|Year : 2017 | Volume
| Issue : 1 | Page : 91-96
Application of National Cancer Institute recommended terminology in breast cytology
P Arul, Suresh Masilamani
Department of Pathology, Dhanalakshmi Srinivasan Medical College and Hospital, Siruvachur, Perambalur, Tamil Nadu, India
|Date of Web Publication||16-May-2017|
83, Ayyanar Kovil Street, Vinayagampet, Sorapet Post, Puducherry - 605 501
Source of Support: None, Conflict of Interest: None
Background: There is a lack of uniformity with regard to the reporting terminology used in breast cytology by pathologists worldwide, resulting in miscommunication of results among health-care providers.
Aim: The present study was aimed to assess the accuracy of fine-needle aspiration cytology (FNAC) in the evaluation of breast lesions using the National Cancer Institute (NCI) recommended terminology.
Materials and Methods: In this prospective study, a total number of 523 breast FNACs were categorized according to the NCI guidelines. Of these, 286 (54.7%) had histopathological follow-up, and their FNAC diagnoses were compared. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) along with 95% confidence interval (95% CI) and accuracy of FNAC were calculated.
Results: Among 286 FNAC cases, 4 were unsatisfactory (C1), 188 were benign (C2), 11 were atypical, probably benign (C3), 21 were suspicious, favor malignancy (C4), and 62 were malignant (C5). On histopathological examination of categories C2 and C3 (total of 199 cases), 193 were confirmed as benign (true negative) and remaining 6 cases were turned out to malignant (false negative). Among categories C4 and C5 (total of 83 cases), 81 were confirmed as malignant (true positive) and remaining 2 were turned out to be benign (false positive). The sensitivity, specificity, PPV, NPV, and accuracy of FNAC were 93.1% (95% CI, 88.2%–95%), 99% (95% CI, 96.8%–99.8%), 97.6% (95% CI, 92.5%–99.6%), 97% (95% CI, 94.9%–97.8%), and 97.2%, respectively.
Conclusion: Our study concluded that FNAC reporting using NCI guidelines highly correlated with the histopathological diagnosis.
Keywords: Breast, cytodiagnosis, fine-needle aspiration cytology, National Cancer Institute
|How to cite this article:|
Arul P, Masilamani S. Application of National Cancer Institute recommended terminology in breast cytology. J Can Res Ther 2017;13:91-6
| > Introduction|| |
In female patients, palpable breast mass is a common problem. majority of these are benign with the exception of carcinoma of breast, which is the leading cause of morbidity and mortality. In India, the information on the epidemiology of breast cancer is very limited except for a few reports on limited sample size. Fine-needle aspiration cytology (FNAC) has become a valuable tool in the preoperative assessment of breast masses, and it shows high sensitivity, specificity, and accuracy. FNAC in breast lesions offers psychological relief to the patients once diagnosed to have benign, fairly precise diagnosis, minimal to no morbidity, useful for evaluation of local chest wall recurrences, and allowed to do ancillary techniques, namely, hormone receptor analysis, flow cytometry, and molecular studies. One of the major goals of FNAC is to differentiate benign from malignant lesions. However, in certain instances, differentiation of benign from malignant lesion is not possible due to significant overlap on smears (in cases of fibroadenoma and proliferative breast diseases and atypical hyperplasia and low-grade carcinoma in situ, or in papillary lesions) and also when there is a paucity of cells., To address these cytomorphologic uncertainties and to bring a degree of uniformity to the reporting terminology, the National Cancer Institute (NCI) proposed five diagnostic categories, namely, unsatisfactory (C1), benign (C2), atypical, probably benign (C3), suspicious, favor malignancy (C4), and malignant (C5) in 1996. These cytologic reporting categories are used to objectively describe their features in cytological terms and to incorporate the groups with uncertainties and also helps the pathologists to define the areas of uncertainties, and the clinicians to offer further investigations. Hence, we decided to evaluate the utility and diagnostic accuracy of FNAC in the evaluation of breast lesions using the NCI recommended terminology by correlating with histopathological results.
| > Materials And Methods|| |
This prospective study was carried out at the Department of Pathology at our institution between May 2014 and December 2015 after obtaining approval from the Institutional Ethical Committee. A total of 523 FNACs were evaluated by pathologists. The breast lesions were aspirated using a 23–25-gauge needle with syringe. All the slides were stained with May-Grunwald Giemsa and hematoxylin and eosin and categorized into C1, C2, C3, C4, and C5 using NCI guidelines proposed in 1996. Informed written consent was obtained from each patient before procedure.
Among 523 patients, 286 (54.7%) undergone surgical intervention either by biopsy or mastectomy. Histopathological examination of these specimens was done, and the results were compared with cytological diagnoses. The C1 results were excluded from the analysis.
Patients with C2 and C3 diagnoses by FNAC but diagnosed as malignant lesions on histopathological examination was considered as false negative, and patients with C4 and C5 diagnoses by FNAC but diagnosed as benign lesions on histopathological examination was considered as false positive.
Master charts were prepared and the results were tabulated. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) along with 95% confidence interval (95% CI), accuracy, false positive rate, and false negative rate of FNAC for diagnosing malignant lesions were calculated similar to previous studies.,, All the statistical analysis was performed using International Business Machines (IBM) Corporation Statistical Package for the Social Sciences Statistics for Windows (version 20.0, IBM Corporation, Armonk, New York, USA).
| > Results|| |
Benign lesions were common in 31–40 years and malignant lesions were in the age group of 41–50 years. In 55% of patients, left breast was involved and in 47.4% patients, upper and outer quadrant was affected.
Among 523 FNAC cases, C1 consisted of 14 (2.7%), C2 consisted of 352 (67.3%), C3 consisted of 27 (5.2%), C4 consisted of 41 (7.8%), and C5 consisted of 89 (17%) cases are shown in [Table 1]. Out of 352 cases of category C2, fibroadenoma (50.6%, 178/352) was most common followed by fibrocystic disease (17%, 60/352), benign phyllodes tumor (9.4%, 33/352), mastitis/breast abscess (6.5%, 23/352), fibroadenosis (5.7%, 20/352), papilloma (4.5%, 16/352), galactocele (3.4%, 12/352), and granuloma (2.8%, 10/352).
|Table 1: Distribution of various diagnostic categories of breast fine-needle aspiration cytologies according to the National Cancer Institute guidelines (n=523)|
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Of these total 523 FNAC cases, histologic report was documented in 286 cases with biopsy rate of 54.7%. Among 286 FNAC cases, 4 (1.4%) were C1, 188 (65.8%) were C2, 11 (3.8%) were C3, 21 (7.3%) were C4, and 62 (21.7%) were C5. The comparison of 286 cases of FNAC diagnoses with corresponding histopathological diagnoses was done. On histopathological examination, 97.9% (184/188) cases of C2 were confirmed as benign and remaining 4 cases turned out to be malignant. In C3, benignancy was confirmed in 81.8% (9/11) and remaining two cases diagnosed to be malignant. In C4, 95.2% (20/21) cases were correctly cytotyped as malignant and one case was reported as benign. In C5, cytohistological concordance was found in 98.4% (61/62) and one case turned out to benign [Figure 1]a and [Figure 1]b. The most common malignant lesion noted in C5 on histopathological examination was invasive ductal carcinoma-not otherwise specified (IDC-NOS) (47.5%, 29/61) followed by invasive lobular carcinoma (ILC) (13.1%, 8/61), malignant phyllodes tumor (13.1%, 8/61), medullary carcinoma (9.8%, 6/61), poorly differentiated carcinoma (6.6%, 4/61), apocrine carcinoma (4.9%, 3/61), papillary carcinoma (3.3%, 2/61), and malignant trichilemmal tumor (1.6%, 1/61) [Table 2].
|Figure 1: False positive case - category C5 turned out to be benign. (a) Cytosmear showing discohesive cluster with moderate nuclear atypia diagnosed as malignant (H and E, ×400). (b) Subsequent histopathological section revealing compressed ducts surrounded by fibrotic stroma confirmed as fibroadenoma (H and E, ×400)|
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|Table 2: Comparison of fine needle aspiration cytology diagnoses with final histopathological diagnoses (n=286)|
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The present study showed sensitivity of 93.1% (95% CI, 88.2%–95%), specificity of 99% (95% CI, 96.8%–99.8%), PPV of 97.6% (95% CI, 92.5%–99.6%), NPV of 97% (95% CI, 94.9%–97.8%), and accuracy of 97.2% for FNAC in the diagnosis of malignant lesions. The false positive and false negative rate was 1% and 6.9%, respectively.
| > Discussion|| |
There are various modalities available for the diagnosis of breast masses include imaging studies, namely, ultrasonography (USG), diagnostic and digital mammography, magnetic resonance imaging (MRI), and tissue-based studies such as FNAC and core needle biopsy (CNB) and excisional biopsy.,, However, each method has its own advantages and limitations. Many countries have now adopted triple approach which comprised clinical breast examination, imaging (mammography and/or ultrasound) with FNAC as the first-line pathological investigation in both screening and in symptomatic patients.,,,,,
Breast USG has a sensitivity of 89% and specificity of 78% in the detection of abnormalities in symptomatic women. This modality may be used to distinguish cystic from solid masses, to know the extent of disease in known or suspected cancers. Diagnostic mammography used to screens the occult disease in surrounding tissue, and it may help the clinicians to determine whether a lesion is potentially malignant or not. The sensitivity, specificity, and PPV of diagnostic mammography are 87%, 88%, and 22%, respectively. Greater diagnostic accuracy has been observed with digital mammography than film screen mammography in premenopausal and perimenopausal women, women younger than 50 years, and women with dense breast tissue. MRI has high sensitivity (85%–100%) and low specificity (47%–67%) in the diagnosis of breast masses. It is not a substitute for mammography and should not be used to preclude biopsy of a suspect finding.,
Despite many imaging techniques are described, pathological characterization still plays an essential role in the evaluation of breast lesions. Even though FNAC of breast lesions is simple, safe, quick, and cost-effective, the role of this technique has been challenged of late by results attained by CNB that seems more robust than former., CNB is more reliable than FNAC and less invasive than surgical biopsy and allows clinicians to plan therapeutic treatment. However, CNB carries certain complications, and it can either be severe or minor. Major complications are severe pain (1.7%), severe bleeding requiring treatment (0.72%), infections (0.15%), and hematoma requiring treatment (0.09%). In the minor complications, bruising is most commonly followed by mild pain (3.7%) and vasovagal reactions (1%). FNAC is an easy and safe procedure in certain circumstances, namely, very small lesions, lesions just under the skin, or lesions very close to the chest wall compared to CNB. In addition, FNAC maintains tactile sensitivity, allows multidirectional passes allowing a broader sampling of lesion, and immediate reporting whenever necessary.,
In the present study, benign and malignant lesions were common in 31–40 years and 41–50 years, respectively. These findings were comparable to Jarwani et al. Our study also documented that benign lesions are common in younger age group and malignant lesions are common in older age group. It is expected that malignancy rates increase with increasing age of patients. Left breast (55%) and upper outer quadrant (47.4%) were commonly involved in the current study, which were comparable to recently published studies.,
We recognized that distribution of the FNAC diagnoses of breast lesions using NCI guidelines (1996) in our institution showed slightly different statistical values compared with published studies.,,,, Categories C1, C2, and C5 of our study were comparable to frequencies found by most of the published studies. However, percentages of C3 and C4 were slightly higher than few studies [Table 3]. This could be due to the level of caution employed by the pathologists in diagnosing atypical lesions in different settings. In our institution, we offer cytological diagnosis of C3, if there was characteristic of benign aspirate with any or a combination of nuclear pleomorphism, some loss of cellular cohesiveness, or nuclear and cytoplasmic changes, and C4, if smears showing some atypical cellular features but without definite evidences of malignancy or aspirate showing some malignant features of greater than those observed in C3 after clinico-radiological correlation.
|Table 3: Comparison of the distribution of various National Cancer Institute guidelines categories of present study with published studies|
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The inadequate rate is influenced by the nature of the lesion, available technology, experience, and skill of the operator. The nature of lesion (68%) was the most common cause for inadequate aspirates followed by experience of the aspirator (32%) for inadequacy rate. Some studies have documented that both aspirator and interpreter should ideally be same to lower the inadequate aspirates and to increase the diagnostic accuracy. In our institution, only pathologists are performing FNAC. In the present study, C1 consisted of 14 (2.7%); this could be due to nature of the lesions either cystic or sclerotic breast lesions.
Categories C2 and C5 are straightforward; hence, it has been associated with a high degree of diagnostic accuracy. The present study also showed similar observation for these categories (97.9% and 98.4%). However, the interpretation of C3 and C4 are difficult and confusing because they do not have strict criteria for diagnosis. According to some researchers, stratification of cases C3 and C4 is beneficial, as it identifies groups of patients who are more likely to have either benign (C3) or malignant (C4) outcomes. Whereas clubbing of C3 and C4 as a single term called equivocal/suspicious category also suggested by few authors and they believe that a CNB or surgical biopsy should be done for this combined category as the incidence of malignancy is significant in both subgroups. There are benign outcomes of 47%–87% with C3 and malignant outcomes of 72%–87% with C4 patients in large-scale studies with histopathological correlation. Moreover, C3 still have malignancy in 13%–53% and C4 have benignancy in 13%–28% patients., Since the current study showed 81.8% benign lesions with C3 and 95.2% malignancy with C4, we feel that it is still useful to maintain the categories C3 and C4 separately.
On histopathological examination, we found more number of benign cases (69.2%, 198/286) and fewer number of malignant cases (30.8%, 88/286). This findings were similar to studies done by Yusuf and Atanda, Nguansangiam et al., Whereas it was in contrast to Sankaye and Dongre, and however, in Ukah and Oluwasola, benign and malignant cases were almost equal [Table 4]. The most common malignant lesion noted on histopathological examination was IDC-NOS followed by ILC, malignant phyllodes tumor, and medullary carcinoma. These findings were almost comparable to study done by Yusuf and Atanda, who found that IDC-NOS was most common followed by ILC, medullary carcinoma, and papillary carcinoma.
|Table 4: Comparison of histopathological cases of the present study with published studies|
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The current study observed false negative rate of 6.9% and false positive rate of 1%. These results were comparable with most of the recently published studies and have documented the false negative and false positive rate for FNAC ranging from 1.7% to 13.3% and 0.6% to 6.5%, respectively.,,,, Three cases of IDC-NOS and a case of ILC were underdiagnosed as fibroadenoma and fibrocystic disease, respectively, in C2 and two cases of IDC-NOS misdiagnosed as C3 on FNAC, contributing to false negative results. Factors contributing to false negative results include small size of the lesion, hypocellularity, and inadequate sampling during aspiration, histological tumor types such as low nuclear grade ILC, scirrhous carcinoma, and well-differentiated intracystic carcinoma. The most attributed cause of false negative rate reported in the literature is sampling error, particularly in small tumor. Fibrosclerotic hypocellular lesions such as scirrhous carcinoma and sclerosed fibroadenoma may not yield sufficient cells to allow a diagnosis by FNAC. The resemblance of ILC to lymphocytes and its subtle cytological atypia are well-known diagnostic problems.
A case each from C4 and C5 was diagnosed as benign (fibroadenoma) on histopathological examination. These results were considered as false positive. Fibroadenoma constitutes the largest cause of false positive and false negative diagnoses. Occasionally, it may reveal cellular discohesiveness and marked pleomorphism leading to wrong diagnoses of atypical or malignant lesions, as seen in the present study.
Both false negative and false positive diagnoses can be reduced by good sampling technique, proper tumor localization, triple assessment, and more importantly availing expert second opinions for doubtful cases.
Recently published review documented that breast FNAC has a sensitivity ranging from 76% to 99%, a specificity from 60% to 100%, and an accuracy from 72% to 95%. The present study showed sensitivity, specificity, PPV, NPV, and accuracy of FNAC were 93.1% (95% CI, 88.2%–95%), 99% (95% CI, 96.8%–99.8%), 97.6% (95% CI, 92.5%–99.6%), 97% (95% CI, 94.9%–97.8%), and 97.2%, respectively. Differences in the categorization of C3 and C4 resulted in wide range of sensitivity and specificity. Some others categorize the C3 as histopathologically benign, while others categorize these lesions as indeterminate along with C4, whereas some authors categorize the C4 as histopathologically malignant, while others categorize these lesions as indeterminate along with C3.
Even though FNAC considered a valuable tool in the preoperative assessment of breast lesions, it has some limitations. The definitive diagnosis of certain lesions such as atypical ductular hyperplasia, low-grade ductal carcinoma in situ, tubular carcinoma, and some special types of invasive carcinoma can be difficult. Furthermore, one cannot distinguish carcinoma in situ from invasive carcinoma. In these situations, CNB plays a crucial role in making definitive diagnosis. Moreover, considerable cytology expertise is required for interpretation of FNAC. Studies proved that CNB is superior to FNAC, but in resource poor countries like India, later technique is still widely used for diagnosis of breast lesions.
| > Conclusion|| |
Our study concluded that FNAC reporting using NCI guidelines highly correlated with the histopathological diagnosis. We also recommend to maintaining the diagnostic categories C3 and C4 in breast cytology as our study found a significant difference between benign and malignant diagnoses among them. FNAC of breast lesions is simple, safe, quick, cost-effective, and first-line procedure. NCI terminologies may help in achieving uniformity of diagnostic categories across institutions/pathologists.
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Conflicts of interest
There are no conflicts of interest.
| > References|| |
Yu YH, Wei W, Liu JL. Diagnostic value of fine-needle aspiration biopsy for breast mass: A systematic review and meta-analysis. BMC Cancer 2012;12:41.
Muddegowda PH, Lingegowda JB, Kurpad R, Konapur P, Shivarudrappa A, Subramaniam P. The value of systematic pattern analysis in FNAC of breast lesions: 225 cases with cytohistological correlation. J Cytol 2011;28:13-9.
] [Full text]
Sankaye SB, Dongre SD. Cytological study of palpable breast lumps presenting in an Indian rural setup. Indian J Med Paediatr Oncol 2014;35:159-64.
] [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 P, Chaudhry M, Nauhria S, Rao D. Cytomorphological patterns of breast lesions diagnosed on fine-needle aspiration cytology in a tertiary care hospital. Int J Med Sci Public Health 2015;4:674-79.
Yusuf I, Atanda AT. Validity of fine needle aspiration cytology of the palpable breast lesions: A teaching hospital experience. Niger J Basic Clin Sci 2014;11:36-40. [Full text]
Arul P, Masilamani S, Akshatha C. Fine needle aspiration cytology of atypical (C3) and suspicious (C4) categories in the breast and its histopathologic correlation. J Cytol 2016;33:76-9.
] [Full text]
Challa VR, Yale Guru BG, Rangappa P, Deshmane V, Gayathri DM. Cytological and pathological correlation of FNAC in assessing breast lumps and axillary lymph node swellings in a public sector hospital in India. Patholog Res Int 2013;2013:695024.
Klein S. Evaluation of palpable breast masses. Am Fam Physician 2005;71:1731-8.
Ravi C, Rodrigues G. Accuracy of clinical examination of breast lumps in detecting malignancy: A retrospective study. Indian J Surg Oncol 2012;3:154-7.
Ghimire B, Khan MI, Bibhusal T, Singh Y, Sayami P. Accuracy of triple test score in the diagnosis of palpable breast lump. JNMA J Nepal Med Assoc 2008;47:189-92.
Kachewar SS, Dongre SD. Role of triple test score in the evaluation of palpable breast lump. Indian J Med Paediatr Oncol 2015;36:123-7.
] [Full text]
Ahmed I, Nazir R, Chaudhary MY, Kundi S. Triple assessment of breast lump. J Coll Physicians Surg Pak 2007;17:535-8.
Daramola AO, Odubanjo MO, Obiajulu FJ, Ikeri NZ, Banjo AA. Correlation between fine-needle aspiration cytology and histology for palpable breast masses in a Nigerian Tertiary Health Institution. Int J Breast Cancer 2015;2015:742573.
Kocjan G, Bourgain C, Fassina A, Hagmar B, Herbert A, Kapila K, et al.
The role of breast FNAC in diagnosis and clinical management: A survey of current practice. Cytopathology 2008;19:271-8.
Jan M, Mattoo JA, Salroo NA, Ahangar S. Triple assessment in the diagnosis of breast cancer in Kashmir. Indian J Surg 2010;72:97-103.
Neal L, Tortorelli CL, Nassar A. Clinician's guide to imaging and pathologic findings in benign breast disease. Mayo Clin Proc 2010;85:274-9.
Pisano ED, Hendrick RE, Yaffe MJ, Baum JK, Acharyya S, Cormack JB, et al.
Diagnostic accuracy of digital versus film mammography: Exploratory analysis of selected population subgroups in DMIST. Radiology 2008;246:376-83.
Capalbo E, Sajadidehkordi F, Colombi C, Ticha V, Moretti A, Peli M, et al.
Revaluation of breast cytology with pathologist on-site of lesions with suspicious sonographic features. Eur J Radiol 2013;82:1410-5.
Arul P, Masilamani S. Comparative evaluation of various cytomorphological grading systems in breast carcinoma. Indian J Med Paediatr Oncol 2016;37:79-84.
] [Full text]
Pagni P, Spunticchia F, Barberi S, Caprio G, Paglicci C. Use of core needle biopsy rather than fine-needle aspiration cytology in the diagnostic approach of breast cancer. Case Rep Oncol 2014;7:452-8.
Bruening W, Fontanarosa J, Tipton K, Treadwell JR, Launders J, Schoelles K. Systematic review: Comparative effectiveness of core-needle and open surgical biopsy to diagnose breast lesions. Ann Intern Med 2010;152:238-46.
Lieske B, Ravichandran D, Wright D. Role of fine-needle aspiration cytology and core biopsy in the preoperative diagnosis of screen-detected breast carcinoma. Br J Cancer 2006;95:62-6.
Jarwani PB, Patel DC, Patel SM, Dayal A. fine needle aspiration cytology in palpable breast lump. GCSMC J Med Sci 2013;2:12-6.
Ukah CO, Oluwasola OA. The clinical effectiveness of fine needle aspiration biopsy in patients with palpable breast lesions seen at the University College Hospital, Ibadan, Nigeria: A 10-year retrospective study. J Cytol 2011;28:111-3.
] [Full text]
Chokshi MH, Mehta NP. Cytological study of palpable breast lumps (407 cases) with their histological correlation. Int J Med Sci Public Health 2014;3:181-5.
Shabb NS, Boulos FI, Abdul-Karim FW. Indeterminate and erroneous fine-needle aspirates of breast with focus on the true gray zone: A review. Acta Cytol 2013;57:316-31.
Nguansangiam S, Jesdapatarakul S, Tangjitgamol S. Accuracy of fine needle aspiration cytology from breast masses in Thailand. Asian Pac J Cancer Prev 2009;10:623-6.
Silverman JF, Saad RS. Breast. In: Bibbo M, Wilbur D, editors. Comprehensive Cytopathology. 3rd
ed. Philadelphia, PA: Saunders Elsevier; 2008. p. 713-72.
Cangiarella J, Simsir A. Breast. In: Orell SR, Sterrett GF, editors. Fine Needle Aspiration Cytology. 5th
ed. Toronto: Churchill Livingstone Elsevier; 2012. p. 185-7.
Chaiwun B, Thorner P. Fine needle aspiration for evaluation of breast masses. Curr Opin Obstet Gynecol 2007;19:48-55.
[Table 1], [Table 2], [Table 3], [Table 4]