Borderline smooth muscle tumors of the uterus.

At present, decision regarding where to place a uterine smooth muscle tumor that deviates from the most obvious leiomyoma and leiomyosarcoma groups still depends on time-honored conventional criteria. The focus of categorization should be the clinical outcome and not nosology. To improve accuracy in predicting clinical behavior, a multivariate approach is needed. This involves combining background clinical information, intraoperative and gross findings,multiple relevant morphologic criteria, and immunohistochemical studies. The authors believe that in future, as the number of cases with intermediate clinical outcome and morphologic features increases, and as molecular markers of prognosis are studied, managing these tumors will become more objective.

Invasive inflammatory pseudotumor of uterine cervix: a case report.

BACKGROUND: Inflammatory pseudotumor (IPT) of the cervix uteri has been reported in only one patient. Here, we present a case of cervical IPT with bilateral parametrial involvement causing hydroureteronephrosis. CASE: A 48-year-old, gravida 2, para 1, woman was referred for evaluation of lower abdominal pain and right-sided hydroureteronephrosis. On speculum and colposcopic examinations, the cervix appeared normal. Computed tomography scan revealed a 5 cm x 4 cm mass in the cervix invading both parametria. At laparotomy, the cervix was globally enlarged and both parametria were infiltrated by a tumor of rubbery consistency. After freeing both ureters, the cervix was removed with bilateral parametria and 2-cm vaginal cuff. Histologically, the tumor was characterized by proliferation of fibroblast-like spindle cells and diffuse infiltration of plasma cells and lymphocytes. Immunohistochemical staining showed that the lymphocytes were polyclonal. Immunostaining for smooth muscle actin was negative. The tumor was thus identified as inflammatory pseudotumor. Cervical stroma, bilateral parametria, and subepithelial tissues of the vagina were involved with tumor. However, invasion was not identified in the epithelia of the cervix and vagina or surgical margins of the resected specimen. Postoperative course was uneventful. There is no evidence of recurrent disease 8 months following surgery. CONCLUSION: The case we present is the second reported case of cervical IPT. It is unique in showing locally aggressive behavior. Surgical resection appears to be the treatment of choice for IPT.

Ovarian dysgerminoma associated with Pseudo-Meigs' syndrome and functioning ovarian stroma: a case report.

BACKGROUND: We present the first case of an ovarian dysgerminoma complicated by pseudo-Meigs' syndrome. Furthermore, this is the fourth reported case of ovarian dysgerminoma with functioning ovarian stroma resulting elevated androgen levels preoperatively. CASE: A 25-year-old white female was referred to our department for abdominal swelling and a rapidly enlarging abdominal mass. Chest X-ray showed massive right pleural effusion. Abdominopelvic CT scan showed a left adnexal solid mass and ascites. Preoperative abnormally elevated hormone levels were as follows: free testosterone 7.7 pg/mL, androstenodione 13.6 ng/mL, and cortisol 29.4 microg/dL. Left salpingo-oophorectomy and wedge resection of the right ovary were performed. Final histopathological investigation of the left ovary was dysgerminoma associated with stromal luteinization. CONCLUSION: Dysgerminoma should be considered in the differential diagnosis in a young patient with a pelvic mass, ascites, and pleural effusion and preoperative counseling should be directed accordingly. In addition, dysgerminomas may be accompanied by ovarian stromal luteinization and steroid hormone production, which occasionally result in chemical or clinical hyperandrogenism.

High concentrations of the CA-125, CA 19-9 and CA 15-3 in the peritoneal fluid between patients with and without endometriosis.

OBJECTIVE: In the present study we compared the levels of CA-125, CA 19-9, and CA 15-3 in the peritoneal fluid (PF) of patients with and without endometriosis, then assessed the possibility of a correlation among these tumor markers. STUDY DESIGN: Our study was a controlled clinical study of patients undergoing laparoscopy for infertility or other benign gynecology conditions. Peritoneal fluid samples were collected from 65 women with endometriosis and 43 women without pelvic disease. Levels of CA-125, CA 19-9 and CA 15-3 in the peritoneal fluid were determined by immunoradiometric assay. RESULTS: The concentration of CA-125 in PF from patients with endometriosis was significantly higher than that in the control group (p<0.001); for CA 19-9 and CA 15-3, PF concentrations were not statistically different between these two groups. Women with endometriosis had significantly higher levels of CA-125 in proliferative and secretory phases than the control group (p<0.001 and p<0.002 respectively); furthermore, in patients with endometriosis the CA 19-9 levels were significantly lower in secretory phase than the proliferative (p<0.004). The levels of CA-125 were significantly lower in women with tubal ligation, in comparison with infertility or pelvic pain in the control group (p<0.001). No significant difference was seen in women with infertility or pelvic pain in endometriosis group and the levels of CA-125, CA 19-9, and CA 15-3. We did not find any correlation between the stages of endometriosis and the concentration of CA-125, CA 19-9 and CA 15-3. A significant correlation between the CA 19-9 levels and CA 15-3 in patients with endometriosis was found (r=0.72, p=0.001). CONCLUSIONS: We found high concentrations of CA-125, CA 19-9, and CA 15-3 in the peritoneal fluid of women with and without endometriosis in the Yale series. However, the levels only of CA-125 were higher in women with endometriosis, but without diagnostic value. The role of simultaneously high concentrations of CA 19-9 and CA 15-3 in women with endometriosis needs to be explored further.

Ovarian hemangioma presenting with hyperandrogenism and endometrial cancer: a case report.

BACKGROUND: Hemangiomas are very rare tumors of the ovary. Here, we report a case of a mixed capillary and cavernous ovarian hemangioma and endometrial carcinoma presenting with postmenopausal bleeding, male pattern receding frontal hairline, and high serum androgen and estradiol levels. CASE: A 70-year-old White female underwent laparotomy for endometrial carcinoma. Intraoperative frozen-section examination of the uterus revealed a 3.5 x 3 cm, grade 1 endometrioid adenocarcinoma of the endometrium with more than 50% myometrial invasion. The left ovary contained a 1.5 x 1 x 1 cm, well-circumscribed hemorrhagic nodule on the cut surface. Final histopathological examination of the small nodule demonstrated multiple, enlarged, blood-filled vascular channels lined by a single layer of flattened regular endothelial cells with no atypical features. Vascular spaces within the tumor were of different sizes, ranging from small to large, and were separated by connective tissue. The surrounding ovarian stroma was hyperplastic and contained clusters of luteinized stromal cells. Microscopy of the right ovary showed minimal stromal proliferation and no luteinization of the ovarian stroma. CONCLUSION: This is the first case of an ovarian hemangioma synchronous with a well-differentiated endometrial carcinoma. Absence of estrogen and progesterone receptors in the endothelial cells of the hemangioma suggests that ovarian hemangiomas may occur independent of stimulation by estrogen and progesterone.

Chemoradiation with 5-fluorouracil and mitomycin C in the treatment of vulvar squamous cell carcinoma.

OBJECTIVE: To investigate the acute and late toxicities associated with the use of chemoradiation therapy (CRT) with 5-fluorouracil (5-FU) and mitomycin C or mitomycin C alone for primary, adjuvant, and salvage therapy for vulvar cancer. METHODS: Medical charts of 17 patients who received CRT with this regimen were reviewed. Toxicity was scored by 1998 standardized common toxicity criteria, Version 2.0, for acute toxicity and the RTOG/EORT Late Radiation Morbidity Scoring Schema for late toxicity. Median follow-up was 20 months (range: 5-74 months). RESULTS: Six patients had grade 4 neutropenia. In three patients, life-threatening neutropenic sepsis developed after the second cycle of chemotherapy. Severe enterocolitis was a direct cause of death in two patients. In four patients, the second cycle of chemotherapy was cancelled because of severe toxicity associated with the first cycle. One patient had grade 4 skin toxicity in the vulvar-perineal area. Six patients had grade 3 and seven patients had grade 2 acute skin toxicity. Skin toxicity necessitated the interruption of CRT in nine patients at a median dose of 32.4 Gy (range: 16.2-48 Gy). One patient developed bowel perforation and colovaginal fistula 1.5 years after completion of CRT. CONCLUSION: Chemoradiation therapy utilizing 5-FU and mitomycin C or mitomycin C alone in the treatment of vulvar cancer can be associated with a high incidence of morbidity and mortality. Strict attention to indications for treatment interruptions or chemotherapy dose adjustments is obligatory for safe delivery of CRT to these patients.

Regulation of endometrial stromal cell matrix metalloproteinase activity and invasiveness by interleukin-8.

OBJECTIVE: To evaluate the effect of interleukin-8 (IL-8) on endometrial stromal cell metalloproteinase (MMP) activity and invasiveness. DESIGN: Experimental laboratory study. SETTING: University medical center. PATIENT(S): Reproductive age women without endometriosis. INTERVENTION(S): Endometrial stromal cells were grown in culture and treated with recombinant IL-8 (0.0001-10 ng/mL) for 24 to 48 hours. Supernatants were collected for soluble assay of collagenase activity and gelatin zymography. Endometrial stromal cells were plated on 8-microm pore membranes coated with Matrigel or human simple matrix and treated with IL-8 for 48 hours. MAIN OUTCOME MEASURE(S): Collagenase activity and MMP2 and 9 activity of control vs. IL-8 treated endometrial cells, and number of endometrial cells that invade through Matrigel or human simple matrix. RESULT(S): Collagenase activity in cells treated with IL-8 (1-10 ng/mL) was higher than in control cells. On gelatin zymograms, MMP2 and MMP9 activity of endometrial stromal cells was stimulated by IL-8 treatment (1-10 ng/mL). The number of cells that invaded the Matrigel or human simple matrix was 1.7-fold higher in the group treated with 10 ng/mL of IL-8 compared with the control group. CONCLUSION(S): IL-8 increases MMP activity and invasive capability of endometrial stromal cells in culture; IL-8 may be involved in the pathogenesis of endometriosis and menstrual physiology.

Expression and regulation of interleukin-8 in human fallopian tubal cells.

OBJECTIVE: The human fallopian tube creates the microenvironment for fertilization and early embryogenesis. Salpingitis may result in infertility and ectopic pregnancy by causing tubal blockage and hydrosalpinx. To better understand the relationship between infectious inflammation and tubal damage, we investigated the expression and regulation of interleukin-8 in human tubal epithelial and stromal cells in culture. STUDY DESIGN: Human fallopian tube epithelial and stromal cell cultures were used to measure interleukin-8 messenger RNA and interleukin-8 protein levels at basal conditions and after stimulation with interleukin-1alpha and tumor necrosis factor-alpha. Northern blot analysis and enzyme-linked immunosorbent assay were used to evaluate messenger RNA and protein levels, respectively. RESULTS: Tubal epithelial cells expressed high levels of interleukin-8 messenger RNA and secreted significantly more immunoreactive interleukin-8 into culture medium than did tubal stromal cells (2065 +/- 153 pg/mg vs 530 +/- 56 pg/mg of total protein, P <.01). Interleukin-1alpha and TNF-alpha treatments induced a concentration-dependent increase in interleukin-8 messenger RNA expression in both epithelial and stromal cells. However, at the protein level, although interleukin-1alpha and tumor necrosis factor-alpha treatments increased the secretion of interleukin-8 from stromal cells significantly, similar treatments had no effect on interleukin-8 secretion from epithelial cells. CONCLUSION: The expression of interleukin-8 in human tubal epithelial and stromal cells is different. Interleukin-8 expression of tubal epithelial and stromal cells in response to inflammatory cytokines such as interleukin-1alpha and tumor necrosis factor-alpha also varies. This may be important in the pathogenesis of salpingitis.

Chemokine receptor expression in human endometrium.

Chemokines play a role in endometrial physiology and pathology and may affect endometrial receptivity and menstrual shedding. Chemokines exert their effect by binding to their relevant receptors, the expression levels of which may modulate their action. In the present study, we examined the expression of chemokine receptors CXCR1 and CXCR2 (receptors for interleukin-8) and CCR5 (receptor for RANTES [regulated-on-activation, normal-T-cell-expressed and -secreted], macrophage inflammatory protein [MIP]-1alpha, and MIP-1beta) in human endometrium. Human endometria (n = 35) were grouped according to the menstrual cycle phase and examined by immunohistochemistry for CXCR1, CXCR2, and CCR5. In both epithelial and stromal cells, CXCR1 and CXCR2 immunoreactivity was detected. Staining was most prominent at the apical and basal aspects of epithelial cells. Intense CCR5 immunostaining was observed in epithelial and stromal compartments throughout the menstrual cycle. Epithelial and stromal staining for CXCR1 reached a peak at the midsecretory phase, during which it was significantly higher than the level of staining during the proliferative phase (P < 0.05). Immunostaining for CXCR2 and CCR5 showed no significant variation across the menstrual cycle. Expression of interleukin-8 and RANTES in endometrium, together with the presence of their receptors, suggests that autocrine and paracrine interactions involving these chemokines may participate in endometrial physiology.

Elevated soluble Fas ligand levels may suggest a role for apoptosis in women with endometriosis.

OBJECTIVE: To evaluate soluble Fas ligand concentrations in serum and peritoneal fluid from women with endometriosis and from fertile controls without endometriosis, and to study levels of soluble Fas ligand in conditioned media of cultured endometrial stromal cells. DESIGN: Prospective, experimental trial. SETTING: Two academic IVF centers. PATIENT(S): Twenty-nine fertile women without endometriosis and 57 infertile women with endometriosis (32 with stage I or II disease and 25 with stage III or IV disease). MAIN OUTCOME MEASURE(S): Enzyme-linked immunosorbent assay was used to measure soluble Fas ligand concentrations in paired samples of serum and peritoneal fluid from women with and without endometriosis. Concentrations were also measured in conditioned media of cultured endometrial stromal cells at basal conditions and after stimulation with interleukin-8 (0.001-10 ng/mL) and tumor necrosis factor-alpha (1-10 ng/mL). RESULT(S): Compared with fertile controls and women with early-stage of endometriosis, women with moderate to severe endometriosis had elevated serum (87.2 +/- 6.4, 88.2 +/- 6.9, and 162.3 +/- 7.8 pg/mL, respectively) and peritoneal fluid (81.0 +/- 6.0, 80.5 +/- 6.8, and 166.2 +/- 10.3 pg/mL, respectively) concentrations of soluble Fas ligand. Serum levels of soluble Fas ligand positively correlated with levels in peritoneal fluid. Comparison of patients in the same menstrual cycle in each group revealed that increased levels of soluble Fas ligand in patients with advanced endometriosis were not attributable to the difference in cycle phases. Soluble Fas ligand was not detected in conditioned media of endometrial stromal cells under baseline conditions or after stimulation. CONCLUSION(S): Serum and peritoneal fluid of women with moderate to severe endometriosis contain elevated concentrations of soluble Fas ligand compared to women with minimal or mild endometriosis and women without endometriosis. These findings suggest a role for apoptotic dysregulation in the pathophysiology of endometriosis.

Vulvar basal cell carcinoma: two unusual presentations and review of the literature.

BACKGROUND: Basal cell carcinoma (BCC) of the vulva comprises 2-4% of all vulvar cancers. In general, vulvar BCCs tend to grow at slow rates. Nonetheless, they may be locally invasive and destructive if they are neglected. Eight cases of vulvar BCC metastatic to regional lymph nodes have been documented in the literature. CASES: Two unusual cases of vulvar BCC are presented. Case 1 is an 86-year-old white woman who presented with vulvar BCC metastatic to the femoral head. This is the first report of hematogeneous metastasis of vulvar BCC. The patient was treated with palliative vulvar resection and radiation to the femoral metastasis. At 6 months, she progressed with multiple bony and intraperitoneal metastases and died with disease. Case 2 is vulvar BCC in a 90-year-old African-American woman. She was managed by wide local excision and remains disease free to date. CONCLUSION: Vulvar BCCs are rare tumors with an unclear etiology. They can be aggressive and are capable of causing significant morbidity and occasional mortality if they are neglected or improperly treated. Hematogeneous metastasis at presentation appears to result in rapidly progressive disease. The literature regarding the pathogenesis, biologic behavior, and treatment of vulvar BCC is reviewed.