Histologic and immunohistochemical analyses of endometrial carcinomas: experiences from endometrial biopsies in 358 consultation cases.

CONTEXT: Uterine serous carcinoma is biologically more aggressive than the endometrioid carcinoma. Because uterine serous carcinoma has a high propensity for lymphovascular invasion and intraperitoneal and extra-abdominal spread, accurate diagnosis of this tumor type in endometrial biopsies/curettings is critical for appropriate clinical management. OBJECTIVE: To share our experience in the evaluation of endometrial biopsy specimens in type I and type II endometrial adenocarcinoma. DESIGN: We retrospectively reviewed 358 biopsies containing endometrial carcinoma during a recent 3 year period of our consultation records. In cases in which our interpretation differed from the submitting diagnosis, a panel of immunostains was performed. The performance characteristics of each antibody in our panel was calculated in this group of challenging cases. RESULTS: Among the endometrial carcinomas we examined, a diagnosis of type I carcinoma accounted for 91% of cases (327 of 358) and type II carcinoma for 9% of cases (31 of 358); 41 cases (11.5%) were ambiguous or discordant (differing from submitted diagnoses and reviewed) based on histology alone. All 41 ambiguous and discordant cases were further evaluated with a battery of immunohistochemical markers. Of the 41 cases, 36 (88%) were ultimately classified (10 cases [24%] were endometrioid carcinoma; 18 cases [44%] were uterine serous carcinoma; 8 cases [20%] resulted in various other outcomes) and 5 cases (12%) remained indeterminate. CONCLUSIONS: Making the distinction between type I and II endometrial carcinoma remains a common problem in general practice. Although no one biomarker provides excellent statistical performance, a panel of immunohistochemical markers is often useful in difficult cases.

HMGA2: a potential biomarker complement to P53 for detection of early-stage high-grade papillary serous carcinoma in fallopian tubes.

Before high-grade papillary serous carcinoma (HG-PSC) becomes invasive, it is believed to be a poorly defined short-lived precursor lesion. A recent characterization of serous tubal intraepithelial carcinoma (STIC) and of the p53 signature suggested that HG-PSC may follow a stepwise progression on cellular and molecular levels. High-mobility group AT-hook 2 (HMGA2), an oncofetal protein, is overexpressed in ovarian cancer. To test whether HMGA2 can be another valuable marker for STIC, we examined HMGA2 expression in 3 groups of patients: (1) 24 patients with STIC and its invasive counterpart, HG-PSC of the fallopian tubes, (2) 24 patients with HG-PSC of the ovaries but without STIC (positive control), and (3) 30 patients with cancer and normal fallopian tubes (negative control). We found that HMGA2 was overexpressed in 75% of patients with STIC, was coexpressed with p53 in more than 50% of patients, and was completely negative in the secretory cells of the 30 patients with normal fallopian tubes. Among 7 patients with cells negative for p53 staining, HMGA2 was positive in 5; among 6 patients whose tumor cells were negative for HMGA2 in STIC, 3 were positive for HMGA2 in the invasive component; about 70% of invasive HG-PSC tumor cells were immunoreactive for both HMGA2 and TP53. In invasive carcinoma, HMGA2 overexpression was correlated with p53 (r=0.45), indicating the role of HMGA2 in p53 mediated tumor progression. Our findings of immunoreactivity for HMGA2 may lead to a novel, useful biomarker to complement p53 in the detection of early-stage serous carcinoma.

Absence of progesterone receptors in a failed case of fertility-sparing treatment in early endometrial cancer: a case report.

BACKGROUND: Fertility-sparing treatment may be offered as an alternative to standard surgical management of early-stage, well-differentiated endometrial cancer in young women. Immunostaining for progesterone receptor (PR) status is not currently part of the standard workup before treatment recommendations are made. CASE: We describe a 29-year-old woman who used oral contraceptive pills on a long-term basis in whom early-stage, well-differentiated endometrial cancer was diagnosed. Progestin therapy failed and the tumor was subsequently found to be PR negative. CONCLUSION: Combination oral contraceptive pills may stimulate clonal expansion of endometrial cells that lack PR, leading to endometrial adenocarcinoma unresponsive to progestin therapy. Consideration should be given to PR immunostaining for confirmation of the receptor status and evaluation of appropriate management options when counseling patients about fertility-sparing therapy.

Postradiation angiosarcoma of the small intestine: a case report and review of literature.

Postradiation angiosarcoma is typically a high-grade sarcoma that presents mainly in the skin and superficial tissues. Postradiation angiosarcoma arising in the small intestine is rare with only 11 cases documented in the English-language literature. Herein, we report a postradiation angiosarcoma of the small intestine 9 years after radiotherapy for uterine cervical adenocarcinoma. The patient presented with symptoms of intestinal obstruction. At exploratory laparotomy, tumor nodules involved the small bowel. Microscopically, the neoplasm was composed of spindled and epithelioid cells arranged in solid aggregates and focally forming vascular channels. The diagnosis of angiosarcoma was confirmed immunohistochemically by tumor cell expression of CD31, CD34, and factor VIII-related antigen. The patient died 10 months after laparotomy. The diagnosis of PRA should be entertained for any poorly differentiated neoplasm arising in a previously irradiated site. The correct diagnosis of PRA depends upon histomorphologic identification of vascular differentiation, coupled with immunohistochemical expression of endothelial-related markers.

Placental site trophoblastic tumor: a review of 7 cases and their implications for prognosis and treatment.

OBJECTIVE: To review cases of placental site trophoblastic tumor (PSTT) for prognostic factors and treatment implications. STUDY DESIGN: Between 1982 and 2003, 7 cases of PSTT were treated at the Brewer Trophoblastic Disease Center. Pathology and operative reports, patient records and laboratory results were reviewed. Data collected included patient age, presenting symptoms, human chorionic gonadotropin (hCG) levels, type of antecedent pregnancy, International Federation of Gynecology and Obstetrics (FIGO) stage at diagnosis, mitotic count and immunohistochemical expression of the tumor, treatments, response to treatments and length of survival. RESULTS: The mean age of patients was 34 years. The most frequent presenting symptom was vaginal bleeding (72%). The antecedent pregnancy was a normal, term vaginal delivery in 4 patients, spontaneous or elective abortion in 2 and unknown in 1. The mean interval from last pregnancy to diagnosis of PSTT was 3.2 years (range, 4 months-8 years). Serum hCG levels at the time of diagnosis ranged from 2 to 456 mIU/mL (mean, 130). All patients initially underwent surgery (hysterectomy and/or other procedures), and those with metastatic disease also received chemotherapy (most commonly etoposide, methotrexate, actinomycin D/etoposide, cisplatin [EMA/EP]). The 4 patients with recurrent or advanced disease had additional surgical procedures (thoracotomy, excision of vaginal metastases or laparotomy with intraperitoneal and retroperitoneal disease resection) as well as multiple other types of chemotherapy (e.g., bleomycin, etoposide and cisplatin; ifosfamide, carboplatin and etoposide; carboplatin/paclitaxel). Survival was 57% overall: 75%for the 4 patients with FIGO stage I disease and 33% for the 3 with FIGO stage IV. The 2 patients with mitotic counts < 2 per 10 high power fields survived. Three patients were alive and without evidence of disease for 17 years, 16 years and 8 months; 1 patient was alive with recurrent metastatic disease at 20 months; and 3 patients were dead of disease 13, 30 and 33 months after diagnosis. CONCLUSION: Advanced FIGO stage, long interval from last known pregnancy to diagnosis and high mitotic count were adverse prognostic indicators for survival in PSTT. All patients with PSTT should undergo initial hysterectomy with other surgical procedures, as indicated. Chemotherapy, usually EMA/EP, should be used in patients with advanced PSTT and may be considered in patients with FIGO stage I disease with length of time from antecedent pregnancy >2 years or high mitotic

Signet-ring cell change versus signet-ring cell carcinoma: a comparative analysis.

Signet-ring cell change (SCC) is a nonneoplastic condition that morphologically simulates signet-ring cell carcinoma (SRCA). The few case reports on SCC have focused on morphologic characteristics in distinguishing benign from malignant. In biopsy specimens, however, SCC can be easily confused with SRCA, which often demonstrates innocuous cytologic features. The object of this study is twofold: 1) to report 14 additional cases of SCC, comparing their morphologic and phenotypic features with that of SRCA; and 2) to evaluate the incidence of SCC in pseudomembranous colitis. Paraffin sections of biopsy or resection specimens containing focal or extensive SCC and 5 cases of colonic SRCA were stained with hematoxylin and eosin, periodic-acid Schiff stain with and without diastase digestion, and by standard ABC immunoperoxidase procedure using antibodies to E-cadherin, p53, and Ki-67. Both cells in SCC and SRCA were strongly positive for neutral mucins. Cells in SCC were strongly positive for E-cadherin and negative for p53 and Ki-67. In contrast, cells in SRCA were strongly positive for p53, exhibited high proliferation, and demonstrated absent or weak positivity for E-cadherin. Although SCC is not well recognized in pseudomembranous colitis, the incidence is fairly high: 14 of 50 (28%) cases showed variable numbers of signet-ring cells. Extensive SCC, although rare, can occur in different clinical conditions and can be easily mistaken for SRCA. When in doubt, routine immunohistochemical stains such as p53, Ki-67, and E-cadherin can help to differentiate SCC from SRCA.