Failure to detect human papillomavirus in Kaposi's sarcoma.
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Aged↗
Biomedical subjects
R J Kurman
Publications and source records attributed to R J Kurman.
Combined assessment of vascular and myometrial invasion as a model to predict prognosis in stage I endometrioid adenocarcinoma of the uterine corpus.
The prognostic significance of vascular invasion as compared with other pathologic features was evaluated in 102 cases of endometrioid adenocarcinoma confined to the uterus (Stage I) treated by hysterectomy. By univariate analysis, survival most closely correlated with patient age, architectural grade, depth of myometrial invasion, vascular invasion, and the presence of perivascular lymphocytic infiltrates. Among these, vascular invasion and the presence of perivascular lymphocytic infiltrates were the best indicators of prognosis. In contrast to perivascular lymphocytic infiltrates, the presence of a lymphocytic infiltrate at the tumor-myometrial junction was not related to outcome. The presence of vascular invasion was found to be associated closely with perivascular lymphocytic infiltrates. These two features may be related biologically and were designated "vascular invasion-associated changes." By multivariate analysis with the Cox proportional hazards model, the depth of myometrial invasion and the presence of vascular invasion-associated changes were found to provide a highly reliable model for predicting outcome. The highly predictive value of vascular invasion as a prognostic factor in Stage I endometrial carcinoma suggests that it is the mechanism by which occult metastasis develops in patients whose disease progresses after hysterectomy. It is likely that other variables correlating with recurrence, such as the presence of deep myometrial invasion and high tumor grade, may act by increasing the probability of vascular invasion and subsequent metastasis.
Adenocarcinoma↗
In situ and invasive vulvar cancer incidence trends (1973 to 1987).
OBJECTIVE: The objective of this study was to examine recent trends in the incidence of vulvar cancer. STUDY DESIGN: Cases of in situ and invasive squamous cell vulvar cancer were identified from nine Surveillance, Epidemiology, and End Results cancer registries. RESULTS: The incidence rate of in situ vulvar cancer nearly doubled between 1973 to 1976 and 1985 to 1987, whereas the rate of invasive squamous cell carcinoma remained relatively stable. CONCLUSIONS: Possible reasons for this discordance include the following: (1) Women affected by the "sexual revolution" are not yet old enough to have invasive vulvar carcinoma; (2) early diagnosis and treatment of in situ carcinoma have mitigated anticipated increases in invasive vulvar carcinoma incidence; (3) in situ and invasive carcinomas of the vulva have different etiologies, with the sexually transmitted human papillomavirus involved in the etiology of in situ carcinoma and other factors involved with most invasive squamous cell carcinoma.
Adult↗
Identification of patients with stage I uterine endometrioid adenocarcinoma at high risk of recurrence by DNA ploidy, myometrial invasion, and vascular invasion.
The presence of vascular invasion-associated changes (VIAC), which include vascular invasion by tumor and/or the presence of myometrial perivascular lymphocytic infiltrates, has been previously described as a key prognostic indicator in patients with stage I endometrioid (typical) adenocarcinoma of the uterus. In the current report, the prognostic significance of DNA ploidy in addition to other clinical and pathologic features including VIAC was determined in 57 previously examined stage I endometrioid adenocarcinomas of the uterine corpus. By univariate analysis, age at the time of diagnosis, architectural and nuclear tumor grades, DNA ploidy, depth of myometrial invasion, and the presence of VIAC all correlated with clinical outcome. By multivariate survival analysis, only the depth of myometrial invasion, DNA ploidy, and VIAC were found to significantly correlate with survival. A statistical model based on these three features permits stratification of patients into four risk groups with 93, 67, 38, and 10% survival, respectively.
Adenocarcinoma↗
Uterine serous carcinoma. A morphologically diverse neoplasm with unifying clinicopathologic features.
This study compares the clinicopathologic features of 13 pure uterine papillary serous carcinomas (UPSC) with 19 tumors consisting of UPSC admixed with other types of endometrial carcinoma and nine UPSC associated with endometrial polyps. The mean patient age, frequency of preoperative clinical understaging, postoperative pathologic stage, and survival of patients was similar for the three groups. Surprisingly, widespread metastasis, recurrence, and death occurred even in those cases where myometrial invasion amounted to less than 1 mm or where tumor was confined to an endometrial polyp. Poor prognosis appeared to be related to a propensity for vascular invasion and multifocal carcinogenesis. The latter was manifested by the presence of cytologically malignant cells closely resembling the invasive serous carcinoma in the surface endometrium adjacent to the tumor in 89% of cases and in multiple sites in the genital tract and abdomen. This lesion, designated "intraepithelial carcinoma," was present in the endocervix in nine (22%) of the 41 cases, in the fallopian tube in two cases (5%), on the surface of the ovary in four cases (10%), and on peritoneal surfaces or omentum in 10 cases (25%). In addition, we found that UPSC display considerable morphologic heterogeneity. Foci of clear-cell carcinoma were identified in 13 (32%) of the 41 tumors. In five (12%) neoplasms, the invasive component was composed primarily of glands; and in 22 (54%) tumors, thin as opposed to thick papillae predominated. Accordingly, UPSC may be broadly defined as a carcinoma that displays foci of well-differentiated papillae lined by cells that are markedly atypical cytologically. UPSC frequently contain areas of clear cells. Glands with papillary infoldings sometimes predominate in the invasive component. Because the behavior of endometrial neoplasms, in which at least 25% of the carcinoma exhibits a glandular or papillary architecture with serous differentiation, is similar, the term "uterine serous carcinoma" is an appropriate designation for these tumors, regardless of whether other patterns of differentiation are present or whether the tumor is associated with a polyp.
Adenocarcinoma↗
Epidermal growth factor receptor expression and the presence of human papillomavirus in cervical squamous intraepithelial lesions.
To determine the relationship between the expression of epidermal growth factor receptor (EGFR) and the presence or type of human papillomavirus (HPV) in cervical squamous intraepithelial lesions (SIL), paired colposcopically directed cervical biopsies were obtained from 88 patients referred for abnormal Papanicolaou smears. One biopsy was formalin-fixed and processed for conventional light microscopy, and the other was immediately frozen. A portion of the frozen tissue was used for Southern blot HPV DNA hybridization and a portion for immunohistochemical studies for EGFR using a monoclonal antibody. Forty-seven cases were SIL and 41 were normal. In 41 (87%) of the cases of SIL and in eight (20%) of the normal cases, HPV DNA was detected. Of the SIL cases, HPV 16 was the most frequently detected type, being present in 12 (25%), followed by 10 (21%) types 31 or 35, nine (19%) types 52 or 56, five (11%) uncharacterized types, three (6%) type 18, and two (4%) multiple types. Regardless of histology, EGFR was detected in all cases. In normal cases, EGFR expression was detected in the basal cells only and in SIL in abnormal proliferating parabasal cells such that it correlated with the grade of SIL. When stratified by grade of SIL, no differential expression of EGFR was seen in cases where HPV was detected; in contrast, in cases where no HPV was detected, no differential expression was seen between cases of different HPV type. Thus, EGFR is expressed by all proliferating squamous epithelial cells and as such correlates with the grade of SIL.(ABSTRACT TRUNCATED AT 250 WORDS)
Biopsy↗
Human papillomavirus infection of the cervix: relative risk associations of 15 common anogenital types.
During the years 1982-1989, 2627 women were recruited into eight studies analyzing the relationship between human papillomavirus (HPV) infection and cervical neoplasia. Subsequently, each individual was assigned as either a case or control, and each cervical sample was rescreened for HPV DNA by low-stringency Southern blot hybridization. Positive samples were retested at high stringency with specific probes for HPVs 6/11, 16, 18, 31, 33, 35, 42, 43, 44, 45, 51, 52, 56, and (in most instances) 58. Most cases (153 cancers, 261 high-grade and 377 low-grade squamous intraepithelial lesions) had target or cone biopsies; all 270 borderline atypia subjects and more than 85% of the 1566 normal controls had cytology plus colposcopy/cytology. Scientists performing HPV testing were masked to the clinical diagnoses. Human papillomavirus DNA was detected in 79.3% of specimens from women with definite cervical disease (627 of 791), in 23.7% of borderline atypia subjects (64 of 270), and in 6.4% of normal subjects (101 of 1566). Graphic analysis of odds ratios at each point in the diagnostic spectrum defined four categories: 1) "low risk" (HPVs 6/11, 42, 43, and 44), present in 20.2% (76 of 377) of low-grade lesions but absent in all 153 cancers; 2) "intermediate risk" (HPVs 31, 33, 35, 51, 52, and 58), detected in 23.8% (62 of 261) of high-grade squamous intraepithelial lesions but only 10.5% (16 of 153) of cancers; 3) "high risk/HPV 16," associated with 47.1% of both high-grade intraepithelial lesions (123 of 261) and cancers (72 of 153); and 4) "high risk/HPV 18" (HPVs 18, 45, and 56), found in 26.8% (41 of 153) of invasive carcinomas but only 6.5% (17 of 261) of high-grade intraepithelial lesions. The presence of an oncogenic HPV type conferred relative risks ranging at 65.1-235.7 for the occurrence of a high-grade lesion and 31.1-296.1 for an invasive cancer.
Blotting, Southern↗
A 45-year-old female with abdominal pain, ascites, and bilateral uterine adnexal masses.
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Abdominal Pain↗
Human papillomavirus and the pathogenesis of vulvar carcinoma.
The pathogenesis of vulvar and cervical cancer are thought to be similar and to be related to a sexually transmitted agent, which, in recent years, has been demonstrated to be human papillomavirus. These two neoplasms differ dramatically in age distribution and relationship to precursor lesions, making a common etiology unlikely. The apparent discrepancies can be explained by a hypothesis that implicates human papillomavirus as an etiologic factor for the majority of cervical carcinomas but for only a small proportion of vulvar carcinomas. Most vulvar carcinomas occur in older women and are not related to human papillomavirus, whereas a subset of vulvar carcinomas occur in young women and are related to this virus. Characterization of two distinct types of vulvar carcinoma may clarify associated risk factors and may have important implications in the clinical management of this disease.
Adolescent↗
Reassessment of the morphological continuum of cervical intraepithelial lesions: does it reflect different stages in the progression to cervical carcinoma?
Currently used histological and cytological classification systems for cervical lesions are reviewed. These suffer from poor inter- and intra-observer reproducibility, and do not allow accurate identification of which mild lesions will progress towards cancer. The Bethesda classification system is described and it is postulated that low-grade and high-grade squamous intraepithelial lesions might represent distinct entities with different potential for progression rather than necessary stages of a continuum leading to cervical cancer. Improved understanding of the etiological role of HPV types in cervical cancer and of the natural history of low- and high-grade intraepithelial lesions might result in more suitable clinical treatment of low-grade lesions.
Carcinoma↗
The Bethesda System. A proposal for reporting abnormal cervical smears based on the reproducibility of cytopathologic diagnoses.
In the Bethesda System, noninvasive squamous abnormalities are classified as atypical squamous cells of undetermined significance (ASQUS), low-grade squamous intraepithelial lesions, and high-grade squamous intraepithelial lesions. The Bethesda System eliminates two diagnostic distinctions that are made in the dysplasia/carcinoma in situ and cervical intraepithelial neoplasia (CIN) classifications, CIN1 vs koilocytotic atypia and CIN2 vs CIN3, and maintains three others, negative vs ASQUS, ASQUS vs koilocytotic atypia, and CIN1 vs CIN2. To determine whether the diagnostic distinctions preserved in the Bethesda System are made more consistently than those eliminated, we analyzed the interobserver reproducibility of two cytopathologists in classifying 257 smears. The findings indicate that the distinctions retained in the Bethesda System are more reproducible than those eliminated. Specifically, cases classified as koilocytotic atypia were distinguished from CIN1 no more reproducibly than predicted by chance, whereas CIN2 and CIN3 were distinguished as consistently as any other pair of diagnoses examined. In 13 cases in which there was interobserver discordance, one reviewer classified the smear as ASQUS and the other reviewer diagnosed CIN2 or CIN3. The findings in this study suggest that smears showing koilocytotic atypia and/or CIN1 may be reported as low-grade squamous intraepithelial lesions without further specification. In contrast, smears showing high-grade squamous intraepithelial lesions may be further classified as CIN2 or CIN3 in accordance with the Bethesda guidelines. Since the diagnosis of ASQUS is applied to smears showing a wide spectrum of changes, management of patients with the diagnosis of ASQUS will be facilitated by providing an explanatory note and/or recommendations when appropriate.
Carcinoma in Situ↗
Possible etiologic heterogeneity of vulvar intraepithelial neoplasia. A correlation of pathologic characteristics with human papillomavirus detection by in situ hybridization and polymerase chain reaction.
A correlated histopathologic and molecular virologic study of 30 cases of vulvar intraepithelial neoplasia Grade 3 (VIN 3) and six associated invasive vulvar carcinomas was performed. Paraffin sections were examined for human papillomavirus (HPV) types 6, 11, 16, and 18 by in situ hybridization for viral transcripts and by polymerase chain reaction (PCR) for amplification of HPV and of the beta-globin gene. Vulvar intraepithelial neoplasia Grade 3 was histologically subclassified into warty (bowenoid) (20 cases) and basaloid (undifferentiated) (ten cases) types. Warty VIN characteristically was composed of squamous cells displaying abnormal proliferation and maturation and an undulating or spiked surface creating a "condylomatous" appearance whereas basaloid VIN had a smooth surface and was composed of undifferentiated basaloid cells resembling carcinoma in situ of the cervix. Human papillomavirus-16 was the only type detected in 16 of 30 VIN 3 and in five of six invasive carcinomas. The HPV-positive women were younger than HPV-negative women (mean age at diagnosis, 49 versus 60 years), their lesions more frequently demonstrated koilocytotic atypia (94% versus 43%), and they were more likely to have warty compared with basaloid VIN lesions (65% versus 30%). These findings suggest that there are at least two different types of VIN which have differing clinical, pathologic, and viral profiles.
Adult↗
The diagnosis of ovarian cancer by pathologists: how often do diagnoses by contributing pathologists agree with a panel of gynecologic pathologists?
The Cancer and Steroid Hormone Study, a multicenter, population-based, case-control study of ovarian, breast, and endometrial cancer in women 20 to 54 years of age, permitted the diagnoses of contributing pathologists to be compared with those of a panel of three gynecologic pathologists. A diagnosis of ovarian cancer was made by contributing pathologists on 477 subjects. Agreement between the two groups of pathologists was 97% for primary epithelial ovarian cancer and 89% for primary nonepithelial ovarian malignancies. Agreement on diagnosis of major cellular subtypes of ovarian malignancy ranged between 73% for endometrioid cancer and 100% for clear cell carcinomas. We conclude that the diagnosis of pathologic features of primary ovarian cancer is highly predictable. Nonetheless, diagnosis by histologic type varies sufficiently that a review process should be considered for clinical or investigative decisions involving specific histologic diagnoses of ovarian cancer.
Adult↗
The morphology, biology, and pathology of intermediate trophoblast: a look back to the present.
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Animals↗
Relationship between surgical-pathological risk factors and outcome in clinical stage I and II carcinoma of the endometrium: a Gynecologic Oncology Group study.
Between June 20, 1977 and February 5, 1983, the Gynecologic Oncology Group entered 1180 women with clinical stage I or II (occult) endometrial carcinoma into a surgical-pathological staging study. Eight hundred ninety-five patients with endometrioid or adenosquamous carcinoma were evaluable for this study which relates surgical-pathological parameters and postoperative treatment to recurrence-free interval and recurrence site. Proportional hazards modeling of time to recurrence was performed. For patients without metastasis determined by surgical-pathological staging the greatest determinant of recurrence was grade 3 histology adenocarcinoma grade 3, relative risk (RR) = 15; adenosquamous carcinoma grade 3, RR = 8.1; all adenocanthomas, RR = 1.0). Of 48 patients with histologically documented aortic node metastases, 47 had one or more of the following features: (1) grossly positive pelvic nodes, (2) grossly positive adnexal metastasis, or (3) outer one-third myometrial invasion. Pelvic radiation was administered to 48.0% and vaginal brachytherapy alone to 10.2% of patients postoperatively; 41.8% received no adjuvant radiation therapy. None of three recurrences in the vaginal implant group were vaginal or pelvic; 7.4% (7 of 95) of recurrences in the pelvic radiation therapy (RT) group were vaginal and 16.8% were pelvic; 18.2% (8 of 44) of recurrences in the no adjuvant radiation group were vaginal and 31.8% pelvic. Because of the high degree of selection bias no valid comparisons can be made of recurrence-free interval in these groups. The 5-year recurrence-free interval for patients with negative surgical-pathological risk factors (other than grade and myoinvasion) was 92.7%; involvement of the isthmus/cervix 69.8%; positive pelvic cytology 56.0%; vascular space invasion 55.0%; pelvic node or adnexal metastases 57.8%; and aortic node metastases or gross laparotomy findings 41.2%. It is not clear that cervix invasion per se diminishes survival, because it is more often associated with poor tumor differentiation (34.7% versus 24.0%, grade 3) and deep myoinvasion (47.0 vs 18.6%) than cases without cervix invasion. The relapse rate among cervix-positive and -negative cases with grade 3 lesions and deep myoinvasion is not dramatically different (48.8% vs 39.8%). The proportion of failures which were vaginal/pelvic (34.6% for the surgery only group compared to 12.5% of the RT group) appears to favor the use of adjuvant radiation for patients with more than one-third myoinvasion and grade 2 or 3 tumor. There were 97 patients in the study group with malignant cytology of which 29.1% had regional/distant failure, which compares to 10.5% of the cytology-negative patients.(ABSTRACT TRUNCATED AT 400 WORDS)
Adenocarcinoma↗
HPV-16 viral transcripts in vulvar neoplasia: preliminary studies.
Specific human papillomavirus (HPV) types are strongly associated with intraepithelial neoplasia and invasive cancer of the cervix. In contrast, the role of HPVs in the pathogenesis of invasive carcinoma of the vulva is poorly understood. We have employed in situ hybridization for the detection of subgenomic transcripts in four vulvar specimens to elucidate the role of HPV type 16 in the development and progression of vulvar cancer. These analyses revealed that the transcripts of the E6-E7 region were more abundant than those of the L1-L2 region in vulvar neoplastic tissues. The transcripts from early and late region of HPV-16 continued to increase with the differentiation of the epithelial cells in both the warty and the basaloid types of vulvar precancerous lesions. This pattern persisted in invasive warty carcinoma but not in basaloid invasive carcinoma; the transcripts in basaloid carcinoma were distributed in an even and discrete pattern. In contrast to earlier studies, L1-L2-region transcripts, as well as viral capsid protein, were detected in focal areas of well-differentiated cells of invasive warty carcinoma. These findings suggest that expression of HPV-16 is regulated by the degree of cellular differentiation.
Carcinoma↗
Probable nonpapillomavirus etiology of squamous cell carcinoma of the vulva in older women: a clinicopathologic study using in situ hybridization and polymerase chain reaction.
A clinical, pathologic, and molecular virologic analysis of 30 cases of invasive squamous cell carcinoma of the vulva was undertaken to investigate the relationship of human papillomavirus (HPV) to this neoplasm. The presence of the virus was detected by the polymerase chain reaction and localized in the tumor and in the adjacent epithelium by in situ hybridization of paraffin sections of vulvectomy specimens. Specimens were examined for nucleic acid sequences of HPVs 6, 11, 16, and 18 were detected by in situ hybridization utilizing 35S-labeled antisense RNA probes and by polymerase chain reaction using HPV type-specific primers for a segment of the E6 gene followed by Southern hybridization of the amplified products. The cases were classified as typical squamous cell carcinoma, basaloid carcinoma, and warty carcinoma. Typical squamous cell carcinoma shows varying degrees of squamous maturation, whereas basaloid carcinoma is characterized by immature basal-type cells showing minimal or no squamous maturation. Warty carcinoma displays an exophytic condylomatous appearance. The squamous cells of this tumor are mature, and many show koilocytotic atypia characterized by a variable degree of nuclear atypia and cytoplasmic vacuolization. The adjacent epithelium was classified as squamous hyperplasia, lichen sclerosus, or vulvar intraepithelial neoplasia (VIN). VIN was subdivided into basaloid or warty VIN using similar criteria as for the invasive carcinomas. Overall, HPV 16 was detected in 11 cases and HPV 18 in two; none of the cases were positive for HPVs 6/11. HPV was detected in four (21%) of 19 squamous cell carcinomas, six (75%) of eight basaloid carcinomas, and three (100%) of three warty carcinomas. The adjacent epithelial lesions also showed a close correlation with the tumor type and presence of HPV. Fourteen (74%) squamous cell carcinomas had adjacent squamous hyperplasia; all of these squamous hyperplasias were negative for HPV. In contrast, seven (87%) of the basaloid carcinomas had adjacent basaloid-VIN and HPV 16 was detected within the VIN in three. Three warty carcinomas (100%) had adjacent warty VIN or basaloid VIN, and HPV was detected within VIN in two. The mean age of women with squamous cell carcinoma was 77 years, for women with basaloid carcinoma 54 years, and for those with warty carcinoma 47 years. The mean age of women with HPV-negative tumors was 77 years compared with 55 years for women with HPV-positive tumors (p less than 0.01). Thus, there appears to be a close correlation between the presence of HPV, specific subsets of invasive carcinoma and VIN, and age.(ABSTRACT TRUNCATED AT 400 WORDS)
Adult↗