ORIGINAL ARTICLE EVALUATION OF BREAST LESIONS USING X-RAY MAMMOGRAM WITH HISTOPATHOLOGICAL CORRELATION

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1 Available online at INTERNATIONAL JOURNAL OF MODERN RESEARCH AND REVIEWS IJMRR ISSN: Int. J. Modn. Res. Revs. Volume 3, Issue 10, pp , October, 2015 ORIGINAL ARTICLE EVALUATION OF BREAST LESIONS USING X-RAY MAMMOGRAM WITH HISTOPATHOLOGICAL CORRELATION *3 Dr. Archana Jayakumar 1 Dr.M.Adaikkappan and 2 Dr.S.Sethurajan 1 Professor, Department of Radiology, RMMCH, Annamalai University, Annamalai Nagar 2 Lecturer, Department of Radiology, RMMCH, Annamalai University, Annamalai Nagar 3 PostGraduate, Department of Radiology, RMMCH, Annamalai University, Annamalai Nagar Article History: Received 15 th September,2015, Accepted 9 th October, 2015, Published 10 th October,2015 ABSTRACT AIM: To use x-ray mammogram for classifying palpable breast lumps into benign and malignant lesions, using various mammographic features and to correlate the findings with histopathological gold standard.methodology: Women referred for the evaluation of palpable breast lumps and nipple discharge were included in the study.result: In this study, mammography had a sensitivity of 94%, specificity of 97 %, positive predictive value of 89% and a negative predictive value of 98%. Sensitivity of x-ray mammogram in younger age group (<40 years) is 89% and in older age group (>40 years) is 96%.CONCLUSION: There is positive correlation between xray mammogram and histopathology. Mammography is a very sensitive and specific test for detection of breast malignancy. Mammographic features like microcalcification and spiculated margin are the most specific findings in malignancy. Mammography has a better sensitivity in older age group than in the younger age group. Keywords: Breast lump, X-ray mammogram, histopathology, sensitivity, specificity, microcalcification, spiculated margin. 1.INTRODUCTION Women present with a number of breast complaints like mastalgia, nipple discharge and a feeling of lump in the breast. Of these a lump in the breast is a matter of great concern for the patients as they equate it to cancer. The most important decision for the radiologist to make, is whether the lesion is benign or malignant. In spite of all the recent advances in breast imaging, mammography remains as the most exclusively used modality for breast cancer screening and early breast carcinoma detection. It is estimated that one in eight women will develop breast carcinoma in their lifetime, which further stresses the importance of early detection of cancer in a treatable stage. This study is an attempt to characterize the mammography features of breast masses and to evaluate the accuracy of each in diagnosing breast lesions and to correlate them with histopathological gold standard. *Corresponding author: Dr. Archana Jayakumar, Department of Radiology, Rajah Muthiah Medical College Hospital,Annamalai University, Chidambaram 2. MATERIALS AND METHODS A descriptive study was done, for a period of 2 years, from October 2013 to October 2015 on 152 patients who presented with palpable breast lumps, in the Department of Radiology and Imaging Sciences of Rajah Muthiah Medical College and Hospital, Chidambaram. All the patients were referred from the Department of Surgery, Rajah Muthiah Medical College and Hospital, Chidambaram. As per inclusion criteria, all patients above 15 years of age with palpable breast lumps and patients with nipple discharge were included in the study. As per exclusion criteria Patients with advanced breast carcinoma (e.g. fungating lesions), known inflammatory lesions (e.g. breast abscess), post operative or previously treated cases, post biopsy cases, patients with known histopathological report and patients who refuse to give consent for imaging are excluded from the study. After detailed history and clinical examination, patients underwent mammography in our dedicated mammography unit Philips Mamodiagnost. The craniocaudal and mediolateral oblique views were employed in all cases. For the craniocaudal view, the cassette is placed at the level of the inframammary fold below the breast and then elevated so 807

2 [ Dr. Archana Jayakumar et al., 2015 that the breast is pulled forward and raised until the skin below the inframammary level is seen taut. Compression is given to the breast from above. X ray beam is also directed vertically from above. For mediolateral oblique view compression is given perpendicular to the long axis of the pectoralis major muscle. And the xray beam is directed perpendicular to the pectoralis major from superomedial to inferolateral direction. criteria used for lesions in mammography are low density, circumscribed margin and presence of macrocalcification. criteria in mammography are high density, spiculated margins and presence of fine pleomorphic/ fine linear/ fine linear branching microcalcifications. 3.RESULT In this study mammography had a sensitivity of 94%, specificity of 97 %, positive predictive value of 89% and a negative predictive value of 98%. Sensitivity of x-ray mammogram in younger age group (<40 years) is 89% and in older age group (>40 years) is 96% Table 1 Association of Age with reference to the type of lesion. Age (in Number Percenta Number Percentage years) ge Maximum number of patients who presented with breast lumps, irrespective of their benign or malignant nature belonged to the age group of years. The most common benign lesion observed in the study population is fibroadenoma, which was present in 77 patients (51% of study population). As per literature, fibroadenoma is commonly seen below 35 years of age. In this study 53 out of 77 patients having fibroadenoma, were below 35 years (68.8%). The youngest patient with malignancy was 27 years of age and the oldest patient with malignancy was 65 years old. In the study no malignancy (0%) was seen in the age group and the lowest percentage of malignancy (11%) was seen in age group. Highest percentage of malignancy (60%) was seen in years age group where 6 out of 10 cases are malignant. This is followed by the age group of years where 9 out of 21 cases i.e. 43% of cases were malignant. Therefore there is a higher chance of malignancy in patients older than 45 years of age. Table 2 Association of quadrant wise distribution with type of lesions Quadrant Upper outer Lower outer Lower Inner Upper Inner Retroareolar Total The most common site of location of both benign as well as malignant lesions is in the upper outer quadrant. This location had lesions in 47% of the study population. 45% of benign lesions are located in the upper outer quadrant. 51.5% of malignant cases had breast lump in the upper outer quadrant and 21.2% in the retroareolar region. As per literature also, more than 50% of carcinomas are located in the upper outer quadrant, probably due to more concentration of terminal ductal lobar units over the same. Table 3 Relationship of Family History with age of onset of disease Age Family History (in years) Absent Present Total p value is which is >0.001 Relationship of family history with the age of occurrence was not found to be statistically significant in the study probably due to the reduced sample size. Table 4 Association of xray mammogram density of lesion to type of lesion Density Type of Lesions of lesion Low High Table 5 Association of Xray mammogram Margin with benign and malignant lesions Margin Type of Lesions Circumscribed Lobulated Indistinct Spiculated Table 6 Association of nature of calcification with type of lesions Calcification Type of Lesions Nil Microcalcific ation Macrocalcifi cation Table 7 Distribution of Type of Lesions in Relation to BIRADS BIRADS Type of Lesions

3 Volume 3, Issue 10, pp , October, 2015 Table 8 Distribution according to mammographic diagnosis Mammographic Number Percentage diagnosis Total Xray mammogram showed 23% of malignant cases and 77 % benign cases. Criteria for benign lesions in Xray mammogram are low density, circumscribed margin and macrocalcification (presence of 2 or more criteria). In the study, 99% of cases with a well circumscribed margin, 92% of the cases with low density, 95% of cases with macrocalcification and 94% of cases with no evidence of any calcifications were found to be benign. All the 95% of cases with macrocalcification were histologically proven to be benign, most of them being calcified fibroadenomas. Of these features well circumscribed margin is found to be the most specific finding in benign lesions. On statistical analysis, all these findings were found to have a significant correlation with benign etiology. Criteria for benign lesions in x-ray mammogram (presence of 2 or more criteria), are high density, spiculated margins and presence of microcalcifications. 100% of cases having spiculated borders and 100% of cases having fine linear or pleomorphic microcalcifications were proven to be malignant. Hence these mammographic findings have a positive predictive value of 100% towards malignancy. 66% of cases presenting with a low density on mammogram showed malignancy. So all these findings are found to have a statistically significant correlation with malignant etiology. As per the criteria of malignancy in xray mammography, 4 cases which were diagnosed as malignant lesions turned out to be benign as per histopathology. 2 cases with high density and spiculated margins (satisfying 2 malignant criteria in xray mammogram) was proven to be granulomatous mastitis or abscess in histopathology. Mammographic appearance of breast abscess can mimic carcinoma. Clinical diagnosis of breast abscess should be employed in such cases. 2 cases had high density and spiculated margins thus satisfying 2 criteria in malignancy, but histopathologicaly it was proved to be a fibroadenoma. Generally fibroadenomas have a regular margin in xray mammography, but rarely the margins can show small lobulations which can be mistaken as a spiculated margin. Applying criteria for benign lesions in xray mammogram, 77% of cases were reported as benign. Of these, 2 cases which were reported as benign turned out to be malignant as per histopathology. These lesions were mammographically categorised as benign lesions as they had a low density with smooth circumscribed margins thus satisfying 2 benign criteria in mammography (satisfying 2 benign criteria in mammography) but on histopathology they were proven to be invasive ductal carcinoma. Circumscribed carcinoma is a well described entity and is difficult to differentiate in earlier stages with imaging. Table 9 Comparison of Xray mammography diagnosis with Histopathological Gold Standard Xray Histopathological type of Lesions Mammography diagnosis Table 10. Xray Mammogram diagnosis and Histopathology Cross tabulation Histopathology Total Mammogra Count m Diagnosis Histopathology 93.9% 3.4% 23.0% Count Histopathology 6.1% 96.6% 76.9% Total Count Histopathology 100.0% 100.0% 100.0% For xray mammography the sensitivity, specificity, positive predictive value, negative predictive value are 93.9%, 96.6%, 88.6% and 98.3% respectively. In the published study conducted on 408 women having palpable breast lumps by Yang et al (11) in 1996 the results obtained for Xray mammography are: Sensitivity: 92%, Specificity: 94% Positive predictive value: 84%. The results obtained are comparable to the study quoted. Table 11. Xray Mammogram Diagnosis and Histopathology Cross tabulation in younger age group <40 years Histopathology Total Mammogra Count m Diagnosis Histopathology 88.8% 4.1% 13.4% Count Histopathology 11.1% 95.8% 86.5% Total Count Histopathology 100.0% 100.0% 100.0% Sensitivity in younger age group (less than 40 years): Xray Mammogram: 89% Table 12. Xray Mammogram Diagnosis and Histopathology Cross tabulation in older age group >40 years Mammogram in Diagnosis Histopathology Total Count Histopathology 95.8% 0% 32.8% Count Histopathology 4.1% 100% 67.1% Total Count Histopathology 100.0% 100.0% % Sensitivity in older age group (more than 40 years): Xray Mammogram: 96% 809

4 Volume 3, Issue 10, pp , October, 2015 ACR pattern breast compositions ACR composition a ACR composition b 810

5 Dr. Archana Jayakumar et al., 2015 A CR composition c ACR composition d Lipid cyst Breast cyst Fibroadenoma Phyllodes tumor Multiple fibroadenoma Coarse heterogenous Popcorn calcification Lucent centered calcification calcification 811

6 Volume 3, Issue 10, pp , October, 2015 Xray-Mammogram Diffuse calcification Regional calcification Grouped calcification Pleomorphic ca lcification Rod like/ Secretory calcification Vascular calcification 812

7 Dr. Archana Jayakumar et al., 2015 Xray-Mammogram Radial Scar BI-RADS 2 BI-RADS 3 BI-RADS 4 BI-RADS 5 BI-RADS 6 In the published study by Kolb et al (12) it is stated that in women with fatty breasts in older age group the sensitivity of mammography was 98%. In this study the results thus obtained, are comparable to the studies quoted. 4.DISCUSSION High resolution mammography is the best imaging tool for identification and characterization of breast calcifications. Development of dedicated mammography units has given a new dimension to breast imaging, by reduced radiation dose and improved resolution which has improved the diagnostic sensitivity of mammography. Various parameters used in xray mammogram are listed below. MASS DENSITY: A mass with a density, which is higher than the rest of the breast fibroglandular tissue is considered malignant while lesions with a density lesser than that of the breast 813

8 Volume 3, Issue 10, pp , October, 2015 parenchyma are more likely to be benign. However according to the study conducted by Jackson V.P et al., this is found to be unreliable. (1) MARGINS: masses usually have well defined circumscribed margins. However, circumscribed margins may also be seen in medullary / mucinous malignancy. Lobulated margin is seen both in benign and well as malignant conditions. Poorly defined / ill-defined / indistinct margins are also seen in both benign and malignant lesions. Spiculated margins have a very high probability for malignancy (> 95%). Only exception is seen in radial scar / post operative changes, which can also present with spiculated borders and mimic malignancy. Apart from this, even the presence of slight spiculation is suggestive of malignancy. (2) CALCIFICATION: Pattern of calcification is a very important mammographic parameter for characterizing breast lesions. Fibroadenomas usually show coarse calcification mainly at the periphery. Egg shell calcification located in the wall of the lesion are suggestive of benign lesions. (2) Popcorn pattern of coarse calcification is also seen in fibroadenoma. Branching pattern of microcalcification is suggestive of malignant pattern usually seen in ductal adenocarcinoma. SHAPE: Various shapes in mammography are described according to the nature of the lesion Oval lesions are usually seen in fibroadenoma. Round lesions are commonly benign. Exception to this is seen in lymphoma, sarcoma and mucinous carcinoma, which also presents as round lesions. Lobular mass having undulations or few microlobulations are seen in both benign and malignant conditions. Irregular shape is a common finding in malignancy. Inflammatory conditions like abscess can also have an irregular shape and mimics malignancy. SIZE STABILITY: Stability of the size of the lesions in the present and previously taken mammograms suggest a benign etiology. A mass which has increased in size, especially in a post menopausal woman suggests a malignant etiology. (3) FAT Presence of fat density in a hamartoma, fat necrosis, intramammary lymphnode or lipoma does not exclude the possibility of malignancy. MULTIPLICITY: Multiple lesions are usually seen in benign conditions such as multiple lymph nodes, multiple cysts and fibroadenomas. Sickles found in his study, a cancer incidence of 2% for solitary masses and 0.4% for multiple masses. (4) PERIFOCAL HAZINESS: It is common feature of malignant lesions and rarely seen in benign ones. ARCHITECTURAL DISTORSION: Sometimes in early stages of malignancy, an area of architectural distortion might be the only finding, with the absence of any other supportive features. TYPES OF CALCIFICATIONS IN BREAST MASSES: Breast calcifications are small deposits of calcium that develop in a woman s breast tissue. They are a very common mammographic finding and most of the cases are benign. In some cases, certain patterns of breast calcification are suggestive of development of early breast cancer. (5-8) On an x-ray mammogram, these calcifications will appear as macrocalcifications or microcalcifications. Macrocalcifications: They are almost always benign and do not require any biopsy or follow up. Typically benign calcifications are coarse or popcorn like calcification, egg shell or rim calcifications, lucent centered calcifications, skin or dermal calcifications, vascular calcifications, round and punctate calcifications, large rod like calcifications, milk of calcium calcifications, suture calcifications and dystrophic calcifications. (9,10) Microcalcifications: They can be non-cancerous but certain patterns of microcalcifications are pathognomic for cancer. They are seen as five, white specks of radiopacity in mammogram. Calcifications suggestive of malignancy are amorphous, coarse heterogenous, fine pleomorphic, fine linear and fine linear branching. STATISTICAL ANALYSIS Patients with breast lumps were classified into both benign and malignant form of the disease, by using the above mentioned radiological parameters, specific to xray mammogram. The findings thus obtained were compared with the histopathological gold standard. The association of age, quadrant, shape, size, margin and calcification are studied with reference to benign and malignant involvement. The chi-square test of association is used to study this relationship. There is a significant association if the p value is less than The mammographic findings are compared with gold standard method by cross tabulation and through sensitivity, specificity, positive predictive value and negative predictive value. The statistical analysis is carried out using Statistical Package of Social Sciences (SPSS 21) and by manual method. Suitable tabular illustrations are also presented alongwith. 6. CONCLUSION 1.In this study, there is a statistically significant correlation between the x ray mammogram features of benign and malignant breast lesions on comparison with the histopathological gold standard. 2. In xray mammography, spiculated borders and fine linear or pleomorphic pattern of microcalcification, is found have a high positive predictive value for malignancy. 3. The sensitivity, specificity, positive predictive value, negative predictive value of xray mammography were 94%, 97%, 89%, 98% respectively which is comparable with international studies. 4. The sensitivity of mammogram is better in older patients (over 40 years) with a sensitivity of 96% when compared to younger age group (less than 40 years) where the sensitivity is 89%. ***** 814