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Primary vaginal malignant melanoma is rare, with < 250 reported cases to date. It accounts for < 1% of all melanomas in women, < 10% of all female genital tract melanomas, and < 3% of all vaginal malignancies. Its clinical behavior is notoriously more aggressive than that of cutaneous and vulvar melanoma, with a 5-year survival rate ranging from 5% to 25%. Tumor size is the strongest predictor of survival, whereas tumor thickness is a weak predictor of survival. A case of F.I.G.O. stage I vaginal melanoma encircling and embracing the entire circumference of the middle third of the vagina is described. Tumor size and thickness were 6 cm and 9 mm, respectively. The patient was treated by wide local excision and pelvic radiotherapy, and to date, 11 months after surgery, she is alive and with no evidence of disease. It is concluded that wide local excision followed by pelvic radiotherapy is an appropriate treatment for melanoma confined to the vagina.

Peritoneal tuberculosis is rare in the western world, although its incidence has been increasing in recent years. The presenting signs and symptoms, imaging examinations and CA-125 status in peritoneal tuberculosis may resemble that of ovarian carcinoma. Thus, the possibility of peritoneal tuberculosis should be considered in the differential diagnosis of ovarian carcinoma, especially in women immigrants from countries with a high prevalence of tuberculosis. A case of peritoneal tuberculosis mimicking ovarian carcinoma in a young woman immigrant from India is described. The patient presented with ascites, abdominopelvic masses and elevated serum CA-125 (1,081 U/ml). Laparoscopy confirmed the diagnosis of peritoneal tuberculosis and no malignancy, and thereby unnecessary extended surgery was avoided. Following treatment with the 4-drug anti-tuberculosis regimen, the patient recovered with disappearance of ascites and abdominopelvic masses, and return of CA-125 to normal range. It is concluded that laparoscopy, if feasible, seems to be a sufficient and safe method to provide diagnosis of peritoneal tuberculosis.

The occurrence of ectopic breast tissue within the vulva is uncommon and the development of breast carcinoma within vulvar ectopic breast tissue is very rare. To date, only 12 cases of primary vulvar breast carcinoma have previously been reported in the English literature. This paper presents the 13th reported case of primary breast carcinoma of the vulva. The patient presented with a vulvar ulcerated lump and the diagnosis was based on a morphologic pattern consistent with breast carcinoma and the presence of estrogen and progesterone receptors. Primary surgery consisted of radical vulvectomy and bilateral groin dissection. The groin lymph nodes were involved bilaterally. Adjuvant therapy consisted of systemic chemotherapy (4 cycles of adriamycin and cyclophosphamide followed by 4 cycles of paclitaxel) and pelvic radiotherapy. Oral tamoxifen 20 mg/day was started for the next five years. It is concluded that the management of primary breast carcinoma of the vulva should be modeled after that for primary carcinoma of the orthotopic breast with primary surgery followed by systemic chemotherapy and pelvic radiotherapy. Chemotherapy should be similar to that employed for breast carcinoma. Tamoxifen should be prescribed for patients whose tumors contain estrogen receptors.

Lymphoma-like lesion of the uterine cervix is a benign reactive lymphoid hyperplasia associated with chronic cervicitis that may pose a problem in differential diagnosis from malignant lymphoma. It is a rare entity and only about 20 cases have been reported in the world literature. Two cases of cervical lymphoma-like lesion are described. In both patients, the diagnosis was based on microscopic examination of biopsies taken from the uterine cervix. One patient subsequently had a cervical conization that confirmed the diagnosis of lymphoma-like lesion. Both patients are well, alive and with no evidence of malignant lymphoma. It is concluded that the diagnosis of lymphoma-like lesion is based on the well-established characteristic microscopic features of this lesion. Immunohistochemical staining is usually not helpful in distinguishing this lesion from malignant lymphoma. No specific treatment is necessary for this condition.

Psammomacarcinoma is a rare histologic subtype of serous carcinoma originating in the ovary or peritoneum, characterized by massive psammoma body formation, invasiveness, and low-grade differentiation. Its clinical behavior appears similar to that of serous borderline tumors rather than that of typical invasive serous carcinomas. Peritoneal psammomacarcinoma is even rarer than its ovarian counterpart with only 10 cases have previously been documented in the literature. A case of F.I.G.O. stage IIIC peritoneal psammomacarcinoma is described. Optimal debulking surgery, including omentectomy, total abdominal hysterectomy, bilateral adnexectomy, and resection of segment of jejunum, was performed. The patient received adjuvant chemotherapy with taxol and cisplatin, and to date, 15 months after surgery, she is alive and with no evidence of disease. It is concluded that peritoneal psammomacarcinoma is a very rare tumor that behaves less aggressively than typical serous carcinoma. The mainstay of treatment is surgical debulking. The role of adjuvant chemotherapy has as yet not been established.

The 185delAG and 5382insC mutations in the BRCA1 gene and the 6174delT mutation in the BRCA2 gene (the Ashkenazi mutations) have been found to be significantly more common among Jews of eastern European ancestry (1 in 40, 2.5%) in comparison to the general population (1 in 800 to 1 in 300, 0.12-0.33%). Carriers of these mutations, especially the BRCA1 185delAG mutation, have a significantly increased lifetime risk of breast and ovarian carcinoma and other carcinomas as compared to non-carriers. A case of three primary malignancies related to the BRCA1 185delAG mutation successively occurring in a carrier of this mutation, is described. The patient successively developed breast carcinoma, ovarian micropapillary serous carcinoma and peritoneal papillary serous carcinoma. Immunohistochemical staining results have indicated that these tumors are three separate primary malignancies. This case illustrates that ovarian serous borderline tumors (including micropapillary serous carcinoma) and peritoneal papillary serous carcinomas should be considered, like breast and ovarian carcinomas, tumors expressed in BRCA mutation carriers.

Several highly attenuated spore-forming nontoxinogenic and nonencapsulated Bacillus anthracis vaccines differing in levels of expression of recombinant protective antigen (rPA) were constructed. Biochemical analyses (including electrospray mass spectroscopy and N terminus amino acid sequencing) as well as biological and immunological tests demonstrated that the rPA retains the characteristics of native PA. A single immunization of guinea pigs with 5 x 10(7) spores of one of these recombinant strains, MASC-10, expressing high levels of rPA (>/=100 microgram/ml) from a constitutive heterologous promoter induced high titers of neutralizing anti-PA antibodies. This immune response was long lasting (at least 12 months) and provided protection against a lethal challenge of virulent (Vollum) anthrax spores. The recombinant B. anthracis spore vaccine appears to be more efficacious than the vegetative cell vaccine. Furthermore, while results clearly suggest a direct correlation between the level of expression of PA and the potency of the vaccine, they also suggest that some B. anthracis spore-associated antigen(s) may contribute in a significant manner to protective immunity.

The prevalence and clinical significance of mucosal epithelial proliferation or hyperplasia of the fallopian tube are controversial in the few studies reported. Some authors have retrospectively examined "routine" sections (one or two submitted from each tube), whereas others have prospectively blocked the entire tubes. In the current study, we prospectively studied a total of 168 tubes from 98 women who had various indications for salpingectomy and compared the diagnosis in an initial single section (to simulate the usual practice) with that in the remainder of the entirely sectioned and submitted tube (mean total number of sections, 9.0). Some degree of mucosal epithelial proliferation was found in 83% of all tubes examined, with no difference between the tubes removed for routine tubal ligation and those in women who had benign ovarian lesions, malignant gynecologic tumors, uterine leiomyomata, or benign tubal lesions (salpingitis or ectopic pregnancy). Mucosal epithelial proliferation graded as more than mild, however, was seen in only 4.5% of the otherwise normal ligated tubes versus 35 to 46% of tubes associated with the other lesions. When the initial sections were compared with the subsequent ones, the diagnosis was identical in 96 tubes (57%). In the other 72 tubes (43%), the difference in diagnosis was never greater than one grade (no, mild, moderate, severe mucosal epithelial proliferation), with the diagnosis more often upgraded (50 tubes) than downgraded (22 tubes) in the additional sections. It is concluded that there is no reason to submit an entire tube for histologic examination to detect clinically significant lesions, and the usual practice of submission of one or two sections is clinically appropriate.

Mullerian adenosarcoma--a variant of mullerian mixed mesodermal tumor of the uterus--is typically composed of benign but sometimes mildly atypical glandular epithelial elements admixed with malignant sarcomatous stroma. This rare tumor, which accounts for only about 8% of all uterine sarcomas, usually originates in the endometrium and grows as a polypoid mass within the endometrial cavity. The most prevailing presenting symptom is abnormal vaginal bleeding and the most common finding is a polypoid mass protruding through a dilated cervical canal. The case of a woman, who at age 62 presented with symptoms and signs of acute pelvic inflammatory disease and on vaginal examination an infected mullerian adenosarcoma protruding through a dilated cervical canal was discovered, is reported. Treatment consisted of extensive antibiotic treatment and surgery comprised of total abdominal hysterectomy and bilateral salpingo-oophorectomy followed by postoperative adjuvant pelvic radiotherapy. One year later, the patient is alive with no evidence of disease.

The term "micropapillary serous carcinoma" (MPSC) has recently been introduced to define a subset of ovarian serous borderline tumors morphologically characterized by a micropapillary pattern and clinically associated with a more aggressive behavior than that of the typical ovarian serous borderline tumors. Ovarian MPSC's are associated with extra-ovarian invasive peritoneal implants and invasive recurrences much more frequently than typical ovarian serous borderline tumors. The case of a women, who at age 28 had bilateral ovarian cystectomy and four months later total abdominal hysterectomy and bilateral salpingo-oophorectomy for bilateral ovarian MPSC, is reported. She was free of disease for the next 15 years and then presented with a central pelvic mass. At laparotomy, a recurrence in the form of a solitary invasive peritoneal implant was discovered and completely resected. No postoperative adjuvant therapy was given. To date, 16 years after initial diagnosis of MPSC, and one year after detection of recurrence, the patient is alive, well and without disease. Literature data and this case report support the view that MPSC's should be classified separately from both typical serous borderline tumors and invasive carcinomas of the ovary.

Background and Objectives: Glassy cell carcinoma (GCC) of the uterine cervix is a rare and highly malignant tumor, accounting for only 1%-2% of all cervical carcinomas. The purpose of this study was to investigate the clinical findings, treatment, and outcome of patients with cervical GCC in the south of Israel., Methods: Data from the files of 5 patients with cervical GCC who were managed at the Soroka Medical Center, Beer-Sheva, Israel, between January 1961 and June 1999 were evaluated., Results: Age at diagnosis ranged from 32 to 84 years, with 1 patient pregnant at the time of diagnosis. Vaginal bleeding was the prevailing presenting symptom. The cervical lesion was exophytic in 4 patients and endophytic ("barrel-shaped") in 1 patient. Mean tumor size was 3.9 cm. Three patients with stage IB(1) disease had radical hysterectomy and bilateral pelvic lymph node dissection followed by either external pelvic radiotherapy or brachytherapy or both. All 3 patients were alive without disease 4, 12, and 18 months after initial diagnosis, respectively. One patient with stage IIIB disease had external pelvic radiotherapy alone and died of disease 12 months after initial diagnosis. One patient with stage IVB disease refused treatment and died of disease 3 months after initial diagnosis., Conclusions: Cervical GCC is a rare variant of cervical cancer with distinct histologic features and an alleged aggressive clinical behavior. For early-stage disease, the treatment of choice seems to be radical surgery followed by chemoradiotherapy., (Copyright 1999 Wiley-Liss, Inc.)

Metastases to the uterus from extragenital cancers are significantly rarer than metastases to the ovaries. Of the approximately 200 cases of metastases to the uterus from extragenital cancers that have been reported in the literature, more than half are cases of metastases from breast carcinoma and only 16 are cases of metastases from colorectal carcinoma. A case of isolated metastases restricted to the myometrium of the right uterine comu from sigmoid colon carcinoma, without involvement of the ovaries, is described. The patient who six months previously had surgery for sigmoid colon carcinoma presented with right lower abdominal pain and a palpable mass in the region of the right uterine cornu. The diagnosis of isolated metastases restricted to the myometrium of the right uterine cornu was confirmed by total abdominal hysterectomy and bilateral salpingo-oophorectomy. This case illustrates that a growing uterine mass in a patient with a history of primary extragenital cancer, regardless of whether abnormal uterine bleeding is present or absent, should alert the physician to consider the possibility of uterine metastases.

Metastases to the female genital tract from extragenital cancers are uncommon. The ovaries are most often affected with the breast and gastrointestinal tract being the most common sites of the primary malignancy. Metastases to the uterus from extragenital cancers are significantly rarer than metastases to the ovaries and in the majority of cases the ovaries are also involved. A case of metastases restricted to the uterine corpus, cervix and vagina from breast carcinoma, without involvement of the ovaries, is described. The patient who had been on tamoxifen therapy presented with postmenopausal bleeding. The diagnosis of uterine metastases was established during endometrial ablation and confirmed by total abdominal hysterectomy and bilateral salpingo-oophorectomy. This case illustrates that abnormal uterine bleeding in a breast cancer patient, regardless of whether she is receiving or not receiving tamoxifen, should always alert the physician to consider the possibility of uterine metastases from breast carcinoma.

We report a rare case of a 35-year-old woman with primary hepatoid carcinoma of the ovary during pregnancy associated with abnormal levels of maternal serum alpha-fetoprotein. This tumor should be considered in the differential diagnosis of pregnant women with very high levels of maternal serum alpha-fetoprotein whenever other maternal or fetal sources are excluded.

Objective: Uterine papillary serous carcinoma (UPSC) is an uncommon highly malignant variant of endometrial carcinoma that histologically and clinically resembles ovarian papillary serous carcinoma. The purpose of this study was to present the conjoined experience of two regional hospitals in the south of Israel (Soroka Medical Center, Beer-Sheva and Kaplan Hospital, Rehovot) of handling this tumour., Study Design: Data from the files of 19 patients with UPSC who were managed at these hospitals between July 1991 and June 1997 were evaluated., Results: The three-year survival rate was 57.3% overall; 83.3% for Stage I and 21.2% for Stages II, III, and IV combined (P<0.02). Eighteen patients had primary surgery which included total abdominal hysterectomy and bilateral salpingo-oophorectomy and 15 (83.3%) of them received postoperative adjuvant therapy which included radiotherapy and/or systemic chemotherapy., Conclusions: The prognosis of patients with UPSC is worse than that of patients with other forms of endometrial carcinoma. Primary surgery comprised of total abdominal hysterectomy, bilateral salpingo-oophorectomy and staging is the mainstay of treatment. The type of postoperative treatment is not consistent. By and large, adjuvant pelvic radiotherapy is usually given in early-stage disease and adjuvant systemic chemotherapy is usually prescribed in advanced-stage disease.

Background and Objectives: Peritoneal papillary serous carcinoma (PPSC) is histologically and clinically similar to stage III-IV ovarian papillary serous carcinoma (OPSC). The purpose of this study was to investigate the clinical findings, treatment, and outcome of PPSC patients compared with stage III-IV OPSC patients., Methods: Data from the files of 15 PPSC patients and 52 stage III-IV OPSC patients who were managed at the Soroka Medical Center between January 1991 and December 1997 were evaluated., Results: With regard to patients' characteristics, presenting signs and symptoms, type and extent of surgery, tumor response to first-line chemotherapy, recurrence-free interval, recurrence site, tumor response to second-line chemotherapy, and serum CA-125 levels, no significant differences were observed between the PPSC patients and the stage III-IV OPSC controls. The prevailing presenting symptoms were abdominal mass and ascites. The mainstay of treatment was debulking surgery followed by adjuvant platinum-containing chemotherapy. The objective response rate to first-line chemotherapy was 80%. The actuarial 5-year survival rate for the PPSC patients and stage III-IV OPSC patients was 52.0% and 20.5%, respectively (0.05 < P < 0.1)., Conclusions: The clinical and surgical characteristics of patients with PPSC are similar to those of patients with stage III-IV OPSC. When treatment strategies for stage III-IV OPSC are applied to PPSC, the survival of PPSC patients may be similar or even better than that of stage III-IV OPSC patients.

The expression levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were evaluated in normal and cancerous ovarian tissue and primary cell lines (PCL). Seven normal and 10 cancerous, formalin-fixed ovarian samples were examined for TNF-alpha and IL-6 expression by immunohistochemical staining using polyclonal rabbit anti-human TNF-alpha and IL-6 antibodies. Fresh normal and cancerous specimens were also examined for TNF-alpha and IL-6 secretion by bioassay and immunoassay prior to and following in vitro stimulation with lipopolysaccharide (LPS). The levels of IL-6 and TNF-alpha were higher in cancerous tissues than in normal specimens. In vitro stimulation of normal and cancerous ovarian tissues and PCL revealed their capacity to secrete IL-6. Cancerous tissue and PCL secreted higher levels than normal tissue and PCL. Stimulation of both groups with LPS increased their capacity to secrete IL-6. Optimal secretion of IL-6 by the cancerous tissue was observed after 72 hours with or without LPS (10 microg/ml). Normal tissue secreted maximal levels of IL-6 after 96 hours with or without LPS. PCL from normal ovarian tissue secreted IL-6 constitutively and optimal expression was detected after 96 hours. Carcinoma PCL from cancerous ovarian tissue demonstrated optimal secretion of IL-6 after 24 hours. Stimulation of both types of cells with LPS, IL-1 or TNF-alpha increased their capacity to secrete IL-6. TNF-alpha activity was detected in vitro only in supernatants of ovarian cancerous tissue and only after LPS stimulation; optimal levels were detected after 48 hours and 1 microg/ml LPS. Our results indicate that IL-6 and TNF-alpha are expressed in cancerous ovarian tissue at a higher level than in normal ovarian tissues. Carcinoma cells of ovarian tissues are the main cellular source of these cytokines. The conditions controlling the secretion of these cytokines, under in vitro conditions, are different in cancerous and normal ovarian tissues.

The diagnosis of malignant melanoma metastatic to the ovary is rarely made in living patients. A case of malignant melanoma metastatic to one ovary, skin of both axillae, and brain occurring 7 years after wide local excision of the primary cutaneous lesion on the patient's back is described. The patient had total abdominal hysterectomy, bilateral salpingo-oophorectomy, infracolic omentectomy, and selective pelvic retroperitoneal lymphadenectomy, followed by whole brain irradiation and chemoimmunotherapy. This case illustrates the clinical variability and unpredictable biologic behavior of malignant melanoma and it is concluded that malignant melanoma metastatic to the ovary should be suspected in any patient who presents with an adnexal mass and has a history of malignant melanoma.

We encountered an unusual case of extramammary Paget's disease (EMPD) recurring on the skin of the lower abdomen and entire right leg two and a half years after simple vulvectomy for minimally invasive Paget's disease of the vulva. Histologic examination of the skin metastases demonstrated that the proliferation of Paget cells was confined to the dermis, most of them were located in lymphatic vascular spaces. This case confirms that minimally invasive Paget's disease of the vulva may sometimes be an aggressive disease. We consider that lymphatic metastases already existed in this patient at the time of initial surgery; thus, the recurrence of EMPD on extragenital skin sites may have been prevented if initial treatment would have included radical vulvectomy and bilateral groin lymph node dissection instead of simple vulvectomy without groin lymph node dissection.

During 1971-1996, 17 patients with mixed mesodermal uterine tumors were treated. Average age at diagnosis was 67.3 years, 12/17 were of European and 5/17 of Afro-Asian extraction. The overall 5-year survival was 21%. 10/17 patients had mixed mesodermal tumors with a heterologous mesenchymal element, and 7/17 had a homologous mesenchymal element (carcinosarcoma). 6/17 had another primary malignancy, including breast cancer (3/17), bilateral metachronous breast tumor (2/17), and malignant lymphoma of the neck region (2/17). All 3 with breast cancer had previously been treated with tamoxifen. I had simultaneous mesodermal tumor and ovarian thecoma. Simultaneous autoimmune manifestations occurred in 2/17, including thrombocytopenic purpura in 1, and myasthenia gravis in another. Mesodermal tumor of the uterus is a relatively rare malignancy with aggressive behavior and poor prognosis. It also had unusual associations with other primary tumors, hormonal treatment, and autoimmune manifestations.

Primary ovarian sarcomas are rare and usually behave very aggressively. Over a ten-year period (1987-1996) five cases of primary ovarian sarcoma were managed at the Soroka Medical Center, Beer-Sheva, Israel. Four patients had malignant mullerian-mixed mesodermal tumor (MMMMT): two had Stage IIIC tumor with chondrosarcoma being the predominant sarcomatous element, one had Stage IIIC tumor with high-grade endometrioid stromal sarcoma (ESS) being the predominant sarcomatous element and one had Stage IC tumor with rhabdomyosarcoma being the predominant sarcomatous element. One patient had Stage IA leiomyosarcoma (LMS). All four patients with MMMMT received postoperative adjuvant chemotherapy, whereas the patient with LMS did not. The four patients with MMMMT died of their disease 10, 10, 13 and 25 months, respectively, after initial surgery. The patient with LMS died of intercurrent disease 21 months after initial surgery. It is concluded that most patients with primary ovarian sarcoma present with extraovarian disease and the prognosis is poor. The mainstay of treatment is debulking surgery consisting of total abdominal hysterectomy, bilateral salpingo-oophorectomy and extirpation of tumor masses. The benefit of postoperative adjuvant chemotherapy and/or radiotherapy is still a subject of debate and has yet not been established.

Objective: To evaluate clinical-pathological aspects of mitotically active leiomyomas., Study Design: Twenty patients with smooth muscle tumors of the uterus, with 5-9 mitotic figures per 10 high power fields and without atypia or necrosis were studied. The clinical and pathological characteristics of these tumors were reviewed and analyzed., Results: Patients' ages ranged from 33 to 63 years (mean 42.5 years). The size of the tumors ranged from 1.5 to 9.5 cm (mean 5.4 cm). On gross examination all tumors appeared as typical leiomyomas. Treatment included hysterectomy in 16 patients and myomectomy in four. Follow-up periods ranged from 1.5 to 11 years (mean 6.8 years). None of the patients developed a recurrent tumor., Conclusion: The benign clinical behavior of such tumors supports their current designation as mitotically active leiomyomas, thus deleting the previous misnomer 'smooth muscle tumors of uncertain malignant potential'. Myomectomy is an appropriate treatment, particularly in young patients interested in reproduction.

Background and Objectives: Endometrial carcinoma is the commonest female genital tract malignancy in the south of Israel. The purpose of this study was to investigate the clinical and histologic findings, treatment and outcome of patients with endometrial carcinoma in the south of Israel., Methods: Data from the files of 231 patients with endometrial carcinoma who were managed at the Soroka Medical Center between January 1961 and December 1994 were evaluated., Results: Endometrial carcinoma was more prevalent among Jewish as compared to Arab-Beduin women, and among Ashkenazi as compared to Sephardic Jewish women. The prevailing presenting symptom was postmenopausal bleeding and most patients (68.8%) had Stage I disease. Most patients (209/225, 92.9%) underwent surgery, 131/222 (59%) had radiotherapy and 15/214 (7%) received chemotherapy. The 5-year survival rate was 79.1% overall; 89% for Stage I, 71.7% for Stage II, 21.6% for Stage III and 0% for Stage IV; 89.8% for Grade 1, 70% for Grade 2 and 60.9% for Grade 3; 100% for adenoacanthoma, 82% for endometrioid carcinoma, 65.8% for adenosquamous carcinoma and 51.6% for papillary serous carcinoma., Conclusions: Endometrial carcinomas are characterized by a relatively favorable prognosis with a 5-year survival of about 80%. Surgical stage, histologic differentiation and histologic subtype are sensitive predictors of survival. The mainstay of treatment is surgery with adjuvant pelvic radiotherapy when necessary.

Immunohistochemical staining of normal and cancerous ovarian tissues has demonstrated that both IL-1 alpha and IL-1 beta are more strongly expressed in cancerous than in normal tissues and are secreted mainly by epithelial cells. We have shown by bioassay and immunoassay that cancerous, but not normal ovarian tissues constitutively secrete IL-1 in vitro. Activation of cancerous ovarian tissues by lipopolysaccharide (LPS) increased its capacity to secrete IL-1. Normal ovarian tissues secreted low amounts of IL-1 only after prolonged stimulation (72-96 h) by high doses of LPS (10-100 micrograms/ml). On the other hand, constitutive IL-1 was detected in homogenates of normal ovarian tissues and stimulation by LPS increased its capacity to produce IL-1. IL-1 beta was the main type of IL-1 secreted by cancerous ovarian tissues. IL-1 alpha was detected at lower levels. In contrast, in normal tissues similar amounts of both IL-1 alpha and IL-1 beta were detected in the supernatants. The levels of both types of IL-1, and also the bioactivity of IL-1 were significantly higher in cancerous than in normal ovarian tissues. Established primary cell lines from normal ovarian tissues did not secrete IL-1 into supernatants but did express it at very low levels. Stimulation with LPS did not affect the capacity of these cell lines to secrete IL-1 but it increased their capacity to express it. In contrast, primary established epithelial cell lines from cancerous ovarian tissues did secrete and express high levels of IL-1 and these levels were increased under stimulation with LPS. Cancerous ovarian tissues did not only secrete higher levels of both IL-1 alpha and beta than normal ovarian tissues, but also the mechanism controlling the secretion of these factors in cancerous ovarian tissues seemed to be different from that found in normal ovarian tissues. Our results suggest that paracrine/autocrine factors may be involved in the regulation of both types of IL-1 secreted by ovarian tissues. These cytokines may play a role in regulating the physiological, pathophysiological and oncogenic processes of the ovary.

Myasthenia gravis is a neurologic disorder characterized by intermittent muscle weakness which improves after anticholinesterase medication. The pathogenesis of myasthenia gravis is associated with production of autoantibodies to nicotinic acetylcholine receptor in the motor end plate. Most patients do not have an underlying neoplasm, but in 10-15% of the cases, a thymoma may be detected. Apart from thymoma, no other tumor type or organ has consistently been associated with myasthenia gravis. We describe an unusual case of myasthenia gravis in a patient with malignant mixed Mullerian tumor of the uterine corpus. Initial histology revealed malignant mixed Mullerian tumor of a predominant carcinomatous element. At that time, there were no symptoms of muscle weakness. Intraabdominal metastases were detected later, concommitantly with symptoms of muscle weakness and the diagnosis of myasthenia gravis. Histology of the metastases disclosed an exclusive mesenchymal element with striated muscle differentiation. To the best of our knowledge this case is the first report of myasthenia gravis in a patient with malignant mixed Mullerian tumor of the uterine corpus. We propose that the mechanism contributing to myasthenia gravis in this patient was closely associated with the evolving histology and with the nature of the tumor, so that antibodies produced to muscle-like epitopes exposed by malignant cells could have cross-reacted with acetylcholine nicotinic receptors and caused myasthenia gravis.

Background: Uterine sarcomas are rare, charaterized by rapid clinical progression and poor prognosis, and their management has been a challenge. The purpose of this study was to investigate the clinical and histologic findings, treatment, and outcome of patients with uterine sarcoma in the south of Israel., Methods: Data from the files of 36 patients with uterine sarcoma who were managed at the Soroka Medical Center between January 1961 and December 1994 were evaluated., Results: The 5-year survival rate was 32% overall; 63% for 9 patients with endometrial stromal sarcoma (ESS). 30% for 14 patients with mixed mesodermal sarcoma (MMS) and 18% for 13 patients with leiomyosarcoma (LMS): 41% for 22 patients with Stage I and 19% for 14 patients with Stages II, III, and IV. Only the difference in the 5-year survival rate between ESS and LMS was statistically significant (P < 0.05). Eleven patients (30.6%) were treated with surgery alone, 4 (11.1%) with surgery followed by pelvic radiotherapy, 11 (30.6%) with surgery followed by chemotherapy, 8 (22.2%) with surgery followed by pelvic radiotherapy and chemotherapy, one (2.8%) with chemotherapy alone, and one (2.8%) had no treatment., Conclusions: Uterine sarcomas are aggressive tumors with a poor prognosis. The treatment is surgery generally followed by adjuvant pelvic radiotherapy and/or systemic chemotherapy.

In a study of 37 patients diagnosed with cervical adenocarcinoma between 1961 and 1994, clinical and pathologic findings were evaluated. Of the 37 patients, 27 (73%) had a pure adenocarcinoma, five (13.5%) had a collision tumor and five (13.5%) had an adenosquamous carcinoma. Twenty-six patients (70.3%) were diagnosed in Stage I, and 11 (29.7%) patients in Stage II, III, and IV. Two patients (5.4%) were treated with simple hysterectomy alone, nine (24.3%) with simple hysterectomy followed by radiotherapy, eight (21.6%) with radical hysterectomy alone, five (13.5%) with radical hysterectomy followed by radiotherapy, nine (24.3%) with radiotherapy alone, one (2.7%) with radiotherapy followed by simple hysterectomy, and three (8.1%) received no treatment. The actuarial 5-year survival rate was 69%. It is suggested that for patients with small early-stage disease, radical hysterectomy should be primary treatment and postoperative adjuvant radiotherapy would be advocated if high-risk features are histologically demonstrated. For all other patients, radiotherapy should be primary treatment.

We examined paraffin sections for the expression of interleukin-1 alpha, interleukin-1 beta and tumor necrosis factor-alpha, in 40 cases of Hodgkin's disease. Our purpose was to study the role of these cytokines in the "inflammatory" histological features and "B" symptoms in this disease. Immunohistochemistry with the avidin-biotin-peroxidase complex method was used. The findings were compared with those of 20 cases of non-Hodgkin's lymphomas and of 20 non-neoplastic lymphadenopathies. Evidence for EBV infection and myc and ras oncoproteins expression was also studied in these patients, but no correlation between any of these features and cytokine expression was found. We found a significant correlation between the expression of interleukin-1 beta and several "inflammatory" histological features, as well as between the expression of tumor necrosis factor-alpha and B symptoms and tumor bulk. The differential correlations between these major pro-inflammatory cytokines expression and the "inflammatory" manifestations in Hodgkin's disease are remarkable, considering the complexity of the cytokines composing the cytokine network involved in this disease.

In a study of 20 patients diagnosed with malignant ovarian germ cell tumors between 1961 and 1993, clinical and pathologic findings were evaluated. Of the 20 patients, seven (35%) had dysgerminoma, two (10%) endodermal sinus tumor, three (15%) malignant teratoma, one (5%) malignant struma ovarii, one (5%) primary ovarian carcinoid, two (10%) benign teratoma with malignant transformation, and four (20%) combination germ cell tumor. Twelve patients (60%) had stage IA, five (25%) stage IC, and three (15%) stage IIIC. Twelve patients (60%) underwent conservative surgery and eight (40%) had at least bilateral salpingo-oophorectomy. At follow-up, 18 patients (90%) were alive free of disease, one (5%) had died of disease, and one (5%) had died of intercurrent disease. The actuarial 5-year survival rate was 93.3%. It is concluded that for young women who wish to preserve child-bearing capacity, regardless of the stage of the tumor, fertility-preserving surgery with complete surgical staging followed, if necessary by cisplatin-based combination chemotherapy is an appropriate and definitive treatment in the absence of involvement of the contralateral ovary and uterus. For patients in whom child-bearing capacity is not an issue, surgery should include total abdominal hysterectomy and bilateral salpingo-oophorectomy with complete staging, followed if necessary by chemotherapy.

The presence or absence of tubal mucosal epithelial proliferation (MEP) and its degree of severity when present were investigated in 191 cases, including 49 ovarian serous tumors of low malignant potential (LMP), 33 nonserous (predominantly mucinous) LMP tumors, various other benign and invasive malignant female genital tract lesions, and 37 cases (73 fallopian tubes) of tubal ligation for sterilization. MEP including all degrees of severity was found to be an almost ubiquitous (83% of all cases) lesion of no clinical significance. On the other hand, MEP of moderate or marked degree was rarely seen (3% of cases) in normal tubes obtained for sterilization, but was identified in from 25% to > 40% of tubes accompanying a wide variety of nonneoplastic and neoplastic lesions. Thus, we recommend that only moderate to marked MEP be considered as a diagnosable lesion in the future. There was no tendency in this material for MEP to show any specific association with ovarian serous LMP tumors, as was previously reported. However, when MEP was present, it was more likely to be widespread and mitotically active when it accompanied an ovarian LMP tumor of any histologic type than when it was found with benign ovarian lesions, invasive gynecologic cancers, uterine leiomyomas, or tubal inflammatory lesions and ectopic pregnancies.

In a study of 18 patients diagnosed with ovarian granulosa cell tumor between 1961 and 1992, clinical and pathologic findings were evaluated. Of the 18 patients, 15 (83.3%) were diagnosed in Stage I and three (16.7%) in Stage III or IV. Six patients (33.3%) underwent conservative surgery and in 12 (66.7%) total abdominal hysterectomy and bilateral salpingo-oophorectomy was performed. At follow-up three patients (16.6%) had died of disease, three, 16 and 288 months, respectively, after initial surgery. The actuarial 5-year survival rate for Stage I was 100%, while that for Stages III and IV combined was 33.3% (P < 0.05). It is concluded that for patients with Stage IA, unilateral oophorectomy seems to be adequate treatment and for those with more than Stage IA, surgery should include total abdominal hysterectomy and bilateral salpingo-oophorectomy. Postoperative adjuvant chemotherapy is advocated for patients in whom spread of tumor beyond the ovaries has occurred.

Dimethyl dioctadecyl ammonium bromide (DDA), a lipophilic quaternary amine, was evaluated in adult chickens for potentiation of immunological responses to subcutaneously administered inactivated Newcastle disease virus (NDV) vaccines. DDA enhanced humoral and cell-mediated immune (CMI) responses to levels which were significantly higher than those induced by the vaccine alone The haemagglutination inhibition antibody titers induced by DDA were slightly lower than those induced by mineral oil although neutralizing antibody titers seemed to be higher. DDA induced strong CMI (DTH and lymphocyte proliferation) responses, more than those induced by Freund's complete adjuvant and mineral oil. Both DDA and mineral oil induced comparable high levels of protection to challenge doses of 200,000 LD50 per chicken. No toxic effects or local tissue damage were observed in any of the inoculated chickens.

Of 50 patients with borderline epithelial ovarian tumors, 32 (64%) had serous, 17 (34%) had mucinous and one (2%) had endometrioid tumor. All patients with mucinous tumor had stage I disease, whereas 4 patients with serous tumor had stage II-III disease. Five patients (10%) were pregnant at the time of diagnosis. Seventeen patients (34%) had initial surgery with ovarian conservation and 7 of them were not subjected to further surgery. Five patients (10%) received adjuvant chemotherapy. Five-year survival and 5-year disease-free survival rates were 100% and 96.4%, respectively. It is concluded that for patients with stage IA disease unilateral salpingo-oophorectomy seems to be adequate treatment and for those with more than stage IA disease, surgery should include total abdominal hysterectomy and bilateral salpingo-oophorectomy. Although the effectiveness of chemotherapy in these tumors is uncertain, adjuvant chemotherapy is advocated for patients in whom spread of the tumor beyond the ovaries has occurred.

The effects of an inadvertent injection of sodium hypochlorite into the cheek during irrigation of the right maxillary central incisor root canal are reported. The patient suffered from severe pain, edema, and necrosis of subcutaneous tissues and mucosa. Surgical intervention was necessary to contain the destructive process which extended from the upper lip to the right eye. The histopathological examination demonstrated the high cytotoxicity of sodium hypochlorite on vital tissue.

Cell nuclei from breast biopsies are a byproduct of routine hormone receptor determination and are usually discarded. We report here that DNA purified from this source is suitable for use in conventional Southern blot or Polymerase Chain Reaction (PCR) techniques to screen for Her-2/neu amplification, enabling efficient use of limited biopsy material.

Hypoglossal nerve palsy occurred in 2 patients with infected second branchial arch cleft cyst. This very unusual complication of the congenital anomaly has been related to the mechanical compression of the mass. Histologic features of the perineural coat were also suggestive for this etio-pathogenesis.

Two cases of endometrial sarcoma that developed many years after exposure to unopposed exogenous and endogenous estrogens, with no previous pelvic irradiation, are described. The literature is reviewed and the possible effect of prolonged unopposed estrogen stimulation is suggested as an etiologic factor in such extremely rare conditions. These cases add additional support to the assumption that prolonged and excessive endogenous or exogenous unopposed estrogen stimulation of the uterus may increase the risk of endometrial sarcoma.

Embryonal rhabdomyosarcoma is a common tumor of children, rarely appearing in the scrotum from tunica vaginalis or paratesticular tissues. In adults it is rare and carries a particularly bad prognosis. A case of paratesticular rhabdomyosarcoma occurring in a seventy-three-year-old man who survived a total of five and one-half years from the time of his original operation, is presented.

Monoclonal antibodies (McAbs) were prepared against carcinoembryonic antigen (CEA), derived from human metastases to the liver of primary colon adenocarcinoma. A stable clone, secreting monoclonal anti-CEA antibody (Ab), was selected. The hybridoma cells were grown in BALB/C mice, forming ascites fluids containing 2-5 mg/ml of the relevant McAbs. Ascites fluids were purified using a DEAE-Sephacel column. The purified immunoglobulin fraction was characterized as IgG2b, having a dissociation constant of 2 X 10(-9)M. The potential use of these McAbs for CEA diagnosis and purification was evaluated: the IgG2b fraction, when bound to Sepharose 4B, facilitated the purification of CEA from spent media of a human colon adenocarcinoma cell line, resulting in iodination grade CEA; the anti-CEA McAbs demonstrated differential histochemical staining of various sections, both fresh and fixed; the McAbs were also found to be suitable as tagging Abs in a CEA RIA.

A case of a 16-year-old girl with lymphoblastic lymphoma confined to the ovaries and the para-aortic lymph nodes, who was treated with intensive radio- and chemotherapy and who is alive and well nine years after treatment, is described. The literature on ovarian involvement by lymphoma is reviewed.

Biochemical pathways which are involved in energy metabolism were examined in the kidney of heat-acclimated hamsters. It was found that heat acclimation caused 47% reduction in glucose-6-phosphatase (G1c-6-Pase) activity and 40% lower rate of gluconeogenesis. No changes were found in the activity of hexokinase, glucose-6-phosphate dehydrogenase, pyruvate kinase, lactic dehydrogenase, or in kidney glycogen content. Isolated kidney mitochondria of heat-acclimated hamsters utilized 15% less oxygen than that of controls, but no differences were found in the P/O ratio. Determination of the content of some cytochromes showed a significant reduction in cytochromes c + c1, but no difference was found in the content of cytochromes a, a3, and b. These results suggest that the kidney plays a role in the reduction of energy metabolism during the process of heat acclimation.

Estrogen and progesterone receptor (ER and PgR) levels and peroxidase activity were measured in the first biopsy and in tissue removed 4-10 days later during mastectomy of previously biopsied tumor. The proportion of ER- and PgR-positive tumors declined from 71% and 63%, respectively, in the biopsy group, to 46% and 36% in the mastectomy group. Peroxidase activity was low or absent in all biopsy specimens, but was present in 16 out of 25 tumors which had been biopsied previously. Receptor levels in paired specimens obtained from the same patient were lower in the mastectomy in 14 out of 18 receptor-positive cases. This decrease in the receptor level was accompanied by a significant increase in peroxidase activity. We suggest that an attempt be made to perform receptor analysis from "virgin" tumor tissues at initial biopsy. If this is not possible, measurement of peroxidase activity could be helpful in evaluating the degree of receptor deterioration.

We report a case of a 71-yr old man with seronegative rheumatoid arthritis, who developed severe enterocolitis during gold therapy. Radiological studies, endoscopy and biopsies showed diffuse involvement of the stomach, duodenum and small and large intestines. The clinical course was prolonged and complicated by multiple infections. Of the 10 cases with chrysotherapy-induced enterocolitis reported in the literature, 3 were from Israel. There may be a relationship between the development of enterocolitis following gold therapy, ethnic group and HLA-B8 and DRw3 antigens.