RESUMEN
The ovaries are a common site of metastasis from different organs, especially from the gastrointestinal tract. However, metastasis from the gallbladder to the ovaries is very rare. Our case involves a 57-year-old female who presented with abdominal pain and distension. Radiologic imaging suggests the possibility of a primary ovarian tumor causing small bowel obstruction. Grossly, the cystic mass in the right ovary closely resembles the typical characteristics of a primary ovarian tumor. Histologic examination revealed adenocarcinoma. Positive immunostaining for CA 19-9, cytokeratin-7 (CK7), CEA, and CDX2 and negative reaction to CK20, PAX8, and CA 125 are compatible with a pancreaticobiliary/gallbladder origin. Considering the results obtained from imaging, which included gallbladder wall thickening and the presence of a mass within the gallbladder, alongside the pancreas appearing normal, the primary site of concern was determined to be the gallbladder. It is important to consider primary sites other than the ovary in the presence of previous or concurrent lesions elsewhere, such as gastrointestinal (GI) or pancreaticobiliary tract since treatment regimens are different. Clinicoradiologic correlation and immunohistochemistry aid in differentiating this secondary ovarian tumor from a primary ovarian carcinoma.
RESUMEN
Interpretation of the mucinous change in the fallopian tubes has been difficult because several reports consider this mucinous change as a metastasis from a mucinous tumor. To clarify this issue, we decided to retrospectively review salpingectomies from 3 institutions looking for mucinous change in the fallopian tubes and documented the clinical history of these patients. Twenty-three cases of fallopian tubes with mucinous changes were found, including 11 patients without evidence of malignancy, 4 patients with mucinous ovarian tumors, 5 patients with nonmucinous gynecologic tumors, 2 patients with mucinous appendiceal neoplasm, and 1 patient with colon carcinoma. As mucinous changes are seen in several patients who do not have a malignant tumor, we believe that these changes represent a metaplastic process. The mucinous changes are frequently seen with chronic inflammation and/or other metaplastic changes and without cytologic evidence of malignancy.
Asunto(s)
Adenocarcinoma Mucinoso/secundario , Neoplasias del Apéndice/patología , Neoplasias de las Trompas Uterinas/secundario , Trompas Uterinas/patología , Neoplasias Ováricas/patología , Adenocarcinoma Mucinoso/cirugía , Adulto , Anciano , Neoplasias del Apéndice/cirugía , Diagnóstico Diferencial , Neoplasias de las Trompas Uterinas/cirugía , Trompas Uterinas/cirugía , Femenino , Humanos , Inflamación/patología , Inflamación/cirugía , Metaplasia/patología , Metaplasia/cirugía , Persona de Mediana Edad , Mucinas , Estadificación de Neoplasias , Neoplasias Ováricas/cirugía , Estudios Retrospectivos , SalpingectomíaRESUMEN
OBJECTIVE: Increasing frequency of severe variable decelerations is associated with acidemia. However, there is little understanding of its development or normalization rate. STUDY DESIGN: To quantify the time course of acidemia, 10 near-term fetal sheep underwent a series of mild (1 minute every 5 minutes), moderate (1 minute every 3 minutes), and severe (1 minute every 2 minutes) umbilical cord occlusions (UCO), lasting 1 hour each or until fetal arterial pH decreased to less than 7.00. RESULTS: Each minute of UCO resulted in base deficit (BD) and lactate increases at rates of 0.56 and 0.35 mmol/L per minute, respectively. During a 2 h recovery, BD and lactate normalized at rates of 0.09 and 0.04 mmol/L per minute. BD correlated highly with lactate (r = 0.95; P < .001). CONCLUSION: Our findings in the near-term ovine fetus suggest that the knowledge of fetal BD deterioration and recovery rates can aid assessing fetal acidemia during labor.
Asunto(s)
Acidosis/diagnóstico , Hipoxia Fetal/fisiopatología , Cordón Umbilical/irrigación sanguínea , Animales , Femenino , Hipoxia Fetal/etiología , Embarazo , Diagnóstico Prenatal , Ovinos , Nacimiento a TérminoRESUMEN
Ménétrier's Disease is a giant fold gastropathy whose precise etiology has remained enigmatic. However, mucosal changes characteristic of Ménétrier's Disease have been linked to diverse pathologies, both infectious and malignant. Here, we describe a novel association: Ménétrier's mucosa developing on top of underlying Kaposi's Sarcoma. Two male patients, ages 24 and 31, with HIV/AIDS underwent gastric biopsies that demonstrated Kaposi's Sarcoma. When the former patient expired, a more complete postmortem histologic examination of his stomach was undertaken. For each patient, endoscopic findings at the time of biopsy revealed thickened gastric mucosa overlying the Kaposi's changes. Microscopically, this thickened mucosa comprised hyperplastic foveolar cells that extended to the muscularis mucosa, characteristic of Ménétrier's mucosa. In both cases, special stains confirmed this impression. Dissection of the 24 year-old patient's stomach at autopsy demonstrated that the Ménétrier's mucosa was limited to areas where there was underlying Kaposi's Sarcoma, and that this mucosa was not present when the underlying stroma was normal. Our findings indicate, therefore, an association between Ménétrier's mucosal changes and Kaposi's Sarcoma; such an association has not, to our knowledge, been described previously in the literature.
Asunto(s)
Gastritis Hipertrófica/complicaciones , Sarcoma de Kaposi/complicaciones , Adulto , Autopsia , Biopsia , Endoscopía , Resultado Fatal , Gastritis Hipertrófica/patología , Humanos , Masculino , Sarcoma de Kaposi/patología , Estómago/patologíaRESUMEN
BACKGROUND: We present a case of a cervical schwannoma, likely originating from the pharyngeal plexus of the vagal nerve. The lesion masqueraded as a thyroid nodule and magnetic resonance imaging (MRI) assisted in preoperative diagnosis. We review the radiographic characteristics of nerve sheath tumors on MRI as well as the diagnostic cytologic stains which can enhance the possibility of a correct preoperative diagnosis. CASE: We describe a 60-year-old female with dysphagia and a neck mass consistent with a nodular goiter. The patient's history, diagnostic images, cytology, pathology, and surgical management are presented and analyzed. The preoperative diagnosis of a cervical schwannoma was suspected by the use of MRI which led to additional specialized cytologic stains. CONCLUSION: Pharyngeal wall schwannomas are important to consider in the differential diagnosis of thyroid nodules when fine needle aspiration cytology indicates cells of neural origin. Imaging by MRI can assist in identifying lesions of neural origin masquerading as thyroid nodules.
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ADN Tumoral Circulante , Neoplasias de la Tiroides , ADN Tumoral Circulante/genética , Análisis Mutacional de ADN , Humanos , Mutación , Proteínas Proto-Oncogénicas B-raf/genética , Cáncer Papilar Tiroideo/genética , Cáncer Papilar Tiroideo/patología , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/patologíaRESUMEN
OBJECTIVE: Elevated levels of umbilical cord nucleated red blood cells (nRBCs) have been used to assess in utero hypoxia. Although the umbilical nRBC value has been the 'gold standard', umbilical blood may not be obtained at delivery. We determined if the levels of nRBCs and white blood cell (WBC) counts in fixed placental sections might serve as a proxy for cord blood values. STUDY DESIGN: Umbilical blood and placenta were collected from 25 deliveries at Harbor-UCLA Medical Center. Umbilical blood and placental sections were analyzed for nRBCs (per 100 WBC) and WBC differential, and compared with the t-test or the Mann-Whitney rank sum test. RESULTS: nRBC counts were equivalent in umbilical cord and placental sections (5 vs. 4/100 WBC). Umbilical lymphocyte and polymorphonuclear leukocyte (PMN) counts were normally distributed, averaging 35 +/- 9 and 56 +/- 2/100 WBC, respectively. Placental lymphocyte (33 +/- 2/100 WBC) and PMN (60 +/- 2/100 WBC) counts were equivalent to cord blood values. CONCLUSION: WBC differentials and nRBC counts are equivalent in umbilical cord blood and processed placental pathology sections. For infants in whom cord blood cell counts are desired though umbilical cord samples are unavailable, fixed placental sections may serve as a proxy.
Asunto(s)
Recuento de Eritrocitos , Sangre Fetal/citología , Recuento de Leucocitos , Placenta/irrigación sanguínea , Placenta/citología , Adulto , Recolección de Muestras de Sangre , Eritroblastos , Recuento de Eritrocitos/métodos , Femenino , Humanos , Recuento de Leucocitos/métodos , Valor Predictivo de las Pruebas , Embarazo , Resultado del Embarazo , Análisis de Regresión , Cordón UmbilicalRESUMEN
BACKGROUND: The cribriform morular variant of papillary thyroid carcinoma (CMVPTC) is a rare subtype of papillary thyroid cancer that occurs most often in association with the familial adenomatous polyposis (FAP) syndrome. PATIENT FINDINGS: A 18-year-old woman presented with recurrence of PTC in her neck. She had a prior diagnosis of FAP syndrome. Review of her original pathology slides reclassified the case as a CMVPTC. The tumor was examined for the four most common mutations found in PTC: BRAF, RET/PTC, RAS, and PAX/PPARγ. SUMMARY: The molecular alterations associated with CMVPTC involve the WNT signaling pathway but are incompletely understood. When CMVPTC is associated with the FAP syndrome, a germline adenomatous polyposis coli (APC) gene mutation is almost always detected. For the initiation of oncogenesis however, one or more additional molecular alterations must occur, such as a new somatic mutation in the APC gene (biallelic inactivation), somatic mutations in the ß-catenin (CTNNB1) gene, or gene-gene interaction (epistasis). To date, of the mutations commonly associated with PTC, only RET/PTC mutations have been reported in CMVPTC. We report a FAP-associated CMVPTC tumor with atypically aggressive features harboring a RAS mutation and review the molecular mechanisms associated with this interesting PTC subtype. The literature was reviewed using MEDLINE (included case presentations, original research, and reviews). CONCLUSION: We report here the first RAS mutation detected in an FAP-associated CMVPTC tumor.
Asunto(s)
Poliposis Adenomatosa del Colon/patología , Carcinoma Papilar/patología , Proteínas Proto-Oncogénicas/genética , Neoplasias de la Tiroides/patología , Proteínas ras/genética , Poliposis Adenomatosa del Colon/genética , Adolescente , Carcinoma Papilar/genética , Femenino , Mutación de Línea Germinal , Humanos , Proteínas Proto-Oncogénicas p21(ras) , Neoplasias de la Tiroides/genética , beta Catenina/genéticaRESUMEN
Our understanding of the molecular mechanisms responsible for follicular thyroid cell oncogenesis has been advanced significantly in recent years. Specific genetic alterations and the molecular pathways they affect have been associated with particular histologic subtypes of well-differentiated thyroid cancer and are now being evaluated for their utility as clinical tools with diagnostic, prognostic and even therapeutic relevance. This paper focuses on the most common and clinically relevant genetic alterations shown to be consistently associated with well-differentiated thyroid carcinoma. We review the impact of recent molecular and technological advances on thyroid cancer standard of care and the practice of clinical medicine.
Asunto(s)
Adenocarcinoma Folicular , Neoplasias de la Tiroides , Adenocarcinoma Folicular/diagnóstico , Adenocarcinoma Folicular/patología , Adenocarcinoma Folicular/terapia , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Humanos , Técnicas de Diagnóstico Molecular , Mutación , Factor de Transcripción PAX8 , Factores de Transcripción Paired Box/genética , Pronóstico , Nivel de Atención , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/terapia , Proteínas ras/genéticaRESUMEN
There is clinical evidence that chronic liver diseases in which MDBs (Mallory Denk Bodies) form progress to hepatocellular carcinoma. The present study provides evidence that links MDB formation induced by chronic drug injury, with preneoplasia and later to the formation of tumors, which develop long after drug withdrawal. Evidence indicated that this link was due to an epigenetic cellular memory induced by chronic drug ingestion. Microarray analysis showed that the expressions of many markers of preneoplasia (UBD, Alpha Fetoprotein, KLF6 and glutathione-S-transferase mu2) were increased together when the drug DDC was refed. These changes were suppressed by S-adenosylmethionine feeding, indicating that the drug was affecting DNA and histones methylation in an epigenetic manner. The link between MDB formation and neoplasia formation was likely due to the over expression of UBD (also called FAT10), which is up regulated in 90% of human hepatocellular carcinomas. Immunohistochemical staining of drug-primed mouse livers showed that FAT10 positive liver cells persisted up to 4 months after drug withdrawal and they were still found in the livers of mice, 14 months after drug withdrawal. The refeeding of DDC increased the percent of FAT10 hepatocytes.
Asunto(s)
Epigénesis Genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas Experimentales/genética , Lesiones Precancerosas/genética , Ubiquitinas/genética , Animales , Carcinógenos/toxicidad , Células Cultivadas , Dihidropiridinas/toxicidad , Modelos Animales de Enfermedad , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Ácidos Hidroxámicos/farmacología , Neoplasias Hepáticas Experimentales/metabolismo , Neoplasias Hepáticas Experimentales/patología , Masculino , Ratones , Ratones Endogámicos C3H , Análisis de Secuencia por Matrices de Oligonucleótidos , Lesiones Precancerosas/metabolismo , Lesiones Precancerosas/patología , Proteínas/genética , Proteínas/metabolismo , Ubiquitinas/metabolismo , Regulación hacia ArribaRESUMEN
Glycogen synthase kinase-3beta (GSK-3beta) is a serine/threonine kinase that plays a role in glycogen synthesis by inhibiting glycogen synthase (GS) through phosphorylation. We hypothesized that GSK-3beta by virtue of its role in glycogen synthesis through the inhibition of GS will play a role in the preparation of the endometrium for blastocyst implantation. Immunohistochemical (IHC) analysis and Western blot analysis (WBA) detected GSK-3beta in the endometrium, myometrium, Fallopian tube and ovary. WBA showed more than 5-fold higher endometrial expression of the phosphorylated GSK-3beta (pGSK-3beta) isoform (inactive) in the secretory phase as compared with the proliferative phase (P < 0.001), whereas no differences in total GSK-3beta expression were detected. IHC analysis confirmed the WBA and showed marked expression of pGSK-3beta predominantly in glandular epithelial cells in early and mid secretory endometrium with scant expression during the proliferative phase. In in vitro experiments using human endometrial-derived epithelial cell line (HES), progesterone did not alter total GSK mRNA or protein expression. However, progesterone induced a dose-dependent increase in the expression of pGSK-3beta, which could be blocked by RU486. Cyclic expression of GSK-3beta's active and inactive forms in the endometrium suggests that sex hormones regulate the expression of this enzyme. In vitro experiments demonstrate that progesterone through receptor-mediated mechanisms induces phosphorylation of endometrial GSK-3beta.
Asunto(s)
Endometrio/enzimología , Glucógeno Sintasa Quinasa 3/metabolismo , Ciclo Menstrual/metabolismo , Progesterona/metabolismo , Adulto , Línea Celular , Relación Dosis-Respuesta a Droga , Endometrio/citología , Endometrio/efectos de los fármacos , Células Epiteliales/efectos de los fármacos , Células Epiteliales/enzimología , Femenino , Glucógeno/metabolismo , Glucógeno Sintasa Quinasa 3 beta , Antagonistas de Hormonas/farmacología , Humanos , Inmunohistoquímica , Mifepristona/farmacología , Fosforilación , Progesterona/antagonistas & inhibidoresRESUMEN
The dynamics of Mallory body (MB) formation are difficult to follow in vivo. Because of the lack of an in vitro mouse hepatocyte culture model, a cellular extract approach was developed. In this model an immunoprecipitate was obtained using an antibody to cytokeratin-8 (CK-8). The isolate contained a large number of compounds: CK-8, ubiquitin, a frameshift mutation of ubiquitin (UBB(+1)), proteasomal subunits beta5 (a catalytic subunit of the 20S proteasome) and Tbp7 (an ATPase subunit of the 26S proteasome), transglutaminase, tubulin, heat shock proteins 90 and 70, and MBs. In Western blots, CK-8 immunoprecipitates showed colocalization of these components in a complex of proteins colocalized in a high-molecular-weight smear. When the CK-8 immunoprecipitate was incubated with the isolate of proteasomes and an energy generating source (ATP), the components of the ubiquitinated protein smear increased. These observations taken together with the in vivo observation that these proteins colocalized at the edge of the MB shown in the present study suggest that these proteins form aggregates through covalent binding of CK-8, ubiquitin, and the proteasomes. Covalent aggregation is suggested by the fact that the protein complex found in the high-molecular-weight smear that forms in vitro fails to dissociate in SDS. This protein complex is present in the CK-8 immunoprecipitates of livers forming MBs but not in control livers. In conclusion, the results support the concept that Mallory bodies are aggresomes which form as the result of the failure of the ubiquitin-proteasome complex to adequately eliminate cytokeratins destined for proteolysis.
Asunto(s)
Cisteína Endopeptidasas/fisiología , Cuerpos de Inclusión/metabolismo , Hígado/metabolismo , Complejos Multienzimáticos/fisiología , Biosíntesis de Proteínas , Ubiquitinas/fisiología , Adenosina Trifosfatasas/metabolismo , Administración Oral , Animales , Western Blotting , Sistema Libre de Células/metabolismo , Clormetiazol/administración & dosificación , Clormetiazol/farmacología , Inhibidores del Citocromo P-450 CYP2E1 , Dihidropiridinas/administración & dosificación , Dihidropiridinas/farmacología , Inhibidores Enzimáticos/farmacología , Hepatocitos/metabolismo , Hepatocitos/ultraestructura , Queratinas/metabolismo , Hígado/citología , Masculino , Ratones , Ratones Endogámicos C3H , Ratones Endogámicos , Péptido Hidrolasas/aislamiento & purificación , Péptido Hidrolasas/metabolismo , Complejo de la Endopetidasa Proteasomal , Proteínas/aislamiento & purificación , Proteínas/metabolismoRESUMEN
The ZZ variant of alpha(1)-antitrypsin deficiency (AATD) is well known to cause liver damage and cirrhosis in some affected children. Ubiquitin abnormality was recently shown to be significant in AATD in childhood cirrhosis. Molecular misreading (MM), defined as faulty transcription of genomic information from DNA into mRNA, as well as its translation into mutant proteins, has been documented in many pathologic processes where aggregation of abnormal proteins occurs. The misread protein, ubiquitin-B(+1) (UBB(+1)), was recently identified in the hallmarks of various neurological disorders. The objective of this study was to determine whether MM of ubiquitin occurs in AATD. Twelve explanted liver specimens from AATD-affected children with cirrhosis were retrieved from archival sources, along with 10 control liver specimens obtained from autopsies of age-matched children with no clinical, gross anatomic, or histologic evidence of liver disease. Double immunofluorescence studies using rabbit polyclonal antibodies against UBB(+1) and AAT were performed on consecutively sectioned tissue. UBB(+1) immunoreactivity was colocalized with AAT in all cirrhotic AATD livers. The control livers were consistently negative. Ubiquitin MM is prominent in AATD-affected cirrhotic livers. This indicates that for children with AATD and cirrhosis, ubiquitin MM is a necessary cofactor to the aggregation of mutant ZZ isoform of AATD.
Asunto(s)
Mutación del Sistema de Lectura , Cirrosis Hepática/metabolismo , Hígado/metabolismo , Ubiquitina/metabolismo , Deficiencia de alfa 1-Antitripsina/metabolismo , Adolescente , Niño , Preescolar , Femenino , Técnica del Anticuerpo Fluorescente , Homocigoto , Humanos , Hígado/patología , Cirrosis Hepática/genética , Cirrosis Hepática/patología , Masculino , Transcripción Genética , Ubiquitina/genética , Deficiencia de alfa 1-Antitripsina/genéticaRESUMEN
BACKGROUND & AIMS: Molecular misreading of the ubiquitin B gene has been documented in the cerebral cortex of patients with Alzheimer's disease and Down syndrome. This novel process consists of the unfaithful conversion of genomic information into aberrant transcripts and its subsequent translation into +1 proteins. METHODS: Because Mallory bodies (MBs) also contain ubiquitinated proteins, we stained 11 autopsied and 6 biopsied MB-containing livers from patients with steatohepatitis with an antibody to ubiquitin(+1) to look for the presence of mutant (ubiquitin(+1)) protein. Antibodies to wild-type ubiquitin were used to document the presence of MBs in all cases. RESULTS: Ubiquitin(+1) immunoreactivity was detected in all MB-containing livers with steatohepatitis; no ubiquitin(+1) immunoreactivity was found in 13 MB-free liver controls. A subpopulation (about one third of the MBs) of the MB-containing hepatocytes in autopsied livers showed ubiquitin(+1) immunoreactivity (i.e., ubiquitin and ubiquitin(+1) colocalized in MBs). MB-containing liver biopsy specimens showed colocalization of ubiquitin and ubiquitin(+1) in every MB. Western blot analysis showed an ubiquitin(+1) band of 11 kilodaltons. Molecular misreading of the ubiquitin B gene (DeltaGU) was shown in one of the livers, which contained numerous MBs using an expression cloning strategy. CONCLUSIONS: The results showed that molecular misreading of the ubiquitin B gene occurred in hepatocytes in virtually all of the MB-containing livers tested. Ubiquitin(+1) protein was only found within the MBs and therefore may act by interfering with the degradation of the MBs because ubiquitin(+1) may inhibit proteolytic function of the proteasome.