ABSTRACT
In chicken, peritoneal cystic lesions have not been clearly categorized. In this study, diffuse peritoneal multiple cysts were observed in two layer hens. The cysts in the serosa were lined with single layers of squamous or cuboidal cells. The papillary proliferations of columnar cells were also observed in one case. The smooth muscle layer or mass were observed around the cysts in both cases. The cystic lining cells were positive for pan-cytokeratin, vimentin, S100 and Wilms tumor 1. Ultrastructurally, they had sparsely microvilli on the luminal surface. The histological results indicated the present cases were multicystic mesothelioma, but also had characteristics of Mullerian epithelium. This is the first report describing the detailed pathological feature of unique multicystic tumor in chicken.
Subject(s)
Chickens , Mesothelioma/veterinary , Peritoneal Neoplasms/veterinary , Poultry Diseases/pathology , Animals , Antibodies, Neoplasm , Cysts/pathology , Cysts/ultrastructure , Cysts/veterinary , Female , Mesothelioma/pathology , Mesothelioma/ultrastructure , Microscopy, Electron, Transmission/veterinary , Peritoneal Neoplasms/pathology , Peritoneal Neoplasms/ultrastructureABSTRACT
The current authors previously reported that a carbonyl reductase 1 (CR1) DNA-dendrimer complex could potentially be used in gene therapy for peritoneal metastasis of ovarian cancer. The aims of the current study were to observe the cellular dynamics of peritoneal metastasis of epithelial ovarian cancer cells and to ascertain changes in the dynamics of ovarian cancer cells as a result of transfection of CR1 DNA. (1) Artificial human peritoneal tissue (AHPT) was seeded with serous ovarian cancer cells, and the process leading to development of peritoneal carcinomatosis was observed over time. (2) Peritoneal carcinomatosis was produced in mice and compared to a model using AHPT to determine the appropriateness of AHPT. (3) CR1 DNA was transfected into cancer cells seeded on AHPT, and the dynamics of cancer cells were observed over time. (1) Cancer cells perforated the mesothelium, leaving normal mesothelium intact. However, the cells proliferated between the layers of the mesothelium, forming a mass. After 24 h, cancer cells had invaded the lymphatics, and after 48-72 h cancer cells had invaded deep into the mesothelium, where they formed a mass. (2) Invasion of the peritoneum by cancer cells in a murine model of peritoneal carcinomatosis resembled that in a model using AHPT, and results substantiated the reproducibility of peritoneal carcinomatosis in AHPT. (3) Proliferation of cells transfected with CR1 DNA was significantly inhibited on AHPT, and necrosis was evident. Nevertheless, cancer cell invasion deep into the mesothelium was not inhibited. Use of a new tool, AHPT, in an in vitro model of peritoneal metastasis revealed that CR1 DNA inhibited cancer cell proliferation. CR1 DNA does not play a role in inhibiting invasion of the mesothelium during peritoneal metastasis, but it does affect cancer cell proliferation. Results suggested that CR1 DNA inhibits cancer cell proliferation via necrosis.
Subject(s)
Alcohol Oxidoreductases/metabolism , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/pathology , Peritoneal Neoplasms/secondary , Alcohol Oxidoreductases/genetics , Animals , Cell Culture Techniques , Cell Line, Tumor , Disease Models, Animal , Female , Gene Expression , Genes, Reporter , Heterografts , Humans , Immunohistochemistry , Mice , Ovarian Neoplasms/genetics , Ovarian Neoplasms/ultrastructure , Peritoneal Neoplasms/ultrastructureSubject(s)
Glioma/diagnosis , Ovarian Neoplasms/diagnosis , Peritoneal Neoplasms/diagnosis , Teratoma/diagnosis , Abdomen/diagnostic imaging , Child , Female , Glioma/diagnostic imaging , Glioma/ultrastructure , Histological Techniques , Humans , Ovarian Neoplasms/diagnostic imaging , Ovarian Neoplasms/pathology , Ovarian Neoplasms/ultrastructure , Peritoneal Neoplasms/diagnostic imaging , Peritoneal Neoplasms/pathology , Peritoneal Neoplasms/ultrastructure , Teratoma/pathology , UltrasonographyABSTRACT
Optical imaging of whole, living animals has proven to be a powerful tool in multiple areas of preclinical research and has allowed noninvasive monitoring of immune responses, tumor and pathogen growth, and treatment responses in longitudinal studies. However, fluorescence-based studies in animals are challenging because tissue absorbs and autofluoresces strongly in the visible light spectrum. These optical properties drive development and use of fluorescent labels that absorb and emit at longer wavelengths. Here, we present a far-red absorbing fluoromodule-based reporter/probe system and show that this system can be used for imaging in living mice. The probe we developed is a fluorogenic dye called SC1 that is dark in solution but highly fluorescent when bound to its cognate reporter, Mars1. The reporter/probe complex, or fluoromodule, produced peak emission near 730 nm. Mars1 was able to bind a variety of structurally similar probes that differ in color and membrane permeability. We demonstrated that a tool kit of multiple probes can be used to label extracellular and intracellular reporter-tagged receptor pools with 2 colors. Imaging studies may benefit from this far-red excited reporter/probe system, which features tight coupling between probe fluorescence and reporter binding and offers the option of using an expandable family of fluorogenic probes with a single reporter gene.
Subject(s)
Aniline Compounds/analysis , Fluorescent Dyes/analysis , Genes, Reporter , Intravital Microscopy , Neoplasms, Experimental/ultrastructure , Optical Imaging/methods , Single-Chain Antibodies/analysis , Activation, Metabolic , Aniline Compounds/pharmacokinetics , Animals , Cell Line , Cell Membrane Permeability , Color , Deamino Arginine Vasopressin/pharmacology , Endocytosis/drug effects , Fluorescence , Fluorescent Dyes/pharmacokinetics , Green Fluorescent Proteins/analysis , HCT116 Cells/transplantation , Humans , Mice , Mice, Nude , Neoplasms, Experimental/chemistry , Peritoneal Neoplasms/chemistry , Peritoneal Neoplasms/ultrastructure , Receptors, Vasopressin/analysis , Receptors, Vasopressin/genetics , Recombinant Fusion Proteins/analysis , Recombinant Fusion Proteins/metabolism , Single-Chain Antibodies/metabolism , Structure-Activity Relationship , Subcellular Fractions/metabolism , Subcellular Fractions/ultrastructure , Transduction, GeneticABSTRACT
Peritoneal dissemination is a frequent metastatic route for cancers of the ovary and gastrointestinal tract. Tumour cells metastasize by attaching to and invading through the mesothelial cell (MC) monolayer that lines the peritoneal cavity. Metastases are influenced by carcinoma-associated fibroblasts (CAFs), a cell population that derives from different sources. Hence, we investigated whether MCs, through mesothelial-mesenchymal transition (MMT), were a source of CAFs during peritoneal carcinomatosis and whether MMT affected the adhesion and invasion of tumour cells. Biopsies from patients with peritoneal dissemination revealed the presence of myofibroblasts expressing mesothelial markers in the proximity of carcinoma implants. Prominent new vessel formation was observed in the peritoneal areas harbouring tumour cells when compared with tumour-free regions. The use of a mouse model of peritoneal dissemination confirmed the myofibroblast conversion of MCs and the increase in angiogenesis at places of tumour implants. Treatment of omentum MCs with conditioned media from carcinoma cell cultures resulted in phenotype changes reminiscent of MMT. Adhesion experiments demonstrated that MMT enhanced the binding of cancer cells to MCs in a ß1-integrin-dependent manner. Scanning electron microscopy imaging showed that the enhanced adhesion was mostly due to increased cell-cell interaction and not to a mere matrix exposure. Invasion assays suggested a reciprocal stimulation of the invasive capacity of tumour cells and MCs. Our results demonstrate that CAFs can derive from mesothelial cells during peritoneal metastasis. We suggest that MMT renders the peritoneum more receptive for tumour cell attachment/invasion and contributes to secondary tumour growth by promoting its vascularization.
Subject(s)
Epithelial-Mesenchymal Transition/physiology , Fibroblasts/pathology , Peritoneal Neoplasms/secondary , Animals , Biopsy , Cell Adhesion , Cell Line, Tumor , Colorectal Neoplasms/pathology , Culture Media, Conditioned/pharmacology , Epithelial Cells/pathology , Epithelial Cells/physiology , Epithelial Cells/ultrastructure , Epithelial-Mesenchymal Transition/drug effects , Female , Fibroblasts/physiology , Heterografts , Humans , Mice , Mice, Nude , Microscopy, Electron, Scanning , Neoplasm Invasiveness , Neoplasm Transplantation , Neovascularization, Pathologic/pathology , Ovarian Neoplasms/pathology , Peritoneal Neoplasms/blood supply , Peritoneal Neoplasms/pathology , Peritoneal Neoplasms/ultrastructureABSTRACT
Implanted human, androgen-independent prostatic carcinoma cells (DU145) into athymic (NCr nu/nu) mice produce diverse tumors on the peritoneal surfaces of many organs. Light and ultrastructural observations show that the mesothelial covering these surfaces are typically microvilli-coated, squamous cells or secretory cuboidal cells. The peritoneal regions colonized by tumors lack mesothelial cells and are covered by actively replicating carcinoma cells that grow as poorly differentiated cell clusters made of cell aggregates to somewhat compact spheroids covered with pleiomorphic microvilli and containing an undifferentiated vascular supply. These xenografts clusters invade the diaphragm and develop into tumors with both a basal solid aspect and an upper region of cribriform morphology. Furthermore, each tumor contains two cell types: (1) a poorly differentiated clear cell type, which grows into intraperitoneal tumors and (2) a large, basophilic cell type, which invades the peritoneal stroma of organs, including of the diaphragm.
Subject(s)
Cell Proliferation , Peritoneum/pathology , Prostatic Neoplasms/pathology , Prostatic Neoplasms/physiopathology , Animals , Cell Line, Tumor , Epithelium/pathology , Epithelium/physiopathology , Epithelium/ultrastructure , Humans , Male , Mice , Mice, Nude , Microvilli/pathology , Microvilli/ultrastructure , Neoplasm Invasiveness/pathology , Neoplasm Invasiveness/physiopathology , Neoplasm Invasiveness/ultrastructure , Peritoneal Neoplasms/physiopathology , Peritoneal Neoplasms/secondary , Peritoneal Neoplasms/ultrastructure , Peritoneum/physiopathology , Peritoneum/ultrastructure , Prostatic Neoplasms/ultrastructure , Transplantation, HeterologousABSTRACT
Deciduoid mesothelioma is a rare variant of epithelioid mesothelioma that was initially considered to occur exclusively in the peritoneum of young women who had no history of asbestos exposure and to be characterized by an aggressive clinical course, but it was later demonstrated that this tumor could also occur in the pleura of older men and women who had been exposed to asbestos. Some subsequent studies have also indicated that the clinical course is no different from that of conventional epithelioid mesothelioma. Herein are reported 21 cases of deciduoid mesothelioma that were investigated using a large panel of immunohistochemical markers, 9 of which were also studied by electron microscopy. Fifteen of the patients were male and 6 were female (mean age, 60 years). Seventeen of the cases originated in the pleura and four in the peritoneum. Histologically, all of the cases were composed of large, polygonal or ovoid cells with well-defined cell borders, dense eosinophilic cytoplasm, and single or multiple nuclei. In some cases, the cells exhibited a wide variation in their size and shape, frequent loss of cell cohesion, marked nuclear atypia, and high mitotic activity (>5 per 10 HPF); whereas, in others, the cells were more cohesive, less pleomorphic, and the mitotic activity low. As the survival of patients in the first group of cases was shorter (mean, 7 months), when compared with that of the latter (mean, 23 months), it is concluded that the differences in prognosis reported in deciduoid mesothelioma are due to the existence of a high-grade subgroup that presents highly aggressive clinical behavior. Therefore, when a high-grade deciduoid mesothelioma is present, it should be reported as it can significantly affect prognosis and treatment. The use of immunohistochemistry and electron microscopy in assisting in the differential diagnosis of deciduoid mesothelioma is also discussed.
Subject(s)
Epithelioid Cells , Mesothelioma , Peritoneal Neoplasms , Pleural Neoplasms , Adolescent , Adult , Aged , Biomarkers, Tumor/analysis , Cell Shape , Cell Size , Diagnosis, Differential , Epithelioid Cells/chemistry , Epithelioid Cells/ultrastructure , Female , Humans , Immunohistochemistry , Male , Mesothelioma/chemistry , Mesothelioma/mortality , Mesothelioma/therapy , Mesothelioma/ultrastructure , Microscopy, Electron , Middle Aged , Mitotic Index , Neoplasm Grading , Peritoneal Neoplasms/chemistry , Peritoneal Neoplasms/mortality , Peritoneal Neoplasms/therapy , Peritoneal Neoplasms/ultrastructure , Pleural Neoplasms/chemistry , Pleural Neoplasms/mortality , Pleural Neoplasms/therapy , Pleural Neoplasms/ultrastructure , Predictive Value of Tests , Survival Analysis , Time Factors , Treatment Outcome , Young AdultABSTRACT
Mesotheliomas with pleomorphic features are rare and only a few studies on this mesothelioma variant have been published. Little information regarding the immunoprofile of these tumors and none on their electron microscopic features was included in these studies. Herein are reported 10 cases of pleomorphic mesothelioma that were investigated using a large panel of immunohistochemical markers, 4 of which were also studied by electron microscopy. All of the patients were men and seven had a history of asbestos exposure. Nine of the cases originated in the pleura and one in the peritoneum. Histologically, the tumors were characterized by being composed of large, often discohesive, cells that varied in size and shape, had dense abundant eosinophilic cytoplasm, and single or multiple irregular nuclei, which often contained one or several large nucleoli. Mitotic activity was high and atypical mitoses frequent. Immunoreactivity for pan-keratin and keratin 7 was strong in all of the cases. Expression for calretinin, WT1, podoplanin, mesothelin and keratin 5/6 was also frequent, but variable. All cases were negative for MOC-31, carcinoembryonic antigen, CD15, TAG-72 and thyroid transcription factor-1. Electron microscopy often showed the presence of abundant long, slender microvilli on the cell membrane of the neoplastic cells. These findings demonstrate that, contrary to what has been suggested by some investigators, both immunohistochemistry and electron microscopy can be very helpful in assisting in the diagnosis of pleomorphic mesotheliomas. That the seven patients who underwent extrapleural pneumonectomy had extensive lymph node metastasis and that the median survival of those patients for whom follow-up information was available was only 8.2 months indicates that mesotheliomas with pleomorphic features are associated with highly aggressive clinical behavior. Therefore, when this subtype of epithelioid mesothelioma is present, it should be reported as it can significantly affect the prognosis and treatment of the patient.
Subject(s)
Mesothelioma/ultrastructure , Peritoneal Neoplasms/ultrastructure , Pleural Neoplasms/ultrastructure , Aged , Biomarkers, Tumor/analysis , Humans , Immunohistochemistry , Male , Mesothelioma/metabolism , Microscopy, Electron, Transmission , Middle Aged , Peritoneal Neoplasms/metabolism , Pleural Neoplasms/metabolismABSTRACT
A 9-year-old Haflinger mare presented to the Liphook Equine Hospital with a history of weight loss, azotemia, and repeated episodes of ascites over a period of 10 days. The horse was euthanized after exploratory laparotomy revealed large numbers of variably sized masses distributed throughout the peritoneal cavity. Macroscopically, some masses were papillary, while others were nodular. Histologically, the masses were comprised of large to giant, variably shaped, and occasionally multinucleated neoplastic cells with marked anisokaryosis and anisocytosis and a high mitotic rate. Small to moderate numbers of neoplastic cells were swollen by 1 to several, moderately sized to large, clear, circular or ovoid vacuoles, which stained positive with oil red O. Immunohistochemically, the neoplastic cells co-expressed vimentin and cytokeratin. Electron microscopy demonstrated tumor cells with tight junctions, microvilli, and numerous intracytoplasmic lipid droplets. These findings are consistent with a lipid-rich form of mesothelioma, which should be considered as a differential diagnosis if lipid vacuoles are present in potentially neoplastic cells in equine abdominocentesis samples.
Subject(s)
Horse Diseases/pathology , Mesothelioma/veterinary , Peritoneal Neoplasms/veterinary , Animals , Female , Horse Diseases/diagnosis , Horses , Lipids , Mesothelioma/diagnosis , Mesothelioma/pathology , Mesothelioma/ultrastructure , Microscopy, Electron, Transmission/veterinary , Peritoneal Neoplasms/diagnosis , Peritoneal Neoplasms/pathology , Peritoneal Neoplasms/ultrastructure , Peritoneum/pathologyABSTRACT
This report describes the macroscopic, histologic, immunohistologic and ultrastructural characteristics ofa biphasic malignant mesothelioma in the peritoneal and pleural cavity of a 13-year-old Icelandic pony mare, which exhibited recurrent ascites clinically. Immunohistology was performed employing multiple monoclonal antibodies against cytokeratins (CK) and vimentin. The ultrastructural examination included the quantitative evaluation of the length to diameter ratio of the microvilli. Post mortem examination revealed a severe ascites and hydrothorax. The serosal surfaces of the peritoneum and pleura displayed poorly-demarcated, multifocal to coalescing laminar masses and small nodules. Histology revealed a bimorphic mass consisting of spindle-shaped cells and microcystic epithelioid areas. A transcoelomic and local invasive growth pattern as well as lymph node metastases were noticed. Immunohistology revealed a strong expression of CK. Though a low and moderate expression of CK5/6 and CK20 was present, respectively, CK7 and CK10-antigens were lacking. Ultrastructurally, the epithelioid mesothelioma cells displayed long microvilli, cytoplasmic tonofilaments, and desmosomes. Quantitative evaluation of the length to diameter ratio of the 10 longest microvilli revealed a mean value of approximately 16.2. Summarized, this report described the case of a malignant biphasic mesothelioma with an atypical CK20 expression but a characteristic ultrastructural morphology including long microvilli.
Subject(s)
Horse Diseases/pathology , Mesothelioma/veterinary , Peritoneal Neoplasms/veterinary , Pleural Neoplasms/veterinary , Animals , Antibodies, Monoclonal , Fatal Outcome , Horses , Immunohistochemistry/veterinary , Keratins/immunology , Male , Mesothelioma/pathology , Mesothelioma/ultrastructure , Microvilli/ultrastructure , Peritoneal Neoplasms/pathology , Peritoneal Neoplasms/ultrastructure , Pleural Neoplasms/pathology , Pleural Neoplasms/ultrastructure , Vimentin/immunologyABSTRACT
AIMS: Low-grade myofibroblastic sarcoma (LGMS) represents a rare soft tissue neoplasm with a predilection for the head and neck. Intra-abdominal LGMS are rare with only four unequivocal examples reported so far. Two further cases in females in their 60s and 70s are analysed here. METHODS: Immunohistochemical stains were applied on fresh-cut sections using the avidin-biotin complex method and the following antibodies: vimentin, alpha-SMA, desmin, h-caldesmon, S-100, CD117, CD34, fibronectin, HMB45, Pan-keratin, Ki-67, beta-catenin, MDM2, PDGFRalpha, PDGFRbeta and ALK-1. Genomic DNA was isolated from microdissected formalin-fixed paraffin-embedded tumour tissue and examined for KIT and PDGFRA mutations by PCR and direct sequencing of KIT and PDGFRA. Ultrastructural studies were also performed. RESULTS: The tumours arose in the mesentery and the pelvic peritoneum. Both revealed features intermediate between conventional fibrosarcoma and leiomyosarcoma with fascicles of spindled, stellated or plump cells possessing fusiform indented vesicular nuclei and pale eosinophilic cytoplasm. Mitotic activity ranged from 1 to 15 per 10 HPFs. The tumour cells strongly expressed vimentin, variably alpha-smooth muscle actin and fibronectin, but were negative for CD117, S-100, desmin, h-caldesmon, beta-catenin, ALK-1, MDM2, PDGFRalpha and PDGFRbeta. One tumour showed a weak expression of CD34. Molecular analysis revealed a wild-type KIT, exons 9, 11 and 13, and PDGFRA, exons 12 and 18. The patients developed multiple peritoneal recurrences at 5, 13 and 25 months, and 10, 19, 25 and 32 months, and were alive at 25 and 32 months, respectively. Distant metastases were not detected. CONCLUSION: Abdominopelvic LGMS follows a more aggressive clinical course characterised by a higher propensity for local recurrence, contrasting their more superficially located counterparts. LGMS may mimic a variety of benign and low-grade malignant neoplasms and might be under-recognised.
Subject(s)
Neoplasm Recurrence, Local/ultrastructure , Peritoneal Neoplasms/ultrastructure , Sarcoma/ultrastructure , Soft Tissue Neoplasms/ultrastructure , Actins/analysis , Aged , Biomarkers, Tumor/analysis , DNA Mutational Analysis , Female , Fibronectins/analysis , Humans , Immunohistochemistry , Mesentery , Middle Aged , Mitotic Index , Neoplasm Recurrence, Local/genetics , Pelvis , Peritoneal Neoplasms/genetics , Proto-Oncogene Proteins c-kit/genetics , Receptor, Platelet-Derived Growth Factor alpha/genetics , Sarcoma/genetics , Soft Tissue Neoplasms/genetics , Vimentin/analysisSubject(s)
Omentum/pathology , Peritoneal Neoplasms/pathology , Trophoblastic Neoplasms/pathology , Adult , Diagnosis, Differential , Female , Humans , Keratin-18/metabolism , Mucin-1/metabolism , Omentum/metabolism , Peritoneal Neoplasms/metabolism , Peritoneal Neoplasms/ultrastructure , Pregnancy , Trophoblastic Neoplasms/metabolism , Trophoblastic Neoplasms/ultrastructure , Trophoblastic Tumor, Placental Site/pathology , Vimentin/metabolismABSTRACT
Introducción: las metástasis peritoneales ocurren en más de la mitad de los pacientes con cáncer gástrico. Los mecanismos involucrados han sido poco estudiados y son pobremente conocidos. Experimentalmente se sabe que las células neoplásicas exfoliadas del tumor primario, sólo pueden implantarse y proliferar en áreas de peritoneo dañado o en áreas de denudación mesotelial. Objetivos: estudiar la ultraestructura peritoneal en controles y en pacientes con cáncer gástrico precoz y avanzado. Material y Método: Se estudiaron 14 pacientes con adenocarcinoma gástrico (4 mucosos/submucosos/musculares y 10 serosos) y 4 pacientes operados por patología benigna como controles. Se tomó muestra de peritoneo sano en la raíz del mesenterio (1,5 x 1,5 cm) y se obtuvo muestra de lavado peritoneal para estudio de células neoplásicas. Cada muestra fue fijada en glutaraldehido al 2,5 por ciento, deshidratada con acetona, secada y metalizada con oro-paladio. Se hizo evaluación ciega de cada muestra con Microscopia Electrónica de Barrido (10 campos con aumento de X 1250). Se excluyó pacientes con cirugía previa abdominal y con citología peritoneal (+) para células neoplásicas. Resultados: En el grupo control se encontró muy abundantes microvellosidades en la superficie y tenue definición de las uniones intercelulares (Normal). En casos con cáncer se observó disminución de las microvellosidades y pérdida de las uniones intercelulares (Patrón de Mosaico). Además se encontró pérdida de la estructura poligonal, aumento de la separación entre las células con pérdida focal de células mesoteliales dejando expuesta la lámina propia (Patrón de Denudación). Para cada grupo se encontró la siguiente distribución según patrones de normalidad, mosaico o denudación. Grupo control: 90,1 por ciento, 7,6 por ciento y 2,3 por ciento respectivamente. Grupo con cáncer mucoso/submucoso/muscular: 97,9 por ciento, 0 por ciento y 2,1 por ciento respectivamente. Grupo con cáncer...
Background: More than half of patients with gastric cancer have peritoneal metastases. Cancer cells exfoliated from the tumor can implant and proliferate in areas of damaged peritoneum or in areas of mesothelial denudation. Aim: To study peritoneal ultrastructure in patients with early and advanced gastric cancer. Material and Methods: Four patients with gastric cancer invading up to the muscular layer, 10 patients with gastric cancer invading the serosa and four patients operated for gastroesophageal reflux, were studied. A peritoneal sample from the root of the mesentery and a sample from peritoneal lavage, were obtained and analyzed by scanning electron microscopy. Patients with previous abdominal surgery or a positive peritoneal cytology for malignant cells, were excluded. Results: Among controls, abundant superficial microvilli and a faint definition on intercellular junctions was observed. In cancer patients, a reduction in microvilli and loss of intercellular junctions (mosaic pattern) or a loss of polygonal structure with focal loss of mesothelial cells, exposing the lamina propia (denudation pattern), were observed. A normal, mosaic or denudation pattern was observed in 90.1 percent, 7.6 percent and 2.3 percent of controls respectively, in 98,0 and 2 percent of patients with cancer invading up to the muscular layer respectively and 41, 42 and 17 percent of patients with cancer invading the serosa respectively (p<0.001 compared with the former two groups). Conclusions: Among patients with gastric cancer that invades the serosal surface, the visceral peritoneum experiences a loss of normal architecture and focal cellular denudation. These changes are not associated with the presence of free cancer cells in the peritoneal cavity and may precede the appearance of peritoneal metastases.
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged, 80 and over , Adenocarcinoma/pathology , Microscopy, Electron, Scanning , Stomach Neoplasms/pathology , Peritoneal Neoplasms/secondary , Peritoneal Neoplasms/ultrastructure , Adenocarcinoma/ultrastructure , Case-Control Studies , Cross-Sectional Studies , Neoplasm Invasiveness , Peritoneum/ultrastructureABSTRACT
We recently established a mouse model of peritoneal dissemination of human gastric carcinoma, including the formation of ascites, by orthotopic transplantation of cultured gastric carcinoma cells. To clarify the processes of expansion of the tumors in this model, nude mice were sacrificed and autopsied at different points of time after the orthotopic transplantation of the cancer cells for macroscopic and histopathologic examination of the tumors. The cancer cells grew actively in the gastric submucosa and invaded the deeper layers to reach the serosal plane. The tumor cells then underwent exfoliation and became free followed by the formation of metastatic lesions initially in the greater omentum and subsequent colonization and proliferation of the tumors on the peritoneum. Although this model allowed the detection of even minute metastases, it was not satisfactory from the viewpoint of quantitative and objective evaluation. To resolve these problems, we introduced a luciferase gene into this tumor cell line with a high metastasizing potential and carried out in vivo photon counting analysis. This photon counting technique was found to allow objective and quantitative evaluation of the progression of peritoneal dissemination on a real-time basis. This animal metastatic model is useful for monitoring the responses of tumors to anticancer agents.
Subject(s)
Peritoneal Neoplasms/pathology , Photons , Stomach Neoplasms/pathology , Animals , Camptothecin/analogs & derivatives , Camptothecin/pharmacology , Cell Line, Tumor , Disease Models, Animal , Disease Progression , Female , Humans , Image Processing, Computer-Assisted/methods , Irinotecan , Luciferases/genetics , Mice , Mice, Inbred BALB C , Mice, Nude , Peritoneal Neoplasms/ultrastructure , TransfectionABSTRACT
Atypical fibroxanthoma (AFX) is a mesenchymal neoplasm usually occurring in sun-exposed skin of elderly patients. The majority have an excellent prognosis, as recurrences are uncommon and metastases are rare. We present a case of an 81-year-old man who developed widespread peritoneal metastases from an AFX on his scalp, which was completely excised 3 years earlier. Histology of the scalp lesion showed a markedly pleomorphic neoplasm characteristic of AFX. Features associated with increased risk of metastasis, namely lymphovascular space invasion, deep invasion, and substantial necrosis, were not present. An extensive immunohistochemical panel was performed. The tumor cells were negative for melanocytic, epithelial, and smooth muscle immunohistochemical stains, and positive for vimentin, CD10, CD99, and focally for CD68. Histologically, the peritoneal tumor was virtually identical to the original scalp lesion and had an identical immunohistochemical profile. Electron microscopy of the peritoneal tumor revealed pleomorphic undifferentiated cells with abundant lipid vacuoles. This is the first reported case of AFX with peritoneal metastases. Although AFXs generally have an excellent outcome, pathologists must remain cognizant of the small but real potential for metastasis and this needs to be conveyed in all reports.
Subject(s)
Head and Neck Neoplasms/pathology , Histiocytoma, Malignant Fibrous/secondary , Peritoneal Neoplasms/secondary , Aged, 80 and over , Humans , Immunohistochemistry , Male , Microscopy, Electron, Transmission , Peritoneal Neoplasms/ultrastructure , Scalp/pathology , Skin Neoplasms/pathologyABSTRACT
Mesotheliomas are uncommon neoplasms that arise from the cells forming the serosal membranes of the body cavities. Approximately 90-95% of mesotheliomas arise in the pleural cavity and 5-10% in the peritoneal cavity. Rare mesotheliomas arise in the pericardium and in the tunica vaginalis. Unlike many neoplasms, mesotheliomas grow in a diffuse distribution and tend to encase the organs in the various body cavities. A combination of histochemical, immunohistochemical, and ultrastructural features are often necessary to accurately diagnose mesotheliomas. These techniques are highlighted in this review article on mesothelioma.
Subject(s)
Mesothelioma , Peritoneal Neoplasms , Pleural Neoplasms , Biomarkers, Tumor/analysis , Humans , Immunohistochemistry , Mesothelioma/chemistry , Mesothelioma/pathology , Mesothelioma/ultrastructure , Microscopy, Electron, Transmission/methods , Peritoneal Neoplasms/chemistry , Peritoneal Neoplasms/pathology , Peritoneal Neoplasms/ultrastructure , Pleural Neoplasms/chemistry , Pleural Neoplasms/pathology , Pleural Neoplasms/ultrastructureABSTRACT
The causative relationship between asbestos exposure and mesothelioma is firmly established. Some information in this regard comes from analysis of the fiber content of lung tissue by means of analytical electron microscopy. The author has had the opportunity to study the lung asbestos content of 396 cases of mesothelioma, including 28 peritoneal cases, by means of analytical scanning electron microscopy. The highest fiber levels occurred in patients who also had asbestosis, which was found in 12% of pleural and 43% of peritoneal cases. Elevated tissue asbestos content was identified in 87% of pleural and 75% of peritoneal cases. Peritoneal cases that are asbestos related have on average a higher lung fiber burden than pleural cases. Mesotheliomas in women have elevated tissue asbestos content in about 60% of cases, and many of these had a history of exposure as a household contact of an asbestos worker. The main fiber type identified in our series was amphibole, predominantly amosite. These fibers have been demonstrated to reach the target tissue, the pleura.
Subject(s)
Mesothelioma/ultrastructure , Microscopy, Electron, Scanning/methods , Peritoneal Neoplasms/ultrastructure , Pleural Neoplasms/ultrastructure , Asbestos, Amosite/adverse effects , Asbestos, Amosite/analysis , Asbestos, Amosite/classification , Electron Probe Microanalysis , Female , Humans , Lung/ultrastructure , Mesothelioma/etiology , Peritoneal Neoplasms/etiology , Peritoneum/ultrastructure , Pleura/ultrastructure , Pleural Neoplasms/etiologyABSTRACT
Mesothelial proliferations, either reactive or neoplastic in nature, often pose difficult diagnostic dilemmas. Electron microscopy continues to be a gold standard in the identification of mesothelial differentiation. However, it is very common to apply long panels of antibodies for that purpose. In most cases, light microscopy and immunohistochemistry will solve the problem. However, the definitive, specific, and sensitive immunohistochemical marker is still lacking. This is particularly true in peritoneal and testicular mesothelial tumors, in which common embryologic origin with epithelial elements results in overlapping immunohistochemistry and morphology. The particularities of peritoneal and testicular mesothelial proliferations, and the main tumors that may mimic them in these sites, as well as the value and limitations of immunohistochemistry and electron microscopy in their differential diagnosis are the subject of this review.
Subject(s)
Epithelium/pathology , Mesothelioma/diagnosis , Ovarian Neoplasms/diagnosis , Peritoneal Neoplasms/diagnosis , Testicular Neoplasms/diagnosis , Uterine Neoplasms/diagnosis , Biomarkers, Tumor/analysis , Cell Proliferation , Diagnosis, Differential , Epithelium/chemistry , Epithelium/ultrastructure , Female , Humans , Immunohistochemistry , Male , Mesothelioma/chemistry , Mesothelioma/ultrastructure , Microscopy, Electron, Transmission , Ovarian Neoplasms/chemistry , Ovarian Neoplasms/ultrastructure , Peritoneal Neoplasms/chemistry , Peritoneal Neoplasms/ultrastructure , Testicular Neoplasms/chemistry , Testicular Neoplasms/ultrastructure , Uterine Neoplasms/chemistry , Uterine Neoplasms/ultrastructureSubject(s)
Meningioma/diagnosis , Mesentery/pathology , Nerve Sheath Neoplasms/diagnosis , Peritoneal Neoplasms/diagnosis , Cell Proliferation , Collagen Type IV/analysis , Diagnosis, Differential , Female , Humans , Immunohistochemistry , Meningioma/chemistry , Meningioma/ultrastructure , Mesentery/chemistry , Mesentery/ultrastructure , Microscopy, Electron, Transmission , Middle Aged , Mucin-1/analysis , Nerve Sheath Neoplasms/chemistry , Nerve Sheath Neoplasms/ultrastructure , Nerve Tissue Proteins/analysis , Peritoneal Neoplasms/chemistry , Peritoneal Neoplasms/ultrastructure , Receptors, Growth Factor/analysis , Receptors, Nerve Growth Factor , Vimentin/analysisABSTRACT
The histologic distinction between peritoneal epithelioid mesotheliomas and serous carcinomas diffusely involving the peritoneum may be difficult, but it can be facilitated by the use of immunohistochemistry and electron microscopy. D2-40 and podoplanin are two recently recognized lymphatic endothelial markers that can be expressed in normal mesothelial cells and mesotheliomas. The purpose of this study is to compare the value of these new mesothelial markers with those that are commonly used for discriminating between mesotheliomas and serous carcinomas, and also to determine the current role of electron microscopy in distinguishing between these malignancies. A total of 40 peritoneal epithelioid mesotheliomas and 45 serous carcinomas of the ovary (15 primary, 30 metastatic to the peritoneum) were investigated for the expression of the following markers: D2-40, podoplanin, calretinin, keratin 5/6, thrombomodulin, MOC-31, Ber-EP4, B72.3 (TAG-72), BG-8 (Lewis(Y)), CA19-9, and leu-M1 (CD15). All 40 (100%) of the mesotheliomas reacted for calretinin, 93% for D2-40, 93% for podoplanin, 93% for keratin 5/6, 73% for thrombomodulin, 13% for Ber-EP4, 5% for MOC-31, 3% for BG-8, and none for B72.3, CA19-9, or leu-M1. All 45 (100%) serous carcinomas were positive for Ber-EP4, 98% for MOC-31, 73% for B72.3, 73% for BG-8, 67% for CA19-9, 58% for leu-M1, 31% for keratin 5/6, 31% for calretinin, 13% for D2-40, 13% for podoplanin, and 4% for thrombomodulin. After analyzing the results, it is concluded that Ber-EP4 and MOC-31 are the best negative mesothelioma markers for differentiating between epithelioid mesotheliomas and serous carcinomas. The best discriminators among the positive markers for mesotheliomas are D2-40, podoplanin, and calretinin. From a practical point of view, Ber-EP4 and MOC-31, in combination with calretinin, and/or D2-40 or podoplanin allow the differential diagnosis to be established between mesothelioma and serous carcinoma in nearly all instances. As a clear distinction could be made between these two malignancies in all of the cases in which electron microscopy was performed, this technique can be very useful in establishing the correct diagnosis when the immunohistochemical results are equivocal or further support of a diagnosis of either mesothelioma or serous carcinoma is needed.