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Objective: The score of the silver-stained nucleolar organizer region (AgNOR) is frequently found to be high in malignant tumors. We studied AgNOR in ovarian epithelial tumors diagnosed in our hospital between 1993 and 1998., Materials and Method: In our study 67 ovarian epithelial tumors (18 cystadenoma, 16 borderline type, 34 cystadenocarcinoma) were stained using the method previously described by Crocker. One-way ANOVA and logistic regression tests were used to find the statistical relationship between grade, recurrence, mortality rates and AgNOR scores in tumors (p values of <0.05 were considered statistically significant)., Results: The mean AgNOR scores of 28 mucinous and 39 serous ovary tumors were calculated. The lowest AgNOR score of 1.33 was found in cystadenomas and the highest AgNOR score of 4.92 was found in serous and mucinous cystadenocarcinomas. In addition the relationship between mortality rate, recurrence and AgNOR score in carcinomas were studied., Conclusion: AgNOR scores in carcinomas were found to be higher than adenomas, and the highest AgNOR score was found in grade-III carcinomas. This shows that the AgNOR score can be used as a prognostic index in malignancies., (Copyright 2001 S. Karger AG, Basel.)

Microcystic cystadenoma of pancreas is a rare benign neoplasm with peculiar pathologic characteristics. It is more frequent in women and in elderly age. Macroscopically it is composed of a spongy, microcystic mass with a starry central fibrous core. Histologically serous cysts are lined by cuboidal or flattened epithelium without nuclear atypias and with PAS positive cytoplasms. A surgical conservative approach is the treatment of choice. Seven cases of microcystic cystoadenomas of the pancreas observed within ten years at Osp. San Carlo Borromeo-Milano and Osp. Santa Maria degli Angeli-Pordenone from 6 women and 1 man aged 54-87 years are described. The preoperative and intraoperative investigations that have been necessary for reaching its diagnosis are discussed.

A cystadenoma arose in the urachus of a 32-year-old man. The mass was a multilocular cystic tumor filled with light yellow mucoid material. It was located in the anterior abdominal wall between the umbilicus and the dome of the urinary bladder. Overall, the mass was 14 cm x 8 cm x 5 cm, with the largest internal cyst being 6 cm in diameter. The lesion was characterized histologically by columnar cells with focal cellular and nuclear stratification. Ultrastructural examination revealed columnar cells with abundant glycogen, moderately pleomorphic microvilli without prominent filamentous cores, and apical mucin vacuoles. Nuclei had pleomorphic contours. An intact basal lamina was present. A similar urachal cystadenoma has not been described.

Hepatobiliary cystadenoma is a rare hepatic lesion characterized by a multiloculated cyst lined by cuboidal or columnar epithelial cells. Four cases of hepatobiliary cystadenoma with mesenchymal stroma (HCMS) and one case of hepatobiliary cystadenoma with intracystic epithelial component were studied by light microscopy, immunohistochemical methods, and electron microscopy. Similar studies were conducted on six fetal gallbladder tissues, representing the biliary tree, and two adult ovarian tissues. By light microscopy, the columnar epithelium of the five cases of hepatobiliary cystadenoma was similar to the epithelium of the developing gallbladder. The spindle cell stroma of the HCMS and the subepithelial spindle cells of the developing gallbladders showed similar reactivity to smooth-muscle actin. Vimentin reactivity was strongly positive in the stroma of the HCMS, and in the fetal gallbladders it was only noted in the subepithelial spindle cells of the 15-week gestation fetal gallbladder tissues. By electron microscopy, the epithelium lining the hepatic lesions showed characteristic gastrointestinal features and was identical to the epithelia lining the embryonic gallbladders. Furthermore, the mesenchymal stroma of the HCMS recapitulated the features found in subepithelial tissues in developing gallbladders. Although the ovarian stroma resembled the stroma of the HCMS by light microscopy, the immunohistochemical reactions and the electron microscopic studies showed dissimilarities. This study supports the hypothesis that the hepatobiliary cystadenomas arise from ectopic embryonic tissues destined to form the adult gallbladder.

We enumerated the number of Ag-NORs in normal pancreatic ducts and exocrine pancreatic tumors to assess their cellular activity. Our results indicate that the mean number of Ag-NOR counts increased stepwise in the following order: normal pancreatic duct (1.26), serous cystadenoma (1.27), mucinous cystadenoma (1.65), mucinous cystadenocarcinoma (2.29), noninvasive intraductal variant of mucin-producing papillary adenocarcinoma (3.16), and a common type of invasive duct cell adenocarcinoma (3.78). These results suggest that cellular proliferative activity is low in normal pancreatic ducts and serous cystadenoma, intermediate in mucinous cystadenoma, and high in mucinous cystadenocarcinoma and duct cell adenocarcinoma. In addition, mucinous cystadenocarcinoma has significantly lower Ag-NOR counts than duct cell adenocarcinoma. We conclude that a clear quantitative difference between the Ag-NOR content of tumor cells of serous cystadenoma, mucinous cystadenoma, mucinous cystadenocarcinoma, and duct cell adenocarcinoma reflects the underlying different biologic behavior (chiefly, grade of malignancy) of these lesions.

Two rare cases of papillary adenoma of the lung were reported. Histologically, the tumor cells had noninfiltrating papillary growth, cuboidal to columnar with eosinophilc granular cytoplasm and without nuclear atypia. Ultrastructurally, the tumor cells had cytoplasmic osmiophilic lamellar bodies. This benign papillary adenoma of the lung has morphologic characteristics consistent with aveolar type II pneumocyte differentiation.

Five cases of pancreatic serous cystadenoma were examined pathologically, and their nuclear DNA ploidy patterns were determined. Four were unifocal tumors, and one was a multifocal tumor. The four unifocal tumors were typical serous cystadenomas. However, the multifocal tumor exhibited an increased N/C ratio, irregular nuclear margins, various-sized nuclei, coarse nuclear chromatin, and neural invasion. All tumor cells were stained with antiCA19-9 but none with antiCEA. In the antiCA19-9 staining, the four unifocal tumors and the tumors of the pancreatic tail in the multifocal case were positive only on the apical membrane, whereas the tumor cells of the pancreatic head in the multifocal case were positive within the whole cytosol. The unifocal tumors were diploid with a DNA Index (DI) of 1.0 and proliferation indices (PI) from 4.9 to 20.9% with a mean of 14.4%. In the multifocal case, the tumor in the pancreatic head was aneuploid (DI = 1.9) and had a PI of 27.8%. The multifocal sites in the pancreatic body were aneuploid (DI = 1.9) with a PI of 22.4%. We suggest that the biological property of serous cystadenoma should be revisited.

Three cases of an unusual neoplasm of the lung appeared as solitary, peripheral pulmonary nodules in asymptomatic patients. These well-circumscribed neoplasms were composed of distinctive papillae covered by uniform cuboidal to columnar cells; more solid areas often were present. Ciliated cells, epithelial mucin, and necrosis were not observed, and mitotic activity was absent. Terminal tight junctions and microvilli were present in the two cases studied ultrastructurally. One specimen contained lamellar bodies and apical cytoplasmic dense bodies. Another case stained positively for a Clara cell-specific antigen, although surfactant apoprotein was not detected by immunostaining in the three cases. All patients have been free of disease (at 11 to 108 months). Papillary adenoma is an uncommon, apparently benign, and morphologically distinctive neoplasm. The immunohistochemical and ultrastructural findings hint at an origin from type II pneumocytes or Clara cells.

A 59-year-old white man presented with painless scrotal swelling, a symptom he stated he had had for "several decades." Pathologic examination (conventional stainings, immunohistochemistry, and electron microscopy) revealed a cystic papillary tumor that was classified as a serous papillary cystadenoma, ovarian type, of borderline malignancy, with focal transition into invasive cancer. This appears to be the ninth reported case of testicular tumors of the serous or mucinous ovarian type and the first reported case with development of a circumscribed carcinoma from serous cystadenoma of borderline malignancy.

Two cases of papillary adenoma of the lung are presented along with results of histological and ultrastructural examinations. The tumors were encountered in two asymptomatic patients in a mass-survey chest X-ray examination. The chest X-ray films showed the tumors as well demarcated small lesions. Histologically, both tumors arose in the bronchioles and consisted of cuboidal cells resembling type II pneumocytes showing papillary growth with accompanying edematous connective tissue. Several tumor cells each possessed a large eosinophilic intranuclear inclusion. In case 1, ciliated cells and Clara-like cells were also present in the tumor. Ultrastructurally, most of the tumor cells had various numbers of lamellar bodies in their cytoplasm, indicative of type II pneumocytes, and some of case 1 showed features of Clara cells and ciliated cells. The intranuclear inclusions appeared as aggregates of tubular structures or had lamellar body-like features. These findings are identical to those of papillary adenoma arising from the bronchiole.

Epidermal growth factor receptor (EGF-R) was studied with monoclonal antibody 2E9 on 50 ovarian tumors of various histological types and 10 non-tumorous ovarian tissues by immunohistochemistry. Enhanced expression was observed in 26/50 (52%) of the tumors. Only 25 out of 46 epithelial tumors (54%) showed positivity in epithelial tumor cells. Staining was cytoplasmic in all cases. No correlation was established between EGF-R expression and the histological type of the epithelial tumor. Apart from EGF-R expression in tumor cells, low immunoreactivity was also observed in stromal and endothelial cells in both normal and tumorous ovarian tissues. Furthermore in 8/9 specimens containing necrotic areas, EGF-R was noticed in these areas as well. Both of the latter observations may have impact on the evaluation of the prognostic value of EGF-R activity in tumors, when based on EGF-R measurements using biochemical binding studies. We therefore recommend that EGF-R is measured with both methods in studies regarding its clinical value.

A case of multifocal pancreatic serous cystadenoma with atypical cells is reported. The patient was a 72-yr-old female who complained of jaundice. The distal common bile duct was obstructed, and the proximal bile duct was remarkably dilated on cholangiography. The main portal vein was obstructed and collateral vessels had developed on portal angiography. Total pancreatectomy was performed. The resected specimen contained one tumor in the head of the pancreas, five in the body, and one in the tail. The tumors of the head and body were morphologically the same. Microscopically, both contained spongelike multilocular cysts on their cut surfaces. These cysts were covered with low cuboid epithelium containing clear cytoplasm and abundant glycogen. Neural invasion was also found. The tumor cells exhibited an increased N/C ratio, variable nuclear size, irregular nuclear margins, and coarse nuclear chromatin. These tumors had aneuploid nuclear DNA with a DNA index of 1.9 and a proliferation index of 0.28. We feel that it is necessary to reconsider the biological concept of serous cystadenoma.

Pancreatic tumors were induced in guinea fowls inoculated with virus strain Pts-56. Sequential high-resolution light microscopic and ultrastructural studies revealed consecutive occurrence of alterations in the pancreas of the infected birds. From the second month p.i., there were nonobligatory, unspecific focal degenerative changes in acinar units that were replaced by tubular complexes, lined with centroacinar-like cells. From the third month, proliferation of ductule structures with mucin-producing or mucin-nonproducing epithelium occurred, giving rise to cystic and papillary adenomas. From the fourth to sixth months, pancreatic adenocarcinomas and poorly differentiated carcinomas arose. The cells of the serous adenomas ultrastructurally resembled the normal pancreatic centroacinar and ductular cells with their regular glandular arrangement on basal lamina, elongated nuclei with finely dispersed heterochromatin, scanty cytoplasmic organelles, microvilli, and occasional cilium. The cells of the mucinous tumors showed similarities to ductal cells with their darker cytoplasmic matrix, larger number of small mitochondria, microfilaments, vesicles, mucin granules, and extensive interdigitations. The cells of the pancreatic carcinomas revealed irregularities in glandular formation, nuclear polymorphism, low cytodifferentiation, and ultrastructural abnormalities, but in most cases retained basic fine structural similarities to the epithelium of the pancreatic ductal system. The present results indicate that the centroacinar cell is the cell of origin of the broad spectrum of pancreatic neoplasms with various differentiation and malignancy induced in guinea fowl by virus strain Pts-56.

Two examples of large, multiloculated, cystic tumors that arose within the pelvis in men of 28 and 37 years of age are described. The tumors were composed of glands and cysts lined by prostatic-type epithelium lying in a hypocellular fibrous stroma. The prostatic nature of the lesions was confirmed by immunohistochemical staining of the epithelium for prostate-specific antigen and prostatic acid phosphatase. Two apparently similar lesions were found in the literature; one tumor was attached to the prostate by a pedicle, and the other arose in the retrovesical space. These tumors, for which we propose the designation "giant multilocular prostatic cystadenoma," appear to be benign, although they may recur if incompletely excised. They may pose considerable diagnostic difficulty if the prostatic nature of the epithelium is not appreciated, an error that is likely if a relationship to the prostate is not recognized. This lesion should be included in the differential diagnosis of retroperitoneal cystic tumors in men.

We describe two patients who presented with solitary pulmonary masses that consisted of unilocular cysts lined by columnar mucinous epithelium. The cysts contained copious mucus. The epithelial lining of the cysts showed foci of stratification and papillary infolding. Histologically identical lesions have previously been termed unusual mucous cysts or mucinous cystadenomas. We believe that these tumors are true neoplasms differentiating toward the respiratory epithelial mucous cell. They should be distinguished from a variety of pulmonary neoplasms including bronchoalveolar carcinoma, bronchial mucous gland adenoma, mucoepidermoid carcinoma, and metastatic adenocarcinoma.

A case of papillary eccrine adenoma was analysed with immunohistochemical and ultrastructural methods regarding their direction of differentiation. It was found that the majority of the structures show either eccrine ductal or glandular differentiation. There were some segments, particularly in those exhibiting papillary growth, where cells similar to eccrine secretory (clear) cells or cells with characteristics of both ductal basal cells and glandular myoepithelial cells were present.

This is the first ultrastructural study of a neoplasm arising in a parovarian Müllerian (paramesonephric) cyst. By light and electron microscopy this tumour bore a close resemblance to the ovarian serous cystadenoma of borderline malignancy. This resemblance to serous neoplasms of the ovary and to other tumours of Müllerian duct derivation was the strongest claim to its origin. Other features which indicated Müllerian origin included the absence of a well-defined basement membrane, the presence of distinct muscle coats and the relatively large size of the epithelial cells and their nuclei. We suggest that the same prognostic criteria used for ovarian serous tumours might be applicable to the present lesion and conclude that Müllerian adnexal tumours like their Wolffian counterparts can also be identified by their morphological characteristics.

A 51-year-old man was found to have two separate intratesticular serous cystadenomas of low malignant potential. Electron microscopy and OC 125 antibody reactivity characterize the neoplasms as serous and suggest müllerian histogenesis.

An examination of body cavity fluid specimens with correlated light, transmission and scanning electron microscopy revealed several surface features that distinguished between malignant cells and atypical mesothelial cells. The microvilli of malignant cells generally were widely distributed and showed a variation in appearance, irregular overlapping and the presence of fused and branched forms. Microvilli on the surface of atypical mesothelial cells were patchy in distribution, relatively uniform in length and diameter and generally lacking in irregular forms. These findings suggest that scanning electron microscopy may be of diagnostic value in the examination of effusions in certain cases.

Fourteen mucinous ovarian cystadenomas of different grades of malignancy (7 benign, 4 borderline and 3 malignant) were investigated by electron microscopy. The main tumour cell type was a columnar mucous epithelial cell with short microvilli. With increasing grade of malignancy the shape and size of these cells became more irregular and the number of mucous granules in them decreased. Most of the mucous granules had a dense core and a less dense reticular component, which stained well with the periodic acid-silver methenamine (PASM) technique. Goblet cells with the usual ultrastructure were found rather frequently. The tumours in a given group of malignancy were relative similar to each other in their light and electron microscopic appearance. However, a number of tumours contained argyrophil and argentaffin cells in addition to the columnar and goblet cells. The findings of the present study support the view that the mucinous ovarian cystadenomas arise from the ovarian surface epithelium via a metaplastic process.

A case of eccrine cystadenoma was studied by electron microscopy. The tumor showed two types of cells, luminal and basal cells. The cells lacked the characteristics of the secretory segment of the sweat glands. The features of the luminal cells are similar to those of the intradermal portion of the eccrine sweat duct. In some areas, the lesion showed features characteristic of apocrine gland structure. Nuclear bodies were very frequent. The ultrastructural findings of eccrine cystadenoma support an origin from the ductal portion of eccrine sweat glands.

Five-hundred-thirty-one cases of primary epithelial tumors of the parotid gland were examined. The incidence of basal cell adenomas was 7.5% (40 cases). The tumors could be classified histologically into these subtypes: basal cell (21/40; 42.5%); tubular, (13/40; 32.5%); trabecular (4/40; 10.0%); and papillary (2/40; 5.0%). The pattern of classic basal cell adenoma predominated in the basal-cell type but was also seen in varying degrees in the latter three types with a reciprocal transition. Accordingly, it could be suggested that tubular, trabecular, and papillary types are variants of basal cell adenoma. The higher incidence of basal cell adenomas in our survey could be accounted for by this categorization. Histologically, basal cell adenomas presented various features; (1) cystic formation (26/40; 65.0%), being most frequently seen in tubular and trabecular types; (2) adenoid cystic pattern (4/40; 10.0%); (3) elastosis in the stromal tissues (2/40; 5.0%). Basal cell adenomas were clinicopathologically compared with 291 cases of pleomorphic adenomas. Basal cell adenomas were seen more often in female patients, (60.0%), as were pleomorphic adenomas (68.4%). They were observed more frequently in patients over 50 years of age and the average was ten years higher than for pleomorphic adenoma. The tumor size tended to be smaller (below 2 cm at the greatest diameter) than pleomorphic adenomas.

In this study benign, malignant and borderline types of ovarian cystadenomas were studied by different morphological, transmission electron microscopical and scanning electron microscopical methods. The main cell type, the tubal cell, contained numerous microvilli projecting into the lumen, some cells also possessed cilia in addition to microvilli. Infrequently endometrial like cells were found with branched cilia intermixed with microvillous projections similar to that of the endometrium. Endocervical-like cells, very uncommon, evidenced numerous cytoplasmic projections extending into the lumen, arranged in a wavelike pattern. The surface structures were well developed in benign tumors, in borderline tumors focal denuded areas with histologically atypias were seen and in malignant ones the surface cells were devoid of specialised structures. The results also support a metaplastic origin from ovarian surface epithelium for these tumors.

Fifty-seven examples of a rare eccrine sweat gland tumor (aggressive digital papillary adenoma and adenocarcinoma) were studied by means of light microscopy, electron microscopy, and immunoperoxidase techniques. The neoplasm occurred as a single, painless mass, almost exclusively on the fingers, toes, and adjacent skin of the palms and soles. Microscopic features were distinct from those of other eccrine sweat gland tumors and often led to the diagnosis of such metastatic carcinoma as that of the breast. The characteristic histologic features included tubuloalveolar and ductal structures with areas of papillary projections protruding into cystic lumina. The stroma varied from thin, fibrous septae to areas of dense, hyalinized collagen. Forty tumors were classified as adenoma (ADPA) and 17 as adenocarcinoma (ADPAca). Histologically, ADPAca was distinguished from ADPA by its poor glandular differentiation and by necrosis, cellular atypia and pleomorphism, invasion of soft tissue and bone, and invasion of blood vessels. Eighteen (50%) patients with ADPA and 8 (47.0%) who had ADPAca developed recurrent lesions (2 months to 9 years) after surgical removal of the tumor. Seven (41.2%) patients with ADPAca developed metastases, of which 5 involved the lung. Three patients died of metastases, 5 to 20 years after surgical treatment of the primary tumor. The histologic malignant features in ADPAca are indicative of potential for distant metastasis and fatality. The recognition of aggressive digital papillary adenoma and adenocarcinoma as a distinct clinicopathological eccrine sweat gland neoplasm is important because of the potential for aggressive local growth and distant metastasis.

A cell line, ROSE 199, derived from rat ovarian surface epithelium (ROSE) formed papillary structures which resembled, histologically, serous papillary cystadenomas of borderline malignancy seen in the human ovary. Crowded cultures produced two layers of cells separated by a thick layer of collagen fibers. Such cultures shed viable cells into the growth medium, while no cells were shed by short-term ROSE cultures. The resemblance to ovarian tumors exhibited by ROSE 199 cells in culture, reinforces the hypothesis that the common epithelial tumors of the ovary are derived from the ovarian surface epithelium. ROSE 199 cells, while retaining their epithelial morphology and ultrastructural characteristics, express stromal activity such as abundant collagen production. Perhaps this ability to express epithelial and stromal behavior is a contributing factor to the ready neoplastic transformation of the ovarian surface epithelium.

Microcystic adenoma (serous cystadenoma) of the pancreas (MA) is an unusual benign tumor of uncertain histogenesis. We have studied 14 cases of MA from 11 women and three men. The average age at diagnosis was 64 years. Six tumors were discovered incidentally. Tumors varied from 2.5 to 12 cm in greatest dimension and all were multicystic; eight tumors were located in the pancreatic head, two in the body, and three in the tail. Each tumor was composed of variably sized cysts lined by simple cuboidal or flattened, focally glycogen-rich epithelium. The stroma was variably collagenized and showed highly vascularized, delicate to broad fibrous septae, which focally contained dystrophic calcification, cholesterol clefts, and hemosiderin. Immunohistochemical studies were performed on eight cases to determine the cell of origin. Epithelial membrane antigen and a low-molecular-weight keratin, detected by monoclonal antibodies PKK1 or AE1/AE3, were diffusely seen in tumor cells of all cases. Tumor cells were uniformly negative for carcinoembryonic antigen, chromogranin, insulin, glucagon, somatostatin, vasoactive intestinal peptide, pancreatic polypeptide, and a low-molecular-weight keratin detected by monoclonal antibody PKK2. Tumor cell antigen reactivity most resembled that seen in normal centroacinar and ductal cells. Electron microscopy of seven cases showed primitive tumor cells with irregularly spaced, short, blunt microvilli, luminal occluding junctions and belt desmosomes, bundles of filaments including dense bodies in both apical and basal cell cytoplasm, sparse organelles, and variable but often pronounced amounts of glycogen. These ultrastructural features most closely resembled the normal pancreatic centroacinar cell. Based on both immunohistochemical and ultrastructural features described above, we conclude that the centroacinar cell is the cell of origin of MA.

The clinical and pathological findings including light microscopic and ultrastructural features of two cases of borderline mucinous and serous cystadenomas that originated in the broad ligament are reported. The tumors did not involve the oviduct or ovary. They probably arose in pre-existing cysts of mesothelial and paramesonephric (primary Müllerian) origin. These rare tumors bear a close resemblance to the borderline epithelial tumors of the ovary and the same prognostic criteria may be applicable to the lesions presented here.

Benign urethral lesions are rather uncommon, and relatively few cases have been described in the literature. Malignant neoplasms, such as squamous and transitional cell carcinomas, occur more frequently. The latter usually present as papillary lesions. Specifically, papillary adenomas of the prostatic urethra are very unusual and rare lesions. They are usually seen in children but occasionally are found in the adult. Symptoms include urinary obstruction, infection, enuresis, sexual disturbances, or hematuria. Two cases of papillary adenomas are presented in this article. The lesion is important because it can be a source of significant hematuria, but can be cured easily at cystoscopy by local excision. This article describes the electron microscopic findings in two of these tumors, trying to elucidate their histogenesis and nature. No ultrastructural studies of these lesions have been reported previously.

Histological and electron microscopic examinations of 7 serous adenocarcinomas of the ovaries permitted to follow all the stages of psammous body formation starting from the submicroscopic level. The formation of psammous bodies was shown to be connected with a relatively differentiated epithelium of the adenocarcinomas. Initially, microcrystals of oxyapatites are deposed on accumulations of protein substances in ergastoplasm cysterns and on mitochondrial cristae. With further accumulation of these crystals relatively large intracytoplasmic inclusions of oxyapatites are formed which after confluence fill the cell which results in its death. In this way a small psammous body becomes free-lying.

Transmission electron microscopic studies have been carried out on psammoma bodies in two benign and seven malignant papillary serous neoplasms of the ovary. Ultrastructurally, psammoma bodies are composed of microcrystals in all respects similar to calcium-phosphate apatite crystals of bone. The formation of psammoma bodies is initiated intracellularly, in both the neoplastic epithelial cells and stromal histiocytes. The initial seeding site of apatite crystals is served by lipid-rich intracellular vesicles. These structures are produced in association with autophagocytosis in the neoplastic epithelial cells and heterophagocytosis of extracellular lipidic material in the stromal histiocytes. Extracellular lipids presumably derive from dehiscent tumor tissue. The close relationship between larger intraepithelial calcific bodies and microfilaments suggests that the latter provide supportive matrix for further intracellular calcification. Large extracellular psammoma bodies result from fused calcific bodies which have been extruded from calcified cells. Mineralization of extracellular collagen fibers is not observed. The results provide supportive evidence to the concept that psammoma bodies in ovarian papillary serous neoplasms and probably in other neoplastic and non-neoplastic conditions are a consequence of dystrophic calcification associated with cellular degeneration.

An 88-year-old man presented with 13 apocrine cystadenomas of both lower eyelids of at least 10 years' duration. The cysts were remarkable for possessing a superior dome of either creamy or yellowish material (probably reflecting the lipid-rich decapitation secretion), surmounting a clearer fluid inferiorly, as well as for being restricted to the eyelid margins where the glands of Moll are located. Light microscopy disclosed a double-layered cuboidal cellular lining, which focally became more plump or hobnailed, exhibited apical decapitation secretion, and was occasionally thrown into papillary folds. Electron microscopy demonstrated cellular debris and segments of interrupted plasmalemmas within the cystic cavity, intercellular widenings constituting canaliculi, cytoplasmic election-dense secretory granules, flocculent mucous vacuoles, and swirls of smooth-surfaced endoplasmic reticulum. Basal cells were focally interspersed between the secretory cells and the basement membrane, and occasionally manifested spotty myofilamentary differentiation. These findings are supportive of an origin of the lesions from the secretory rather than the ductal portion of the glands of Moll. They corroborate conclusions drawn from dermatologic investigations that the cysts are an essentially proliferative process as opposed to the result of passive ductal dilatation.

In the human gastrointestinal tract the amphicrine cells are described as a special form of endocrine cells. Depending on their behaviour under silver impregnation, they are divided into three subgroups: the mucoargentaffine, the mucoargyrophilic and the mucoargyrophobic cells. They were detected electron microscopically in 1969, but they were histologically verified and identified as mucus-excreting endocrine elements only in 1977. Since 1969 such cells have also been observed in normal and regenerating rat and mouse stomachs. Our own human material includes stomach (3 cases), appendix (12 cases), colon (1) and a series of amphicrine proliferations and tumours. Two cases of chronic gastritis and one chronic peptic ulcer with metaplastic and regenerating epithelium contained mucoargyrophilic cells with mucus below the nucleus in the atypical glands. The possibility of endocrine granules being sluiced out in the mucous grains is discussed. Of the appendices only two were normal (ages 6 and 7 years), 10 showed pathological changes: there were seven neurogenic appendicopathies (14-58 years), one lymphatic hyperplasia, and one hyperplasia of mucoargyrophobic cells with mucostasis. Mucoargentaffine cells far outnumbered the mucoargyrophilic and mucoargyrophobic cells. The mucus may have either an apical or basal location; in the latter case, paracrine secretion into the subepithelial lamina propria was seen. As neoplastic cells, the amphicrine cells form the rare amphicrine tumours (goblet-cell and muco-adenoid carcinoids) of the appendix and colon. They are also found in mucinous cystadenomas of the ovary [26], in the enteral type of a nasal carcinoma [27,28], and in a 5-HT-carcinoid of the ovary [15]. They are therefore to be regarded as a differentiation disorder of the endocrine cells under the pathological conditions of appendicopathy, hyperplasia, metaplasia and true neoplasias.

Two cystadenomas occurring near the frenulum of the penis revealed a predominantly secretory pseudostratified columnar epithelium with PAS-reactive dome-shaped cytoplasmic protrusions at the luminal cellular parts. The content of secretory vacuoles was discharged into the cyst lumen by an exocytotic (eccrine) and ballooning type of extrusion. There were no indications of a real apocrine extrusion mechanism. No histogenetic derivation of these penile cystadenomas from apocrine sweat glands could be proved. An antennalike filamentous fuzzy coat on the luminal cytoplasmic membrane was most remarkable. Regionally, an epidermoid differentiation had developed. Morphologically, this process had begun just above the basal cell layer which had remained unchanged and led to the establishment of a stratified epithelium. Hyalin lamellarlike flattened cells at the luminal part displayed necrobiotic features and resembled periderm cells. There was no keratin pattern. Luminal cells of epidermoid differentiation still revealed a filamentous fuzzy coat which indicated that the undifferentiated cuboidal basal cells basically had a prospective secretory meaning and probably represented the target cells in the process of metaplasia.

A cystic tumor composed of atypical glands in a cellular stroma arose in the pelvis of a 49-year-old man. Two years later an identical tumor was again excised from the pelvis. Morphologic, immunohistochemical and ultrastructural studies indicate that this neoplasm arose in the seminal vesicle, possibly from a seminal vesicle cyst. The tumor did not involve the prostate gland, and immunohistochemical stains for prostate-specific antigen and prostatic acid phosphatase were negative. Ultrastructural study showed that both the glandular and mesenchymal components of the tumor recapitulated features of normal seminal vesicle, further establishing origin from this site. This tumor resembles the rare cystadenoma of the seminal vesicle, yet the cytologic atypia suggests low grade malignant potential. Following the second excision, the patient has had a disease-free interval of 18 months. Long term follow-up and recognition of additional cases is necessary to define the biologic potential of this unusual tumor.

The authors describe two mucinous ovarian tumors that were hormonally active due to Sertoli-Leydig elements within the septal stroma. Carcinoid was also present in each case. The mesenchymal stromal cells within the septa of the mucinous tumors have undergone neoplastic proliferation with the Sertoli and Leydig differentiations, leading to the formation of arrhenoblastoma. The carcinoid component of these tumors is thought to have originated from argentaffin cells of the "intestinal" mucinous epithelium.

Microcystic adenomas are rare tumors, which have only recently been distinguished from other cystic pancreatic lesions. This study details eight cases diagnosed at the Cleveland Clinic. Seven occurred in females. The mean age at diagnosis was 66 years. Abdominal or epigastric pain was the most common symptom. A history of extrapancreatic tumors was frequent, and one patient had a concomitant renal carcinoma with adrenal and renal cysts. The adenomas were multicystic, ranging in size from 2 to 14 cm. Cuboidal epithelial cells with vacuolated or clear cytoplasm containing abundant glycogen lined the cysts. The intervening stromal septa were collagenous and hypocellular. The epithelial cells exhibited strongly positive immunostaining for cytokeratins AE1 and AE3, but did not stain with CEA and Uro-2,3, and 4. Ultrastructurally, the epithelial cells rested on well-formed basal lamina and a delicate subepithelial capillary network. They had blunted apical microvilli and contained glycogen, few lipid droplets, and occasional apical secretory granules. Five adenomas were resected, and three had only a diagnostic biopsy. There were no metastases, but one patient died of postoperative complications following local excision. Elderly or high-risk patients may benefit more from biopsy alone than from attempts at total surgical resection of these benign tumors.

Electron microscopic study of borderline serous and mucinous ovarian tumours was carried out and revealed marked heterogeneity of both types of these tumours. On the basis of the remote results of surgical treatment of the patients the most dangerous subtype from the point of view of its malignancy, the so-called proliferating, tumour with atypical epithelium, was established.

Thirty mucinous cystadenomas, borderline tumors and cystadenocarcinomas were analyzed by scanning and transmission electron microscopy. Results were compared to those obtained by light microscopy. Benign tumors consisted of endocervical-type columnar, mucus-containing cells with microvilli and cilia, goblet cells and intestinal-type microvillous cells. Borderline tumors showed a decrease in number and size of specialized surface structures in relation to degree of cellular atypia, the number of nucleoli and nuclear indentations indicating areas of incipient malignancy. Invasive carcinomas consisted mainly of intestinal-like surface cells varying in size and shape in relation to degree of tumor differentiation.