Concurrent Core Needle Biopsy with Fine Needle Aspiration Biopsy in The Diagnosis of Palpable and Clinically Suspicious Breast Lesions
*Sharmin S,1 Dewan MR,2 Jinnah SA,3 Sharmin R,4 Runa NJ,5 Ambiya AS,6 Rahman N,7 Afrin SS,8 Hussain M9
- *Dr. Shegufta Sharmin, Assistant Professor, Department of Pathology, US Bangla Medical College, Dhaka. sheguftasharmin1982@gmail.com
- Md. Rezaul Karim Dewan, Professor & Head, Department of Pathology, Dhaka Medical College, Dhaka.
- Shahed Ali Jinnah, Associate Professor, Department of Pathology, Dhaka Medical College, Dhaka.
- Rumana Sharmin, Lecturer, Department of Pathology, Dhaka Medical College, Dhaka.
- Nusrat Jahan Runa, Assistant Professor, Department of Pathology, Dhaka Central Inrernational Medical College, Dhaka.
- Ahmed Shahed e Ambiya, Resident Medical Officer, Department of Medicine, Holy Family Red Crescent Medical College Hospital, Dhaka.
- Najibur Rahman, Assistant Professor (Rtd), Department of Pathology, Dhaka Medical College Hospital, Dhaka.
- Syeda Sadia Afrin, Resident, Department of Pathology, Dhaka Medical College Hospital, Dhaka.
- Maleeha Hussain, Professor of Pathology Department, Dhaka Medical College Hospital, Dhaka.
*For correspondence
Abstract
Background: Breast lump is one of the most common surgical problem in female patients. Though excision biopsy of palpable breast lump is considered to be the gold standard method for diagnosis, there should be an improved and definitive method for establishing an accurate diagnosis of breast masses prior to surgery.
Objectives: The aim of this study was to determine the diagnostic accuracy of concurrent fine needle aspiration biopsy (FNAB) and core needle biopsy (CNB) in cases of suspicious breast lesions and to study the discordance between them.
Methods: This descriptive cross sectional study included 72 female patients with breast lumps, presented to Dhaka Medical College Hospital over a period of two years and subsequently underwent concurrent FNAB and CNB in the same sitting. The results were then compared with final histopathological findings and the correlations between FNAB and CNB were determined.
Results: Out of 72 cases included in the study, histopathological diagnosis was available in 42 cases. There were four false negative cases in FNAB (14.28%) and two false negative cases (7.14%) in CNB. The false negative rate in the combined approach was 3.57% which is lower than the rate in individual tests. The sensitivity of combined approach was 96.5%, where FNAB and CNB had 85.71% and 92.85% respectively. The specificity and positive predictive value of both FNAB and CNB were individually 100%, so the concurrent result was also the same. The diagnostic accuracy of combined FNAB and CNB was higher than individual results, which was statistically significant (p<0.05).
Conclusion: Concurrent FNAB and CNB can provide accurate preoperative diagnosis of breast lesions and provide important information for appropriate treatment. Identification of discordant results and, therefore, careful correlation can reduce false negative rate.
[Journal of Histopathology and Cytopathology, 2019 Jul; 3 (2):107-116]
Key Words: Breast lesions, FNAB, CNB, Histopathology
Introduction
Breast cancer is the second most common cancer in the world and the most frequent cancer among women with an estimated 1.67 million new cancer cases diagnosed in developing countries in 2012.1 Breast cancer is the leading cause of cancer death in women in the less developed regions (324,000 deaths, 14.3% of total) and the second cause of cancer death in the more developed countries (198,000 deaths, 15.4%) after lung cancer.2 According to the Globocan estimate, more than half of the 1.67 million new breast cancer cases were diagnosed in developing countries in 2012 which is about 52.9%, whereas the corresponding figure for 1980 was only 35%.3,4 In Bangladesh, the number of new cases of breast cancer in the year 2008 was 17,781.5
Breast cancer usually presents with a palpable breast lump. Most breast lumps are benign and of no serious consequence. Fine needle aspiration biopsy (FNAB) and core needle biopsy (CNB) are both used in the evaluation of breast lesions and play an important role in the management.6 Both have their specific advantages and limitations. Recent studies have shown the high accuracy and cost effectiveness of FNAB to identify cancer in patients with palpable breast lump.7
FNAB is often used as a first priority investigation in patients with breast lump, but this technique is highly dependent on the skill and expertise of the aspirator.8 FNAB cannot confirm the presence of tumor invasion and therefore cannot be used to differentiate between invasive and in situ neoplasia. In addition, low grade breast lesions, such as atypical ductal hyperplasia, ductal carcinoma in situ and tubular carcinoma cannot be accurately diagnosed using this modality alone. Therefore, erroneous diagnosis can occur due to sampling error or due to misinterpretation.
Tru cut biopsy, also known as core needle biopsy (CNB) is now one of the most useful means of obtaining histopathological diagnosis.9 Besides, core biopsy allows the discrimination between in situ and invasive lesions and is a more accurate method to distinguish between invasive ductal and invasive lobular carcinoma.9 A well sampled CNB specimen usually has greater diagnostic efficacy and provides more tissue for ancillary studies.10 However, CNB still has some pitfalls.11 In some cases, even with image guidance, CNB can miss the lesion and yield inadequate material.12 During the procedure, blood vessels may be injured by large bore needles; in such cases the invasive biopsy procedure will only yield clotted blood on repeated puncture.13 In these instances, core biopsies cannot produce adequate samples which in turn will cause a delay in the histological interpretation.
If FNAB and CNB are used concurrently in cases of suspicious breast lesions, the sensitivity and specificity may be better than either alone.
This study was aimed to find out the diagnostic accuracy of concurrent CNB and FNAB of palpable and clinically suspicious breast lesions.
Methods
The present cross sectional study was carried out in the Department of Pathology, Dhaka Medical College over a period of two years from January 2015 to December 2016. Female patients of any age group with clinically suspicious and palpable breast lumps who were advised for FNAB or CNB were enrolled and were subjected to concurrent FNAB and CNB in the same sitting with their informed written consent.
With proper aseptic measures, fine needle aspiration was done using a 5 cc or 10 cc disposable syringe for each puncture and for each patient and two to six smears were prepared in glass slides for each patient according to need. The core needle biopsy was performed by an automated biopsy device equipped with a 14 gauge needle having a sample notch of 15 mm in length. Samples were obtained from different areas of the lesion, usually from the center and close to the borders at the 3, 6, 9 and 12 O’clock positions and were placed in a vial containing 10% neutral buffered formalin. For each CNB procedure, the number of biopsies taken was recorded. The outcomes of FNAB and CNB were reported using the standard National Health Service Breast Screening Programme (NHSBSP) criteria.
In this study, histopathological examination of mastectomy or lumpectomy or excisional biopsy was considered as gold standard. Statistical analysis of the results was obtained by window based computer software devised with Statistical Packages for Social Sciences (SPSS).
Results
A total 72 cases were included in the study in whom FNAB and CNB were performed, and subsequently lumpectomy or mastectomy specimen were available in 42 cases. Histopathological diagnosis was the gold standard of the study. Individual and combined FNAB and CNB were compared and validity test results were calculated. It was observed that the majority (44.4%) of patients belonged to the age group of 31-40 years. The mean age was found 40.94±7.9 years with range from 28 to 62 years (Table I).
More than one third (43%) of the samples were cytologically diagnosed as malignant, 07(9.72%)were diagnosed as suspicious and 09(12.5%) showed atypia. 25(34.72%) cases were cytologically diagnosed as benign(Table II). On the other hand in CNB, 34 (47.2%) cases were found to be malignant cases, 26(36.11) benign , 06 suspicious of malignancy, 05(6.94%) of uncertain malignant potential and 01 (1.38%) unsatisfactory tissue (Table III). Finally, after histopathology of the 42 cases, where surgical biopsy were available, 28(66.66%) cases were confirmed as malignant and 14(33.33%) cases were found to have benign lesions. It was observed that 25(59.52%) patients with duct cell carcinoma was the most frequent diagnosis, followed by 2(4.8%) papillary carcinoma and 1(2.3%) lobular carcinoma (Table IV)
Of the 20 malignant cases and 4 suspicious cases diagnosed by FNAB, all proved to be malignant by histopathology. Among the 05 cases presented with atypia in FNAB, 4 were diagnosed histologically as malignant and 1 was benign. None of the benign cases diagnosed by FNAB was otherwise in histology (Table V).Of the 19 patients diagnosed as malignancy by CNB, 17(79.2%) were diagnosed as duct cell carcinoma, 01(100.0%) as lobular carcinoma and 01(100.0%) as papillary carcinoma by histopathology (Table VI). All 07 suspicious cases in CNB were histologically diagnosed as malignancy and the 04 cases presented with atypia in CNB, ultimately diagnosed as benign in 03 cases and malignant in 01 case (Table VI).
ith concurrent FNAB and CNB, true positive cases were 27 in number, true negative cases were 14 and false negative cases was 1 in number. There were no false positive case (Table VII). In the present study, the sensitivity of FNAB is 85.71%, specificity 100%, PPV (positive predictive value) 100%, NPV (negative predictive value) 77.77% and accuracy 90.47%. In comparison, the sensitivity of CNB is 92.85%, specificity 100%, PPV (positive predictive value) 100%, NPV (negative predictive value) 87.5% and accuracy 95.23%. When both FNAB and CNB are combined, the sensitivity is 96.05%, specificity 100%, PPV (positive predictive value) 100%, NPV (negative predictive value) 93.33% and accuracy 97.61% (Table VIII). So the combined results are superior to FNAB or CNB alone (p<0.05) statistically significant
Discussion
Fine needle aspiration biopsy and core needle biopsy currently are the most widely used methods for pathological diagnosis of breast lumps. They have their specific advantages and limitations. To minimize the limitations of individual procedure, in the current study simultaneous FNAB and CNB was used for the diagnosis of clinically suspicious and palpable breast lumps. Results of the combined approach were compared with FNAB and CNB separately.
With a population of over 163 million, Bangladesh is one of the most densely populated countries in the world.14 Not much information on breast cancer in Bangladesh is available as there is no population based cancer registry in our country. However, the only hospital based cancer registry at the National Institute of Cancer Research and Hospital tracks new cancer cases systematically in this country. According to NICRH report, 5255 breast cancer cases were diagnosed during the period of 2005-2010.15,16 The data of NICRH states that breast cancer has overtaken cervical cancer as the most common female cancer in Bangladesh. (Breast cancer cases 26% and cervical cancer cases 21.1% during the period 2008-2010: NICRH, Cancer registry report).16
In the present study, a total of 72 cases of clinically suspicious and palpable breast lumps were included. FNAB and CNB were done in all of them but surgical biopsy was available in 42 cases only. Of these 42 cases, 28 were malignant and 14 were benign. The firm to hard consistency, irregularity and larger size of the lumps in these 14 benign cases made them to be clinically suspicious. Histopathology was the gold standard in this study and the validity test results of FNAB and CNB were evaluated and compared with it.
In this study, among the 48 cancer patients diagnosed either by core needle biopsy or fine needle aspiration biopsy, age ranged from 33 years to 62 years with a mean age of 42.5 years. In this present study, 26(54.16%) cancer patients out of 48 malignant cases were premenopausal and 22(45.83%) cases were postmenopausal.
Fine needle aspiration biopsy is a routine procedure in the diagnosis of breast lesions in our laboratories. It is a relatively rapid, inexpensive, maintains tactile sensitivity and allows multidirectional passes allowing a broader sampling of the lesions and immediate reporting where it is necessary. However, it has some limitations in the assessment of tumor invasion, tumor grade or receptor status. In this perspect, use of core needle biopsy has been shown to be an excellent tool while working with the tissue specimens because it permits the evaluation of both the architectural and cytological patterns and provides adequate material to perform diagnostic ancillary studies.
However, the performance of CNB has a few disadvantages. Missampling can occur, even with image guidance.12 Improper processing of small tissue fragments may lead to tissue distortion and challenge sample adequacy. These technical errors or missampling can lead to false negative results. The study showed that the sensitivity of FNAB was 85.71% in the diagnosis of breast cancer with a false negative rate of 14.28%. The specificity was 100%. This result is similar to other studies done by Mahmood H. Hasssan in Iraq (2014).17 Mohammed Bdour et al (2008) in Pakistan18 and Tiwarie M. in Nepal (2007).19
All four false negative cases in FNAB belonged to proliferative breast disease with atypia group. The false negative results of FNAB were mainly due to underestimation of cellular atypia.
In our study, CNB had a sensitivity of 92.85% and specificity of 100% in the diagnosis of breast cancer. The false negative rate was 7.14%. The results are comparable to others studies done by Mahmood H. Hasssan in Iraq(2014),17 Mohammed Bdour in Pakistan (2008),18 Karimian F. in Iran (2008),9 AD Baildum in UK (1989)19 and Stanley Minkowitz in USA (1986)20 which showed 95.0%, 90.0%, 98.07%, 95.0% and 89.0% sensitivity, respectively .
We found that, there were two false negative cases in CNB. Out of the two cases, one showed cystic change in ultrasonography. The repeated missing of the lesion in core biopsy may be due to this cystic change. . In this case as FNAB could cover much more area, it yielded adequate material from solid area.
Though accuracy of CNB is superior to FNAB,to minimize the limitation, the aim of pathologist should be to diagnose all the breast cancers confidently and not a single case should be missed. With this aim, the concurrent FNAB was done in this study and it showed sensitivity of 96.5%. In this present study, the number of cores taken from each patient was four or above. The combined approach of FNAB and CNB yielded better diagnostic accuracy than FNAB and CNB alone. The sensitivity of combined approach is 96.5%, where FNAB and CNB had 85.71% and 92.85% respectively. The specificity and positive predictive value of both FNAB and CNB are individually 100%, so the concurrent result is also the same. The 100% specificity of FNAB or CNB should not be generalized for all breast lesions in this study, because all the cases in the present study had breast lumps more than 2 cm in size and all were palpable.
The false negative rate in the combined approach was 3.57% which is lower than the rate in individual tests (14.28% in FNAB and 7.14% in CNB). A false negative diagnosis may delay the treatment of breast cancer. The concurrent examination of FNAB and CNB reduced the false negative rate by 50 %(7.14% to 3.57%), in comparison to CNB alone.
Conclusion
It is established that CNB is superior to FNAB regarding sensitivity and specificity. 9,10,11,13 In our country with poor resource setting, guided FNAB and CNB are not always possible. So to increase the sensitivity and to reduce the numbers of false negative cases of CNB, combined approach are helpful.
Reference
1. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D and Bray F. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. International journal of cancer, 2015;136(5):359-86.
2. Globocan, IARC 2012 IARC, 2012. Latest world cancer statistics Global cancer burden rises to 14.1 million new cases in 2012: Marked increase in breast cancers must be addressed. http://globocan.iarc.fr.
3. IARC, 2012. Latest world cancer statistics Global cancer burden rises to 14.1 million new cases in 2012: Marked increase in breast cancers must be addressed. http://globocan.iarc.fr.
4. Forouzanfar MH, Foreman KJ, Delossantos AM, Lozano R, Lopez AD, Murray CJ and Naghavi M, Breast and cervical cancer in 187 countries between 1980 and 2010: a systematic analysis. The lancet, 2010; 378(9801):1461-84.
5. IARC, 2008. World cancer report 2008. International Agency for Research on Cancer. http://globocan.iarc.fr/
6. Cochrane RA, Singhal H, Monypenny IJ, Webster DJT, Lyons K and Mansel RE. Evaluation of general practitioner referrals to a specialist breast clinic according to the UK national guidelines. European Journal of Surgical Oncology (EJSO), 1997; 23(3):198-201.
7. Touhid Uddin Rupom, Tamanna Choudhury, Sultana Gulshana Banu. Study of Fine Needle Aspiration Cytology of Breast Lump:Correlation of Cytologically Malignant Cases with their Histological Findings. BSMMU J, 2011;4(2):60-64.
8. Yong WS, Chia KH, Poh WT and Wong CY. A comparison of trucut biopsy with fine needle aspiration cytology in the diagnosis of breast cancer. Singapore medical journal, 1999;40(9):587-89.
9. Karimian F, Aminian A, Hashemi E, Meysamie AP, Mirsharifi R and Alibakhshi A. Value of core needle biopsy as the first diagnostic procedure in the palpable breast masses. Shiraz E Medical Journal, 2008;9(4):188-192.
10. Pieter J, Westenend Ali R, Sever, Hannie JC., Beekman-de Volder et al. A comparison of Aspiration Cytology and Core Needle Biopsy in the evaluation of breast lesions. Cancer cytopathol 2001,93:146-150.
11. Liberman L, Dershaw DD, Rosen PP, Giess CS, Cohen MA, Abramson AF and Hann LE. Stereotaxic core biopsy of breast carcinoma: accuracy at predicting invasion. Radiology, 1995;194(2):379-81.
12. Yao-Lung Kuo, Tsai-Wang Chang. 2010, :Can concurrent core biopsy and fine needle aspiration biopsy improve the false negative rate of sonographically detectable breast lesions? BMC cancer, 2010;10(371):1-7.
13. Berner A, Davidson B, Sigstad E, Risberg B. Fine needle aspiration cytology vs. core biopsy in the diagnosis of breast lesions. Diagnostic cytopathology, 2003;; 29(6):344-8.
14. CIA. The world factbook; 2014.
15. NICRH. Cancer Registry Report National Institute of Cancer Research and Hospital 2005-07; 2009.
16. NIRCH. Cancer Registry Report National Institute of Cancer Research and Hospital 2008-2010; 2013.
17. Mahmood H. Hassan Ahmed R, HizamSafa, M. Al-Obaidi. The role of Tru-cut needle biopsy in the diagnosis of palpable breast masses. J Fac Med Baghdad, 2014;56: 292-295.
18. Mohammed Bdour, Saleh Hourani, WaseemMefleh, Ashraf Shabatat, Samer K.A. Radsheh, et al. Comparision between Fine needle aspiration cytology and Tru-cut biopsy in the diagnosis of breast cancer: Journal of surgery Pakistan international 2008: 13; 19-21.
19. Tiwari M. Role of fine needle aspiration cytology in diagnosis of breast lumps.Kathmundu University Medical Journal, 2007;5:215-17.
20. Baildam AD, Turnbull L, Howell A, Barnes DM and Sellwood RA, 1989. Extended role for needle biopsy in the management of carcinoma of the breast. British Journal of Surgery, 1989;76(6):553-58.
21. Stanley Minkowitz, Robert Moskowitz, Rene A., Khafif Martha N, Tru-cut needle biopsy of the breast and analysis of its specificity and sensitivity. Cancer 1986;15;320-323.