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One hundred thirty-four patients with bulky and barrel-shaped cervix cancers were treated with preoperative radiation to 40-45 Gy, intracavitary therapy using Cs-137 or Cf-252 and extrafascial total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAHBSO) 4-6 weeks after radiotherapy. Outcome of therapy was traced for patients with residual tumor (positive) in the hysterectomy specimen and those who had no residual tumor (negative) in the specimens. All specimens were studied by a set protocol to carefully evaluate the TAHBSO specimen for gross or residual tumor. Ninety-two percent of the patients with negative specimens survived 5 years, but this dropped to 71% if the specimen was positive. These findings were observed in both the Cs-137- and Cf-252-treated patients. Patients with negative specimens failed mainly in distant sites, whereas those with positive specimens failed locally and distantly. Patient survival was less in patients with positive specimens. There was no difference in outcomes for adenocarcinoma and squamous cell carcinomas. The specimen histological findings have predictive value in patients treated with preoperative radiation and surgery.

Seventy-four patients with Stage II endometrial cancer were treated by a combination of preoperative radiation therapy followed by extrafascial hysterectomy, bilateral salpingo-oophorectomy, and paraaortic lymph node sampling at the University of Kentucky Medical Center from 1967 to 1988. All patients had histologically confirmed endometrial cancer with involvement of the endocervix. The cell types and numbers of the tumors treated were as follows: adenocarcinoma, 58; adenoacanthoma, six; adenosquamous carcinoma, nine; and clear cell carcinoma, one. Preoperative radiation consisted of 4500 cGy external therapy followed by one intracavitary implant providing an additional 2000 cGy to point A. Surgery was done 4 to 6 weeks after completion of radiation therapy. Five patients (7.1%) had paraaortic lymph node metastases. Four were treated with extended-field radiation therapy and one with platinum-based combination chemotherapy. After treatment, the patients were followed at regular intervals from 2 to 22 years (mean, 5.4 years). Eleven patients (15%) had recurrent cancer, with the vagina and upper abdomen being the most common sites of spread. The estimated 5-year and 10-year disease-free survival rates of these patients are 88% and 76%, respectively. Cell type, depth of myometrial invasion, and lymph node status were the most important prognostic variables in the patients evaluated. These data confirm that the combination of preoperative radiation therapy and surgery produces excellent long-term survival in patients with Stage II endometrial cancer.

Plasma carcinoembryonic antigen (CEA) levels in 75 patients with invasive cervical cancer were measured during and after radiation therapy. Initial CEA levels were elevated in 65% of the patients, the incidence varying with stage of disease. Of the 32 patients followed during therapy, CEA levels rose in 26 (81%). CEA values after therapy in the same 32 patients showed three patterns: (1) decline to normal, associated with a disease-free state; (2) decline but not to normal, associated with heavy cigarette smoking or persistent disease; and (3) decline to normal, followed by a rise to abnormal, associated with tumor recurrence. Elevation of CEA levels preceded recognition of recurrent cervical cancer by as much as 4 months in five of seven patients.

Surgical specimens from 111 patients with Stage I endometrial cancer were reviewed for the presence of lymph-vascular space invasion by tumor cells. Lymph-vascular space invasion was noted in 16 cases, and occurred most frequently in poorly differentiated tumors with deep myometrial penetration. Tumor recurrence developed in 44% of patients whose tumors demonstrated lymph-vascular space invasion as opposed to only 2% of patients without this finding (p less than 0.001). Of seven patients with lymph-vascular space invasion who experienced tumor recurrence, five developed extra-pelvic metastases. Discriminant function analysis of these data revealed a statistically significant correlation between lymph-vascular space invasion and tumor recurrence, independent of histologic differentiation of myometrial penetration. These findings suggest that lymph-vascular space invasion by tumor cells is an important prognostic variable in Stage I endometrial cancer which should be considered in treatment planning.

One hundred seventy-seven patients with squamous cell carcinoma that invaded the cervical stroma to a depth of 5.0 mm or less were the subjects of this investigation. Fifty-one patients were treated primarily by vaginal hysterectomy, 42 by total abdominal hysterectomy, and 84 by radical hysterectomy with pelvic lymphadenectomy. In 52 patients with lesions that invaded the cervical stroma to a depth of 3.0 mm or less, 984 lymph nodes were examined and none contained metastatic tumor. Conversely, lymph node metastases were present in three of 32 patients with lesions that had stromal invasion of 3.1 to 5.0 mm. After therapy, all patients were followed up from 2 to 14 years, and none was lost to follow-up. Among 145 patients with lesions that invaded the stroma to a depth of 3.0 mm or less, only two developed recurrences, both of which were intraepithelial. Among the 32 cases of carcinoma that invaded the stroma 3.1 to 5.0 mm, there were three invasive recurrences, and two deaths.

The clinical and histologic features of eight cases of carcinoma of the endometrium which developed following radiation therapy for squamous cell carcinoma of the cervix are described. No patient had a well-differentiated tumor and significant myometrial invasion was present in all cases. Three of the eight tumors were papillary serous adenocarcinoma. Five of the eight patients developed recurrent tumor and died of their disease. The risk of endometrial cancer in patients previously radiated for cervical cancer is evaluated.

Prognostic parameters were evaluated in 22 patients with small (less than or equal to 2 cm) superficially invasive (less than 5 mm) squamous cell carcinoma of the vulva. Primary surgery included radical vulvectomy with bilateral superficial and deep inguinal lymph node dissection in 11 patients, and wide local excision with ipsilateral superficial inguinal lymph node dissection in 11 patients. Of the 22 patients studied, only 2 (9%) had lymph node metastases. Both patients had a single positive ipsilateral superficial inguinal node. Perineural invasion was strongly associated with lymph node metastases (P less than 0.01). In this group of patients, grade, depth of invasion, lymph-vascular space invasion, and lymphoplasmacytic infiltration were not predictive of lymph node metastases (P greater than 0.05). Two patients initially treated with wide local excision and ipsilateral superficial inguinal lymph node dissection developed recurrent vulvar neoplasia on the contralateral vulva, and both were successfully retreated by wide local excision. All patients are presently alive and well with no evidence of disease. None of the histomorphologic parameters studied were predictive of tumor recurrence. These data suggest that wide local excision with ipsilateral superficial inguinal lymphadenectomy is effective in the treatment of patients with small, superficially invasive carcinomas of the vulva.

From 1962 to 1985, 2201 patients with invasive cervical cancer were staged, evaluated, and treated at the University of Kentucky Medical Center. After a thorough evaluation, 25 cases (1.1%) fulfilled the histologic criteria for small cell cancer defined by Reagan and coworkers. These patients were computer-matched for age, disease stage, and lesion size to 25 patients with large cell nonkeratinizing cancer and 25 patients with keratinizing squamous cell cancer. Morphometric analyses of nuclear size and maximum nuclear diameter were performed on all cases without knowledge of cell type. Small cell cancers were characterized by a nuclear area of 160 mu 2 or less and a maximum nuclear diameter of 16.2 mu, which was significantly lower than that for large cell tumors. Thirty-three percent of the small cell carcinomas stained positively for the neuroendocrine markers (neuron-specific enolase [NSE] and chromogranin [CGR]), whereas the remainder contained only epithelial markers such as cytokeratin (CYK) and epithelial membrane antigen (EMA). Small cell cancers were associated with a high frequency of lymph-vascular space invasion and a diminished lymphoplasmacytic response. Patients with small cell cancer had a significantly higher recurrence rate, particularly to extrapelvic sites, than the matched patients with large cell cancers, and their survival was lower. Clinical trials to determine the efficacy of adjuvant chemotherapy in the treatment of small cell cervical cancer are needed.

Pelvic lymph nodes from 80 patients with primary invasive cervical cancer undergoing radical hysterectomy and pelvic lymphadenectomy were evaluated morphologically. Six to 25 (mean 14) lymph nodes from each patient were examined histologically and classified as follows: lymphocyte preominant, germinal center predominant, unstimulated, or lymphocyte depleted. Tumors were classified according to their primary cell type: large cell non-keratinizing, keratinizing squamous cell, small cell, and adenocarcinoma. There was no direct relationship between lymph node morphology and patient age, lesion size, or tumor cell type. A lymphocyte predominant nodal pattern was associated with a statistically significant decrease in lymph node metastases, and tumor recurrence, and an increase in patient survival. In contrast, patients with a lymphocyte depleted nodal pattern had a high incidence of metastatic disease and tumor recurrence, and a decreased survival. Patients with lymph nodes showing an unstimulated or germinal center predominant pattern had an intermediate incidence of nodal metastases and tumor recurrence. These findings suggest that regional lymph nodal morphology may be of prognostic significance in patients with invasive carcinoma of the uterine cervix.