|Year : 2020 | Volume
| Issue : 1 | Page : 5-9
Diagnostic pitfalls in the fine needle aspiration cytology of the breast
Prema Saldanha1, Farhana C Kannoli2
1 Department of Pathology, Yenepoya Medical College, Mangaluru, Karnataka, India
2 DDRCSRL Diagnostics Services, Kozhikode, Kerala, India
|Date of Submission||28-Apr-2020|
|Date of Acceptance||07-May-2020|
|Date of Web Publication||06-Jun-2020|
Dr. Prema Saldanha
“Flushing Meadows,” Pandeshwar, Mangalore 575001, Karnataka.
Source of Support: None, Conflict of Interest: None
Background: Fine needle aspiration cytology (FNAC) of the breast is a reliable, simple, minimally invasive, cost-effective procedure with high sensitivity, specificity, and diagnostic accuracy. It is commonly used for the assessment of breast lesions and as a guide to preoperative evaluation and management. Objective: The objective of this study was to assess the accuracy of fine needle aspiration of the breast and critically evaluate the cases, which showed discordance between cytology and histopathology. Materials and Methods: This is a retrospective study of cases of FNAC done for breast lumps. The slides were retrieved from the archives of the Pathology Department. Breast cytology findings were reported according to the six standard categories—positive for malignancy, suspicious for malignancy, atypical, proliferative without atypia, benign/unremarkable, and unsatisfactory. The FNAC findings were correlated with the histopathology diagnosis. Cases showing cytological and histological disparity were reevaluated for the detection of possible causes of the discrepancy. Results: The study consisted of 100 cases. For the diagnosis of carcinoma, the sensitivity was found to be 92.9%, specificity was 100%, positive predictive value was 100%, negative predictive value was 97.2%, and the total accuracy was 99%. False positives were not seen, and two cases were false negatives. Suboptimal material, lack of extensive sampling, and absence of all the characteristic features caused under diagnoses were recognized as common pitfalls. Conclusion: This study highlights the causes of cytological pitfalls. Strict adherence to the proposed criteria and extensive sampling of the lesions are of paramount importance in reducing the number of false-positive and false-negative cases.
Keywords: Breast, fine needle aspiration cytology, pitfalls
|How to cite this article:|
Saldanha P, Kannoli FC. Diagnostic pitfalls in the fine needle aspiration cytology of the breast. MGM J Med Sci 2020;7:5-9
|How to cite this URL:|
Saldanha P, Kannoli FC. Diagnostic pitfalls in the fine needle aspiration cytology of the breast. MGM J Med Sci [serial online] 2020 [cited 2022 Aug 13];7:5-9. Available from: http://www.mgmjms.com/text.asp?2020/7/1/5/286109
| Introduction|| |
Fine needle aspiration cytology (FNAC) of the breast is a reliable, simple, minimally invasive, cost-effective procedure with high sensitivity, specificity, and diagnostic accuracy. FNAC has been used routinely as a useful and indispensable tool in the preoperative diagnosis of breast lesions. FNAC has been shown to be able to categorize lesions as benign and malignant, and hence has been able to guide therapeutic protocols. Like any other diagnostic procedure, FNAC has its limitations. There is some “gray zone” where the diagnostic efficacy declines sharply, rendering it difficult to exactly categorize the lesions, resulting in the discrepancy in the diagnosis between benign and malignant lesions.,,,, The aim of the study was to assess the accuracy of fine needle aspiration of the breast and critically evaluate the cytohistologically discordant cases.
| Materials and methods|| |
This is a retrospective study of 100 consecutive cases of breast FNAC. The aspiration was done using a 22G needle and a 10-mL syringe. In cases of unsatisfactory samples, the aspiration was repeated using a 21G needle. In cases with small or ill-defined nodules, ultrasonographic guidance was used. The smears were fixed in absolute methanol and stained with Papanicolaou stain. Relevant clinical details and mammographic findings if available were recorded.
The FNAC findings were reported according to the classification, which includes six categories, that is, positive for carcinoma, suspicious for carcinoma, an epithelial proliferative lesion with atypia, epithelial proliferative lesion without atypia (benign with specific diagnosis), unremarkable (benign with no specific diagnosis), and nondiagnostic/unsatisfactory.,
Diagnosis of positive for carcinoma was considered when all four of the following criteria were met: (1) Cellular dyshesion, (2) cytologic atypia, (3) one-cell population, and (4) hypercellularity (referring to the atypical cell population only). The FNAC findings were correlated with a needle biopsy/lumpectomy/mastectomy diagnosis. Cases showing cytohistological disparity were reevaluated for the detection of possible causes of the discrepancy.
| Results|| |
The study consisted of 100 cases. The patients were in the age-group of 14–76 years. There were three male patients. There were 21 cases in the positive for carcinoma category, in which typing was possible on FNAC in 16 cases as invasive ductal carcinoma. In carcinoma breasts, the smears are moderate to highly cellular, showing only a single population of epithelial cells without any myoepithelial cells. The cell clusters show a loss of cohesion. Individual cells show moderate to severe nuclear atypia with enlargement, polymorphism, irregular chromatin, and nuclear membranes. Single cells with intact cytoplasm can also be seen [Figure 1] and [Figure 2].,
|Figure 2: Cell clusters show loss of cohesion and composed of cells showing moderate nuclear enlargement, pleomorphism, and irregular chromatin. Single cells with intact cytoplasm are also seen (Pap ×40)|
Click here to view
These were confirmed as invasive ductal carcinoma by histopathological examination (HPE) in 14 cases, and in one case each, the diagnosis on HPE was medullary and atypical medullary carcinoma, respectively. There were five cases suspicious for carcinoma [Figure 3] and two cases of proliferative lesions with atypia, which were diagnosed as carcinoma on HPE.
|Figure 3: A cell cluster showing a single population of cells with mild nuclear pleomorphism, which is suspicious for carcinoma (Pap ×10)|
Click here to view
There were 70 cases in the benign category, 38 cases of which were epithelial proliferative lesions without atypia (benign with specific diagnosis), and 32 cases that were benign with no specific diagnosis. Fibroadenoma shows cellular smears with a bimodal pattern containing epithelial component in the form of large, branching sheets of bland epithelial cells, numerous single, bare bipolar nuclei [Figure 4] and [Figure 5], and fragments of fibromyxoid stroma.
|Figure 4: A cellular smear of composed fragments of ductal epithelium and single bipolar nuclei in the background (Pap ×10)|
Click here to view
|Figure 5: A monolayered sheet of regularly arranged cells with uniform nuclei with interspersed myoepithelial cells (Pap ×40)|
Click here to view
In two cases, the aspirate was unsatisfactory due to the lack of cellularity. In 16 cases, a discrepancy was observed in the cytological and histopathological correlation. Cases with a discrepancy in the cytology and histopathology reports are shown in [Table 1]. The sensitivity for the diagnosis of malignancy was found to be 92.9%, specificity was 100%, positive predictive value was 100%, negative predictive value was 97.2%, and the total accuracy was 97.9%. False positives were not seen, and two cases were false negative.
| Discussion|| |
A breast lump is the most common presentation of breast diseases. The most accepted protocol followed for breast lumps is “triple assessment,” which includes clinical assessment, radiological imaging, and pathological diagnosis. As FNAC forms the most important aspect of cytopathology as a part of triple assessment, it is expected to be an efficient technique that can be relied on in terms of avoiding unnecessary surgery and discomfort during an open biopsy for preoperative diagnosis.,,
FNAC may be regarded as a preliminary diagnostic procedure, as a screening procedure, or as a follow-up procedure for postmastectomy or lumpectomy. Accuracy in the diagnosis can be increased by multiple sampling of appropriate sites by ultrasonography guidance and/or mammographic localization. FNAC can also be used to diagnose lesions of male breasts, such as gynecomastia and carcinoma, accessory breast tissue, and status of the axillary lymph nodes in cases of malignancy.
Guidelines were laid down in 1992 by the National Health Service Breast Screening Programme (NHSBSP), UK, and were further modified in 1996 by the National Cancer Institute, Maryland, USA. These guidelines had proposed five categories to report breast lesions on FNAC, namely inadequate (C1), benign (C2), atypia probably benign (C3), suspicious of malignancy (C4), and malignant (C5).,
However, currently the preferred classification for reporting the FNAC findings includes six categories, positive for carcinoma, suspicious for carcinoma, an epithelial proliferative lesion with atypia, epithelial proliferative lesion without atypia (benign with specific diagnosis), unremarkable (benign with no specific diagnosis), and nondiagnostic/unsatisfactory.,
It has been assumed that for better accuracy, the diagnosis of positive for carcinoma may only be considered when all four of the following criteria were met—(1) cellular dyshesion, (2) cytologic atypia, (3) one-cell population, and (4) hypercellularity (referring to atypical cell population only).
Several studies show similar sensitivity and specificity, the details of which are given in [Table 2].
The success rate of FNAC for obtaining a definite diagnosis also depends both on the palpability and the size of the lesion. False-negative diagnoses remain unavoidable and may delay the diagnosis and treatment of breast cancer. The most common reasons for false-negative diagnoses are represented by technical or sampling errors. Among the false-negative factors, some of the major denominators are inadequate sampling, mislocalization of the tumor, or the presence of a well-defined tumor showing only minimal atypia. The widespread adoption of breast screening and advances in imaging techniques has resulted in the detection of very small lesions, causing difficulties in sampling. Technical difficulties with deeply located or densely fibrotic lesions can also cause inaccurate sampling, but can be reduced by using modified standard techniques.,, In two cases, only fluid was obtained without any cells, making it difficult for a definite diagnosis.
Various benign lesions could be easily diagnosed at FNAC; however, they have cytologic features overlapped with malignant lesions. Low cellularity is defined by some as 10 or fewer cell clusters, moderate cellularity as 11–30 clusters, and high cellularity as more than 30 clusters. False-negative diagnoses can also occur due to overinterpretation of inadequate or unsatisfactorily prepared material. Interpretative errors leading to false-negative diagnoses of breast lesions are usually associated with low-grade malignancies, such as lobular, tubular, or papillary carcinomas.,
A “gray zone” in breast cytology has long been recognized. This is an unequivocal diagnosis, which cannot be reached with FNAC findings. It is due to overlapping features of benign epithelial proliferative lesion, mostly fibroadenoma, and a well-differentiated carcinoma as well as borderline lesions of the breast. The gray zone in breast FNAC is a broad spectrum that changes from proliferative fibrocystic disease to sclerosing adenosis to malignancy. It is necessary to follow up with such lesions with a repeat FNAC or core needle biopsy after a reasonable interval. Fibroadenoma with atypia has the potential to be diagnosed as low-grade malignancy. Another important type of biphasic tumor, the phyllodes tumor also constitutes an important gray zone lesion. Gynecomastia in the male breasts is also a lesion that causes a dilemma in some cases due to the presence of atypia.
It may be necessary to strongly suggest the necessity of surgical biopsy for all patients with atypical/suspicious cytologic findings due to the high probability of an underlying malignancy. Therefore, the use of a single term, such as “equivocal,” rather than separate designations of “atypical” and “suspicious,” may be used to describe in conclusive breast FNAC diagnoses.
Grade 1 carcinomas make up approximately 45% of screening-detected breast carcinomas and approximately 20% of symptomatic breast cancers. It has been found that low-grade carcinomas have a distinctly lower sensitivity due to the low degree of cellular atypia that may be difficult to appreciate. Preoperative FNAC diagnosis of Grade 1 breast carcinoma has a high sensitivity in ductal carcinomas. A definitive preoperative diagnosis is less likely in invasive lobular and tubular carcinomas., Benign phyllodes tumor appears similar to fibroadenoma on cytology. Stromal predominance, hypercellularity, more bare nuclei, and size of stromal cells aid in diagnosis.[1-4],
| Conclusion|| |
This study highlights the possible causes of cytological pitfalls. Although cytology is not 100% accurate in most cases, there is a clear distinction between benign and malignant lesions, greatly reducing the need for preoperative surgery. Strict adhering to diagnostic criteria and extensive sampling are of paramount importance in reducing false-positive and false-negative cases.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Cangirella J, Simsir A. Breast. In: Orell SR, Sterett GF, editors. Fine Needle Aspiration Cytology. 5th ed. London, England: Churchill Livingstone; 2012. Chapter 7: p. 156-209.
Saad RS, Silverman JF. Breast. In: Bibbo M, Wilbur D, editors. Comprehensive Cytopathology. 3rd ed. Philadelphia, PA: W.B. Saunders; 2008. Chapter 26: p. 712-72.
Gray W, Kocjan G. Diagnostic Cytopathology. 3rd ed. London, England: Churchill Livingstone; 2010. p. 954.
National Breast Cancer Centre. Breast Fine Needle Aspiration Cytology and Core Biopsy: A Guide for Practice. 1st ed. Camperdown, NSW, Australia: National Breast Cancer Centre; 2004. Available from: https://canceraustralia.gov.au/sites/default/files/publications/fna-fine-needle-aspiration-cytology-and-core-biopsy-guide-for-practice_504af03488799.pdf. [Last accessed on].
Obaseki DE. Fine needle aspiration cytology in tumor diagnosis. Benin J Postgraduate Med (BJPM) 2008;10:7.
Pandya AN, Shah NP. Breast fine needle aspiration cytology reporting: A study of application of probabilistic approach. Indian Med Gazette2013;147:54-9.
Singh S, Chandra P, . Jitendra. Diagnostic accuracy of fine needle aspiration cytology of breast lump in rural population of Western U.P. Sch J App Med Sci 2015;3:467-9.
Mitra S, Dey P. Grey zone lesions of breast: Potential areas of error in cytology. J Cytol 2015;32:145-52.
] [Full text]
Mendoza P, Lacambra M, Tan PH, Tse GM. Fine needle aspiration cytology of the breast: The nonmalignant categories. Patholog Res Int 2011;2011:547580.
Singh A, Haritwal A, Murali B. Pattern of breast lumps and diagnostic accuracy of fine needle aspiration cytology; a hospital based study from Pondicherry, India. Internet J Pathol2010;11:1-6.
Moschetta M, Telegrafo M, Carluccio DA, Jablonska JP, Rella L, Serio G, et al
. Comparison between fine needle aspiration cytology (FNAC) and core needle biopsy (CNB) in the diagnosis of breast lesions. G Chir 2014;35:171-6.
Karimzadeh M, Sauer T. Diagnostic accuracy of fine-needle aspiration cytology in histological grade 1 breast carcinomas: Are we good enough? Cytopathology 2008;19:279-86.
Layfield LJ, Dodd LG. Cytologically low grade malignancies: An important interpretative pitfall responsible for false negative diagnoses in fine-needle aspiration of the breast. Diagn Cytopathol 1996;15:250-9.
Iqbal MH, Iqbal K, Nadeem A. Diagnostic accuracy of fine needle aspiration cytology (FNAC) in patients with breast lump. PJMHS 2015;9:1210-12.
Kanhoush R, Jorda M, Gomez-Fernandez C, Wang H, Mirzabeigi M, Ghorab Z, et al
. “Atypical” and “suspicious” diagnoses in breast aspiration cytology. Cancer 2004;102:164-7
Layfield LJ, Mooney EE, Glasgow B, Hirschowitz S, Coogan A. What constitutes an adequate smear in fine-needle aspiration cytology of the breast? Cancer 1997;81:16-21.
Saldanha P, Lobo FD. Diagnostic dilemma in the cytological diagnosis of benign phyllodes tumor. J Cytol 2002;19:145-7.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2]