Impact of Microscopic Wall Invasion of the Renal Vein or Inferior Vena Cava on Cancer-specific Survival in Patients with Renal Cell Carcinoma and Tumor Thrombus: A Multi-institutional Analysis from the International Renal Cell Carcinoma-Venous Thrombus Consortium.

BACKGROUND: Microscopic vein invasion (MVI), with local destruction and invasion of the endothelium by tumor, is of controversial predictive value in renal cell carcinoma (RCC). OBJECTIVE: To assess the impact of venous extension and wall invasion in RCC on survival. DESIGN, SETTING, AND PARTICIPANTS: Data for 1023 RCC patients with vena cava thrombus treated with radical nephrectomy and complete tumor thrombectomy were collected within a prospectively maintained international consortium (1995-2012). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The Kaplan-Meier method and univariable and multivariable Cox regression analyses were used to assess the impact of MVI on cancer-specific survival (CSS). The main two variables of interest were microscopic renal vein wall invasion (MRVI) and microscopic vena cava wall invasion (MVCI). RESULTS: MRVI was found in 725 cases (70.9%) and MVCI in 230 (22.5%). Patients with MRVI had larger tumors (p=0.005), longer hospital stay (p<0.001), higher clinical stage 0.039), higher Fuhrman grade (p=0.028), and more frequent fat invasion. Presence of MVCI was associated with larger tumors (p<0.001), longer hospital stay (p<0.001), higher clinical stage (p<0.001), lymph node involvement (p=0.045), higher Fuhrman grade (p<0.001), and higher thrombus level (p<0.001). With median follow-up of 52 mo, overall 5-yr CSS was 57.4%. Multivariable analysis showed that presence of MRVI was an independent factor related to CSS (hazard ratio 2.24, 95% confidence interval 1.24-3.59, p=0.006). The main limitation was the inability to report MVI percentages. CONCLUSIONS: Patients with MRVI experience significantly worse survival outcomes after radical nephrectomy and tumor thrombectomy. Consideration of MRVI at final pathology is appropriate to improve decision-making for risk-adapted follow-up. PATIENT SUMMARY: The behavior of locally advanced renal cell carcinoma (RCC) depends on clinical and pathologic factors. Analysis revealed that RCC patients with microscopic renal vein wall invasion experience significantly worse cancer-specific survival.

Mechanical and structural comparison between primary tumor and lymph node metastasis cells in colorectal cancer.

SW480 and SW620 colon carcinoma cell lines derive from primary tumour and lymph-node metastasis of the same patient, respectively. For this reason, these cells represent an ideal system to analyse phenotypic variations associated with the metastatic process. In this study we analysed SW480 and SW620 cytoskeleton remodelling by measuring the cells' mechanics and morphological properties using different microscopic techniques. We observed that different specialized functions of cells, i.e. the capacity to metastasize of elongated cells inside the primary tumour and the ability to intravasate and resist shear forces of the stream of cells derived from lymph node metastasis, are reflected in their mechanical properties. We demonstrated that, together with stiffness and adhesion between the AFM tip and the cell surface, cell shape, actin organization and surface roughness are strictly related and are finely modulated by colorectal cancer cells to better accomplish their specific tasks in cancer growth and invasion.

Computer aided measurement of melanoma depth of invasion in microscopic images.

This paper presents a novel computer aided technique for measurement of melanoma depth of invasion. Melanoma is the deadliest form of skin cancer with worldwide increasing incidences. For a conclusive diagnosis of melanoma, skin biopsies should be examined under a microscope. Visual inspection of microscopic samples is often subjective, time-consuming, cumbersome and prone to human errors. This fact demonstrates the necessity of developing an automated method which assists pathologists in evaluating histopathological samples more accurately in the busy clinical environment. To the best of our knowledge, this is the first time that a computer-assisted diagnosis algorithm has been applied in measurement of melanoma invasion depth. The proposed method uses a clustering algorithm for granular layer extraction and a pre-trained SVM classifier for detection of malignant melanocytes. The experimental results with average error of 3.9µm demonstrate that the proposed method is reliable and effective.

Human prostate DU145 carcinoma cells implanted in nude mice remove the peritoneal mesothelium to invade and grow as carcinomas.

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.

The RalB small GTPase mediates formation of invadopodia through a GTPase-activating protein-independent function of the RalBP1/RLIP76 effector.

Our recent studies implicated key and distinct roles for the highly related RalA and RalB small GTPases (82% sequence identity) in pancreatic ductal adenocarcinoma (PDAC) tumorigenesis and invasive and metastatic growth, respectively. How RalB may promote PDAC invasion and metastasis has not been determined. In light of known Ral effector functions in regulation of actin organization and secretion, we addressed a possible role for RalB in formation of invadopodia, actin-rich membrane protrusions that contribute to tissue invasion and matrix remodeling. We determined that a majority of KRAS mutant PDAC cell lines exhibited invadopodia and that expression of activated K-Ras is both necessary and sufficient for invadopodium formation. Invadopodium formation was not dependent on the canonical Raf-MEK-ERK effector pathway and was instead dependent on the Ral effector pathway. However, this process was more dependent on RalB than on RalA. Surprisingly, RalB-mediated invadopodium formation was dependent on RalBP1/RLIP76 but not Sec5 and Exo84 exocyst effector function. Unexpectedly, the requirement for RalBP1 was independent of its best known function as a GTPase-activating protein for Rho small GTPases. Instead, disruption of the ATPase function of RalBP1 impaired invadopodium formation. Our results identify a novel RalB-mediated biochemical and signaling mechanism for invadopodium formation.

Visualización por resonancia magnética del drenaje venoso en las masas pélvicas: una ayuda para filiar su origen / MRI visualization of venous drainage helps determine the origin of pelvic masses

Objetivo Evaluar la utilidad de la detección en la resonancia magnética (RM) de un pedículo vascular ovárico y de la presencia de vasos prominentes entre el útero y las tumoraciones de gran tamaño como signos para filiar el origen de las masas en el ovario o el útero, respectivamente. Material y métodos Se revisan los estudios de RM de 80 pacientes con masas pélvicas >7cm y confirmadas histológicamente. Se valoró la presencia de venas gonadales que drenaran las tumoraciones y la presencia de vasos interpuestos entre la superficie de la lesión y el útero. Resultados Se detectaron venas gonadales que drenaban las masas pélvicas en 36 de las 43 tumoraciones de origen ovárico (84%), mientras que en 30 de las 37 tumoraciones de origen uterino se demostraron vasos interpuestos entre ellas y el útero (81%). La sensibilidad, especificidad, valores predictivos positivo y negativo de los signos de presencia de vasos gonadales drenando la lesión fueron del 84, 95, 95 y 83% para masas ováricas, y del 81, 91, 88 y 85% para los vasos interpuestos entre el útero y la masa en los miomas subserosos, respectivamente. ConclusiónLa valoración del drenaje venoso de tumoraciones pélvicas resulta de gran utilidad cuando el origen de las tumoraciones no resulta fácil de establecer (AU)

Objective To evaluate the usefulness of detecting at MRI an ovarian vascular pedicle or prominent vessels between the uterus and large tumors for determining whether masses originate in the ovary or uterus. Material and methods We reviewed MRI studies from 80 patients with histologically confirmed pelvic masses greater than 7cm in diameter. We evaluated the presence of gonadal veins draining the tumors and the presence of vessels between the surface of the lesion and the uterus. ResultsWe detected gonadal veins draining the pelvic masses in 36 of the 43 tumors originating in the ovaries (84%); we detected vessels between the uterus and the pelvic mass in 30 of the 37 tumors that originated in the uterus (81%). The sensitivity, specificity, and positive and negative predictive values for the presence of gonadal veins draining the lesion were 84%, 95%, 95%, and 83%, respectively, for ovarian masses, and 81%, 91%, 88%, and 85%, respectively, for vessels between the uterus and the mass in subserous myomas. Conclusion Evaluating the venous drainage of pelvic tumors is very useful in cases in which it is not easy to establish the origin of the tumor (AU)

Sonographic lesion size of ductal carcinoma in situ as a preoperative predictor for the presence of an invasive focus.

BACKGROUND AND OBJECTIVES: To investigate the preoperative factors associated with upstage to invasive cancer in patients with core needle biopsy (CNB) diagnosis of ductal carcinoma in situ (DCIS) by ultrasound guidance alone. METHODS: Between 2000 and 2007, 201 patients with DCIS diagnosed at 11- or 14-gauge CNB by ultrasound guidance alone were examined. Preoperative factors were all analyzed to correlate with the presence of invasive cancer after definitive resection. The Pearson chi-square test and stratified analysis with the Mantel-Haenszel chi-squire test were used to assess the association between the preoperative factors and upstage to invasive cancer. RESULTS: Compared with the overall underestimation rate (84 of 201, 41.8%), 47 (60.3%) of 78 patients with abnormal breast palpation, 46 (55.4%) of 83 patients with mammographic finding of a mass lesion, and 38 (67.9%) of 56 patients with a sonographic lesion size >20 mm had invasive cancer components on the final pathology review (Odds ratio [OR] = 2.45; P = 0.04, OR = 3.66; P = 0.002, and OR = 4.13; P = 0.002 respectively). CONCLUSION: A sonographic lesion size >20 mm can be used as another guideline for surgeons to consider sentinel lymph node biopsy in patients with DCIS diagnosed by a sonographically guided CNB.

Regulation of lamellipodia formation and cell invasion by CLIP-170 in invasive human breast cancer cells.

Lamellipodia formation necessary for cell invasion is regulated by Rac1. We report here that lamellipodia formation and three-dimensional invasion were significantly promoted by HGF and serum, respectively, in invasive human breast cancer cells. Rac1 formed a complex with CLIP-170, IQGAP1, and kinesin in serum-starved cells, and stimulation of the cells with HGF and serum caused the partial release of IQGAP1 and kinesin from Rac1-CLIP-170 complex. The HGF-induced release of the proteins and promotion of lamellipodia formation were inhibited by an inhibitor of PI3K. Moreover, downregulation of CLIP-170 by siRNA released IQGAP1 and kinesin from Rac1 and promoted lamellipodia formation and invasion, independent of HGF and serum. The results suggest that promotion of lamellipodia formation and invasion by HGF or serum requires PI3K-dependent release of IQGAP1 and kinesin from Rac1-CLIP-170 complex and that CLIP-170 prevents cells from the extracellular stimulus-independent lamellipodia formation and invasion by tethering IQGAP1 and kinesin to Rac1.

Spindle cell carcinoma of the external auditory meatus with intracranial extension: histological, immunohistochemical and electron microscopic evaluation.

We present a case of squamous spindle cell carcinoma of the external auditory meatus in a 38-year-old man. The tumour was extended to the inner ear, the temporal bone, the middle cranial fossa and the meningo-cerebral tissue. The surgical intervention of temporo-occipital craniotomy removed most of the neoplasia. At pathologic examination, the tumour showed an undifferentiated spindle cell pattern. Immunohistochemistry with a large antibody panel found a weak positivity only to EMA. The diagnosis was made when the electron microscopy showed rare junctional structures and tonofilaments.

[Analysis of adrenocortical tumors morphology as regards their structure and potential malignancy]. / Analiza morfologii guzów kory nadnerczy pod wzgledem ich struktury i potencjalnej zlosliwosci.

INTRODUCTION: A consequence of diagnosis of adrenocortical carcinoma (ACC) is introduction of pharmacological therapy, precise monitoring of the patients and in some cases re-operation. The aim of the study is to analyse morphology of adrenocortical tumours as regards their malignancy by use of criteria proposed by Weiss. MATERIAL AND METHODS: 110 adrenocortical tumours in 107 patients were analysed (M 27.1%, F 72.9%; age 32 to 77 years, mean 55.2 +/- 9.7). Conn syndrome was diagnosed in 16 patients (14.9%), Cushing syndrome in 12 (11.2%), and virilisation in 3 (2.8%). In 76 patients (71.0%) biochemical tests did not reveal hormonal hyperactivity of the tumour. RESULTS: In routine histopatological examination ACC was diagnosed in 6 tumours (5.4%), adrenocortical adenoma (ACA) in 92 (83.6%) and adrenocortical hyperplasia in 12 (10.9%). Nuclear grade III or IV was observed in 8 tumours (7.3%), mitotic rate > 5/50 high power fields in 6 (5.4%), atypical mitoses in 5 (4.5%), clear cells constituting < 25% of the tumour in 10 (9.1%), diffuse architecture in 8 (7.3%), necrosis in 16 (14.5%), veins infiltration in 4 (3.6%), sinusoids infiltration in 7 (6.3%), and tumour capsule infiltration in 5 (4.5%). Among ACC tumours 4-9 features of malignancy were present, among ACA--0-3 features. Statistical analysis revealed correlation between number of criteria proposed by Weiss and maximal tumour size (p < 0.05). CONCLUSION: The structure and cell arrangement in adrenocortical adenoma are heterogeneous. Application of criteria proposed by Weiss in histopathological examination of adrenocortical tumours can be useful in differentiating adrenocortical adenoma from carcinoma.

Novel use of ultrasound-guided surface marking of head and neck tumors invading facial skin.

Malignant tumors of deep head and neck structures can invade skin, but the tumor periphery is difficult to assess clinically. The surgeon's dilemma is achieving tumor clearance with safe margins while at the same time minimizing skin loss on the face. We show, in 2 cases involving the face, that high-resolution diagnostic ultrasound was superior to CT scan in demonstrating the periphery of the tumor. The tumor was distinguished from surrounding edema by its lower echogenicity and homogeneous echotexture. The maximum contour of the tumor was marked on the skin surface with ink under ultrasound guidance. The ink marking aided excision and reconstruction planning. Subsequent histology showed the surgical margins were clear of tumor. The patients remained tumor-free for more than 3 years. Ultrasound imaging therefore shows good potential for planning surgical resection with a safe margin and for aiding decisions on donor site and type of flap for reconstruction.

Shedding of membrane vesicles by tumor and endothelial cells.

Shedding of membrane vesicles is a vital phenomenon frequently observed in tumor cells and suggested to be involved in several aspects of tumor progression. Our previous studies have shown that human breast tumor cells rapidly shed membrane vesicles containing matrix metalloproteinases (MMPs). In this study we present that human umbilical vein endothelial cells (HUVEC) as well as different tumor cell lines (human ovarian cancer, CABA I and A2780, and hepatocarcinoma cell line, SK-Hep 1) shed vesicles in the extracellular medium. These vesicles carry MMPs and their inhibitors TIMPs. We conclude that tumor and endothelial cells shed MMP-containing vesicles and this may represent a mechanism for regulating focalized proteolytic activity and a way to interact with microenvironment during tumor angiogenesis.

Novel spatiotemporal patterns of epithelial tumor invasion in Drosophila discs large egg chambers.

Loss of Discslarge (Dlg) in early Drosophila egg chambers causes invasion of tumor follicle cells from the anterior epithelium, a pattern that resembles developmental border cell migration during mid-oogenesis. Here, we have analyzed novel spatial and temporal patterns of dlg invasion. Even though Dlg is ubiquitously expressed in all follicle cells, invasions are biased at the anterior and posterior termini. The patterns of invasion correlate with both a higher rate of follicle cell proliferation and with a greater frequency of loss of epithelial polarity at the termini compared with central regions of the egg chamber. Nonetheless, the average number of cells that invade per invasion event from terminal vs. central regions is approximately equal. Of interest, patterns of dlg invasion appear to coincide with boundaries established by proto-oncogene signals responsible for anterior-posterior patterning. The Drosophila egg chamber may thus be a useful model for exploring how epithelial tumor invasion might be a neomorphogenetic process organized by signals essential for developmental pattern formation.

Testing the "Go or Grow" hypothesis in human medulloblastoma cell lines in two and three dimensions.

OBJECTIVE: The "Go or Grow" hypothesis proposes that cell division and cell migration are temporally exclusive events and that tumor cells defer cell division to migrate. The purpose of this study was to assess the Go or Grow hypothesis using medulloblastoma cell lines in directional migration and invasion assays in monolayer and three-dimensional cultures. METHODS: Time-lapse videomicroscopy was used to continually monitor the directional migration, invasion, and mitosis of individual cells. The mitotic activity observed by time-lapse videomicroscopy was compared with staining for the proliferating cell nuclear antigen Ki-67. RESULTS: A positive correlation exists between the migratory/invasive and mitotic activities of the four medulloblastoma cell lines studied. Within individual cell lines, however, migration and invasion distances are not influenced by the number of cell divisions. Time-lapse videomicroscopy and Ki-67 staining revealed similar trends in mitotic activity between migrating and nonmigrating cells within cell lines. Analysis of cell velocities before, after, and between cell divisions revealed an increase in cell velocity after cell divisions. CONCLUSION: In the models studied, four medulloblastoma cell lines do not defer cell proliferation for migration across an uncoated surface or invasion of a Type I collagen matrix, contrary to the Go or Grow hypothesis. Migrating and invading cells continue to proliferate and migrate/invade a cell line-dependent distance irrespective of the number of divisions that take place. These findings emphasize the need to evaluate the effect of future therapies on both biological events and, if possible, to identify intracellular signaling proteins that negatively regulate medulloblastoma migration/invasion and proliferation.

Magnifying endoscopy, stereoscopic microscopy, and the microvascular architecture of superficial esophageal carcinoma.

BACKGROUND AND STUDY AIMS: In this study we clarify the microvascular architecture of superficial esophageal carcinoma as observed by ultra-high magnification endoscopy and stereoscopic microscopy with Microfil injection. PATIENTS AND METHODS: We observed two surgically resected specimens of superficial esophageal cancer under stereoscopic microscopy with Microfil injection. In addition, in the histological investigation, we measured the caliber of the vessels at the surface of the tumor. We carried out ultra-high magnification before treatment in 82 patients with superficial esophageal neoplasms. We classified the depth of tumor penetration of superficial esophageal carcinoma into four categories: m1 to m3 (mucosal cancer) and sm (submucosal cancer). RESULTS: By observing the normal esophageal mucosa under a stereoscopic microscope and an ultra-high magnification endoscope, we were able to visualize the intrapapillary capillary loops (IPCL). In cancer lesions, we observed characteristic changes in the superficial microvascular architecture according to the depth of tumor invasion. In m1 invasion, there was dilatation of the IPCL; in m2 invasion, there was dilatation and elongation of the IPCL; in m3, there was a mixed appearance of the IPCL and tumor vessels; and in sm invasion, complete replacement by tumor vessels. On the basis of the above criteria, ultra-high magnification endoscopic observation before treatment showed a rate of agreement between histological depth of invasion and magnified appearance of 60/72 cases (83.3 %) for which satisfactory pictures were obtained. The histological investigation showed the caliber of the IPCL of the m1 cancer lesions (12.9 +/- 3.9 microm) to be significantly greater than that of the normal esophageal mucosa (6.9 +/- 1.5 microm) (P < 0.0001). CONCLUSIONS: Observation of the microvascular architecture of superficial esophageal carcinoma is useful in the diagnosis of the depth of invasion.

The long-term significance of microscopic dural invasion in 354 patients with pituitary adenomas treated with transsphenoidal surgery.

OBJECT: Pituitary adenomas are considered benign tumors; however, they may infiltrate surrounding tissues including the dura mater. In this paper the authors analyze the clinical significance of microscopically confirmed dural invasion by comparing a range of variables (age and sex of patients, adenoma type, adenoma size on magnetic resonance [MR] images, remission, residual pituitary disease, recurrence, survival, and disease-free interval after surgery) between patients with noninvasive adenomas and those with invasive ones. METHODS: Between 1992 and 1997 dural specimens were obtained in 354 patients with pituitary adenomas who underwent transsphenoidal surgery performed by the senior author (E.R.L.). Dural specimens were examined using routine histological methods and assessed for invasion by pituitary adenoma tissue. The dura was invaded by the pituitary adenoma in 161 patients (45.5%), and in 192 patients (54.5%) no evidence of dural invasion was found. Dural invasion was present significantly more frequently in the repeated surgery group (69%, 55 patients) than in the primary transsphenoidal surgery group (41%, 291 patients). The mean age of patients undergoing primary transsphenoidal surgery was significantly older in cases of invasive adenomas (50 years) compared with cases of noninvasive adenomas (43 years), and these age differences also correlated with adenoma size. Women tend to develop clinically evident, smaller adenomas at a younger age than men. Of the patients with pituitary adenomas that were 20 mm or smaller, 117 (76%) of 154 were women, whereas of the patients with adenomas that were larger than 20 mm, 74 (54%) of 137 were men. The frequency of dural invasion increased with increasing size of the pituitary adenoma as measured on MR images. In 291 patients who underwent primary pituitary surgery, the frequency of dural invasion according to adenoma size was 24% (< or = 10 mm), 35% (> 10 to < or = 20 mm), 55% (> 20 to < or = 40 mm), and 70% (> 40 mm). In patients who underwent primary transsphenoidal surgery, dural invasion was present in more than 50% of those with nonfunctioning adenomas and in 30 to 35% of patients with endocrinologically active adenomas. The mean diameter of the gonadotrophic adenomas and null-cell adenomas was significantly larger than that of each of the endocrinologically active adenomas. In 58 (20%) of 291 patients who underwent primary pituitary surgery there was residual pituitary disease postsurgery, and 20% of this subset of patients showed clinical improvement to such an extent that no further management was recommended. After pituitary surgery, residual tumor tissue was demonstrable significantly more frequently in patients with invasive adenomas than in those with noninvasive adenomas. Recurrences after initial remission (cure) of pituitary disease occurred in 18 (8.8%) of 205 patients between 2 and 79 months after primary pituitary surgery (median 25 months). The recurrence rate was not related to dural invasion in a consistent or significant fashion. Seven patients died between 14 and 79 months after pituitary surgery and all had invasive adenomas identified on gross observation at surgery and on microscopy. The survival rate was slightly but significantly decreased for patients with invasive adenomas (91%) compared with patients with noninvasive adenomas (100%) at 6 years postsurgery. CONCLUSIONS: The principal significance of dural invasion by pituitary adenoma is the persistence of tumor tissue after transsphenoidal surgery (incomplete adenomectomy; 20% in primary pituitary tumor resections). The increase in adenoma size with time and the concurrent development of dural invasion are the major factors that determine an incomplete adenomectomy. When the adenoma remains restricted to the sellar compartment or shows only moderate suprasellar extension, dural invasion may not yet have developed and conditions for complete selective adenomectomy are improved.

Ultrastructurally "invasive" microvilli in an aggressively metastasizing biphasic malignant mesothelioma.

The presence of long, slender, often branching microvilli on cell surfaces is a characteristic feature of malignant and benign mesothelial cells. However, these typical microvilli are seen only in better-differentiated lumens within epithelial areas of malignant mesotheliomas. Presented here are the clinical and ultrastructural findings in a biphasic malignant mesothelioma that lacked lumens, but possessed very long microvilli. These invaginated deeply into the cytoplasm of neighboring tumor cells, as well as into the surrounding stromal matrix. The tumor cells had well-formed intercellular desmosomal junctions. The primary tumor was localized to the pleura and invaded the chest wall, but only minimally the lung. Lobectomy demonstrated the presence of metastatic tumor in 2 peribronchial lymph nodes. The disease progressed rapidly and, within 6 months, killed the patient. An autopsy revealed widespread metastases in multiple systemic organs. The authors speculate that the unique ultrastructural features of this case may be a clue to the unusually aggressive course of the neoplasm.

Critical steps in hematogenous metastasis: an overview.

Metastasis is responsible for most cancer deaths. A better understanding of the process provides opportunities to develop new treatments to prevent metastasis. This article summarizes findings from experimental in vivo videomicroscopy and quantitative studies on metastatic inefficiency, which indicate that early steps in hematogenous metastasis may be quite efficient, but that regulation of cancer cell growth in secondary sites determines metastatic outcome. The authors have identified three key stages of this growth regulation: survival of a subset of single cells, proliferation of a subset of these cells to form preangiogenic micrometastases, and persistence of growth of a subset of these to form vascularized metastases. Formation of clinically relevant metastases is determined by the proportion of cells that proceeds successfully through each stage, and surviving single cells and preangiogenic micrometastases both represent possible sources of tumor dormancy.

Estudio comparativo de tres modelos de melanomas murinos Harding-Passey, B16 y B 16F 10 / Comparative study of three murine melanoma models: Harding-Passey, B16 and B16F10

Planteamiento: Estudiamos las características clinicopatológicas, ultraestructurales y el comportamiento biológico de tres líneas de melanomas murinos: Harding-Passey. B16 y B16F10. Material y métodos: Se han utilizado 80 ratones C57B1/6J, a los que se inyectó una suspensión de 10° células tumorales por vía subcutánea a nivel inguinal. Se procesaron muestras de los tumores para el estudio microscópico óptico y electrónico. Se realizó el estudio estadístico. Resultados: Las tres líneas originaban tumores fácilmente trasplantables. De los tres modelos, el Harding-Passey supone el tumor de crecimiento más lento, presentando los menores pesos medios, el menor índice mitótico y una supervivencia mayor de los animales huéspedes. El B16 muestra un crecimiento intermedio con pesos tumorales de casi el doble que el anterior, un índice mitótico ligeramente superior y una supervivencia de los ratones ligeramente inferior. El B16F10 muestra la mayor capacidad de crecimiento, siendo los pesos medios de los tumores seis y cuatro veces mayores, respectivamente, que los de Harding-Passey y B16, con un índice mitótico más alto y una supervivencia de los animales inferior a la mitad de los anteriores. Conclusiones: Las tres líneas estudiadas constituyen modelos experimentales idóneos para el estudio del melanoma. Los tumores muestran un comportamiento biológico distinto, con una capacidad proliferativa variable, siendo el B16F10 el de mayor crecimiento. La baja supervivencia de los animales hace que sea un modelo ideal para estudios cortos. Todos mostraban alteraciones en la ultraestructura de los melanosomas (AU)

Light and electron microscopy of the pagetoid spread of germ cell carcinoma in the rete testis: morphologic evidence suggestive of field effect as a mechanism of tumor spread.

The purpose of this study is to investigate the mechanism of tumor spread in the pagetoid spread of germ cell tumors in the rete testis (PSRT). Twenty consecutive cases of germ cell tumor of the testis (9 seminomas, 3 embryonal carcinomas, and 8 teratocarcinomas) were retrieved to identify the cases with PSRT. The areas of pagetoid spread were examined by the serial sectioning of the entire thickness of the tissue block. Available fresh tissue was submitted for electron microscopic study. Ten cases were associated with PSRT and had focal or extensive areas of intratubular germ cell neoplasia (IGCN) in the proximity of the tumor and the rete testis (RT). In the remaining 10 cases, 6 were associated with IGCN distant from the RT and the last 4 were not associated with IGCN. Seminiferous tubules with IGCN were seen connecting with the RT with pagetoid spread. Isolated single intraepithelial tumor cells also were identified at the periphery of the areas with PSRT. Electron microscopic study of the RT of 4 cases with PSRT (2 seminomas, 1 embryonal carcinoma, and 1 teratocarcinoma) revealed desmosome-type junctions between tumor cells with RT epithelial cells. Direct tumor expansion and cell motility as mechanisms of tumor spread in PSRT does not explain the presence of isolated cells and desmosome-type junctions of the tumor cells as demonstrated in this study. The authors believe that the field effect plays an important part in the pathogenesis of this pagetoid spread in the RT. It is likely that this field effect is induced by the germ cell tumor and is operated through the immature germ cells or undifferentiated epithelial cells in the RT adjacent to the tumor cells.