The human papillomavirus status of 114 endocervical adenocarcinoma cases by dot blot hybridization.

The reported rate of human papillomavirus (HPV) positivity in cases of endocervical adenocarcinoma averages 38% (range, 0% to 100%) and, in contrast to cervical squamous cell carcinoma, HPV type 18 rather than type 16 is the predominant type. The HPV positivity rate and distribution of types (status) in 114 endocervical adenocarcinoma cases (37 in situ and 77 invasive) were determined by dot blot hybridization using biotinylated probes to HPV types 6, 11, 16, 18, 31, 33, and 35. Human papillomavirus DNA was present in 27% of in situ and in 44% of invasive adenocarcinomas, and in nearly all histologic subtypes of invasive adenocarcinoma. Human papillomavirus status was not predictive of tumor grade, volume, depth of invasion, lymph-vascular space involvement, age at presentation, or year of diagnosis. Type of HPV might influence the histologic subtype of invasive adenocarcinoma, as HPV type 16 predominated in the adenosquamous carcinomas while HPV type 18 was more frequently found in all other subtypes. Since only types 16, 18, and 33 were identified, an oncogenic role for HPV in endocervical carcinogenesis was supported.

The human papillomavirus status of invasive cervical adenocarcinoma: a clinicopathological and outcome analysis.

Accumulating evidence highlights the human papillomavirus (HPV) as a risk factor for cervical adenocarcinoma. However, the part played by the HPV in predicting tumor outcome or the increasing frequency of cervical adenocarcinoma is incompletely studied. In a retrospective study the association between HPV status and the clinicopathological characteristics of 77 cases of cervical adenocarcinoma was investigated. The data were then analyzed for temporal differences in HPV status and to identify outcome predictors. Human papillomavirus status was determined by dot blot hybridization using probes for HPV 6, 11, 16, 18, 31, 33, and 35, followed by polymerase chain reaction amplification of the dot blot negative cases. Seven type-specific and consensus HPV primers were used. Human papillomavirus type 16, 18, or 33 was present in 53 (70%) cases. Human papillomavirus status did not correlate with disease outcome or any clinicopathological variable, except that tumors presenting in and after 1981 were more frequently HPV positive than those presenting before 1981 (P = .014). In a multivariate analysis only clinical stage at presentation was predictive of disease outcome. Because temporal differences in clinicopathological characteristics were not identified, the increasing frequency of cervical adenocarcinoma may relate to a more important oncogenic role for the HPV in tumors presenting after 1980.

Estrogen and progesterone receptor, human papillomavirus, and DNA ploidy analysis in invasive carcinoma of the cervix in pregnancy.

From 1980 to 1991, 13 patients had pregnancy-associated invasive carcinoma of the cervix: four carcinomas were stage IA; eight were stage IB; and one was stage IVB. Gestational ages range from 8 weeks to 3 months postpartum. Two patients are dead of disease and a third is alive with metastases. Results of immunoenzyme studies for estrogen receptors (ER) were variably positive in all except one tumor, whereas results of studies for progesterone receptors (PR) were uniformly negative. Thus, these hormone receptor studies are unlikely to be of prognostic significance. Six tumors contained human papillomavirus (HPV) DNA by in situ or dot blot hybridization (three, HPV 16; two, HPV 18; one, HPV 31/33/35). Thus, neither ER nor PR expression appears to be related to the infecting HPV type. Using flow cytometry, three tumors were determined to be aneuploid and a fourth, tetraploid. To correlate HPV or DNA flow cytometry data with prognosis will require study of larger numbers of patients from multiple centres.

A comparison of cervical scrapes for HPV typing by dot-blot hybridization obtained by wood and plastic spatulas.

A cross-over study was designed to determine whether the type of spatula used to collect cervical cells influences the ability of dot-blot hybridization to detect HPV DNA. Fifty-nine patients had a cervical scrape with a wood spatula first and a plastic spatula second: 60 were scraped in the inverse order. The order of sampling did not affect the HPV DNA positivity rate, which was nearly similar for both wood and plastic spatulas (30 and 32%, respectively). Wood spatulas collected more cells and greater than 1 x 10(5) cells more often than plastic spatulas (P = 0.001 and 0.06, respectively). Non-purple (negative) dots were more frequent in samples obtained by wood than by plastic spatulas (P = 0.001). The study showed that cervical cell collection by wood spatulas is preferred as they harvest more cells, thus optimizing the sensitivity of the hybridization method, and the spatulas are also more economical. Although they yielded more non-purple dots, a reduction in these dots by using plastic spatulas did not result in a significantly increased HPV positivity rate.

Comparative study of the ThinPrep Pap test and conventional cytology results in a Canadian cohort.

OBJECTIVE: To compare the frequency of Pap test results in a prospective series of direct to vial ThinPrep tests to a cohort of conventionally prepared tests. To follow-up all test results for a minimum of 2 years and assess performance based on this outcome. METHODS: All women presenting for either routine screening or colposcopic examination in 2001 were enrolled in the ThinPrep cohort. A similar, population of conventionally prepared tests was extracted from the year 2000 laboratory data. Information on all concurrent and follow-up cervical specimens over the ensuing 2 years was retrieved. RESULTS: The ThinPrep cohort comprised 2288 Pap tests and the conventional, 2211. The frequency of normal [within normal limits (WNL) and benign cellular changes (BCC)] results in the ThinPrep cohort was 6% lower and the frequency of abnormal [> or =atypical squamous cells of undetermined significance (ASCUS)] results was 6.8% higher. Respective ThinPrep and conventional cohort results were 1156 (51%) and 1291 (58%) WNL, 625 (27%) and 561 (25%) BCC, 101 (4%) and 65 (3%) ASCUS, 21 (1%) and 2 (0.1%) atypical glandular cells of undetermined significance, 301 (13%) and 224 (10%) low-grade squamous intraepithelial lesion (LSIL), and 74 (3%) and 40 (2%) high-grade SIL (HSIL) (P < 0.0001). Follow-up was available for nearly 80% of each cohort. LSIL or higher was confirmed in 57.5% (n = 266) of the abnormal ThinPrep and 60.9% (n = 190) of the abnormal conventional tests. The ThinPrep yield of confirmed tests however was almost 50% higher than the conventional test. CONCLUSION: In this population, ThinPrep was superior to the conventional Pap test.

Ovarian carcinoma of low malignant potential: staging and treatment.

A review of 65 cases of ovarian carcinoma of low malignant potential registered at the Manitoba Cancer Treatment and Research Foundation over a 7 1/2-year period was undertaken. Eighty-four percent of patients presented with Stage I disease, which was confirmed by primary staging laparotomy in 25%. The average age at diagnosis was younger than that commonly found in patients with invasive carcinoma. Fourteen patients received postoperative chemotherapy, of whom 10 were evaluated with second-look laparotomy. No patient with macroscopic residual disease after initial surgery was cured by chemotherapy. This report emphasizes the need for a prospective controlled study to evaluate adjunctive chemotherapy in the treatment of these tumors.

Outpatient laser cone biopsy under local anesthesia.

The authors report on 60 patients who had abnormal findings on cervical cytologic examination, necessitating conization of the cervix. The procedure was done in an ambulatory setting, with a carbon-dioxide laser unit and local anesthesia. The average operative time was 16.9 minutes. Fifty-one (85%) patients experienced no complications, and there were no cases of excessive bleeding. In all patients, the specimen was satisfactory for histologic review. Only 5% (three) of patients would have preferred to have the procedure performed under general anesthesia. Laser cone biopsy of the cervix can be performed in an outpatient setting, with local anesthesia. Morbidity is minimal and there is potential for economic saving when compared with conventional methods for biopsy of the cervix.

Risk-specific follow-up for endometrial carcinoma patients.

OBJECTIVE: To propose a risk-specific follow-up protocol for endometrial carcinoma patients. METHODS: A retrospective cohort of endometrial carcinoma patients was used to identify risk factors for recurrence. Based on a profile of risk factors, women were classified at either low or high risk for recurrence (median follow-up 70 months). The classification system was validated on a subsequent cohort. RESULTS: Surgical stage, grade, and histology were found to be significant predictors (P < 0.001) of recurrence. In the original cohort, patients with stage Ia, grade 1 or 2, or stage Ib, grade 1 adenocarcinoma, had a recurrence rate of 4/98 (4.1%). The remaining high-risk patients had a recurrence rate of 37/158 (23.4%). When applied to the subsequent cohort, the rates were similar: low risk 3/113 (2.7%) and high risk 30/140 (21.4%). Seventy-five percent of recurrences occurred within 3 years of diagnosis and the majority were heralded by site-specific symptoms. CONCLUSIONS: Women with endometrial carcinoma can be successfully classified for low or high risk of recurrence. It is proposed that low-risk patients not be maintained on routine follow-up and that a tailored schedule of follow-up be used for high-risk patients. These changes would serve patients more appropriately and use health care resources more efficiently.

Intraperitoneal interferon in the management of malignant ascites.

BACKGROUND: Ascites secondary to malignancy is a major cause of recurring morbidity in patients with ovarian cancer. In patients previously treated with cisplatin, other chemotherapeutic agents are not likely to be effective in relieving symptoms. METHODS: A pilot group of ten patients was treated with intraperitoneal alpha-2B-interferon (alpha-2B-IFN) in an effort to provide symptomatic relief of their ascites. All patients had advanced epithelial ovarian cancer at the time of therapy and were receiving treatment for palliation only. Symptoms included abdominal distention (100% of patients), nausea and vomiting in the absence of mechanical intestinal obstruction (60%), and dyspepsia (40%). RESULTS: At a dose of 10 M units/m2 given intraperitoneally every 2 weeks for one to four treatments, the toxicity was low, but the benefits were minimal. Five (50%) patients reported symptomatic improvement of 2-7 weeks' duration. The most common side effects included fever (temperature of more than 38.5 degrees C) and abdominal pain. CONCLUSIONS: At the dose of 10 M units/m2 of intraperitoneal alpha-2B-IFN, this regimen did not appear to produce clinically significant palliation of the ascites in most patients.

Laser vaporization of vaginal intraepithelial neoplasia.

Laser vaporization was used to treat 27 women diagnosed at the Tom Baker Cancer Centre, Calgary, Alberta, Canada, as having vaginal intraepithelial neoplasia. The diagnosis was established after review of vaginal cytologic examination and a histologic biopsy. Treatment was performed with a carbon dioxide laser unit attached to an operating microscope. All but three patients had general anesthesia for the purpose of treatment. Tissue destruction was accomplished to a depth of 2 to 3 mm. Patients were followed up for an average of 14.4 months with regular colposcopy, cytologic evaluation, and biopsy when persistent or recurrent disease was suspected. Failure of therapy was defined as evidence of intraepithelial neoplasia in any one of these three parameters. Four patients required a second treatment. After one or two treatments the success rate of therapy was 78%. In our institution, laser vaporization with the patient under general anesthesia on an outpatient basis is the treatment of choice for vaginal intraepithelial neoplasia.

Spontaneous rupture of the urinary bladder: a late complication of radiotherapy--case report and review of the literature.

The spontaneous intraperitoneal rupture of the urinary bladder is an extremely rare life-threatening event. There are often difficulties in establishing the diagnosis. A patient with spontaneous perforation of the urinary bladder, 15 years after pelvic radiotherapy for carcinoma of the cervix is reported. Aspects of etiology, clinical presentation, diagnosis, and management are described. Special emphasis is placed on surgical management as it relates to long-term outcome.

Laser therapy of vulvar lichen sclerosus et atrophicus.

Seven patients with a histologic diagnosis of lichen sclerosus et atrophicus of the vulva were treated by laser ablation of the affected area to a depth of 1.0 to 2.0 mm. The inpatient procedure was performed under general anesthesia with a carbon dioxide laser unit. Healing was complete 6 weeks postoperatively. All but one patient was free of recurrent symptoms at follow-up, which ranged from 12 to 37 months. Laser ablation is an acceptable treatment for patients who have symptoms due to lichen sclerosus of the vulva that are refractory to other measures.

Evaluation of surgical staging in stage I low malignant potential ovarian tumors.

The charts and pathology specimens of 27 patients with ovarian tumors of low malignant potential were reviewed in an attempt to document the rationale for a second laparotomy in those patients with clinical stage 1 disease and who did not have a complete staging laparotomy at their initial surgery. Four of 13 patients with serous tumors, none of 12 patients with mucinous tumors, and one patient with a mixed tumor of LMP were upstaged at the staging laparotomy. The major morbidity rate associated with the procedure was 7.4%. The low yield of a staging laparotomy in patients with mucinous tumors (0%) does not warrant a second operation. The higher yield of a staging laparotomy in patients with serious tumors (30.8%) suggests that the likelihood of upstaging the disease exceeds the potential morbidity, and for this reason, the procedure may be warranted. However, the specific role of a staging laparotomy even in those with serous tumors awaits further study of the prognostic significance of invasive versus noninvasive implants.

Review of the screening history of Alberta women with invasive cervical cancer.

OBJECTIVE: To conduct a failure analysis of cervical cancer screening among women with invasive cervical cancer in Alberta. DESIGN: Descriptive study. Review of demographic, staging and treatment information from cancer registry records; generation of documented screening history from Alberta Health billing records and self-reported history from subjects who agreed to be interviewed; and comparison of findings in initial cytology reports with those from subsequent review by at least 2 pathologists of all cytology slides for each patient for the 5 years before diagnosis. Cases were assigned to 1 of 6 categories of identified screening failure. SETTING: Alberta. SUBJECTS: All women with diagnosis of invasive cervical cancer reported to a population-based provincial cancer registry from January 1990 to December 1991. OUTCOME MEASURES: Demographic, staging and treatment information; documented and self-reported screening histories; correlation of test results in initial cytology report with those generated from slide review; category of identified screening failure. RESULTS: Of the 246 women identified with invasive cancer of the cervix, 37 (15.0%) had stage IA disease; 195 (79.3%) had squamous-cell carcinoma, and 35 (14.2%) had adenocarcinoma. According to the categories of screening failure, 74 women (30.1%) had never been screened, 38 (15.4% had not been screened within 3 years before diagnosis, 42 (17.1%) had had a false-negative cytology result, and 20 (8.1%) had been managed outside of conventional protocols. Of the 23 women (9.3%) who had been screened appropriately and had true-negative results, 19 had smears that were considered technically limited. It was not possible to classify 49 (19.9%) of the cases. Agreement between the documented and the self-reported screening histories was exact for only 39 (36.1%) of the 108 women interviewed. CONCLUSIONS: Despite widespread use of opportunistic cervical screening, many women in Alberta are still not being screened adequately. In most cases women are being screened too infrequently or not at all. Self-reported screening histories are unreliable because many women may overestimate the number of smears. An organized approach to screening, as recommended by the National Workshop in Cervical Cancer Screening, may assist in reducing the incidence of invasive cervical cancer.

Ependymoma of the uterosacral ligament.

Extraspinal ependymomas have been described in the subcutaneous sacrococcygeal and presacral areas. Since 1984, eight pelvic ependymomas have been reported that have originated in the ovary, broad ligament, mesovarium, and omentum. This report documents an additional case arising from the right uterosacral ligament in a 48-year-old woman. The diagnosis of ependymoma was supported by a histologic pattern of true rosettes and pseudo-rosettes, glial fibrillary acidic protein (GFAP) positivity, and electron microscopic findings of cilia, blepharoplasts, and intermediate filaments. The tumor was positive for cytokeratin and vimentin. Ultrastructurally, neurosecretory granules were present within the cytoplasm. These features have not been described previously in pelvic ependymomas. These tumors, although easily confused with serous papillary carcinoma, should be distinguished from serous papillary carcinoma because of their apparently better prognosis and tendency for late recurrence.

Uterine atypical polypoid adenomyoma and ovarian endometrioid carcinoma: metastatic disease or dual primaries?

Atypical polypoid adenomyoma (APA) is an uncommon uterine tumor that rarely metastasizes, although it closely resembles a well-differentiated endometrioid carcinoma. A 37-year-old woman with a history of pelvic endometriosis and oral contraceptive use developed an APA and later presented with bilateral ovarian endometrioid carcinomas. DNA ploidy analysis and human papilloma virus (HPV) typing of the APA and ovarian carcinomas were performed to characterize the primary or metastatic nature of the tumors. Both tumors were aneuploid. The APA had a DNA index of 1.53, compared with 1.19 for the ovarian carcinoma. The APA contained HPV 18, and the ovarian carcinoma a mixed infection of HPV 6, 11, 16, and 18, with types 6 and 11 predominating. These differences in DNA index and HPV type supported the autonomous nature of the APA and the ovarian carcinomas. The report affirms the benign outcome of APA, highlights its complication by a second malignancy, and suggests an etiological role for endometriosis, steroid hormones, and possibly the HPV in the formation of one or both tumors.

Invasive squamous cell carcinoma of the cervix in women less than 35 years old: recurrent versus nonrecurrent disease.

Invasive cervical squamous cell carcinoma was diagnosed in 45 patients less than 35 years old from 1980 to 1985. Thirty-two cases were Stage IB; 10, Stage IIB; and three, Stage IIIB. Twenty-two patients developed persistent or recurrent disease. Only one of these is now alive with no evidence of tumor. The mean interval from diagnosis to recurrence was 8.7 months (median of 7.0) and from diagnosis to death was 14.7 months (median of 12.0). Eleven of 32 patients with Stage IB disease developed a recurrence; the intervals to recurrence in Stage IB disease were similar to those for more advanced stages. Factors predicting recurrence included advanced stage of the disease and tumor bulk (maximum size, depth of invasion, and number of involved quadrants) as well as an exophytic or ulcerative tumor and a symptomatic presentation. These factors may identify the patient at high risk for recurrence who would benefit from adjuvant therapy.

Recurrent and persistent squamous cell cervical carcinoma in women under age 35.

Forty-five patients with invasive cervical squamous cell carcinoma were registered in the Tom Baker Cancer Centre from 1980 to 1985. The natural history of 22 patients (48.9%) who developed persistent or recurrent disease including 11 Stage IB, 8 Stage IIB, and 3 Stage IIIB is reported. Only one patient who had the uncommon papillary variant is alive without evidence of residual disease. The remainder are either dead (16) or alive with residual disease (5). Four patients never achieved a disease-free status and in the remainder recurrences developed on average in 8.7 months. Central or regional disease was not controlled in 20 of 22 patients. Neither radical surgery nor radiotherapy was evidently more effective in preventing persistent or recurrent disease. A reliable predictive marker for persistent or recurrent disease is required: lymph-vascular invasion in the radical hysterectomy specimens was present in 5 of 6 cases but it is subject to interpretive error. Since the disease is frequently systemic at the time of diagnosis, early adjuvant therapy and improved staging techniques are required to improve the survival.

Malignant transformation occurring in mature cystic teratomas of the ovary.

Two cases in which tumours of contrasting malignant potential arose in mature cystic teratomas (dermoid cysts) of the ovary are presented: one patient had a spindle-cell sarcoma and the other a trabecular carcinoid. The first patient's clinical course was characterized by rapid recurrence of the tumour and death 3 months after surgery. The second patient is alive and well with no evidence of residual carcinoid, although the follow-up time is short. Since the surgical procedure of choice differs substantially if malignant transformation occurs in an ovarian dermoid cyst, the pathologist should be consulted intraoperatively in selected cases.

Adenocarcinoma in situ of the endocervix: human papillomavirus determination by dot blot hybridization and polymerase chain reaction amplification.

The frequency of human papillomavirus (HPV) in series of endocervical adenocarcinoma in situ (AIS) ranges from 6 to 100%. Some of this variability can be attributed to small study numbers and such technical considerations as the sensitivity of the hybridization method employed. Consequently, the role of the HPV in AIS oncogenesis is unclear. The frequency and relative distribution of HPV DNA types 6, 11, 16, 18, 31, 33, and 35 in 37 cases of AIS were determined and correlated with clinical variables. All cases were first typed by dot blot hybridization (DBH), and those found to be HPV negative were subsequently typed by polymerase chain reaction amplification with DBH enhancement (PCR/DBH). The HPV DNA positivity rate was 27% by DBH alone and 52% by PCR/DBH amplification. Combining the results of both methods, the overall HPV positivity rate was 66%: HPV 18 in 15 cases (43%), HPV 16 in eight cases (23%). The HPV status did not correlate with any clinical variable. This study showed that the sensitivity of the hybridization method is principally accountable for the variable frequency of HPV in AIS. The identification of only high-risk oncogenic HPV types in two-thirds of the cases suggests a significant role for the virus in AIS oncogenesis; HPV status, however, does not delineate a clinical profile.