Behavior of borderline tumors with particular interest to persistence, recurrence, and progression to invasive carcinoma: a prospective study.

PURPOSE: Borderline tumors account for 10% to 20% of epithelial ovarian tumors, and their prognosis is outstanding; nevertheless, a mortality of up to 20% has been reported, particularly in earlier reports. There is a lack of information about the actual mortality and the rate of progression into invasive carcinoma in large and prospectively accrued populations. PATIENTS AND METHODS: All women with borderline ovarian tumors undergoing primary surgery in our department or referred within 3 months from surgery performed elsewhere from 1982 to 1997 were prospectively accrued and observed. RESULTS: We studied 339 women (83.4% stage I, 7.9% stage II, and 8.5% stage III). The median age at diagnosis was 39 years. A total of 150 women underwent radical surgery, and 189 underwent fertility-sparing surgery. After surgery, 13 women had macroscopic residual disease. With a median follow-up of 70 months, 317 women are alive with no clinical disease (eight with documented subclinical persistence of implants), three are alive with clinical disease, two died of disease, 10 died of other reasons, and seven women have been lost to follow-up. The recurrence of disease was higher after fertility-sparing surgery (35 of 189 cases) than after radical surgery (seven of 150 cases); nevertheless, all but one woman with recurrence of borderline tumor or progression to carcinoma after conservative surgery were salvaged. We observed seven progressions (2.0%) into invasive carcinoma, five in serous tumors (2.4%), and two in mucinous tumors (1.6%). The disease-free survival is 99.6% in stage I patients, 95.8% in stage II, and 89% in stage III. CONCLUSION: The survival of patients with borderline tumors is higher than previously described in some retrospective studies. Conservative surgery is safe and may be proposed to several patients with early and disseminated disease after thorough discussion of all therapeutic options. Progression to carcinoma is approximately 2% and may be observed in both mucinous and serous tumors.

Survival and reproductive function after treatment of malignant germ cell ovarian tumors.

PURPOSE: Germ cell ovarian tumors are curable. The possible sequelae of chemotherapy on long-term survivors are still unknown, but these patients may expect normal lives. The aim of this study was to evaluate the outcome and reproductive function in a population of women treated since 1982. MATERIALS AND METHODS: Between 1982 and 1996, 169 women with malignant germ cell ovarian tumors were seen (70 dysgerminomas, 28 endodermal sinus tumors, 24 mixed tumors, and 47 immature teratomas). Seventy-one had advanced or recurrent disease. Fertility-sparing surgery was performed in 138 (81%) women, 81 of whom received postoperative chemotherapy. RESULTS: With a median follow-up of 67 months, the survival rate was 94% for dysgerminoma, 89% for endodermal sinus tumors, 100% for mixed types, and 98% for immature teratoma. For women who were treated conservatively, the survival rate was 98%, 90%, 100%, and 100%, respectively. Two women had adnexal recurrences, and both received salvage treatment. After treatment, all but one postpubertal woman had recovery of menses within 9 months. During follow-up, 12 untreated and 20 treated patients had 55 conceptions. We recorded 40 pregnancies at term, six terminations, and nine miscarriages. Four malformations were observed: one in 14 conceptions of patients who had not received chemotherapy and three in 41 conceptions of treated patients. CONCLUSION: Irrespective of subtype and stage, conservative surgery should become the standard approach to treating most patients with malignant ovarian germ cell tumors. Fertility seems to be only marginally affected by treatments. Miscarriages are in the expected range for the general population. The malformation rate is slightly higher than in the general population, but no significant difference was seen between patients who did and did not receive chemotherapy.

p53, cyclin-D1, PCNA, AgNOR expression in squamous cell cancer of the lip: a multicenter study.

BACKGROUND: The development of squamous cell carcinoma of the lower lip is an interesting model of photocarcinogenesis because of the structural and topographic characteristics of the lips. The purpose of this study was to evaluate the expression of immunohistochemical markers on the lips of patients with lower lip squamous cell carcinoma (LLSCC), compared with a control population. METHODS: Of the 98 subjects involved in the study, 58 were suffering from squamous cell carcinoma of the lower lip. The remaining 40 acted as a control. The case studies were taken from six university and hospital dermatology and plastic surgery departments. Questionnaires were administered to assess the risk factors for LLSCC. The cases involving squamous cell carcinoma underwent surgical excision and punch biopsy specimens were obtained from 20 control patients. Tissues were prepared in 5-microm-thick sections to carry out the following immunohistochemical study: PCNA, p53, AgNOR, cyclin-D1, bcl-2. RESULTS: The lower lip was the predominant location of squamous cell carcinoma, with the following factors playing important roles: chronic sun exposure, history of smoking, alcohol use and familial risk of cutaneous tumors. The male/female ratio in our survey was 5:1. The p53 protein was positive in approximately 50% of SCC cases and in 20% of controls. This protein is mostly associated with chronically photoexposed skin areas. AgNOR positivity increased with the loss of cellular differentiation; a progressive increase in size and a poorly defined shape were evident in poorly differentiated carcinomas. CONCLUSIONS: The results of this multicenter study showed that there is a noticeable difference in the expression of PCNA, p53, cyclin-D1, and AgNOR in tissues from patients with LLSCC and controls.

Conservative treatment followed by chemotherapy with doxorubicin and ifosfamide for cervical sarcoma botryoides in young females.

Sarcoma botryoides of the cervix is an extremely rare tumour and seems to be associated with a better prognosis than its vaginal counterpart. Recent studies have suggested that it is possible to limit surgery to local excision in stage I cases. We report three cases of young subjects treated successfully with polypectomy or diathermy loop excision followed by adjuvant chemotherapy. One patient had a local recurrence which was treated with further local excision. All subjects remain alive without evidence of recurrence and with normal menstrual function 36, 38 and 38 months following initial diagnosis. A conservative surgical approach to early cervical sarcoma botryoides is possible. The efficacy of adjuvant chemotherapy and the regimen of choice still need to be investigated.

The accuracy of staging: an important prognostic determinator in stage I ovarian carcinoma. A multivariate analysis.

BACKGROUND: Several prognostic factors for stage I ovarian carcinoma have been analyzed. Some of them are biological and clinical in nature, but others such as the thoroughness of the staging procedure, the extent of the surgery and the philosophy of treatment, are defined by the human element. PATIENTS AND METHODS: We reviewed the records of 351 patients with Stage I ovarian cancer who had been treated from 1981 to 1991. For all patients the following information was available: age, size of the tumor, FIGO sub-stage, tumor grade, histologic type, rupture of the tumor, cytology, extent of the staging and of the surgery (hysterectomy and bilateral salpingo-oophorectomy vs. fertility-conserving surgery) and use of adjuvant treatments. The thoroughness of the staging was defined as: optimal staging: total abdominal hysterectomy and bilateral salpingo-oophorectomy or fertility-conserving surgery, peritoneal cytology or washing, omentectomy, multiple peritoneal biopsies, sampling of the retroperitoneal nodes or formal lymphadenectomy, peritoneal staging: all the criteria described above were met with the exception of retroperitoneal sampling, incomplete staging: lack of any of the previously-cited criteria. RESULTS: An optimal staging was performed in 100 patients, a peritoneal staging in 107 and an incomplete staging in 144. Radical surgery was performed in 295 women and fertility-conserving surgery in 56. With a median follow-up of 108 months (range 14-184) 64 patients had recurrence of the tumor. Fifty-three died of the disease, two are currently alive with disease and nine were salvaged by surgery and/or chemotherapy. In a multivariate analysis only the tumor grade and the type of staging were significant independent prognostic factors for both disease-free and overall survival. CONCLUSIONS: As described by other authors, we confirm that tumor grade is the single most important biological prognostic factor in early ovarian carcinoma. The thoroughness of the staging impacts significantly on survival, particularly in poorly differentiated carcinomas. Fertility-sparing surgery is not associated with a worse outcome than standard radical surgery.

Fertility-sparing surgery in uterine leiomyosarcoma.

BACKGROUND: Leiomyosarcoma of the uterus is a rare malignancy with a poor prognosis. Total abdominal hysterectomy is considered the treatment of choice. Occasionally, the diagnosis is made on myomectomy specimen, and in young patients the role of conservative management is not well defined. PATIENTS AND METHODS: Between 1982 and 1996, eight patients with a diagnosis of uterine leiomyosarcoma following myomectomy were conservatively managed at our institution. Median age of the patients was 29 years (range 19-32 years), and all were nulliparous. The tumor was confined to a myoma in all patients. Patients were adequately informed about the risk and were submitted to strict follow-up including pelvic examination, hysteroscopy, ultrasonography, chest X-ray, and abdominopelvic MRI or CT scan. RESULTS: Mean mitotic count of leiomyosarcomas was 6 per 10 HPF, ranging between 5 to 33. At a median follow-up of 42 months three pregnancies were recorded. Two patients had a spontaneous delivery at term. The third patient had diagnosis of recurrent disease at the time of cesarian section. Despite further surgery and chemotherapy, she died of disseminated disease 26 months after diagnosis. The remaining seven patients are alive and well. Two patients received a second surgical procedure after diagnosis of leiomyosarcoma, 24 and 16 months after primary operation. Both were found to have leiomyomas. CONCLUSIONS: Selected cases of uterine leiomyosarcoma might be managed conservatively in young nulliparous women desiring pregnancy. A strict follow-up is mandatory, and at the completion of the reproductive life, a demolitive procedure could be considered.

Conservative surgery for stage I ovarian carcinoma in women of childbearing age.

OBJECTIVE: To assess the results of a policy of tailored conservative surgical management for young women with stage I ovarian carcinomas. DESIGN: Retrospective study. PARTICIPANTS: Ninety-nine women aged 40 years or younger who underwent either primary surgery in our department or were referred after primary surgery performed elsewhere. METHODS: Of the 99 women in our study, 56 underwent fertility-sparing surgery and 43 more radical surgery. Minimal requirements for conservative management were adequate staging and complete information about the therapeutic options. Factors important in the choice of the treatment were, age, wish to preserve fertility, histologic type and grade, and the stage of the tumour. RESULTS: Conservative treatment was conducted in 84% of nulliparous and in 33% of parous women; 62% of grade 1 tumours, 48% of grade 2, and 50% of grade 3 were treated conservatively. With a median follow up of seven years, we observed five recurrences (9%) of carcinoma in women treated conservatively and five (12%) in those treated more radically. Two women (one in each treatment arm) were saved after recurrence. Two recurrences after conservative surgery involved the residual ovary (3.6%). Two women developed borderline tumour in the contralateral ovary and both were treated by surgery. CONCLUSION: After adequate staging and accurate information is given to the patient, conservative treatment may be safe in some women with early ovarian cancer. The risk of recurrence in the contralateral ovary is low. Conservative surgery may be also considered in some Stage I grade 3 tumours and in some women with stage JC tumours.

Choriocarcinoma coexistent with intrauterine pregnancy: two additional cases and a review of the literature.

Choriocarcinoma coexistent with normal intrauterine pregnancy is rare and poses questions about its origin. Although the development from trophoblastic remnants of previous pregnancies can not be excluded in some cases, the findings of incidental macro- and microscopic foci of choriocarcinoma in apparently normal placentas show the possible transformation of normal trophoblast into choriocarcinoma during an otherwise normal pregnancy. The diagnosis and management of choriocarcinoma coexistent with intrauterine pregnancy have changed dramatically over the decades but the survival rates are still unsatisfactory. In this review, we summarize some of the most common features of this disease.

Pre-operative morphological and colour Doppler features of borderline ovarian tumours.

OBJECTIVE: To evaluate pre-operatively the sonographic morphology and colour Doppler findings of borderline ovarian tumours and to compare these findings to those of benign and malignant tumours. METHODS: Pre-operative transvaginal and colour Doppler ultrasound examinations were performed on 150 women with adnexal tumours. Pulsatility index, resistance index, peak systolic velocity, site, number and confluence of vessels were recorded. RESULTS: Fifty-six women had malignant ovarian tumours, 74 had benign and 20 had borderline tumours. No biological, morphological or demographic parameters were specifically predictive of borderline tumours. Intratumoral vessels with a pulsatility index of below 1.0 were observed in 19 of the 20 borderline tumours; a morphological score suggested malignancy in 15 women whereas the CA125 exceeded 30 u/ml in 10 cases. Confluence of blood vessels was observed only in three cases. A model including intracystic complexity (either vegetations or septa), pulsatility index of less than 1.0, absence of confluence of vessels, CA125 of less than 150 u/L, in a woman under 60 years of age allowed borderline tumours to be detected with 85% sensitivity, 92% specificity and 91% accuracy. CONCLUSION: Borderline tumours have haemodynamics resembling those of malignant tumours but the distribution of vessels is often similar to that observed in benign tumours; this observation should be considered when proposing multiparameter scoring systems including colour Doppler ultrasound to identify malignancies of the ovary. Colour Doppler findings may be of assistance in the follow up of women after conservative surgery for ovarian malignancies.

[Association of a granular-cell tumor with an epidermoid carcinoma of the esophagus]. / Associazione di tumore a cellule granulose e carcinoma epidermoide dell'esofago.

Granular cell tumor is a rare tumor, described for the first time by Abrikossoff in 1926. Occurrence in the esophagus is rare (1.6% of digestive localizations). This paper reports a case of granular cell tumour associated with squamous cell carcinoma of the esophagus.

Cancer of the cervix, FIGO stages IB and IIA: patterns of local growth and paracervical extension.

The relationship between patterns of local growth and paracervical extension of cervical cancer was evaluated in operative specimens of 230 patients with squamous cell carcinoma FIGO stage IB and IIA who were primarily treated, between January 1989 and December 1993, by abdominal radical hysterectomy with pelvic lymphadenectomy. Twelve cervical giant sections, each representing an area of 30 degrees, including the corresponding paracervical tissues (lateral parametria, vesicocervical ligaments, and uterosacral ligaments), were made parallel to the cervical canal, and serial horizontal step sections at 3 &mgr;m were cut. Cervical carcinoma spread endocervically equally in all directions; higher frequencies were observed in the front and back cervical quadrants (about 28%) than in the lateral ones (about 22%) (P = NS). The corresponding tumor extension beyond the cervix was into the vesicocervical ligaments (anterior parametria) and the vesicocervical septum in about 23% of cases, into the uterosacral ligaments (posterior parametria) and the rectovaginal septum in about 15% of cases, and into right and left lateral parametria in about 28% and 34% cases, respectively. Paracervical extension (26%) was significantly related to the maximum depth of stromal invasion (chi2 = 19.11; P < 0.01), minimum thickness of uninvolved fibromuscular cervical stroma (chi2 = 32.34; P < 0.01), lymphatic invasion (chi2 = 17.91; P < 0.01), pelvic lymph node metastases, (chi2 = 48.37; P < 0.01) and tumor size (chi2 = 26.38; P < 0.01). Furthermore, involvement of anterior and posterior paracervical tissues was related to high percentages of the minimum thickness of unaffected cervical stroma in the corresponding front (92%) and back (88%) quadrants, whereas these percentages were much lower (30%) in lateral cervical quadrants with carcinomatous extension to lateral parametria. These patterns of growth suggest that surgery is only radical with respect to lateral parametria in the treatment of cervical cancer.

Overexpression of the T-cell receptor beta-chain variable region TCRBV14 in HLA-A2-matched primary human melanomas.

We have shown previously that peripheral blood lymphocytes (PBL) of patients with metastatic melanoma include cytotoxic T-cell clones that recognize Melan-A/MART-1 in a HLA-A2-restricted fashion. Such clones preferentially use the variable (V) regions TCRBV14 or TCRBV7 in the beta-chain of their T-cell receptor (TCRB). It was not known, however, whether this finding is associated with the presence of the HLA-A2 allele in tumor tissue and whether evidence of the predominance of these TCRBV families can also be observed in primary tumor tissue. To address these issues, we have used a semiquantitative PCR to examine the TCRBV repertoire in six HLA-A2-matched primary melanomas in comparison with their autologous PBL. Although each patient had his or her own pattern of skewed TCRBV utilization, in all patients, T-cells that used TCRBV14 were significantly overrepresented in the neoplastic site compared with PBL. All of the primary tumors studied had detectable expression of Melan-A/MART-1 and gp100, and immunohistochemical analysis confirmed the presence of the HLA-A2 allele. Additional samples of Melan-A/MART-1-positive, gp100-positive primary melanomas from six non-HLA-A2 patients and four autologous normal skin controls failed to reveal a TCRBV14 predominance in such tissues. These results point to a role of TCRBV14 T lymphocytes in the HLA-A2-restricted immune recognition of primary melanomas.

Pre-operative interleukin-2 immunotherapy induces eosinophilic infiltration in colorectal neoplastic stroma.

Interleukin-2 (IL-2) may induce peripheral eosinophilia and this phenomenon is related with response to IL-2 immunotherapy in patients with metastatic renal cell carcinoma. In previous experiences is reported that preoperative course with IL-2 may reverse the surgery-induced immunosuppression. This study's objective is to evaluate the histological changes of inflammatory infiltration in tumour stroma, in patients pretreated with IL-2 immunotherapy. 7 patients admitted to our surgical department with resectable recurrent colorectal cancer were treated with pre-operative course of IL-2; the tissue samples were analyzed for eosinophilic and inflammatory infiltration and compared with the samples obtained in the primary operation, performed without immunotherapy. In all patients were observed an increase of eosinophilic infiltration in tumour tissue. The mean increase were 200%, with high statistical significance (p < 0.0001). IL-2 pre-operative immunotherapy is able to change the interaction between host and tumour, by modifying the histological inflammatory infiltration in colorectal cancer tissue.

Abnormalities of Doppler waveform of the hepatic veins in patients with chronic liver disease: correlation with histologic findings.

OBJECTIVE: Changes in the Doppler waveform of the hepatic veins are associated with chronic liver disease, particularly cirrhosis. We correlated abnormalities in Doppler waveforms of hepatic veins with histologic findings in the liver to determine the accuracy of Doppler imaging in the detection of cirrhosis. SUBJECTS AND METHODS: Fifty-two patients with chronic hepatitis C were examined prospectively and blindly by two sonographers. In the same session, a liver biopsy specimen was obtained from each patient and submitted to three independent pathologists for conventional interpretation and for grading of severity according to a predetermined scoring system. Duplex sonography of the hepatic veins was also performed in 50 control subjects. RESULTS: Abnormal hepatic vein waveforms were detected in 12 of 16 patients with cirrhosis and in eight of 36 patients without cirrhosis. However, histologic examination of the biopsy specimens showed that only two of the eight patients without cirrhosis had no significant abnormalities, other than mild portal inflammation. Abnormal waveforms were seen in no control subjects. We found a correlation between fibrosis and steatosis and abnormalities in the Doppler waveform of the hepatic veins (r = .50, p < .001). Portal inflammation, intralobular degeneration, and necrosis did not correlate with an abnormal waveform. CONCLUSION: Duplex sonography of the hepatic veins may be useful for studying liver disease associated with fibrosis and steatosis. In patients with well-compensated liver disease, flattening of the Doppler waveform of the hepatic vein suggests the presence of cirrhosis.

Primary ovarian small cell carcinoma: four more cases.

A case report of four patients affected by primary ovarian small cell carcinoma is presented. The surgical and chemotherapeutic approaches are described for each case. Cisplatin-based chemotherapy obtained objective responses in two of four patients, but three of four patients died of disease progression within 2 years from the diagnosis. One patient, who was stage Ib and underwent bilateral salpingo-oophorectomy, total hysterectomy, and adjuvant chemotherapy is still alive 58 months after surgery. Accurate diagnosis and a multidisciplinary approach are needed to ameliorate the prognosis of this tumor that, at present, remains very poor.