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Background: A broad papillary proliferation resembling that in transitional cell carcinoma (TCC) of the urinary bladder was seen in 12 of 21 primary carcinomas of the Fallopian tube (PCFT)., Methods: According to their predominant histologic pattern (more than 50%), PCFT were classified into 9 TCC-predominant and 12 non-TCC-predominant tumors. The two groups were compared by clinicopathologic, histochemical, and immunohistochemical means., Results: TCC-predominant tumors were grossly solid and microscopically demonstrated more frequent tumor necrosis and spindled tumor cells than non-TCC-predominant tumors. Mucin histochemistry revealed a correlation between TCC-predominant tumor and sulfomucin-predominant secretion and between non-TCC-predominant tumor and sialomucin-predominant secretion. Immunohistochemical studies for cytokeratins, vimentin, epithelial membrane antigen (EMA), Leu-M1, carcinoembryonic antigen (CEA), and CA 125 were not useful for discrimination between the two groups. Both groups showed similar features in patient age, clinical stage, cytology of ascites or peritoneal washing, and serum CA 125 level. Despite the similarity in treatment (surgery and postoperative chemotherapy) between the two groups, TCC-predominant tumors tended to relapse later (mean, 31.2 months after diagnosis) than non-TCC-predominant tumors (mean, 14.4 months after diagnosis), resulting in a significant difference in the 2-year disease-free survival rate., Conclusions: TCC pattern and non-TCC pattern are considered to be worthy of distinction in PCFT.

Background: Malignant fibrous histiocytoma (MFH) of bone is a rare bone tumor, and its prognosis has been controversial., Methods: Thirty-four patients with MFH of bone were examined clinicopathologically for prognostic factors., Results: The most common skeletal site of the tumor was the femur (15 cases), followed by the pelvic bones (6 cases), tibia (5 cases), and fibula (5 cases). Of 29 patients available for follow-up, the 5-year survival rate of 17 who underwent adequate surgical treatment was 63%. The 5-year survival rate of the remaining 12 patients, including 5 with MFH of the pelvic bone who received inadequate or palliative surgery, was 17%. All six patients who received intensive chemotherapy combined with adequate surgical treatment were alive and well 5 years after the initial treatment. Histologically, the presence of desmoplasia and chronic inflammatory infiltration in the tumor tended to be prognostic indicators, although not to a statistically significant extent. Patients whose tumors contained wide areas of desmoplasia had a worse prognosis (5-year survival rate, 20%). In contrast, those with a prominent chronic inflammatory infiltrate had a 5-year survival rate of 78%., Conclusions: These histologic variables would be helpful for predicting the prognosis of MFH of bone. Adjuvant intensive chemotherapy combined with adequate initial surgery may effect a clinical cure.

Background: Gastric carcinoma is clinicopathologically divided into differentiated and undifferentiated types. The former is grossly protuberant and often causes hematogenous metastasis to the liver or lung, whereas the latter is mostly depressed or ulcerated from its early stage and rarely causes blood-borne metastasis. The purpose of this study is to clarify the microvascular architecture of early gastric carcinoma with reference to the histologic subtypes., Methods: A silicone rubber compound (Microfil) injection method with a methyl salicylate clearing technique was used in 32 resected early gastric carcinomas. The microvascular architecture was observed both in the carcinoma and its surrounding noncancerous tissue in each specimen under a stereomicroscope and light microscope., Results: Compared to the surrounding normal mucosa, the differentiated carcinomas (DC) mostly were hypervascular (24%) or normovascular (65%), whereas the undifferentiated carcinomas (UC) often were hypovascular (60%). Irregularity of tumor vessels (67%) and an arcade-like appearance (33%) was encountered frequently in UC, whereas hypervascularity of the surrounding noncancerous mucosa (29%) often was noticed in DC. Quantitative analysis, including vascular volume, mean vascular diameter, and cut section area, supported these differences between DC and UC., Conclusions: The results suggest that vascular structures of gastric carcinomas are characteristic with regard to their histologic subtypes; DC is normovascular or hypervascular, whereas UC is hypovascular.

Background and Methods: A univariate and multivariate analysis for the correlation between histomorphologic factors and prognosis was made using data from 1116 patients with soft tissue sarcoma, including 1005 cases available with complete histologic and follow-up data., Results: The overall 5-year survival rate was 43.6%. The univariate analysis using Kaplan-Meier survival curves showed that tumor differentiation, cellularity, nuclear atypia, cellular pleomorphism, mitotic activity, amount of fibrous stroma, extent of myxoid areas, extent of tumor necrosis, and histologic grading (determined by the estimated range of malignancy for each type of sarcoma using a reported guideline) were all significant prognostic factors in the overall soft tissue sarcoma group. By a multivariate analysis using a procedure based on the Weibull model to failure data, the histologic grading and extent of tumor necrosis were proved to be prognostically significant in the overall sarcoma group. However, after additional analysis on each histologic type of sarcoma, it was determined that both tumor necrosis and histologic grading were applicable in only two types: malignant fibrous histiocytoma and leiomyosarcoma. Liposarcoma, synovial sarcoma, and malignant schwannoma each also showed some determinable factor of prognostic significance., Conclusions: It was concluded that there seemed to be no single universal prognostic parameter that could be applied to each soft tissue sarcoma type. These results suggest that the predictive significance of the various histologic parameters should be based on each specific type of sarcoma.

Background: Despite perpetual efforts of investigators, the histogenesis of retinoblastoma is still in dispute and histologic classification satisfactorily predictive of prognosis does not seem to be in use., Methods: The authors studied 88 cases of retinoblastoma clinicopathologically and immunohistochemically, paying special attention to the presence of a "bipolar-like cell" element that would be used as one of the criteria for the diagnosis of differentiated retinoblastoma., Results: Twelve cases of retinoblastoma with the bipolar-like cell element in the absence of rosettes and 41 cases of the tumor with rosettes were classified as differentiated retinoblastomas. The other 35 cases without rosettes or bipolar-like cells were classified as undifferentiated tumors. Tumor cells forming rosettes usually had positive results for synaptophysin and neuron-specific enolase (NSE) and negative results for glial fibrillary acidic protein (GFAP) and S-100 protein; however, undifferentiated cells had negative results for these four antibodies. The bipolar-like cells had positive results for synaptophysin and NSE but negative results for GFAP and S-100 protein. Twelve tumors with bipolar-like cells that lacked rosettes showed no optic nerve invasion, and the patients had a significantly better prognosis (100% 5-year survival rate) than 35 patients with undifferentiated tumors (71% 5-year survival rate) (P < 0.01)., Conclusions: The findings support a neuronal origin of the tumor and indicate that, not only the rosettes symbolizing the photoreceptor differentiation, but also other neuronal elements, such as bipolar-like cells, can be used as criteria for histologic classification of retinoblastoma.

Background: Despite recent advances in diagnosis and treatment, gastric carcinoma remains a major cause of death in the world., Methods: The clinicopathologic profile of 10,000 consecutive patients who underwent primary gastrectomy during 1962-1989 were reviewed and prognostic factors influencing survival in those with gastric carcinoma were analyzed in 7031 patients., Results: Incidence of gastrectomy for carcinoma has increased steadily and the rate of early carcinoma exceeded that of advanced carcinoma in the recent period of 1985-1989. Five-year and 10-year survival rates were 46.1% and 35.2% in 3868 patients with advanced carcinoma, and 88.8% and 77.3% in 3163 patients with early carcinoma, respectively. In patients with advanced carcinoma, significantly poorer survival rates were noticed for patients older than 70 years of age, those who underwent total gastrectomy, tumors involving the entire stomach or greater than 10 cm in diameter, a macroscopic diffusely infiltrative pattern, adenosquamous histologic type, positive surgical resection margins, or lymph node metastasis. None of the above poor prognostic features were identified in patients with early gastric carcinoma group except for those older than 70 years of age. Although lymph node metastases were present in 10% of early gastric carcinomas, this feature did not impart a poor prognosis. Patients with advanced carcinoma grossly resembling an early carcinoma had an intermediate prognosis, suggesting the existence of a developmentally midstage lesion between early and advanced carcinoma., Conclusions: The study illustrates that the most important role for clinicians treating with gastric carcinoma should be early detection and aggressive surgery for resectable tumors, followed by detailed pathologic examination.

The clinicopathologic and immunohistochemical features in 120 cases of gastrointestinal stromal tumor (GIST) were reviewed. Excluding 24 cases of gastric schwannoma, 96 cases of GIST consisting of 62 benign tumors and 34 sarcoma (low grade, 17; high grade, 17), with 9 cases arising in the esophagus, 57 in the stomach, 28 in the small intestine, and 2 in the colon, were studied. All esophagus and colon tumors were benign and resembled a conventional leiomyoma histologically. However, the gastric and small intestine benign tumors mostly showed histologic features of cellular or epithelioid leiomyoma. Immunohistochemically, desmin caused a positive reaction in all esophagus and colon tumors, but only 26% of gastric and small intestine tumors. However, muscle-specific actin (HHF35) caused a positive reaction in most GIST (92%). The 10-year survival rates of the patients with gastric sarcoma and those with intestinal sarcoma were 74% and 17%, respectively. These results showed that histologic and immunohistochemical features were distinctly different, depending on the location in the gastrointestinal tract; that most GIST, excluding schwannoma, had smooth muscle differentiation; and that sarcomas had a more favorable prognosis when they occurred in the stomach rather than the intestine.

The histogenesis of malignant fibrous histiocytoma (MFH) is controversial. To elucidate the cellular origin and characteristics of this neoplasm, the authors analyzed cell lines grown from 17 patients (15 soft tissue MFH and 2 bone MFH) by using light and electron microscopy, immunocytochemistry, enzyme cytochemistry, and functional tests for receptors for the Fc portion of immunoglobulin (Fc receptors) and immunophagocytosis. Each culture exhibited a storiform/pleomorphic pattern with mixed cellular populations consisting of spindle cells, polygonal cells, and bizarre giant cells; these morphologic features corresponded to the histologic characteristics of the primary tumors. The cells in each MFH line displayed histiocytic functional markers such as lysosomal enzymes, Fc receptors and immunophagocytosis. However, these cells differed from monocyte-derived macrophages (histiocytes) in immunoreactivity; the MFH cells expressed a mesenchymal antigen (FU3) distributed among perivascular cells and fibroblasts but demonstrated no positive reactions with Leu-M1 (CD15) and Leu-M3 (CD14), which recognize the cells of the monocyte-macrophage lineage. In conclusion, these findings suggest that MFH is not a tumor of true histiocytes but of facultative histiocytes showing mesenchymal differentiation in vitro. Chromosomal analysis performed in one MFH line demonstrated abnormal karyotypes; the modal chromosome number was 58, with 5 marker chromosomes.

For 52 patients with depressed adenomas of the stomach, histopathologic studies were done on 56 tumors and for 43 of them, histochemical and immunohistochemical features were examined. In addition, nondepressed adenomas (n = 57) and the depressed type of early gastric adenocarcinomas of the well-differentiated variety (n = 44) were studied as the controls. Depressed adenomas in the majority (73%) involved the entire thickness of the mucous membrane of the stomach with tubules of atypical epithelium, presenting a severe grade in many of the cases (41%). Paneth's cells were found in cases of a depressed adenoma, in significantly higher percentages (61%) than in those with a nondepressed adenoma (P less than 0.01). The frequency of cases with argyrophil cells was also higher in depressed adenoma (63%) than in nondepressed adenoma (36%) or in cases of early gastric carcinoma (32%). Carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 were noticed in tumor cells, immunohistochemically in 28% of the cases with depressed adenoma, the frequency being intermediate between cases of a benign nondepressed adenoma (6% for both CEA and CA 19-9) and cases of early gastric carcinoma (71% for CEA and 66% for CA 19-9). No difference was noticed in lectin reactivity and mucin content between depressed and nondepressed adenomas, whereas tumor cells in the early depressed carcinoma had a higher lectin reactivity and less mucin content than those seen in the adenomas. It would thus appear that depressed adenoma is a benign neoplastic lesion; however, the malignant potential of this lesion is somewhat higher than the nondepressed counterpart, as indicated by the immunoreactivity to tumor markers and follow-up results reported by colleagues previously.

Endoscopic biopsy specimens of the gastric mucosa from 13 patients who were found at follow-up examination to have gastric carcinoma were compared for abnormal histologic features, type of intestinal metaplasia, and presence of immunoreactive carcinoembryonic antigen (CEA), with specimens from 40 tumor-free controls. Villus-like changes and angular infolding, cytologic nuclear pleomorphism, distinct nuclear border, irregular thickness of the nuclear membrane, irregular chromatin clumping, prominent nucleoli, and distinct nucleoli were manifestations of the carcinoma group. Angular infolding, distinct nuclear border, irregular thickness of the nuclear membrane, and distinct nucleoli were also observed in the latent stage before detection of carcinoma. The individual features, however, lacked specificity. Histochemically, a IIB subtype of intestinal metaplasia, and immunoreactive CEA in the cytoplasm of foveolar epithelium appeared exclusively in the patients with carcinoma. These findings indicate that the gastric epithelium of patients with gastric carcinoma tends to be morphologically and histochemically abnormal even before the recognition of classical dysplasia. This can be described as abnormal epithelium and is believed to provide the soil on which gastric carcinoma develops.

This clinicopathologic study concerns 27 cases of "dedifferentiated" soft tissue sarcoma (DSTS), including 14 liposarcomas, six leiomyosarcomas, five chondrosarcomas, and two rhabdomyosarcomas. In addition, the authors conducted an immunohistochemical survey of 23 cases and an electron microscopic examination of three. The findings were compared with observations of 32 cases of de novo malignant fibrous histiocytoma (MFH). All tumors contained additional distinct anaplastic portions indistinguishable from MFH under conventional light microscopy, ultrastructurally, and in cases of immunoreactivity for alpha-1-antichymotrypsin and alpha-1-antitrypsin and on lectin histochemical findings for ricinus communis agglutinin and concanavalin agglutinin. The desmin reactivity present in anaplastic portions of 14 DSTS and in eight de novo MFH is taken to mean that myofibroblasts are present in these tumors. The anaplastic components of DSTS are presumed to represent the proliferation of another clone of undifferentiated mesenchymal cells that fail to differentiate along any specific lineage other than fibroblast-like cells, histiocyte-like cells, and myofibroblasts. Nineteen patients died of tumor and four are alive and well 1.6, 1.7, 2.1, and 5.2 years after the initial treatment, respectively.

Sixty-three gastrectomy specimens (21 with early intestinal type carcinoma, 21 with early diffuse carcinoma, and 21 with benign nonneoplastic lesions) were examined histochemically to determine the distribution of intestinal metaplasia (IM), particularly the sulphomucin-secreting type (Type IIB IM). The frequency and distribution of Type IIB IM were similar, irrespective of the disease, when age of the patient was matched and if the extension of the IM was similar. Type IIB IM was usually observed in the mucosa along the lesser curvature of the lower portion of the stomach, particularly in elderly patients and was mainly located in the deeper foveolae and intermingled with or transient to those in other types of IM. These findings suggest that a casual relationship between Type IIB IM and intestinal type carcinoma is dubious.

The authors examined the localization and behavior of beta-human chorionic gonadotropin (HCG)-positive cells in human gastric noncancerous mucosa and in gastric malignant tumors, using immunohistochemistry and the anti-beta-HCG antibody. The beta-HCG-positive cells were located mainly in the antral mucosa and were generally restricted to the neck portion of the pyloric glands, although a few were present in fundic glands of the gastric body. The beta-HCG-immunoreactive cells were found in gastric carcinomas in 53% of the 92 cases examined. These cells were observed more often in advanced carcinomas that were histologically poorly differentiated than in early carcinomas or in well-differentiated tumors, but this prevalence had no statistical significance. The presence of the beta-HCG-positive cells in the gastric carcinomas suggested no appreciable prognostic significance, even quantitatively. In the syncytiotrophoblast-like tumor cells seen in four gastric tumor samples with histologic features of a choriocarcinoma, immunoreactivity to the beta-HCG was striking. There was, however, no recognizable dominance in the number of beta-HCG-reactive cells in the noncancerous mucosa around the tumor.

Eighty-six cases of advanced gastric carcinoma simulating early gastric carcinoma were studied clinicopathologically. Cytophotometric DNA analysis was also performed in 33 cases. Most of these particular carcinomas were of the depressed type on gross inspection. Histologically, the tumors were of diffuse type in 60%. The rate of the carcinomas restricted to within the muscularis propria was 48% and high in comparison with those in conventional advanced gastric carcinomas. There were four main growth patterns: small invasion type (Type A, 43 cases), ulcer-connected type (Type B, 19 cases), vessel permeation type (Type C, six cases), and diffusely infiltrative type (Type D, 13 cases). There was a relationship between growth patterns, lymph node metastasis, and prognosis: Types A and B had a small percentage of lymph node metastasis and a good prognosis, whereas Types C and D a high percentage and a poor prognosis. DNA analysis revealed that two thirds of the examined cases showed a low ploidy pattern. The DNA ploidy patterns were concerned with the tumor growth pattern: high-ploidy cases were rarely seen in Types A and B yet were frequent in Types C and D. The 5-year survival rate was 73%, but results were poor in cases of tumors with blood vessel permeation, in those with lymph node metastasis, in those with the Type D or C growth patterns, and in those with high DNA ploidy pattern. Since these carcinomas can be understaged endoscopically and by gross examination, a precise study of the surgically excised tissues will aid in making an accurate prognosis.

Five hundred sixty-two cases of angioleiomyoma in our files on soft tissues were reappraised clinicopathologically. There was a preponderance in females with a ratio of 1.7:1. The angioleiomyoma could be separated into three histologic subtypes: capillary or solid (374 cases), cavernous (61 cases), and venous (127 cases) types. Five hundred (89%) occurrences were in the extremities, 48 in the head, and only 14 in the trunk. The tumors caused pain and/or tenderness in 327 cases, in which 262 were of the solid type. In 16 cases, small groups of mature fat cells were demonstrated within the tumor, suggesting the hamartomatous nature of these smooth muscle tumors.

The autopsies of three cases of esophageal anaplastic carcinoma with an oat cell pattern are presented. Grossly, each case revealed a fungating growth and showed extensive metastases all over the body. The histology bears a striking resemblance to that of oat cell carcinoma of the lung, occasionally showing rosette formation, mucin secretion, and intracytoplasmic argyrophil granules in each case. These peculiar carcinomas most probably were derived from the esophageal submucosal glands. They were composed of both a cell group of argyrophil variety and a group of mucus-secreting variety which may have originated from the more primitive cells capable of differentiation into either variety.

Modes of cancer growth and DNA ploidy were studied in 66 patients with mucosal carcinoma of the stomach. The modes of growth were classified into five histologic patterns; elongated tubular (three patients), expansive (18 patients), tubular and solid (14 patients), carcinoma in situ (10 patients) and infiltrative (21 patients). In every patient, all or most lesions with elongated tubular, expansive, and carcinoma in situ growths were located in the pyloric gland area of the stomach, and were less than 4 cm in diameter. Histologically, the adenocarcinomas papillary or well-, or moderately differentiated. Most lesions with an infiltrative growth were located in the intermediate pyloric and fundic glands areas, depressed in gross appearance, and composed of poorly differentiated glandular or signet ring tumor cells. The lesions with a tubular and solid growth were present in the pyloric gland or intermediate area, and were classified as well-, moderately, or poorly differentiated adenocarcinoma. All lesions with an elongated tubular, tubular and solid, and carcinoma in situ growths, and most lesions with an infiltrative growth showed a narrowly restricted DNA distribution (Type I or II), while most lesions with an expansive growth had mostly a widely scattered DNA distribution (Type III), representing a higher malignant potential.

Twenty-eight cases of primary adenosquamous carcinoma (ASC) of the stomach were studied clinicopathologically. These cases were classified into two types, 16 with differentiated type adenocarcinomatous component (DAC) and 12 with undifferentiated type adenocarcinomatous component (UAC), according to the degree of glandular formation of the adenocarcinomatous elements. A large number with adenocarcinomas, including 131 with differentiated type and 133 with undifferentiated type, were studied as controls. As a consequence, with respect to biologic behavior, ASC with DAC was similar to the differentiated type adenocarcinoma, and ASC with UAC to the undifferentiated type adenocarcinoma. Accordingly, the behavioristic feature of ASC seemed to be governed by the adenocarcinomatous component. Histologically, a close relationship between neoplastic adenomatous and squamous components was evident in the intermingling areas, thereby suggesting a transition of both elements. In addition, a mucoepidermoid pattern was occasionally detected in the squamous component. Judging from the biologic behavior and histologic findings, the majority of ASC probably derives from the squamous metaplasia in an adenocarcinoma. The prognosis of ASC was less favorable than that of adenocarcinoma because of the more extensive tumor depth and higher frequencies of lymphatic and vascular permeations of the carcinoma cells.

This clinicopathologic study concerns 63 instances of glomus tumor of the soft tissues. The tumors occurred at different ages but were more common in earlier adult life and most commonly occurred on the fingers (35 cases), frequently as subungual nodules (26 cases). Other sites of occurrence were the forearm in seven, the knee in seven, and the leg in six. All patients but one complained of pain. Histologically, the tumors, showing endothelium-lined vascular spaces surrounded by masses of epithelioid cells, could be divided into three varieties: vascular (29 cases), myxoid (23 cases), and solid (11 cases). Under electron microscope the tumor cells in four cases proved to be smooth-muscle cells. The clinicopathologic evidence presented supports the hypothesis that the glomus tumor is a tumor-like lesion of mesodermal disorder rather than a true neoplasm.

Tissue samples from 103 patients with gallbladder carcinoma were examined, using 5-mm stepwise tissue sections. Three pathologic stages were used: Stage I; carcinoma invading not further than the muscle coat of the gallbladder, with or without extension along Rokitansky-Aschoff sinuses in the subserosa (11 cases); Stage II, carcinoma extending to the subserosal fibroadipose tissue of the gallbladder (73 cases); and Stage III: carcinoma invading the adjacent organs such as the duodenum, liver, and colon (19 cases). In the 11 patients with Stage I carcinoma, there was no apparent lymph node metastasis and all remained well for 3 months to 14 years after the initial operation. The cumulative 3-year survival rate of Stage I (100%) was significantly higher than of Stage II (40%) and Stage III (10%) (P less than 0.01, P less than 0.001). The Stage I tumors, therefore, can be defined as early carcinoma of the gallbladder. Dysplastic epithelium was seen in the mucosa adjacent to the malignant lesion in 57% of those with gallbladder carcinoma: 73% in Stage I, 59% in Stage II, and 42% in Stage III. Nine gallbladders had multiple foci of adenocarcinoma in a background of a diffuse dysplasia. Immunohistochemical study for carcinoembryonic antigen and carbohydrate antigen 19-9 resulted in positive staining of the dysplastic epithelial element adjacent to the invasive carcinoma and, in a similar fashion, in the carcinoma itself, thereby indicating a close relation between the epithelial dysplasia and adenocarcinoma of the gallbladder.

A 14-year-old girl with numerous café-au-lait spots in her skin was hospitalized because of fever, weight loss, and a mass of the right upper quadrant of the abdomen. Despite intensive chemotherapy, she died 6 months after admission. The autopsy revealed a right adrenal tumor with metastases to liver, lungs, vertebrae, and lymph nodes. Histologically the tumor was a pheochromocytoma with small foci of ganglioneuroblastoma. The catecholamine contents of the tumor were markedly elevated, as confirmed by the catecholamine fluorescence technique. Electron microscopically, the tumor cells contained intracytoplasmic membrane-bound chromaffin granules of varying sizes and shapes. This may be the first report of the concomitant occurrence of malignant catecholamine-secreting pheochromocytoma with ganglioneuroblastoma elements in a patient with von Recklinghausen's disease.

Cell cultures were carried out from fresh tumor tissues obtained from seven cases of histiocytic tumors of the soft tissues including four of malignant fibrous histiocytoma, two of benign fibrous histiocytoma, and one of giant cell tumor of tendon sheath. The cultured cells were studied by light and electron microscopy, rosette formation for surface receptors, immune phagocytosis, and enzyme cytochemistry. The culture of each tumor revealed a mixture of histiocyte-like cells, fibroblast-like cells, amd intermediate forms. Bizarre giant cells were numerous in the early cultures of malignant fibrous histiocytoma, but they were absent in the cultures of benign fibrous histiocytoma and giant cell tumor of tendon sheath. In all the seven cases the cultured cells exhibited several features characteristic of histiocytes: (1) surface receptors for the Fc-portion of immunoglobulin G; (2) surface receptors for the third component of complement; (3) immune phagocytosis of opsonized erythrocytes; and (4) lysosomal enzymes including alpha-naphthyl butyrate esterase, and acid phosphatase. These findings suggest that the histiocytic tumors of the soft tissues in discussion actually comprise the cells that have the functional property of histiocyte. The tumor cells in the surgical specimens presented essentially the same ultrastructural and enzyme histochemical characteristics as those of the cultured cells.

Three cases of infantile digital fibromatosis were studied by electron microscopy, enzyme histochemistry, and tissue culture. The tumors were made up equally of myofibroblasts containing electron-dense inclusions which were composed chiefly of microfilaments measuring about 5 to 7 nm. Dense bodies usually observable in the smooth muscle cells were found in the bundles of these microfilaments and in the process of the inclusions, suggesting that these inclusions may represent an abnormal accumulation of contractile protein in the cytoplasm of tumor cells. Two cell lines were established from culture of the tumor cells, and the cultured cells also contained inclusion bodies showing the same morphologic characteristics as those of the original tumor cells. Lysosomal enzymes were abundant in the cultured cells, but they were scant in the cells of the fresh tissue specimens. Cocultivation of the cultured cells with human embryonic lung cells yielded no cytopathic effect.

Cell cultures were carried out from four patients with infantile digital fibromatosis. The cultured cells, which contained cytoplasmic inclusions identical to those of the original tumor cells, possessed cortical bundles of microfilaments, rich network of granular endoplasmic reticulum, and well-developed Golgi complex. To demonstrate the distribution of actin filaments in the cultured cells, the heavy meromyosin-binding method was applied to saponin-treated cells from one of the four patients. The microfilaments constituting the inclusions as well as the cortical bundles were decorated with heavy meromyosin, presenting the "arrowhead complexes" specific for actin filaments. The inclusion may represent abnormal contraction of actin filaments in the cytoplasm of myofibroblasts.

A clinicopathologic study was done of 21 cutaneous, sarcoma-like lesions previously diagnosed as atypical fibroxanthoma, spindle cell carcinoma, or dermal sarcoma. These lesions were most commonly presented as a solitary, often ulcerated nodule, occurring on exposed skin of the face in the elderly or, occasionally, on roentgen-damaged or burnt skin of the head, leg, or hand. Microscopic features of the 21 lesions were, however, not alike, thereby implying that such sarcoma-like lesions had derived from heterogeneous origins. The immunohistochemical staining in a comparative study with two other cases of unequivocal spindle cell squamous carcinoma suggested that these lesions could be histogenetically divided into two different groups: (1) the major group of true atypical fibroxanthoma, consisting of 19 cases, and (2) the minor group of probable spindle cell squamous carcinoma, consisting of 2 cases. Despite a wide histologic spectrum and of heterogeneity of these lesions, there was a benign clinical course in the majority, due in part to the small size and superficial location of the lesions.

This clinicopathologic study concerns 25 cases of leiomyosarcoma of the external soft tissues, including an immunohistochemical survey of 19 cases and an electron microscopic examination of six. There was a female preponderance in a ratio of 16:9. The most common site of tumors was the thigh (nine cases), followed by the knee (five cases). Three tumors were located in the dermis, 9 were confined down to the subcutis, 2 involved the deep fascia, and 11 involved the skeletal muscle. Superficially located tumors were smaller than deeply located ones. According to the predominant histologic features, the tumors were classified into well (6), moderately (14), and poorly (5) differentiated. In addition to the classical microscopic features, dedifferentiated areas resembling malignant fibrous histiocytoma were noted in three primary tumors and one recurrent tumor. In six tumors, the anatomical location and histologic features were highly suggestive of leiomyosarcoma arising in the venous wall. Many tumor cells immunoreactive for actin were seen in 13 and for desmin in 9 of the 19 cases. Four tumors contained a few tumor giant cells positive for alpha-1-antichymotrypsin. Ultrastructurally, the tumors were characterized by smooth muscle tumor cells showing a spectrum of differentiation of varying degrees. In two cases, histiocyte-like tumor cells were detected. The most reliable prognostic parameter was the depth of the initial tumors; all patients with a leiomyosarcoma confined down to the subcutis are living, most of them more than 5 years after excision, whereas seven of the nine patients with a tumor involving the muscle have died within 5 years after excision.

Sarcoma of the chest wall following postoperative radiation therapy (2500 rads) for breast carcinoma is presented; it appeared 16 years after the initial radiation, and had light and electron microscopic features of malignant fibrous histiocytoma (MFH). Unique ultrastructural finding was the presence of Langerham cell granules in some of the tumor cells. This appears to be the first documented instance of a soft tissue MFH containing such granules in the tumor cells.

A "depressed adenoma" was detected in surgically removed stomachs. There were 40 such lesions (11%) of a total of 357 lesions of gastric adenomas. Macroscopically, these lesions often occurred along the lesser curvature of the stomach, had shallow depressions of a light-brown color, a round or oval shape with irregular margins, and could hardly be distinguished from a depressed early carcinoma. Although 14 of the lesions were detected preoperatively with confirmation by endoscopic biopsy, the other 26 remained unrecognized until the gross examination of the formalin-fixed specimens. Histologically, all were tubular adenomas of the intestinal type with varying degrees of epithelial atypia. Carcinoma in adenoma was present in 5% of these depressed lesions, in contrast to 2.5% of the conventional protruded adenoma. Thus, depressed adenoma seems to be a variant of gastric adenoma which has a somewhat higher malignant potential.

Gastric tissues from 85 patients with advanced carcinoma were studied immunohistochemically for localization of carcinoembryonic antigen (CEA), secretory component (SC) and alpha-fetoprotein (AFP), and for S-100 protein-positive cells. Our objective was to determine if these factors could serve as prognostic indicators. Forty patients died of recurrence or metastases within 2 years (Group I), and the remaining 45 survived 10 years or longer (Group II) after resection. CEA-positive cells were present in 93% and 89% of Groups I and II, respectively. In case of staining for CEA, positive results were seen not only in the malignant cells but also in the stroma in 35% of Group I but none in Group II. The immunohistochemical status of SC was not essentially different between Groups I and II; the positive staining was recognized in 50% and in 57%, respectively. Gastric carcinomas rarely reacted to AFP. S-100 protein-positive cells, which play an important role in local immunity, were often present in Group II (47%) but rarely in Group I (10%). Thus, in addition to the various prognostic factors available to the surgical pathologist, the presence of CEA and the appearance of S-100 protein-positive cells in tumor tissue will aid in predicting the prognosis of patients with advanced gastric carcinoma.

A clinicopathologic study was done of four cases of hepatoblastoma with precocious puberty, together with an analysis of 21 such cases reported in the literature. All four patients were males, the age ranging from 11 to 35 months. Three of the four patients died within 12 months after operation, but the fourth is living. Histologically, all patients had a hepatoblastoma with the coexistence of both fetal and embryonal type cells, although predominantly fetal in two and predominantly embryonal in the other two. Tumor giant cells were rarely encountered in all these cases. Both alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) in the serum or urine increased in our four cases and in five other cases reported in the literature. Though the serum AFP level paralleled the severity of clinical symptoms, the serum or urine hCG did not necessarily correspond to the clinical course. It is likely that these poorly prognostic virilizing hepatoblastomas secrete two different tumor markers, AFP and hCG, from different cells, and that these functioning tumor cells may not always exist concurrently in the recurrent or metastatic tumor.

This clinicopathologic study concerns 17 cases of intramuscular myxoma, including an immunohistochemical survey of 10 cases and an electron microscopic examination of 4. There was a female preponderance in a ratio of 14:3. The most common sites of tumors were the large muscles of the thigh (seven cases), followed by those of the buttock (three) and the lower leg (three). The size of the tumor ranged from 1.5 to 20 cm (median, 6 cm) in the greatest diameter. Neither recurrence nor metastasis was seen in any of 15 patients for whom information was available. In addition to the conventional microscopic features, such as hypocellularity, absence of a plexiform capillary network, and no detection of typical glycogen-rich lipoblasts, the following findings were regarded as helpful to differentiate an intramuscular myxoma from myxoid liposarcoma: hypovascularity of the tumor, demonstrated by angiography; a homogeneous computed tomography appearance with low density, absence of S-100 protein immunoreactive cells such as lipoblasts; and electron microscopically, the constituent cells were predominantly fibroblast-like cells with a prominent secretory activity, together with a small number of primitive mesenchymal cells and histiocyte-like cells, but with no lipoblasts. After simple excision, the 15 patients who could be followed are well with no recurrence during various periods of follow-up.

A review of 195 patients with carcinoma of the esophagus disclosed 41 cases (21.0%) with glandular and/or mucus-secreting components, in addition to the ordinary component of squamous cell carcinoma. These tumors could be grouped into three types according to representative histologic features of glandular and mucus-secreting portions: glandular type (23 cases), cribriform type (11 cases), and mucoepidermoid type (7 cases). The histologic features of the three types were reminiscent of those of adenocarcinoma, adenoid cystic carcinoma, and mucoepidermoid carcinoma of salivary glands, respectively. Moreover, areas showing glandular or mucus-secreting differentiation were in greater part located in the submucosa and the lamina propria mucosae, thereby suggesting that such differentiation had arisen in the esophageal glands or their ducts. In all 41 cases, the ordinary element of squamous cell carcinoma, invasive, or noninvasive, was admixed in various proportions with the glandular components, indicating that this type of esophageal tumor had originated not only from the covering squamous epithelium but also from esophageal mucous-gland or ductal epithelium. The findings also support the concept of the field origin of carcinogenesis in esophageal carcinoma.

Clinicopathologic, enzyme histochemical, and electron microscopic findings in 207 cases (208 lesions) of giant cell tumor of tendon sheath (GCTTS) are presented. The GCTTS could be divided into two groups according to the anatomic location, the first occurring in the digits (digit group, 182 cases) and the second, in the larger joints (large joint group, 25 cases). In the majority of cases of the digit group, the tumor occurred in one of the fingers (158 cases), whereas in the large joint group, the tumor was common in the ankle (10 cases) and knee joints (8 cases). The lesion was more common in women (67%) than in men (33%). Microscopically, the GCTTS in both groups consisted of a mixture of abundant histiocyte-like, foam, and multinucleated giant cells of the osteoclast type. However, worthy of special mention were the large clefts or wide pseudoglandular spaces lined by synovial cells and that were more striking in the large joint group than in the conventional digit group. The component cells had functional properties of macrophages, as determined in the enzyme histochemical study. Electron microscopically, the tumors consisted essentially of histiocyte-like, fibroblast-like, and intermediate cells, together with myofibroblasts.

Two cases of polypoid carcinoma with pseudosarcoma and one of so-called carcinosarcoma of the esophagus are presented. The clinical and morphologic characteristics of these tumors are described and the literature is reviewed. It is postulated that pseudosarcomas and so-called carcinosarcomas belong essentially to the same pathologic entity because of their similar morphologic and biologic aspects. The histogenesis of the sarcoma-like elements of these tumors support the theory of epithelial origin on the basis of the sarcoma-like transformation of squamous cell carcinoma and of the presence of epithelial elements in the "sarcomatous" areas.

A case of dedifferentiated hepatocellular carcinoma with osteoclast-like giant cells resembling those of giant cell tumor of bone is presented. The clinicopathologic findings are described, and the literature concerning this type tumor is reviewed. The tumor differed histologically from a pleomorphic variant of hepatocellular carcinoma in that there were numerous osteoclast-like giant cells with numerous, small, uniform, benign-appearing nuclei. To the knowledge of the authors, there has been only one report of this type of tumor arising in the liver. The tumor contained a separate area of a histologically conventional hepatocellular carcinoma, in addition to the above giant cell areas.

Two extraskeletal myxoid chondrosarcomas with a solid soft tissue mass occurred on the right upper arm of a 4-year-old boy and on the chest wall of a 1-year-old boy. Microscopically, both tumors were characterized by lobular configuration and were sparsely cellular with a background of myxoid matrix. The cells were small and round, and appeared undifferentiated, sometimes with a narrow eosinophilic cytoplasm. They grew in nests or strands and sometimes in a single file. They were strongly positive for S-100 protein and vimentin. Ultrastructural features suggested that the cells had a poorly differentiated mesenchymal nature with chondrocytic differentiation. These are the sixth and seventh reported cases of extraskeletal myxoid chondrosarcoma occurring in children. There are definite differences between this tumor with immature features and the extraskeletal myxoid chondrosarcoma in adults. Problems of differential diagnoses from other small round cell sarcomas also are discussed.

A type of gastric carcinoma was specified under the designation carcinoma with lymphoid stroma. Grossly, this carcinoma was characterized by clear circumscription, usually with a central ulceration. A histologic feature distinguishing this carcinoma was the presence of a nondesmoplastic stroma infiltrated uniformly with an abundance of lymphocytes and plasma cells throughout the entire area of the tumor. Sparse population of less pleomorphic cancer cell nests of thin trabecular, microalveolar, or primitive tubular pattern widely separated by the intervening stroma was another feature peculiar to this tumor. Carcinoma of this type was found in 4% of a total of 1041 cases of gastric carcinoma removed surgically. A high survival rate was noted among the patients undergoing surgery for this carcinoma. A proposal was made on the separate classification of this tumor from common gastric carcinomas.

Among 284 cases of carcinoma of the gallbladder, 21 were identified as undifferentiated carcinoma (UC), with little glandular or other specific epithelial differentiation. These tumors were classified into three histologic types according to the components: (1) small cell type (eight cases); (2) pleomorphic cell type (eight cases); and (3) spindle cell or pseudosarcomatous type (five cases). Histochemical and immunohistochemical study by the immunoperoxidase technique revealed that most of the tumors (13/21) contained mucosubstances, and that all examples of the UC were immunoreactive for epithelial membrane antigen (EMA), keratin, and carcinoembryonic antigen (CEA), thereby indicating the epithelial nature of the neoplastic cells. Vimentin immunoreactivity was found in nine tumors. In 19, the tumor contained various neoplastic endocrine cells, including somatostatin-immunoreactive (14/19), gastrin-immunoreactive (14/19), human chorionic gonadotropin (HCG)-immunoreactive (9/19), pancreatic polypeptide-immunoreactive (4/19), and serotonin-immunoreactive cells (4/19). The prognosis of patients with UC of the gallbladder was poorer than that of patients with differentiated adenocarcinoma.

Ten cases of small cell carcinoma of the esophagus were studied clinicopathologically and immunohistochemically. Seven of the ten were also examined by electron microscopy. Histologically, six were oat cell type, four the intermediate cell type, and multiple histologic sections revealed squamous and glandular differentiations in small or minute areas of seven and two tumors, respectively. In four of the six polypoid tumors, the epithelium covering the tumor showed a malignant conversion accompanied by a proliferation of small anaplastic cells. Another one showed a cribriform pattern in a small area of the tumor. Argyrophilic tumor cells were seen in six cases and tumor cells immunohistochemically positive for ACTH and calcitonin were seen in six, and three cases, respectively. Neurosecretory granules were evident in three of the seven cases examined by electron microscopy. These findings suggest that a small cell carcinoma of the esophagus differentiates toward a squamous, glandular, or neurosecretory lesion, thereby supporting the idea of a totipotential stem cell origin of this tumor. The prognosis of patients with this tumor was poor, in accord with the evidence of aggressive lymphatic and blood vessel permeation.

A total of 109 cases of carcinoma and 5 cases of adenoma of the ampulla of Vater were studied by preparing 5-mm step-wise whole tissue sections in each case. Carcinoma of the ampulla of Vater could be divided into four stages (I, II, III and IV), according to the microscopically verified extent of involvement by the tumor. All 12 patients with a Stage I tumor, defined as one restricted to within the muscle of Oddi as a boundary, showed no lymph node involvement and carried an excellent life expectancy with a relative 5-year survival rate of 85%. Thus, categorization of such a tumor as early carcinoma of the ampulla of Vater is valid. Excluding two unclassifiable cases, the remaining 95 patients with Stage II, III, or IV tumors extending beyond the boundary of Oddi carried relative 5-year survival rates of 11%, 25%, or 24%, respectively. Of the 109 carcinomas, 20 had areas of unequivocal adenoma at the margins, and of the five adenomas, two larger ones had foci of atypical epithelium suggestive of carcinoma in situ. These findings show the close relationship between adenoma and adenocarcinoma of the ampulla of Vater.

A clinicopathologic and immunohistochemical study of fifty-two primary carcinomas of the small intestine (20 duodenal, 18 jejunal, and 14 ileal) was performed. Most of these neoplasms were located in the proximal duodenum, proximal jejunum, and distal ileum. Most of these tumors produced both sialomucin and sulfomucin, although the adjacent mucosa showed hyperplastic changes with increased sialomucin secretion. Argyrophil cells were recognized in seven duodenal (35%), 13 jejunal (72%), and nine ileal (69%) carcinomas. Eighteen of the 29 tumors showing positive argyrophil reactions also had argentaffin cells. The common features of mucins and endocrine cells in these tumors suggest the multipotency of small intestinal carcinoma. The prognosis correlated with the histologic type, carcinoembryonic antigen (CEA) grading, invading pattern of tumor margins, and vascular permeation and regional lymph node metastasis.

Fifty-seven cases of juvenile xanthogranuloma that fulfilled the classic description of histologic findings of the disease were analyzed clinicopathologically and immunohistochemically. Two forms could be distinguished: 47 cases of the infantile form and 10 of the adolescent and young adult form. The infantile lesion was found at birth in 8 patients (17%), and was noted within 1 year after birth in 33 (70%). Twenty-two had multiple lesions and five of the six for whom follow-up was feasible had spontaneous involution. About half of the lesions were located on the head and neck, 30% on the trunk, and 20% on the extremities. All six adolescents had a solitary tumor located in the head and neck region. Comparison of the latter form with reticulohistiocytoma and cutaneous fibrous histiocytoma was established from a differential point of view. Immunohistochemically, most lesions of juvenile xanthogranuloma displayed a positive reaction for lysozyme and alpha-1-antichymotrypsin and were negative for S-100 protein, thereby suggesting that the essential constituents of this lesion would derive from the mononuclear phagocyte system.

A clinicopathologic study was done on 21 cases of early carcinoma of the gastric cardia. The disease was preponderant in men, with a male-female ratio of 17:4. Five patients had no symptoms, while the other 16 had epigastric pain, epigastric discomfort, or other symptoms. Melena or hematemesis occurred in five patients. The first detection was made by barium study in 16 and by endoscopy in five. Detailed examinations using double-contrast radiography in both the prone right anterior oblique and supine left lateral projections were useful to detect the early carcinoma of the gastric cardia. All depressed-type carcinomas were incidentally detected during endoscopic examinations of benign peptic ulcers, therefore, whenever endoscopic examinations are being done for other entities, all the stomach including the cardia should be examined, carefully and continuously. Compared with early carcinomas of the other areas of the stomach, grossly elevated and histologically well-differentiated early carcinomas were more common in the gastric cardia. In the mucosa adjacent to the carcinoma, chronic gastritis was apparent in almost all cases, although intestinal metaplasia was found less frequently than in other areas of the stomach.

Electron microscopy of two cases of clear cell sarcoma of tendons and aponeuroses showed different fine structures. On the basis of these differences a proposed division is made of melanotic and synovial types of the tumor. A subsequent comparative histological study carried out on these tumors showed that there were histological criteria to separate the melanotic and synovial types of sarcoma. Using these histological criteria eleven further cases of clear cell sarcoma in the files of the Tumor Registry were subdivided. Review of the Tumor Registry material showed that eight were melanotic type tumors and one was a further synovial type tumor. Using these histological criteria there are two further cases in the Tumor Registry which are not clearly classifiable into either group. The present observations indicate that the majority of the so-called clear cell sarcomas are in reality "melanomas of soft parts" with a minority of this type of tumor being of "synovial type".

Dendritic cells (DC) in 121 colorectal adenocarcinomas were investigated immunohistochemically, using anti-S-100 protein antibody. S-100(+)DC were recognized among the malignant cells and/or around the tumor and differed in distribution either from lysozyme-positive macrophages or from neuron-specific enolase-positive neural tissue. Patients with many S-100(+)DC (more than 30 cells per 10 high-power fields) in the tumor survived longer than did those with few such cells (less than 30 cells), most often with no metastases (P less than 0.001). The grade of S-100(+)DC infiltration was related to both density of lymphocytic infiltration in the primary tumor and the degree of paracortical hyperplasia in the regional lymph nodes (P less than 0.05). Dendritic cells, therefore, as antigen-presenting cells, conceivably mediate cell immunity in a tumor with lymphoid infiltration and in the regional lymph nodes. The number of S-100(+) DC in the primary colorectal carcinomas represents one aspect of such a series of antitumor immunoreaction, in vivo.

Eight cases of epithelioid sarcoma were examined immunohistochemically, in order to clarify the adjunct epithelial profile of the tumor and to ascertain the intermediate filaments contained in the tumor cells. All tissues showed a strongly positive immunoreactivity for epithelial membrane antigen (EMA) and tissue polypeptide antigen (TPA). In the case of carcinoembryonic antigen (CEA), one showed a strong reaction, whereas the others were variably less stained. Cytokeratins (45 kd and 54 kd) specific for simple epithelia, including coelomic epithelium, were regularly found in all cases; a small number of cells were positive for high molecular weight cytokeratin (57 kd) and none for 66 kd cytokeratin. Coexpression of both cytokeratin and vimentin was confirmed using fresh-frozen materials. Therefore, both microscopic and immunohistochemical evidence supports the hypothesis that epithelioid sarcoma masquerades as a carcinoma.