The ASCUS : SIL ratio and the reference laboratory pathologist

The atypical squamous cells of undetermined significance (ASCUS) : squamous intraepithelial lesion (SIL) ratio was proposed to monitor laboratory use of the ASCUS diagnosis. This study addresses problems associated with comparing pathologists by this means. An intuitive example showed the ASCUS : SIL ratio depends on the prevalence of smears from patients who actually have SIL. In this study of 2000 cervical smears, each of five pathologists made 400 diagnoses. Differences among proportions of SIL diagnoses were statistically significant; differences among proportions of ASCUS diagnoses were not. Had an ASCUS : SIL ratio upper limit of 3.0 been used, two pathologists would have been misidentified as having high ASCUS diagnosis rates. Unlike the situation for laboratories, potential variability in SIL prevalence requires caution in the use of this ratio in assessing pathologists. An alternative measure that is independent of prevalence, the ASCUS : SIL odds ratio, is posited.     

Triage of women with equivocal or low-grade cervical cytology results: a meta-analysis of the HPV test positivity rate

Consistent evidence underlines the utility of human papillomavirus (HPV) DNA testing in the management of women with equivocal cervical cytological abnormalities, but not in case of low-grade lesions. We performed a meta-analysis including studies where the high-risk probe of the Hybrid Capture-II is used to triage these two cytological categories. The triage test-positivity rate reflects the colposcopy referral workload.Data were pooled on the HPV test positivity rate in women with atypical squamous cells of undetermined significance (ASCUS/ASC-US) or low-grade squamous intraepithelial lesions (LSIL), derived from different cytological classification systems. The meta-analysis was restricted to studies, published between 1991 and 2007. A random-effect model was applied for meta-analytical pooling and the influence of covariates on the HPV positivity rate was analyzed by meta-regression. The variation by age was assessed within individual studies since age strata were not defined uniformly. On an average, 43% (95% CI: 40–46%) of women with ASCUS/ASC-US were high-risk HPV positive (range 23–74%). In women with LSIL, the pooled positivity rate was 76% (95% CI: 71–81%; range 55–89%). In spite of considerable inter-study heterogeneity, the difference in HPV positivity between the two triage groups was large and highly significant: 32% (95% CI: 27–38%). HPV rates dropped tremendously as age and cutoffs of test positivity increased. Other factors (cytological classification system, country, continent, collection method and year of publication) had no statistically significant impact, except in LSIL triage where HPV positivity was significantly lower in European compared to American studies. Women with LSIL, especially younger women, have high HPV positivity rates suggesting limited utility of reflex HPV triaging these cases. Research is needed to identify more specific methods to triage women with low-grade squamous cervical lesions.     

Cytologic detection of esophageal squamous cell carcinoma and its precursor lesions using balloon samplers and liquid-based cytology in asymptomatic adults in Llinxian, China

OBJECTIVE: Esophageal squamous cell carcinoma (ESCC) is associated with very high regional mortality rates in several countries. Our initial test of esophageal cytology screening devices found them not sensitive enough for an early detection program. The current study tested a newly designed "mechanical" balloon and a traditional Chinese inflatable balloon, followed by liquid-based cytology, to detect biopsy-proven squamous dysplasia and early cancer. STUDY DESIGN: Participants were randomized to a cytologic sampler, followed by endoscopy with iodine staining. For each patient, the cytologic diagnosis (test) was compared with the worst endoscopic biopsy diagnosis (truth). RESULTS: Seven hundred forty subjects completed both examinations. Approximately 30% showed atypical squamous cells of undetermined significance (ASCUS), and 10% showed squamous intraepithelial lesions. Seven hundred twenty-five subjects (98%) had satisfactory biopsies, and 32% had low grade dysplasia or worse disease. Defining > ASCUS, favor neoplastic, as a positive screening test, the sensitivities/specificities of the mechanical and inflatable balloons were 39%/85% and 46%/84%, respectively, for detecting any squamous dysplasia or cancer. CONCLUSION: These esophageal cell samplers performed equivalently, but the accuracy was still too low for a primary screening test. These results highlight the need to develop new cytologic criteria or molecular markers that can better detect early squamous esophageal disease [corrected]     

Significance of high-risk human papillomavirus detection by polymerase chain reaction in primary cervical cancer screening

The purposes of this study were to evaluate the incidence of high-risk human papillomavirus (HPV) infection by polymerase chain reaction (PCR) and to assess its diagnostic usefulness in primary cervical screening. PCR testing for HPV type 16, 18, 31 and 33 was performed on 1305 specimens obtained during routine cervical cancer screening. We analysed the concurrent cervical smears and biopsy, and correlated them with the HPV infection status. We also evaluated histologically-proven cases with ASCUS smears according to HPV infection. HPV DNA was identified in eight (0.7%) of 1144 cytologically normal patients; nine (10.5%) of 86 ASCUS; seven (25.0%) of 28 LSIL; 26 (78.8%) of 33 HSIL; and in all of three squamous cell carcinomas (SCC). HPV positivity was significantly associated with cytohistological diagnosis for HSIL of more. In addition, HPV-positive ASCUS cases were found to be associated with histological abnormality rather than HPV-negative. The results indicate that high-risk HPV testing by PCR could be a useful adjunct tool for Pap smear in primary cervical screening. The combination of Pap smear and high-risk HPV testing by PCR might reduce unnecessary colposcopy-guided biopsy of women with cytological diagnosis of ASCUS.     

Use of a liquid-based, thin-layer Pap test in a community hospital. Impact on cytology performance and productivity

OBJECTIVE: To evaluate the direct-to-vial efficacy of the SurePath Pap test (TriPath Imaging, Burlington, North Carolina, U.S.A.) in a community hospital laboratory and to assess its impact on productivity, as measured by Pap test turnaround times (TATs). STUDY DESIGN: A total of 8,771 SurePath Pap tests were compared to 5,055 conventional Pap smears collected and processed over the same 12-month period. SurePath histologic correlation rates were compared to historical correlation rates for conventional Pap smears. Pap test TATs for 3 months prior to implementing SurePath were compared to TATs for the last 3 months of the study, which included an approximate 70:30 ratio of SurePath to conventional Pap tests. Laboratory staffing was unchanged, and mean monthly accessions were relatively constant. RESULTS: SurePath showed statistically significant improvements in the detection of low grade (LSIL) (196%) and high grade (HSIL) (243%) squamous intraepithelial lesions (SILs) relative to conventional Pap smears. The atypical cells of undetermined significance (ASCUS) rate remained nearly constant with SurePath, while the ASCUS/SIL ratio decreased by 68%. Unsatisfactory rates declined 81%. Histologic correlation rates with SurePath increased over those of conventional Pap smears. Pap test mean TATs improved 73% with SurePath. CONCLUSION: Sure-Path detected significantly more cases of LSIL and HSIL than conventional smears without compromising specificity. The ASCUS/SIL ratio and unsatisfactory rate declined dramatically. Pap test TATs also improved markedly with SurePath.     

Variables associated with squamous intraepithelial lesions among women with a cytologic diagnosis of atypical squamous cells of undetermined significance.

OBJECTIVE: To identify factors among women with atypical squamous cells of undetermined significance (ASCUS) cytologic diagnosis that are associated with either low grade squamous intraepithelial lesions (LSILs) or high grade squamous intraepithelial lesions (HSILs). STUDY DESIGN: From January 1992 to June 1995, 1,660 women with a diagnosis of ASCUS were followed until the next follow-up appointment after the ASCUS diagnosis. Logistic regression analysis with either LSIL or HSIL at follow-up examination as a dependent variable was done with the following independent variables: patient age, method of follow-up, follow-up time, type of health care coverage and household income. RESULTS: In multivariate analyses, there was a 2.7-fold increase in the odds of LSIL (OR = 2.7, 95% CI = 1.3-5.8) for young women (< or = 25 years), a 2-fold decrease in the odds of LSIL (OR = .5, 95% CI .3-.9) for long time to follow-up (> 18 weeks after ASCUS diagnosis) and an 7.8-fold increase in the odds of LSIL (OR = 7.8, 95% CI = 5.1-11.9) for follow-up by colposcopic biopsy. For the odds of HSIL, there was a 6.8-fold increase (95% CI = 3.2-14.5) for follow-up by colposcopic biopsy as compared to Pap smears and a 3-fold decrease in the odds of HSIL (OR = 3, 95% CI = .1-.7) for high-income women (> $34,857). CONCLUSION: Our findings suggest that among ASCUS patients, younger women and those with shorter follow-up time are more likely to be diagnosed with LSIL. Women with a high income showed a protective association for HSIL. Colposcopic biopsy identified more LSIL and HSIL as compared to repeat Pap smear.     

Atypical squamous cells of undetermined significance in women over 55. Comparison with the general population and implications for management.

OBJECTIVE: To determine the significance of atypical squamous cells of undetermined significance (ASCUS) in patients 55 years or older. STUDY DESIGN: From January 1994, to January 1997, 8,175 cervicovaginal smears were obtained from patients 55 years or older (mean age, 64.8; range, 56-84) at University Hospitals of Cleveland. Ninety-six of these patients were diagnosed with ASCUS only or ASCUS with a qualifying statement on the smear. Patient records, follow-up cervicovaginal smears and biopsies were reviewed for a period of one to four years following the diagnosis of ASCUS. RESULTS: The incidence of ASCUS only or ASCUS with a qualifying statement for patients 55 years or older was 1.8%. The ASCUS:SIL ratio was 2.6:1. An estrogen stimulation test was recommended in two cases. Women older than 55 with ASCUS were three times more likely to be receiving hormonal replacement therapy than similar-aged women with normal cervicovaginal smears. Follow-up cervicovaginal smears or biopsies were obtained on 93 (80 cervicovaginal smears, 13 biopsies). The results were the following: LSIL (13), squamous carcinoma in situ (1) and ASCUS (53); the remainder of the cases were normal. In the patients who received a second diagnosis of ASCUS, follow-up cervi covaginal smears or biopsies revealed low grade dysplasia in six. CONCLUSION: Although the incidence of ASCUS and the frequency of underlying dysplasia is lower in postmenopausal women than the general population, there is still a real risk that a postmenopausal woman with ASCUS has underlying intraepithelial neoplasia. Therefore, these patients should be managed as is the general population.     

Clinical impact of atypical squamous cells of undetermined significance. A cytohistologic comparison

OBJECTIVE: To assess the percentage of squamous intraepithelial lesions (SILs) in the atypical squamous cells of undetermined significance (ASCUS) cytologic diagnosis. STUDY DESIGN: From January 1994 to December 1995, 421 cervical Pap smears with a diagnosis of ASCUS were followed with cervical biopsies within three months. The ASCUS cytologic diagnosis was correlated with the histologic findings and stratified according to age group, previous abnormal history and cell type of ASCUS (squamoid vs. metaplastic). RESULTS: Histologic diagnosis showed that of ASCUS diagnoses, 13% were normal, 34% were reactive, 4.8% were atypical, 43% were low grade SIL, 4% were high grade SIL, 1% were carcinoma in situ, and none were invasive lesions. The patients in the youngest group, up to 25 years, demonstrated the highest percentage of SIL. Patients with a previous abnormal gynecologic history showed a higher percentage of SIL than those without an abnormal history. SILs were observed in 51.5% of squamoid ASCUS and 36.5% of metaplastic ASCUS. CONCLUSION: Forty-eight percent of females having an ASCUS diagnosis on Pap smears had SIL and thus a preneoplastic lesion. The highest percentage of SIL was found in females 25 years and younger. Our findings suggest that an ASCUS diagnosis warrants ongoing follow-up.     

Fine needle aspiration cytology in the diagnosis of tuberculous mastitis

OBJECTIVE: To study the relationship between granulomas in the breast and tuberculous mastitis. STUDY DESIGN: Retrospective analysis of 22 breast aspirates that showed epithelioid cell granulomas. The aspirates were reviewed and the cytomorphologic findings summarized. RESULTS: Aspiration cytology revealed epithelioid cell granulomas along with giant cells, necrosis and inflammatory cell infiltrate. Overall acid-fast bacillus (AFB) positivity was 22.7%. AFB positivity was greater in the presence of necrosis when epithelioid cells were absent. CONCLUSION: In a country like India, the diagnosis of granulomatous mastitis must be made with caution, even in the absence of AFB. Only after a sufficient trial of antituberculosis treatment has been given and the patient fails to respond should an alternative diagnosis be suggested.     

Variation in the incidence of AGUS between different patient populations

OBJECTIVE: To determine the frequency of atypical glandular cells of undetermined significance (AGUS) for three consecutive calendar years from three different referral sources. STUDY DESIGN: Cervicovaginal smears with a diagnosis of AGUS were identified from January 1995 through December 1997. The smears were submitted from three different sources: two were city government hospital clinics, one with predominantly African American and Hispanic patients and the other with predominantly Asian and Hispanic patients. The third referral source was private practitioners' offices with predominantly Caucasian patients. RESULTS: A diagnosis of AGUS was made in 707 cases, accounting for 0.56% of all smears examined. This was in contrast to 6,872 smears reported as atypical squamous cells of undetermined significance (ASCUS) (5.4%) and 3,347 reported as squamous intraepithelial lesions (SIL) or above (2.7%). The incidence of AGUS ranged from 0.16% to 1.00% among different patient populations. This difference was also noted in the rate of ASCUS and SIL in the same patient population. There was a steady increase in the rate of AGUS for each referral source during the study period. The overall rate of patients who underwent histologic evaluation and the incidence of biopsy-proven preinvasive and invasive lesions were 62.4% and 23%, respectively. There was no significant difference in the rate of significant lesions after a diagnosis of AGUS during the study period or between the three referral sources. CONCLUSION: The AGUS rate in our laboratory was low and within the range (0.17-1.83%) reported in the literature. The AGUS rate varies with different patient populations, particularly with the incidence of SIL and age distribution.     

Significance of high-risk human papillomavirus DNA-positive atypical squamous cells of undetermined significance pap smears in perimenopausal and postmenopausal women

OBJECTIVE: To determine the risk of high-grade squamous intraepithelial lesion (HSIL)/cervical intraepithelial neoplasia (CIN) 2 or 3 in perimenopausal and postmenopausal women with high-risk human papillomavirus (HPV) DNA-positive atypical squamous cells of undetermined significance (ASCUS) on Pap tests. STUDY DESIGN: A total of 752 perimenopausal and postmenopausal women (patients 45 years) with an ASCUS interpretation on ThinPrep Pap tests were identified in 2002 and 2003. High risk HPVDNA was detected in 191 (25.4%) women. The follow-up results in these 136 women were compared with those of women <45 years. RESULTS: Of the 136 perimenopausal and postmenopausal women, 64.7% became negative on cytology or biopsy and 30.9% revealed persistent low-grade SIL (LSIL)/CIN 1. Furthermore, 5 women (3.68%) were diagnosed with HSIL/CIN 2 or 3, and 1 patient had squamous cell carcinoma (0.74%). The rate of HSIL/CIN 2 or 3 or worse detected in perimenopausal and postmenopausal women was significant lower than 10.6% in women <45 years (p = 0.028). CONCLUSION: Our study showed that perimenopausal and postmenopausal women with high-risk HPV positivity and an ASCUS interpretation have a significantly lower risk of HSIL/CIN 2 or 3 detected. Nonetheless, the risk of a significant finding on workup, including invasive carcinoma, indicates the need for colposcopic evaluation of these women.     

Individual Profiling of Circulating Tumor Cell Composition and Therapeutic Outcome in Patients with Hepatocellular Carcinoma

BACKGROUND AND AIMS: Circulating tumor cells (CTCs) have been proposed as a monitoring tool in patients with solid tumors. So far, automated approaches are challenged by the cellular heterogeneity of CTC, especially the epithelial-mesenchymal transition. Recently, Yu and colleagues showed that shifts in these cell populations correlated with response and progression, respectively, to chemotherapy in patients with breast cancer. In this study, we assessed which non-hematopoietic cell types were identifiable in the peripheral blood of hepatocellular carcinoma (HCC) patients and whether their distribution during treatment courses is associated with clinical characteristics. METHODS: Subsequent to few enrichment steps, cell suspensions were spun onto glass slides and further characterized using multi-immunofluorescence staining. All non-hematopoietic cells were counted and individual cell profiles were analyzed per patient and treatment. RESULTS:We detected a remarkable variation of cells with epithelial, mesenchymal, liver-specific, and mixed characteristics and different size ranges. The distribution of these subgroups varied significantly between different patient groups and was associated with therapeutic outcome. Kaplan-Meier logrank test showed that a change in the ratio of epithelial to mesenchymal cells was associated with longer median time to progression (1 vs 15 months; P = .03; hazard ratio = 0.18; 95%confidence interval = 0.01-2.75). CONCLUSIONS: Our data suggest that different CTC populations are identifiable in peripheral blood of HCC patients and, for the first time in HCC, that these individual cell type profiles may have distinct clinical implications. The further characterization and analysis of patients in this ongoing study seems to be warranted.     

Synthetic lethal hubs associated with vincristine resistant neuroblastoma

Chemotherapy of cancer experiences a number of shortcomings including development of drug resistance. This fact also holds true for neuroblastoma utilizing chemotherapeutics as vincristine. We performed a comparative analysis of molecular and cellular mechanisms associated with vincristine resistance utilizing cell line as well as human tissue data. Differential gene expression analysis revealed molecular features, processes and pathways afflicted with drug resistance mechanisms in general, and specifically with vincristine significantly involving actin associated features. However, specific mode of resistance as well as underlying genotype of parental, vincristine sensitive cells apparently exhibited significant heterogeneity. No consensus profile for vincristine resistance could be derived, but resistance-associated changes on the level of individual neuroblastoma cell lines as well as individual patient profiles became clearly evident. Based on these prerequisites we utilized the concept of synthetic lethality aimed at identifying hub proteins which when inhibited promise to induce cell death due to a synthetic lethal interaction with down-regulated, chemoresistance associated features. Our screening procedure identified synthetic lethal hub proteins afflicted with actin associated processes holding synthetic lethal interactions to down-regulated features individually found in all chemoresistant cell lines tested, therefore promising an improved therapeutic window. Verification of such synthetic lethal hub candidates in human neuroblastoma tissue expression profiles indicated the feasibility of this screening approach for addressing vincristine resistance in neuroblastoma.     

Prevalence of human papillomavirus infection and genotype distribution determined by the cyclic-catcher melting temperature analysis in Korean medical checkup population

Although cytology screening has reduced the incidence and mortality rate of cervical cancer significantly, its usefulness is limited to samples from the site of the lesion, resulting in its low sensitivity and unsuitability for use in medical checkups. The purpose of the present study was to evaluate the prevalence of HPV infection using genotype distribution and to analyze the correlation of the HPV DNA test results with cytological results. We also evaluated the benefits of quantitative information obtained from cyclic-catcher melting temperature analysis (CMTA) in screening for cervical cancer. We performed cyclic-CMTA using Anyplex? II HPV28 Detection in combination with cervical cytology for 2,181 subjects. The following HPV positivity types were detected using cyclic-CMTA and HPV positivity was found to increase together with the severity of the cytology results: (1) For 419 HPV positive specimens, HPV DNA was detected in 18.1% of normal specimens, 78.3% of ASCUS, and all of LSIL and HSIL; (2) high-risk HPV DNAs were detected in 63.3% of normal (N=547), 65.9% of ASCUS (N=41), 76.9% of LSIL (N=13), and 88.9% of HSIL (N=9) among total detected HPV DNA regardless multiple detection; (3) multiple HPV genotypes were detected in 4.8% of normal specimens (N=2,146), 52.2% of ASCUS (N=23), 57.1% of LSIL (N=7), and 40.0% of HSIL (N=5). In addition, a high level of viral DNA was observed using cyclic-CMTA in all specimens beyond the LSIL stage according to cytology, while only 6% of specimens with normal cytology showed a correlation with viral quantitation by cyclic-CMTA. The combination of HPV genotyping with a quantitative assay and cytology will allow for a more accurate diagnosis of cervical cancer.     

Cervicovaginal smear abnormalities in sexually active adolescents. Implications for management

OBJECTIVE: To assess the prevalence and spectrum of Pap smear (PS) abnormalities in sexually active adolescents in comparison to adult women in order to determine whether management of adolescents should differ from that of adults. STUDY DESIGN: Five hundred twenty-four adolescents who had an initial PS at our institution from January to September 1997 were followed for 36 months with repeat PS and/or cervical biopsy. Initial PS results were compared with those of adult women. The chi 2 test was used to calculate the statistical significance of differences between the two groups. The qualified atypical squamous cells of undetermined significance (ASCUS) cytologic diagnosis in adolescents was correlated with follow-up data. RESULTS: The overall prevalence of squamous intraepithelial lesions (SILs) in adolescents was 29% as compared to 23% in adults. Almost all initial squamous lesions were ASCUS and low grade squamous intraepithelial lesion (LSIL); only one case of high grade squamous intraepithelial lesion (HSIL) was detected. On follow-up 18% and 2.4% of adolescents developed LSIL and HSIL, with a LSIL/HSIL ratio of 8/1 as compared to 5/1 in adults. The average time from initial PS to detection of HSIL was 20 months. All patients with HSIL except one had had one or more previous abnormal PSs. The positive predictive values (PPVs) for subsequent dysplasia for ASCUS favor reactive (ASCUS.R), ASCUS not otherwise specified (ASCUS.NOS) and ASCUS favor dysplasia (ASCUS.D) in adolescents were .13, .17 and .31, respectively. ASCUS.NOS (P = .01) and ASCUS.D (P = .007) were strong indicators of dysplasia as compared to ASCUS.R. CONCLUSION: PS abnormalities are more common in sexually active adolescents, with a significantly higher prevalence of LSIL over HSIL as compared to adult women. Given the natural history of HPV infection, we recommend follow-up with cytology rather than colposcopy/biopsy for adolescents with ASCUS and LSIL PSs. Qualification of ASCUS is useful in determining which adolescents are at the highest risk of cervical dysplasia.     

Cytopathologic features of pituitary carcinoma with cervical vertebral bone metastasis: a case report

BACKGROUND: Pituitary carcinomas are extremely rare tumors of the adenohypophysis. The presence of craniospinal and/or systemic extracranial metastases is the only reliable criterion for the diagnosis of pituitary carcinoma. To date, only 2 cases have been reported correctly by fine needle aspiration biopsy (FNAB). We present an additional case of pituitary carcinoma with FNAB features. CASE: A 60-year-old woman presented with clinical features of Cushing's disease and a pituitary tumor. She underwent transsphenoidal resection of the tumor. The initial diagnosis was an adrenocorticotrophic hormone (ACTH)-producing invasive pituitary adenoma. The patient presented again with neck pain 6 years after the operation. Magnetic resonance imaging revealed metastatic tumor masses at the level of C5-C6 of the cervical vertebrae. Intraoperative fine needle aspiration and incomplete excision of metastatic tumors were performed. Cytologically, tumor cells were composed of a combination of loose groups and single cells. Neoplastic cells had a relatively monotonous appearance and displayed characteristic neuroendocrine tumor features. Immunocytochemistry from cell block sections revealed AE1/ AE3, synaptophysin chromogranin A and ACTH positivity in the tumor cells. CONCLUSION: Pituitary carcinoma with extracranial systemic metastases demonstrates typical neuroendocrine features on fine needle aspiration. In the differential diagnosis, metastatic neuroendocrine carcinomas should be kept in mind. In the absence of sufficient clinical data, these 2 entities cannot be distinguished correctly through the cytologic features.     

Glassy cell carcinoma of the uterine cervix. Cytologic features and expression of estrogen and progesterone receptors

OBJECTIVE: To identify the cytomorphologic features and investigate the expression of estrogen receptor (ER) and progesterone receptor (PR) in glassy cell carcinoma (GCC) of the uterine cervix. STUDY DESIGN: A retrospective analysis of nine GCCs encountered at Korea Cancer Center Hospital between January 1990 and April 1999 was undertaken. The cervical smears were obtained prior to histologic diagnosis of GCC. The cytomorphologic and clinical features were reviewed, and the expression of ER and PR was investigated immunohistochemically on histologic sections. RESULTS: Smears of GCC were hypercellular and remarkably cohesive. The tumor cells were large and characterized by abundant granular cytoplasm, distinct cell membranes and round to polygonal, large nuclei with prominent nucleoli. In the background tumor diathesis and numerous inflammatory cells containing eosinophils were present. The inflammatory cells (mainly eosinophils) were intimately associated with tumor cells to form "granuloepithelial complex." Immunohistochemically, ER was identified in two of the nine cases and PR in one of them. CONCLUSION: Cytology of GCC has characteristic features that differ from those of other carcinomas or atypical reparative cells. Although there are deceptive mimics of GCC, the characteristic cytologic findings should prompt a diagnosis of GCC. ER and PR positivity was found in two cases (22%) and one case (11%), respectively, of GCC, suggesting that this tumor might be hormonally responsive.     

Exfoliative cytology of lymphoepitheliomalike carcinoma of the uterine cervix. A report of two cases

BACKGROUND: Lymphoepitheliomalike carcinomas (LECs) are morphologically similar to undifferentiated nasopharyngeal carcinoma but occur at sites other than the nasopharynx. They rarely occur in the uterine cervix. Sixty-five cases of LEC of the cervix have been published to date, and the pitfalls of histopathologic interpretation have been discussed. This undifferentiated carcinoma with a prominent lymphocytic infiltrate represents a challenge for the pathologist examining a scant cervical biopsy or Pap smear. Distinguishing LEC as a separate entity is important. Despite the fact that the epithelial component is poorly differentiated, this neoplasm is associated with a lower frequency of lymph node metastases, is potentially radiosensitive and has a better prognosis. Although mentioned in passing in several papers, the exfoliative cytology of this cervical neoplasm has not been adequately discussed. We report the cytologic features of LEC in cervical smears obtained from two patients. CASES: The first patient presented with menometrorrhagia and postcoital bleeding. The cervical smear taken at the time of presentation was reported as unsatisfactory for evaluation. ASCUS was diagnosed on a vaginal smear obtained one year earlier. The second patient presented with a complaint of postcoital bleeding. A cervical smear and the cervical biopsy taken at the time of presentation were reported as ASCUS and high grade dysplasia versus carcinoma, respectively. A retrospective review of the cervical smears revealed rare malignant cells occurring singly or in small groups. The tumor cells had a high nuclear/cytoplasmic ratio, irregular nuclear membrane and hyperchromatic nuclei with coarse chromatin and were obscured by heavy inflammation and blood. The background resembled that of a menstrual smear. CONCLUSION: The diagnosis of LEC of the cervix is often made on a loop electrical excision procedure or on a hysterectomy specimen. The presence of heavy inflammation and blood, which can obscure the malignant nature of the cells, presents the cytopathologist with a challenging diagnosis of LEC in cervical smears. In view of the prognostic implications, it is desirable for the pathologist to classify LEC as a distinct entity.     

Metastatic balloon cell melanoma: a case report

BACKGROUND: The protean morphology of malignant melanoma is diagnostically challenging. Balloon cell melanoma is a histologic variant composed predominantly or entirely of large cells with abundant, vacuolated cytoplasm. It shares the cytologic features of the other subcategories of malignant melanoma, such as discohesion, nuclear pleomorphism and intranuclear cytoplasmic pseudoinclusions, but generally lacks melanin pigment and, as the name would suggest, is characterized by the presence of numerous cytoplasmic vacuoles. CASE: A 55-year-old man presented with an enlarged right cervical lymph node. Clinically and radiographically this mass was considered to be metastatic; however, the patient had no known primary neoplasm. Fine needle aspiration biopsy (FNAB) and cytologic examination showed numerous discohesive, variably sized, malignant cells with abundant, vacuolated cytoplasm and pleomorphic nuclei with irregular nuclear contours, macronucleoli and frequent intranuclear cytoplasmic pseudoinclusions. Pigment was not identified. These features, along with strong immunohistochemical positivity for S-100, HMB-45 and Melan-A, suggested the diagnosis of balloon cell melanoma. A right parotidectomy and lymph node dissection were performed, and histologic tissue evaluation confirmed the diagnosis. CONCLUSION: This case of lymph node balloon cell melanoma metastasis was diagnosed by FNAB.     

Cytologic predictors of cervical intraepithelial neoplasia in women with an ASCUS Pap smear

OBJECTIVE: To identify cytologic parameters on Pap smears of women with an atypical squamous cells of undetermined significance (ASCUS) diagnosis that could help cytologists to indicate whether a particular ASCUS case is most likely related to cervical intraepithelial neoplasia (CIN) grade 1 or 2/3. STUDY DESIGN: A total of 360 eligible women diagnosed with ASCUS and referred to the colposcopy clinic of Saint-Sacrement Hospital participated in the study. Eligible women were those aged 18-50 years, newly diagnosed with ASCUS, with no history of cervical biopsies or treatment, and not pregnant at the time of the visit. Colposcopically directed biopsies of lesions were obtained. All Pap smears were reviewed according to 36 different cytomorphologic criteria. The regression logistic model was used to estimate the odds ratios (ORs) for the associations between cytologic criteria observed in smears and the diagnosis of CIN made on biopsies. All cytologic criteria significantly (P < .05) associated with CIN were entered in the models, and a backward selection was done to determine independent cytologic predictors of CIN 1 and 2/3. RESULTS: Biopsies revealed that 22.2% of the study population had concurrent CIN. CIN I and 2/3 were identified in 61 (16.9%) and 19 women (5.3%), respectively. Clear perinuclear spaces (OR = 2.5, P = .002) and moderate nuclear atypia (OR = 4.4, P = .02) were two cytologic criteria independently associated with CIN 1. Four independent predictors of CIN 2/3 were identified: the presence of clear perinuclear spaces (OR = 5.9, P = .004), hyperchromasia (OR = 3.9, P = .04), moderate anisokaryosis (OR = 13.1, P = .01 and increased nuclear volume of metaplastic cells (OR = 5.1, P = .007). CONCLUSION: These observations may help cytologists to better categorize ASCUS lesions as intraepithelial ones and will also contribute to improving the Bethesda definition of ASCUS. Further studies are planned to validate these observations.