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.

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.

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.

[A case of pseudosarcoma of the esophagus (author's transl)]. / Un caso di pseudosarcoma dell'esofago

Pseudosarcoma of the esophagus previously has been described and documented in only 13 patients. Our case, after a successful total esophagectomy with esophagogastroplasty, is physically well without any symptoms of recurrence to date (18 months postoperative).

Malignant testicular germ cell tumor in father and son: a case report.

This is the eighteenth case of testicular tumor in a father and son reported in the literature. The father had a seminoma and the son an embryonal carcinoma. The trend favoring more malignant tumors occurring at younger ages in the sons is confirmed by this report.

Ki-67 labeling index in breast cancer.

Measurements of cell cycle kinetics have been found to correlate with the clinical course of patients with breast cancer. However, the thymidine labeling index and more rapid methods like flow cytometry remain complicated and costly. We assessed cell proliferation of 67 breast carcinomas by an immunoperoxidase procedure using a monoclonal antibody, Ki-67, which reacts with a nuclear antigen in proliferating cells. The percentage of Ki-67 positive cells ranged from 2% to 70%. Tumors with high mitotic rate, high nuclear grade, high histologic grade, and negative estrogen receptors had statistically higher Ki-67 labeling rates. We found no significant differences between the Ki-67 labeling rate and other clinical (age at diagnosis, menopausal status) or pathologic (necrosis, fibrosis, vascular invasion, lymphatic invasion, cellular reaction, tumor size, lymph node metastases) features assessed. These results parallel previously reported data, and confirm that this immunohistochemical staining of breast carcinoma by Ki-67 monoclonal antibody can be considered a rapid and convenient method for assessing cell cycle kinetics. However, further studies, evaluating the correlation between Ki-67 labeling rate and prognosis are needed to better define the real usefulness of this analysis in clinical practice.

[Perforations of the small intestine]. / Perforazioni del tenue

Six cases of perforation of the small intestine, one secondary to anaphylactoid purpura and five spontaneous, are reported. Ingestion of an iced drink acted as a trigger in two cases. A vascular genesis is put forward to explain the aetiopathogenesis of two cases and it is noted that perforation of this type is present in the final ileal ansa, at the mesenterial margin. In three cases, histology revealed the presence of double refraction crystal. These came from vegetal residues and are probably capable of penetrating from the lumen into the mucosa causing a foreign body reaction, abscess and subsequent perforation. In these cases, perforation occurred in an ansa located further away than the last ileal ansa (about 3 m) and on the mesenterial margin. Intestinal resection and subsequent end-to-end, single layer anastomosis were performed in all cases.