|Year : 2014 | Volume
| Issue : 3 | Page : 326-331
Histopathological and cytological correlation of tumors of breast
Sushma Yalavarthi1, Ramamurti Tanikella2, Shailaja Prabhala2, Uma Shankar Tallam2
1 Department of Pathology, Mamata Medical College, Khammam, Andhra Pradesh, India
2 Department of Pathology, Kamineni Institute of Medical Sciences, Andhra Pradesh, India
|Date of Web Publication||18-Mar-2014|
Department of Pathology, Mamatha Medical College, Khammam, Andhra Pradesh
Source of Support: None, Conflict of Interest: None
Background :0 With the advent of fine needle aspiration cytology (FNAC), the approach to diagnosis and management of breast lesions has been revolutionized. Its accuracy in many situations can approach that of histopathology in providing an unequivocal diagnosis. Aim :0 The aim of this study is to examine the cytological details in aspirated smears from lumps in the breast and to evaluate the role of FNAC in improving the quality of diagnosis by comparing with histopathological features. Materials and Methods: Over a period of 2 years, 334 aspirations, including 16 bilateral were performed. Suppurative and inflammatory lesions and gynecomastia were excluded from the total aspirates. A total of 56 cases were followed-up by histopathologic examination. Results: Cytohistologic correlation was 73.68%, 42.85%, 94.44% for fibroadenoma, fibrocystic disease and duct cell carcinoma respectively. False positives were observed in proliferative lesions. No false negative cases observed. The sensitivity of the fine needle aspiration (FNA) procedure was 100%, specificity, 88.5% and the predictive value of a positive result was 84%. Conclusion: Proliferative lesions may be misinterpreted as malignancy in FNA without complete clinical and mammographic details.
Keywords: Breast tumors, fine needle aspiration cytology, histopathology, proliferative lesions
|How to cite this article:|
Yalavarthi S, Tanikella R, Prabhala S, Tallam US. Histopathological and cytological correlation of tumors of breast. Med J DY Patil Univ 2014;7:326-31
|How to cite this URL:|
Yalavarthi S, Tanikella R, Prabhala S, Tallam US. Histopathological and cytological correlation of tumors of breast. Med J DY Patil Univ [serial online] 2014 [cited 2019 Jun 16];7:326-31. Available from: http://www.mjdrdypu.org/text.asp?2014/7/3/326/128975
| Introduction|| |
A palpable breast lump is a common diagnostic problem to both general practitioners and surgeons. Excisional biopsy was accepted practice in the past, but presently needle biopsy makes it possible to reduce surgical excision of benign breast lesions to a minimum. The main purpose of fine needle aspiration cytology (FNAC) of breast lumps is to confirm cancer pre-operatively and to avoid surgery in specific benign conditions.
Many countries have breast cancer screening programs aimed at detecting early disease in asymptomatic women. The diagnostic process involves the "Triple test" consisting of clinical examination, mammography and FNAC. 
However, the aspiration cytology is not a substitute for conventional surgical histopathology as a definitive diagnosis is not always possible by cytology, but categorization of disease and differential diagnosis can be provided in the majority of cases. With this in mind, an attempt was made to subjectively evaluate the breast tumors in FNAC material and to compare it with histopathological details.
| Materials and Methods|| |
The study was conducted in the Department of Pathology, from 1 st October 2006 to 31 st September 2008. During this period, 334 fine needle aspiration (FNA) were performed for various breast masses. These 334 aspirations were obtained from breast masses of 318 patients. 16 patients had bilateral breast masses. Out of these cases, inflammatory lesions, gynecomastia was excluded. Both benign and malignant tumors were followed-up. Specimens were received from 56 patients who underwent surgery, which formed the material of this study. Aspirations were carried out using a 23 gauge needle and 10 ml disposable syringe. Cytological smears were fixed in 95% alcohol and stained with H and E and Papanicolaou stains. Criteria such as cost-effectiveness, use of anesthesia, turn-around time, patients' hospital stay and most importantly, reliability in deciding subsequent treatment, are all factors to be taken into account in this regard. The surgical specimens were fixed in 10% formalin. The gross and cut section findings were noted. Several bits were taken from appropriate sites for processing and paraffin embedding. From each block, sections were cut at 4-5 microns thickness and stained by H and E.
| Results|| |
The 334 (including 16 bilateral) aspirations were performed over a period of 2 years. Suppurative and inflammatory lesions (41) were excluded from the total aspirates. Cytological diagnosis of 293 aspirations was reviewed and lesions were classified into four diagnostic classes revealing 164 benign lesions, 45 malignant, 25 suspicious and 59 inadequate. Female patients comprised 315 and male patients three of total cases. The age of the patients ranged from 10 to 80 years. The oldest case (80 years) was diagnosed as proliferative lesion with atypia and the youngest (10 years) was a juvenile fibroadenoma. Of the benign lesions, 45.12% cases were reported in the third decade. The maximum number of malignant lesions (46.66%) was reported in the fifth decade [Table 1].
The anatomical and topographical distribution revealed, most of the lesions were in the left breast (52.22%). Maximum distribution of the lesions was noticed in the upper outer quadrant (59.04%). Malignant lesions were more in the right breast (8.19%) and benign lesions were in the left breast (28.66%).
In benign breast lesions, fibrocystic change constituted the largest disease group with maximum incidence in the fourth decade, followed by fibroadenoma with maximum incidence in the third decade [Figure 1] and [Figure 2]. Apart from these, one case of phyllodes tumor and one case of giant fibroadenoma were reported. In the malignant breast lesions, maximum cases were reported as infiltrating duct carcinoma with maximum incidence in the fifth decade [Figure 3] and [Figure 4]. One case of duct cell carcinoma associated with Paget's disease was reported in the seventh decade. A single case of infiltrating duct cell carcinoma exhibiting focal neuroendocrine differentiation with rosette formation was reported. One case of medullary carcinoma was reported histologically, having pushing margins and extensive lymphocytic infiltrate and tumor cells arranged in syncytial pattern. Out of 26 cases diagnosed as benign on FNA and included in cytohistologic correlation, fibroadenoma comprised the maximum cases (19) followed by fibrocystic change (7). Cytohistologic correlation was 73.68% for fibroadenoma, 42.85% for fibrocystic disease, 94.44% for duct cell carcinoma [Table 2].
|Table 2: Cytological and histopathological correlation of the lesions (N = 56)|
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Following histopathologic correlation, sensitivity, specificity, positive predictive values were calculated in accordance with park. There were four false positive cases and no false negative cases in this study. Among 56 patients with cytohistologic correlation, 25 (44.64%) had a final tissue diagnosis of malignancy and 31 (55.36%) had benign condition. False positives were observed in the proliferative lesions [Figure 5]. In the present study, the sensitivity was 100%, specificity, 88.5% and the predictive value of a positive result was 84% [Table 3].
|Figure 1: (a) Cell rich smear of elongated, branching fragments of ductal epithelial cells (H and E, ×100) (b) Large, branching sheet of cohesive epithelial cells (H and E, ×400) (c) Histopathological section showing both intracanalicular and pericanalicular patterns of fibroadenoma (H and E, ×40)|
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|Figure 2: (a) Smears of fi brocystic disease showing cyst macrophages, clusters of apocrine cells (H and E, ×100) (b) Section of fi brocystic disease showing cystic dilatation (H and E, ×100) (c) High power view of apocrine change and cystic dilatation (H and E, ×400)|
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|Figure 3: (a) Grade 1 ductal carcinoma with well-preserved cell cohesion (H and E, ×100) (b) Grade 2 ductal carcinoma with individually dispersed cells (H and E, ×400) (c) Typical Grade 3 ductal carcinoma|
showing cells with high nuclear: Cytoplasmic ratio (H and E, ×400)
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|Figure 4: Histopathological patterns of infi ltrating duct cell carcinoma (a) Cribriform pattern (b) Comedo type (c) Typical nesting pattern (d) Tubular type (H and E, ×100)|
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|Figure 5: (a) Smears of atypical ductal hyperplasia showing aggregates of atypical epithelial cells showing prominent nuclear enlargement and some irregularity (H and E, ×400) (b) Histopathological section of ductal epithelial hyperplasia (H and E, ×100)|
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|Table 3: The diagnostic accuracy of FNAC in 56 histologically correlated cases|
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| Discussion|| |
Many countries have breast cancer screening programs aimed at detecting early disease in asymptomatic women. FNAC occupied a major role in the "Triple test." 
In the present study, 334 (including 16 bilateral) aspirations were performed over a period of 2 years. Suppurative and inflammatory lesions (37), gynecomastia (4) were excluded from the total aspirates. 237 cases were lost to follow-up. Out of 293 aspirations, 56 cases were followed-up by histopathologic confirmation. These 56 cases were considered as the study group for the present study of cytological and histopathological correlation of tumors of the breast.
Frable used 22 gauge needles, 1.5 inches length for aspirating various lesions and felt that careful clinical examination of the breast mass to confirm its presence and consistency are important for the needle aspiration and suggested that there is a need to explain the aspiration procedure to the patient. 
Swapan aspirated 408 cases by using 20 ml disposable syringes and 23 gauge needles. Frable and Zajicek used special syringe holders. ,
In this study, 22 or 24 gauge disposable needles, measuring 1.5 inches in length and 10 ml disposable syringes without holders were used.
The age of the patients ranged from 10 to 80 years. The oldest case (80 years) was diagnosed as proliferative lesion with atypia and youngest (10 years) was a juvenile fibroadenoma. Of the benign lesions, 44.80% cases were reported in the third decade.
No malignant cases were reported in this age group. Maximum malignant lesions (46.66%) were reported in the fifth decade. Proliferative lesions were more in the fourth decade.
In a series of 125 aspirations by Ishita, maximum benign lesions (40%) were reported in the third decade, while only 4% of the malignant lesions were reported in this age group. Maximum malignant lesions (56%) were reported in the fifth decade. 
Pinto had a range of 12-82 years. The oldest case was diagnosed (82 years) as breast abscess and the youngest (12 years) was a benign phyllodes tumor. 
Swapan determined the topographic distribution of different breast lesions and observed that the left breast was found to be more common site of malignancy and the upper outer quadrant being the most common site. 
Most of the lesions in this study were in the left breast. Malignant lesions were more in the right breast whereas benign lesions in the left breast. Maximum distribution of the lesions in the upper outer quadrant (59.04%) coincided with the work of Swapan (46.66%) and Ishita (47.2%). ,
Various authors proposed different reporting protocols in classifying the breast lesions. Feichter analyzed 1472 aspirations and classified the lesions into four categories; benign, suspicious, malignant and inadequate.  Ishita classified the lesions into four diagnostic classes. i.e., benign, malignant, suspicious, inadequate. 
In this study, the lesions were divided into four categories. They are benign, malignant, proliferative/suspicious and inadequate.
In the present study, cytological diagnoses of 293 aspirations were reviewed and lesions were classified into four diagnostic classes revealing 164 benign lesions, 45 malignant, 25 suspicious and 59 inadequate lesions. In the series of benign breast lesions, fibrocystic change constituted the largest disease group with maximum incidence in the fourth decade, followed by fibroadenoma with maximum incidence in the third decade. Apart from these, one case of phyllodes tumor was reported in the sixth decade.
Ishita, Swapan also reported the same finding that the fibrocystic change was the most common benign lesion, followed by fibroadenoma. ,
According to Pinto fibroadenoma was the most common lesion. Next common lesion was fibrocystic disease. In males, gynecomastia was the most common lesion. 
Among malignant lesions, infiltrating duct cell carcinoma was the most common, which coincided with the many authors. ,,,
Thomas performed 2800 fine needle aspiration biopsy during the period 1987-1992. 257 were cytologically diagnosed as proliferative breast disease (PBD) with or without atypia. Out of these 84 cases were operated. Of these 40 were designated PBD without atypia by cytology. 23 (58%) were in agreement with histology. 44 cases were designated PBD with atypia. 24 (55%) were in agreement with the histologic diagnosis. 
Karthik selected 12 cases of palpable breast lesions with histopathological diagnosis of PBD and their FNA smears were reviewed retrospectively. Among eight patients histologically diagnosed as moderate to florid ductal hyperplasia, two of them were interpreted cytologically as non proliferative breast disease (NPBD) (False negative), two of them as PBD with atypia (False negative) and four of them as PBD without atypia. Of the two cases with histopathological diagnosis of ductal hyperplasia with atypia, one was cytologically interpreted as PBD with atypia and one was PBD without atypia (False negative). Two cases with the diagnosis of ductal carcinoma in situ (DCIS) were interpreted as PBD with atypia. 
In the present study, three cases were cytologically diagnosed as florid epithelial hyperplasia. Two of them were interpreted histologically as fibroadenoma, one of them turned out to be malignancy in histopathology. Out of four cases of cytological ductal hyperplasia with atypia, histopathological diagnosis of two cases were benign fibroadenoma and fibroadenosis and two cases were diagnosed as infiltrating duct cell carcinoma.
Lopez-Ferrer studied 362 cases of fiboadenoma. Cytohistological agreement was present in 287 of the 362 cases (79.28%). Lack of correlation was present in 75 cases. Diagnostic errors accumulated in the older patient group.  In Pinto study, the cytohistologic correlation for fibroadenoma was 89.7%. In benign lesions, the overall cytohistological agreement was 82.4%. 
In the present study, cytohistologic correlation was 73.68% for fibroadenoma, 42.85% for fibrocystic disease. Out of 19 cases of fibroadenoma, 14 were diagnosed histologically also as fibroadenoma, three as fibrocystic diseases, one case was fibroadenosis and one was phyllodes tumor. Out of seven case of fibrocystic disease, three diagnosed as fibroadenoma, one case was phyllodes tumor histologically. One case of phyllodes tumor was reported in the sixth decade, but it was not followed-up.
Dash studied fine needle aspirates from 108 invasive ductal carcinomas over a period from December 2000 to November 2003. Out of these in 93 patients, the diagnosis was confirmed by histopathological examination. Positive correlation between cytologic and histologic grade was seen 77.4% of cases. 
In the present study, cytohistologic correlation was 94.44% for duct cell carcinoma. One case of infiltrating duct cell carcinoma was diagnosed histopathologically as medullary carcinoma.
In this study, 59 aspirations were inadequate (17.66%). The incidence of inadequate reports in other series ranged from 0% to 57.2%, with a mean of 13.4%. In this study, five inadequate cases were analyzed. Histology of all the five cases revealed benign nature of either fibroadenoma or fibrocystic disease.
Poor cellularity was the main reason for inadequate smears, which could be due to lack of experience in performing aspiration technique or getting the material on to the slide. Aspiration of ill-defined fibrocystic lesions, fibroadenoma with hyalinization and deep location of tumors also contributed to the inconclusive diagnosis.
The rate of false negatives, false positives varied from 1% to 10% in various studies. In the present study, no false negatives were observed. False positives were 7.14%. False positives were noticed in analyzing proliferative, suspicious lesions.
Ariga performed 1,158 FNAs on women being evaluated for a clinically palpable breast masses. The patients were divided into two groups. Group I consisted of 231 patients aged 40 years and younger and Group II consisted of 927 patients aged 41 years and older. In Group I, there were 117 (51%) malignant FNA diagnosis and only 1(1%) false-positive case, subsequently diagnosed on histopathological material as an atypical papillomatosis. There were 20 (9%) cases diagnosed as suspicious on FNA. On histopathology, 10 were malignant and 10 were benign. Of the 91 (3%) cases interpreted as benign, only one was false-negative. In Group II, which comprised 927 patients, there were 693 (74%) malignant FNA diagnosis and 3 (<1%) false-positive cases, which on follow-up histopathological examination revealed two atypical ductal hyperplasia and one atypical papilloma. For cases suspicious on FNA, 90 (10%) were diagnosed On histopathology, 68 were malignant and 22 were benign. Of the 131 (14%) lesions interpreted as benign, there were 18 false-negative cases (14%) which included 17 infiltrating carcinomas and one DCIS. For the study, 12 (1%) cases were inadequate. Group I had 99% sensitivity, 99% positive predictive value, 99% specificity, 99% negative predictive value. Group II had 98% sensitivity, 97% specificity, 99% positive predictive value and 86% negative predictive value. 
Feichter analyzed 1472 FNAs of the breast obtained over 3 years. The cytologic diagnoses were benign in 1003 cases (68.1%), suspicious in 49 (3.3%) and malignant in 181 (12.3%), 239 (16.2%) of the aspirates were inadequate. Among invasive carcinomas, the sensitivity was 89.9%, specificity 99.3% and overall accuracy 88.5%. Among the cases diagnosed cytologically benign, 182 were compared with biopsies. Of these, 79.9% were true negative, 0.5% (1 case) was false positive and 15.4% had insufficient cells for evaluation. 
Ishita performed 125 FNAs of breast over a period of 1 year. Of these 60 cases were followed-up by histopathologic confirmation. The diagnostic accuracy of this series was assessed. The sensitivity of the FNA procedure was 93.10%, specificity 97.06%, with a positive predictive value 96.43%. The overall diagnostic accuracy was 95.24% [Table 4]. 
|Table 4: Comparison of overall diagnostic accuracy of fi ne needle aspiration in breast tumors|
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Pinto did 58 FNAs of the breast with subsequent histopathology. The youngest patient was 12 and the oldest 82. Females comprised 555 (95.4%) and males 27 (4.6%). Out of 582 aspirations 295 cases (50.7%) were negative (benign) on cytology and in 107 cases (18.4%) the smears were inconclusive and biopsy was advised. Fibroadenoma (188 cases) was the most common benign neoplasm. In males, gynecomastia was the most common lesion (21 cases out of 27). The cytohistologic correlation was 89.7% for fibroadenoma, 65.2% for fibrocystic change, 60% for benign phyllodes tumor, 57.1% for fibroadenosis and 33.3% for breast abscess. 
| Conclusion|| |
Considering patient's comfort, lack of requirement of anesthesia, rapid analysis and reporting and an absence of false positive results makes FNAC an ideal initial diagnostic modality in breast lumps. However, cytologically it is difficult to subcategorize the lesions without clinical and mammographical details. Adhering to the principle of Triple test, with the acquisition of technical, observational and interpretative skills will further enhance the diagnostic accuracy of lesions of the breast. 
| Acknowledgment|| |
It is my privilege and honor to express my gratitude to the principal and management of Kamineni Institute of Medical College, Narketpally for giving me permission to send my work as article.
| References|| |
|1.||Ahmed I, Nazir R, Chaudhary MY, Kundi S. Triple assessment of breast lump. J Coll Physicians Surg Pak 2007;17:535-8. |
|2.||Frable WJ. Needle aspiration biopsy: Past, present, and future. Hum Pathol 1989;20:504-17. |
|3.||Swapan KR, Ranjana B. FNAC of breast with reference to topography and nuclear grading in malignant lesions. J Cytol 2002;19:187-92. |
|4.||Ishita P, Singh PK. Cytomorphologic study of palpable breast lesions and histopathologic correlation. J Cytol 2003;20:129-32. |
|5.||Pinto RG, Kulwant S. A statistical analysis of fine needle aspiration biopsies in palpable benign (neoplastic and non-neoplastic) breast lesions. J Cytol 2004;21:64-7. |
|6.||Feichter GE, Haberthür F, Gobat S, Dalquen P. Breast cytology. Statistical analysis and cytohistologic correlations. Acta Cytol 1997;41:327-32. |
|7.||Dash A, Mohanty R, Mallik R, Dash K. Aspiration smear pattern as a predictor of biological behaviour in breast carcinoma. J Cytol 2005;22:19-21. |
|8.||Thomas PA, Cangiarella J, Raab SS, Waisman J. Fine needle aspiration biopsy of proliferative breast disease. Mod Pathol 1995;8:130-6. |
|9.||Karthik K, Ganapathy H, Alavandar E. Evaluation of fine needle aspiration smears of proliferative breast lesions. J Cytol 2004;21:26-9. |
|10.||López-Ferrer P, Jiménez-Heffernan JA, Vicandi B, Ortega L, Viguer JM. Fine needle aspiration cytology of breast fibroadenoma. A cytohistologic correlation study of 405 cases. Acta Cytol 1999;43:579-86. |
|11.||Ariga R, Bloom K, Reddy VB, Kluskens L, Francescatti D, Dowlat K, et al. Fine-needle aspiration of clinically suspicious palpable breast masses with histopathologic correlation. Am J Surg 2002;184:410-3. |
|12.||Bhattarai S, Kapila K, Verma K. Phyllodes tumor of the breast. A cytohistologic study of 80 cases. Acta Cytol 2000;44:790-6. |
|13.||Venegas R, Rutgers JL, Cameron BL, Vargas H, Butler JA. Fine needle aspiration cytology of breast ductal carcinoma in situ. Acta Cytol 1994;38:136-43. |
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2], [Table 3], [Table 4]