Observation of the cytoarchitecture of the human esophageal mucosa with special attention to the lamina muscularis mucosae and the distribution of lymphatic vessels.

The cytoarchitecture of the esophageal mucosa was examined by using light microscopy, transmission electron microscopy, and scanning electron microscopy. The cytoarchitecture of the muscularis mucosae varied greatly among the cervical, thoracic, and abdominal esophagus, especially in the cervical esophagus, the muscularis mucosae suffered a loss and the distribution of lymphatic vessels also varied according to the site. It was suggested that these morphological differences would have a strong influence on the infiltration of esophageal cancer and the mode of lymph node metastasis.

STAT3 inhibitor stattic enhances radiosensitivity in esophageal squamous cell carcinoma.

The radioresistance of esophageal squamous cell carcinoma (ESCC) remains an obstacle for the effective radiotherapy of ESCC. This study aimed to investigate the radiosensitization of ESCC by signal transducer and activator of transcription 3 (STAT3) inhibitor stattic. ECA109, TE13, and KYSE150 cell lines were exposed to hypoxia and treated with stattic or radiation, alone or in combination. Cell proliferation, colony formation, apoptosis, and double-stranded DNA breaks (DSBs) were examined. In addition, ECA109 cells were xenografted into nude mice and treated with radiation and/or stattic. The levels of STAT3, p-STAT3, hypoxia-inducible factor 1α (HIF-1α), and vascular endothelial growth factor (VEGF) in ESCC cells and xenografts were detected by Western blot and immunohistochemical analysis. Our results showed that stattic efficiently radiosensitized ESCC cells and xenografts, especially under hypoxia. Moreover, stattic inhibited STAT3 activation and downregulated HIF-1α and VEGF expression. In conclusion, stattic confers radiosensitivity in ESCC cells in vitro and in vivo and is a potential adjuvant for the radiotherapy of ESCC in the clinical setting.

Endocytoscopic observation of various esophageal lesions at ×600: can nuclear abnormality be recognized?

Endocytoscopy (ECS) is a novel endoscopic technique that allows detailed diagnostic examination of the gastrointestinal tract at the cellular level. We previously reported that use of ECS at ×380 magnification (GIF-Y0002) allowed a pathologist to diagnose esophageal squamous cell carcinoma (ESCC) with high sensitivity (94.9%) but considerably low specificity (46.7%) because this low magnification did not reveal information about nuclear abnormality. In the present study, we used the same magnifying endoscope to observe various esophageal lesions, but employed digital 1.6-fold magnification to achieve an effective magnification of ×600, and evaluated whether this improved the diagnostic accuracy in distinguishing neoplastic from non-neoplastic lesions.We examined the morphology of surface cells using vital staining with toluidine blue and compared the histological features of 40 cases, including 19 case of ESCC and 21 non-neoplastic esophageal lesions (18 cases of esophagitis, 1 case of glycogenic acanthosis, 1 case of leiomyoma, and 1 case of normal squamous epithelium). One endoscopist classified the lesions using the type classification, and we consulted one pathologist for judgment of the ECS images as 'neoplastic', 'borderline', or 'non-neoplastic'. At ×600 magnification, the pathologist confirmed that nuclear abnormality became evident, in addition to the information about nuclear density provided by observation at ×380. The overall sensitivity and specificity with which the endoscopist was able to predict neoplastic lesions using the type classification was 100% (19/19) and 90.5% (19/21), respectively, in comparison with values of 94.7% (18/19 cases) and 76.2% (16/21), respectively, for the pathologist using a magnification of ×600. The pathologist diagnosed two non-neoplastic lesions and one case of ESCC showing an apparent increase of nuclear density with weak nuclear abnormality as 'borderline'. Among the 21 non-cancerous lesions, two cases of esophagitis that were misdiagnosed by the endoscopist were also misinterpreted as 'neoplastic' by the pathologist. We have shown, by consultation with a pathologist, that an ECS magnification of ×600 (on a 19-inch monitor) is adequate for recognition of nuclear abnormality. We consider that it is feasible to diagnose esophageal neoplasms on the basis of ECS images, and that biopsy histology can be omitted if a combination of increased nuclear density and nuclear abnormality is observed.

Visualization of blood supply route to the reconstructed stomach by indocyanine green fluorescence imaging during esophagectomy.

BACKGROUND: Ensuring an adequate blood supply is essential to the safe performance of an anastomosis during esophagectomy and the prevention of anastomotic leakage. Recently, indocyanine green (ICG) fluorescence imaging has been used to visualize the blood supply when anastomosis is performed in vascular surgery. We used ICG fluorescence imaging to visualize the blood supply for reconstruction during esophagectomy. METHODS: Since January 2009, we have performed ICG fluorescence imaging in 33 patients with thoracic esophageal cancer who underwent thoracic esophagectomy. After pulling up the reconstructed stomach, 2.5 mg of ICG was injected as a bolus. ICG fluorescence imaging was performed with a near-infrared camera, and the images were recorded. RESULTS: ICG fluorescence was easily detected in all patients 1 min after injection. Vascular networks were well visualized in the gastric wall and omentum. The blood supply route was located in the greater omentum beside the splenic hilum in 22 (66.7%) of the 33 patients. CONCLUSIONS: ICG fluorescence can be used to evaluate the blood supply to the reconstructed stomach in patients undergoing esophagectomy for esophageal cancer. On ICG fluorescence imaging, the splenic hiatal vessels were the major blood supply for the anastomosis in most patients.

Nanoscale markers of esophageal field carcinogenesis: potential implications for esophageal cancer screening.

BACKGROUND AND STUDY AIMS: Esophageal adenocarcinoma (EAC) has a dismal prognosis unless treated early or prevented at the precursor stage of Barrett's esophagus-associated dysplasia. However, some patients with cancer or dysplastic Barrett's esophagus (DBE) may not be captured by current screening and surveillance programs. Additional screening techniques are needed to determine who would benefit from endoscopic screening or surveillance. Partial wave spectroscopy (PWS) microscopy (also known as nanocytology) measures the disorder strength (Ld ), a statistic that characterizes the spatial distribution of the intracellular mass at the nanoscale level and thus provides insights into the cell nanoscale architecture beyond that which is revealed by conventional microscopy. The aim of the present study was to compare the disorder strength measured by PWS in normal squamous epithelium in the proximal esophagus to determine whether nanoscale architectural differences are detectable in the field area of EAC and Barrett's esophagus. METHODS: During endoscopy, proximal esophageal squamous cells were obtained by brushings and were fixed in alcohol and stained with standard hematoxylin and Cyto-Stain. The disorder strength of these sampled squamous cells was determined by PWS. RESULTS: A total of 75 patient samples were analyzed, 15 of which were pathologically confirmed as EAC, 13 were DBE, and 15 were non-dysplastic Barrett's esophagus; 32 of the patients, most of whom had reflux symptoms, acted as controls. The mean disorder strength per patient in cytologically normal squamous cells in the proximal esophagus of patients with EAC was 1.79-times higher than that of controls (P<0.01). Patients with DBE also had a disorder strength 1.63-times higher than controls (P<0.01). CONCLUSION: Intracellular nanoarchitectural changes were found in the proximal squamous epithelium in patients harboring distal EAC and DBE using PWS. Advances in this technology and the biological phenomenon of the field effect of carcinogenesis revealed in this study may lead to a useful tool in non-invasive screening practices in DBE and EAC.

Structural alterations of the mucosa stroma in the Barrett's esophagus metaplasia-dysplasia-adenocarcinoma sequence.

BACKGROUND AND AIM: Accumulating evidence suggests that the extracellular matrix play important roles in intercellular communications and contribute to the development of a number of diseases, including diseases of the gastrointestinal tract. The present study examined the structural characteristics and alterations of the extracellular matrix of the mucosa stroma in the Barrett's esophagus metaplasia-dysplasia-adenocarcinoma sequence. METHODS: A total of 41 esophageal tissue specimens (15 esophageal adenocarcinoma, 10 Barrett's esophagus intestinal metaplasia, seven dysplasia and nine normal esophagus) were studied. The present study used transmission electron microscopy and computerized quantitative electron-microscopic analysis in order to investigate the characteristics of the extracellular matrix of the mucosa. RESULTS: The study revealed that marked structural alterations of the mucosa stroma, relating to changes in the distribution and appearance of collagen fibers as well as to changes in numbers of matrix microvesicles, occur in Barrett's esophagus and esophageal adenocarcinoma. It was found that there were 3.1 times more microvesicles in the stroma in Barrett's esophagus than in the stroma of the normal esophagus (P<0.0001) and that there were 5.8 times more microvesicles in esophageal adenocarcinoma than in the normal esophagus (P<0.0001). There were 1.9 times more microvesicles in esophageal adenocarcinoma than in Barrett's esophagus (P=0.0043). CONCLUSIONS: The study demonstrates distinctive alterations of the mucosa stroma extracellular matrix in the metaplasia-dysplasia-adenocarcinoma sequence. The findings suggest that the redistribution of collagen fibers and increases in numbers of matrix microvesicles may play roles in the formation of specialized intestinal metaplasia and the development of adenocarcinoma.

Autophagy inhibition contributes to radiation sensitization of esophageal squamous carcinoma cells.

Radiotherapy is a useful component of treatment strategies for esophageal cancer. The role of autophagy in response to ionizing radiation was investigated in human esophageal squamous carcinoma cells. Cell viability and clonogenic survival assay were used to evaluate the radiosensitivity of autophagy inhibitor (3-MA) on esophageal squamous carcinoma cells. The percentage of apoptotic cells and cell cycle analysis were assessed by flow cytometry; DAPI staining was used to detect apoptotic cells. The expression of beclin-1 and LC3 was measured using a Western blot. The ultrastructural analysis was under the electron microscope. 6 Gy irradiation induced a massive accumulation of autophagosomes accompanied by strong upregulation of beclin-1 and LC3-II expression in TE-1 cells. Compared with radiation alone, 3-MA combined with radiation significantly decreased cell viability, as well as autophagic ratio, beclin-1, and LC3-II protein level. Inhibition of autophagy increased radiation-induced apoptosis and the percentage of G2/M-phase cells. Blockade of autophagy with 3-MA enhanced cytotoxicity of radiotherapy in human esophageal squamous carcinoma cells. It suggests that inhibition of autophagy could be used as adjuvant therapy to treat esophageal squamous cell carcinoma.

Standardization of esophageal adenocarcinoma in vitro model and its applicability for model drug testing.

FLO-1 cell line represents an important tool in esophageal adenocarcinoma (EAC) research as a verified and authentic cell line to study the disease pathophysiology and antitumor drug screenings. Since in vitro characteristics of cells depend on the microenvironment and culturing conditions, we performed a thorough characterization of the FLO-1 cell line under different culturing conditions with the aim of (1) examining the effect of serum-free growth medium and air-liquid interface (A-L) culturing, which better reflect physiological conditions in vivo and (2) investigating the differentiation potential of FLO-1 cells to mimic the properties of the in vivo esophageal epithelium. Our study shows that the composition of the media influenced the morphological, ultrastructural and molecular characteristics of FLO-1 cells, such as the expression of junctional proteins. Importantly, FLO-1 cells formed spheres at the A-L interface, recapitulating key elements of tumors in the esophageal tube, i.e., direct contact with the gas phase and three-dimensional architecture. On the other hand, FLO-1 models exhibited high permeability to model drugs and zero permeability markers, and low transepithelial resistance, and therefore poorly mimicked normal esophageal epithelium. In conclusion, the identified effect of culture conditions on the characteristics of FLO-1 cells should be considered for standardization, data reproducibility and validity of the in vitro EAC model. Moreover, the sphere-forming ability of FLO-1 cells at the A-L interface should be considered in EAC tumor biology and anticancer drug studies as a reliable and straightforward model with the potential to increase the predictive efficiency of the current in vitro approaches.

Prospective replacement of magnifying endoscopy by a newly developed endocytoscope, the 'GIF-Y0002'.

Endocytoscopy has the potential to reduce the need for histologic examination of biopsy specimens in cases of esophageal squamous cell carcinoma. Up to now, two types of endocytoscope have been used: the probe type and the integrated type. In this study we examined the utility of a newly developed endocytoscope, the 'GIF-Y0002,' which has a single lens allowing consecutive magnification from the conventional endoscopy level up to ×380. Using the GIF-Y0002, we examined 24 examples of normal esophageal mucosa to clarify the appearance of the microvasculature of the normal squamous epithelium in vivo. We also examined 11 cases of esophageal cancer in the same way, employing methylene blue as a vital dye to stain the surface cells. In normal squamous epithelium, we clarified the relationship between the subepithelial capillary network, IPCLs and subepithelial venules. With methylene blue staining, we observed typical squamous cells (low nuclear density and low N/C ratio without nuclear abnormality). When cancerous lesions were observed using lower-power magnification, we were able to visualize their microvascular architecture to the same extent as when conventional magnifying endoscopy was used. Furthermore, at higher magnification, we were able to visualize the features of blood flow in both superficial and advanced cancer. Methylene blue staining revealed an increase of nuclear density in all cases of cancer. The pathologist agreed to omit biopsy histology in 81.8% (9/11) of cancer cases considering the nuclear density and nuclear abnormality. The GIF-Y0002 provides information on cell abnormality in addition to the features revealed by currently available magnifying endoscopy.

Subcellular localization pattern of protoporphyrin IX is an important determinant for its photodynamic efficiency of human carcinoma and normal cell lines.

Photodynamic therapy (PDT) is a combination of light with a lesion-localizing photosensitizer or its precursor to destroy the lesion tissue. PDT has recently become an established modality for several malignant and non-malignant conditions, but it can be further improved through a better understanding of the determinants affecting its therapeutic efficiency. In the present investigation, protoporphyrin IX (PpIX), an efficient photosensitizer either endogenously induced by 5-aminolevulinic acid (ALA) or exogenously administered, was used to correlate its subcellular localization pattern with photodynamic efficiency of human oesophageal carcinoma (KYSE-450, KYSE-70) and normal (Het-1A) cell lines. By means of fluorescence microscopy ALA-induced PpIX was initially localized in the mitochondria, whereas exogenous PpIX was mainly distributed in cell membranes. At a similar amount of cellular PpIX PDT with ALA was significantly more efficient than photodynamic treatment with exogenous PpIX at killing all the 3 cell lines. Measurements of mitochondrial membrane potential and intracellular ATP content, and electron microscopy showed that the mitochondria were initially targeted by ALA-PDT, consistent with intracellular localization pattern of ALA-induced endogenous PpIX. This indicates that subcellular localization pattern of PpIX is an important determinant for its PDT efficiency in the 3 cell lines. Our finding suggests that future new photosensitizers with mitochondrially localizing properties may be designed for effective PDT.

Light and electron microscopic studies of perineural invasion by esophageal carcinoma.

Light and electron microscopic findings on perineural invasion by human esophageal squamous cell carcinoma are reported. Perineural invasion was observed histologically in 30 of a total of 129 cases (23%) of esophageal squamous cell carcinoma and in 11 of the 24 cases (46%) in which tumors infiltrated other organs by passing through the esophageal adventitial layer. Electron microscopic observation showed that the perineurium of peripheral nerves was completely surrounded by carcinoma cells and that marked degeneration and loss of perineural cells occurred. Irregularly thickened basal laminae were detected in the perineurium. For nerves incompletely surrounded by carcinoma tissue, the free portion of the perineurium revealed degenerative findings similar to those for completely surrounded nerves. Cytoplasmic projections of the leading margin of the invading cancer tissue were located in the degenerated perineurium, contained many lysosomes, and were not always surrounded by basal laminae. These observations suggest that invading carcinoma tissue actively contributes to the degeneration of the perineural sheath and that the special pattern of carcinoma tissue surrounding the peripheral nerves results from infiltration along the degenerated sheath of the perineurium.

Biologic properties of three newly established human esophageal carcinoma cell lines.

Three epithelial cell lines, CE-48T/VGH, CE-69T/-VGH, and CE-81T/VGH, were established from human squamous cell carcinoma of the esophagus. The cells were polygonal with a high nucleus-to-cytoplasm ratio. Many cells were multinucleate. Electron microscopy revealed the presence of tonofilaments and desmosomes. Chromosome analysis showed that these 3 cell lines were heteroploids of human origin. When transplanted into BALB/c (nu/nu) mice, CE-69T/VGH and CE-81T/VGH produced tumors, the histology of which proved to be carcinomas. All 3 cell lines secreted carcinoembryonic antigen. However, the secretion patterns were different. These 3 cell lines may provide useful models for the study of human esophageal cancer.

Esophageal carcinoma with a rhabdoid phenotype: a case report of diagnosis by endoscopic ultrasound-guided fine-needle aspiration.

Malignant extra renal tumors with rhabdoid phenotype are aggressive neoplasms associated with a poor prognosis. These tumors have been reported in soft tissue and various organs including the gastrointestinal tract. We report one of such tumors arising in the esophagus and discuss the cytopathologic, immunohistochemical, and ultrastructural features. Endoscopic ultrasound-guided fine-needle aspiration (FNA) cytology revealed a highly cellular tumor, consisting of polygonal poorly cohesive cells with prominent eosinophilic paranuclear cytoplasmic inclusions. Immunohistochemical staining showed strong cytoplasmic positivity for vimentin and cytokeratin. Electron microscopy revealed presence of numerous intermediate filaments. To the best of our knowledge, this is the first example of carcinoma with rhabdoid phenotype of the esophagus diagnosed by FNA cytology.

Absolute CT perfusion parameter values after the neoadjuvant chemoradiotherapy of the squamous cell esophageal carcinoma correlate with the histopathologic tumor regression grade.

PURPOSE: To analyze value of the computed tomography (CT) perfusion imaging in response evaluation of the esophageal carcinoma to neoadjuvant chemoradiotherapy (nCRT) using the histopathology as reference standard. METHODS: Forty patients with the squamous cell esophageal carcinoma were re-evaluated after the nCRT by CT examination, which included low-dose CT perfusion study that was analyzed using the deconvolution-based CT perfusion software (Perfusion 3.0, GE). Histopathologic assessment of tumor regression grade (TRG) according to Mandard's criteria served as reference standard of response evaluation. Statistical analysis was performed using Spearman's rank correlation coefficient (r(S)) and Kruskal-Wallis's test. RESULTS: The perfusion CT parameter values, measured after the nCRT in the segment of the esophagus that had been affected by neoplasm prior to therapy, significantly correlated with the TRG: blood flow (BF) (r(S)=0.851; p<0.001), blood volume (BV) (r(S)=0.732; p<0.001) and mean transit time (MTT) (r(S)=-0.386; p=0.014). Median values of BF and BV significantly differed among TRG 1-4 groups (p<0.001), while maximal esophageal wall thickness did not (p=0.102). Median BF and BV were gradually rose and MTT decreased as TRG increased, from 21.4 ml/min/100 g (BF), 1.6 ml/100 g (BV) and 8.6 s (MTT) in TRG 1 group, to 37.3 ml/min/100 g, 3.5 ml/100 g and 7.5 s in TRG 2 group, 81.4 ml/min/100 g, 4.1 ml/100 g and 3.8 s in TRG 3 group, and 121.1 ml/min/100 g, 4.9 ml/100 g and 3.7 s in TRG 4 group. In all 15 patients who achieved complete histopathologic regression (TRG 1), BF was <30.0 ml/min/100 g. CONCLUSIONS: CT perfusion could improve the accuracy in response evaluation of the esophageal carcinoma to nCRT.

Aberrant DNA hypermethylation reduces the expression of the desmosome-related molecule periplakin in esophageal squamous cell carcinoma.

Periplakin (PPL), a member of the plakin family of proteins that localizes to desmosomes and intermediate filaments, is downregulated in human esophageal squamous cell carcinoma (ESCC). Little is known, however, about the molecular mechanism underlying the regulation of PPL expression and the contribution of PPL loss to the malignant property of the cancer is unclear. We demonstrated that PPL mRNA expression was significantly reduced in ESCC tissues compared with that in normal tissues. Therefore, we hypothesized that CpG hypermethylation is the cause of the downregulation of PPL. Bisulfite-pyrosequencing of 17 cases demonstrated that the frequency of PPL methylation was higher in ESCC tissues than in normal tissues. When human ESCC cell lines were treated with 5-aza-2'-deoxycytidine (5-aza-dC), a DNA-methyltransferase inhibitor, PPL transcription was induced. Human KYSE270 ESCC cells do not stratify under ordinary culture conditions and rarely produce desmosomes; however, the forced expression of PPL promoted cell stratification. PPL induction also promoted adhesion to extracellular matrix but delayed cell migration. The abundance of desmosome-like structures was greatly increased in PPL transfectant as determined by transmission electron microscopy. Very low expression of another desmosome protein EVPL in ESCC, even in PPL transfectant, also supported the significant role of PPL in desmosome formation and cell stratification. Our results first indicate that the downregulation of PPL mediated by DNA hypermethylation, which may play an important role in the loss of ESCC stratification and likely in metastatic phenotype.

Expression of peanut agglutinin-binding mucin-type glycoprotein in human esophageal squamous cell carcinoma as a marker.

BACKGROUND: The TF (Thomson-Friedenreich) blood group antigen behaves as an onco-foetal carcinoma-associated antigen, showing increased expression in malignancies and its detection and quantification can be used in serologic diagnosis mainly in adenocarcinomas. This study was undertaken to analyze the sera and tissue level detectable mucin-type glycoprotein (TF-antigen) by Peanut agglutinin (PNA) and its diagnostic index in serum as well tissues of human esophageal squamous cell carcinoma as marker. RESULTS: We examined 100 patients for serological analysis by Enzyme Linked Lectin Assay (ELISA) and demonstrated a sensitivity of 87.5%, specificity of 90% and a positive predictive value of 95%. The immuno-histochemical localization of TF antigen by Fluorescence Antigen Technique (FAT) in 25 specimens of normal esophageal squamous epithelium specimens and 92 specimens with different grades of, allowed a quicker and more precise identification of its increased expression and this did not correlate with gender and tumor size. There was a positive correlation between membrane bound TF antigen expression with different histological progression, from well differentiated to poorly differentiated, determined by PNA binding. Specimens showed morphological changes and a pronounced increase in PNA binding in Golgi apparatus, secretory granules of the cytosol of well differentiated and an increased cell membrane labeling in moderately and poorly differentiated, when compared with ESCC and normal tissues. CONCLUSION: The authors propose that the expression of TF-antigen in human may play an important role during tumorigenesis establishing it as a chemically well-defined carcinoma-associated antigen. Identification of the circulating TF-antigen as a reactive form and as a cryptic form in the healthy individuals, using PNA-ELLA and Immunohistochemical analysis of TF antigen by FAT is positively correlated with the different histological grades as a simple and cost-effective method for the early diagnosis of ESCC. The present study reveals that, during tumorigenesis, an aberrant glycosylation takes place in Golgi apparatus leading to over secretion of TF antigen into the cytoplasm along with mucin granules and later into cell membrane. We suggest that the further characterization of TF antigen may unravel pathogenetic aspects of this silent disease.

Primary malignant melanoma of the esophagus.

Primary malignant melanoma of the esophagus is exceedingly rare. We identified six patients seen at Memorial Hospital for Cancer and Allied Diseases over a period of 35 years. All patients were Caucasian, with an age range of 30 to 74 years (mean: 60 years). There were three men and three women. No association was noted with tobacco or ethanol use, nor was there a personal or family history of malignant melanoma. Symptoms were related to obstruction or hemorrhage. All tumors were polypoid and had attained large size at the time of initial diagnosis. Histologically, the melanomas had epithelioid, spindle-cell, and pleomorphic areas with focal melanin production. An intraepithelial "in situ" component was present in five cases and melanosis of the non-neoplastic esophagus in five. All six neoplasms were immunoreactive for S-100 protein, and none reacted with anticytokeratins. Two cases examined ultrastructurally showed premelanosomes. All patients were treated by esophagogastrectomy. The mean survival for four patients was only 2.1 months. The two remaining patients are alive at 5.5 and 11 months.

Adenocarcinoma of the upper esophagus arising in ectopic gastric mucosa. Two case reports and review of the literature.

Although ectopic gastric mucosa is often mentioned as a source of upper esophageal adenocarcinoma, few such cases have actually been documented. We report two cases and offer a review of the literature. Ectopic gastric mucosa in the upper esophagus is a relatively common congenital condition, but the risk of malignant transformation is extremely low. Ectopic gastric mucosa should be distinguished from Barrett's esophagus, an acquired condition with a well-documented predilection for developing adenocarcinoma.

Polypoid carcinoma of the esophagus. A unifying term for "carcinosarcoma" and "pseudosarcoma".

Polypoid carcinomas with spindle-cell sarcomatous features have been designated either as carcinosarcoma or pseudosarcoma. The distinction between these two tumors has depended on the presence of "intermingling" of the carcinomatous and sarcomatous components in so-called carcinosarcoma. But unlike the carcinosarcoma, the sarcomatous component in pseudosarcoma has been considered benign. A polypoid tumor of the esophagus in a 57-year-old male was predominantly composed of spindle cell, sarcomatous cells. The presence of adjacent intraepithelial epidermoid carcinoma with transitional and ultrastructural features confirmed the epithelial origin of this tumor. Because of the absence of "intermingling," the primary tumor was considered to be a pseudosarcoma. However, our postmortem examination showed metastases composed of both carcinomatous and sarcomatous features. A review of the literature on carcinosarcomas and pseudosarcomas shows that only one case of pseudosarcoma reported by Hughes and Cruickshank showed a similar situation and indicates that the sarcomatous component in pseudosarcomas has the same metastatic potentiality as has been reported in carcinosarcomas. We conclude from these studies a basic similarity of the carcinosarcoma and pseudosarcoma. The term polypoid carcinoma is proposed for both these lesions.