Reporting of atypical squamous cells,cannot exclude a high‐grade squamous intraepithelial lesion (ASC‐H) on cervical samples: Is it significant?

"Atypical squamous cells, cannot exclude a high-grade squamous intraepithelial lesion (ASC-H)" is a new diagnostic category in the 2001 Bethesda nomenclature system for cervical cytology. The purpose of this 7-mo retrospective study (March 1, 2002-September 30, 2002) was to evaluate the significance of ASC-H on cervical Thin Prep Pap Tests. During this period, 25 (0.27%) of 9,214 Pap Tests were diagnosed as ASC-H, 22 of which resulted in either follow-up cervical biopsies and/or cervical cones, and which formed the basis of this study. Tissue specimens (22 cases) were negative in 5 cases (23%) and positive in 17 cases (77%). Of the positive specimens, there were 2 (12%) low-grade squamous intraepithelial lesions (LSIL) and 15 (88%) high-grade squamous intraepithelial lesions (HSIL). Of the 22 cases, ASC-H diagnoses included immature/atypical squamous metaplasia vs. a squamous intraepithelial lesion (SIL) in 19 (86%) cases, and tight clusters of small cells with a high nuclear to cytoplasmic ratio in 3 (14%) cases. The results of this study indicate that the reporting of ASC-H on cervical samples does lead to the detection of HSILs in a significant number of cases (68% in this study). Therefore, further evaluation of the patient is warranted.     

Women ≥30 years of age with low grade squamous intraepithelial lesion (LSIL) have low positivity rates when cotested for high‐risk human papillomavirus: Should we reconsider HPV triage for LSIL in older women?

High‐risk human papillomavirus (HR‐HPV) testing for colposcopy triage of low grade squamous intraepithelial lesion (LSIL) is not recommended because of high positive rates in young women. It remains unclear whether HR‐HPV testing may be useful for triage of older women. We compiled HR‐HPV data for women aged ≥30 years with LSIL for the period March 1, 2006 to February 28, 2008. Follow‐up cervical biopsy information was collected for the period March 1, 2006 to August 15, 2008. We used the Hybrid Capture II test performed on residual material from liquid‐based Pap tests. Of 735 women, 254 had HR‐HPV testing, and of these 144 had positive HR‐HPV results. Among women with positive HR‐HPV results 79 underwent biopsy (54.9%) and 11 had cervical intraepithelial neoplasia (CIN) 2 or 3 (13.9% of women with biopsy follow‐up). A total of 481 women did not undergo HR‐HPV testing, of whom 192 underwent biopsy (39.9%) and 11 had CIN 2 or 3 (5.7% of biopsied women [P = 0.04]). Among women who tested negative for HR‐HPV and had follow‐up biopsies, only one had a high grade lesion found (CIN 2). The overall HR‐HPV positive rate in tested women ≥30 years old with LSIL was 56.7% if women who had reflex HR‐HPV testing for ASC‐US are included. The HR‐HPV positive rate in residual material from Pap tests interpreted as LSIL was 63.8%. Among women ≥30 years of age with LSIL, CIN 2‐3 is significantly more likely in HR‐HPV positive women. Relatively few older women with LSIL test positive for HR‐HPV. Colposcopy triage using HR‐HPV may be justified in this population. Diagn. Cytopathol. 2010. © 2009 Wiley‐Liss, Inc.     

Do neutralizing antibody responses generated by human papillomavirus infections favor a better outcome of low‐grade cervical lesions?

To determine the role of neutralizing antibody generated by human papillomavirus (HPV) infections, baseline levels of serum neutralizing antibodies directed against HPV 16 and cervical HPV DNA were determined in 242 unvaccinated women with low‐grade cervical abnormalities, who were then monitored by cytology and colposcopy every 4 months. In women infected with HPV 16 (n = 42), abnormal cytology persisted longer in those positive for HPV 16‐specific neutralizing antibodies at baseline (median time to cytological regression: 23.8 vs. 7.2 months). Progression to cervical precancer (cervical intraepithelial neoplasia grade 3) within 5 years occurred only among women carrying HPV 16‐specific neutralizing antibodies (P = 0.03, log‐rank test). In women infected with types other than HPV 16 (n = 200), detection of HPV 16‐specific neutralizing antibodies was not correlated with disease outcome. In conclusion, development of specific neutralizing antibodies following natural HPV 16 infection did not favor a better outcome of low‐grade cervical lesions induced by HPV 16 or by other types; rather, detection of neutralizing antibodies generated by current infection may reflect viral persistence and thus help identify those who are at high risk of disease progression. J. Med. Virol. 84: 1128–1134, 2012. © 2012 Wiley Periodicals, Inc.     

Nuclear localizaiton of β-catenin is associated with poor survival and chemo-/radioresistance in human cervical squamous cell cancer

Nuclear expression of β-catenin has been suggested as an independent prognostic marker in a variety of cancers. The objective of this study was to investigate the clinicopathologic significance of nuclear β-catenin expression in patients with cervical squamous cell carcinoma (CSCC). In this original research article, we detected nuclear β-catenin expression in 29/171 CSCC tissues (17.0%). Patients without nuclear β-catenin expression had a significantly better outcome than patients with nuclear β-catenin expression (93.7% versus 82.7% P = 0.027). Furthermore, nuclear β-catenin expression was predictive of prognosis in CSCC patients with early stage disease (FIGO stage I or tumor size ≤ 4 cm), with well/moderately differentiated tumors, or lymph node metastasis. Interestingly, nuclear β-catenin expression correlated with poor outcome in patients who received postoperative chemotherapy or radiotherapy. Multivariate analysis suggested that nuclear β-catenin expression is an independent prognostic indicator in CSCC. Our findings suggest that nuclear β-catenin expression may be used as a prognostic biomarker in CSCC, especially for patients with early stage disease, well/moderately differentiated tumors, or lymph node metastasis. Moreover, nuclear β-catenin expression has potential as a predictive marker of chemoresistance and radioresistance in CSCC.     

Is high‐grade prostatic intraepithelial neoplasia (HGPIN) a reliable precursor for prostate carcinoma? Implications for clonal evolution and early detection strategies

High‐grade prostatic intraepithelial neoplasia (HGPIN) is a documented putative precursor lesion for invasive prostate adenocarcinoma. However, the precise mechanisms of the carcinoma's development from HGPIN are unclear. Many studies have attempted a comparative molecular genetic characterisation of HGPIN and its corresponding carcinoma to study this transformation. However, to date, some HGPIN mimickers, such as intraductal carcinoma, which can engage in retrograde colonisation of the prostatic acini in an HGPIN‐like manner, have been described. In this work, we hypothesise that the lesion formerly known as HGPIN adjacent to invasive carcinoma does not necessarily represent its respective precursor lesion. This hypothesis stems from recent morphological, experimental, and theoretical evidence on the development of tumour clonality, as well as recent studies outlining the three‐dimensional architecture of prostate adenocarcinomas (most importantly, their interconnection with the tumoural glandular system). Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Should cervical cancer screening begin at age 21 for everyone? A quantitative analysis in a high‐risk,low‐income,African American/Hispanic young‐adult population

The American College of Obstetricians and Gynecologists has recommended modifying the baseline cervical cancer screening age from earlier of three years after first sexual intercourse or age 21 to age 21. In this study, we tracked abnormal cytologic diagnoses, with an emphasis on high‐grade cervical lesions, in a high‐risk, low‐income, African American/Hispanic young‐adult population. The intention was to assess if delaying cancer screening to 21 years of age would be effective in this subpopulation. A search of the cytopathology database between January 1, 2001 and December 31, 2009 was performed to identify all women with their first abnormal cytologic diagnosis prior to turning 21 years of age. All of the available follow‐up cytologic and/or histologic diagnoses, made both prior to and after turning 21 years of age, were recorded and the results analyzed. Amongst the 8,011 total number of women under 21 years of age screened for cervical cancer at our institution from January 1, 2001 to December 31, 2009 the overall abnormal cytology rate was 25%, with a rate of 1% for HSIL, 3% for ASC‐H/LG‐H, and 22% for LSIL/ASC‐US. The youngest subject diagnosed with HSIL was 14 years of age. Not a single study subject developed invasive cervical cancer prior to turning 21 years of age. In spite of the limitations of the study, we found that for patients served by our institution, delaying cervical cancer screening until 21 years of age is effective for the detection of early precancerous lesions. Diagn. Cytopathol. 2014;42:205–212. © 2013 Wiley Periodicals, Inc.     

Are adjunctive markers useful in routine cervical cancer screening? Application of p16INK4a and HPV‐PCR on ThinPrep samples with histological follow‐up

The objectives of the study were to evaluate 1) the diagnostic sensitivity and specificity of p16(INK4a) as a marker for high-grade cervical lesions, 2) the results of a real-time polymerase chain reaction detecting high-risk human papillomavirus, and 3) the interobserver variability of the p16(INK4a) interpretation.A total of 232 ThinPrep samples were stained for p16(INK4a), and HPV-DNA PCR was performed on 107 specimens with inclusion of both benign and abnormal cytology. Histological follow-up information was collected. The diagnostic sensitivity of ASC+ with CIN2+ in histology as endpoint was 96% for p16(INK4a) and 100% for HR-HPV DNA PCR, and the diagnostic specificity was 41% and 27%, respectively. If p16(INK4a) had been used for triage of the ASC samples, then 18 patients (42%) could have been spared unnecessary follow-up procedures compared to six patients (21%) with the HR-HPV DNA test.     

Antibody response against three epitopic domains on human chorionic gonadotropin (hCG) in women and rodents immunized with a βhCG-based immunocontraceptive vaccine

The antibody repertoire generated against human chorionic gonadotropin (hCG), following immunization with an immunocontraceptive vaccine based on the beta subunit of the hormone, in humans was compared with that generated in rats. Three epitopic domains represented by the hCG loop peptide 38–57, the carboxy-terminal peptide (CTP) 109–145, and a region defined by monoclonal antibody (MAb) 206 were probed. In both species, the titer of antibodies against the MAb 206-defined epitopic domain had a good correlation with the total anti-hCG antibody titers. However, the antibody response against the hCG loop peptide (38-57) was not observed in human subjects and there was a weak response against this peptide in rats. Despite the good anti-hCG antibody titers in all animals (n=8), only two had antibodies against this domain. A good antibody response was observed against CTP in rats, whereas in humans this region was weakly immunogenic. Antibodies against CTP were detected in random samples in only 57% of the subjects and this response had no correlation with the total anti-hCG antibody titers. The high antibody response against CTP in rodents compared to humans may be due to its recognition as a foreign determinant. Our results demonstrate that contraception can be achieved in women despite a poor antibody response against the CTP (109-145) and a receptor binding domain (38–57) of hCG.     

Metastatic adenoid cystic carcinoma with high‐grade transformation (“dedifferentiation”) in pleural effusion and neck lymph node: A diagnostic challenge on cytology?

High‐grade transformation (HGT) or “dedifferentiation” is an uncommon phenomenon among salivary gland carcinomas including adenoid cystic carcinoma (ACC), which is important to recognize because it is associated with increased tumor aggressiveness, with a high propensity for lymph node and distant metastases. ACC with HGT is histologically characterized by a distinct population of poorly differentiated cells with loss of the typical biphasic ductal and myoepithelial differentiation seen in conventional ACC, associated with pleomorphism, necrosis and increased mitotic activity. We report the cytologic features of a case of metastatic ACC‐HGT in cervical lymph node and effusion, which, to the best of our knowledge, have not been described previously. When ACC presents both in atypical locations and with HGT, the danger of misdiagnosis is increased if the clinical history is lacking, incomplete or inaccurate. Since ACC‐HGT are rare (and possibly underdiagnosed) and do not have a specific set of cytological and/or immunohistochemical features, it is important for practicing cytopathologists to be aware of the possibility of encountering them, especially in specimens from patients with a history of ACC, in order to render the correct diagnosis.