Reappraisal of cytology-histology correlation in cervical cytology based on the recent American Society of Cytopathology guidelines (2017) at a cancer research centre.

OBJECTIVE: To assess the impact of recently published American Society of Cytopathology (ASC) guidelines (2017) on the conduct of cervical cytology-histology correlation (CHC). METHODS: A retrospective review was conducted for cervical biopsies with their corresponding conventional cervical smears over a 7.5-year period (January 2011-June 2018). As per the ASC guidelines, a discrepancy assessment grid was prepared. Major cytology-histology discordance was defined as a diagnosis of high-grade squamous intraepithelial lesion (HSIL) or CIN2+ in one of the tests with negative result in the other. Smears and biopsies of all discordant cases were reviewed for reasons of overcall and undercall. RESULTS: Of the 341 cervical biopsies with corresponding Papanicolaou smear, cytology-histology agreement was noted in 249 (73%) cases. Major discordance was observed in 22 cases (6.4%)-16 undercalls and six overcalls on cytology-while minor discrepancies were noted in 70 cases. Atypical metaplasia and repair changes were the main reasons for overcall while small HSIL cells in atrophic smear and scant HSIL cells were important causes of undercall on cytology review. Using the ASC guidelines, we could improvise upon the existing CHC methodology for categorisation of cyto-histological pairs of cases with a cytological diagnosis of atypical glandular cells. CONCLUSION: The present study demonstrates, for the first time, that the recent ASC guidelines facilitate cervical CHC, especially for categorisation of cases with atypical glandular cells on cytology. Uniform application of these guidelines would standardise the conduct of cervical CHC internationally and provide scope for inter-laboratory comparison of data as well as enhance self-learning and peer learning.

Clinically unsuspected thyroid involvement in cysticercosis: a case report.

BACKGROUND: Disseminated cysticercosis is rare in humans. This case highlights the utility of fine needle aspiration (FNA) in diagnosis of cysticercosis in an unusual site. CASE: A 28-year-old woman underwent FNA from a midline swelling in the neck, clinically suspected to be a nodular goiter or thyroiditis. Giemsa-stained smears revealed a mixed inflammatory infiltrate, foreign body giant cells, and an occasional epithelioid cell granuloma. Thick colloid and occasional clusters of follicular cells were seen. In addition, a single large hooklet, characteristic of cysticercus, and a few calcospherules were also present. Further workup revealed subcutaneous nodules on both thighs, and cystic lesions were detected in the thyroid, brain, and lungs. FNA from a subcutaneous swelling confirmed cysticercosis. A final diagnosis of disseminated cysticercosis involving the thyroid gland was made. CONCLUSION: FNA is a useful procedure to identify parasitic lesions even in unusual sites and in clinically unsuspected cases.

Cervical high-grade squamous intraepithelial lesion on conventional cytology: Cytological patterns, pitfalls, and diagnostic clues.

BACKGROUND: Conventional cervical cytology, which has a relatively low sensitivity in diagnosing high-grade lesions as compared to liquid-based cytology, is still being practiced in low resource settings. This study aimed at elucidating various cytomorphological patterns, pitfalls, and subtle clues to high-grade squamous intraepithelial lesion (HSIL) diagnosis on conventional cervical cytology through cytologic-histologic correlation. METHODS: Cervical biopsies reported as CIN2/3 were correlated with their corresponding Pap smears over a 10-year period to determine the frequency of undercalls. For characterization of overcalls, cervical smears reported as HSIL and their corresponding biopsies during the same period were correlated. The discordant cases in both the groups were reviewed for problematic patterns and pitfalls in cytological diagnosis of HSIL. RESULTS: Of the 142 biopsies with CIN2/3, 29 (20.4%) cases had been undercalled on cytology. Sixteen (16) of these could be reclassified as ASC-H/HSIL on smear review. Smears showing predominant cells of low-grade squamous intraepithelial lesion grade with a few HSIL cells and those with small abnormal cells in an atrophic background formed the main confounders for HSIL underdiagnosis. Thirteen (13) out of 130 (10%) Pap smears called as HSIL, where biopsy diagnosis was less than CIN2, were labeled as overcalls. Atypical metaplasia, hyperchromatic crowded groups, and reparative changes constituted the major diagnostic pitfalls on cytology. A diligent smear review helped to reduce the undercall and overcall rates to 9.1% and 2.3%, respectively. CONCLUSION: Awareness of morphological challenges in interpretation of HSIL among cytopathologists practicing cervical cytology would assist in reducing the diagnostic errors and ensure better patient management.

Utility of imprint cytology for early presumptive diagnosis in clinically suspicious cervical cancer.

OBJECTIVE: To determine the utility of imprint cytology (IC) in providing an early presumptive diagnosis of clinically suspected cervical carcinoma. STUDY DESIGN: A total of 219 clinically suspicious cervical cancer cases underwent Pap test, punch biopsy and IC at the same sitting. Correlations were performed between these diagnostic modalities to determine the sensitivity and specificity of IC in diagnosis of cervical cancer. RESULTS: The overall accuracy of IC in detecting cervical cancers was 96.2%. About 78% of squamous cell carcinomas (SCC), 60% of adenocarcinomas and 100% of small cell carcinoma could be accurately typed on imprints. Twelve malignant lesions were diagnosed on IC among 26 unsatisfactory biopsies. Although there was no false positive result, 3.5% false negative diagnoses were given on IC. The sensitivity and specificity of imprint smear cytology to detect malignancy was 96.2% and 100%. Agreement between imprint cytology and Pap smear diagnosis of malignancy was 95.3%. kappa Statistics revealed excellent agreement between imprints and biopsies and between imprints and Pap smears in diagnosis of malignant lesions. CONCLUSION: IC can be used as an adjunctive technique for an early and reliable preliminary presumptive diagnosis of cancer of the uterine cervix.

TNFalpha-308G/A polymorphism as a risk factor for HPV associated cervical cancer in Indian population.

BACKGROUND: Investigation of the potential association of single nucleotide polymorphisms (SNPs) at -308 G/A and -238 G/A of Tumor necrosis factor alpha (TNFalpha) with susceptibility to HPV-16 associated cervical cancer in Indian women. METHODS: The study included 165 histologically confirmed cases with 45 precancer and 120 cancer patients and an equal number (165) of healthy controls with normal cervical cytology. PCR-RFLP was employed to analyze TNFalpha promoter polymorphisms, which were confirmed by direct sequencing. Both patients and controls were screened for Human Papillomavirus (HPV) infection. RESULTS: The frequency of -308 A allele in TNFalpha was significantly higher in cases compared with control subjects (21% in cases vs. 9% in controls; p<0.01), with an odds ratio of 2.7 (95% CI = 1.41-5.15). Also, women carrying A allele for this locus presented 3 times increased susceptibility to HPV 16 infection as evident from carrier genotype distribution between HPV positive cases and control subjects (24% in HPV positive cases vs. 9% in controls; p<0.01; OR = 3.1; 95% CI = 1.60-6.03). No such association was found for TNFalpha-238 (G/A) polymorphism with the risk of development of cervical cancer. CONCLUSION: It suggests that SNP at -308 (G/A) of TNFalpha promoter may represent an increased risk for HPV infection and development of cervical cancer in Indian women.

Spectrum of epithelial cell abnormalities of uterine cervix in a cervical cancer screening programme: implications for resource limited settings.

OBJECTIVE: (1) To compute the frequencies and peak age incidences of epithelial cell abnormalities (ECA) of uterine cervix in a cytology-based screening programme and (2) to analyze the comparative frequencies of squamous intraepithelial lesions (SIL) and malignancies in age groups <40 and > or =40 years, in order to assess the implications for screening protocol in resource limited settings. STUDY DESIGN: Pap smears form 29,475 women were cytologically screened over a 4-year period as a part of hospital-based screening programme. The frequencies, peak age incidences and mean age of various ECA detected were computed. The data was further stratified in to age groups <40 (Gp 1) and > or =40 (Gp 2) and comparative profile of the lesions was analyzed. RESULTS: On cytologic screening of the smears 5.6% ECA were detected. Atypical squamous cells-undetermined significance (ASC-US) and low grade SILs (LSIL) were diagnosed more frequently in Gp 1 (p<0.001) while atypical glandular cells (AGC) and malignancies were more significantly more frequent in Gp 2 (p<0.001). The frequency of HSIL was similar in the two groups. The SILs predominated in the fourth decade while the malignant lesions were most frequent in age >50 years. The mean age for LSIL and HSIL was 34.7 and 37.7 years, respectively, while for malignancy it was 51.8 years thus corroborating the hypothesis that a prolonged latent phase exists between the precursor lesions and the onset of invasive cancer. CONCLUSIONS: Since the goal of any screening programme should be to pick up majority of the precursor lesions and not frank cancers, it is desirable to initiate screening before 40 years of age. The WHO recommendation of once in a life time screening between 35 and 40 years of age seems appropriate for resource limited settings like ours.

Outcome of "Atypical squamous cells" in a cervical cytology screening program: implications for follow up in resource limited settings.

(1) To study the incidence and outcome of "Atypical squamous cells (ASC)" diagnosis in a hospital based cytology screening programme. (2) To work out a feasible strategy for follow up of Atypical squamous cells-undetermined significance (ASC-US) and Atypical squamous cells-cannot exclude high grade squamous intraepithelial lesion (ASC-H) in resource limited settings. A total of 29,475 women were screened cytologically through Pap tests. The epithelial cell abnormalities (ECA) detected on screening were reviewed by the cytopathologists and classified according to Bethesda 2001 system. The women with ASC-US reports were followed up by two repeat cytology tests at 3 and 6 months of the initial visit. The persistent ASC-US cases or the cases which revealed squamous intraepithelial lesion (SIL) on follow up smears; as well as all ASC-H and above cases were referred for coloposcopic evaluation. ASC diagnosis comprised 3.6% of all reports. These were qualified as ASC-US (3.36%) and ASC-H (0.22%). On follow up, only 7 CIN 2 or worse (3.2%) lesions were detected on 218 biopsies in ASC-US category while in ASC-H qualifier 16 CIN 2 and above lesions (30.8%) were picked up on 52 colposcopic biopsies. The difference between ASC-US and ASC-H categories for a CIN 2 or worse outcome was highly significant (P < 0.001). ASC-H qualifier has a high likelihood for an ominous histological outcome and warrants an immediate colposcopic evaluation. On the other hand, ASC-US cases can be managed conservatively by repeat cytology tests at regular intervals without a significant risk of missing a high grade lesion. Diligent screening of cervical smears can judiciously downgrade some cases overcalled as ASC because of inflammatory atypia and thereby reduce referrals in geographic settings with high prevalence of reproductive tract infections. High risk HPV (HR HPV) testing may be a useful adjunct to further reduce referrals by selecting the women who require colposcopic evaluation.

Cervical Cancer Screening in Resource-Constrained Countries: Current Status and Future Directions

Cervical cancer continues to be a major public health problem affecting large numbers of women in many developing countries. Limitations of various screening modalities and the lack of ready availability of a cost-effective point-of-care screening tool have hindered the efficient implementation of population-based screening programs in these settings. It has not proved possible for many countries to adopt cytology as a screening modality due to inadequate infrastructure and trained manpower. However, recent developments, notably design and testing of a low-cost HPV test kit and initiatives by countries like India in developing and putting into operation a framework for large-scale screening of women, have raised hopes that cervical cancer control may be possible even in resource-constrained locations. With the advent of HPV vaccination, primary prevention of cervical cancer also seems a distinct possibility. However, wide availability and acceptability of vaccination is still an unresolved issue for developing countries. The possible future effects of vaccination on test characteristics of various screening strategies also need to be evaluated. This review gathers information on the current status of cervical cancer screening with a special focus on low resource settings. It revisits the strengths and limitations of the available screening modalities for cervical cancer viz. cytology, visual methods and HPV testing, in the context of their applicability in developing countries. In addition, the role of newer HPV-detection methods, for instance DNA, RNA and protein-based techniques, in triage of screen-positive women is discussed. The contemporary issue of impact of HPV vaccination on cervical cancer screening is also addressed briefly. The main highlight of the review is the reference to 'operational framework guidelines' for population-based cervical cancer screening, which have recently been formulated and are in the process of being implemented in India. The guidelines may serve as a model for other similar low-resource settings where implementation of cancer screening is desired.

Bacterial Vaginosis and Cervical Intraepithelial Neoplasia: Is there an Association or is Co-Existence Incidental?

Objectives: To determine associations, if any, of bacterial vaginosis with cervical pre-neoplastic lesions and evaluate any effects of sub-categorization of smears with bacterial vaginosis. Methods: All cervico-vaginal smears reported as positive for bacterial vaginosis over a five-year period were reviewed and sub-categorized into 'type I (dysbacteriosis)' and 'type II (pure Gardenerella infection)' smears by two cytopathologists (PS, SG). The proportion of smears with healthy flora and pre-neoplastic lesions was compared with those having bacterial vaginosis in conjunction with such changes. In addition, a comparison was also attempted between the frequencies of pre-neoplastic lesions with the two categories of bacterial vaginosis smears. Results: Bacterial vaginosis was diagnosed in 28.6% (7017 of the 24,565) of the 24,565 smears received in the Institute during the study period. Of these 7,017 smears with bacterial vaginosis, 53% (3717) were categorized as type I and 42.7% (3000) as type II by both cytopathologists. Pre-neoplastic lesions were detected in 10.2% of smears with bacterial vaginosis compared to 5.7% of those with healthy flora (P<0.0001). Of the sub-categories of bacterial vaginosis, the risk of detecting precancerous lesion was higher for type II smears (P<0.001). Conclusion: Sub-categorization of bacterial vaginosis, as performed in the Dutch coding system, may be worthwhile due to the strikingly different risk of associated preneoplasia.

Cytohormonal and morphological alterations in cervicovaginal smears of postmenopausal women on hormone replacement therapy.

The objective of the study was to study the cytohormonal and morphological alterations in cervicovaginal smears associated with the use of hormone replacement therapy (HRT) and to assess the utility of vaginal cytology in determining the response to HRT. Ninety postmenopausal women (30 on estrogen-progesterone combination (HRT) for 1 to 24 mo (user 1), 30 on estrogen therapy (ERT) for 1 to 44 mo (user 2), and 30 not on any hormones (nonusers)) were included in the cross-sectional study. Their lateral vaginal wall smears and cervical smears were examined for hormonal and morphological assessments, respectively. The smear pattern showed predominance of parabasal cells in 46.6% of nonusers, while none of the users had >70% parabasal cells. A high percentage (>70%) of intermediate cells was found in 46.6% of users and only in 16.6% of nonusers. A high maturation value (MV) was found in more than 75% of users but in only 16.6% of nonusers. The women with high MV (>50) were significantly less symptomatic than did nonusers. Atrophic changes were present in cervical smears of 14/20 (46.6%) nonusers when compared with 1/60 (1.66%) users. Atypical squamous cells of undetermined significance (ASC-US) were diagnosed in seven users and three nonusers. It persisted on follow-up in four users and one nonuser. Histology revealed one mild dysplasia among users. Lactobacilli were more frequently observed in users. The cytohormonal pattern on vaginal smears correlates well with the response to hormonal therapy and clinical symptoms. Awareness of the morphological alterations associated with the use of replacement hormones would enable the cytologists to reduce the false-positive diagnoses while evaluating postmenopausal smears.

Sensitivity of the Pap test in detecting high grade lesions: what should be the acceptable cytologic threshold for colposcopic referral?

OBJECTIVE: To devise an optimal cytology threshold for colposcopy referral in resource-limited settings. STUDY DESIGN: Four hundred seventy-two symptomatic women 20-60 years old were screened by both cytology and colposcopy. Onsite biopsy was taken if lesions grade 1 or above were detected on colposcopy. Women found to have cervical intraepithelial neoplasia (CIN) 2 and above lesions on histopathology were stratified according to their cytologic diagnosis (atypical squamous cells of undetermined significance [ASCUS]+ threshold, low grade squamous intraepithelial lesion [LSIL]+ threshold, and high grade squamous intraepithelial lesion [HSIL]+ threshold). The comparative sensitivity, specificity and predictive values in each group were calculated, taking biopsy as the gold standard. RESULTS: The sensitivity of LSIL + cytology to detect CIN 2+ lesions was 91.5% (referral load, 30.7%). While the sensitivity of ASCUS+ cytology threshold was almost the same (92.3%), the referral load was much higher (42.2%). With HSIL+ cytology threshold, though the referral load was reduced substantially (21.9%), the sensitivity also decreased, to 81.5%. CONCLUSION: The results indicate that in order to achieve high sensitivity, the LSIL cytology threshold appears to be optimum for colposcopic referrals.

Prevalence of bacterial vaginosis in a community setting and role of the pap smear in its detection.

OBJECTIVE: To study the revalence of bacterial vaginosis (BV) in symptomatic and asymptomatic women in a community setting, to assess the validiy of the Pap smear in the detection of BV and to determine the sensitivity and specificity of clinical criteria for the diagnosis of BV. STUDY DESIGN: Gram staining was performed on vaginal secretions collected from 301 women to determine the prevalence of BV. Each smear was assigned a score on the basis of the bacterial morphotypes identified. The bacterial pattern was also studied on 270 adequate, Pap-stained cervical smears and compared with the gold standard, the morphotypes on gram stain, to derive the validity of the Pap smear in diagnosing BV. Also each clinical criterion defined for diagnosis of BV was independently evaluated to determine their sensitivity and specificity. RESULTS: The overall prevalence of BV was 41.5% in the study subjects using Amsel's and Nugent's criteria. The Pap smear was 78.3% sensitive and 86.9% specific in detection of BV. Among the clinical criteria, the presence of clue cells on wet mounts was both highly sensitive (76.7%) and specific (92.4%) for diagnosing BV, while a positive whiff test had a specificity of 86.9% with sensitivity of 33.9%. Vaginal pH > 4.5 was sensitive (88.3%) but less specific (58.6%). The presence of a thin, homogeneous discharge clinging to vaginal mucosa had low sensitivity (56.3%) and specificity (48.9%). In this study, BV was prevalent in both symptomatic and asymptomatic women. The routine Pap smear was able to detect BV in the majority of women. Its utility can be greater in asymptomatic women, in whom this infection may go undetected otherwise, resulting in future complications related to reproductive health. Among Amsel's clinical criteria, the most sensitive and specific was the presence of clue cells in wet mounts. They can be detected easily by laboratory staff with little training in primary health care seting

Spindle cell lipoma with predominant nerve sheath tumor-like areas: A potential diagnostic pitfall on aspiration cytology.

Spindle cell lipoma (SCL) is an uncommon variant of lipoma that usually is present in subcutaneous fat of adult men. This tumor has a low rate of local recurrence and no risk of malignant behavior. Although histological features of SCL are well documented, cytological descriptions have been few. We present the case of a 41-year man with a right arm swelling, which on fine-needle aspiration cytology showed adipose tissue fragments, spindle cell areas mimicking benign nerve sheath tumor, and bundles of ropy collagen in a myxoid background, suggesting a diagnosis of SCL. SCL with predominant spindle cell component may mimic benign nerve sheath tumor on aspiration cytology. Subtle cytological features like presence of adipose tissue, ropy collagen, and mast cells help in accurate diagnosis.

Glutathione S-transferase M1 and T1 Polymorphisms, Cigarette Smoking and HPV Infection in Precancerous and Cancerous Lesions of the Uterine Cervix.

Glutathione S-transferases (GSTs) play an important role in detoxification of carcinogenic electrophiles. The null genotypes in GSTM1 and GSTT1 have been implicated in carcinogenesis. Present study was planned to evaluate the influence of genetic polymorphisms of GSTM1 and GSTT1 gene loci in cervical carcinogenesis. The study was conducted in Lok Nayak hospital, New Delhi. DNA from clinical scrapes of 482 women with minor gynaecologic complaints attending Gynaecology OPD and tumor biopsies of 135 cervical cancer cases attending the cancer clinic was extracted. HPV DNA was detected by standard polymerase chain reaction (PCR) using L1 consensus primer pair. Polymorphisms of GSTM1 and GSTT1 were analysed by multiplex PCR procedures. Differences in proportions were tested using Pearson's Chi-square test with Odds ratio (OR) and 95% confidence interval (CI). The risk of cervical cancer was almost three times in women with GSTM1 homozygous null genotype (OR-2.62, 95%CI, 1.77-3.88; p<0.0001). No association of GSTM1 or GSTT1 homozygous null genotypes was observed in women with normal, precancerous and cervical cancerous lesions among ≤35 or >35 years of age groups. Smokers with null GSTT1 genotype had a higher risk of cervical cancer as compared to non-smokers (OR-3.01, 95% CI, 1.10-8.23; p=0.03). The results further showed that a significant increased risk of cervical cancer was observed in HPV positive smoker women with GSTT1 (OR-4.36, 95% CI, 1.27-15.03; p=0.02) and GSTM1T1 (OR-3.87, 95% CI, 1.05-14.23; p=0.04) homozygous null genotypes as compared to HPV positive non smokers. The results demonstrate that the GST null genotypes were alone not associated with the development of cervical cancer, but interacted with smoking and HPV to exert effects in our Delhi population.

Rehydration of air-dried cervical smears: a feasible alternative to conventional wet fixation.

OBJECTIVE: To evaluate the effect of rehydration of air-dried cervical smears on staining quality and to find out whether rehydration techniques can be adopted as an alternative method, especially in high-volume, resource-limited settings. METHODS: A total of 950 paired wet-fixed and air-dried-rehydrated cervical smears collected by paramedical workers from an urban slum of Delhi, India, were compared for staining quality by assessing different cytoplasmic and nuclear parameters. RESULTS: The staining quality in air-dried-rehydrated smears was satisfactory and comparable to wet-fixed smears (61.3% versus 63.6%). The staining was superior in rehydrated smears in 26.5%, as compared with 15.4% in wet-fixed ones (P <.001). Unsatisfactory staining was observed in 12.2% of rehydrated smears, as compared with 21% of wet-fixed smears. The smear background was cleaner in rehydrated smears. Red blood cells were observed in only 3% of rehydrated smears, in comparison to 12% in wet-fixed ones (P <.001). CONCLUSION: Rehydration of air-dried cervical smears is a suitable alternative to wet-fixed smears. The staining quality is either the same as or better than wet-fixed smears, and the unsatisfactory rate is lower. This technique is simple and can be conveniently adopted in resource-limited settings.

Melanoma of the soft parts: diagnosis of metastatic and recurrent tumors by aspiration cytology.

Three cases of melanoma of the soft parts diagnosed by aspiration cytology and immunochemistry are described. Unusual clinicoradiological features, variable cytomorphology, absence of melanin, and lack of awareness due to rarity of the lesion caused diagnostic dilemma. Morphological similarity to alveolar soft part sarcoma, synovial and epithelioid sarcoma, cutaneous melanoma, poorly differentiated carcinoma, and plasmacytoma were noted. Consideration of clinical data such as age, site, and radiology was helpful in narrowing down the diagnosis. A presumptive cytologic diagnosis helped in selecting the antibody panel, which established the definitive diagnosis in all cases. This approach is valuable in preoperative management and obviates the need for an open biopsy in primary, metastatic, or recurrent tumor. Increasing experience in fine-needle aspiration of this rare entity and correlation with immunochemistry and histopathology are valuable in narrowing down the differential diagnosis, reducing diagnostic errors, and widening its clinicocytological spectrum.

Macroconidia of Fusarium species. An unusual finding in cervical smears.

OBJECTIVE: To screen cervical smears for early detection of precancerous and cancerous lesions of the uterine cervix in a hospital-based cancer screening program. STUDY DESIGN: Cervical smears were collected from women attending the gynecology outdoors of various Delhi hospitals. The smears were wet fixed, processed for Papanicolaou staining and screened cytologically. RESULTS: A total of 130,000 satisfactory smears were screened. Benign cellular changes were found in 48%. Of these, 6.9% had evidence of specific infections, while the remainder showed nonspecific, reactive changes due to inflammation/repair. In two cases, unusual, large, crescentic, septate structures were identified. These were labelled macroconidia of Fusarium species on the basis of their unique microscopic morphology. The diagnosis was confirmed on fungal culture in one case. The patient responded well to antifungal therapy. CONCLUSION: Cytology is a useful tool for identification of unusual fungi with characteristic microscopic morphology. A prompt cytodiagnosis in these cases can assist clinicians with management.

Acantholytic cells exfoliated from pemphigus vulgaris of the uterine cervix. A case report.

BACKGROUND: Pemphigus vulgaris of the uterine cervix is rare and almost always associated with cutaneous or mucosal lesions elsewhere on the body. Without a history of pemphigus, acantholytic cells in cervical smears may be misdiagnosed as malignant ones. CASE: A 52-year-old female presented with a vaginal discharge, and a routine cervical smear was collected for cytology. The smear displayed atypical cells lying singly and in loose clusters, having vesicular nuclei, a thin nuclear membrane, prominent nucleoli and well-defined cytoplasmic margins. These were labeled atypical glandular cells of undetermined significance, and colposcopic examination and biopsy were advised. On colposcopy vesicular lesions and erosions were noticed on the cervix. The biopsy revealed typical intact as well as denuded suprabasal bullae of pemphigus vulgaris. On reevaluation of the cytologic smear, the cytomorphologic features correlated well with the acantholytic cells of pemphigus. Thorough reexamination of the patient revealed 2 tiny vesicles on the oral mucosa that, on biopsy, confirmed the diagnosis of pemphigus vulgaris. CONCLUSION: Cytopathologists should be aware of the typical cytomorphologic features of pemphigus vulgaris and, in an appropriate clinical setting, should be able to diagnose or at least suspect this entity in even rare sites like the cervix. A false positive diagnosis of malignancy can be avoided if the cytologic findings are judiciously correlated with the history and with clinical and colposcopic examinations.