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Indian Journal of Surgery
Medknow Publications on behalf of Association of Surgeons of India
ISSN: 0972-2068
Vol. 68, Num. 6, 2006, pp. 302-305

Indian Journal of Surgery, Vol. 68, No. 6, November-December, 2006, pp. 302-305

Original Article

Accuracy of intra-operative imprint smears in breast tumours: A study of 40 cases with review of literature

Department of Surgery, KLES Hospital and Medical Research Centre, Belgaum - 590 010, Karnataka
Correspondence Address:145, Mahantesh Nagar, Belgaum - 590 016, Karnataka Email: drabhijit_h@yahoo.co.in

Code Number: is06088

Abstract

Context: Imprint smears are invaluable diagnostic tool for intra-operative evaluation of breast tumours.
Aims:The aim of this study was (1) to evaluate the accuracy of intra-operative imprint smears in breast tumours. (2) to compare the results with that of published literature on imprint smears of breast tumours.
Materials and Methods:
40 cases of breast tumours underwent intra-operative imprint smears between March 2003 to April 2004, the results of which were compared to the post-operative final histopathological sections.
Statistical Analysis Used: The sensitivity, specificity, positive predictive value and negative predictive value were calculated.
Results:
Of the 40 cases, 21 were malignant and 19 were benign. The accuracy rate for benign lesions was 100% and that for malignant lesions was 97.5% with a false negative rate of 2.5%. The sensitivity, specificity, positive predictive value and negative predictive value were 95.24%, 100%, 100% and 95% respectively.
Conclusions: Intra-operative imprint smears like frozen sections help in on table diagnosis, wherein the fine needle aspiration cytology is inconclusive or suspicious. Imprint smears is a simple, accurate, rapid and cost-effective diagnostic tool, intra-operatively wherein facilities for frozen section are not available.

Keywords: Accuracy, breast tumours, imprint smears

One of the most prevalent reasons for a woman to seek consultation with a surgeon is the evaluation of a breast abnormality.[1] Fine needle aspiration cytology (FNAC) has its own limitations in terms of sensitivity and specificity. Many a times FNAC leads to a diagnosis that is "suspicious, but not confirmatory." The frozen-section biopsy requires specialized equipment, which may not be always available. Therefore as an alternative to frozen-section technique, imprint smears from these tumours are taken and stained with hematoxylin and eosin (rapid H&E). The method does not require any specialized equipment, is less time consuming and the disadvantages of freezing the tissue and serial sectioning are avoided.[2] Hence the present study is undertaken to note the accuracy of intra-operative imprint smears in breast tumours.

Materials and Methods

Source of data: Patients who underwent elective breast surgeries in our hospital from April 2004 to March 2005.
Sample Size: 40 patients.
Inclusion criteria: All female patients undergoing elective surgeries for breast lump.
Exclusion criteria: Patients with acute breast abscess.
Method of collection of data: Institutional ethical clearance was obtained. Detailed clinical history and thorough physical examination were done in each patient. Complete pre-operative work-up investigations and medical fitness for surgery were obtained. Each patient was informed about the procedure and informed consent was obtained.
Preoperative FNAC in these 40 cases, suggested 17 to be benign; 14 to be malignant and nine were reported suspicious. As per the report of FNAC in each case, patients underwent either an excisional biopsy or quandrantectomy or modified radical mastectomy or simple mastectomy with or without axillary sampling. The tumour was bisected to note the macroscopic features. Then the cut surfaces were pressed onto a clean glass slide and fixed in 95% methanol. Special emphasis was given to tumour- bearing area. Rapid H&E staining was done. The smears were interpreted by the cytopathologist. The results of the imprint smears were compared with the final paraffin sections.

Results

Out of the 40 cases, 21 were malignant and 19 were benign [Table - 1][Table - 2]. The age incidence ranged from 13 to 65 years (mean age 37.93 yrs). The most common age group for benign lesions was between 21 to 30 years and that for malignant lesions was 31 to 50 years. The duration of symptoms varied from few weeks to few years. The mean duration of symptoms was five months. The mean duration of symptoms for benign lesion was 5.3 months (range eight days to one year) and for malignant lesion was 11.5 months (range eight days to two years). Four patients of carcinoma breast had a strong family history of carcinoma breast. One patient of bilateral multiple fibroadenomata who had 14 lumps all together gave history of multiple, recurrent fibroadenomata in her mother. In one patient, who underwent modified radical mastectomy during same week and same admission, the imprint smear was benign and paraffin section revealed infiltrating ductal carcinoma.

The accuracy rate for benign lesions was 100% and that for malignant lesions was 97.5%, with a false negative rate of 2.5% [Table - 3]. All the 21 cases of malignancy were intraductal carcinomas.

Discussion

Carcinoma of the breast is the second most common cancer among female Indian population next only to carcinoma cervix. However in the urban population, carcinoma of breast has surpassed the incidence of carcinoma cervix. FNAC diagnosis depends only on the aspirated material. The tissue immediately adjacent to or contained within another part of tissue may harbour malignant cells. In a clinical scenario, the consultant surgeon will be in a dilemma to counsel and propose the appropriate surgical modality of treatment. Another major concern about breast FNAC has been the fear that mastectomy may be performed on a false positive cytological diagnosis with clinical and medico-legal implications.

Though core needle biopsy (CNB) can routinely be done and is superior to FNAC because insufficient specimens are unusual. Some investigators believe that CNB is inappropriate for lesions that are highly suggestive of malignancy. The surgeon may choose to discuss treatment options with the patient pre-operatively and proceed directly to one stage surgery, which reduces costs by eliminating a separate biopsy for tissue diagnosis. CNB is cost-effective for lesions that are highly suggestive of malignancy only if a two-stage procedure is planned. There are some contraindications to CNB. Certain mammographic findings indicate a condition, best managed with complete excision for example, if calcifications are few in number and not tightly clustered, CNB sampling errors are highly likely to occur. There are also limitations related to the location of the lesion or the size of the breast. A lesion very close to the skin or located in a very small breast may not be suitable for CNB because of the required throw of the needle. It may not be possible to visualize lesions adjacent to chest wall on a stereotactic biopsy unit.[3]

Diagnostic pitfalls of breast FNAC[4]

Lobular carcinoma cells are relatively small and their malignant nature may be overlooked. The low-grade ductal carcinomas (e.g., tubular carcinoma) can be mistaken for a benign hyperplasia. Fibroadenomas can present a very worrying appearance, leading to a risk of a false positive diagnosis, particularly in pregnancy or when they occur in an elderly woman. A small carcinoma can be overshadowed by a more dominant benign lesion. Pregnancy or lactation can be associated with atypical epithelial changes and are open to misinterpretation. Previous radiotherapy can produce cytological abnormalities in patients where the index of suspicion is already very high. Complex proliferative, papillary and atypical hyperplasic lesions may be over-diagnosed as malignant. These can be accompanied by a mammographic appearance that may raise the index of suspicion. Apocrine cells can give a spurious appearance of atypia, particularly when they become degenerate. Necrotic debris is seen in necrotic tumours as well as in inflammatory conditions. Inflammatory conditions such as simple abscess can be associated with marked reactive atypia of epithelial cells.

Rare problems with FNAC

Fat necrosis can be associated with reactive macrophages that can mimic carcinoma cells, conversely some tumours have associated fat necrosis. Skin adnexal tumours, soft tissue tumours of the chest wall and secondary carcinomas can all present in a way that mimics a primary breast lesion. Organizing haematoma may contain degenerate material, large spindle cells, large cells containing pigment and prominent nucleoli giving a potential for misdiagnosis as metastatic melanoma. The granular cell tumour and macrophages of the commoner duct ectasia can present a similar appearance. Herpetic infection and eczema of the nipple may be mistaken for Paget's disease of the nipple.

The need for intra-operative consultation of the nature of the breast tumour has paved way for the utilization of imprint smears and scrape smears popularly known as touch preparation cytologies.[5] Imprint smears were initially described in the early 20th century and recently have gained more popularity for the evaluation of margins in breast conservation surgeries.[6],[7],[8]

In our series we have evaluated the accuracy of intra-operative imprint smears in breast tumours. The proposed ideology is that the cancer cells are more adherent to a glass surface than benign cells. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) in our study is comparable to other studies [Table - 4].

Imprint smears have proved superior to frozen-sectioning due to the inherent disadvantages in the latter [Table - 5].[9] Proponents of touch preparation claim that in the hands of an experienced cytopathologist, it may even be more accurate than permanent sections because it samples the entire surface area of the resected specimen.[2]

Because imprint smears sample the entire surface of the specimen, is less time consuming and avoids the issues of specimen loss and freezing artifacts, it is gaining popularity as a technique for intra-operative evaluation of margin status.

Khanna,[14] reported a sensitivity of 98.4%, a specificity of 100%; Scopa,[15] reported an accuracy rate of 94.3%. The data suggest that intra-operative pathologic evaluation of margin status may be useful to reduce the need for reexcision. Kim, reported the efficacy of intra-operative imprint cytology to be superior to frozen-section analysis.[16] Ku reported a sensitivity of 100%, specificity of 97.1% and a diagnostic accuracy of 97.7% for imprint cytology.[17] Veneti reported a sensitivity of 97.1%, a specificity of 99.4% and accuracy of 98.3% for imprint cytology.[18] England assessed the adequacy of wide local excision of breast cancer using specimen scrape cytology and tumour bed biopsy.[19] Pinotti concluded that intra-operative pathological monitoring of surgical margins is a safe and accurate method to prevent additional surgery for insufficient margins and to reduce the recurrence rate.[20] Dutta reported that the combination of FNAC and imprint cytodiagnosis gave a diagnostic accuracy of 96%.[21]

Shidham in reported a strong favour for routine practice of imprint cytology during intra-operative consultation.[22] Creager concluded that the sensitivity and specificity of imprint cytology are similar to that of frozen-section evaluation.[23] Cendan concluded that intra-operative analysis of margins using frozen-section is effective but ductal carcinoma in situ is more difficult to identify in frozen-section analysis.[24] In our series, we reported a sensitivity of 95.24%, Specificity of 100%, PPV of 100% and NPV of 95%. These results correlate well with other workers. We had one false negative case, which was reported benign on imprint smear and final histopathology was intraductal carcinoma.

The recent consensus of breast conservation surgery for carcinoma of breast is assuming more importance.[8] Intra-operative imprint smears are the key tools to assess the margin status during these surgeries. Reexcision of the margins can be performed during same surgery if imprint smears are positive; thus avoiding a second surgery.

Intra-operative imprint smears are being increasingly used to evaluate the sentinel lymph node, which is the first node to receive lymphatic drainage from the site of the primary tumour. Worldwide research is in progress even with regard to immunohistochemistry and DNA markers in imprint smear cytology. This is proving beneficial in tumours of the breast, thyroid, parathyroids, head and neck tumours, kidneys, reproductive organs and in general the deep seated solid viscera wherein pre-operative access for biopsy is difficult. The danger of misdiagnosis of a cancer is studiously avoided by maintaining a cautious and conservative threshold for diagnosing a cancer. Having realized the limitations of FNAC, any questionable diagnosis that is stated to be suspicious, an open biopsy is most often suggested wherein centers an intra-operative frozen section analysis is not available. Intra-operative imprint smears do not require any specialized equipment. Finally we conclude that imprint smears is a simple, accurate, rapid and cost-effective diagnostic tool for intra-operative evaluation of breast tumours. The sensitivity and specificity support their utility intra-operatively wherein facilities for frozen-sections are not available.

References

1.Baker RJ, Fischer JE. Mastery of surgery. Vol. 1. 14th ed. 2001. p. 574.  Back to cited text no. 1    
2.Creager AJ, Shaw JA, Young PR, Geisinger KR. Intra-operative evaluation of lumpectomy margins by imprint cytology with histologic correlation: A community hospital experience. Arch Pathol Lab Med 2002;126:846-8.  Back to cited text no. 2  [PUBMED]  [FULLTEXT]
3.Bland and copeland. The Breast. Vol. 1, 3rd ed. 2004. p. 648-9.  Back to cited text no. 3    
4.Gray W, McKee GT. Diagnostic cytopathology. 2nd ed. 2003. p. 251.  Back to cited text no. 4    
5.Jatoi I. Screening clinical breast examination. Surg Clin North Am 2003;83:789-801.  Back to cited text no. 5  [PUBMED]  
6.Shaw EH. The immediate microscopical diagnosis of tumours at the time of operation. Lancet 1910;2:939.  Back to cited text no. 6    
7.Dudgeon LC, Patrick CV. A new method for the rapid microscopical diagnosis of tumours: With an account of 200 cases so examined. Br J Surg 1927;25:250.  Back to cited text no. 7    
8.Abraham SC, Fox K, Fraker D, Solin L, Reynolds C. Sampling of grossly benign breast reexcisions: A multidisciplinary approach to assessing adequacy. Am J Surg Pathol 1999;23:316-22.  Back to cited text no. 8  [PUBMED]  [FULLTEXT]
9.Klimberg VS, Harms S, Korourian S. Assessing margin status. Surg Oncol 1999;8:77-84.  Back to cited text no. 9  [PUBMED]  [FULLTEXT]
10.Cox CE, Ku NN, Reintgen DS, Greenberg HM, Nicosia SV, Wangensteen S. Touch preparation cytology of breast lumpectomy margins with histologic correlation. Arch Surg 1991;126:490-3.  Back to cited text no. 10  [PUBMED]  
11.Saarela AO, Paloneva TK, Rissanen TJ, Kiviniemi HO. Determinants of positive histologic margins and residual tumour after lumpectomy for early breast cancer: A prospective study with special reference to touch preparation cytology. Surg Oncol 1997;66:248-53.  Back to cited text no. 11  [PUBMED]  [FULLTEXT]
12.Klimberg VS, Westbrook KC, Korourian S. Use of touch preparations for diagnosis and evaluation of surgical margins in breast cancer. Ann Surg Oncol 1998;5:220-6.  Back to cited text no. 12  [PUBMED]  
13.Creager AJ, Shaw JA, Young PR, Geisinger KR. Intra-operative evaluation of lumpectomy margins by imprint cytology with histologic correlation: A community hospital experience. Arch Pathol Lab Med 2002;126:846-8.  Back to cited text no. 13  [PUBMED]  [FULLTEXT]
14.Khanna AK, Singh MR, Khanna S, Khanna NN. Fine needle aspiration cytology, imprint cytology and tru-cut needle biopsy in breast lumps: A comparative evaluation. J Indian Med Assoc 1991;89:192-5.  Back to cited text no. 14  [PUBMED]  
15.Scopa CD, Melachrinou M, Apessou D, Bonikos D. Tissue imprints in surgical pathology: A rapid intra-operative diagnostic aid. Diagn Cytopathol 1990;6:5-8.  Back to cited text no. 15  [PUBMED]  
16.Kim K, Philips ER, Paolino M. Intra-operative imprint cytology: Its significance as a diagnostic adjunct. Diagn Cytopathol 1990;6:304-7.  Back to cited text no. 16    
17.Ku NN, Cox CE, Reintgen DS, Greenberg HM, Nicosia SV. Cytology of lumpectomy specimens. Acta Cytol 1991;35:417-21.  Back to cited text no. 17  [PUBMED]  
18.Veneti S, Ioannidou-Mouzaka L, Toufexi H, Xenitides J, Anastasiadis P. Imprint cytology. A rapid, reliable method of diagnosing breast malignancy. Acta Cytol 1996;40:649-52.  Back to cited text no. 18    
19.England DW, Chan SY, Stonelake PS, Lee MJ. Assessment of excision margins following wide local excision for breast carcinoma using specimen scrape cytology and tumour bed biopsy. Eur J Sur Oncol 1994;20:425-9.  Back to cited text no. 19  [PUBMED]  
20.Pinotti JA, Carvalho FM. Intra-operative pathological monitorization of surgical margins: A method to reduce recurrences after conservative treatment for breast cancer. Eur J Gynecol Oncol 2002;23:11-6.  Back to cited text no. 20  [PUBMED]  
21.Dutta SK, Chattopadhyaya A, Roy S. Evaluation of fine needle aspiration and imprint cytology in the early diagnosis of breast lesions with histopathological correlation. J Indian Med Assoc 2001;99:421-3.  Back to cited text no. 21  [PUBMED]  
22.Shidham V, Gupta D, Galindo LM, Haber M, Grotkowski C, Edmonds P, et al . Intra-operative scrape cytology: Comparison with frozen sections, using receiver operating characteristic (ROC) curve. Diagn Cytopathol 2000;23:134-9.  Back to cited text no. 22    
23.Creager AJ, Geisinger KR, Perrier ND, Shen P, Shaw JA, Young PR, et al . Intraoperative imprint cytologic evaluation of sentinel lymph nodes for lobular carcinoma of the breast. Ann Surg 2004;239:61-6.  Back to cited text no. 23    
24.Cendan JC, Coco D, Copeland EM 3rd. Accuracy of intraoperative frozen section analysis of breast cancer lumpectomy bed margins. J Am Coll Surg 2005;201:194-8.  Back to cited text no. 24  [PUBMED]  [FULLTEXT]

Copyright 2006 - Indian Journal of Surgery


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