Search

Objectives: New human papillomavirus (HPV)-related biomarkers may allow better identification of clinically significant lesions that warrant excision and, conversely, identification of the false positive cases that have been overreported by traditional techniques. The aim of this study was to investigate how the expression of several HPV-related biomarkers correlates to the severity of the lesion at treatment., Design: Prospective observational study., Setting: University Hospital (2009-2011)., Population: All women submitted for excisional treatment., Methods: A liquid-based cytology sample was obtained before treatment and was tested for HPV typing, mRNA E6 & E7 with NASBA or flow cytometry and p16. All women had histological diagnosis in the form of excisional cone (gold standard)., Main Outcome Measures: Correlation of HPV biomarker positivity rates to the grade of the lesion at treatment histology., Results: Two hundred women were recruited: 23 were found to have negative histology (11.5%), 79 (39.5%) CIN1, 50 (25.0%) CIN2 and 48 (24.0%) CIN3. All biomarkers (HPV DNA typing, HR HPV, single HPV 16/18, mRNA E6 & E7 expression and p16) revealed an increased linear positivity rate with increasing severity and grade of the lesion (chi-squared test for trend p < 0.05). This was stronger for HPV (all and high-risk) followed by mRNA with NASBA, flow cytometry, HPV 16/18 and ultimately p16 immunostaining., Conclusions: The linear correlation between various HPV-related biomarkers and the grade of the lesion suggests that these biomarkers may prove to be useful in the prediction of CIN grade and, as a result, the need for treatment., (© 2013 Nordic Federation of Societies of Obstetrics and Gynecology.)

Background: The fine-needle aspiration (FNA) diagnosis of proliferative breast lesion is an indeterminate category. The aim of this correlative study was to determine whether a subcategory of "proliferative breast lesion with atypia" was achievable and whether this subcategory has management utility., Methods: Breast FNA cases from 2000 through 2005 diagnosed as proliferative breast lesion and proliferative breast lesion with atypia were retrieved. Both cytologic and surgical slides of these cases were reviewed blindly. A cytologic diagnosis of proliferative breast lesion (without atypia) or proliferative breast lesion with atypia was used if the findings of the proliferative breast lesion did not fit a more specific category., Results: Of the 3934 breast FNAs performed on palpable breast masses from January 2000 to December 2005 at the LAC + USC Medical Center, 317 (8.1%) were diagnosed cytologically as proliferative breast lesion with atypia, without atypia or without mention of atypia. There was subsequent histopathology on 201 of these cases. After the cytologic smears were reviewed, 29 cases were excluded from this study. Of the 172 remaining cases, 21 (12.2%) were found to be malignant and the remaining 151 (87.8%) were found to be benign on histology. Of the malignant cases, 90% had an FNA diagnosis of proliferative breast lesion with atypia; of the benign cases, 78% were interpreted as proliferative breast lesion without atypia., Conclusions: Proliferative breast lesion with atypia was clinically significant because it was associated with a significantly increased likelihood of malignancy compared with proliferative breast lesion without atypia. Most of the malignancies had hypocellularity or low nuclear grade on the FNA smears. Fibroadenoma accounted for most of the benign lesions in both proliferative breast lesion and proliferative breast lesion with atypia., ((c) 2009 American Cancer Society.)

Background: Histopathologic diagnosis of endometrial biopsies is used to estimate the risk of progression to carcinoma and guide clinical management. Problems with the widely used World Health Organization (WHO) system for classifying endometrial hyperplasia (EH) have prompted the development of an alternative system based on endometrial intraepithelial neoplasia (EIN). The authors estimated progression risk associated with EIN among endometrial biopsies in a nested case-control study of EH progression., Methods: Index biopsies with original community pathology diagnoses of disordered proliferative endometrium (DPEM) or EH that were independently confirmed by a panel of pathologists were independently reviewed and assigned EIN classifications (inadequate, benign, EIN, or cancer) by a second panel of pathologists. Cases (N = 138) progressed to carcinoma at least 1 year (median, 6 years) after their index biopsy. Controls (N = 241) also had EH, did not progress to carcinoma, and were individually matched to cases based on age at EH, date of EH, and length of follow-up. By using conditional logistic regression, the authors estimated relative risks (RRs) with 95% confidence intervals (95% CIs) for progression to carcinoma for EIN versus benign., Results: In the EIN system, 71 (52.6%) cases and 159 (66.8%) controls were classified as benign and 42 (31.1%) cases and 65 (27.3%) controls were classified as EIN. The RR for EIN versus benign was 7.76 (95% CI, 3.36-17.91). In the WHO system, the RR for atypical hyperplasia (AH) versus DPEM, simple hyperplasia, or complex hyperplasia was 9.19 (95% CI, 3.87-21.83)., Conclusions: Among women observed for at least 1 year after receiving a biopsy-based EH diagnosis, EIN and AH were both found to have similarly increased risks of progression to carcinoma., ((c) 2008 American Cancer Society.)

The distinction between actinic keratosis (AK) and squamous cell carcinoma in-situ (SCCIS) is a subject of discussion among dermatopathologists. A previous study determined that there was excellent interobserver agreement among dermatopathologists using the current two-tiered grading system. Presently, we assessed concordance among dermatopathologists using a three-tiered keratinocytic intraepithelial neoplasia (KIN) diagnostic system. At the 2006 meeting of the American Society of Dermatopathology (ASDP), registration personnel solicited 125 registrants by randomly inserting an invitation into 125 registration packets. Participants reviewed 15 glass slides representing a spectrum of keratinocytic atypia from AK to SCCIS. Participants were asked to choose 1 or 2 but not 3 grades of KIN that best reflected the changes on each slide. Thirty-two of the 125 solicited enrollees participated in the study. There were 16 volunteers for a total of 48 participants. The inter-observer agreement for all participants was 0.575 (moderate agreement). The overall inter-observer agreement for anatomic pathologist-dermatopathologists (AP-DP), dermatopathologist-dermatologists (DP-D) and anatomic pathologist-dermatologist-dermatopathologists (AP-DP-D) was 0.665, 0.609 and 0.670 (substantial agreement), respectively. There is high concordance among dermatopathologists using a three-tiered diagnostic system for KIN. The observed agreement suggests that dermatopathologists are reliably able to categorize the continuum of keratinocytic atypia in a manner that may have diagnostic relevance.

Cervical cytological pathology is common. Prevention of cervical cancer by detecting the disease process at an early and pre-malignant stage is practised globally either through population-based screening programmes (PSP) or through non-organised ones. High-grade cervical intraepithelial neoplasia (CIN) detected by cervical cytological screening is extensively visualised by colposcopy and successively treated by, for instance, large loop electro-surgical excision of the transformation zone. Persistent infections with certain high-risk human papillomavirus (hr-HPV) genotypes play an essential role in cervical cancer carcinogenesis by mechanisms discussed in this review. HPV assessment, either DNA detection or HPV genotyping, could enhance the current cervical cancer screening programmes. Furthermore, primary prevention of cervical cancer through the introduction of HPV vaccines looks promising although the current vaccines merely protect against two hr-HPV genotypes, leaving a niche for at least 11 other hr-HPV's. Cervical screening in the post-vaccination era cannot be abolished but could be altered, as discussed in this review. Algorithms with the primary objective of hr-HPV testing followed by subjective cytology assessment in HPV-positive women could be a solution for both pre- and post-vaccination screening.

Pulsed laser-induced autofluorescence spectroscopic studies of pathologically certified normal, premalignant, and malignant oral tissues were carried out at 325 nm excitation. The spectral analysis and classification for discrimination among normal, premalignant, and malignant conditions were performed using principal component analysis (PCA) and artificial neural network (ANN) separately on the same set of spectral data. In case of PCA, spectral residuals, Mahalanobis distance, and scores of factors were used for discrimination among normal, premalignant, and malignant cases. In ANN, parameters like mean, spectral residual, standard deviation, and total energy were used to train the network. The ANN used in this study is a classical multiplayer feed-forward type with a back-propagation algorithm for the training of the network. The specificity and sensitivity were determined in both classification schemes. In the case of PCA, they are 100 and 92.9%, respectively, whereas for ANN they are 100 and 96.5% for the data set considered., (Copyright 2005 Wiley Periodicals, Inc.)

Diagnostic concordance of intraepithelial malignancy is generally only fair. Because the diagnosis of actinic keratosis (AK) and squamous cell carcinoma (SCC) is not uniform and because such terms are not consonant with the nomenclature of other human epithelial malignancies, nomenclature revisions have been attempted. One hundred dermatopathologists were solicited to review 15 tissue sections representing a spectrum of varying thickness epidermal malignancy and to choose either AK or SCC as the diagnosis. Among the 77 participating dermatopathologists, intraclass correlation was high for what was perceived as AK, SCC, and their differentiation. Development of a two-tiered diagnostic system that retains our present diagnostic capabilities, but better fits the pathobiology of superficial epidermal malignancy is suggested. Davis DA, Donahue JP, Bost JE, Horn TD. The diagnostic concordance of actinic keratosis and squamous cell carcinoma.

Background: Actinic cheilitis (AC) is a widely recognized precancerous lesion of the lip. Varying degrees of epithelial dysplasia may be present. However, no studies have correlated epithelial changes with cytokeratin expression that might reflect the disordered maturation that is probably occurring., Methods: Thirty-four cases diagnosed as AC were classified according to dysplasia degree, and submitted to immunohistochemical staining for the detection of cytokeratins (CKs) 7, 8, 13, 14, 16 and 19. Normal mucosa adjacent to the lesions was also evaluated., Results: The results obtained showed that CK10 immunostained only superficial keratinized epithelial layers in 11 cases, and also intermediate spinous layers in 18 cases. Cytokeratin 14 was expressed in all epithelial layers of 31 cases, in two cases its expression was in the basal and intermediate layers, and one case was negative. Cytokeratin 13 immunostained 26 cases and was negative in eight cases. In these eight cases, CK13 was apparently replaced by CK16. Cytokeratin 16, besides these eight cases, was also expressed in the spinous intermediate layers of a further eight cases. The remaining CKs tested were all negative. No relation between the degree of dysplasia and the CK expression was noted., Conclusions: Cytokeratin expression in AC is different from that of normal oral mucosa, and is not related to the degree of dysplasia.

Background: We conducted a quality improvement project in a cervical cancer screening programme in Helsinki in order to see if detection of precancerous lesions could be influenced by external (participation rate) and internal (laboratory praxis) quality measures., Methods: In order to increase the participation rate, a second personal invitation to Pap-test was mailed to nonparticipants of the first call. In order to improve the quality of screening, the cytotechnicians monitored their performance longitudinally by recording the number of slides reviewed per day, the pick-up rate of abnormal smears, the report of the consulting cytopathologist, and the number of histologically verified lesions detected from the cases that they had screened. Regular sessions were held to compare the histological findings with the cytological findings of all cases referred for colposcopy. No pressure was applied on the cytotechnicians to ensure that they felt comfortable with their daily workload., Results: A total of 110 000 smears were screened for cervical cancer at the Helsinki City Hospital during 1996-99. Initially, the overall participation rate increased from 62% to 71%. The number of histologically confirmed precancerous lesions (CIN 1-3) more than doubled and their detection rate increased from 0.32% to 0.72%., Conclusions: Continuous education and feedback from daily work performance were important, yet rather inexpensive means in increasing laboratory performance. Additional measures are needed to further increase the participation rate. Impact of the quality measures on cancer incidence needs to be assessed later on.

Background: In the 1998 World Health Organization and International Society of Urologic Pathology (WHO/ISUP) classification system for bladder neoplasms, flat intraepithelial lesions of the urinary bladder were categorized as reactive atypia, atypia of unknown significance, dysplasia, and carcinoma in situ. The clinical outcomes of patients diagnosed with these atypical urothelial proliferations are uncertain., Methods: The authors studied a series of patients who were diagnosed with reactive atypia of the urinary bladder (25 patients), urothelial atypia of unknown significance (35), or urothelial dysplasia (26) between 1985 and 1993. All histologic slides were reviewed and classified according to the 1998 World Health Organization and International Society of Urologic Pathology classification system. Patients with a concomitant or prior history of carcinoma in situ or urothelial carcinoma were excluded., Results: Patient age at diagnosis ranged from 24 to 88 years (mean, 65 years). The male-to-female ratio was 3:1. The mean follow-up was 3.9 years (range, 0.1-13.4 years; median, 3.5 years). None of the patients with reactive atypia or atypia of unknown significance developed dysplasia, carcinoma in situ, or urothelial carcinoma. Four patients (15%) with urothelial dysplasia developed biopsy-proven cancer, including 3 patients with muscle-invasive cancer. The mean interval from the diagnosis of urothelial dysplasia to the development of cancer was 4.5 years., Conclusions: Patients with a diagnosis of urothelial atypia of unknown significance or reactive atypia do not have adverse clinical outcomes, whereas patients with urothelial dysplasia of the bladder have an increased risk for the development of carcinoma in situ and urothelial carcinoma., (Copyright 2000 American Cancer Society.)

Background: Research studies on the relationship between benign breast diseases and cancer risk typically identify certain conditions as risk factors, and others as carrying no prognostic significance. This study addresses several issues concerning the relevance of such research results for advising individual patients in a clinical setting., Methods: Data were obtained as part of a "blinded" retrospective pathology review of benign breast biopsies. A random sample of cases was reviewed twice, providing information about reliability. Comparisons with diagnoses that used information from the operative reports and gross pathology descriptions as well as microscopic histology were used to assess validity., Results: Among cases that were reviewed twice, excellent agreement was achieved for diagnosing carcinoma and lobular neoplasia, good agreement for adenosis and intraductal papilloma, and relatively poor agreement about levels of hyperplasia and atypia, and whether ducts or lobules were involved. Distinctions among levels of hyperplasia also apparently were influenced by the number of slides available for review. The "blinded" review diagnoses frequently differed from the diagnoses that used all information available at the time of surgery in detecting the presence or absence of gross cystic disease, and in distinguishing solitary from multiple papillomas., Conclusions: Problems with reliability of precise distinctions among levels and sites of hyperplasia and atypia seem to limit the usefulness of such classifications as guidelines for individual patient care. For conditions with some clinical manifestations, diagnoses based exclusively on histologic review of biopsy specimens often are not accurate.

Background: Recent studies concerning an association between benign breast diseases and risk of subsequent breast cancer have focused on benign proliferative lesions recognized in biopsy specimens. Some have implicated atypical hyperplasia as being associated with the greatest risk., Methods: The histologic sections of specified benign breast lesions from 1799 women were reviewed and reclassified, using published criteria for proliferative disease. Prognostic significance was assessed by relating the pathologic findings to the development of breast cancer observed during an average 21 years of follow-up, in which time 157 women developed the disease., Results: Benign proliferative changes were recognized in 85% of the patients, with a corresponding relative risk of subsequent carcinoma equal to 2.2 times population rates (95% confidence limits, 1.9 and 2.6). Increasing levels of hyperplasia and atypia in lobules or ducts were associated with modest increases in risk, ranging from 2.1 to 2.3 to 3.0 for proliferative changes with no atypia, mild atypia, and moderate to severe atypia, respectively. This trend was not statistically significant. The most significant risk indicators in this study were the presence of adenosis (relative risk, 3.7), and moderate or severe atypia in ducts (relative risk, 3.9)., Conclusions: Benign proliferative breast disease recognized in biopsy specimens is associated with an increased risk of future breast cancer, but fine distinctions among levels of hyperplasia and atypia did not significantly distinguish risk among patients in this study.

Epithelial lesions of the vulva with patterns of dysplasia or carcinoma in situ may be associated with underlying invasive squamous cell carcinoma or the presence of dysplasia or carcinoma elsewhere on the vulva. These lesions may regress spontaneously, particularly when they appear as multiple papules in young patients. Two major classifications of precancerous lesions of the cervix are in current usage: 1) mild to severe dysplasia and carcinoma in situ; 2) cervical intraepithelial neoplasia, grades I to III. Both of them imply a more complete understanding of the nature of these changes than exists at the present time. Precancerous lesions of the cervix, vagina, vulva, and/or perineum are often associated synchronously or asynchronously. Although there are numerous designations for precancerous lesions of the endometrium, relatively little precise information exists about their significance. In managing women with these lesions, the gynecologist should communicate with the pathologist about the meaning of his diagnostic term, inquiring how far along the road toward invasive carcinoma the precancerous process is judged to be.