Endometrial stromal sarcoma: a clinicopathologic study.

BACKGROUND: This study is a clinicopathologic evaluation of five patients with endometrial stromal sarcoma. PATIENTS AND METHODS: Over a period of 9 years 5 cases of ESS were observed in our Unit. The patients were retrospectively staged according to the FIGO staging system for endometrial cancer. The neoplasm was divided into two groups based on mitotic activity. Patients underwent endouterine curettage, surgery therapy and, except one of them, chemotherapy. RESULTS: Two patients had low-grade ESS stage Ib and Ic. The other three had high-grade ESS, and were in stage IIIa. Treatment was surgery for all patients, and adjuvant chemotherapy for 4 out of 5. Both patients in stage I are alive, clinically free from the disease, 25 and 36 months after diagnosis. In stage III all patients died 14, 25 and 36 months after diagnosis. CONCLUSION: ESS is a rare uterine neoplasm. Histologic grade is the most important prognostic factor.     

Endometrial stromal sarcoma: clinicopathological and immunophenotypic study of 16 cases

Purpose

Endometrial stromal sarcomas (ESSs) are rare tumors and are divided into two groups: low-grade endometrial stromal sarcoma (ESS-LG) and undifferentiated endometrial sarcoma (UES). The purpose of this study was to compare the clinicopathological features and immunophenotypes of ESS-LG and UES.

Methods

The authors evaluated 16 patients diagnosed with ESS at the Hyogo Cancer Center, reviewed their files and data, and performed an immunohistochemical study for oncogenic proteins (EGFR, PDGFR-α, and PDGFR-β) and cell cycle regulators (cyclin D1, cyclin E, p16^INK4a, p21^cip1, p27^kip1, and p53) to compare ESS-LG and UES using the World Health Organization (WHO) classification.

Results

Four cases (25 %) were classified as ESS-LGs and 12 (75 %) as UES. Patients with UES had a significantly worse overall survival than did those with ESS-LG (p = 0.0445). Although no ESS-LGs showed expression of p16^INK4a, 10 of 12 (83 %) UESs showed expression of p16^INK4a. UESs showed a trend toward higher expression of cyclin D1, p21^cip1, and p53 compared with ESS-LGs.

Conclusions

Our data emphasize the clinical importance of the WHO classification of ESS. It is of utmost importance to establish a proper classification to increase the consistency of data that may be useful for improving clinical and therapeutic management of patients with ESS.     

Sclerosing stromal tumors of the ovary: a clinicopathologic, immunohistochemical and cytogenetic analysis of three cases

Sclerosing stromal tumors (SSTs) are uncommon ovarian neoplasms of the sex cord-stromal category, that usually occur below 30 years of age. In the present study three cases of SSTs, diagnosed during the last eight years in our hospital, were examined immunohistochemically with stains for estrogen receptors, alpha and beta, progesterone receptors, and stains for markers that have been reported to be of use in the diagnosis of sex cord-stromal tumors. They were also examined by fluoresence in situ hybridization (FISH) for the presence of trisomy 12 and 7. Positivity for ERbeta was observed in a significantly larger number of cells than ERalpha. Positivity for calretinin and A103 was observed in tumor cells. In two cases 20-30% of the nuclei showed trisomy 12. No aberration of chromosome 7 was detected. The finding of increased ERbeta expression needs further investigation.     

Prognostic parameters in endometrial stromal sarcoma: a clinicopathologic study in 31 patients

OBJECTIVE: The aim of this study was to evaluate the behavior of endometrial stromal sarcomas (ESS) in relation to their clinical and pathologic features and to identify possible prognostic factors. METHODS: Thirty-one patients with histologically proven ESS were included in the analysis. Endometrial stromal sarcoma is characterized by proliferations composed of cells with endometrial stromal cell differentiation. A breakpoint of 10 mitoses per 10 high-power fields was used in the statistical analysis to distinguish between low-grade and high-grade endometrial stromal sarcoma and to evaluate the prognostic value of mitotic count in patients with ESS. RESULTS: The median follow-up time was 72 months (range 34-110). The median overall survival of the 31 patients was 127 months, resulting in a 5-year overall survival rate of 62%. Adjuvant therapy was administered to 25 patients; among those, 20 patients received postoperative radiotherapy and 5 patients received chemotherapy. Ten of the irradiated patients and 3 patients undergoing chemotherapy developed disease recurrence. Concerning the response rate to adjuvant chemotherapy, 1 patient showed a complete response, 1 patient a partial response, 1 patient stable disease, and 2 patients progressive disease. Altogether, 14 patients developed recurrent disease with a median disease-free survival of 11 months (range 5-60). Twelve patients died of the disease. A univariate model revealed that early tumor stage (P < 0.0007), low myometrial invasion (P < 0.008), and low mitotic count (P < 0.005) were associated with a lengthened overall survival in patients with endometrial stromal sarcoma. Age and adjuvant therapy did not influence overall survival of patients with ESS. CONCLUSION: Early tumor stage, low myometrial invasion, and low mitotic count are associated with a lengthened overall survival in patients with ESS.     

Endometrial stromal sarcoma arising in extrauterine endometriosis: a case report

We report a rare case of a 46-year-old woman developing endometrial stromal sarcoma (ESS) on the grounds of extrauterine endometriosis. The patient presented with symptoms of stenosis of the rectosygmoid colon. The tissue samples were submitted to histological and immunohistochemical analyses using antibodies for indirect staining. The trial showed multiple foci of endometriosis and mesenchymal malignant tissue described as ESS in the bowel wall, mesentery and in the remnants of the left adnexae. According to our findings, we suspect that ESS might have arisen in colon endometriosis.     

Low-grade endometrial stromal sarcoma with cardiovascular involvement--a report of three cases

Ovarian carcinomas typically metastasize to multiple sites via exfoliation, lymphatic spread, or direct invasion. Gastrointestinal tract involvement is usually the result of exfoliation with direct invasion of tumor within the mesentery or through serosal surfaces. We present a case of late recurrence of ovarian carcinoma isolated to the sigmoid mucosa, heralded only by brief left lower quadrant pain with hematochezia in a patient otherwise disease free for 9 years. This unusual presentation illustrates the therapeutic dilemma faced by clinicians when a tumor is of uncertain origin and underscores the need for continued follow-up and close scrutiny of new symptoms in patients with stage I disease and for those who enjoy prolonged disease-free intervals.     

Low-grade stromal sarcoma: DNA flow cytometric analysis and estrogen progesterone receptor data

DNA flow cytometry (FCM) data and estrogen receptor (ER) and progesterone receptor (PR) status were studied in three cases of low-grade stromal sarcoma (LGSS). One case was a primary presentation and the remaining two were recurrent tumors. DNA FCM showed a DNA index (DI) equal to 1.00, consistent with a diploid cell population, for four of the six specimens studied. The other two showed near-diploid populations. Proliferation indices (PI) were low in two of the patients' tumors (8.0 and 12.7%). These findings are consistent with the clinical history of LGSS and its propensity for indolent growth, long intervals between recurrences, and generally favorable prognosis. In case 2, a patient with several recurrences, the PI was increased to 20.3% in a specimen from the first recurrence. She subsequently recurred within 1 year with a more aggressive tumor, characterized by a mitotic index of greater than 10 mitoses/10 high-power fields (HPF), absence of ER and PR, and an aneuploid population (DI = 1.19). Receptor data, obtained by dextran-coated charcoal assay, showed that all tumors except the aggressive recurrence in case 2 had high ER (average 316 fmole/mg protein) and high PR (average 753 fmole/mg protein) levels. These ER and PR data are similar to the two other reports in the literature and the usual clinical response to progestational therapy was demonstrated. Further studies will help define the possible role of FCM and ER and PR determinations in patients with LGSS. These preliminary data suggest that they may be of prognostic significance.     

Recurrence of prolactin-producing endometrial stromal sarcoma with sex-cord stromal component treated with progestin and aromatase inhibitor

INTRODUCTION: Endometrial stromal tumors with sex-cord-like elements are relatively rare. We report a case of this neoplasm with prolactin as a tumor marker for recurrent disease. We also report response of recurrent disease to progesterone and aromatase inhibitor. CASE REPORT: A 48-year-old woman was diagnosed with Stage I endometrial stroma sarcoma with sex-cord component at the time of hysterectomy for presumed fibroid uterus. One and a half years later, she presented with recurrent disease in the abdomen associated with breast tenderness, galactorrhea, and an elevated prolactin level. She received three cycles of BEP (Bleomycin, Etoposide, Cisplatin) with partial response and followed by an optimal debulking procedure. Two out of a six additional planned cycles of BEP were administered with complete tumor response and normalized prolactin level. Second recurrence, 9 months later, again presented with galactorrhea and rising prolactin. Disease was progressive through three cycles of Docetaxel and Gemcitabine therapy, but had an objective response to treatment with anastrozole and megestrol acetate. Prolactin level normalized. Two years later there is stable disease and the patient remains symptom-free. DISCUSSION: Endometrial stromal sarcoma with sex-cord stromal component may be hormonally functional. Similarly to pure endometrial stromal sarcomas, they may respond to hormonal treatment, and further study is warranted.     

Endometrial adenocarcinoma with variable-level myometrial involvement limited to adenomyosis: a clinicopathologic study of 23 cases

Endometrial adenocarcinoma (EA) with myometrial involvement limited to foci of adenomyosis has been associated with a better 5-year survival than EA with myometrial invasion at the corresponding depth. We identified 23 cases of stage I EA diagnosed between 1975 and 1981 in which myometrial involvement was confined entirely to adenomyotic foci. Histopathological criteria used to determine adenomyotic involvement by EA included presence of endometrial stroma; presence of adjacent benign "marker" glands to indicate partial replacement of adenomyosis; either bulging expansion of the endomyometrial junction by EA or a smooth rounded contour of entirely intramyometrial tumor nests; and absence of peritumoral desmoplasia or stromal loosening around such foci. In any one case no single criterion was sufficient to differentiate adenomyotic involvement from true invasion; however, none of the cases showed the last phenomenon. Adenomyotic involvement extended to the inner third of the myometrium in 15 cases, the middle third in 6 cases, and the outer third in 2 cases. Twenty-one cases were pure adenocarcinoma, with one adenocarcinoma with squamous differentiation (adenoacanthoma) and one adenosquamous carcinoma; 18 cases were FIGO grade 1 and 5 were FIGO grade 2. Adenomyosis containing atypical hyperplasia was seen in 13 cases, suggesting that EA may arise de novo in adenomyosis at variable levels in the myometrium. Current follow-up data were available for all patients, with 19 presently alive and free of disease. Four died of unrelated causes, three of whom had inner third involvement and one, middle third involvement. Twelve patients were treated with preoperative or postoperative radiation. This study supports previous smaller series suggesting that cases of EA in which myometrial involvement is limited to adenomyosis have a better prognosis than those with true myometrial invasion at an equivalent level and that adenocarcinoma may arise de novo in adenomyosis.     

Uterine adenosarcoma: a clinicopathologic study of 11 cases with a reevaluation of histologic criteria

Eleven biphasic uterine tumors with epithelial components and homologous stroma were reevaluated. Originally these were diagnosed as adenofibroma, adenosarcoma, carcinosarcoma, or mixtures thereof, but were now reclassified as adenosarcomas of which seven were "pure" and four mixed with foci of carcinosarcoma. Nine of the tumors arose in the endometrium and two in the endocervix. The mean patient's age was 55 years. The most common complaint was vaginal bleeding. Macroscopically these tumors presented as polypoid masses. The epithelial component consisted mainly of endometrial, endocervical, ciliated, and clear cells. Squamous metaplasia and focal hyperplasia were occasionally observed. Malignant epithelial change was only present in foci of carcinosarcoma. The stroma showed prominent cellular periglandular cuffs, occasionally round solid or perivascular nodules, and areas of focal or diffuse stromal hypercellularity. In all these areas stromal cells were atypical and/or pleomorphic. Stromal foam cells were seen in three cases. Mitotic activity was low ranging from one to three mitoses per 10 high power fields (HPF). Follow-up was negative exept in two cases with recurrence and abdominal metastases. It was concluded that stromal hypercellularity with atypism and pleomorphism in periglandular, perivascular location as well as of focal or diffuse nature, is characteristic of uterine adenosarcoma. Adenofibromas present a fibro-collagenous stroma lacking the crowded cellular areas. Mitotic activity is too variable to serve as a reliable diagnostic criterion. Uterine adenosarcomas are usually tumors of low grade malignancy but the lack of correlation between histologic appearance and biologic behaviour precludes prognostication in the individual patient.     

Small-cell carcinoma of the uterine cervix: a clinicopathologic study of 11 cases

We report the clinical profiles and immunohistochemical features of small-cell carcinoma of the uterine cervix. Eleven cases that we have encountered at the Department of Gynecology, Kitasato University Hospital, between 1971 and 2003 are presented. Of 1370 invasive carcinomas of the uterine cervix, the incidence of small-cell carcinoma was 0.8%. Patient ages ranged between 32 and 65 years, with a mean age of 46.3 years. The clinical stages at diagnosis were Ib in four patients, IIb in three, IIIb in three, and IVb in one. All patients presented with abnormal vaginal bleeding. Two patients who are alive with no evidence of disease for 12 years and 3 years 6 months, while eight patients died of primary carcinoma between 4 and 25 months after treatment. Histopathologic findings showed solid nests with marked peripheral palisading pattern and rosette formation. Small tumor cells with scant cytoplasm demonstrated a very high nuclear/cytoplasm ratio and indistinct cell borders. The nuclei were round to oval and demonstrated increased but fine granular chromatin. Nucleoli were indistinct in all cases. Immunohistochemical findings were positive in 81.8% each for neuron-specific enolase and protein gene product 9.5, 72.7% for synaptophysin, 63.6% for chromogranin A, and 54.5% for neural cell adhesion molecule. All specimens were positive for at least one of the above. In conclusion, small-cell carcinoma of the uterine cervix revealed poor prognosis. Making an accurate diagnosis of small-cell carcinoma before performing treatment is of great significance but often difficult. Immunohistochemical analysis using several kinds of neuroendocrine markers is helpful in establishing the correct diagnosis in addition to focusing on characteristic histo- and cytopathologic features.     

Endometrial histology and bleeding patterns in menopausal women treated with estrogen and continuous or cyclic progestin

Thirty-six postmenopausal women were randomized to three groups in a double-blind, prospective study. All were treated for three months with conjugated estrogens (Premarin), 0.625 mg daily, and three different doses of a progestin (Provera), 2.5 mg daily, 5 mg daily or 5 mg during the last 12 days of a 28-day cycle. We found that the endometrium was maintained in an inactive phase in 100% of the women given continuous daily progestin but in only 25% of those given cyclic progestin. Bleeding occurred in 100% of subjects given cyclic progestin and in 50% of those given continuous progestin; however, bleeding episodes diminished with time in those on continuous progestin. A hormonal regimen that leads to reduced or absent bleeding and an inactive endometrium is preferable for postmenopausal women if estrogen therapy is to be used for the long term after menopause.     

Secondary tumors of the intestines in females: a retrospective clinicopathologic study of seven cases

OBJECTIVE: To investigate the primary site and the pathological features of secondary intestinal tumors in females, with emphasis on their differential diagnosis from primary neoplasms of the intestines. METHODS: Seven cases of secondary intestinal tumors in females were retrieved from the archival files of our laboratory. The relative clinical data were also reviewed. Inmmunohistochemistry was performed in cases with diagnostic difficulties. RESULTS: The primary site of the tumor was defined as follows: the ovary (ovarian adenocarcinoma) in five cases (71.4%), the skin (cutaneous malignant melanoma) in one case (14.28%) and the uterine corpus (mixed mullerian tumor) in one case (14.28%). In two cases the primary site was not determined initially, but the investigation showed that the primary tumor was ovarian in origin. In five cases the existence of a primary tumor was already known. Immunohistochemistry was applied in three cases for confirmation of the suspected primary tumor by histological examination. CONCLUSION: Histological diagnosis of secondary intestinal tumors may be extremely difficult, especially when the primary site is not previously known, and because of the tendency of certain secondary tumors to mimic, both grossly and microscopically, the primary ones. Immunohistochemistry is extremely helpful in resolving these diagnostic difficulties.     

Immunoreactive and estrogen-binding estrogen receptors, and progestin receptor levels in uterine leiomyomata and their parental myometrium

Estrogen receptor (ER) and progestin receptor (PR) levels in the myometria and uterine leiomyomata of forty-four women were studied. A radio-ligand method and an immuno-enzymatic method were used for ER measurement, and only a radio-ligand method was used for PR measurement. The leiomyomata contained significantly more PR and estrogen-binding ER than their parental myometria but not the immunoreactive ER per mg of DNA. Nuclear extracts from the myometria contained a high amount of the estrogen-nonbinding immunoreactive ER; in the leiomyomata, the bulk of this particular ER fraction was extracted with cytosol. Dissimilar distribution patterns of immunoreactive, estrogen-nonbinding ER in leiomyomata and normal myometria suggest that an impaired metabolism of ER may contribute to myoma growth.     

Primary sarcoma of the adult vagina: a clinicopathologic study

Combination chemotherapy has dramatically improved the results of treatment for embryonal rhabdomyosarcoma of the vagina in children, but little attention has been directed toward vaginal sarcomas in adults. This report of 17 cases of primary sarcoma of the adult vagina includes ten leiomyosarcomas, four mixed mesodermal tumors, one undifferentiated sarcoma, one stromal sarcoma, and one neurofibrosarcoma. The leiomyosarcomas, mixed mesodermal tumors, and the stromal sarcoma were morphologically similar to their uterine counterparts. Thirty-five percent of the patients had received pelvic irradiation for carcinoma of the cervix. Three of four patients treated by pelvic exenteration are alive and disease free after 84 to 161 months of observation. All 13 patients who received other forms of primary therapy died of recurrence. The pelvis was the first site of recurrence in all treatment failures and the only site of failure in 50%.     

Carcinosarcomas and mixed mesodermal tumors of the ovary: a clinicopathologic study of six cases.

A clinicopathologic study of three ovarian carcinosarcomas and three mixed mesodermal tumors of the ovary is presented. None of the patients survived for more than 1 year, irrespective of chemotherapeutic treatment or the extent of surgery. No prognostic differences were noted between the histologic patterns of varying tumor sizes of carcinosarcomas and mixed mesodermal tumors. The association of these two entities with other neoplasms of Müllerian nature suggests a multicentric tumor response of Müllerian tract derivatives. The necessity of adequate sampling, both for correct diagnosis and to exclude the possibility of teratoma (which behaves in a more benign fashion), is emphasized.     

Germ cell tumors of the ovary: a clinicopathologic study of 121 cases from Nepal

BACKGROUND: Although many reports have been published about germ cell tumors of the ovary in developed countries, there has been no such documentation from Nepal. The retrospective study presented here reports the clinicopathologic profile of germ cell tumors of the ovary studied at B. P. Koirala Institute of Health Sciences, Dharan, Nepal. METHODS: A retrospective analysis of 121 histopathologically proven cases of germ cell tumor of the ovary operated on at either our institute or somewhere else (but processed in our institute) from November 1995 to April 2001 (5.5 years) was done. Clinical data, histopathologic findings and complications were recorded. RESULTS: The prevalence of germ cell tumors was 43.36% (121/279) of all ovarian neoplasms. Patient age varied from 8 to 65 years (median 31 years). Tumor occurrence was most frequent in patients aged 21-40 years. Only eight of 121 cases (6.61%) were malignant; the rest (93.39%) were mature teratomas. Of great interest was the unexpectedly high number of cases (47.93%) found in patients who were hill natives such as Rai and Gurung. Pain and abdominal fullness were common symptoms noted in 85.95% and 79.31% of patients, respectively. Seventeen (14%) asymptomatic cases were found either on routine physical examination (12 cases) or during pregnancy (five cases). The left ovary was involved in 39.7% cases and the right in 35.5%. Bilateral involvement was seen in 24.8% of cases. Torsion was noted in 20.66% and was the most common complication. Of all the germ cell tumors 93.39% were cystic and only 6.61% were solid on gross appearance. There were three cases of monodermal benign teratoma, four cases of immature teratoma and one case of malignant transformation. CONCLUSION: Mature teratoma is the most common germ cell tumor and accounts for 40.50% of all ovarian neoplasms. The high prevalence of germ cell tumors of the ovary found among patients who were hill natives needs to be explored further.