Med jdy patiluniv73326-1028691_025126

326 Medical Journal of Dr. D.Y. Patil University | May-June 2014 | Vol 7 | Issue 3

Address for correspondence: Dr. Sushma Yalavarthi, Department of Pathology, Mamatha Medical College, Khammam, Andhra Pradesh, India. E-mail: [email protected]

Histopathological and cytological correlation of tumors of breastSushma Yalavarthi, Ramamurti Tanikella1, Shailaja Prabhala1, Uma Shankar Tallam1

Departments of Pathology, Mamata Medical College, Khammam, 1Kamineni Institute of Medical Sciences, Andhra Pradesh, India

ABSTRACTBackground: With the advent of fi ne 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: 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 infl ammatory 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 fi broadenoma, fi brocystic disease and duct cell carcinoma respectively. False positives were observed in proliferative lesions. No false negative cases observed. The sensitivity of the fi ne needle aspiration (FNA) procedure was 100%, specifi city, 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, fi ne needle aspiration cytology, histopathology, proliferative lesions

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DOI:

10.4103/0975-2870.128975

Original Article

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 fi ne needle aspiration cytology (FNAC) of breast lumps is to confi rm cancer pre-operatively and to avoid surgery in specifi c 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.[1]

However, the aspiration cytology is not a substitute for conventional surgical histopathology as a defi nitive 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 1st October 2006 to 31st September 2008. During this period, 334 fi ne 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, infl ammatory 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 fi xed 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

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Yalavarthi, et al.: Cytohistological correlation of breast tumors

Medical Journal of Dr. D.Y. Patil University | May-June 2014 | Vol 7 | Issue 3 327

treatment, are all factors to be taken into account in this regard. The surgical specimens were fi xed in 10% formalin. The gross and cut section fi ndings were noted. Several bits were taken from appropriate sites for processing and paraffi n 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 infl ammatory 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 fi broadenoma. 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 fi fth 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, fi brocystic change constituted the largest disease group with maximum incidence in the fourth decade, followed by fi broadenoma with maximum incidence in the third decade [Figures 1 and 2]. Apart from these, one case of phyllodes tumor and one case of giant fi broadenoma were reported. In the malignant breast lesions, maximum cases were reported as infi ltrating duct carcinoma with maximum incidence in the fi fth decade [Figures 3 and 4]. One case of duct cell carcinoma associated with Paget’s disease was reported in the seventh decade. A single case of infi ltrating 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 infi ltrate and tumor cells arranged in syncytial pattern. Out of 26 cases diagnosed as benign on FNA and

Table 1: Age distribution among breast FNAs (N=293)

Age group (years) Benign n = 164 (%) Malignant n = 45 (%) Proliferative, suspicious n = 25 (%) Inadequate n=59 (%)10-20 27 (16.46) · · 7 (11.86)21-30 74 (45.12) · 3 (12.00) 21 (35.60)31-40 48 (29.27) 8 (17.77) 14 (56.00) 19 (32.20)41-50 12 (7.32) 21 (46.66) 3 (12.00) 7 (11.86)51-60 3 (1.94) 8 (17.77) 4 (16.00) 2 (3.39)61-70 · 8 (17.77) · 2 (3.39)71-80 · 1 (4.00) 1 (1.69)FNA-Fine needle aspirations

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 fi broadenoma (H and E, ×40)

c

b

a

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)

c

b

a





included in cytohistologic correlation, fibroadenoma comprised the maximum cases (19) followed by fi brocystic change (7). Cytohistologic correlation was 73.68% for fi broadenoma, 42.85% for fi brocystic disease, 94.44% for duct cell carcinoma [Table 2].

Following histopathologic correlation, sensitivity, specifi city, 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%, specifi city, 88.5% and the predictive value of a positive result was 84% [Table 3].

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.”[1]

In the present study, 334 (including 16 bilateral) aspirations were performed over a period of 2 years. Suppurative and

infl ammatory 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 confi rmation. 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 confi rm 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.[2]

Swapan aspirated 408 cases by using 20 ml disposable syringes and 23 gauge needles. Frable and Zajicek used special syringe holders.[2,3]

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 fi broadenoma.

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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Table 2: Cytological and histopathological correlation of the lesions (N = 56)

Histo DiagnosisCyto diagnosis

Fibro Adenoma Fibrocystic Disease

Fibro Adenosis

Phyllodes Tumor

Duct Cell Carcinoma

Medullary Carcinoma

Total n (%)

Fibro adenoma 14 (73.68) 3 (15.78) 1 (05.26) 1 (05.26) · · 19 (100.00)Fibrocystic disease 3 (42.85) 3 (42.85) · 1 (14.29) · · 7 (100.00)Florid epithelial hyperplasia 2 (66.67) · · · 1 (33.33) · 3 (100.00)Atypical hyperplasia 1 (25.00) · 1 (25.00) · 2 (50.00) · 4 (100.00)Duct cell carcinoma · · · · 17 (94.44) 1 (05.55) 18 (100.00)Inadequate 3 (60.00) 1 (20.00) 1 (20.00) · · · 5 (100.00)

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)

dc

ba





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 fi fth 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 fi fth decade.[4]

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.[5]

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.[3]

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%).[3,4]

Various authors proposed different reporting protocols in classifying the breast lesions. Feichter analyzed 1472 aspirations and classifi ed the lesions into four categories; benign, suspicious, malignant and inadequate.[6] Ishita classifi ed the lesions into four diagnostic classes. i.e., benign, malignant, suspicious, inadequate.[4]

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, fi brocystic change constituted the largest disease group with maximum incidence in the fourth decade, followed by fi broadenoma 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 fi nding that the fi brocystic change was the most common benign lesion, followed by fi broadenoma.[3,4]

According to Pinto fi broadenoma was the most common lesion. Next common lesion was fi brocystic disease. In males, gynecomastia was the most common lesion.[5]

Among malignant lesions, infi ltrating duct cell carcinoma was the most common, which coincided with the many authors.[3-5,7]

Thomas performed 2800 fi ne 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.[8]

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),

ba

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)

Table 3: The diagnostic accuracy of FNAC in 56 histologically correlated cases

FNAC result Histopathological diagnosis TotalPositive Negative

Positive for malignancy 21 (TP) 4 (FP) 25Negative for malignancy - 31 (TN) 31Total 21 35 56TP: True positive, FP: False positive, TN: True negative, FNAC: Fine needle aspiration cytology





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.[9]

In the present study, three cases were cytologically diagnosed as fl orid epithelial hyperplasia. Two of them were interpreted histologically as fi broadenoma, 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 fi broadenoma and fi broadenosis and two cases were diagnosed as infi ltrating 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.[10] In Pinto study, the cytohistologic correlation for fi broadenoma was 89.7%. In benign lesions, the overall cytohistological agreement was 82.4%.[5]

In the present study, cytohistologic correlation was 73.68% for fi broadenoma, 42.85% for fi brocystic disease. Out of 19 cases of fi broadenoma, 14 were diagnosed histologically also as fi broadenoma, three as fi brocystic diseases, one case was fi broadenosis and one was phyllodes tumor. Out of seven case of fi brocystic disease, three diagnosed as fi broadenoma, 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 fi ne 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 confi rmed by histopathological examination. Positive correlation between cytologic and histologic grade was seen 77.4% of cases.[7]

In the present study, cytohistologic correlation was 94.44% for duct cell carcinoma. One case of infi ltrating 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, fi ve inadequate cases were analyzed. Histology of all the fi ve cases revealed benign nature of either fi broadenoma or fi brocystic 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-defi ned fi brocystic lesions, fi broadenoma 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 infi ltrating carcinomas and one DCIS. For the study, 12 (1%) cases were inadequate. Group I had 99% sensitivity, 99% positive predictive value, 99% specifi city, 99% negative predictive value. Group II had 98% sensitivity, 97% specifi city, 99% positive predictive value and 86% negative predictive value.[11]

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%, specifi city 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 insuffi cient cells for evaluation.[6]

Ishita performed 125 FNAs of breast over a period of 1 year. Of these 60 cases were followed-up by histopathologic confi rmation. The diagnostic accuracy of this series was assessed. The sensitivity of the FNA procedure was 93.10%,





specifi city 97.06%, with a positive predictive value 96.43%. The overall diagnostic accuracy was 95.24% [Table 4].[4]

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 fi broadenoma, 65.2% for fi brocystic change, 60% for benign phyllodes tumor, 57.1% for fi broadenosis and 33.3% for breast abscess.[5]

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 diffi cult 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.

AcknowledgmentIt 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.

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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 fi ne 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 fi ne 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 fi broadenoma. 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.

Table 4: Comparison of overall diagnostic accuracy of fi ne needle aspiration in breast tumors

Statistical parameters

Feichter[6] N = 1472%

Ishita[4] N = 60 %

Present study N = 56 %

Sensitivity 89.90 93.10 100.00Specificity 99.30 97.06 88.50

Predictive value of positive result

· 96.43 84.00

How to cite this article: Yalavarthi S, Tanikella R, Prabhala S, Tallam US. Histopathological and cytological correlation of tumors of breast. Med J D Y Patil Univ 2014;7:326-31.

Source of Support: Nil. Confl ict of Interest: None declared.



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