Biomedical subjects

C P Crum

Publications and source records attributed to C P Crum.

At least 127 records · Page 7Linked to original sources

PubMed1985

Cervical papillomaviruses segregate within morphologically distinct precancerous lesions.

We combined molecular hybridization and histological analysis of 58 biopsy samples from the uterine cervix to correlate the presence of certain strains of human papillomaviruses (HPVs) with specific pathological changes. HPV sequences were frequently detected (85%) in biopsies that contained a broad spectrum of precancerous changes. The presence of HPV 16 correlated strongly with precancers that exhibited morphological aberrations commonly found in invasive carcinomas and precancers that have a high risk of progression. This association underscores the potential importance of HPV type 16 in the genesis of genital cancers and emphasizes the value of histological analysis for detecting potentially oncogenic HPVs.

Base Sequence↗

PubMed1985

Outpatient management of cervical intraepithelial neoplasia. A summary of 279 cases.

Two hundred seventy-nine patients with cervical condylomas or cervical intraepithelial neoplasia (CIN) were treated as outpatients with cryotherapy. Every patient followed received a Papanicolaou smear, colposcopic evaluation, cervical biopsy and endocervical curettage four months following treatment. The treatment failure rates for CIN 1/condyloma, CIN 2 and CIN 3 were 2.9%, 5.7% and 4.3%, respectively. The percentage of patients eventually requiring conization was 0.7, 1.6 and 2.7, respectively. No patient who had a negative clinical and histologic examination at four months subsequently had a recurrence. The mean follow-up was 23.1, 26.0 and 35.0 months for CIN 1/condyloma, CIN 2 and CIN 3, respectively. Proper triage is important with CIN 3, and a complete colposcopic examination at the initial follow-up visit is valuable for predicting outcome.

Ambulatory Surgical Procedures↗

PubMed1984

Vulvar intraepithelial neoplasia (severe atypia and carcinoma in situ). A clinicopathologic analysis of 41 cases.

Forty-one cases of vulvar intraepithelial neoplasia (VIN) were analyzed clinicopathologically with emphasis on the changes in age-specific incidence rates, coexisting condylomata, coexisting koilocytotic atypia, subsequent invasive carcinoma and response to therapy. The number of cases referred to in the interval from 1975 to 1982 was 26 compared with 15 in the interval from 1966 to 1974. In addition, the percentage of patients in each group younger than 45 years of age was 66% after 1975 versus 33% prior to 1975. The yearly incidence of patients older than 45 years of age remained constant. The association of condyloma or marked koilocytosis in the neoplastic epithelium per se correlated with a younger mean age (31.1 and 31.8 years, respectively) than the absence of condyloma or marked koilocytosis (45.5 years and 47.5 years, respectively). Carcinoma developed in five patients (10.2%), and the mean age of the group was 55 years. Four of the five developed carcinoma within 3 years of diagnosis of the VIN. The incidence of persistence of the VIN lesion or recurrence following local excision was 22% over a mean following of 6.1 years. Spontaneous regressions were not reported in this patient population. Vulvar intraepithelial neoplasia appears to be a disease of multiple etiology which affects at least two populations. The younger patients are associated with papilloma-virus infection, and have a low risk of progression to cancer. The older patients have a variable history of condylomata, and a higher risk of developing invasive cancers of the anogenital region. The most important risk factor from the clinicopathologic standpoint appears to be age.

Adult↗

PubMed1984

Genital warts and cervical cancer. VI. The relationship between aneuploid and polyploid cervical lesions.

Human papillomaviral infection is now widely implicated in the causation of cervical neoplasia. Genotype analysis provides the best guide to biologic outcome; most polyploid lesions regress and most aneuploid ones persist or progress. This prospective survey examined the relationships between cell ploidy and 24 objectively validated criteria of human papillomaviral infection or premalignant change in 52 biopsies from a dysplasia clinic. Histologic evidence of benign warty expression and human papillomaviral capsid antigen production decreased steadily as DNA content ranged from diploidy to polyploidy to aneuploidy. In contrast, premalignant change increased with progressive distortion of nuclear DNA content. No absolute discriminants were found between polyploidy and aneuploidy, as evidenced by the detection of human papillomaviral proteins in three of 21 aneuploid epithelia and the recognition of abnormal mitotic figures in five of 17 polyploid lesions. Polyploid and aneuploid lesions differed only in severity, and it appears that some polyploid epithelia may be transition forms between diploidy and aneuploidy.

Animals↗

PubMed1984

Genital warts and cervical cancer. IV. A colposcopic index for differentiating subclinical papillomaviral infection from cervical intraepithelial neoplasia.

Five colposcopic signs (thickness, color, contour, vascular atypia, and iodine staining) were graded into three objective categories representing (1) subclinical papillomaviral infection, (2) lower-grade dysplasia, and (3) grade 3 cervical intraepithelial neoplasia. Seventy-two colposcopically different biopsy specimens (25 of subclinical papillomaviral infection and 18 of grade 1, 18 of grade 2, and 11 of grade 3 cervical intraepithelial neoplasia) were collected from 52 women and interpreted by validated, quantitative histologic analysis. Attempts to grade lesions by the prominence of the acetowhitening reaction or the mere presence of aberrant surface capillaries were unsuccessful. In contrast, each of five new colposcopic criteria were significantly correlated with histologic severity. Differences in color, vascular atypia, and iodine staining were more predictive than those of thickness and contour. Combined into a weighted index, these colposcopic features were 96% correct in forecasting approximate histologic findings. Because this method relies upon critical analysis rather than pattern recall, the use of this colposcopic index greatly simplifies the learning of colposcopy.

Animals↗

PubMed1984

Genital warts and cervical cancer. V. The tissue basis of colposcopic change.

Histologic differences between subclinical papillomaviral infection and cervical intraepithelial neoplasia are quantitative rather than qualitative. Both entities are characterized colposcopically by acetowhite epithelium and aberrant surface capillaries. This study correlates five new colposcopic signs (variations in contour, thickness, color, vascular patterns, and iodine staining) with 12 histologic signs of human papillomaviral infection and 12 features of premalignant change. Acetowhitening and capillary abnormalities in minor colposcopic lesions are attributable to human papillomaviral disturbance of cell growth and maturation, seen histologically as parabasal layer proliferation, papillomatosis, koilocytosis , and dyskeratosis. Alteration in cell ploidy is usually minimal. Major colposcopic abnormalities reflect extensive disorganization of cell phenotype and tissue architecture, increased DNA content, and aneuploid stem cell populations. Intermediate colposcopic patterns generally denote polyploid lesions in which tissue changes are a composite of two reciprocal events: the extent of benign warty expression and the severity of premalignant change.

Animals↗

PubMed1984

Human papillomavirus type 16 and early cervical neoplasia.

Flat warts (condylomata) of the uterine cervix are sometimes cytologically atypical and have abnormal mitotic figures; they are thought to be possible precursors of cancer of the cervix. Flat warts are caused by any of a number of types of human papillomaviruses (HPVs), one of which (HPV 16) has been previously associated with invasive cancer of the cervix. To determine whether HPV 16 is also associated with flat warts with abnormal mitoses, we analyzed 23 flat warts by DNA-hybridization techniques for the presence of HPV 16 and other HPV types, and correlated the results with the histology. Of 10 lesions with abnormal mitotic figures, 7 contained HPV 16, and 1 contained another type of HPV. Of 13 lesions without abnormal mitotic figures, only 1 contained HPV 16, and 7 contained other types of HPV. We conclude that the presence of HPV 16 correlates with the presence of abnormal mitotic figures in flat warts of the cervix, and that this type of flat wart is a precursor of invasive cancer of the cervix.

Cervix Uteri↗

PubMed1984

Koilocytotic lesions of the cervix. The relationship of mitotic abnormalities to the presence of papillomavirus antigens and nuclear DNA content.

It has been reported that abnormal mitotic figures (AMFs) occur principally in aneuploid lesions and that aneuploidy is a diagnostic feature of non-endocrine-dependent epithelial cancer precursors and cancers. Recently, AMFs have been reported in cervical lesions interpreted as flat condylomata, and it has been suggested by several authors that AMFs may not be diagnostic or aneuploidy or neoplasia, particularly in human papillomavirus-(HPV)-induced lesions. Although it is conceivable that AMFs may be a regular feature of HPV infection, their association with cytologic atypia and their presence in higher grades of cervical intraepithelial neoplasia (CIN) suggests that AMFs may herald the presence of a different lesion than the pure flat condyloma. In the current study, koilocytotic cervical lesions thought to be HPV-induced were examined microscopically for the presence of AMFs, and the findings were correlated with the presence of HPV as determined by immunoperoxidase and nuclear DNA distribution patterns as measured by Feulgen microspectrophotometry. In unselected lesions originally diagnosed as flat cervical condylomata, AMFs were surprisingly common (22.6%), and did not correlate with the extent of koilocytosis. Immunoperoxidase (IMPO) stains were performed in 35 cases with AMFs, and were negative for HPV in 74.3% and positive in 22.8%. However, among the cases evaluated by IMPO, there was an inverse relationship between the presence of mitotic abnormalities and the expression of HPV antigen. Nine of 11 (81.8%) lesions containing AMFs were aneuploid, and 2 of 11 (18.2%) were polyploid. Abnormal mitotic figures have a range of morphology and frequency in koilocytotic cervical lesions. Although the biology of these lesions is not well-defined, the presence of AMFs may identify a subgroup of HPV-induced cervical atypias which represent a transition between flat cervical conylomata and CIN.

Animals↗

PubMed1984

Genital warts and cervical cancer. III. Subclinical papillomaviral infection and cervical neoplasia are linked by a spectrum of continuous morphologic and biologic change.

Human papillomaviral (HPV) infection is now widely advanced as an important etiologic factor in cervical cancer. This study was undertaken to clarify morphologic relationships within the biologic spectrum linking subclinical papillomaviral infection (SPI) to cervical intraepithelial (CIN). Two pathologists analyzed 72 colposcopic biopsies, using a semi-objective rating scheme that scored 24 different histologic criteria. Each individual criterion was checked for reproducibility, and validated against an objective measure of papillomaviral infection (immunoperoxidase staining) or premalignant change (microspectrophotometry). The individual criteria were then combined into histologic indices of benign warty change, presumed viral atypia, abnormal cell phenotype, and disturbed tissue maturation. Histologic expression of papillomaviral infection decreased with increasing degrees of premalignant change. Plotting the index of abnormal cell phenotype against that of disturbed tissue maturation produced a linear plot in which cases clustered into four diagnostic groups. The histologic indices of papillomaviral infection displayed significant curvilinear correlations with genotypic distortion, benign warty change being maximal in the CIN 1 range and presumed viral atypia in the CIN 2 range. Disturbance of nuclear DNA content also increased with worsening diagnosis; diploidy being most common in SPI (67%), polyploidy in CIN 1 (59%), and aneuploidy in CIN 2 (65%) and CIN 3 (82%). Conversely, capsid antigen production decreased from 36% in SPI to 9% in CIN 3. Three aneuploid epithelia were immunoperoxidase positive. These inverse relationships between late viral expression and nuclear distortion fit experimental models of viral oncogenesis. The gradual transition and morphologic overlap between diagnostic groups support the postulate that SPI and CIN are a single disease spectrum, in which differences are those of degree rather than of kind.

Adolescent↗

PubMed1984

Uterine sarcomas: a clinicopathologic study, 1965-1981.

Forty-six cases diagnosed as uterine sarcoma from 1965 to 1981 were analyzed. Using mitotic count, 7 of 21 leiomyosarcomas (LMS) were redesignated leiomyomas and all are NED. The actuarial survival rates for the 38 considered sarcomas were 55 and 27% at 2 and 5 years. (The 22 patients eligible for 5-year follow-up had a 27% absolute survival, with 3 of 22 NED.) Fourteen LMS patients had a superior 5-year actuarial survival (42%) than 18 malignant mixed mesodermal (MMM) patients (15%), but the difference disappears when only patients under 70 are considered. Stage and age were the most important prognostic indicators. Complete surgical resection was essential for long-term survival. Six resected patients given adjuvant chemotherapy (mostly VAC) had an improved actuarial survival (61 vs 15% for the 23 resected patients not receiving chemotherapy). Seventy percent of 23 recurrences occurred within 2 years and average survival post-recurrence was 7.6 months. Survival post-recurrence for 8 patients was not improved by chemotherapy. Seventy-eight percent of recurrences had a distal component, with lung being the most common site.

Actuarial Analysis↗

PubMed1984

Chlamydial cervicitis and cervical intraepithelial neoplasia: an immunohistochemical analysis.

Studies using serological and culture techniques indicate that chlamydial infection is frequently associated with cervical intraepithelial neoplasia (CIN). This relationship was investigated by examining a series of biopsies containing normal epithelium, non-neoplastic condylomatous epithelium, and neoplastic epithelium (CIN). In each case the degree of inflammation and the presence of reparative atypia were recorded from an examination of the hematoxylin and eosin stained sections and serial sections were stained for chlamydial antigens using a polyclonal antichlamydial antibody and the immunoperoxidase technique. Overall, staining for chlamydia was positive in 0, 2, and 16% of biopsies with mild, moderate, and severe inflammation, respectively. In cases of severe inflammation positive staining was present in 20, 25, and 8% of biopsies containing non-neoplastic, condylomatous, and neoplastic epithelium, respectively. In all positive cases the staining was most prevalent in areas of the most intense inflammation. A spectrum of squamous epithelial changes was found in the infected biopsies and their distinction from CIN is discussed. This study suggests that tissue staining for chlamydia is related more to the extent of the coexisting inflammation than the presence or absence of CIN. Chlamydial infection, however, was frequently associated with inflammation-related squamous atypia in the transformation zone, which may be confused histologically with CIN.

Antigens, Bacterial↗

PubMed1984

Localizing chlamydial infection in cervical biopsies with the immunoperoxidase technique.

One hundred and two cervical biopsy specimens containing varying degrees of chronic inflammation were stained for chlamydial antigens with the immunoperoxidase technique. Seven cases (6.9%) were positive. Histologically, six (84%) of the Chlamydia-positive cases contained severe chronic inflammation, all contained reparative atypia, and two (28%), follicular cervicitis. When evaluated separately, 22% (six of 27) of the specimens with severe inflammation were positive in contrast to 0% (0 of 45) of cases with mild inflammation. Positively staining cells were located primarily in columnar epithelium and reparative atypia and occasionally in areas of immature squamous metaplasia. The cytological finding which correlated with positive staining was cytoplasmic vacuolation; however, cytoplasmic vacuoles were common in cells which did not stain positively, and it was impossible to predict on histological grounds which cells/specimens would stain positively by immunoperoxidase. Because of these findings, the presence of chlamydial infection should be strongly suspected whenever the cervical biopsy specimen contains severe inflammation and repair. Although tissue staining may not be as sensitive as culture for diagnostic purposes, it can be performed rapidly and simply and may be a useful special stain in cases where the diagnosis of chlamydial infection is not suspected clinically or cultures are not immediately available.

Biopsy↗

PubMed1984

Human papillomavirus infection and cervical neoplasia: new perspectives.

This review addresses several problems associated with human papillomavirus (HPV) infection of the cervix and lower female genital tract. These include the definition of HPV infection and its distinction from HPV-associated neoplasia, the distinction of HPV infection from reactive epithelial changes induced by other infections, and the transmission of HPV infection via the male partner. The available evidence indicates that there are two distinct intraepithelial processes in the cervix associated with HPV. One is the classical condyloma and its counterpart in immature epithelium, atypical immature metaplasia. The other is intraepithelial neoplasia, which, like classical infection, may be mature [cervical intraepithelial neoplasia (CIN) with koilocytosis] or immature (high grade CIN or carcinoma in situ). Molecular hybridization studies indicate that HPVs 6 and 11 are most commonly detected in the former, whereas HPVs 16 and 18 DNA are most common in the latter and in invasive cancer. From the clinical standpoint the most important distinction is between HPV-related disease (condyloma or CIN) and reactive changes associated with other pathogens, such as Chlamydia. The former should be removed from the cervix, whereas the latter should be treated medically or followed. It is stressed that therapy should not hinge upon the histological distinction of HPV infection from neoplasia and that all lesions should be removed, by conservative means if possible. This is underscored by the fact that a high proportion of CIN lesions contain areas identical to condyloma and that lesions with deep endocervical canal involvement, including those with features suggesting condyloma, should be treated by cone biopsy to exclude the presence of invasive cancer. Histological classifications for nonneoplastic, HPV-infected, and neoplastic epithelium are proposed. The management of the male partner is still unsettled. However, a large proportion of male partners of these patients have penile lesions and should be included in diagnostic and therapeutic protocols of women with genital HPV infections or neoplasms.

Animals↗

PubMed1984

Human papillomavirus infection and cervical intraepithelial neoplasia: histopathology and DNA content.

To evaluate the reliability of diagnostic criteria for separating intraepithelial squamous lesions into low- and high-risk categories, 25 lesions of the cervix were diagnosed as flat condyloma, atypical immature metaplasia, or cervical intra-epithelial neoplasia with koilocytosis based on well-defined histologic criteria. The presumption was that flat condyloma and atypical immature metaplasia would be diploid/polyploid as compared to low-grade cervical intraepithelial neoplasia, which should be aneuploid. Using the major histologic parameter of the presence or absence of abnormal mitoses to distinguish the low- and high-risk lesions, it was found that all of five typical flat condylomas were diploid/polyploid and seven of eight atypical immature metaplastic lesions were diploid/polyploid; 11 of 13 cervical intraepithelial neoplasms with koilocytosis, however, were aneuploid. An additional histologic parameter of anisocytosis (variation in nuclear size) appeared much less reliable for segregating these lesions than the nature of the mitoses. Lesions for which ploidy values were particularly difficult to predict were extremely well-differentiated koilocytotic lesions with occasional abnormal mitoses. Whether these are true polyploid lesions in which the abnormal mitoses are a response to the virus, or whether they are very early aneuploid lesions that cannot be confirmed by microspectrophotometry, remains to be determined.

Aneuploidy↗

PubMed1984

Cervical papillomavirus infection and intraepithelial neoplasia: a study of male sexual partners.

The male sexual partners of 34 women with cervical condyloma or cervical intraepithelial neoplasia (CIN) were examined for penile condylomata and/or urinary tract lesions. External lesions were detected in 18 (53%) of the male consorts of women with cervical lesions including 14 of 22 whose consorts had cervical condyloma or low grade CIN, one of six whose consorts had CIN 2, and three of six whose consorts had CIN 3. The majority of lesions were present either on the glands or the penile shaft, and one patient had a lesion in the urethral meatus. The urinary cytology specimens from the men with and without penile lesions contained nonspecific abnormalities consisting of squamous metaplasia with mild degrees of cytologic atypia. Koilocytotic atypia characteristic of condyloma was not found except in cases with documented distal urethral condylomata. Hence, at present the diagnosis of human papillomavirus infection in the man is best made by careful clinical examination. Whether or not papillomavirus resides deep in the urinary tract of these patients remains to be determined.

Animals↗

PubMed1984

Pitfalls in the diagnosis of endometrial neoplasia.

One hundred consecutive cases of hyperplasia of the endometrium were referred to the Sloane Hospital for Women. The referral diagnoses and consultation diagnoses were compared for the purpose of analyzing common diagnostic problems in interpretation of endometrial hyperplasias and the use of diagnostic terminology as it applies to prognosis and therapy. The consultation diagnosis was a down grade of the original diagnosis in 69% of the reviewed cases. The most common endometrial pathology misinterpreted as hyperplasia was endometrial polyps, followed by the endometrial metaplasias, and architectural distortion caused by necrosis and mechanical artifact. In 14% of the referral diagnoses, the use of terminology was vague, with such terms as endometrial, epithelial, or glandular hyperplasia, and did not communicate the prognostic intent of the referring pathologist to the consulting physician. The careful use of endometrial diagnostic terms accompanied by a statement of the system of classification used and its corresponding clinical intent is suggested.

Adenocarcinoma↗

PubMed1984

Chlamydial endometritis. A histological and immunohistochemical analysis.

A series of 90 endometrial biopsies and curettings originally diagnosed as chronic endometritis were reviewed and histological findings of plasma cells, lymphoid infiltrate, stromal necrosis, acute inflammation, lymphoid follicles, and epithelial atypia were correlated with the demonstration of chlamydial antigens by the immunoperoxidase technique. Chlamydial antigens were localized within endometrial epithelial cells in four cases. Although these four cases represented only 4% of the total number, chlamydial immunoperoxidase positivity was best discriminated by the severity of the inflammation and the presence of an acute inflammatory infiltrate. Among cases of severe endometritis 22% were chlamydia-positive, and in those cases with an associated acute inflammatory infiltrate, 57% were positive. A high index of suspicion of chlamydial infection should exist when severe endometritis is diagnosed in patients with clinical histories of post-abortal state, pelvic inflammatory disease, secondary infertility or menometrorrhagia, and chronic pelvic pain.

Adult↗

PubMed1983

Chronic endometritis: the role of immunohistochemistry in the detection of plasma cells.

The diagnosis of chronic endometritis depends upon the detection of plasma cells within the inflammatory infiltrate in the endometrium. To determine whether an immunohistochemical stain for plasma cells would enhance the detection of them and the diagnosis of chronic endometritis, we investigated 65 cases, including normal, proliferative, and secretory endometria, late menstrual endometria, endometrial polyps, and cases suspected of being, or diagnostic for, chronic endometritis. Twenty cases were positive by immunoperoxidase staining, 14 of which were positive by morphologic evaluation. Scattered isolated plasma cells which had been missed by histologic examination were detected by immunoperoxidase in three cases of early proliferative endometrium, and one case each of cystic glandular hyperplasia, 16-day endometrium, and late menstrual endometrium. Hence, the immunoperoxidase technique was more sensitive for detecting isolated plasma cells which were missed by standard screening techniques. In addition, the immunoperoxidase stain was useful for defining the spectrum of plasma cell morphologic characteristics within endometrium and, in retrospect, confirmed the differences between plasma cell and endometrial stromal cell morphologic features on hematoxylin and eosin sections.

Chronic Disease↗