Touch imprint cytology of core needle biopsy specimens: a useful method for immediate reporting of symptomatic breast lesions

Touch imprint cytology of core needle biopsy specimens: a useful method for immediate reporting of symptomatic breast lesions

EJSO (2005) 31, 490–494 www.ejso.com Touch imprint cytology of core needle biopsy specimens: a useful method for immediate reporting of symptomatic ...

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EJSO (2005) 31, 490–494

www.ejso.com

Touch imprint cytology of core needle biopsy specimens: a useful method for immediate reporting of symptomatic breast lesions M.B. Klevesatha,*, R.J. Godwinb, R. Bannonb, L. Munthalic, E. Coveneya a

Department of Surgery, West Suffolk Hospital, Bury St Edmunds, England, UK Department of Radiology, West Suffolk Hospital, Bury St Edmunds, England, UK c Department of Pathology, West Suffolk Hospital, Bury St Edmunds, England, UK b

Accepted for publication 11 January 2005 Available online 25 February 2005

KEYWORDS Breast neoplasms; Biopsy, needle/methods; Cytodiagnosis; Cytological techniques; Retrospective studies

Abstract Aims. The aim of this study was to determine the diagnostic value and accuracy of touch imprint cytology (TIC) of core needle biopsy (CNB) specimens in predicting the final benign or malignant histology in patients presenting with symptomatic breast lesions. Methods. One hundred and twenty-eight patients underwent CNB under ultrasonographic guidance with subsequent TIC preparation. TIC results were correlated with the histology of the core or the surgical resection specimen. Results. The 128 lesions analysed included 106 malignancies and 22 benign lesions. TIC accurately predicted the final histology in 96.7% of cases, with a sensitivity of 96.2% and a specificity of 100%. Conclusions. The routine use of TIC to complement CNB can provide an immediate and reliable cytological diagnosis of symptomatic breast lesions. The potential use of this technique in a breast clinic setting may help allay patient anxiety and expedite the planning of further surgical management. q 2005 Published by Elsevier Ltd.

Introduction Core needle biopsy (CNB) is an adjunct to open surgical biopsy and fine needle aspiration cytology (FNAC) in the assessment of breast lumps. While less invasive than open surgical biopsy, CNB is * Corresponding author. Address: Cambridge Breast Unit, Box 97, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 2QQ, UK. Tel.: C44 1223 586627; fax: C44 1223 257219. E-mail address: [email protected] (M.B. Klevesath). 0748-7983/$ - see front matter q 2005 Published by Elsevier Ltd. doi:10.1016/j.ejso.2005.01.004

superior to FNAC with greater sensitivity and specificity and lower inadequate rates.1–7 Moreover, CNB allows the pre-operative determination of oestrogen receptor status and preserves histological architecture. The main disadvantage of CNB is that its results are not immediately available. Touch imprint cytology (TIC) of core needle biopsy specimens would allow immediate reporting with no additional intervention or risk to the patient other than the CNB itself. Imprint cytology of CNB specimens may achieve high levels of sensitivity and

Touch imprint cytology of core needle biopsy specimens accuracy, which are comparable to FNAC. TIC has so far mainly been used in the diagnosis of screen detected, impalpable breast lesions or in a mixed case load (i.e. screen-detected and symptomatic lesions).8–16 The aim of this study was to determine the accuracy of CNB touch imprints in predicting benign and malignant histology in patients presenting with symptomatic breast lesions.

Patients and methods Patients Between February 2000 and April 2001, 128 women with symptomatic breast lesions underwent core needle biopsy with subsequent TIC preparation at the West Suffolk Hospital (Bury St Edmunds, England). All patients underwent further complementary assessment including clinical, mammographic and ultrasonographic examination of both breasts. The imprints were prepared so that a preliminary cytological result was available for the multidisciplinary breast meeting (MDM). Patients ranged in age from 32 to 89 years. All biopsies were obtained under ultrasonographic guidance using a disposable, spring-loaded biopsy system with a 14gauge needle (Achievee, Allegiance, UK).

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using Diff-Quik (Fig. 1). Two smears were prepared from each core biopsy specimen. The core biopsy specimen was put into formalin for 6–8 h prior to processing for histological evaluation (Fig. 2). Imprint cytology was deemed adequate if five or more ductal cell groups were identified. The CNB specimen and TIC slides were reported independently by either one of two pathologists. TIC slides were categorised according to the five categories used in the national health service breast screening C1Z programme guidelines (NHSBSP): 17 inadequate, C2Zbenign, C3Zatypia, probably benign, C4Zprobably malignant, C5Zmalignant. Imprints categorised as C5 or C4 were considered positive, while imprints classified as C2 or C3 were scored as negative. We chose to use the NHSBSP guidelines for TIC reporting as they were well established, ensured consistency with our FNAC reporting and enabled reproducibility in our reporting standards. TIC results were correlated with the final histological diagnosis of the core biopsy specimen or with the surgical resection specimen. A separate correlation was made between TIC results and the histology of the CNB specimen in order to enable a comparison between previous studies as well as between touch imprints and core biopsy histology.

Results Preparation and reporting of TIC The biopsies and subsequent imprints were performed by either one of two radiologists. A maximum of three samples was taken from each lesion. For the preparation of the imprints the core biopsy specimen was rolled between two glass slides. The slides were air-dried and then stained

Figure 1 Touch imprint cytology of an invasive ductal carcinoma, showing a cluster of loosely cohesive malignant epithelial cells with large nuclei.

Histopathological characteristics of the study population Of the 128 patients who underwent TIC preparation, 22 had a benign and 106 a malignant diagnosis on final histology (Table 1). The 22 benign cases included eight fibroadenomas, three

Figure 2 The corresponding core biopsy histology to the touch imprint cytology in Fig. 1, showing an invasive ductal carcinoma.

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Table 1 Correlation of touch imprint cytology results with final histology Touch imprint cytology Benign Malignant Inadequate Total

Histology

Analysis of benign cases

Benign

Malignant

Combined

17 0 5 22

4 100 2 106

21 100 7 128

hyalinised breast tissue, two granulomatous mastitis, two fibrocystic disease, one fat necrosis, one usual type hyperplasia and five benign breast tissue not otherwise specified. Of the 106 malignant cases, there were 76 cases of invasive ductal carcinoma, five cases of ductal carcinoma in situ (DCIS), 17 cases of invasive lobular carcinoma, seven cases of mucoid carcinoma and one case of a malignant Phylloides tumour with liposarcomatous stromal differentiation.

Analysis of all cases When correlated to the final histology, the sensitivity of TIC for malignancy was 96.2% with an inadequate rate of 5.5% and a false negative rate of 3.3%. There were no false positives and the specificity was 100%. The accuracy of TIC for predicting the final histological diagnosis was 96.7%, with a positive predictive value of 100% and a negative predictive value of 81% (Table 2). When the imprints were correlated to the core biopsy specimen histology, the corresponding values for accuracy, sensitivity, specificity and Table 2 Diagnostic parameters of touch imprint cytology of core needle biopsy specimens

Inadequate False negative False positive Specificity PPV NPV Sensitivitya Accuracy

inadequacy were 95.9%, 96.1%, 94.4% and 5.5%, respectively.

Benign (nZ 22)

Malignant (nZ106)

Combined (nZ128)

5 –

2 4

7 4

0





– – – – 17

– – – – 100

100% 100% 81% 100 117

Inadequate imprints were excluded for the calculation of false negatives, specificity, accuracy and sensitivity. a For malignancy; PPV, positive predictive value; NPV, negative predictive value.

In the benign group (nZ22), the accuracy was 100% with an inadequate rate of 22.7% (one hyalinised stroma, one fibrocystic change and three benign breast tissue not otherwise specified). Of the remaining 17 imprints, 14 were categorised as C2 and three as C3 (two fibroadenomas and one fibrocystic change). There were no false positive imprints.

Analysis of malignant cases In the malignant group (nZ106), the accuracy was 94.3%, with 90 imprints scored as C5 and 10 imprints scored as C4 (four invasive ductal carcinoma, four invasive lobular carcinoma, one mucinous carcinoma and one DCIS). Two imprints (1.9%) produced cytology deemed inadequate for diagnosis (Table 3). There were four cases (3.8%) of false negative touch imprints (Table 3). One false negative (C2) was classified as a Phylloides tumour of borderline type on core biopsy. The final histology revealed a malignant Phylloides tumour with liposarcomatous stromal differentiation. The second false negative imprint (C3) was obtained from one of two biopsies from two separate lesions in the same breast. Both core biopsies and the imprint of the second CNB specimen were reported as malignant (C5). The mastectomy specimen revealed two invasive ductal carcinomas with apocrine differentiation. The final histology of the remaining two false negative cases (both C3) showed a DCIS with apocrine differentiation and an invasive ductal carcinoma, respectively. The core biopsy accurately predicted the final histology in 99.2%. Interestingly, the one core biopsy that failed to predict the final histological result (an invasive carcinoma with apocrine differentiation categorised as benign on core biopsy) was classified as malignant (C5) on the corresponding TIC.

Discussion Touch imprint cytology (TIC) of CNB specimens allows immediate reporting while retaining the inherent benefits of the CNB. In our hands, TIC was highly accurate (97%) in predicting the final histological result. Results from previous studies confirm that TIC achieves a high degree of

Touch imprint cytology of core needle biopsy specimens Table 3

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False negative and inadequate touch imprint cytology results of malignant cases

TIC report

Final histology

Clinical and radiological assessment

Inadequate Inadequate Negative

Invasive lobular carcinoma Invasive ductal carcinoma Malignant Phylloides tumour with liposarcomatous stromal differentiation Invasive ductal carcinoma DCIS with apocrine differentiation Invasive ductal carcinomas with apocrine differentiation

Malignant Malignant Benign

Negative Negative Negative

sensitivity (74–97%) and accuracy (93–97%) for predicting malignancy on final histology.8–16

TIC in benign lesions The main difficulties for TIC, as for FNAC, arise in interpreting imprints of benign breast conditions, such as fibroadenomas.10,11 While there were no false positive imprints in our study, the number of benign lesions was low. The studies on TIC that contain the largest number of benign cases have reported different rates of false positive results. In their analysis of TIC on impalpable breast lesions, March et al. recorded two false positive cases (both fibroadenomas) out of a total of 86 benign lesions (2%).12 Similarly, Kass et al. reported three false positive results (one fibroadenoma, one inframammary lymph node and one papilloma) in a series of 142 benign breast lesions (3%).15 In contrast, when Newman et al. reviewed their results of TIC from CNB specimens of breast calcifications, they found no false positive results in 146 benign lesions.8 Other studies have recorded false positive rates for TIC between 0 and 5%.9–11,13 This compares favourably with published figures for false positive rates in FNAC, which range from 0% to as high as 32% (mean 7%).4,5,19

Inadequate TIC Inadequate samples in TIC can occur in malignant and benign cases, but seem to be commoner in imprints of benign lesions, with overall rates ranging from 0 to 29%.8,10,12,13,15 With 6%, our inadequate rate lies at the lower end of the spectrum. This may be due to the low number of benign lesions in our study. Overall, the inadequate rates for TIC are similar to those reported for FNAC, which range from 0 to 38% (mean 13%).3–5,18,19

Improving the accuracy of TIC Several suggestions have been advanced to reduce

Malignant Malignant Malignant

the number of inadequate or false negative and false positive imprints. Liberman et al. and Dennison et al. demonstrated that, in the case of CNB, the diagnostic yield increases with the number of CNB specimens taken.7,20 A similar approach might reduce the number of inadequate or false negative rates in TIC. The presence of a cytopathologist could further increase the number and quality of the slides prepared, thus improving the overall accuracy. Finally, since the imprints would usually be reviewed in the context of the clinical and radiological findings, any incongruity between the different modalities would lead the clinician to defer the diagnosis until the core histology becomes available. In our study, all false negative imprints (with the exception of the malignant Phylloides tumour) had been classified as malignant on clinical and radiological examination. On the other hand, it could be argued that the need for the presence of an experienced breast cytopathologist and the growing dependence on histological rather than cytological results may limit a wider adoption of this technique.

Conclusion This study shows that TIC of CNB specimens can accurately predict malignancy on final histology in patients presenting with symptomatic breast lesions. Immediate reporting of touch imprints may expedite the planning of further surgical management and may allow a guarded comment to the patient about their possible diagnosis. A malignant result may help allay patient anxiety through earlier participation of patients in support and counselling services. A benign result would reassure patients on the day of their attendance and allow them to be discharged, pending final confirmation by the core histology. TIC could further be used to provide a preliminary cytological diagnosis for multidisciplinary meetings where, for logistic or other reasons, the core histology is not

494 yet available. Finally, as Newman et al. and Jacobs et al. have shown, TIC can be a valuable adjunct to CNB as it allows an immediate assessment of the adequacy of the core biopsy sample, thereby reducing the number of passes required.8,11 The value of TIC in predicting a benign histological result is less definite. This is mainly due to lower specificity, higher rates of inadequate samples and a potential for false positive results. Larger prospective studies with a higher number of benign cases are needed to address these issues and to determine the value of TIC of CNB specimens in benign breast lesions.

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