Quiste linfoepitelial pancreático. Caracterización morfológica y dificultades en el diagnóstico radiológico / The morphological characteristics of lymphoepithelial cyst of the pancreas and the problems in its radiological diagnosis

Las lesiones quísticas verdaderas del páncreas son entidades raras que, a pesar de los avances radiológicos y de las técnicas de abordaje quirúrgico, aún siguen mostrando problemas de diagnóstico diferencial. Presentamos el caso de un varón joven con una masa abdominal asintomática, que fue interpretada por TC como una tumoración probablemente sólida localizada en el cuerpo pancreático, y por RM como una neoplasia quística, manejándose diferentes diagnósticos que variaban entre neoplasia papilar y sólida, tumor intraductal papilar mucinoso de páncreas o cistoadenoma/cistoadenocarcinoma mucinoso pancreático. El diagnóstico histopatológico determinó la naturaleza quística benigna linfoepitelial de la lesión. La comunicación entre radiólogos, cirujanos y patólogos es de especial relevancia en este tipo de patología, ya que con procedimientos diagnósticos sencillos puede evitarse una cirugía con excesiva morbilidad(AU)

True lymphoepithelial cysts of the pancreas are rare entities which still pose a diagnostic challenge, despite the latest radiological and surgical advances. We present a case of young male who presented with an asymptomatic abdominal mass. An abdominal CT reported it as a probable solid tumour located in the body of the pancreas, whist the MR showed a cystic neoplasm. Various differential diagnoses were considered, such as papillary neoplasm, solid epithelial neoplasm, intraductal papillary mucinous neoplasm of the pancreas or mucinous cystadenoma/cystadenocarcinoma of the pancreas. However, histopathology revealed its benign, cystic lymphoepithelial nature. Close collaboration between radiologists, surgeons and pathologists is especially crucial for this lesion, since simple diagnostic procedures can prevent high risk surgery(AU)

Oncocytic biliary cystadenocarcinoma: a case report and review of the literature.

We report an unusual case of biliary cystadenocarcinoma with oncocytic differentiation. The patient was a 43-year-old woman who presented with right upper quadrant pain. Imaging revealed a 16 x 10 x 10-cm, heterogenous, right hepatic mass with extension into the right atrium. Surgical resection revealed a papillary neoplasm of malignant cells with atypical hyperchromatic nuclei and prominent nucleoli lining fibrovascular cores. Mesenchymal stroma was not present. The majority of the epithelial cells had abundant eosinophilic granular cytoplasm, consistent with oncocytic differentiation. There was extensive stromal and hepatic parenchymal invasion. Immunohistochemical staining revealed a "biliary pattern" of cytokeratin subset immunoreactivity, with positivity for cytokeratin 7 and an absence of staining with cytokeratin 20. The tumor was negative for mucin, carcinoembryonic antigen, alpha-fetoprotein, calretinin, CD31, and chromogranin. There was granular cytoplasmic staining with phosphotungstic acid hematoxylin, consistent with the presence of abundant mitochondria. Electron microscopy revealed abundant mitochondria within the neoplastic cells. This case is quite unusual because female patients only rarely lack the characteristic ovarian-like mesenchymal stroma of biliary cystadenomas/cystadenocarcinomas. Furthermore, to our knowledge, oncocytic differentiation in this neoplasm has been reported previously on only 2 occasions. The biologic behavior and prognostic significance, if any, of the lack of mesenchymal stroma in female patients or the presence of oncocytic differentiation remains to be further elucidated as more of these cases are described.

Prognostic importance of the nucleolar organizer region score in ovarian epithelial tumors.

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.

Centrosome abnormalities in human carcinomas of the gallbladder and intrahepatic and extrahepatic bile ducts.

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

[Diagnostic value of electron microscopy on epithelial tumors of the ovary].

The study on transmission electron microscopy (TEM) and scanning electron microscopy (SEM) in 52 cases of ovarian epithelial tumors (OET) was presented. The characteristic features of ultrastructure and cell surface structure of different types of OET, also the diagnostic features of cancer cells were determined and discussed. It has a great value in differentiation of histologic types of OET and in early diagnosis of cancer. In 3 cases of borderline malignant tumor, some malignant cells, which were impossible to distinguish by light microscopy, were discovered by TEM and SEM. The diagnostic value of electron microscopy in early malignancy of tumors is more important.

Bilateral mucinous cystadenocarcinoma of the testis and epididymis.

We describe an intratesticular mucinous cystadenocarcinoma in a 59-year-old man. The tumor was bilateral and appeared in the right testis and the left epididymis. The testicular tumor was a well-demarcated nodule, 3.5 cm in diameter, that extended from the lower testicular pole (close to the albuginea) to the epididymis compressing the corpus and infiltrating the cauda. The contralateral tumor, a 2.5-cm nodule located in the corpus epididymidis, compressed the ductus epididymidis. Both tumors consisted of multiple cavities varying in size, separated from one another by connective tissue septa that were incompletely lined by a columnar pseudostratified epithelium. The epithelial cells immunostained positively for carcinoembryonal antigen and comprised two cell types: cells showing a hyperchromatic nucleus, located in the basal portion of the cell, abundant rough endoplasmic reticulum, apical vacuoles, and numerous microvilli; and mucous cells. The cystic lumen showed a mucous content and sloughed epithelial cells. The differential diagnosis and histogenesis of these tumors is discussed.

Argyrophilic nucleolar organizer region counts in exocrine pancreatic tumors.

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.

Differential diagnosis of borderline and invasive serous cystadenocarcinomas of the ovary by computerized interactive morphometric analysis of nuclear features.

Whether borderline serous tumors of the ovary can be differentiated from invasive serous cystadenocarcinomas by morphometric analysis of nuclear features of the neoplastic epithelium was examined. Multiple descriptors extracted from nuclear tracings and intranuclear gray-level analysis of argyrophilic nucleolar organizer regions were evaluated in 11 borderline and 18 invasive tumors using computerized interactive morphometric analysis. These descriptors included: nuclear area and perimeter; number, area, and perimeter of argyrophilic nucleolar organizer regions; standard deviations of these findings; and a size distribution of nuclear areas in discrete classes. Multivariate statistical analysis showed the internal consistency of the two groups in terms of physical descriptors and the discriminating value of the parameters of nuclear size and pleomorphism (independently of nucleolar organizer region parameters). The results indicated that interactive morphometric analysis of nuclear features, combined with appropriate statistical methods, could be used to distinguish between these tumors.

[The morphogenetic potentials of endometrial and ovarian tumor cells when cultured on soft agar]. / Morfogeneticheskie potentsii kletok opukholei éndometriia i iaichnikov pri kul'tivirovanii v miagkom agare.

Morphofunctional peculiarities of tumor cells from 15 endometrial adenocarcinomas and 2 ovarian tumors have been investigated at the ultrastructural level. These cells could develop two types of colonies in soft agar: those with histotypical differentiation (numerous microvilli, well developed tight junctions, desmosomes, secretory granules), and those without it (absence of epithelial features, ability of tumor cells to produce filamentous extracellular matrix and striated collagen fibrils which are characteristic of fibroblastic cells). The addition of progesterone and tamoxifen to cell cultures resulted in rising the level of cell differentiation in the colonies. The fact that endometrial and ovarian cancer cells can express the properties specific of connective tissue cells may suggest a multipotention of the Mullerian epithelium derivatives to shed light on the histogenesis of the mixed Mullerian tumors of uterus.

Occurrence of epidermal growth factor receptors in benign and malignant ovarian tumors and normal ovarian tissues: an immunohistochemical study.

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.

Serous tumors of the ovary: ultrastructural observations.

One borderline primary serous ovarian tumor and six carcinomas were studied by means of electron microscopy. Borderline malignant tumor evidenced concomitant presence of both benign and malign serous epithelium. Ultrastructural observations revealed differentiation characteristics which involved complex architecture of cell arrangement and polarity in the distribution of the organelle and intercellular junctions. The cilia believed to be more frequent in benign tumors were also reported in poorly differentiated carcinomas and so may not be considered as reliable prognostic markers.

Argyrophilia in ovarian serous tumors. A comparative study in 127 epithelial ovarian tumors.

The distribution of argyrophil cells in epithelial ovarian tumors was studied in 127 cases. The results showed that not only mucinous tumors and endometrioid tumors contained argyrophil cells, but also some serous tumors expressed argyrophilia. 31% of serous tumors including 40% of serous adenocarcinomas contained variable numbers of argyrophil cells. Argyrophilia has been demonstrated in mucinous tumors, endometrioid tumors and Brenner tumors before. However, this is the first time the presence of argyrophilia in serous tumors has been noticed. Moreover, the argyrophil cells in 5 serous carcinomas showed reactivity with Neuroendocrine (chromogranin A) antibody but not with serotonin. The expression pattern of argyrophilia in the serous tumors was different from that of the mucinous tumors; in the former, argyrophil granules appeared in apical portions or throughout the cytoplasm of single or clustered cells. In addition, the argyrophilia in some serous tumors and endometrioid tumors decreased after diastase digestion. Ultrastructurally, no typical neurosecretory granule was found in the argyrophilic serous tumors. The findings in this study suggest that argyrophilia could be quite frequently found in ovarian epithelial tumors and in itself is not a very specific differential characteristic of carcinoid tumors. The argyrophilia found in a variety of epithelial ovarian tumors might lend additional support to the histogenesis and close relationship between the common epithelial tumors of the ovary.

Establishment and characterization of a cell line (OMC-3) originating from a human mucinous cystadenocarcinoma of the ovary.

A new human ovarian carcinoma cell line, designated OMC-3, was established from the mucinous cystadenocarcinoma of a 59-year-old woman. This cell line has grown well for 65 months and has been subcultured more than 50 times. Monolayer-cultured cells are polygonal in shape, showing a pavement-like arrangement and a tendency to pile up without contact inhibition. The chromosomal number shows aneuploidy and the modal chromosomal number is in the hypodiploid range. The cells were transplanted into the subcutis of nude mice and produced tumors resembling the original tumor. Ten thousand OMC-3 cells produced CA-125 (228-580 U) and CA-19-9 (2900-5640 U) during 17 days in culture media. CA-125 and CA-19-9 were demonstrated immunohistochemically in the original tumor, heterotransplanted tumor, and OMC-3 cells. The cells contain no estrogen or progesterone receptors. OMC-3 cells were sensitive to actinomycin D, 4-hydroperoxycyclophosphamide, and mitomycin C in vitro. Three other reports of ovarian mucinous carcinoma cell lines are reviewed.

Immune effect of tumor-infiltrating lymphocytes and its relation to the survival rate of patients with ovarian malignancies.

Tumor-infiltrating lymphocytes (TIL) in histological sections from 94 patients with ovarian malignancies were quantitated for their relation to the prognosis of the patients. It was found that the degree of lymphocyte infiltration directly affected the patients' survival rate and also related to clinical staging of the patients, as well as grading and histologic typing of the tumor. T lymphocytes characterized by alpha-naphthyl acetate (ANAE) staining were the major cells in the stroma of ovarian malignancies. Ultrastructural study of TIL and cancer cells suggested that tumor cell degeneration is related to the effect of TIL.

Nonmucinous, glycogen-poor cystadenocarcinoma of the pancreas.

True cystic neoplasms of the pancreas generally have mucinous, glycogen-rich, or acinar-type-cyst-lining epithelium. A malignant polycystic pancreatic neoplasm in a 74-year-old black woman whose cyst-lining epithelium had none of the above-cited attributes and thus appears to represent an exception is described. The primary tumor was a large, encapsulated mass whose cysts contained watery fluid. Basically, two types of epithelium lined the cysts: a single layered, low-grade malignant-appearing type and a proliferative, overtly malignant-appearing pseudostratified and papillary type. Oncocytic metaplasia, canaliculi, and microvilli were ultrastructural features.

Expression of "myelomonocytic" antigens in mesotheliomas and adenocarcinomas involving the serosal surfaces.

Because of the demonstrated efficacy of Leu-M1 as a discriminant between malignant epithelioid mesothelioma (MEM) and adenocarcinomas involving the serosal surfaces (ACSs), the authors assessed the reactivities of related "myelomonocytic" antigens in this context. Paraffin sections from 41 MEMs and 43 ACSs (pulmonary, "serous surface papillary," and metastatic mammary adenocarcinomas) were evaluated for their expression of Leu-M1, LN1, LN2, and the Mac 387 antigen. Diagnoses were based in each case on the results of conventional histologic and electron microscopic examinations. Leu-M1 was detected only in minute foci of three peritoneal MEMs and was absent entirely in pleural mesotheliomas. Conversely, 38 of 43 ACSs expressed this marker. Three cases of peritoneal MEM and one pleural mesothelioma were multifocally LN2 positive, as were 39 of 43 ACSs. LN1 was the most frequently expressed antigen in MEM, being observed in 18 such tumors (10 pleural; 8 peritoneal); it was also detected in 37 of 43 ACSs. Mac 387 failed to label any of the neoplasms assessed in this series. These results demonstrate similar patterns of "myelomonocytic" antigen expression by diverse ACS and a general absence of Leu-M1 and LN2 in MEM. LN1 and the Mac 387 antigen appear to have no additional value when compared with Leu-M1 and LN2 in the immunohistochemical evaluation of serosal neoplasms.

Establishment and characterization of two new human ovarian cancer cell lines UWOV1 and UWOV2 and a subline UWOV2 (Sf) growing in serum-free conditions: growth characteristics, biochemical, and cytogenetic studies.

The establishment, growth, and characterization of two new continuously growing human ovarian cancer cell lines (UWOV1 and UWOV2) as well as a subline (UWOV2 Sf) grown in chemically defined, serum-free medium are described. The cell lines were derived from ascitic tumors of two patients suffering from cystadenocarcinomas of the ovary. Both UWOV1 and UWOV2 lines grow in anchorage-dependent fashion as monolayers, whereas UWOV2 (Sf) forms multilayered domelike structures. Cytogenetic studies revealed nonrandom abnormalities involving chromosomes 1 and 11 in all three cell lines. Secretion of soluble collagen was detected in all three lines. In addition, UWOV2 (Sf) produces and secretes large amounts of extracellular matrix material with an ordered fibrillar structure which may function as an attachment factor for the serum-free cells. These cell lines seem to be useful for further studies of the biology of human ovarian cancer.

Immunohistochemical and ultrastructural localization of T antigen in ovarian tumors.

Thomsen-Friedenreich (T) antigen, the immediate precursor antigen of the human blood group MN system, has been found in many carcinomas, but it is suppressed in normal tissues and nonmalignant diseases. Using a monoclonal antibody specific for the T epitope and an indirect immunoperoxidase technique at light and electron microscopic levels, the authors studied the expression of T antigen and its potential diagnostic value in ovarian tumors. Among 30 serous and mucinous ovarian cystadenocarcinomas, 20 (67%) were positive and 10 (33%) were negative for T antigen. In carcinomas, positive rates increased in parallel with the tumor grade and were 37%, 75% and 80% for grade 1, 2, and 3 tumors, respectively. Of the nine patients with metastasis, seven (78%) had positive and two had negative reactions in their primary and metastatic tumors. T antigen staining was observed at the intraluminal cell surfaces and peripheral cell membranes. The ultrastructural localization of T antigen revealed electron-dense reaction products at the cell surface and microvillous surfaces. Of the ten benign ovarian tumors, three (30%) were weakly positive and seven (70%) were negative for T antigen. These findings indicate a positive correlation between the presence of immunoreactive T antigen and conventional unfavorable prognostic indicators in ovarian carcinoma. The surface location of T antigen suggests that it may have a functional role at the cell membrane and the membrane may be involved in secretion (shedding) of T antigen. Detection of T antigen may be a useful marker of prognosis in ovarian carcinoma.