Rapid pre-screening: a validated quality assurance measure in cervical cytology

We present the results of 3 years' experience of rapid pre-screening in cervical cytology. In our laboratory we rapidly pre-screen all smears. The performance of each primary screener can be assessed. In addition, the relative sensitivity and specificity of each rapid pre-screener can itself be continuously monitored using the final report as a yardstick. In our laboratory individual sensitivity of rapid pre-screening for the detection of high-grade abnormalities was in the range of 44-90% with an overall laboratory sensitivity of 69%. Specificity was in the range of 94-99% with an overall laboratory specificity of 98%. Rapid pre-screening allows checking of the checkers and pathologists and tends to promote uniformity in the assessment of smear adequacy. This form of continuous quality assurance is practical, convenient and acceptable to staff.     

Laboratory performance measures: evidence against low-risk women explaining low detection rates of high-grade abnormalities

OBJECTIVE: When a laboratory has a low reporting rate of high-grade abnormality for its cervical cytology specimens, the question arises whether this is due to the laboratory screening a low-risk group of women. This study was undertaken to explore the hypothesis that a low-risk group of women were screened by Victorian laboratories not meeting the recommended minimum standard for the detection of high-grade abnormalities. METHODS: A cohort of 28 094 women was established comprising women whose cervical cytology was reported in 2000 by laboratories not meeting the recommended standard of 0.5% high-grade abnormalities in their reporting of community smears. Outcome measures included the prevalence of high-grade abnormality on the next cytology test for the women, the positive predictive value of the cytology reports of high-grade abnormality, and the standardized incidence ratio for a later diagnosis of cervical cancer. RESULTS: The prevalence of high-grade abnormality was 0.36% on the index cytology compared with 0.68% on the first subsequent cytology report. Sixty-nine per cent (60/87) of the index cytology reports of high-grade abnormality were confirmed as high-grade abnormalities on histology, compared with 70.8% (121/171) for the first subsequent reports of high-grade abnormality. During 70 015 person-years at risk, nine cases of cervical cancer were observed compared with 5.21 expected cases, giving a standardized incidence ratio of 1.73 (95% CI 0.79-3.28). CONCLUSIONS: These results do not support a hypothesis that the low detection rate for high-grade abnormalities is due to the women comprising a low-risk group for cervical neoplasia.     

Rapid review in cervical cytology: a retrospective review of cases detected on rapid review within a DGH cytology department and subsequent outcome

We retrospectively reviewed smears detected by rapid review within a district general hospital (DGH) laboratory over a period of 33 months and the subsequent histological or cytological outcome. Sixty-three cases had adequate follow-up data: 32 subsequently had two negative smears and 31 had a histological abnormality on subsequent biopsy. Twenty were high-grade lesions (CIN2, CIN3 or a glandular lesion) and eight of these were preceded by a low-grade smear abnormality. We reviewed and compared the pattern and distribution of smear abnormalities in these 63 cases. Abnormalities were often present within few cells (76%, n = 48 with 50 abnormal cells or less) or in micro-biopsies (27%, n = 17). There was no statistical difference in the pattern and distribution of smear abnormality between the rapid review-detected smears with a biopsy-proven abnormality and those with negative follow-up smears. Overall, the positive predictive value for high-grade CIN detected by rapid review (75%) was within NHSCSP achievable standards targets. This review of rapid review-detected abnormalities and the biopsy and cytological follow-up reiterates the importance of the method in cervical screening.     

O-10THE ACCURACY OF CERVICAL CYTOLOGY: A COMPARISON BETWEEN THE THINPREP IMAGING SYSTEM AND CONVENTIONAL METHODS

Douglass Hanly Moir is a large Australian laboratory which has recently introduced the ThinPrep Imaging System (TPI) for reading ThinPrep slides, which is still performed using a split-sample technique. The Imager is a computerized system which identifies 22 fields for the cytologist to review using automated light microscopy. We compared the accuracy of TPI and conventional cytology (CC) during normal laboratory operation. The ThinPrep sample was prepared after taking a conventional Pap smear. TPI and CC reading was done without knowledge of the result of the other reading. The final cytology report issued to the referring doctor reflected the more severe of these two results. Histology results for all cases in which TPI and CC cytology results showed more than minimal disagreement were sought from the NSW Pap Test Register. Of 55 164 split sample pairs, 3.1% of CC of slides and 1.8% of TPI slides were unsatisfactory. There were 1758 women for whom there was more than minimal discrepancy between TPI and CC cytology results. TPI gave the more severe result in 1193 of the 1758 cases. In cases where only one of each pair of discrepant cytology results was CIN1 or higher grade, TPI detected 133 cases of high-grade histology among 380 biopsies (35%), whereas CC detected 62 cases among 210 biopsies (29.5%). A repeat analysis based on reading of histology by one pathologist blinded to initial Pap smear result showed a similar result. Reading times were measured over 5 months for both TPI and CC for twenty cytologists who read both types of smears. On average, they read 13.3 TPI slides per hour and 6.1 CC slides per hour. This study provides evidence that cervical cytology read using the TPI detects more histological high-grade disease than does CC. Further evidence shows that reading times are significantly reduced for cytologists using the TPI.     

The endoscopic diagnosis of gastroesophageal malignancy. A cytologic review

Cytologic reports were compared to final diagnoses for 1,157 gastroesophageal samples from an eight-year period in order to evaluate the diagnostic accuracy of endoscopic cytology and to determine the significance of a "suspicious" cytologic report. In the subgroup of patients with adenocarcinoma evaluated by paired endoscopic biopsy and cytology, the relative and combined sensitivities of the sampling methods were studied. Cytologic examination was reported as positive or suspicious in 85% of 229 cases of malignancy. There were three false-positive diagnoses of squamous-cell carcinoma of the esophagus, representing 0.3% of all submitted samples. Suspicious cytologic reports were issued in 5% of all cases. The majority (63%) of patients with a suspicious cytologic report had a final diagnosis of malignancy, with gastric adenocarcinoma present in almost half of the cases. Adenocarcinoma was diagnosed in 168 of the patients. Combined endoscopic biopsy and cytology was more sensitive (96%) than biopsy alone (90%) in making the initial diagnosis. Cytology may be of particular value in the diagnosis of gastroesophageal malignancy when the lesions are small and superficial or where stricture precludes adequate biopsy. Regardless of the biopsy findings, patients with "suspicious" cytologic reports require careful reevaluation since a high percentage of those cases in our series were subsequently verified as having malignancy.     

Internal quality assurance in cervical cytology—one laboratory's experience

The results of an internal quality assurance exercise in one cervical cytology laboratory in England are presented, using differing types of partial percentage re-screening of cervical smears. An overall false-negative dyskaryotic rate of up to 4.3% was demonstrated, with the final cytology report diagnosis differing from the primary screening diagnosis in 1.3% of cases. These findings are discussed, with the aim of helping to foster debate on the setting of national laboratory internal quality assurance standards.     

Internal quality assurance in cervical cytology—one laboratory’s experience

The results of an internal quality assurance exercise in one cervical cytology laboratory in England are presented, using differing types of partial percentage re-screening of cervical smears. An overall false-negative dyskaryotic rate of up to 4.3% was demonstrated, with the final cytology report diagnosis differing from the primary screening diagnosis in 1.3% of cases. These findings are discussed, with the aim of helping to foster debate on the setting of national laboratory internal quality assurance standards.     

Clinicopathological significance of borderline nuclear change – high grade dyskaryosis not excluded

During a recent discussion on classification of cervical cytology, the introduction of a 'Borderline Nuclear Change - High Grade Dyskaryosis Not Excluded' (BNCH) category was proposed. BNCH cases diagnosed prospectively were retrieved from laboratory records. Questionnaires were sent to referring practitioners regarding clinicopathological outcome. Cytopathological features resulting in the BNCH classification were recorded on slide review. A total of 103 reports on conventional cervical smears diagnosed as BNCH from 1999 to 2002 were retrieved, comprising 0.096% of 107 634 smears. Of 86/103 cases with clinical follow-up, CIN2 or worse was present in 30 (35%); 15 (17%) showed a borderline/low-grade abnormality and 41 (48%) were negative. No individual cytopathological feature was predictive of high-grade disease on follow-up. The yield of high-grade abnormalities on follow-up of BNCH supports the introduction of this terminology.     

Cytological aspects of uterine cervical adenocarcinoma, adenosquamous carcinoma and combined adenocarcinoma-squamous carcinoma: appraisal of diagnostic criteria for in situ versus invasive lesions

Cytological aspects of uterine cervical adenocarcinoma, adenosquamous carcinoma and combined adenocarcinoma-squamous carcinoma: appraisal of diagnostic criteria for in situ versus invasive lesions
This paper reports the cytological findings based on air-dried smears in a retrospective series of 143 cases of endocervical adenocarcinoma, combined adenocarcinoma-squamous carcinoma and adenosquamous carcinoma drawn from the files of the BC Cancer Registry. Cervical cytology smears were available before biopsy in 131 patients, but in 18 cases the cytology showed no abnormality. Malignant changes or high-grade atypia of glandular and/or squamous cells (defined as moderate or severe dyskaryosis) were detected in 103 cases. In 46 cases, only a high-grade squamous abnormality was detected. Low-grade glandular and/or squamous lesions were detected in nine cases and one showed atypical endometrial-type glands. The cervical smears of 64 cases were reviewed in detail to determine the important cytomorphological criteria of in situ and invasive adenocarcinoma in air-dried smears, the technique used for preparing PAP smears in British Columbia. Endocervical cells were absent in four cases. Numerous (>10) groups of glandular cells were present in 51 cases. Important clues to the diagnosis of adenocarcinoma included crowding of nuclei, stratification of nuclei, loss of polarity, syncytial balls and papillary groups of glandular cells, nuclear enlargement, nuclear pleomorphism, and the presence of free-lying atypical glandular cells. Nuclear hyperchromatism, chromatin pattern, nuclear borders, nuclear membranes, and numbers and morphology of nucleoli were not helpful criteria in our material. Criteria enabling reliable distinction between in situ and invasive adenocarcinoma and/or mixed adenocarcinoma-squamous carcinoma could not be established.     

Interpretation of fine needle aspiration cytology of the breast: a comparison of cytological, frozen section, and final histological diagnoses

This study examines the performance of the preliminary, on-site interpretation by the pathologist of fine needle aspiration (FNA) cytology smears compared to the final cytology report, the frozen section diagnosis and the final histopathological report. We found that both the preliminary and the final cytology reports gave satisfactory results over the minimum standards for quality assurance required by both the Norwegian breast screening programme and the NHS BSP in the UK with the exception of the 'suspicious' rate. We noted that the preliminary report had fewer false negatives (2.1%) than the final report (4.3%). We show that an unequivocal cytological diagnosis of malignancy is a reliable diagnosis, and in cases where mammography/ultrasonography and clinical examination are in agreement with FNA, frozen section examination is unnecessary. However, cases with a suspicious or equivocal FNA should be considered for frozen section analysis.     

Rapid pre-screening is more sensitive in liquid-based cytology than in conventional smears

Rapid pre-screening (RPS) is a useful tool to measure and improve performance in the cytology laboratory. Whether RPS is more or less effective in liquid-based cytology than in conventional smears is unknown. We compared the estimated sensitivity in a laboratory of 11 cytotechnologists which converted from conventional smears to SurePath? (Becton Dickinson, Franklin Lakes, N.J., USA) liquid based cytology. In the 9 months prior to conversion, 23,286 smears were screened compared with 30,610 smears in the 12 months immediately after conversion. The estimated sensitivity of rapid pre-screening for 90 s improved significantly with liquid based cytology for all abnormalities (58.7 vs. 68.7%, p<0.001), atypical squamous cells of undetermined significance+low-grade squamous intra-epithelial lesion (52.6 vs. 63.1%, p<0.001), and high-grade squamous intra-epithelial alone (76.2 vs. 85%, p<0.001). Histologic follow up for 156 cases identified by rapid pre-screening of SurePath slides showed 32 (21%) cases of CIN1 or greater and 18 cases (12%) with CIN3 or worse. We conclude that rapid pre-screening is significantly more sensitive in liquid-based cytology compared with conventional smears, and detects significant lesions that are missed by routine screening.     

Liquid-based cytology improves productivity in cervical cytology screening.

Objectives: The ThinPrep test was introduced into our institution on a phased basis over 3 years between January 2002 and December 2004. This study set out to assess its effect on productivity (as measured by output of cases per medical scientist per day) during the changeover period. Numbers of high and low-grade lesions and of unsatisfactory slides were also monitored. Methods: The percentage conversion from conventional preparation to liquid-based cytology (LBC) and output of cases per medical scientist per day were calculated from our database at 6-month intervals. The average backlog, average number of cases received per month and percentage of unsatisfactory and abnormal cases were calculated similarly. Results: Over the study period 92 084 cases were received. The percentage of cases using ThinPrep increased: from 9% in January 2002 to 73% in December 2004. During the study there was an increase in output from 17.0 to 22.3 cases per medical scientist per day, representing a 31% improvement at 73% conversion. Numbers of unsatisfactory cases decreased substantially and the numbers of low and high-grade diagnoses were relatively constant. Conclusions: The change to ThinPrep has improved productivity and decreased the number of unsatisfactory cases. There was no adverse effect on quality during the changeover.     

The number of dyskaryotic cells on an initial ThinPrep® cervical sample showing mild dyskaryosis has predictive value

OBJECTIVES: Recent National Health Service Cervical Screening Programme (NHSCSP) guidelines suggest referral for colposcopy following an initial result of mild dyskaryosis. The aim of this study was to investigate if the number of dyskaryotic cells counted on an initial ThinPrep cervical sample showing mild dyskaryosis has predictive value. METHODS: Cases of mild dyskaryosis on ThinPrep cervical samples from 2002 were retrieved from the cytology department records of St Luke's Hospital. A total of 123 sequential cases with a first-time result of mild dyskaryosis on ThinPrep slides with follow-up cytology available in the same institution were identified. While blinded to outcome, the number of dyskaryotic cells was counted in each case. Follow-up colposcopy/histology information was retrieved where indicated. The number of dyskaryotic cells counted on each slide was collated with outcome data. RESULTS: Of the 123 cases, six women were lost to follow-up. Seventy-three had a negative outcome, 27 had a low-grade outcome and 17 had a high-grade outcome. Only one of 17 high-grade outcome cases had < or = 15 dyskaryotic cells on the initial slide. The distribution of women with a negative/low-grade outcome and those with a high-grade outcome with >15 and < or = 15 dyskaryotic cells on the initial slide was tested using a chi-square test (P = 0.008). The negative predictive value for a high-grade outcome when < or = 15 dyskaryotic cells were present on the initial slide was 97.7%. CONCLUSION: The number of dyskaryotic cells on ThinPrep slides showing mild cervical dyskaryosis has predictive value. The number of dyskaryotic cells may be used to select women suitable for cytological rather than colposcopic follow-up.     

Presence of human papillomavirus DNA sequences in cervical intraepithelial neoplasia.

Twenty two patients referred to a district colposcopy clinic because of an abnormal cervical cytology report or a suspicious cervix and found to have a cervical epithelial abnormality were studied. The techniques of cytology, histology, immunohistochemistry, and DNA-DNA hybridisation were used to detect infection by human papillomavirus. Using an indirect immunoalkaline phosphatase technique human papillomavirus antigen was found in biopsy specimens from six of the 22 patients and DNA of papillomavirus type 6 in biopsy specimens from 13 of these women, including four out of six whose histological diagnosis was cervical intraepithelial neoplasia grade 3. In eight cases where cytological, colposcopical, and histological investigations all indicated the presence of wart virus infection, papillomavirus type 6 DNA was found in seven. Papillomavirus type 6 DNA was found in more than half of the proved cases of cervical intraepithelial neoplasia. The presence of this viral DNA in women with no cervical abnormality is to be studied.     

Front-to-back & dabbing wiping behaviour post-toilet associated with anal neoplasia & HR-HPV carriage in women with previous HPV-mediated gynaecological neoplasia

BackgroundAnal cancer is a human papillomavirus (HPV)-mediated neoplasia of the anal squamous epithelium. Anal cancer is much more common among women, particularly those with a previous high-grade gynaecological neoplasia.MethodsCross-sectional study of women with a previous HPV-mediated gynaecological neoplasia in Tasmania, Australia. Women presenting for follow-up gynaecological care had anal swab samples taken for anal cytology by Hologic Liquid ThinPrep, followed by HPV genotyping. Women with abnormal anal cytology were invited for high-resolution anoscopy. Potential risk factors, including post-toilet wiping behaviours, were queried by questionnaire while clinical covariates were extracted from medical records. Covariates of anal outcomes evaluated by log-binomial and log-multinomial regression.ResultsFrom 163 women enrolled in the study, 65 (39.9%) had abnormal cytology, with 46 (28.2%) being high-grade. Of the 50 women with abnormal anal cytology having high-resolution anoscopy, 32 (64.0%) had abnormal histology with 13 (26.0%) being high-grade. Of the 123 women tested for HR-HPV DNA, 48 (39.0%) had HR-HPV detected, the most common genotypes being 16 and 51 (14/123, 11.4% for both).In addition to some known anal cancer risk factors, we found front-to-back wiping was associated with significantly increased (Prevalence ratio (PR) range: 1.99⿿3.60) prevalence of cytological and histological abnormality and HR-HPV carriage/co-carriage, while dabbing post-toilet was significantly associated with decreased prevalences (PR range: 0.50⿿0.62).ConclusionsPost-toilet wiping behaviours were significantly associated with the prevalence of anal cytological, histological and HR-HPV carriage outcomes. This suggests a biologically plausible mechanism for HR-HPV introduction and the higher frequencies of anal neoplasia in women.     

Role of urinary NMP-22 combined with urine cytology in follow-up surveillance of recurring superficial bladder urothelial carcinoma

OBJECTIVE: To determine efficacy and utility of NMP-22 in follow-up of bladder urothelial carcinoma (UC) and compare NMP-22 as a single evaluating test vs combination with cytology. STUDY DESIGN: Ninety-four consecutive urine cytology samples of bladder UC were identified. Patients received follow-up urine cytology, NMP-22 testing and cystoscopy with surgical biopsy. RESULTS: NMP-22 specificity was 100%, sensitivity 45%, positive predictive value (PPV) 100% and negative predictive value (NPV) 87%. NMP-22 showed lower sensitivity for high-grade lesions and higher for low-grade lesions. Cytologic diagnosis had a high inconclusive rate; when regarded as positive, it resulted in 75% sensitivity, 58% specificity, 33% PPV and 89% NPV. NMP-22 correctly classified 60% of false negative cases diagnosed by cytology with low-grade UC and clarified 27 inconclusive cytologic diagnoses. NMP-22 misclassified 9 cases as false negative, all with high-grade UC; all were correctly identified on cytology as true positive. Combined interpretation showed 90% sensitivity, 92% specificity, 75% PPV and 98% NPV. CONCLUSION: NMP-22 complements cytology by its higher sensitivity for low-grade lesions; its values are not affected by bacillus Calmette Guérin therapy changes, which are limiting in cytology. Combined interpretation of NMP-22 and cytology shows promise as an effective, noninvasive method for surveillance of UC.     

Colposcopic management of high‐grade referral smears: a retrospective audit supporting ‘see and treat'?

OBJECTIVE: The National Health Service Cervical Screening Programme monitors the quality of colposcopy services through the annual KC65 returns. The 2002 returns demonstrated that Standard 7c, which specifies a biopsy rate > or = 90% at first colposcopy visit for high-grade referrals, was not met in the assessed 3-month period. This was investigated along with the other standards. METHODS: Retrospective colposcopy records were accessed for the 597 new referrals, excluding 10 pregnant patients, seen at the colposcopy clinic at the Royal Victoria Infirmary between 1 July 2001 and 31 December 2002, following an abnormal high-grade smear. Cytology and histopathology computer records were checked for confirmation. The results were assessed against the colposcopy standards applicable at that time and the revised standards (2004). RESULTS: Biopsies were taken from 94.47% (Standard > or = 90%) of women at index colposcopy visit including wire loop excision biopsies from 66.16% (87.97% of high-grade colposcopic appearances). Cervical intraepithelial neoplasia (CIN) on histology was found in 91.79% in the study group (Standard > or = 85%) and in 96.71% of index visit biopsies (Standard > or = 90%), meeting the applicable colposcopy standards. The revised 2004 standards specify a biopsy in > or = 95% of high-grade referrals and excision biopsies in 95% if colposcopic appearances are also high-grade, if colposcopy is low grade but the smear is severely dyskaryotic, or when the lesion extends into the canal. The positive predictive value of high-grade cytology for this entire group was 75.54% with CIN present in 90.95%. CONCLUSION: From this study it appears that high-grade cytology in this centre reliably indicates high-grade CIN. Therefore, in women referred for colposcopy following a high-grade smear, excision biopsies should be performed in a higher proportion at the first visit to comply with the revised standards.     

Cytologic presentation of malignant mesothelioma in pleural effusions

1,601 pleural effusions were found to be malignant between 1976 and 1987. Among these were 26 (1.6% of the malignant effusions) mesothelioma. Only 2 cases showed pronounced cytologic features that made a definite diagnosis possible on cytologic criteria alone. In 20 cases diagnosis of mesothelioma was strongly suggested by the patient's history and cytology of the effusion was compatible with mesothelioma. In the other 4 cases special examinations (histo- and immunohistochemistry, electron microscopy) led to the final diagnosis. The cytologic features of mesothelioma and other examination techniques, needed to resolve the differential diagnosis of mesothelioma versus other neoplasm in pleural effusions, are discussed.     

Intraoperative squash cytology: accuracy and impact on immediate surgical management of central nervous system tumours

N. Krishnani, N. Kumari, S. Behari, C. Rana and P. Gupta
Intraoperative squash cytology: diagnostic accuracy and its impact on immediate surgical management of central nervous system tumours Objective: To assess the diagnostic accuracy of squash cytology, reasons for deferment, disagreement and partial agreement, and assess its impact on immediate surgical management of central nervous system tumours. Study design: All cases of squash cytology received from January 2007 to July 2010 were reviewed and correlated with final histopathological diagnoses. Deferments, disagreements and partial disagreements were reviewed to look for possible reasons. The impact of disagreements and partial agreements on immediate surgical management was evaluated in consultation with neurosurgeons. Results: Overall accuracy (including complete and partial agreement) for squash smear diagnosis of 334 cases was 94.9% while complete agreement was 79.9%, excluding deferred cases. Disagreement was seen in 17 cases and 31 cases were deferred for final histopathology diagnosis. Good correlation was seen in astrocytoma, meningioma, schwannoma, medulloblastoma, pituitary adenoma and metastatic carcinoma, whereas poor correlation was seen in oligodendroglioma, ependymoma and lymphoma. Among 17 cases with disagreement and 50 cases with partial agreement, an adverse impact on immediate surgical management was found in six (35.3%) cases and one (2.0%) case, respectively. The sensitivity and specificity of squash for diagnosis of neoplastic lesions were 98.7% and 87.5%, respectively. Conclusion: Squash cytology is a rapid, reliable, simple technique for intraoperative consultation in neurosurgical practice with high overall accuracy. Causes causing an adverse impact on surgical management were rare and potential avoidable reasons for them were identified.     

Cervical cytology/histology discrepancy: a 4‐year review of patient outcome

E. L. Moss, A. Moran, G. Douce, J. Parkes, R. W. Todd and C. E. W. Redman Cervical cytology/histology discrepancy: a 4‐year review of patient outcome Objective: To investigate the diagnosis, review and management of women identified as having a cytology/histology discrepancy. Methods: A review of all patients diagnosed with a discrepancy between referral smear and cervical histology was performed between January 2003 and December 2004. Cases were followed for a minimum of 4 years and patient management and outcome reviewed. Results: A significant discrepancy was identified in 79 cases, 0.1% of all smears (n = 80 926) analysed during the study period. A discrepancy between cytology and histology, obtained from large loop excision of the transformation zone (LLETZ), was confirmed by multidisciplinary review in 42 cases (53.2%). In 37 cases (46.8%) the cytological and/or histological diagnosis was revised; the cytology was significantly more likely than the histology to be amended (chi square P = 0.005), most often because cytology had been overcalled. Of the confirmed discrepancy cases, 33 (78.6%) were due to high‐grade squamous cell or glandular abnormalities on cytology with a negative, inflammatory or human papillomavirus (HPV) infection on histology (HGC/NH). HGC/NH cases were managed by cytological follow‐up in 29 (87.9%), of which 72.4% of the smears were negative when performed at least 6 months post‐excision. During the 4‐year follow‐up period six women with a confirmed HGC/NH underwent a repeat cervical excision (hysterectomy or LLETZ), and of these, HPV effect was seen in two cases but no cervical intraepithelial neoplasia was detected in any of the histological specimens. Conclusion: Cytology overcall was responsible for the majority of cytology/histology discrepancies. A confirmed discrepancy is not an indication for a further excisional biopsy but follow‐up is essential because a small percentage of patients may have disease that has been missed.