The basement membrane components type IV collagen and laminin were examined immunohistochemically in 14 cases of adenocarcinoma of the cervix. The patterns of staining in adenocarcinoma in situ, invasive adenocarcinoma, and early invasive adenocarcinoma were compared to see whether characteristic patterns could be delineated. Adenocarcinoma in situ had a uniform intact basement membrane, whereas the basement membrane of invasive adenocarcinoma was fragmented and irregular. Cases of early stromal invasion showed early gland buds and outpouchings with defective basement membrane staining. The degree of histologic differentiation of the tumor was not clearly related to the amount of basement membrane component staining. The concept of early stromal invasion in cervical adenocarcinoma, as supported by our immunohistochemical studies, is discussed as it relates to a possible pathogenic mechanism in early invasion and infiltration of adenocarcinoma of the cervix.

Basement membrane immunostaining was performed on pepsin-digested, paraffin-embedded blocks of 29 squamous cell carcinomas of the cervix (invasive and in situ) and 13 of the vulva, using polyclonal rabbit antibodies to human laminin and type IV collagen, both staining identically. Laminin with varying defectiveness surrounded invasive foci, whereas adjacent carcinoma in situ or normal epithelium had intact laminin. The amount of laminin usually reflected the degree of tumor differentiation. Absence of laminin around totally keratinized or necrotic tumor nests indicated its dependency on viable cells. New buds from established invasive tumor nests were often more laminin-defective than the parent nest and suggested a cyclic invasive process, with laminin loss during a growth surge followed by laminin reformation during quiescence. In cases of questionable early stromal invasion, deficient laminin could sway the decision toward making a positive diagnosis. The tendency of laminin gaps and tumor buds to contain large malignant cells with pleomorphic nuclei supports the concept of a change in tumor cell metabolism during active invasion. Laminin also appeared around metastatic tumor within lymph nodes. The relationship of inflammation to tumor laminin defectiveness varied.

Histological grade and cell type were major prognostic factors in a retrospective study of 63 patients with Stage I epithelial carcinoma of the ovary. Grading by architectural pattern seemed to predict relapse better than cytological grading. With serous, mucinous, and endometrioid cystadenocarcinomas, relapses increased with higher grades. Relapse occurred in none of 18 tumors of borderline malignancy, 2 of 27 (7%) with Grade I or II tumor, and 4 of 6 (67%) with Grade III. The upper abdomen and pelvis were both at risk. Because most recurrences were limited to the peritoneal surface in Grade III serous, mucinous, and endometrioid carcinoma, local and regional radiation therapy are justified; postoperative therapy is not recommended for borderline or Grade I tumors unless ascites or cytological evidence of peritoneal disease is present. Clear-cell carcinoma was uncommon and unfavorable; of 12 cases, 5 involved relapse, with 3 recurrences developing outside the abdomen.

Between July 1968 and December 1976, 26 patients with surgical-pathologic Stage III adenocarcinoma of the endometrium were treated at the Joint Center for Radiation Therapy. In 15 patients, extrauterine disease was confined to the ovary and/or fallopian tube (Group A). In 11 patients, disease extended beyond these organs to the vagina or other pelvic structures (Group B). Treatment included a combination of radiation therapy and surgery in all but one patient, who was treated by radiation therapy alone. The median follow-up was 65 months and the median time to relapse 9 months. The actuarial relapse-free 5-year survival for all Stage III patients was 54%; it was significantly different (P = 0.01) for Group A (80%) and Group B (15%). The nature of extrauterine involvement in surgical-pathologic Stage III adenocarcinoma of the endometrium is of major prognostic significance.

Between September 1968, and December 1975, 40 patients with Stage II epithelial tumors of the ovary were treated at the Joint Center for Radiation Therapy. Thirty-six patients had undergone a total abdominal hysterectomy and bilateral salpingo-oophorectomy (BSOH) with attempted total removal of disease, and all patients received postoperative pelvic irradiation. The five-year actuarial relapse-free survival rate is 66% and the overall survival rate 70% for the entire group of patients. The histology was reviewed in all cases and graded for the percentage of solid vs. papillary or glandular in the specimen. Of the 36 patients treated with a BSOH, 18 had well-differentiated tumors defined as containing less than a 10% solid architectural pattern. There have been no relapses in this group of patients. In contrast, 9 of 18 patients with moderately or poorly differentiated tumors containing a 10% or more solid pattern have relapsed; five diffusely in the abdomen, two in the pelvis, and two in the lungs or pleura. It appears that a BSOH followed by pelvic irradiation is sufficient treatment for Stage II patients with well-differentiated tumors showing less than a 10% solid pattern. In contrast, patients with less well-differentiated tumors have a high risk of relapse outside of the pelvis and need additional treatment. Alternative treatment options are discussed.

In order to properly stage patients with ovarian carcinoma, we are routinely removing and microscopically examining sample aortic lymph nodes in these patients, since aortic lymph node metastases may affect long-term survival. Inasmuch as benign glandular inclusions can be found in pelvic and aortic lymph nodes, we have run into difficulty distinguishing such inclusions from genuine metastases in cases of low-grade or borderline serous ovarian carcinomas. Atypical epithelium in these tumors may closely resemble the lining of benign glandular lymph node inclusions. Moreover, like metastases benign glandular inclusions may grow in the peripheral sinusoid, show epithelial papillae and psammoma bodies, and may even proliferate as small sheets of cells. Just how crucial it is to recognize aortic lymph node metastases in these low-grade tumors will be clarified when the prognostic importance of aortic node metastases becomes understood.

In the entire world literature, there are only seven reported cases of malignant hemangioendothelioma arising in the uterus. An eighth case, reported here, was a 17-year-old girl who lived for 8 years after curettings and subsequent hysterectomy revealed malignant hemangioendothelioma of the endometrium with extension to the left ovary. Pelvic recurrences were temporarily controlled with chemotherapy, X-ray treatment, and repeated surgery. However, the patient eventually succumbed to massive growth of malignant hemangioendothelioma in the pelvis, with extension into the inferior vena cava and left external iliac vein. Growth within blood vessel lumens was also striking in the surgical specimens of recurrent tumor. Microscopically, the important diagnostic feature was the presence of numerous capillaries lined by malignant endothelial cells.

Twenty-seven (24.5%) of the 110 newly diagnosed cases of invasive cervical cancer at the Boston Hospital for Women from January 1975 through June 1978 were 35 years of age or younger. Twenty-five of these young patients (93%) had Stage I cervical cancer and 2 had Stage II disease. Seven (26%) of these patients had cervical adenocarcinomas. All young patients with Stage I disease are presently clinically free of tumor. Fifteen of the young patients (55.5%) had reportedly negative cervical cytology smears prior to the detection of a symptomatic cervical malignancy. The cervical smears from 10 of the patients with reportedly negative cervical cytology were reexamined at the Boston Hospital for Women, and our review demonstrated missed cervical neoplasia in 5 cases and unsatisfactory technique for adequate interpretation in 2 cases. Abnormal cervical cytology precipitated the diagnosis of invasive cervical cancer in only 37% of the young patients. All suspicious and symptomatic cervical lesions in young women should be promptly biopsied regardless of prior reassuring cervical cytology.

The present case reports the concurrence of endometriosis of the vaginal cuff with endometrial stromal sarcoma in association with high-dose estrogen. This case raises the question of whether chronic high-dose estrogen might be associated with malignant transformation of endometrial stroma. Although there is no definitive evidence of a causal relation between estrogen and endometrial stromal sarcoma, the possibility should be explored further. Therapy of this neoplasm is discussed and salient clinical and pathologic features are reviewed.