Minimal-deviation Endometrioid Adenocarcinoma of the Cervix: A Case Report With Ultrastructural Analysis Demonstrating Abnormal Ciliation of the Tumor Cells.

Minimal-deviation endometrioid adenocarcinoma (MDEA) of the uterine cervix is a rare tumor that may be confused histologically with a number of benign lesions as well as other types of endocervical neoplasia. The histologic and immunohistochemical features of MDEA have been described in case reports and in small series, but correlation of these findings with ultrastructural examination has not been documented. Herein we report a 51-yr-old patient who underwent hysterectomy for menorrhagia and was found to have a clinically unsuspected, stage IB cervical MDEA. The light microscopic, immunohistochemical, and electron microscopic features of the tumor are described, with the most significant ultrastructural abnormality being the presence of abnormal cilia and ciliogenesis.

Nuclear characteristics of the endometrial cytology: liquid-based versus conventional preparation.

The aim of this study was to assess the utility of liquid-based cytologic preparation (LP) compared with conventional preparation (CP) for the assessment of nuclear findings in endometrial glandular and stromal breakdown (EGBD) which may be misdiagnosed as carcinoma in EGBD cases. The material consists of cytologic smears including 20 cases of proliferative endometrium (PE), 20 cases of EGBD, and 20 cases of endometrioid adenocarcinoma grade1 (G1) for which histopathological diagnosis was obtained by endometrial curettage at the JA Suzuka General Hospital. Nuclear findings were examined in PE cells, EGBD-stromal cells, EGBD-metaplastic cells, and G1 cells, respectively. It was examined about the following items; (1) nuclear shape; (2) A long/minor axis ratio in cell nuclei; (3) an area of cell nuclei; (4) overlapping nuclei. Results are as follows: (1) nuclear shape; as for the reniform shape of EGBD-stromal cells and spindle shape of EGBD-metaplastic cells, the ratio of the LP method was a higher value than the CP method. (2) The long axis and area of cell nuclei; LP in all groups was a recognizable tendency for nuclear shrinkage. (3) The long/minor axis ratio in cell nuclei; only EGBD-metaplastic cells recognize a significant difference between CP and LP. (4) Overlapping nuclei; LP was a higher value in comparison with CP in the other groups except PE cells, and the degree of overlapping nuclei was enhanced about three times. Therefore, although a cell of LP has a shrinking tendency, (1) it is excellent that LP preserves a characteristic of nuclear shape than CP; (2) a cellular characteristic becomes clearer, because three-dimensional architecture of LP is preserved of than CP. As for the standard preparation method for endometrial cytology samples, we considered that a concrete introduction of the LP method poses no problems.

Quantitative analysis with atomic force microscopy of cisplatin-induced morphological changes in HeLa and Ishikawa cells.

Because the cell membrane is an important regulator of cell function, its morphological changes are important markers of cell apoptosis. These changes can differ for each cell type, and depend on the treatment conditions, including the drug, doses, and treatment time. To quantify morphological changes, HeLa and Ishikawa cells were investigated with atomic force microscopy. Both cells were treated with cisplatin (1 mM) for 24 hours. The viability and proliferation of the cells were analyzed with methylthiazol tetrazolium method. The proliferation rates of both cells treated with cisplatin decreased more than 50%. The morphological changes induced by cisplatin were dependent on the cell type, and the results were determined quantitatively. The surface of HeLa cells became rougher with cisplatin treatment, whereas cisplatin-treated Ishikawa cells were smoother than untreated cells. In both cases, cell height was decreased with cisplatin treatment. These results suggest that atomic force microscopy can be used to analyze anticancer drug activity in cancer cells.

Morphological characteristics and co-stimulatory molecule (CD80, CD86, CD40) expression in tumor infiltrating dendritic cells in human endometrioid adenocarcinoma.

OBJECTIVE: The purpose of this study was to investigate changes of the antigen-presenting function of tumor infiltrating dendritic cells (TIDCs) in human endometrioid adenocarcinoma. STUDY DESIGN: The TIDCs from 45 cases of endometrioid adenocarcinoma were compared with 20 cases of normal human endometrial tissue, using transmission electron microscopic examination, and the expression of CD80, CD86, and CD40 was analyzed by flow cytometry. RESULTS: In comparison with the control group, the ultrastructure of TIDCs in human endometrioid adenocarcinoma showed the following differences: numerous TIDCs were small in volume and round in shape but some were oval and multi-angular. The cytoplasmic processes were obviously decreased in number and stubbed. Round primary lysosomes with high electron-dense granules, and secondary lysosomes with high or low electron-dense granules were seen frequently in the cytoplasm. TIDCs contained much rough endoplasmic reticulum (RER). Vacuoles with flocculent electron-dense granules were rare. High electron-dense contents in the granules were near one side and the other side was bright. The nucleus became markedly small in volume, nephroid or hoofed in shape. The nucleus had little euchromatin and lots of heterochromatin under the nuclear membrane. The levels of expression of CD80, CD86 and CD40 on TIDCs were low or even nonexistent. The expression levels of CD80, CD86 and CD40 on DCs in human normal endometrium were significantly higher than those on TIDCs in endometrioid adenocarcinoma. CONCLUSION: It is suggested that morphological differences and low expression of co-stimulatory molecules on TIDCs in endometrioid adenocarcinoma reflected the functional changes of the TIDCs in uptake, processing and presenting antigen, which may lead to the occurrence of tumor immune escape.

Prognostic markers for coexistent carcinoma in high-risk endometrial hyperplasia with negative D-score: significance of morphometry, hormone receptors and apoptosis for outcome prediction.

OBJECTIVES: Hysterectomy represents the current routine therapy for high-risk endometrial precancers. More sophisticated methods are needed for treatment decision among women who want to preserve fertility and seriously ill patients. Among women diagnosed with high-risk hyperplasia, approximately 40% show signs of endometrial cancer in the hysterectomy specimen. Thus, more sophisticated methods are needed to select the women at risk. SETTING: University Hospital of Tromsø, Regional Center for Gynecological Oncology in northern Norway. POPULATION: From 1999 to 2004, 258 consecutive patients had endometrial hyperplasia diagnosed by D-score; 57 among these were high-risk cases (D-score < 0) and 10 had coexisting endometrial carcinoma. No further cancers were detected after long-term follow-up (4-10 years). DESIGN: From the initial histological specimens, material from the 10 patients with cancer and from the 13 cases without cancer (high-risk D-score < 0) was analyzed with selected histomorphometric (architectural and nuclear) and immunohistochemical (hormone receptors and apoptotic) features blinded to the investigator. METHOD: Original slides were used for computerized histomorphometry (4-class rule and related procedures). Serial sections from the paraffin embedded material were used for immunohistochemical investigations. Immunohistochemical expression in glands and stroma was evaluated by the semi-quantitative H-score (ER-alpha, ER-beta, PR-A, PR-B, RCAS-1, Bcl-2, BAX, and Caspase-3). RESULTS: The histomorphometric 4-class rule differentiates between presence and absence of cancers with a sensitivity of 80% and specificity of 77%. Several morphometric and immunohistochemical features were significantly different in cases with cancer and hyperplasia. CONCLUSIONS: Histomorphometry seems superior in predicting coexistent carcinoma in high-risk endometrial hyperplasia and should be considered for clinical use.

Subjective sonographic assessment for differentiation between malignant and benign adnexal masses.

OBJECTIVE: To determine the accuracy of subjective sonographic assessment in distinguishing between benign and malignant adnexal masses. STUDY DESIGN: Cross-sectional descriptive study. METHODS: The patients scheduled for elective surgery due to adnexal masses were recruited into the study. All patients were sonographically examined within 72 hours of surgery were subjectively evaluated by the experienced sonographer, who had no any information of the patients, to differentiate between benign and malignant adnexal masses based on sonographic morphology. The final diagnoses, used as gold standard, were based on either pathological or operative findings. RESULTS: One hundred and fifty-eight patients with 174 adnexal masses, (benign; 108 and malignant; 66) were recruited into the study. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were of 89.7%, 84.9 % and 92.6 %, 87.5% and 90.9%, respectively. CONCLUSIONS: Subjective evaluation of sonographic morphology has high accuracy in differentiating between benign and malignant adnexal masses.

Sonographic morphology scores (SMS) for differentiation between benign and malignant adnexal masses.

OBJECTIVE: To determine the sensitivity and specificity of a scoring system for distinguishing between benign and malignant adnexal masses and to detect threshold scores for prediction of malignant ovarian tumors. STUDY DESIGN: Cross-sectional diagnostic testing. SETTING: Department of Obstetrics and Gynecology, Faculty of Medicine, Chiang Mai University. SUBJECTS: A total 158 patients scheduled for elective surgery due to ovarian tumors at Maharaj Nakorn Chiang Mai Hospital between June 16, 2002 and August 8, 2004 were recruited into the study. METHODS: All patients were sonographically examed within 72 hours before surgery by the same sonographer to evaluate the morphology including wall structure, shadowing, septum, echogenicity and score the tumors. The final diagnosis was based on either pathological or operative findings. MAIN OUTCOME MEASURE: Sensitivity and specificity of the best cut-off score. RESULTS: A score of 5 from the receiver operating characteristic curve was found to be the best cut-off score, giving a sensitivity and a specificity of 85% and 70%, respectively. CONCLUSION: Sonographic morphology scores are useful in distinguishing adnexal malignancies from benign lesions in some selected cases.

Differential expression of laminin isoforms in ovarian epithelial carcinomas suggesting different origin and providing tools for differential diagnosis.

Immunohistochemistry was used to study the distribution of laminin (Ln) chains, collagen types IV (alpha 1/2), VII, and XVIII and Lutheran antigen (Lu) in 36 frozen ovarian carcinoma samples. Surface epithelial basement membrane (BM) of the normal ovary showed immunoreactivity for Ln alpha1, alpha3-alpha5, beta1-3, gamma1, and gamma2 chains and type IV and XVIII collagens. Chains of Ln-5 (alpha3beta3gamma2) and Ln-10 (alpha5beta1gamma1) as well as type IV and XVIII collagens were found in most tumor BMs, but Ln alpha2 chain and type VII collagen were detected only in few tumors. Contrary to serous tumors, BMs of mucinous carcinomas showed Ln alpha4 chain, but not Ln alpha1 and beta2 chains. Ln alpha1 chain was found in most endometrioid carcinomas, whereas chains of Ln-5 were only moderately detectable in comparison with serous and mucinous carcinomas. In the normal ovary, Lu immunoreactivity was confined to basal aspect in the ovarian epithelial cells, but in tumor specimens Lu immunostainings showed variable polarized and nonpolarized patterns. The results suggest that the three types of ovarian carcinoma have distinct differences in their Ln distribution and can be grouped based on their expression pattern. This suggests that they may have histogenetically different precursors and may help to distinguish these tumors from each other.

Collision of uterine rhabdoid tumor and endometrioid adenocarcinoma: a case report and review of the literature.

Extrarenal malignant rhabdoid tumors have been reported in a variety of anatomic sites but infrequently in the female genital tract. In the uterus, they have been described as a pure tumor, in association with endometrial stromal sarcomas, and as a component of a malignant mullerian mixed tumor. This study reports an unusual uterine neoplasm in a 49-year-old woman, in which a malignant rhabdoid tumor occurred as a collision tumor with a well-differentiated endometrioid adenocarcinoma. The tumor was a 14-cm polypoid mass that filled the endometrial cavity. The two neoplastic components were distinct on microscopic and immunohistochemical examination. Ultrastructural examination confirmed the rhabdoid phenotype of the sarcomatous component. The patient died of disease 4 months after diagnosis with progression of the malignant rhabdoid tumor. The highly aggressive behavior of the rhabdoid (i.e., nonepithelial) component in this collision tumor lends support for a distinction of this neoplasm from a malignant mullerian mixed tumor, with which it may be confused.

Changes in the ultrastructure of human cells related to certain biological responses under hyperthermic culture conditions.

It has been reported that human cancer cells are more sensitive to high temperatures than normal human cells, and that cell proliferation and viability are affected by the temperature environment. In this study, we proceeded further, and turning our attention to the close relationship between cell morphology and temperature, used two human cancer cell lines and two normal cell strains to investigate how intracellular fine structure changes in a high temperature environment. The results showed that 1) both of the human cancer cell lines were more sensitive to high temperature than the normal human cell strains, and a difference between the temperature sensitivity of the human cancer cell lines was also confirmed. 2) There is no clear difference between the manner in which normal human cells and malignant human cells are affected by hyperthermia. 3) Among other cell structures, effects on the membrane system were observed as early changes in cell structure. The mitochondria were particularly affected, followed by the rER. 4) Changes in the nucleoplasm, as well as the nuclear membrane (inner membrane), and then the intranuclear chromatin, etc., were observed as late changes. 5) Changes in mitochondria were observed in the early stage, but temporarily tended to recover, and were then fatally affected again in the late stage. We discuss the relationship between cell proliferation, cell viability, and cell ultrastructure based on the above results.

Endometrioid carcinoma of the endometrium with sertoliform differentiation.

Ovarian endometrioid tumors with areas mimicking sex cord-stromal tumors are well documented in the literature, but it is unclear whether a similar tumor occurs in the endometrium. We report here a patient with an endometrial endometrioid adenocarcinoma resembling a Sertoli cell tumor. Immunohistochemical and ultrastructural investigations proved it was an adenocarcinoma rather than a true sex cord-stromal tumor. The features of the endometrial tumor were similar to those described in ovarian endometrioid tumors mimicking sex cord-stromal tumors and we compare them to true sex cord-stromal cell tumors. This case confirms that endometrioid adenocarcinoma with sertoliform differentiation can arise in the endometrium as well as in the ovary.

Intracytoplasmic lumina and mucinous inclusions in ovarian carcinomas.

Intracytoplasmic mucinous inclusions and lumina have been previously described in non-glandular neoplasms such as urothelial carcinoma. We describe their presence in 93% of non-mucinous ovarian carcinomas. They were found in abundance in all 25 cases (100%) of clear cell carcinoma, in 48 of 50 cases (96%) of serous carcinoma and 20 of 25 cases (80%) of endometrioid carcinoma. The degree of the differentiation of the tumour did not influence the number of inclusions or lumina observed. These results suggest that the presence of intracytoplasmic lumina and mucinous inclusions is more widespread than hitherto appreciated. Their presence in an otherwise poorly differentiated metastatic carcinoma might, at the very last, prompt one to consider the ovary as a possible primary site. In addition, an abundance of intracytoplasmic mucinous inclusion and lumina with microcyst formation, in an otherwise poorly differentiated malignant primary ovarian epithelial tumour, might suggest the possibility of a clear cell carcinoma.

Endometrioid carcinoma of the ovary and endometrium, oxyphilic cell type: a report of nine cases.

Six endometrioid carcinomas of the ovary and three of the endometrium composed predominantly or entirely of large eosinophilic (oxyphilic) cells are reported. The ovarian tumors occurred in women 31-75 years of age, with a mean of 58 years, and the endometrial tumors occurred in women 37-50 years, with a mean of 44 years. All the ovarian tumors and one endometrial tumor contained focal areas typical of endometrioid carcinoma, with round to oval tubular glands lined by simple or stratified columnar cells and focal squamous differentiation. Two endometrial tumors were composed almost exclusively of oxyphilic cells lining glands. One endometrial tumor contained prominent luminal and intracytoplasmic mucin. Five of the ovarian tumors were grade 2/3 and one was grade 3/3, whereas two of the endometrial tumors were grade 1/3 and one was grade 2/3. The prominence of the oxyphilic cells posed diagnostic difficulty in most of the cases. Electron microscopic examination performed on all tumors showed abundant mitochondria in only one, an ovarian tumor. Other organelles, especially microfilaments and tonofibrils, are cited as other possible reasons for the eosinophilia. Four of the nine cases were recent; follow-up of the remaining five showed a biological behavior similar to the typical endometrioid carcinoma of the ovary and endometrium. We suggest that the diagnosis of "endometrioid carcinoma, oxyphilic cell type" is appropriate for this variant of carcinoma largely composed of eosinophilic cells that may or may not be "oncocytic" in nature. The importance of recognizing this entity lies in distinguishing it from diverse other primary and metastatic oxyphilic cell tumors of the ovary and eosinophilic cell metaplasia and rare other types of primary carcinoma with eosinophilic cells of the endometrium, which may be especially challenging in a curettage or biopsy specimen.

Cytomorphologic characterization of cell subsets isolated by density gradient centrifugation from tumor effusions of ovarian endometrioid carcinoma.

AIMS: Cytomorphologic characterization of tumor cell subsets, according to the stage of pathologic differentiation, and comparison of cellular composition in tumor cyst and ascitic fluids were carried out on individual patients with ovarian endometrioid carcinoma. METHODS: A density gradient centrifugation technique was applied to fractionate the cells from tumor effusions. RESULTS: The enrichment of cell forms representing individual stages of pathologic differentiation by gradient centrifugation facilitated their cytomorphologic characterization. According to cytomorphologic features, 5 discrete cell subpopulations were identified and catalogued. The cellular composition of tumor cyst and ascitic fluids in individual patients was similar, but the number of fractions and percentage of cell subsets differed. CONCLUSIONS: The estimation of precise cytomorphologic criteria for cell forms in tumor effusions facilitated the cytologic diagnosis of ovarian endometrioid carcinoma. The possibility to concentrate poorly differentiated, frankly malignant cell subsets in low densities could significantly improve the diagnosis of tumor effusions.