Can Molecular Breast Imaging With Tc-99m Sestamibi Safely Rule Out Malignancy in Pathologic Nipple Discharge?

Abstract

Purpose: Nipple discharge is the third most common breast-related complaint. It is recommended to exclude malignancy in pathologic nipple discharge (PND). Mammography and ultrasound are the first-line conventional diagnostic (CD) imaging. Although magnetic resonance is often used as a complementary modality, molecular breast imaging (MBI) with Tc-99m sestamibi may be a suitable alternative. Considering the lack of information on this subject and its clinical importance, this study aimed to evaluate the role of MBI in ruling out malignancy in patients with PND and negative/indeterminate CD.

Patients and methods: Retrospective cohort single-center study including all patients with PND evaluated by CD and MBI between 2012 and 2020. Pathology was considered the gold standard. Follow-up was used when pathology was not available.

Results: Of the 96 cases of PND included, 78 were benign, and 18 (20%) corresponded to breast cancer (BC). Although CD and MBI were concordant in the BIRADS classification in 81% (78/96), half of BC were detected by MBI only. BC was located directly behind the nipple in a minority of patients (11%), meaning that MBI could significantly prevent futile central ductal excision. MBI presented higher sensitivity (83% vs. 33%) and negative predictive value (96% vs. 86%) than CD alone, with similar specificity (89% vs. 92%) and positive predictive value (63% vs. 50%). The area under the curve of MBI and CD was 0.86 ( P -value<0.001 [95% CI: 0.75-0.97]) and 0.63 ( P -value=0.091 [95% CI: 0.47-0.79]), respectively.

Conclusions: MBI showed good diagnostic accuracy for detecting BC in patients with PND with negative/indeterminate findings on CD imaging.

Keywords: Tc-99m sestamibi; breast cancer; breast imaging; gamma-camara scintigraphy; molecular breast imaging; nipple discharge.

FIGURE 1

Flowchart representing the investigation procedure of PND (pathologic nipple discharge).

FIGURE 2

Schematic representation of the concordance between imaging findings and final diagnosis. CD indicates conventional diagnostic imaging with mammography and ultrasound.

FIGURE 3

Illustration of a deep breast cancer lesion occult on CD but diagnosed after MBI-guided biopsy. Seventy-four-year-old woman with unilateral nipple discharge from the left breast. MG/US revealed an area of breast duct ectasia and cysts in the retroareolar region but no suspicion of malignancy (BIRADS 2). MBI performed 15 days after MG/US, showed increased uptake in the upper lateral quadrant of the left breast in a segmental pattern, measuring 7 cm, suspicious of malignancy (BIRADS 4). MBI-guided biopsy was compatible with a DCIS G2, and surgery revealed multifocal ADC NST in large area of DCIS G2. CC indicates craniocaudal; ML, mediolateral; MLO, mediolateral oblique.

FIGURE 4

Illustration of the benefits of MBI-guided biopsy in case of discordant findings between CD and US-guided biopsy. Seventy-two-year-old woman with left nipple retraction and unilateral nipple discharge. MG/US showed asymmetry in the left upper lateral quadrant, suspicious of malignancy (BIRADS 4). US-guided biopsy revealed benign cells (sample error?). MBI performed 5 days after MG/US described a large area of pathological uptake affecting all quadrants, in an extension of 7 cm. MBI-guided biopsy was compatible with DCIS G2, which was confirmed after surgery. CC indicates craniocaudal; ML, mediolateral; MLO, mediolateral oblique.

FIGURE 5

Illustration of a retroareolar breast lesion, occult on CD, but identifiable on MBI. Seventy-six-year-old woman with unilateral nipple discharge from the left breast. MG/US revealed duct ectasia and cysts in the retroareolar area of the left breast but no suspicion of malignancy (BIRADS 2). MBI performed 8 days after MG/US showed a linearly increased uptake behind the left nipple measuring 3.5 cm, suspicious of malignancy (BIRADS 4). Two days later, the substrate was found on the second look US. The US-guided biopsy revealed DCIS G3, which was also confirmed with surgery. CC indicates craniocaudal; ML, mediolateral; MLO, mediolateral oblique.