Fibrocystic change (FCC) of the breast is a benign alteration in the terminal ductal lobular unit of the breast. It is one of the common diseases encountered in day-to-day practice. FCCs are commonly observed among women of the reproductive age group, between 20 and 50 years, with a peak in the perimenopausal age group. 123 Cole et al. observed that the age standardized incidence rate for fibrocystic diseases was 89.4 per 100,000 woman years. 1 FCCs commonly have diffuse, multifocal abnormalities affecting both breasts. Clinical presentation is usually mastalgia, lump in the breast, or nipple discharge. The lesions arise from the terminal ductal lobular unit (TDLU) due to aberrations in the TDLU resulting in various imaging and pathological manifestations. Evaluation is done using imaging modalities like ultrasound, X-ray mammogram and MRI. BIRADS assessment is done using American College of Radiology (ACR) guidelines and suspicious lesions need further pathological analysis. In this study, we evaluated the various imaging manifestations of FCC on ultrasound and X-ray mammogram with further histopathological correlation.

This study was carried out to evaluate the radiological presentation of FCC and to correlate them with histopathological examination. We consider this topic on the spectrum of fibrocystic changes (FCC) and its mimics as FCC is one of the most common benign diseases. Although it commonly presents as benign appearing cysts, it can sometimes appear as suspicious lesions. Hence, an effort was made to review the various imaging appearances of FCC along with histopathological correlation for better understanding of the different imaging appearances of fibrocystic disease spectrum.

This retrospective study was carried out among all the patients with pathological/radiological diagnosis of fibrocystic disease in our tertiary teaching institution for a period of 16 months. Data of 172 women were entered and analyzed in this study.

Patients with either radiological or pathological diagnosis of fibrocystic disease were included. The radiological diagnosis was made in line with the 5 th edition of ACR BI-RADS. The pathological criteria included features of adenosis, fibrosis and cyst formation. Features like apocrine metaplasia or columnar cell metaplasia in the biopsy/excision specimens were also considered. Other parameters included sclerosing adenosis, intraductal papilloma and ductal hyperplasia with or without atypia.

Patients with breast malignancy diagnosed by either radiology or histopathology were excluded.

Participants under 40 years of age underwent breast ultrasound and participants over 40 years underwent X-ray mammogram with ultrasound correlation. In participants who were symptomatic and had dense glandular parenchyma, ultrasound screening was performed in addition to X-ray mammography.

Computed radiography (CR) mammogram was performed using GE Alpha ST® machine (Exposure parameters -35kV, 100mA). Digital Xray mammography (automated exposure) was performed using Fujifilm AMULET Innovality® machine. Ultrasound breast and guidance for interventions was done using Toshiba Aplio® 500 ultrasound machine using linear high frequency probe 45678. Depending on the imaging findings, the appropriate BI-RADS category was assigned based on the recent American College of Radiology (ACR) BI-RADS guidelines (5 th edition). 9 Ultrasound guided intervention was performed in all the lesions categorized under BIRADS4a/b/c. BI-RADS 3 lesions were either followed up or intervention was performed for symptomatic relief to reduce the patients' anxiety in cases of strong family history of breast cancer. BI-RADS 2 lesions were termed as benign and intervention was performed if the cyst was large and causing discomfort to the patient.

Ultrasound guided fine needle aspiration (FNA) was done using 24 Gauge needle and slides were prepared and sent for cytological analysis. Ultrasound guided core biopsy was done using 14 gauge, 10cm length needle and the tissue samples obtained were sent for histopathological correlation. The pathology results and the imaging findings were retrospectively analyzed.

Overall, 62% of the lesions were identified on ultrasound and most of the lesions (62%) were assigned to BI-RADS 2 category. Simple cysts were the most common pathology (65.7%) identified followed by complicated cysts (50 %) and clustered cysts (45%) being the next commonly identified lesions in the FCC spectrum.

Pathologically simple cyst formation (45%) was the most commonly identified finding and ducts with apocrine metaplasia epithelial hyperplasia without atypia were the second most common finding (24%).

The age distribution of the study population was from 21 to 80 years, with a mean age of 43 years. Ultrasound was performed on 110 patients. Xray mammogram with ultrasound correlation was performed on 62 patients. Among 172 patients, BI-RADS 2 was assigned to 67 patients (39%), BI-RADS 3 to 59 patients (34.3%), BI RADS 4a to 28 patients (16.2%), BI-RADS 4b and 4c to 16 (9.3%) and 2 (1.1%) patients, respectively (Table 1).

Focal abnormality (single focus of clustered cysts/solid lesion/dilated duct, located either unilaterally or bilaterally) was seen in 10 patients (5.8%). Diffuse abnormalities (scattered throughout the breast, either unilaterally or bilaterally) were seen in t h e rest of t h e 162 (94.2%) the patients. Most of the findings were bilateral (163 patients, 94.8%), with a few cases (9 patients, 5.2%) having a unilateral distribution.

The most common ultrasound imaging finding was simple cysts (113 patients), followed in order by complicated cysts (50 patients), clustered cysts (45 patients), complex solid cystic masse (26 patients), solid lesions (26 patients), duct ectasia (26 patients) and intraductal lesions (12). Common findings on X-ray mammogram were dense fibro-glandular pattern (42 patients), followed in order by equal density lesions (20 patients), calcifications (15 patients) and asymmetry (4 patients) ( Table 2). As for the correlation of imaging and pathological findings, simple and complicated cysts revealed cyst formation in 95% of the cases and epithelial hyperplasia in 5% of the cases. Complex solid cystic masses revealed cyst formation in 88% of the cases, with 10% showing epithelial hyperplasia and 2% showing atypical ductal hyperplasia. Simple duct ectasia lesions revealed dilated ducts with epithelial hyperplasia without atypia in all cases (100%). Ducts with internal echoes and clustered cysts showed apocrine metaplasia in 75% of the cases and epithelial hyperplasia without atypia in 25% of the cases. Dilated ducts with solid components showed intraductal papilloma in 75% of the cases and atypical ductal hyperplasia in 25% of the cases (Table 4).

The basic functional unit in the breast is the terminal ductal lobular unit (TDLU). 104 TDLU is the most important component as all the major diseases pertaining to the breast originate from the functional unit. The development of fibrocystic disease is linked to the hormonal status, as studies have shown a positive link between estrogen and fibrocystic disease. The fibrocystic disease is a consequence of aberration in the normal process of development and involution (ANDI) with associated hormonal irregularities. There is a high prevalence of FCC among patients with polycystic ovarian disease (PCOD) and those on hormone replacement therapy. 56 ANDI results in apocrine metaplasia, clear cell changes, eosinophilic change and microcystic involution. These epithelial changes result in epithelial hyperplasia, and accumulation of secretions causing dilatation of ducts, which in turn result in cyst formation, causing calcifications on mammography. Histologically, the normal breast tissue may also show aberrations, many of which are not detected clinically or on imaging. 7 On ultrasound, the lesions were commonly bilateral. Focal abnormalities were less common compared to diffuse widespread abnormalities. Simple cysts (Figure 1a) were the most common imaging finding in FCC on ultrasound. 8 They were usually multiple and bilateral, either single or clustered together. These groups of lesions were categorized as BI-RADS 2 as per ACR guidelines. 1112 Complicated cysts (by infection/inspissated secretions) showing internal echoes within ( Figure 1b) were another feature on ultrasound which was categorized as BI-RADS 3. The two above categories were commonly followed up. Intervention was performed either for symptomatic relief or to allay the patients' anxiety. (Figure 2b). The lesions were either well circumscribed or showed partly obscured borders (Figure 2c), with the former classified as BI-RADS 3 and the latter as BI-RADS 4a/4b. On color Doppler imaging, lesions showing increased vascularity were classified as either 4b or 4c. They generally presented as solid lesions with a few mimicking malignancy. 1314 On light microscopy, most of the solid lesions showed compressed ducts surrounded by dense stroma and a few cystically dilated ducts (Figure 2d). The most common ductal abnormality was simple duct ectasia commonly encountered in the central sub areolar region and seen more often bilaterally (Figure 3a). These lesions were categorized as BI-RADS 2. Sometimes the ducts show internal echoes / debris with no internal vascularity/mild wall thickening (Figure 3b). These lesions were categorized as BI-RADS 3. Light microscopy of the lesions indicated dilated ducts showing apocrine change (Figure 3c). Breast tissue showing group of ducts was surrounded by sclerosis (Figure 3d). Features of duct ectasia that should raise suspicion for an underlying malignancy include a peripherally dilated duct (one well away from the retro areolar region), overall irregularity of the duct margin, focal wall thickening, and adjacent hypoechoic tissue.

The most common abnormality on X-ray mammography was dense fibro-glandular pattern (type C or type D). The problem of dense fibroglandular parenchyma generally obscures t he underlying mass lesions (Figure 5a and 5b). The other common abnormality includes opacities caused due to cysts and solid lesions (Figure 5c and 5d), clearly seen on ACR type A breasts.

Benign micro-calcifications were commonly associated with fibrocystic disease. Lobular patterns of rounded calcifications were the most In our study the calcifications were seen in both breasts, with diffuse /regional distribution being the most common pattern. In a few patients, the calcifications were in a group and seen as three or more grouped areas of calcifications. As per ACR guidelines, the calcifications were assigned BI-RADS category in correlation with ultrasound findings.

Asymmetry and architectural distortion were also observed. Compression and magnification views were performed to differentiate from the overlapping breast tissue. Targeted ultrasound was performed and, if associated with an abnormality, it was either followed up or intervention was performed depending on ultrasound appearances. As to the correlation with imaging and pathological findings, the clear cysts and complicated cysts show features of cyst formation and epithelial hyperplasia without atypia (epitheliosis). Complex solid cystic masses, when completely excised with ultrasound guided vaccumm assisted biopsy and proven to be benign on histopathological examination, do not require any further imaging follow up or surgery. 15 Complex solid cystic masses also showed features of apocrine metaplasia, cyst formation, and epithelial hyperplasia without atypia (epitheliosis). Solid lesions were commonly sclerosing adenosis. Ductal lesions showed either simple duct ectasia, epithelial hyperplasia without atypia or intraductal papilloma. A few of the ductal lesions and complex solid cystic masses showed features of atypical ductal hyperplasia. Lesions showing features of sclerosing adenosis or epithelial hyperplasia (proliferative lesions without atypia) and epithelial hyperplasia with atypia should be followed up or surgically excised due to their association with breast malignancies. 1617 CONCLUSION Fibrocystic change in the breast is one of the most common groups of breast disorders we come across in day today practice, varied imaging manifestations on ultrasound and X-ray mammogram. In our study, these cystic lesions did not reveal any abnormality as these patients had dense glandular patterns. It is essential for radiologists to be familiar with imaging and pathological findings of fibrocystic disease of the breast for further workup and management as it is not only the most common benign disease of the breast but it can also sometimes present as suspicious lesions.

Approval was obtained from the Institutional Ethics Committee prior to the commencement of the study.