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We report the case of a sarcomatoid carcinoma with a rhabdoid tumor component originating in the gallbladder, along with immunohistochemical and electron microscopic findings. A 61-year-old woman presented with a 5-month history of right upper quadrant pain. Ultrasonography and a computed tomographic scan indicated gallbladder cancer. She underwent a cholecystectomy and a common bile duct resection. A firm mass (4.5 cm in greatest dimension) was present in the neck portion of the gallbladder. The mass was firm, solid, yellowish gray, and granular with areas of necrosis. Microscopically, the tumor was a biphasic sarcomatoid carcinoma and consisted of diffusely arranged pleomorphic cells, focally showing rhabdoid features and neoplastic glands with focal mucin production. Heterologous components such as osteoid, chondroid, and rhabdomyoblastic elements were not identified. By immunohistochemical staining, we demonstrated that the rhabdoid cells coexpressed cytokeratin and vimentin. On electron microscopic examination, the rhabdoid tumor cells showed cytoplasmic whorls of intermediate filaments in the cytoplasm and eccentric nuclei. Two months postoperatively, the follow-up computed tomographic scan showed multiple intrahepatic metastases and omental seedings.

A cholecystectomy was performed on a 10-year-old spayed female mixed-breed dog with chronic weight loss, persistently increased liver enzyme activities, and cholecystomegaly identified by ultrasonographic examination. A subsequent diagnosis of a biliary carcinoid was made based on a neuroendocrine-type histologic pattern, cytoplasmic argyrophilia by Grimelius staining, immunopositivity for chromogranin A, and the ultrastructural finding of cytoplasmic secretory granules in neoplastic cells. Extrahepatic biliary carcinoid tumors are rare tumors of humans and have not been documented in domestic animals.

During mitosis, 2 centrosomes ensure accurate assembly of bipolar spindles and fidelity of the chromosomal segregation. The presence of more than 2 copies of centrosomes during mitosis can result in the formation of multipolar spindles, unbalanced chromosome segregation, and aneuploidy. Recent studies have provided evidence that centrosome hyperamplification plays a pivotal role in carcinogenesis. Using immunofluorescence analysis with gamma-tubulin and pericentrin antibodies, paraffin-embedded sections from 40 malignant biliary diseases including gallbladder cancers (GC; n = 13), intrahepatic cholangiocellular carcinoma (CCC; n = 19), and extrahepatic bile duct cancers (BDC; n = 8) were examined. Thirty-seven benign biliary diseases including chronic cholecystitis, gallbladder adenoma, hepatolithiasis, and choledochal cyst were included as benign controls. The frequencies of the centrosome abnormalities were 70% for GC, 58% for CCC, and 50% for BDC, respectively. The frequencies of centrosome abnormalities in malignant biliary diseases were significantly higher than in their benign counterparts (GC, CCC, BDC; P =.001,.002, and.001, respectively). The results of current study also indicated that biliary malignancy in the advanced stage (III-IV) displayed a higher frequency of centrosome abnormalities than in the early stage (I-II) (P <.001). We conclude that abnormalities in size, number, and shape of the centrosome are frequently observed in biliary tract malignancy. Centrosome abnormalities started to occur in the early stage of biliary malignancy and became very frequent in the advanced stage. This implies that centrosome abnormality might relate to the transition from early to advanced malignancy in biliary malignancy.

We report a case of carcinoma of the gallbladder in a 67-year-old woman. The description comprises the histological, immunohistochemical, ultrastructural and cytogenetical picture of the tumor. The ultrastructural features as well as chromosomal changes may denote the epithelial derivation of the tumor studied.

Mucinous carcinomas of the gallbladder are relatively uncommon. Their radiological findings have not been described previously. We describe the CT and US findings of mucinous carcinoma of the gallbladder in 3 cases. Tumors (thickened wall and/or intraluminal polypoid mass) showed hyperechogeneity or isoechogeneity on US and water density on CT. US clearly detected large polypoid lesions, but CT was unable to detect these lesions in 2 cases. Therefore, we stressed the discrepancy between the findings of US and CT. These features can be explained by the fact that a tumor containing a large amount of mucin produces a mass of near-water density in the gallbladder on CT. It is of value to know the radiological findings of these tumors because the diagnosis is easily missed by CT study alone.

Oat cell carcinomas arising in the gallbladder are an extremely rare and aggressive form of gallbladder cancer. These neoplasms are morphologically identical to their pulmonary counterparts, contain neurosecretory granules on ultramicroscopic examination, and demonstrate immunohistochemical staining for cytokeratin, neuron-specific enolase, and other neuroendocrine markers. Oat cell carcinomas typically occur in elderly women with cholelithiasis, and pursue a fulminant course with extensive metastases, especially to the liver. The mean survival is less than 7 months. We present a well-documented case of oat cell carcinoma of the gallbladder and review the literature on this unusual entity.

Background: Gallstone disease remains a leading cause of morbidity and mortality in humans. Despite extensive research into the physiology of the gallbladder, little is known about mucosal events that precede and contribute to stone formation. Here, we describe and partially characterize a cultured epithelial model of human gallbladder mucosa., Experimental Design: Cells originally obtained from a well-differentiated gallbladder mucosal carcinoma were cultured in modified Eagle's minimum media (supplemented with fetal calf serum and antibiotics) on polycarbonate supporting matrices., Results: Cell cultures were observed to come to confluence with 6 to 9 days. Light and transmission electron microscopy demonstrated the resultant epithelia to be predominantly one cell thick, to be polar in orientation, and to have apical villi. Epithelia exhibited cytokeratin markers consistent with their epithelia origin, functionally acidified the mucosal bathing solutions, and secreted mucin. Further experiments demonstrated transepithelial potential differences, mucosal-to-serosal transfer of sodium which could be inhibited with amiloride and 4-acetamido-4'-isothiocyanatostilbene-2-2'-disulfonic acid, and paracellular movement of neutral molecular probes inversely related to size., Conclusions: This culture model of human gallbladder mucosal carcinoma cells exhibits parameters consistent with native gallbladder and may offer a convenient new research tool for the study of the pathophysiology of gallstone formation.

Silver-binding nucleolar organizer regions (AgNOR) were investigated and compared in 43 cases of gall-bladder cancers and 10 normal gall-bladder samples using an image analyzer. The mean numbers of AgNOR per nucleus (AgNOR number) were 3.28 +/- 1.38 in the gall-bladder cancers and 1.86 +/- 0.20 in the normal gall-bladder cases. The respective mean areas of AgNOR per nucleus (AgNOR area) were 6.96 +/- 3.78 microns2 and 1.89 +/- 0.21 microns2. The differences were statistically significant (P < 0.0001) for both parameters. In addition, increased frequency and enlargement were both apparently correlated with poor prognosis (P < 0.011 and P < 0.046, respectively), with AgNOR number and AgNOR area showing tendencies for increase in cases of histologically high grade malignancy, advanced cancer and regional lymph node involvement. In conclusion, AgNOR number and AgNOR area appear to be useful indicators for the grading of malignancies and for the prediction of gall-bladder cancer prognosis.

Small cell (endocrine cell) carcinoma of the gallbladder in a 62-year-old woman is reported. The palliative cholecystectomy specimen revealed a submucosally invading tumor with extensive hemorrhagic necrosis. At autopsy, performed five months after surgery, a huge tumor measuring 14 x 12 x 8 cm was located at the liver hilus. No signs or symptoms related to overproduction of hormones were recorded throughout her illness. Neither lung lesions nor gall stones were identified. Histologically, diffuse proliferation of small, spindle-shaped atypical tumor cells with numerous mitoses was evident. Intraepithelial tumor cell proliferation in the gallbladder mucosa was seen focally. The neuroendocrine nature of the tumor cells was confirmed by the histologic pattern of growth with pseudo-rosette formation, positive reaction for Grimelius' argyrophilia, neuron-specific enolase and Leu 7, and ultrastructural demonstration of neuroendocrine-type granules. Immunostaining for a variety of hormones was all negative. Characteristically, foci with squamous and adenocarcinomatous differentiation were identified in the tumor tissue. The glandular components were immunoreactive for carcinoembryonic antigen, secretory component, epithelial membrane antigen and CA19-9. The histogenesis and totipotentiality of the neoplasm were discussed.

We report a case of a 55-year-old male with lymphoproliferative disease of granular lymphocytes. In the first year of follow-up reactive expansion of granular lymphocytes was observed during infectious episodes additionally to malignant proliferation. Histopathological studies revealed malignant lymphocytic infiltrations of the liver and gallbladder walls. The number of GL varied from 1.1 G/l to 17.8 G/l. Immunophenotyping studies showed surface phenotype CD3+, CD8+. There was markedly reduced NK cell function. The patient exhibited lack of severe parenchymal involvement, moderately increased white cell count (up to 21.0 G/l), severe neutropenia (0.06 G/l - 0.8 G/l) and recurrent infectious episodes.

We describe a rare carcinoma of the gallbladder containing osteoclast-like giant cells. Well-differentiated adenocarcinoma was found in the mucosa of the fundus, and osteoclast-like giant cells were present mainly in a haemorrhagic mass protruding from the mucosal surface. The metastatic hepatic tumour was composed chiefly, if not exclusively, of osteoclastoma-like cells, but minute carcinomatous elements were also present. There was an apparent transition between the giant cells and tubular structures in both the gallbladder tumour and hepatic tumour. However, ultrastructural study did not reveal any evidence of epithelial differentiation in the giant cells. Immunohistochemical studies suggested that the mononuclear and giant cells were mesenchymal and histiocytic in nature (vimentin and factor XIIIa positive). A few exceptional giant cells transforming from the fine tubular structure were positive for epithelial membrane antigen. In conclusion, the osteoclast-like giant cell tumour component was thought to represent mesenchymal metaplasia in pre-existent adenocarcinoma.

For the purpose of studying the histological types of gallbladder polyps and their relations to the clinical features, 40 specimens of postoperative polypoid lesions of the gallbladder collected from Changhai Hospital were observed by means of light and electron microscopy. The results demonstrated that the histological types of gallbladder polyps might be divided into: cholesterol polyp, inflammatory polyp, mixed-type polyp and adenomatoid polyp. Cholesterol polyp was the most frequently encountered and the next was inflammatory polyp. A mixed-type polyp is proposed. The adenomatoid polyp might have atypical hyperplasia and potential malignancy. The cholesterol polyp had no relationship with cholesterolosis of the gallbladder.

An unusual carcinoma of the gallbladder in a seventy-one-year-old woman displayed features of a well-differentiated adenocarcinoma, atypical carcinoid and small cell undifferentiated carcinoma. The patient died from progressive hepatic failure four months after surgery. Autopsy showed bulky liver masses and several peritoneal nodules exclusively composed of small, hyperchromatic cells. The neuroendocrine nature of the small cell component of the tumor was documented by the presence of neurosecretory granules at the ultrastructural level and by immunocytochemical positivity to NSE and Synaptophysin. The epithelial markers, cytokeratin and CEA, were also positive in the carcinoid and in the undifferentiated portions of the tumor. A common endodermal origin is suggested for carcinoid and small cell carcinoma of the gallbladder.

A 58-year-old man was seen with obstructive jaundice and discomfort in the upper abdomen. Computed tomographic and ultrasound examinations revealed a soft-tissue mass in the gallbladder. Cholecystectomy and choledochotomy revealed a soft black mass in the gallbladder and a second one in the intrapancreatic portion of the common bile duct. Each was diagnosed as malignant melanoma. Subsequently, a Whipple resection of the pancreas, duodenum, and distal bile duct revealed a melanoma circumferentially invading and obstructing the distal common duct. No lymph node or distant metastasis was identified. Repetitive searches for another primary site have been negative. The tumor apparently originated in the biliary tract. The patient remains almost well 2 years after diagnosis.

The ultrastructure of four well-differentiated adenocarcinomas of the gallbladder was investigated by scanning and transmission electron microscopy and compared with the ultrastructure of nonneoplastic mucosa in the same specimens and of the mucosa of gallbladders with gallstones. The tumor cells seen by scanning electron microscopy had severe disorganization of the regular arrangement of columnar cells. They were bizarre in shape and size and were covered with less developed pleomorphic microvilli that were irregularly distributed. No such findings appeared in the control specimens. The tumor cells seen by transmission electron microscopy exhibited pleomorphic microvilli, well-developed cytoplasmic organelles, various mucus granules, abundant lysosomes, and nuclear changes. These findings suggest increased secretory and metabolic activity in the tumor cells. Gobletlike cells, Paneth-like cells, and endocrine cells were scattered in two of the carcinomas. These cells were also noted in the nonneoplastic mucosa of the carcinoma specimens but were rare in the mucosa when cholelithiasis was present.

The authors present the histologic features, immunohistochemical findings, and ultrastructure of a carcinosarcoma of the gallbladder containing rhabdomyosarcoma as a mesenchymal element. A pedunculated polypoid tumor protruded into the lumen from the fundus of the gallbladder. The neoplasm contained two divergent components. One was malignant mesenchymal tissue with rhabdomyoblastic differentiation; the other was ordinary adenocarcinoma which was observed predominantly at the base of the polyp. Immunohistochemically, the cytoplasm of the rhabdomyoblasts stained with anti-myoglobin, myosin, and muscle actin antibodies. Ultrastructurally, there were a large number of malignant mesenchymal tissues in which various stages of differentiated rhabdomyoblasts were noted. Ultrastructural study was particularly valuable for the identification of sarcomatous elements.

In order to examine whether our subdivision of gall-bladder adenoma and adenocarcinoma into non-metaplastic and metaplastic types is reasonable from the viewpoint of their cytological features, a morphometrical analysis was conducted on 17 adenomas and 59 adenocarcinomas. The morphometrical parameters used were nucleo-cytoplasmic ratio (N/C ratio) and nuclear areas (NA). N/C ratio in the metaplastic type of both adenoma and adenocarcinoma was significantly larger than that in the non-metaplastic. This result shows that the different tumour types are associated with a different N/C ratio. Continuous measurement of N/C ratio and NA in progressing from non-cancerous mucosa to the lesion was made and the data obtained were analysed by the Lowess method. In some adenomas the total area of polypoid lesions was serially measured and these data were also analysed by the Lowess method. The results showed different processes in non-metaplastic and metaplastic types of adenoma and adenocarcinoma from the standpoint of nuclear changes of N/C ratio and NA. These results indicate that our histogenetic classification of adenocarcinoma is reasonable in morphometrical nuclear analysis. We also investigated the adenoma-carcinoma sequence as a possible histogenesis for gall-bladder carcinoma. Eight (72.7%) of 11 metaplastic adenomas and two (33.3%) of six non-metaplastic adenomas had foci of atypical gland proliferation and were considered to be carcinomas. Moreover, these carcinomatous areas were surrounded by severe dysplasia. These findings indicate that adenoma-carcinoma sequence accounts for one of the histogenesis of gall-bladder carcinoma.

Estrogen receptors (ER) in human gallbladders were examined immunohistochemically using a specific monoclonal antibody against human ER. ER immunoreactivity was positive in 6 (19.4%) of 31 cases of cholelithiasis, 6 (33.3%) of 18 cases of epithelial polyp, 14 (53.8%) of 26 cases of adenoma, and 26 (22.8%) of 114 cases of adenocarcinoma. ER immunoreactivity was located at the nucleus of the epithelium of both non-neoplastic and neoplastic tissues, although the number of ER-immunoreactive cells was small. There was no sex difference in the incidence of ER immunoreactivity. No significant difference in survival rates could be demonstrated between ER-positive and ER-negative carcinomas. Epithelial polyps, adenomas and carcinomas were divided into metaplastic type and non-metaplastic type based on the presence or absence of metaplastic changes for comparison of the incidence of ER immunoreactivity. The incidence of ER immunoreactivity in the metaplastic type was significantly higher than that in the non-metaplastic type. We conclude that ER are present in the gallbladder mucosa in various disease states and suggest that the presence of ER is related to metaplasia of the gallbladder mucosa.

A case of carcinoid tumor of the gallbladder associated with adenocarcinoma in a 56-year-old man is reported and a review of the literature is made. The tumor was a polypoid mass with a size of 5.5 X 4.0 X 2.8 cm. Histologically, the tumor showed carcinoid and adenocarcinoma with areas of mucous change. Tumor cells containing argyrophil granules were observed in both carcinoidal and adenocarcinomatous areas, but no argentaffin granules were detected in either of the neoplastic areas. Some of the tumor cells had both argyrophil granules and mucin in the same cytoplasm. The electron microscopic study revealed several tumor cells containing neurosecretory granules; however, no clinical signs of hormonal activities of the tumor were observed. The patient died of generalized bone metastases 16 months after surgery. This appears to be the second case of composite tumor of the gallbladder.

A cell line designated GBK-1 was established from a patient with anaplastic carcinoma of the gallbladder, marked neutrophilia and fever, and has been propagated for the past 18 months. The cells grew as a monolayer sheet with a doubling time of 43 hr. The GBK-1 cells were of a pleomorphic polygonal epitheloid shape and they were transplantable into nude mice. Mice bearing the tumor developed marked granulocytosis. In the culture supernatant of GBK-1 cells, high colony stimulating factor (CSF) activity was evident with both human bone marrow cells and C57BL mouse bone marrow cells, and granulocytic colonies, macrophage colonies or granulocyte-macrophage mixed colonies were produced. The CSF activity was distributed in the molecular weight range of 25,000 to 60,000 with two distinct peaks at molecular weights of approximately 50,000 and 30,000. CSF activity was inactivated by heat treatment at 70 degrees for 30 min. GBK-1 is a new human cell line that produces heat-labile human GM-CSF.

Six Swedish cases of primary sarcoma of the gallbladder from the period 1958-1973 and 1 case from 1975 were studied by light and electron microscopy. the literature was reviewed for the period after 1970. Ultrastructural features of sarcoma were investigated in order to exclude poorly differentiated carcinoma. One case was considered to be an embryonal rhabdomyosarcoma, three cases leiomyosarcoma and two were diagnosed as fibrosarcoma. One case, diagnosed as sarcoma of the gallbladder by light microscopy, was omitted because electron microscopical examination revealed a squamous cell carcinoma.

A cell strain (FU-GBC-1) was established from cancerous ascites of a 68-year-old male patient with well-differentiated adenocarcinoma of the gallbladder. By light and electron microscopy, the cultured cells showed the morphologic features of adenocarcinoma characterized by gland-like structures, intracellular microcystic spaces, and mucous production. Immunoperoxidase stains showed that FU-GBC-1 cells expressed several epithelial tumor antigens including CA 19-9, carcinoembryonic antigen (CEA), and epithelial membrane antigen (EMA). The cell strain has been in continuous culture up to passage 44 for 1 1/2 years, with the population doubling time of 120 hours. The cytogenetic analysis by a G-band technique showed a constant loss of chromosome Y in FU-GBC-1 cells. The modal chromosome number at passage 12 was 82 with a range of 77 to 85. Flow cytometry with an ethidium bromide technique additionally confirmed aneuploid DNA content (4C) in the cultured cells at passage 12 and 35. Inoculation of FU-GBC-1 cells into the dermis of BALB/c nude mice produced transplantable adenocarcinoma identical to the original tumor. Because no continuous cell lines of the well-differentiated type of gallbladder adenocarcinoma have been reported in the literature currently, the newly established cell strain we report may yield a useful system for studying the morphologic and biologic characteristics of gallbladder adenocarcinoma.

A rare case of primary malignant melanoma of the gallbladder was studied with the electron microscope. Two interesting patterns were observed: numerous melanophages were present in the tumor tissue and wrapped compound melanosomes were found in nonneoplastic mucosal epithelium. The infiltration of melanophages was considered to be a reaction to degenerated tumor cells. Concerning the mechanism of melanosome transport into the epithelial cells, a cooperative action between epithelial and melanoma cells seemed to be the most important factor.

The results of the study of ten cholangiocarcinomas from intrahepatic or extrahepatic origins are reported. Using both light microscopic immunohistochemistry and transmission electron microscopy the scirrhous stroma of the tumour showed clear evidence for the production of its collagenous, elastic and possibly other fibrillar elements by the neoplastic cells. Our findings refute the view that the occasional spindle cells (i.e. fibroblasts, myofibroblasts or even smooth muscle cells) could play a major role in the production of such a voluminous amount of the various connective tissue elements. Therefore, it seems reasonable to suggest that the scirrhous stroma of cholangiocarcinomas is produced by the malignant cells similar to those of the breast, oesophagus, stomach and ureter.

Nine malignant epithelial tumors of the gallbladder were examined electron microscopically. The tumors included the following subtypes: well-differentiated adenocarcinoma, signet ring cell carcinoma, adenosquamous carcinoma, and oat cell carcinoma. Well-differentiated adenocarcinomas recapitulated the ultrastructure of the normal surface epithelium of the gallbladder. Although columnar cells predominated, the narrow and dark-staining pencil-like cells were also present. The former appeared immature and secreted more mucin than normal columnar cells. Microvilli with long dense core rootlets were seen in one tumor. The most characteristic ultrastructural features of the signet ring cell carcinoma were the multiple mucin vacuoles and the intracytoplasmic lumina some of which appeared cystically dilated. Adenosquamous carcinomas were composed of four different cell types. Well-differentiated adenocarcinomas and adenosquamous carcinomas showed in addition a few endocrine cells similar to these seen in the human gallbladder mucosa in association with intestinal metaplasia. Oat cell carcinomas contained neurosecretory granules but also exhibited glandular markers. Electron microscopy seems the most reliable method for the identification of oat cell carcinomas.

Primary malignant melanomas of the gallbladder are rare lesions that have been the subject of debate. Only 11 such cases have been reported. The debate is reviewed and conflicting opinions of workers in the field are discussed. Attention is drawn to some of the features that are said to characterize the lesions presumed to be primary melanomas of the gallbladder, such as polypoid growth, "junctional" changes in the normal mucosa, and, above all, absence of other demonstrable primary foci of malignant melanomas. What at first appeared to be the 12th case of this rare entity, and in the youngest patient at that, is now described by light and electron microscopy, but a more likely possibility, supported by biopsy of the skin, is that an undiagnosed malignant melanoma in the skin had undergone complete regression after it had metastasized to the gallbladder.

A case of leiomyosarcoma of the gallbladder in a 55-year-old woman is presented. The definitive diagnosis of leiomyosarcoma according to the histologic structure of the tumor was made by electron-microscopic study. Ultrastructure of this tumor type is characteristic of presence of myofilaments and cytoplasmic vesicles in the cytoplasm.

Papillomatous transformation of the gallbladder was found in a patient with metachromatic leukodystrophy who presented with an abdominal mass. Cholecystectomy was performed, and involvement of the gallbladder was confirmed by metachromatic stains and electron microscopy.

A case of granular cell myoblastoma of the gallbladder in a 39-year old Japanese female is presented. Granular cell myoblastomas arising in the biliary tract are a rare occurrence. This tumor has not yet been reported in the gallbladder.

Among 448 malignant epithelial tumors of the gallbladder, 19 were classified as oat cell carcinomas. Seventeen cases occurred in elderly women. Eighteen of the patients had cholelithiasis. The neoplasms were highly lethal, metastasizing early and causing death shortly after diagnosis. All 19 patients died as a direct result of the tumors, with liver, regional lymph node, and/or lung metastases. Combination chemotherapy produced objective responses in two patients, the longest survivors of the series (11 and 13 months). The salient morphologic features of oat cell carcinomas of the gallbladder include large size at the time of diagnosis, extensive necrosis, and propensity for submucosal growth. Histologically, these tumors are composed of variable proportions of two cell types, round and fusiform, arranged in solid sheets, cords, or festoons. In areas of necrosis, the deposition of DNA in vessel walls is seen occasionally. Four tumors contained neoplastic glands similar to those present in well-differentiated adenocarcinomas of the gallbladder. These tumors were considered to be a combined form of oat cell carcinoma. With the use of immunoperoxidase stains, focal carcinoembryonic antigen reactivity was demonstrated in three of 11 tumors. Electron microscopic examination revealed neurosecretory granules. Morphologically, these tumors resembled the oat cell carcinomas that occur at other sites.

Carcinomas of the gallbladder with pleomorphic spindle cell histology are unusual. We report such an occurrence in a 47-year-old male with a neoplasm showing both a mixed squamous and a pleomorphic spindle cell pattern. Ultrastructural studies supported the likelihood that this lesion represented a pleomorphic carcinoma and revealed unique paracrystalline structures intimately associated with tonofilaments. For this reason we believe that this and some other previously diagnosed sarcomas and carcinosarcomas of the gallbladder are in reality poorly differentiated carcinomas of either adeno, squamous, or mixed type. This illustrates the need for critical ultrastructural assay to determine the nature of poorly defined and differentiated neoplastic growths.

A human gall bladder carcinoma cell line was established from ascites of a patient of peritonitis carcinomatosa. The pathological diagnosis of this patient was adenocarcinoma tubular ++, moderately differentiated. This cell line was composed of polygonal, spindle and round shaped cells. Each cell types were cloned by single cell cloning technique and each cloned cell secreted CEA or Ferritin or none of them. The doubling time of cell number was 48 hours, and plating efficiency was 14-19%. NOZ cell was transplantable to nude mouse. The morphological feature of transplanted tumor was similar to the original one.

An ultrastructural study of the cell surface of lumen-forming tumors was carried out to determine the distribution of two morphologic markers seen in relation to the microvilli. These are membrane-bound glycocalyceal bodies and microvillous filament cores that penetrate the underlying cytoplasm as rootlets. They were found (especially when in combination) to be valuable in identifying tumors of what is referred to as intestinal-type epithelium, and could be seen in cases in which brush borders were absent. They have been demonstrated in intestinal-type carcinomas of the stomach and gallbladder, in adenocarcinomas of the small and large intestines and pancreatic ducts, in mucin-forming bronchiolar carcinomas, and in certain mucinous ovarian and endocervical tumors. Other tumors, whether mucin-producing or not, have been found to consistently lack these structures.