Ergotamine, flunarizine and sumatriptan do not change cerebral blood flow velocity in normal subjects and migraneurs.

Changes in the diameter of extracranial and intracranial arteries resulting in changes in cerebral blood flow have previously been assumed to be the most important pathophysiological factor in migraine. To test this hypothesis 20 normal subjects, and three groups of patients (n = 29) with migraine were investigated by means of transcranial Doppler sonography. Blood flow velocities in the middle cerebral (MCA) and in basilar (BA) arteries were measured. Data from patients were obtained in the interval between migraine attacks, during migraine attacks and following treatment with either ergotamine (0.5 mg i.m.; n = 10); flunarizine, a calcium overload blocker (20 mg i.v.; n = 13); or a 5-HT1-like agonist (sumatriptan, 4 mg s.c.; n = 6). Ergotamine and sumatriptan are constrictors of cerebral arteries in animal experiments. The arithmetic mean of flow velocity in the BA was reduced in normal subjects (45 cm/s) as compared with patients with migraine measured in between attacks (53 cm/s). Mean flow velocity in MCA was not different in normals (72.5 cm/s) as compared with migraineurs (75 cm/s). Neither ergotamine nor the 5-HT1 agonist and flunarizine resulted in a significant change in blood flow velocity in MCA and BA. This was true irrespective of whether the drugs were given in the headache-free period, during a migraine attack or during the withdrawal phase of drug-induced headache. Ergotamine was effective in improving headache during migraine attacks and sumatriptan attenuated headache during drug withdrawal from chronic analgesic intake. These results indicate that the action of ergotamine and the 5-HT1-receptor agonist is probably not mediated by their vasoconstrictor action on cerebral arteries.

Basement membrane of cervical adenocarcinoma: an immunoperoxidase study of laminin and type IV collagen.

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.

Malignant mixed müllerian tumor of the ovary with prominent neuroectodermal differentiation (teratoid carcinosarcoma).

We report a unique carcinosarcoma of the ovary having an organoid growth pattern that resembled immature teratoma. The tumor contained both adenocarcinoma and squamous carcinoma (focally sebaceous) admixed with chondrosarcoma, rhabdomyosarcoma, and malignant neuroectodermal components. The neuroectodermal components were prominent, resembling ependymoblastoma, medulloepithelioma, ganglioneuroblastoma, glioblastoma multiforme, and pigmented neuroectodermal tumor. Immunohistochemical studies dramatically revealed carcinoma and rhabdomyosarcoma admixed with malignant neuroectodermal tumor. Implants of papillary serous carcinoma (with psammoma bodies) were present in the opposite ovary, uterine serosa, omentum, and appendiceal serosa. Although a variant not previously described in the ovary, this ovarian carcinosarcoma closely resembled nasopharyngeal tumors described as teratoid carcinosarcoma or terato-carcinosarcoma.

An immunoperoxidase study of laminin and type IV collagen distribution in carcinoma of the cervix and vulva.

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.

Histologic prognosticators in stage I squamous cell carcinoma of the vulva.

Sixty-four cases of stage I vulvar squamous cell carcinoma were analyzed histologically to define a patient subset at minimum risk for recurrence or nodal metastases. Three patterns of invasion were predefined: carcinoma in situ with early stromal invasion (33%), pushing (8%), and infiltrative (59%). Infiltrative pattern and invasion deeper than 1.5 mm equally predicted nodal metastases (P = .045), although depth measurement in biopsy specimens was subject to sampling error. Confluence and absence of carcinoma in situ each predicted extranodal recurrence (P = .011). Local recurrence appeared more related to inadequate surgical margins than failure to perform radical vulvectomy. Carcinoma in situ with early stromal invasion represents a group at zero risk for nodal metastases. We recommend wide local excision for all stage I lesions. In general, omission of lymphadenectomy should be reserved for cases of carcinoma in situ with early stromal invasion.

Conjugated estrogen use and risk of endometrial cancer.

The relation between use of conjugated estrogens and the risk of uterine cancer was examined among 188 white women with newly diagnosed endometrial cancer and 428 controls hospitalized for nonmalignant conditions requiring surgery at the Boston Hospital for Women-Parkway Division, Boston, Massachusetts, in January 1970-June 1975. As in prior studies, the greatest increases in risk were associated with dosages of 0.625 mg or greater (relative risk (RR) = 3.8, 95% confidence interval (CI) = 2.2-6.6) and duration of use of 10 or more years (RR = 7.6). Risk was elevated whether or not use was cyclic. Cyclic use was associated with a higher risk (RR = 3.6, 95% CI = 2.2-6.6) than continuous use (RR = 2.4, 95% CI = 1.3-4.1), but the difference between these risk estimates was not statistically significant. Risk remained increased even among women who had discontinued use of conjugated estrogens five or more years previously (RR = 4.5). Cases who were previous users had less advanced lesions at diagnosis than had never users. The highest risk associated with use of conjugated estrogens was that for stage I, grade 1 disease with no myometrial invasion. However, increases in risk of more advanced disease were seen among long-term users.

The role of postoperative local or regional irradiation in the treatment of stage I ovarian cancer.

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.

Radiation therapy in stage II ovarian carcinoma: the influence of histologic grade.

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.

Distinguishing lymph node metastases from benign glandular inclusions in low-grade ovarian carcinoma.

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.

Clear cell carcinoma of the uterine endocervix with an in situ component.

In the past all clear cell carcinomas of the female genital tract were thought to arise from mesonephric remnants. Recently increasing evidence has related their origin to müllerian rather than mesonephric epithelium. One of the main reasons that has been advanced to support their mesonephric origin has been their occurrence in the uterine cervix and vagina, sites of mesonephric remnants. However, no clear evidence for mesonephric origin of clear cell carcinoma of the cervix and vagina has been ever provided. In contrast, there is substantial evidence that diethylstilbestrol-related clear cell carcinomas of the cervix and vagina are müllerian in origin. We report here a case of an exophytic clear cell carcinoma with an in situ component, involving the endocervical epithelium. The in situ lesion clearly indicates müllerian origin of the tumor, which occurred in the absence of prenatal exposure to diethylstilbestrol. This supports the general agreement that clear cell carcinomas of the cervix are müllerian in origin, whether diethylstilbestrol-related or not.

The cytologic diagnosis of breast aspirations.

A series of 1,792 breast cytology specimens were evaluated from the Boston Hospital for Women for the years 1970-1974. The majority (1,684) were needle aspiration smears, the remainder (108) were nipple secretion smears. The cytologic criteria for diagnosing breast specimens were presented. Of the 1,792 breast specimens examined cytologically, 48 cases were histologically proven cancers with 33 smears containing malignant or suspicious cells, indicating 92% accuracy (after correction for unsatisfactory smears). A suspicious or positive interpretation of the smears prompted a biopsy and led to early diagnosis. Although needle aspiration cytology is not a new technique, it is one which is economical, easy, accurate and lacking in complications to the patient. Hopefully in the near future, it will be a more widely accepted procedure for the early detection of breast cancer.

Endometrial stromal sarcoma arising from vaginal endometriosis.

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.

Microscopic appearance of the human fallopian tube following a reanastomosis procedure.

Microscopic evaluation of a human fallopian tube following end-to-end anastomosis over a polyethylene stent was performed 10 days after the initial surgical procedure. The stent was removed on the 3rd postoperative day. Examination of the excised tube revealed a patent lumen without any evidence of mucosal compromise. The submucosa adjacent to the anastomotic site revealed a mild polymorphonuclear leukocytic infiltration, although a marked inflammatory response was observed around the 5-0 chromic sutures used in the reanastomosis. This case and recent animal studies suggest that early removal of the stent does not appear to jeopardize the patency of the tube and may be preferable to removal after 3 to 4 months.