Search

All patients with carcinoma of the cervix, FIGO Stage IB, treated at the University of Minnesota Hospitals during a 10-year period were reviewed. Of the 220 patients 31 (14.0%) developed recurrent disease and did not survive. Thirteen patients had pelvic wall recurrences, with concurrent cervical involvement. No patient had a resectable pelvic recurrence. Hysterectomy was subsequently performed on 10 of the 172 patients who received radiation therapy. Carcinoma was not present in any of the operative specimens although two patients with adenocarcinoma later died of metastatic cancer. Median time of recurrence was 9 months, with median survival following recurrence of 6 months. Cervical cytology was not of value in the early diagnosis of recurrent disease. The 5-year adjusted actuarial survival rate for patients with adenosquamous carcinoma was significantly lower than that for patients with squamous cell carcinoma. The median age of patients not surviving with adenosquamous carcinoma was significantly lower than that for patients not surviving with squamous cell carcinoma. Patients with invasive carcinoma presumably confined to the cervix may have disseminated disease. It is essential such selected patients receive primary treatment that includes systemic therapy.

All patients with cervical carcinoma, FIGO Stage I-B, admitted to the Gynecologic Oncology Service of the University of Minnesota Hospitals during the 10-year period ending December 31, 1979, were reviewed. The 5-year survival rate without evidence of disease was 75.3%, the corrected rate being 80.8%. During the last half of the study there was a significant increase in the percentage of patients with adenosquamous carcinoma. The survival rate for younger patients with this diagnosis was significantly lower. Patients frequently had normally interpreted Pap smears in the years just prior to the diagnosis of invasive carcinoma. Early diagnosis of cervical carcinoma is essential. Reliance cannot be placed on a normally interpreted Pap smear, particularly for those patients who have adenosquamous carcinoma or adenocarcinoma.

Presumed precursors of adenocarcinoma of the uterine cervix were investigated with specific techniques to identify human papillomavirus (HPV) DNA. The presence of HPV DNA in 36 lesions of glandular dysplasia and 16 lesions of microglandular hyperplasia of the uterine cervix was studied by in situ hybridization using 3H-labeled HPV 16 and HPV 18 DNA probes. Only two of 36 lesions (6%) of glandular dysplasia contained HPV 18 DNA, although 64% of coexisting adenocarcinoma in situ, microinvasive adenocarcinoma, and cervical squamous intraepithelial neoplasia III lesions contained HPV 18 and/or HPV 16 DNA. Two lesions of HPV 18 DNA-positive glandular dysplasia coexisted with adenocarcinoma in situ that contained the same type of HPV DNA. None of the microglandular hyperplasia lesions contained HPV 16 DNA or HPV 18 DNA. These results suggest that, if HPV infection is an initial step toward carcinogenesis, it is unlikely that glandular dysplasia and microglandular hyperplasia are precursor lesions of adenocarcinoma of the uterine cervix. A large proportion of glandular dysplasia may represent reactive lesions of endocervical columnar epithelium. Two lesions of HPV 18 DNA-positive glandular dysplasia may represent well-differentiated components of adenocarcinoma in situ of the uterine cervix.

Trophoblastic pseudotumor, the histopathologic entity described by Kurman and associates (R. J. Kurman, R. E. Scully, and H. J. Norris, Cancer 38 , 1214–1226 (1976)), has been considered in the scheme of gestational trophoblastic neoplasia as an exaggerated form of syncytial endometritis and, therefore, associated with a benign outcome. The manifestation of malignant sequalae and ultimate demise of a patient in a recognized case of trophoblastic pseudotumor is presented. Light and electron microscopic studies and autopsy findings are discussed. Therapies, both surgical and chemotherapeutic, and serum assay of the β subunit of human chorionic gonadotropin are correlated to the clinical course.

A mixed intestinal adenocarcinoma-argentaffin carcinoma of the vagina in a 32-year-old woman is reported. Special stains showed the argentaffin and argyrophil reactions of the small cell population of this tumor. The small cells also contained serotonin as demonstrated by immunocytochemistry. Electron microscopy revealed characteristic cytoplasmic neurosecretory granules. The large cells were columnar and contained mucin droplets similar to those in Goblet cells in the intestines. The observations suggest that the tumor was mixed intestinal adenocarcinoma-argentaffin carcinoma (malignant carcinoid), which probably arose in aberrant intestinal epithelial cells in the vagina. The patient died with metastases of pure argentaffin carcinoma in 1 year.

Members of the Editorial Board who have been active in the study of female genital HPV-related lesions have responded to a series of questions related to the histopathologic diagnosis of such lesions in the uterine cervix, the performance of auxiliary studies, therapeutic choices, and the correlation of cytologic and tissue diagnoses.

A prospective randomized study was undertaken to determine whether the administration of oral contraceptives after the evacuation of a hydatidiform mole affects the human chorionic gonadotropin serum level in a way that leads to an increased frequency in the diagnosis of postmolar trophoblastic disease. Between 1981 and 1988, 266 patients were randomly assigned to either oral contraceptives or barrier contraception after evacuation of a hydatidiform mole. Patients were followed up until serum levels of human chorionic gonadotropin were normal or until specific criteria for the diagnosis of postmolar trophoblastic disease were met. Twenty-three percent of patients receiving oral contraceptives had postmolar trophoblastic disease, whereas those using a barrier method had a rate of 33%. The median time to spontaneous regression in the oral contraceptives group was 9 weeks, whereas the median time to regression in the barrier group was 10 weeks. Twice as many patients in the barrier group became pregnant in the immediate follow-up period. We conclude that oral contraceptives are the preferred method of contraception after evacuation of a hydatidiform mole.

The currently accepted method of treatment of patients with nonmetastatic gestational trophoblastic neoplasia (NMGTN) is single-agent chemotherapy. While methotrexate and actinomycin D have shown superiority over other cytotoxic agents, doses of drug and length of treatment are subject to controversy. Recently, the demonstration of the long half-life of actinomycin D in both animal models and humans has necessitated a reevaluation of the method of administration of this drug for NMGTN. Following the demonstration of minimal severe toxicity of pulse actinomyin-D scheduling by E. S. Petrilli and C. P. Morrow (Actinomycin D toxicity in the treatment of trophoblastic disease, Gynecol. Oncol. 9, 18-22 (1980), 12 consecutive patients with nonmetastatic gestational trophoblastic neoplasia were treated. The remission rates, toxicity, and cost effectiveness of pulse actinomycin-D scheduling in these 12 patients are reported.

Summary A case of metastasizing basal cell carcinoma (BCC) of the vulva is presented and compared with 10 nonmetastasizing tumors of the same histologic type by various clinicopathologic parameters. The former neoplasm manifested several features that distinguished it from most of the nonmetastasizing tumors, such as vaginal bleeding at presentation; advanced clinical stage; invasion of subcutaneous fat, urethra, and vagina; tumor thickness greater than 1 cm; and a morphealike pattern of growth. This series, in conjunction with previously published observations, would suggest that vulvar BCC behaves much like its counterpart in sites other than the vulva, locally recurring but metastasizing only on rare occasion. Simple wide excision of the tumor is curative in the majority of cases. More aggressive surgery may be warranted for large tumors that are locally destructive and extend into the subcutaneous fat, like our metastasizing case and the two other examples of metastasizing vulvar BCC in the literature. In this report, treatment options for vulvar BCC are discussed, as well as the use of the term “basosquamous” carcinoma, and whether vulvar BCC may be a manifestation of a more generalized syndrome of cutaneous basal cell neoplasia in some cases.

Epithelioid sarcoma (ES) and malignant rhabdoid tumor (MRT) have heretofore been regarded as two separate clinicopathologic entities. However, they have some histologic similarities, and both represent histogenetic and phenotypic enigmas. This study reports the pathologic and immunohistochemical findings of four vulvar neoplasms occurring in young women that represented diagnostic dilemmas because of their similarity to both ES and MRT. Only one case had the classic histologic features of ES, whereas, in our opinion, the other three cases fulfilled the histologic criteria of MRT, despite the fact that two of the three cases were reported earlier as examples of ES. Neither electron microscopy nor immunohistochemistry has been found to be helpful in separating ES from MRT, mainly because they share several ultrastructural and immunophenotypic features. The behavior of these vulvar tumors--ours and the few published examples of ES--is generally aggressive, more in keeping with MRT than classic ES. We believe that some, if not most, putative ES of the vulva are in fact MRT, a neoplasm with an unfavorable prognosis.

Previously, human papillomavirus (HPV) DNA, mainly HPV-18 DNA, was detected in more than 40% (17/40 cases) of invasive adenocarcinoma of the uterine cervix in our laboratory. In order to identify HPV DNA in the precursor lesions of adenocarcinoma of the cervix, 11 cases of adenocarcinoma in situ containing microinvasive adenocarcinoma and 10 cases of adenocarcinoma in situ were studied for the presence of HPV DNA by in situ hybridization using highly sensitive 3H-labeled HPV-16 and HPV-18 DNA probes. HPV types present in cervical squamous intraepithelial neoplasia (CIN) coexisting with adenocarcinoma in situ and microinvasive adenocarcinoma were also studied. Apart from the coexisting CIN II-III with glandular neoplasms, 48 cases of CIN III (severe dysplasia and squamous carcinoma in situ) removed by conization or hysterectomy and known to be free of adenocarcinoma were used for comparison. HPV DNA was detected in 64% of microinvasive adenocarcinoma, 70% of adenocarcinoma in situ, and 63% of the control CIN III. HPV-18 DNA was the preponderant type of HPV DNA found in adenocarcinoma in situ and microinvasive adenocarcinoma. All cases of HPV DNA-positive microinvasive adenocarcinoma contained the same type of HPV DNA as the lesions of coexisting adenocarcinoma in situ. CIN coexisting with microinvasive adenocarcinoma or adenocarcinoma in situ contained the same type of HPV as identified in the glandular lesions, whereas all of the HPV DNA-positive control CIN III cases contained HPV-16 DNA. These results suggest that adenocarcinoma in situ is a precursor lesion of adenocarcinoma of the cervix that contains HPV DNA, and that CIN coexisting with adenocarcinoma may be a result of a metaplastic process of adenocarcinoma or of bidirectional differentiation of the affected reserve cells.

Cases of invasive carcinoma of the uterine cervix were analyzed to determine whether the presence or absence of human papillomavirus (HPV) DNA in the neoplasms was a contributing factor to their outcome. The presence of HPV DNA was evaluated using in situ hybridization on formalin-fixed, paraffin-embedded tissue sections. Eighty-five patients with cervical carcinoma who had been surgically evaluated were included in the study. Data from these patients was analyzed retrospectively to determine survival, recurrence, presence of nodal metastases, tumor grade, mode of therapy, peritoneal fluid cytologic results, and age in relation to presence or absence of HPV DNA. No significant statistical differences were found between the HPV-16-positive, HPV-18-positive, and HPV DNA-negative patients.

Concurrent weekly cis-platinum in a dose escalating manner and conventional radiotherapy was evaluated in advanced cervical cancer. The toxicity of weekly cis-platinum given 2 hr before standard fractionation of radiotherapy was assessed using the modified GOG toxicity criteria. Sixteen patients having parameters indicating high risk for conventional therapy failure including positive pelvic and paraaortic nodes and intraperitoneal spread were entered. There was no life-threatening toxicity. The toxicity of the administered chemotherapy was only moderate. Patient compliance was good as at the 20 mg/m2 dose level, 79% of the prescribed doses were administered. The use of adjuvant cis-platinum in poor prognosis advanced cervical cancer merits further study.

From 1978 to 1983, 112 women with advanced cervical carcinomas received radiotherapy after pretreatment surgical staging. Five-year actuarial relapse-free survival rates were a strong function of lymphatic spread: 40% with periaortic node metastases, 50% with pelvic node metastases, and 84% without node metastases. Primary treatment failure had a distant component in 75% of recurrences (50% of recurrences with negative nodes and 85% of recurrences with positive nodes). It was concluded that adjuvant systemic therapy is necessary to substantially raise the probability of cure.

Forty-two cases of recurrent and 14 cases of advanced clinical stage (III and IV) endometrial carcinoma are presented, in which progesterone and estrogen receptors from the metastatic sites were measured. Mean survival time (time from recurrence or, in advanced stages, from the time of diagnosis to death or last follow-up), mean total survival time (time from diagnosis to death or last follow-up), and mean time to recurrence (time from diagnosis of primary tumor to the time of recurrence) were positively correlated with positive progesterone and estrogen receptor status and with histologic grade of tumor. No correlation was found with age, clinical stage, depth of myometrial invasion, or site of metastasis. However, when multiple variables were considered with the Cox regression model, the combination most highly correlated with survival included progesterone receptor, grade of tumor, and site of metastasis (pelvis vs. other sites). All differences were statistically significant (p less than 0.05). We conclude that measurement of progesterone and estrogen receptors in metastatic or recurrent endometrial tumors may be used as an additional prognostic variable.

Patients with female phenotypes and dysgenetic gonads harboring testicular tissue have a markedly increased risk of developing gonadal tumors. Cytogenetic demonstration of Y chromatin is the currently accepted criterion for performing prophylactic gonadectomies in these women. We studied four patients with dysgenetic gonads containing either testicular tissue or germ cell tumors. All had small sex chromosomal fragments which could not be characterized by conventional cytogenetic studies. Clinical features, DNA replication studies, and immunologic assays of Xg a and H-Y antigens failed to correlate consistently with the gonadal histology. We recommend prophylactic gonadectomies and subsequent hormone replacement in all patients with female phenotypes, gonadal dysgenesis, and cytogenetically indeterminate sex chromosomal fragments.

From 1973 through 1983, 27 women received postoperative open-field external beam abdominal radiotherapy as primary treatment of endometrial carcinoma. The 5-year survival rate was 71%. Two distinct prognostic groups were demonstrated. Patients with spread to the adnexa, peritoneal fluid, or both, had a 5-year relapse-free rate of 90%. Patients with macroscopic spread of cancer beyond the adnexa had a 5-year relapse-free rate of 0%. Guidelines are suggested for the radiotherapeutic management of endometrial cancer metastatic to the peritoneal cavity.

A retrospective investigation of infectious morbidity in gynecologic oncology patients documented that 54 (11%) of 494 patients and 68 (6%) of 1204 patient admissions were complicated by a serious infection. The highest rate of infectious morbidity by admission was 21%, occurring in patients admitted for cancer of the vulva. The highest surgical infectious morbidity, 22%, occurred in patients admitted for cervical cancer. important factors in determining infection risk include multiple host factors, radical surgical procedures, factors inherent in the tumor itself, and additional irradiation and chemotherapy. These serious polymicrobial infections dictate intelligent selection of antimicrobials and appropriate monitoring to anticipate complications inherent in antimicrobial therapy. β-Lactamase induction, superinfection, nephrotoxicity, and necrotizing enterocolitis are documented problems in these patients.

From 1971 through 1981, 83 nonsurgically staged women with cervical cancer received extended-field radiotherapy on the basis of abnormal lymphangiogram, obstruction on intravenous pyelogram, or extensive pelvic tumor volume. From 1978 through 1981, 61 surgically staged patients underwent radiation therapy; of these, the 21 with positive lymph nodes received periaortic radiation. No increase in morbidity was found in these patients. Survival, relapse rate, and sites of treatment failures were similar in the positive lymphangiogram group and in the surgically staged patients with positive nodes.

Application of morphometry to discrete processes was used to study the stroma-epithelial interface in benign proliferative processes of human cervical epithelium. This method with the use of two-dimensional transmission electron micrographs quantifies the number of pseudopodia and other features of the basal cell. The number of pseudopodia per basal cell and other basal cell features in reserve cell hyperplasia, immature squamous metaplasia, intermediate squamous metaplasia, and mature squamous metaplasia of human uterine cervix were measured. The number of pseudopodia per basal cell in reserve cell hyperplasia was 6.77 +/- 1.46 and comparable to that previously observed in advanced cervical intraepithelial neoplasia. The number of pseudopodia per basal cell in the three subtypes of squamous metaplasia ranged from 10.67 to 19.12 and was approximately half that observed in normal control epithelium. The concept of a continuum existing from reserve cell hyperplasia through immature squamous metaplasia to mature squamous metaplasia is supported with the demonstration of increasing numbers of pseudopodia per basal cell with cellular maturation.

Decision theory analysis is a systematic approach to decision making under conditions of uncertainty. Using formal decision analysis, we analyzed the clinical course of 275 patients with advanced cervical cancer. As selection in the application of surgical staging made survival comparisons difficult, enteric morbidity was used as a valued outcome. While the probability of severe enteric morbidity in patients who undergo extended field radiotherapy and surgical staging is twice as high as that in those not receiving extended portals and undergoing surgical staging (0.095 versus 0.050), the increased precision of defining those patients in need of extended portals resulted in very little increased morbidity in the total group. The difference in probability of enteric morbidity in patients with surgical staging and those without was 0.065 versus 0.061. Efforts to increase the proportion of patients with metastatic disease in the surgical staging group by using as stratifying parameters undifferentiated histology or possibly, in premenopausal patients, progesterone receptor levels may allow for the best survival therapeutic ratio as the maximum survival benefit will be gained by a minimum of enteric morbidity.

Immunologic evaluations of women with genital neoplasia-papilloma syndrome demonstrated the presence of subclinical immunodeficiency when compared with results in 20 control women. All patients with genital neoplasia-papilloma syndrome were previously found to have human papillomavirus deoxyribonucleic acid in genital neoplasias or papillomas occurring either synchronously (in at least two genital organs at the same time) or metachronously (at different times during a period of months to years). Immunologic tests included blastogenic responses of lymphocytes to mitogens (phytohemagglutinin, concanavalin A, pokeweed mitogen, and tetanus antigen) and lymphocyte phenotyping with the use of monoclonal antibodies (OKT3, OKT4, OKT8, and OKT11). As compared with those of control subjects, the responses of the lymphocytes of patients with genital neoplasia-papilloma syndrome to mitogens were significantly decreased. The group with genital neoplasia-papilloma syndrome had a significantly higher percentage of suppressor-cytotoxic T cells (OKT8-positive cells) when compared with that of control subjects (mean 33% versus 18%) and a lower proportion of helper T cells (OKT4-positive cells) when compared with that of control subjects (35% versus 50%). The mean helper-to-suppressor/cytotoxic T-cell ratio (mean OKT4/OKT8 ratio) in the human papillomavirus-infected women was 1.72 +/- 0.29 (SE) as compared with 3.21 +/- 0.33 (SE) in the control group, demonstrating a significant reduction of the ratio in the patients with genital neoplasia-papilloma syndrome. These findings suggest that patients with genital neoplasia-papilloma syndrome have a reduced suppressor/cytotoxic T-cell ratio (mean OKT4/OKT8 ratio; that in the human papillomavirus-infected women was 1.72 +/- 0.29 (SE) as compared with 3.21 +/- 0.33 (SE) in the control group, demonstrating a significant reduction of the ratio in patients with genital neoplasia-papilloma syndrome. These findings suggest that patients with genital neoplasia-papilloma syndrome have reduced immunocompetence of unknown etiology.

From 1978 to 1985, 159 women with advanced cervical cancer received definitive radiation therapy following extraperitoneal surgical staging including pelvic lymph node dissection and periaortic lymph node sampling. Relapse-free survival was a strong function of peritoneal and nodal metastases but was independent of clinical stage. The 5-year relapse-free rate fell from 86% in women without pelvic node metastases to 0% in those with unresectable pelvic node metastases. Women with microscopically positive pelvic node metastases had virtually the same (56%) relapse-free rate as those with grossly positive but completely resected metastases (57%). The overall pelvic failure rate was 16.4% and was significantly higher in women with unresectable pelvic node metastases. Periaortic and peritoneal metastases substantially increased the probability of recurrence. Although histologic grade was prognostically significant, histopathologic category was not. Severe enteric morbidity occurred in 3.6% of patients treated solely to the pelvis and in 7.9% of patients treated to the pelvis and periaortics. Therapeutic implications of debulking pelvic node metastases are discussed.

A retrospective review and a histopathologic analysis were conducted of 18 cases of malignant melanoma of the vulvar. FIGO staging did not correlate well with survival. Microstaging, as defined by the combination of Clark's level and Breslow's depth of invasion, was the most significant prognostic factor.

Patients with locally advanced vulvovaginal carcinomas with pubic bone encroachment or fixation pose a treatment dilemma. The purpose of this study was to evaluate the outcome in 12 patients who have undergone pubic bone resection at the University of Minnesota as part of treatment of locally extensive primary, recurrent, or metastatic vulvovaginal carcinomas. Six patients with primary vulvar carcinomas and six patients with recurrent or metastatic vulvovaginal carcinomas underwent bone resection as part of their surgical therapy. Survival in the primary treatment group was 50%, with no local recurrences. Survival in the recurrent/metastatic disease group was 83%, with a follow-up time of 9 months to 15 years. One vulvar and one groin recurrence have occurred in the recurrent/metastatic group. Pubic bone resection added little to surgical morbidity and gave good functional results. Pubic bone resection, in combination with radical extirpative procedures, is an option for treatment of patients with locally extensive vulvovaginal carcinomas, particularly those with previous radiation therapy.(Obstet Gynecol 73:1022, 1989)

The spectrum of vulvar intraepithelial neoplasia (VIN) was investigated with human papillomavirus (HPV) DNA probes by Southern blot hybridization technique. The results of vulvar tissue examinations from 25 patients were compared to prior genital and systemic diseases, clinical presentation, and histopathologic manifestations. The presence of HPV DNA in these lesions was largely associated with multifocality of the lesions, the presence of synchronous and metachronous multicentric genital neoplasia, and depressed immunocompetence. These findings indicate that VIN is associated with HPV and may have an infectious etiology.

alpha-Fetoprotein (AFP) has been found to be clinically important in the management of patients with gynecologic malignancies. Serum AFP levels are used as tumor markers for ovarian tumors, namely endodermal sinus tumors (EST) and embryonal tumors. In two cases of immature teratoma of the ovary without a yolk sac component, evidence for AFP production was found in a wide variety of cells of both endodermal and ectodermal origin suggesting a heterogeneous origin of AFP. To complement this finding, a summary of the ontology of AFP along with current and potential uses of an antigenically active tumor marker are presented.

Cases of carcinoma of the vulva with a warty appearance were reviewed. Altogether, 27 cases of warty carcinoma of the vulva were treated at the University of Minnesota Hospitals between 1976 and 1980, which accounted for 22.4% of all vulvar epithelial malignancies. As compared to the previous experience between 1951 and 1970, this relative frequency increased fourfold. Clinical history indicated that warty carcinoma of the vulva was not necessarily preceded by long lead periods of in situ lesions. The lesions seamed to occur in all ages after adolescence, were multifocal in one third of the cases, were frequently locally recurring, and were relatively benign despite their often large size. Many of them were originally diagnosed as condyloma acuminatum. Virus-like particles were seen in eight of the 12 cases (67%) examined with transmission electron microscopy, which included six cases of invasive lesions. These observations suggest that human papillomavirus (HPV) may be the important etiologio agent of this group of tumors. Warty carcinoma of the vulva must be clearly separated from conventional invasive squamous cell carcinoma of the vulva, as its clinical behavior and a possible etiology appear unique.

Steroid hormone action in specific target cells has been under intense study for the last three decades. Refinements in the technique of radioreceptor assay combined with the availability of radio-labeled steroid analogues have increased the precision and sensitivity in the measurement of hormone receptors. These assays were first used as clinical adjuvants in breast and prostate malignancies which are thought of as hormone ‘responsive’. In parallel with studies of breast carcinoma, quantification of cytosolic estrogen receptors (ERc) and cytosolic progesterone receptors (PRc) in endometrial carcinoma has been touted as an prognostic index [1–5]. In addition, association of receptor quantity with response to hormone treatment in endometrial carcinoma has been documented [1, 6].

In the investigation of carcinogenesis and its product neoplasia, limits to the information derived from histopathological studies are evident. Interpretation of morphological alterations in neoplasia often have a subjective character which creates disagreements between investigators. A search for specific parameters which parallel and predict tissue behavior continues. Examples of such study include tissue culture methods, specific histochemical reactions, and electron microscopic observation. Descriptive morphology is the backbone of the histopathologic study. To give such descriptions quantitative character, a relatively new discipline has arisen. This discipline, morphometry, seeks to increase the scope of descriptive morphology by measuring recurring ordered structures. With these measurements, combined with mathematical conceptualization, models can be constructed which allow extrapolation from two dimensional to three dimensional space, hence the term sterology is also used.

Twenty-seven patients with advanced adenocarcinoma of the endometrium were accessioned into this Phase II study evaluating the efficacy of ICRF-159 (razoxane) as second-line chemotherapy between February 1981 and September 1983. One patient was ineligible because of an undocumented primary. One patient was invaluable because of concurrent use of adjunctive therapy and one patient had an inadequate trial. Twenty-four evaluable patients with measurable disease were given ICRF-159 orally at a starting dose of 1.5 g/m2 weekly until response could be determined. Grade 4 hematologic adverse effects were the only significant toxicity. There was no evidence of tumor response in any of the patients. Fourteen patients had stable disease and 10 had progressive disease. No activity was noted in advanced adenocarcinoma of the endometrium with ICRF-159 administered in the above dose and schedule.

We have demonstrated that the number of pseudopodia is directly correlated with cell differentiation and carcinogenesis in the squamous epithelium. Microprocesses over T-lymphocytes may also reflect cell differentiation or a functional state of the cells as seen in the epithelial cell model, although their functions are not well understood. Visual quantification of spatially distributed bodies such as microprocesses observed with a scanning electron microscope (SEM) is inherently poor. That is, exact quantitation of the number of microprocesses per cell may be necessary to demonstrate a smaller difference in frequency of such structure. One drawback of previous attempts to use such a method was that the quantitation of a structure over a surface which was at a steep angle to the film plane could not be accurate. We developed a modified method of enumeration with SEM and another method with a transmission electron microscope (TEM), using cultured murine T-lymphoma cells (EL-4) as a model, and the results were compared.

OCCASIONALLY, because of clinical considerations, cytotoxic drug therapy is necessary during pregnancy, or unfortunately a patient conceives while under treatment. It is known that the human fetus is the most susceptible to teratogenic agents, such as x-radiation 1 and rubella virus, 2 during the first trimester, and it seems probable that this is also the case for cytotoxic chemotherapy. 3 It is important to assess the risks to which the fetus is subjected under these circumstances. The teratogenicity of antineoplastic agents has been proved in laboratory animals. Similar phenomena are seen in human fetal development when such drugs are administered during the first trimester of pregnancy. Aminopterin, which has been used in the past as an abortifacient, has been reported to cause profound abnormalities in a high percentage of fetuses. 2 Alkylating agents, especially cyclophosphamide, when administered during the first trimester, have been associated with major and minor abnormalities, including

Patients with nonmetastatic gestational trophoblastic disease were entered into this Gynecologic Oncology Group study to determine the efficacy, toxicity, and cost-effectiveness of weekly intramuscular (IM) methotrexate. Treatment was initiated with 30 mg/m2 of weekly IM methotrexate. If no major toxicity was encountered, the weekly dose was escalated 5 mg/m2 at three-week intervals until a maximum dose of 50 mg/m2 each week was achieved. Complete response was defined as three normal beta-hCG values measured on consecutive weeks. Fifty-one of 63 evaluable patients (81%) had a complete response to weekly IM methotrexate. Duration of therapy ranged from three to 19 weeks, with a median of seven. No major toxicity occurred. Thirteen patients experienced leukopenia at a median of 3300/microL, with a range of 2300-3900. Three patients had platelet nadirs of 66,000, 127,000, and 135,000/microL. Eleven patients with weekly IM methotrexate failure had a complete response after one to eight courses of dactinomycin administered 0.5 mg/m2 intravenously daily for five days; one refused therapy after three courses. Weekly IM methotrexate for nonmetastatic gestational trophoblastic disease is efficacious, minimally toxic, and cost-effective.

The favorable results Drs Casey and Madden experienced with the Gravlee jet irrigation technique are to be commended. Certainly, strict control of all variables will increase the reliability of this technique. As the correspondents suggest, it is possible that our results could have been improved by varying the processing method; however, our pathology department tested and then discarded the permeable membrane filter (Millipore) technique, as did Dr Gravlee, 1 since it added little information. In our study, collection of gross tissue fragments was accomplished by rinsing the tip of the irrigator in the fixing solution as a terminal step in gathering the specimen. It is perhaps teleologic that the onset of symptoms is directly proportional to the extent of the disease. Thus, the accuracy of a given technique would increase in patients with symptoms and presumably more advanced lesions. Possibly, this is not the case. On the other hand

The sensitivity in detecting human papillomavirus (HPV) by histological observation of koilocytosis, immunocytochemistry, and electron microscopy with reference to the results of Southern blot deoxyribonucleic acid (DNA) hybridization were reviewed in 41 lesions (37 patients) of cervical and vaginal condylomata acuminata and intraepithelial neoplasia. Human papillomavirus DNA was demonstrated in fresh tissues by Southern blot DNA hybridization in all but one lesion of moderate dysplasia (98%). The rate of koilocytosis observed in tissue sections was 80% in condyloma, and ranged from 89-20% in cervical intraepithelial neoplasia (CIN), with steady reduction as the grade of CIN or vaginal intraepithelial neoplasia (VaIN) was higher. The immunocytochemistry for HPV capsid antigens was positive in 80% of condylomata and ranged from 61-0% in CIN or VaIN. The rate declined in inverse proportion to the grade of CIN or VaIN. Electron microscopy of preselected areas containing intranuclear inclusions in paraffin sections of 10 lesions demonstrated HPV-like particles in 90% of the lesions. Although immunocytochemistry and observation of koilocytosis may be useful in detecting HPV in condylomata acuminata and mild dysplasia, their sensitivity was poor in CIN or VaIN of higher grades. Electron microscopy on preselected areas in paraffin blocks showed better sensitivity, presumably due to its ability to detect immature virions.

Of 128 patients receiving primary treatment for molar pregnancy at Women's Hospital, Los Angeles County/University of Southern California Medical Center, after uterine evacuation 12 (10.7%) developed self-limited, acute pulmonary complications characterized by tachycardia, tachypnea, and hypoxemia. Multiple contributing factors have been identified which include trophoblastic deportation, hyperthyroidism, fluid overload, dilutional anemia, and pre-eclampsia. While the final outcome was uniformly benign in our group, deaths have been reported. These patients are also at an increased risk for postmolar trophoblastic disease. The diagnosis and management of the postmolar pulmonary complications are discussed.