Srinivas Mandavilli

Dysplasia associated with atypical glandular cells on cervical cytology

OBJECTIVES: To estimate the rates of and identify risk factors for disease in women with atypical glandular cells of undetermined significance (AGUS). METHODS: From 1998–2001, 477 Pap tests at Hartford Hospital were classified as AGUS and met the inclusion criteria of this study. Findings were evaluated for 2 years from the initial test. Disease was defined as histology results with a finding of high-grade squamous intraepithelial lesion or greater. RESULTS: Disease was diagnosed in 9% of the women, including malignancy in 3%. Women with malignant-appearing AGUS Pap tests had a higher rate of disease (29%) than women with benign-appearing (5%, P < .01) and unspecified AGUS Pap tests (13%, P < .03). Malignancies were associated with all subclassifications of AGUS Pap tests. Women aged less than 35 years were more likely to have disease than women aged 35 years or older (P < .02). Most women aged younger than 35 years had a squamous abnormality, whereas women aged 35 years or older had a greater diversity of squamous and glandular lesions and accounted for all cases of endometrial cancer, adenocarcinoma in situ, and cervical adenocarcinoma. Women with persistent AGUS Pap tests had a 31% rate of disease. The rate of disease among women with AGUS Pap tests collected by liquid-based cytology was 11%, compared with 6% among samples collected by the conventional method. CONCLUSION: These data suggest that women with atypical glandular cells are at substantial risk for dysplasia and malignancy. The rate of disease varies with the method of Pap test collection, age, presence of persistent AGUS Pap tests, and AGUS subclassification. LEVEL OF EVIDENCE: II-3

Lack of adherence to practice guidelines for women with atypical glandular cells on cervical cytology.

OBJECTIVE: We sought to estimate the rates and types of evaluation in women with atypical glandular cells of undetermined significance (AGC-US) on cervical cytology and to assess these findings on the basis of published management guidelines. METHODS: The rates of histologic sampling, comprehensive initial evaluations, and secondary evaluations were assessed in 477 women with an AGC-US Pap test from 1998 to 2001. A comprehensive evaluation was defined as a colposcopy and an endocervical curettage with or without a cervical biopsy. For women aged 35 or older, a comprehensive evaluation also included an endometrial biopsy. A secondary evaluation consisted of a diagnostic cone biopsy. RESULTS: Sixty-four percent of women with an AGC-US Pap test had histologic sampling; 36% were followed by repeat Pap test only. Thirty-six percent of women with an AGC-US Pap test had a comprehensive evaluation. Women with an AGC-US Pap test that was subclassified as malignant-appearing had higher rates of histologic and comprehensive evaluations than women with a benign-appearing or unspecified AGC-US Pap test (P < .01). Twenty-eight percent of women aged 35 or older had comprehensive evaluations compared with 57% of women younger than the age of 35 (P < .01). Secondary evaluations were performed in 8% of women with persistent AGC-US Pap tests and 2% of women with malignant-appearing AGC-US Pap tests after negative initial histologic evaluations. Twelve of the 42 cases of disease (29%) were diagnosed more than 1 year from the initial AGC-US Pap test. CONCLUSION: On the basis of accepted management guidelines, these data suggest that women with AGC-US Pap tests are undermanaged in both their initial and secondary evaluations. LEVEL OF EVIDENCE: III

The Prevalence of Cervical HPV and Cytological Abnormalities in Association with Reproductive Factors of Rural Nigerian Women

OBJECTIVE To estimate the prevalence of cervical human papillomavirus (HPV) and cytological abnormalities while addressing demographic and reproductive variables in a sample of rural Nigerian patients. METHODS In March 2004, a medical project was conducted in Okene, Nigeria. The obstetrics/gynecology team collected demographics of 231 patients and 199 ThinPrep Pap smears (Cytyc, Marlborough, MA), which were analyzed cytologically and for the presence of HPV DNA. RESULTS Of 231 patients (mean age 32.2), 76% had seen a physician four times or less. From 199 Pap smears performed, 21.6% had high-risk (HR) HPV, low-risk (LR) HPV, or both. HR HPV was present in 16.6% of the women. There were 13 (6.5%) abnormal Pap smears, of which 9 (4.5%) had atypical squamous cells of undetermined significance (ASCUS), 1 (0.5%) had atypical glandular cells (AGC), 2 (1%) had low-grade squamous intraepithelial lesions (LSIL), and 1 (0.5%) had a high-grade SIL (HSIL). Other findings were Trichomonas vaginalis in 18 patients (9%) and Candida in 27 patients (13.5%). CONCLUSIONS The prevalence of cervical HPV and SIL in Okene, Nigeria, is consistent with reports from other African regions. Improved access to healthcare and cervical cancer screening programs may help to decrease transmission of HPV and subsequent cervical cancer in underprivileged areas.

Rapid Detection of HSV from Cytologic Specimens Collected into ThinPrep Fixative

OBJECTIVE Herpes simplex virus (HSV) infection is associated with substantial morbidity and mortality in neonates. A diagnosis of HSV on cervical cytologic studies could lead to a cesarean section, with an increase in the risk of maternal morbidity. The identification of viral lesions in sexually active women has medical and social implications. There have been reports of false positive diagnoses of HSV in patients with altered endocervical cells and with cervical intraepithelial neoplasia 3. We evaluated a polymerase chain reaction (PCR)-based assay to detect HSV-1 and HSV-2 in routinely collected cervical cytology specimens in ThinPrep fixative (Cytyc Corp., Marlborough, Massachussets, U.S.A.). STUDY DESIGN DNA was extracted from five cases that demonstrated cytologic changes suggestive of an HSV infection. PCR amplification with subsequent gel electrophoresis was performed to detect the presence of HSV. RESULTS HSV DNA was detected in three of five cases that were cytologically diagnosed as suspicious or strongly suspicious for HSV infection. CONCLUSION The combination of the ThinPrep liquid-based method for cervical cytology with PCR allows prompt confirmation of the diagnosis of HSV without sacrificing the diagnostic morphology on the slide.

CD34-reactive trichodiscoma.

Background:  Trichodiscomas are rare hamartomas of the dermal portion of the hair disc, a specialized component of the perifollicular mesenchyme. They are usually found as asymptomatic multiple skin‐colored papules on the face and extremities and may have an autosomal dominant inheritance pattern. However, a solitary variant has been described.

Prevalence of high-risk cervical human papillomavirus and squamous intraepithelial lesion in Nigeria

Objective The prevalence of cervical cancer and high-risk human papillomavirus (HPV) in Nigerian women remains poorly studied. Our objective was to estimate the prevalence of high-risk HPV and associated squamous intraepithelial lesions (SILs) in Nigeria. Methods After institutional review board approval, data collection was performed by volunteers of FaithCare, Inc, between 2004 and 2008 in 3 regions of Nigeria (Okene, Katari, and Abuja). Demographic data and ThinPrep Pap smears (Cytyc, Marlborough, MA) were collected from 410 women. Pap smears were analyzed for both the presence of SIL and HPV DNA. Results The prevalence of high-risk HPV and SIL was 15.6% and 6.8%, respectively. Of the 28 abnormal Pap tests, 42.9% had atypical squamous cells of undetermined significance, 39.3% had low-grade SIL, 14.3% had high-grade SIL, and 3.6% had atypical glandular cells. There was a strong association between high-risk HPV and SIL in both the combined (p < .001) and individual group data (p < .001, p = .013, and p < .001 for Okene, Abuja, and Katari, respectively). However, there were no statistically significant correlations between either high-risk HPV or presence of SIL and known risk factors including age, history of sexually transmitted disease, and the number of sexual partners. There was also no statistical difference in the prevalence of high-risk HPV and SIL among the 3 locations. Conclusions A strong association exists between high-risk HPV and SIL. The prevalence of cervical high-risk HPV and SIL, however, did not vary in the 3 different locations and is consistent with reports from other regions in Africa.

The utility of PAX8 and IMP3 immunohistochemical stains in the differential diagnosis of benign, premalignant, and malignant endocervical glandular lesions

UNLABELLED Glandular lesions of the endocervix can be diagnostically challenging and occasionally the differential diagnosis includes endocervical adenocarcinoma in situ (EC AIS) and well-differentiated endocervical adenocarcinoma (ECA). PAX8 and IMP3 are two markers which have not been well studied in the endocervix. Our aim was to evaluate their immunohistochemical (IHC) expression in benign and malignant endocervical glandular lesions as well as to compare them to the traditionally used panel (Ki-67, p16, CEA). DESIGN We searched our surgical pathology files for a cohort of benign endocervical glandular lesions as well as premalignant and malignant groups including EC AIS and ECA. An IHC panel consisting of PAX8, IMP3, Ki-67, p16, and CEA was performed on all cases. Immunoreactivity was scored on a degree of positivity (S0=no immunoreactivity, S1=up to 10% cells, S2=between 10 and 50% cells, S3=>50% cells) and intensity (Int0 - absent, Int1 - mild/faint, Int2 - moderate, Int3 - strong). RESULTS PAX8 showed diffuse positivity (S3) with at least a moderate intensity of staining (Int2) in the benign group. PAX8 was focal (S1) in ECA and faint (Int1), compared to EC AIS, which was moderate (S2) and faint (Int1). IMP3 expression was focal in the benign group (S1), moderate (S2) in EC AIS and moderate-to-diffuse (S2-3) in ECA. IMP3 intensity was faint (Int1) in benign lesions, moderate (Int2) in EC AIS, and strong (Int3) in ECA. Significant Ki-67, p16, and CEA expression was noted in the premalignant/malignant cohort. CONCLUSION PAX8 and IMP3 can be helpful in the differential diagnosis of benign vs. malignant endocervical glandular lesions. Our study, however, shows that there is some degree of overlap of staining in both the benign and malignant group. As such, PAX8 and IMP3 should always be interpreted with caution and in combination with the histomorphology.

Prevalence of the human papillomavirus in an inner-city indigent population with previously normal Pap tests.

Objective. To determine the prevalence of human papillomavirus (HPV) in our inner-city indigent population (clinic population) of women with previously normal Pap tests and to identify any associated risk factors. Materials and Methods. A prospective cohort of 187 women between the ages of 15 and 49 years, with previously normal Pap tests, was recruited from a university affiliated outpatient clinic. A demographic questionnaire of social and sexual history was elicited, and ThinPrep cytology (Cytyc, Marlborough, MA) and HPV Digene Hybrid Capture II results (Digine, Gaithersburg, MD) were obtained. Results. The prevalence of HPV in our primarily Hispanic clinic population was 21%. The mean age of women with HPV was 28.9 years and those without were 32.1 years (p <.046). In women with HPV, 24% had abnormal Pap tests, whereas in those without HPV, 5% had abnormal Pap tests (p <.001). Women who were older and parous were less likely to have HPV (7.5%; p <.024). The presence of HPV was not influenced by sexual behaviors, sexually transmitted diseases, smoking, race, or contraceptive use. Conclusions. The prevalence of HPV in an inner-city indigent population, despite previously normal cytology, was consistent with earlier reported rates of HPV. Our data suggest that younger, nulliparous women have a high prevalence of HPV.

CD34-reactive trichodiscoma [3]

To the Editor, We thank Drs Collins, Somach and Morgan for their recent comments on our case report of CD34 reactivity in the mesenchymal component of a trichodiscoma and for bringing our attention to their similar observation. We acknowledge that Drs Collins et al. reported CD34 and vimentin reactivity in the spindle cell component of both sporadic and Birt-Hogg-Dube syndrome-associated fibrofolliculomas and trichodiscomas. In response, we would like to enumerate a number of points. First, their findings were not included in our case report, as our observation of CD34 reactivity in a trichodiscoma was submitted and accepted for publication prior to their original article’s publication. Second, in their recent letter, Drs Collins et al. stated that an important conclusion drawn from (their) study was the finding of CD34 mesenchymal immunoreactivity, bolstering the concept of their derivation from the hair follicle mantle and suggesting a common histogenic lineage for trichodiscoma and fibrofolliculoma.’ However, in their original description, Drs Collins et al. also stated that an identical immunohistochemical profile as demonstrated between these entities and the hair disk is not proof positive for a common histogenesis.’ In view of the numerous cutaneous entities reported to be CD34 reactive (i.e. lack of specificity of this antibody), we do not believe that any conclusion regarding a common histogenic lineage for trichodiscoma and fibrofolliculoma can be drawn from the presence of CD34 reactivity within the mesenchymal component of these tumors.

Fine-needle aspiration diagnosis of a neck mass using immunocytochemical stains performed on stained cytology slides

Abstract Superficial neck lesions such as those in lymph nodes or thyroid and salivary glands are amenable to fine-needle aspiration biopsies. The use of ancillary studies, including immunocytochemistry, performed on cytologic material can provide useful information used to formulate a diagnosis when tumor cells are identified. We present a case of a 59-year-old male with a neck mass where the diagnosis was established on the basis of immunocytochemical stains performed on alcohol-fixed, H&E-stained cytology slides. Subsequent clinical studies and surgical excision of the tumor confirmed the diagnosis. (The J Histotechnol 25:275, 2002)