Cytohistological correlation and effectiveness of FNAC as Single Primary Diagnostic Modality in Palpable Breast Lesions
Vindu Srivastava1, Josephine Arun2, Sai Sudha Muddha3, Krishna Prasanth B4
1Professor of Pathology, Sree Balaji Medical College and Hospital, Bharath Institute of Higher Education &
Research
2Associate Professor of Pathology, Sree Balaji Medical College and Hospital, Bharath Institute of Higher Education & Research
3Assistant Professor of Pathology, Sree Balaji Medical College and Hospital, Bharath Institute of Higher Education & Research
4Epidemiologist & Assistant Professor of Community Medicine,Sree Balaji Medical College and Hospital, Bharath Institute of Higher Education & Research
ABSTRACT
The aim of this study is to evaluate cytohistological features of palpable breast lesions and to assess the diagnostic accuracy of FNAC of the breast lesions when compared with corresponding histopathological findings. This will justify the usefulness of FNAC as an accurate first step technique in the diagnosis of palpable breast mass. Breast mass is the most common presentation of breast disease and main reason for women seeking medical opinion. The mass can be inflammatory, benign or malignant. A prompt evaluation and diagnosis is essential to rule out malignancy and alleviate anxiety. Triple test, a combination of clinical, radiological and cyto-pathological assessment is considered to be the gold standard in making a definitive diagnosis of breast lumps. But all centers may not have imaging facilities. Tissue biopsy is an invasive procedure requiring preparation and expertise.FNAC offers valuable first step diagnostic option because of ease of procedure, minimal discomfort, no preparation required and shorter turnaround time for the report. It has high patient acceptance. Shorter turnaround time with same day report ensures further spot decisions in patient management. It also reduces health cost by obviating other investigations .All these factors favour FNAC as a primary diagnostic modality in resource limited medical centers.
Keywords: FNAC, Palpable breast mass, Malignancy, Accuracy, Biopsy.
Corresponding author- Dr.Josephine Arun MD Pathology , Associate Professor of Pathology Sree Balaji Medical college and Hospital, #07 Works road , Chrompet,Chennai-600044,TN, India
INTRODUCTION
Palpable breast mass is the most common presentation of breast lesion and makes a patient to seek medical attention [1,2]. The mass can be inflammatory, benign or malignant. Carcinoma breast is one of the most common malignancy in women, causing significant morbidity and mortality. It is the second most cause of cancer related death in women [3] . Rapid Diagnosis is essential to exclude malignant lesion and plan further management. Fortunately, most breast masses are non-malignant. The most common benign mass is Fibroadenoma, common in women less than 35 years [4]. Breast abscess can present as a breast mass and is common in 10%-33% of lactating women [5] .Granulomatous mastitis can present as mass and clinically mimic carcinoma, the most common cause being tuberculosis in developing countries like India. Diabetic women and those with immune suppression are at high risk [6]. Breast cysts are more common in the age group of 35-50 yrs
[7]. Benign proliferative lesion presenting as breast mass also includes usual and atypical ductal hyperplasia.
Usual ductal hyperplasia is seen in 1 in 4 women, atypical ductal hyperplasia is seen in 1 in 25 women [7]. The combination of FNAC, clinical breast examination and radiological evaluation now called Triple test (diagnostic triad) has increased the diagnostic accuracy of breast lesions. When all the above three modalities favour a benign or malignant diagnosis, the diagnostic accuracy is close to 100% [8]. FNAC is the widely used pathological assessment in diagnosis of palpable breast lesions because of its high diagnostic accuracy and good patient acceptance[9,10]. The main role of FNAC is to differentiate benign lesions from malignant lesions of the breast, as the treatment varies in these two entities.
Mammography and or ultrasound may not be available in all centres. CNB is an invasive procedure requiring preparation and expertise. FNAC offers a useful first line of investigation especially in resource the limited centre. The resource limitation can be lack of imaging facilities, access to medical centre, financial/lack of insurance, socio-economical, psychological and cultural. In such scenario, for patient seeking medical opinion for palpable breast mass, FNAC can be performed immediately as a outpatient procedure. FNAC can be used as reliable and valuable diagnostic technique in the initial evaluation of palpable breast lumps. It is simple, cost effective, safe and with minimal or no complications [11,12].It is minimally invasive with good patient acceptance with Short turnaround time. The patient can avail the report on the same day and further planning of treatment can be done onspot .This is an advantage in rural and remote areas.FNAC can be easily done in patient with medical disease or on medication, in whom invasive procedure may pose a high risk. By giving accurate pre-operative diagnosis FNAC also obviates unnecessary biopsies, an another advantage in centres with resource limitations. There are inherent false positives and false negatives. Inadequate aspirate is usually due to faulty techniques .The reporting pathologist must be aware of these pitfalls, which will require discussion with the clinicians and plan for tissue biopsy to arrive at a diagnosis.
The present study was undertaken to evaluate the cytological findings of FNAC done on patients with a palpable breast mass in the outpatient and compare with histopathology studies available for those who underwent biopsy for the same lesion.
MATERIALS AND METHODS
A total number of 154 cases presenting with a palpable breast mass in the outpatient department were included in this study, done over a period of 14 months. Informed consent was taken prior to the procedure. Aspiration was carried out by using 10cc syringe, 23 gauge needle from the mass under aseptic precautions. Needle contents were smeared over the pre-labelled glass slides. In case of cystic swellings, aspirated fluid was centrifuged and slides were prepared from the sediment .Smears were fixed in ethanol and stained with H& E stain. Cyto-morphological features of aspirates are studied in detail. Histopathological diagnosis was available for 68 cases who had undergone a biopsy of the mass after the FNAC.FNAC results were compared with histopathological diagnosis. Sensitivity, specificity , positive predictive value and negative predictive value were derived to estimate the diagnostic accuracy of FNAC findings.
OBSERVATION AND RESULTS
In this study age of the patients ranged from 17 – 76 years. All were females. Most Women presented with breast mass were in the age group of 31-40 yrs.(TABLE 01) Right breast was more commonly affected (98cases).
Table 1 : Age of 154 patients of breast lesions
Age group Number of cases
10-20 8
21-30 38
31-40 39
41-50 34
51-60 21
61-70 9
>70 5
In the present study out of 154cases subjected to FNAC, 130cases were non- malignant lesions(84%), 22 cases were malignant breast lesions(14%) and 02 cases were reported as inadequate (2%).Among benign breast mass, Fibroadenoma was the most common lesion account for 67 cases(52%), followed by 29cases of Fibrocystic disease(22%), Acute inflammatory mastitis 11cases( 9%), Ductal hyperplasia 10 cases(7%), 06 cases of Non- neoplastic simple cyst (5%), Granulomatous mastitis 5 cases (4%), and 2 cases of Fat necrosis (1%)[ Table 2].
Table 2 : FNAC diagnosis of 130 Benign breast lesions
Benign lesion Number
of cases
Percentage
Fibroadenoma 67 52%
FCD 29 22%
Acute inflammatory mastitis 11 9%
Duct hyperplasia 10 7%
Simple cyst 6 5%
Granulomatous mastitis 5 4%
Fat necrosis 2 1%
Out of 154 cases , 68 patients had tissue biopsy of breast mass during the period of study and histopathology report was available from correlation . Out of 16 cases reported as malignant in cytology, all were malignant in histology also( True positive). Out of 52 cases reported as benign in cytology, 2 cases were found to be malignant in histology (False negative rate - 3.03% ) [Table 3 ,4] . Sensitivity of the test was 88.88%, Specificity was 100% and overall diagnostic accuracy was 97.05% [Table 5].
Table 3: Cytohistological correlation of all breast lesions Table 4: Analysis of results Histopathology diagnosis Total
FNAC diagnosis Benign lesions Malignant lesions
Benign lesions 50 2 52
Malignant lesions 0 16 16
50 18 68
Table 5 : Diagnostic validity of FNAC Diagnostic validity Percentage
Sensitivity 88.88%
Specificity 100%
Positive predictive value 100%
Negative predictive value 96.15%
False positive rate 0%
False negative rate 3.03%
Overall diagnostic accuracy 97.05%
DISCUSSION
In 1930s the Memorial hospital , New York , United states was recorded for the earliest large scale use of FNAC as a diagnostic tool in the management of palpable masses but it didn’t gain importance during the
True positive 16
False positive 0
True negative 50
False negative 2
ensuing years[13]. The technique had resurgence in scandivania during the 1950s and 1960s. True FNAC for breast aspirations were first introduced by Franzen and Zajicek at karolinska hospital in Stockholm. Later in 1980s FNAC gain importance and became the widely used procedure [14].
In the current study, FNAC was done in 154 patients, out of which histopathology was available in 68 cases. By correlating FNAC results with histopathology diagnostic accuracy of FNAC was calculated .In the present study, most women presenting with a palpable breast mass were in the age group of 31-40 yrs, this was similar to studies done by kumar R[15]. The oldest female was 76 years and diagnosed as Infiltrating duct cell carcinoma, NOS and the youngest patient 17 years was diagnosed as Fibroadenoma. Similar results were observed in other studies conducted by kumar R[15], Pinto RG[16] and Ahmed HG[17]. Out of 154 cases subjected to FNAC 130 were benign breast mass (84%) , this finding was similar to studied done by IshithaP[18], Y D Choi[19], Ashwin et al[20] and Anshulekha et al [21] [Table 6]. Fibroadenoma was the most common benign breast lesion observed in our study(52%) followed by Fibrocystic disease (22%).similar results were observed in other studies conducted by shirish et al[22], Farkhanda et al[23] and Tiwari M [24].
Table 6: Comparative analysis of breast lesions
Breast lesions Ishita pant[18] Y D Choi[19] Ashwin[20] Anshulekha[21] Present study
Benign 68% 75.64% 77.24% 79.84% 84.4%
Malignant 20% 14.03% 18.4% 20.15% 14.3%
The diagnosis of fibroadenoma was made based on the presence of cohesive clusters of duct epithelial cells and fibromyxoid stroma and plenty of bare bipolar nuclei in the background [Figure 01]. In few cases(n=5) the diagnosis of suggestive of fibroadenoma was made when there is either one or two of the above characteristic features of fibroadenoma. 4 cases of fibroadenoma also show degenerative changes like cyst macrophages, giant cells and mild nuclear atypia. Presence of marked nuclear atypia in cases of fibroadenoma makes it a pit falls or common cause of a false positive diagnosis on breast FNAC [25]. In our study none of the cases show marked nuclear atypia. In the present study, 29 cases were diagnosed as Fibrocystic disease based on the cyto- morphological features like presence of apocrine cells, cyst macrophages and benign duct epithelial cells[
Figure 02].In our study , 11 cases of Acute mastitis were diagnosed on FNAC. Cytology showed presence of
acute inflammatory infiltrate of neutrophils. Few cases showed giant cells, and suppurative necrosis also [ Figure03].
Figure 1: Fibroadema breast showing cohesive clusters of duct epithelial cells (H&E, 10X)
Figure 2 : Fibrocystic Disease with apocrine cells and foamy macrophages (H&E, 10X)
Figure 3 : Acute Mastitis showing plenty of polymorphs ( H&E, 45X )
Granulomatous mastitis was diagnosed in 5 cases in our study. Cytology showed the presence of epitheloid granuloma, clusters of bland duct epithelial cells and chronic inflammatory cell composed of lymphocytes and plasma cells in the background [ Figure 04]. Ziehl Nielsen staining with 20% sulphuric acid, failed to demonstrate the organisms in all five cases.
Figure 4: Granulomatous Mastitis showing epitheloid cell clusters and multinucleated giant cells. (H&E 10X)
The diagnosis of simple cyst was made in 6 cases, in which smears showed plenty of cyst macrophages and few inflammatory cells . In one case complete disappearance of swelling was noticed after aspiration of the cyst fluid.
10 cases diagnosed as Duct hyperplasia on FNAC. Cellular smears showed large sheets of cohesive epithelial cells. Cells show focal crowding and overlapping of nuclei without nuclear atypia. Two cases of fat necrosis was diagnosed in our study. cytology revealed fat droplets, numerous foamy macrophages and background shows granular debris.
Among the malignant lesions, Infiltrating carcinoma, NOS was the common lesion, which was supported by other studies by Ashwin et al(20) and Anshulekha et al [21]. Cytology revealed cellular smears with loosely cohesive clusters of epithelial cells exhibiting nuclear atypia and absence of myoepithelial cells[ Figure 5]. One case showed predominantly discretely arranged plasmacytoid cells in the smears.
Figure 5 : Infiltrating Duct Cell Carcinoma Showing dyscohesive clusters of malignant duct epithelial cells.( H&E, 45X)
Out of 130 benign breast lesions in FNAC, 52 patients had biopsy done and reports available for correlation.
Histopathology confirmed 50 cases to be benign breast lesions and two cases turned out to be malignant lesions.
Both cases were reported as Ductal hyperplasia in cytology found to be infiltrating carcinoma, NOS in histopathology. Study conducted by Anshulekha patel et al[21]also shows similar results. Out of 22 malignant lesions reported in FNAC, biopsy was done in 18 patients. Histopathology confirmed malignancy in all 18 cases with cytohistological concordance of 100%.
In FNAC both false positive and false negative can occur[26].Hypocellularity, degenerated cells, necrosis and epithelial hyperplasia are the common factors associated with False positive diagnosis. The false positive rate is significantly lower when compared to false negative diagnosis. The false negative cases of breast in FNAC are commonly due to poor sampling technique, small tumour size, deeply localized tumour and presence of well differentiated histology of the tumour. Hence all these factors should be considered while interpretation FNAC benign breast lesions.
The present study achieved 100% positive predictive value with no false positive and 3.03% false negative rate, which is comparable with Ashwin[20], Anshulekha[21] , David [27]et al and Madubogwu[28] . Our study achieved accuracy of 97.05% which is again similar to studies conducted by Ashwin[20], Anshulekha[21] and David E et al[27] .(Table 07)
Table 7: Comparative analysis of diagnostic validity of breast lesions by different authors
Study Sensitivity Specificity PPV NPV Accuracy
Y D Choi[19] 77.7 99.2 98.4 88 91.1
Ashwin[120] 96.97 100 100 98.63 99.05
Anshulekha[21] 97.46 100 100 100 99.02
Madubogwu[28] 90.0 95.5 94.7 91.3 92.9
David e et al[27]
99.4 100 100 66.7 99.37
Present study 88.88 100 100 96.15 97.05
CONCLUSION
FNAC is safe, reliable and cost effective outpatient procedure, especially in resource limited centres. FNAC has high sensitivity, specificity and diagnostic accuracy in identifying and differentiating benign from malignant breast mass. The pathologist must be aware of inherent False positives and false negatives associated with a diagnosis of malignant mass. This must be effectively communicated to the clinicians for planning further tissue biopsy. FNAC therefore can be used as the first step in management and further planning of breast cancer .This can further help reduce significant mortality and morbidity that is associated with cancer breast.
ABBREVIATIONS USED:
FNAC – Fine Needle Aspiration Cytology CNB – Core Needle Biopsy H&E- Hematoxylin and Eosin
REFERENCES:
[1] SR Orell, GF Stenet, Max N-J Walters, D Whitaker Manual and Atlas of Fine needle aspiration cytology 3rdedition.London, Churchill Livingstone; 1999;1-8.
[2] Khemka A, Chakrabarthi N, Shah S, Patel V. Palpable breast lumps: Fine needle aspiration cytology versus histopathology: A correlation of diagnostic accuracy. Int J Surg 2009; 18:1.
[3] Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA CANCER J Clin.2019 jan. 69 (1): 7-34.
[4] Kaneda HJ, Mack J, Kasales CJ, Schetter S. Pediatric and adolescent breast masses: a review of pathophysiology, imaging, diagnosis and treatment. AJR Am J Roentgenol.2013 Feb.200(2): W204 -12 [5] Givens ML, Luszczak M. Breast disorders: a review for emergency physicians. J Emerg Med. 2002
Jan. 22(1): 59-65.
[6] Dixon JM. Breast infection. BMJ .2013 Dec 16. 347: f3291.
[7] American cancer society. Breast cancer facts and figures 2009-2010. American cancer society.
Available at http://www.cancer.org/Research/CancerFactsFigures/BreastCancerFactsFigures/breast- cancer-facts--figures-2009-2010. Accessed: Feb 1, 2010.
[8] Wells CA, Ellis IO, Zakhour HD, Wilson AR. Editorial working party, Cytology subgroup of the National Co-ordinating Committee for breast cancer screening pathology. Guidelines for cytology procedures and reporting on fine needle aspirates of the breast. Cytopathol . 1994;5(5):316-334.
[9] Dixon JM, Anderson TJ, Lamb J, Nixon SJ. Fine needle aspiration cytology in relation to clinical examination & mammography in the diagnosis of solid breast masses. British journal of surgery 1984;7:593-596.
[10] Jindal U, Singh K, KochharA . Fine needle aspiration cytology of breast lumps with histopathological correlation : A Four year and eight month study from rural india. Internet J Pathol.2012;13(3).
[11] Nguansangiam S, Jesdapatarakul S, Tanjitgamol S. Accuracy of fine needle aspiration cytology from breast masses in Thailand. Asian Pac J Cancer Prev 2009; 10: 623-26.
[12] Kalhan S, Dubey S, Sharma S, Dudani S, Preethi, Dixit m. Significance of nuclear morphometry in cytological aspirates of breast masses. J Cytol 2010; 27:16-21.
[13] Das DK. Fine needle aspiration cytology : Its origin, development and present status with special reference to a developing country, India. Diagncytopathol . 2003; 28(6): 345-351.
[14] Franzen S, Zajicek J. Aspiration biopsy in the diagnosis of palpable lesions of breast: critical review of 3479 consecutive biopsies. ActaradiolTherPhys Biol. 1968;7:241-262.
[15] Kumar R, A clinicopathological study of breast lumps in Bhairahwa Nepal. Asian Pac J Cancer Prev.2010;11(4):855-8.
[16] Pinto RG, Kulwant S. A statistical analysis of fine needle aspiration cytology in palpable benign (neoplastic and non neoplastic ) breast lesions JCytol 2004;21:64.7.
[17] Ahmed HG, Ali AS, Almobarak AO. Utility of fine needle aspiration as a diagnostic technique in breast lumps. Diagncytopathol. 2009 Dec;37(12):881-4.
[18] Ishitha P Singh PK. Cytomorphologicstudy of palpable breast lesions and histopathologic correlation . J Cytol 2002;19:18 7 – 92.
[19] Y D Choi, Y H Choi, J H Lee, J H Nam, S W Juhng, C Choi. Analysis of fine needle aspiration cytology of breast: A review of 1297 cases and correlation with histological diagnosis . ActaCytol 2004;48(6): 801-806.
[20] AshwinPattanshettyKhageshan et al, Diagnostic utility of FNAC in Evaluation of breast masses.
International journal of recent scientific research Vol 6, Issue 8 5827-5831, August 2015.
[21] Anshulekhapatel, TapaswiniBhuyan, R.C.Mohanty, Raghumanymohanty. Diagnostic utility of FNAC in breast lesions and its correlation with histopathology. IOSR-JDMS. Volume 17, Issue 2 ver, 13 February 2018, PP 31-40.
[22] Shirishchandanwale, MohitRajpal, PradeepJadhav, Sonamsood, Kanika Gupta, Nidhigupta. Pattern of benign breast lesions on FNAC in consecutive 100 cases: A study at tertiary care hospital in India.
IJPBS, Volume 3, Issue 4, OCT-DEC 2013 : 129-138.
[23] Farkhanda JD, Muhammad SA, Ahsan AL, Noor MK, Imtiaz S, Zulfiqar IM. An early diagnosis of benign breast diseases. Journal of surgery, Pakistan 2010;15(4): 74-78.
[24] Tiwari M. Role of fine needle aspiration cytology in diagnosis of breast lumps. Kathmandu university medical journal 2007;5(2):215-217.
[25] Orell SR, Farshid G. False – positive reports in fine needle biopsy of breast lesions. Pathology 2011;33:428-436.
[26] Bukhari MH, Arshad M, Jamal S, et al. use of fine needle aspiration in the evaluation of breast lumps.
Patholog Res Int.2011::689521.
[27] David E Ibikunle, John A Omotayo, Olufemi O Ariyibi. Fine needle aspiration cytology of breast lumps with histopathologic correlation in Owo, Ondo state, Nigeria: a five year review. Ghana Med J.2017 Mar;51(1):1-5.
[28] CI Madubogwu, CO Ukah, SNC Anyanwu, GU Chianakwana, IV Onyiaorah and DCD Anyiam. Sub- classification of breast masses by Fine needle aspiration cytology. Eur J Breast Health. 2017 Oct
;13(4): 194-199.
