, 2 mucinous (mucocele) and 2 adenocarcinoma. All the patients with a carcinoid tumour presented with features suggestive of acute appendicitis and were diagnosed postoperatively following appendicectomy and formal histology. No further surgical intervention was required as these lesions were less than 1cm away from the base of the appendix. One of the patient with mucinous cystadenoma presented acutely and underwent an appendicectomy; in the other patient with chronic pain, apreoperative MRI suggested the diagnosis leading to a planned hemicolectomy as the lesion was close to the base of the appendix. While one of the patient with an adenocarcinoma localized to the appendix did well following a right hemicolectomy, the other patient with disseminated disease succumbed within a year. Carcinoid tumours are the commonest appendiceal tumours, which present often as acute appendicitis. While appendicectomy would be adequate in most of these patients, in patients with a cystadenoma close to the base of the appendix or in case of a carcinoma, a right hemicolectomy is the appropriate option. While the prognosis is good in patients with carcinoid tumour and cystadenoma, it remains dismal in patients with disseminated malignant disease.
Asunto(s)
Neoplasias del Apéndice/epidemiología , Adenocarcinoma/epidemiología , Adenocarcinoma/etiología , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Adulto , Anciano , Apendicectomía/estadística & datos numéricos , Neoplasias del Apéndice/etiología , Neoplasias del Apéndice/patología , Neoplasias del Apéndice/cirugía , Tumor Carcinoide/epidemiología , Tumor Carcinoide/etiología , Tumor Carcinoide/patología , Tumor Carcinoide/cirugía , Cistoadenoma Mucinoso/epidemiología , Cistoadenoma Mucinoso/etiología , Cistoadenoma Mucinoso/patología , Cistoadenoma Mucinoso/cirugía , Femenino , Humanos , Incidencia , Masculino , Registros Médicos , Persona de Mediana Edad , Omán/epidemiología , Estudios RetrospectivosRESUMEN
Primary retroperitoneal mucinous cystadenoma is an uncommon tumor found exclusively in women. Herein, we describe a patient who had resection of a large retroperitoneal cystic mass. Histologic, immunohistochemical, and electron microscopic examination of the lining epithelial cells showed features of mesothelial cells in addition to ovarian mucinous cystadenoma. These findings suggest that these tumors arise from inclusions of mesothelial cells and subsequent mucinous metaplasia of the lining cells to form a cystadenoma. Estrogen receptors may be implicated in tumor promotion, explaining the occurrence exclusively in women.
Asunto(s)
Cistoadenoma Mucinoso/diagnóstico , Cistoadenoma Mucinoso/etiología , Neoplasias Retroperitoneales/diagnóstico , Neoplasias Retroperitoneales/etiología , Adulto , Biomarcadores de Tumor/análisis , Cistoadenoma Mucinoso/química , Femenino , Humanos , Inmunohistoquímica , Reacción del Ácido Peryódico de Schiff , Receptores de Estrógenos/análisis , Neoplasias Retroperitoneales/química , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Mucinous tumors of the ovary have been thought to originate in two ways: by müllerian-type metaplasia of surface epithelium, and as monodermal teratomas. To gain a better understanding of their pathogenesis, the authors analyzed these tumors for their expression of estrogen receptors (ER) and progesterone receptors (PR) as markers of müllerian-type differentiation and for their content of gastric-type mucin as a marker of gastric differentiation. METHODS: The histochemical expression of ER, PR, and gastric-type mucin was studied in 10 specimens of the cervix with normal endocervical glands (as a representative of müllerian-derived mucin-containing cells), 3 ovary specimens with surface epithelial inclusion cysts that contained endocervical-like mucin-containing cells (representing müllerian-type metaplasia), and 47 mucinous tumors of the ovary (29 benign, 8 with low malignant potential, and 10 malignant). RESULTS: Normal endocervical glands expressed ER and PR and rarely expressed gastric-type mucin. Ovarian inclusion cysts showed strong expression of ER and PR in the cuboidal cells and drastically reduced expression in the endocervical-like mucin-containing cells. The cuboidal cells were negative for gastric-type mucin, but the endocervical-like mucin-containing cells expressed gastric-type mucin. Endocervical-like mucinous cells in benign and borderline mucinous tumors showed expression of PR and/or gastric-type mucin in all cases. CONCLUSIONS: The staining results for the inclusion cysts support the thesis that the endocervical-like mucinous cells encountered in the ones that express ER and PR weakly or not at all and have histochemical properties of normal gastric epithelium have their origin in metaplasia of müllerian-type epithelium. Application of the same staining methods to benign ovarian tumors and those with low malignant potential suggests strongly that similar müllerian-type metaplasia is a major pathway in their pathogenesis.
Asunto(s)
Adenocarcinoma Mucinoso/química , Adenocarcinoma Mucinoso/etiología , Cistoadenoma Mucinoso/química , Cistoadenoma Mucinoso/etiología , Conductos Paramesonéfricos/patología , Neoplasias Ováricas/química , Neoplasias Ováricas/etiología , Adenocarcinoma Mucinoso/patología , Adulto , Anciano , Diferenciación Celular , Transformación Celular Neoplásica , Cuello del Útero/química , Cuello del Útero/patología , Concanavalina A , Cistoadenoma Mucinoso/patología , Femenino , Galactosa Oxidasa , Mucinas Gástricas/análisis , Humanos , Inmunohistoquímica , Metaplasia/complicaciones , Persona de Mediana Edad , Quistes Ováricos/química , Neoplasias Ováricas/patología , Receptores de Estrógenos/análisis , Receptores de Progesterona/análisis , Coloración y Etiquetado/métodosRESUMEN
Concerns have been raised recently about the possible association between superovulation and ovarian cancer. In order to contribute to the limited literature on this important issue, two cases of ovarian tumours in women who had undergone multiple ovulation inductions are presented. In the first case, the patient had secondary anovulatory infertility. She was treated with human menopausal gonadotrophin (HMG) alone and in combination with clomiphene citrate or buserelin for six cycles. She then underwent ovarian stimulation with buserelin/HMG in the long protocol for in-vitro fertilization (IVF) and embryo transfer. In preparation for a new IVF/embryo transfer attempt, 8 months later, the screening ultrasound revealed a cystic formation of the left ovary and an enlargement of the right. During laparotomy, both ovaries were found to bear large tumours (approximately 6 x 5 x 4 cm) which were removed. Histological examination showed that they were epithelial tumours (serous-papillary cystadenomas) of borderline malignancy. The patient conceived spontaneously 1.5 years after the operation. In the second case, the patient presented with secondary anovulatory infertility. She underwent ovulation induction with clomiphene/HMG and with buserelin/HMG in the long protocol, and intra-uterine insemination with husband's spermatozoa and conceived (singleton pregnancy). She was delivered by Caesarean section, during which a cystic tumour of the left ovary was removed. Histological examination revealed a benign mucous cystadenoma of the ovary.(ABSTRACT TRUNCATED AT 250 WORDS)