Breast cancer cryoablation with radiologic-pathologic correlation

Abstract

Breast cryoablation has become a viable option for the treatment of breast cancer in properly selected patient populations. With the increase in the use of cryoablation, post-treatment follow-up imaging and pathology has also gained increased importance. By using the proper imaging combination of diagnostic mammography, ultrasound and MRI, physicians are able to detect residual or recurrent malignancy and differentiate it from expected post-treatment findings. If suspicious imaging findings are seen, prompt biopsy and pathological diagnosis are essential. The pathologist must also be able to differentiate the expected post-procedural histological findings from those of recurrent or residual malignancy. These imaging and pathological findings must also be compared in order to ensure concordance and appropriate patient treatment.

Figure 1.

73-year-old female with biopsy-proven IDC, Nottingham Grade II of III, ER/PR+ HER2-, demonstrating TP imaging at 12 months status post-cryoablation, consistent with tumor recurrence at the margin of the ablation zone. Paired images from mammography, axial subtracted contrast-enhanced MRI, and hematoxylin and eosin stained core specimen from percutaneous biopsy are provided before ablation, 6 months post-ablation, and 12 months post-ablation. 1A: 1: Pre-ablation. Mammography and MRI demonstrate the biopsy clip (yellow arrows) within the center of the mass. 2: High powered hematoxylin and eosin staining demonstrates invasive ductal carcinoma, Nottingham Grade II of III from initial percutaneous biopsy. 3: 6-month post-ablation. Mammography demonstrates the clip well centered within the ablation zone with near-complete resolution of the mammographically visible mass, an expected finding. On MRI, there is no suspicious enhancement (red arrow) within the ablation zone, however, in retrospect, there is asymmetric thickening at the posterolateral margin of the ablation zone. 4: 12-month post-ablation. Mammography and MRI demonstrate a new mass at the lateral margin of the ablation zone (blue arrow). 1B: Expected post-ablative histological changes seen status post ultrasound-guided 9-gauge core biopsy of the ablation zone at 6 months post-ablation. 1. Medium powered hematoxylin and eosin staining shows necrotic debris initially after ablation therapy. 2. Medium powered hematoxylin and eosin staining shows fat necrosis, histocytes, chronic inflammation, and giant cells 6 months post-ablation. 3. Medium powered hematoxylin and eosin staining shows fat necrosis and histocytes 6 months post ablation. 4. Medium powered hematoxylin and eosin staining shows fibrosis, myofibroblastic proliferation, histocytes, and giant cells 12 months post-ablation. 1C: Status post-MRI-guided 9-gauge core biopsy of the mass at the margin of the ablation zone 12 months after cryoablation. Low powered hematoxylin and eosin staining of the core biopsy specimen shows post-treatment fibrosis (blue arrows), post-treatment chronic inflammation (yellow arrow), post-treatment fat necrosis (black arrow), and recurrent invasive carcinoma (white arrow). 1D: Status post-MRI-guided 9-gauge core biopsy of the mass at the margin of the ablation zone 12 months after cryoablation. Medium powered hematoxylin and eosin staining shows post-treatment fibrosis and fibroblastic reaction (blue arrow) and recurrent invasive carcinoma (yellow arrow). 1E: Status post-MRI-guided 9-gauge core biopsy of the mass at the margin of the ablation zone 12 months after cryoablation. High powered hematoxylin and eosin staining shows viable invasive carcinoma with mitotic figures (blue arrows). This malignant pathology is concordant with the imaging findings. 1F: Status post-surgical excision of the biopsy-proven recurrent cancer 12 months after cryoablation. Hematoxylin and eosin staining shows invasive carcinoma at the margin of the ablation zone, better demonstrating radiologic–pathologic correlation with 12 month follow-up mammography and MRI (1A). IDC, invasive ductal carcinoma; TP, true positive.

Figure 2.

78-year-old female with biopsy-proven invasive ductal carcinoma, Nottingham Grade I of III, ER/PR+ HER2-, demonstrating late FP imaging at 24 months status post-cryoablation, consistent with fat necrosis within the ablation zone. Contrast-enhanced breast MRI showing FP for recurrence 24 month post-cryoablation. Follow-up ultrasound-guided biopsy (not shown) demonstrated fat necrosis on histological review. Paired images from MIP subtracted contrast-enhanced MRI and hematoxylin and eosin stained core specimen from percutaneous biopsy are provided before ablation, 6 months post-ablation, and 24 months post-ablation. 2A: 1: Pre-ablation. MRI demonstrates an enhancing mass (yellow circle). 2: 6-month post-ablation. MRI demonstrates resolution of previously seen mass enhancement, consistent with successful ablation of the previously seen cancer (blue circle). 3: 24-month post-ablation. MRI demonstrates a new irregular enhancing mass at the site of the previously ablated breast cancer (yellow arrow). 2B: Status post pre-ablation ultrasound-guided core biopsy of the mass. Hematoxylin and eosin staining demonstrates invasive ductal carcinoma, Nottingham Grade I of III. 2C: Status post-ultrasound-guided core biopsy of the ablation zone 6 months after cryoablation. Hematoxylin and eosin staining demonstrates fibrosis (1) and fat necrosis (2). This benign pathology is concordant with the imaging findings. 2D: Status post-MRI-guided core biopsy of this new mass 24 months after cryoablation. Hematoxylin and eosin staining demonstrates fibrosis (1), fat necrosis (1), histiocytes (2), giant cells (2), and chronic inflammation (2). This benign pathology is concordant with the imaging findings. FP, false positive; MIP, maximal intensity projection.

Figure 3.

91-year-old female with biopsy-proven invasive ductal carcinoma, Nottingham Grade II of III, ER/PR + HER2-, demonstrating early false-positive imaging at 6 months status post-cryoablation, consistent with fat necrosis at the margin of the ablation zone. Paired images from mammography and hematoxylin and eosin stained core specimen from percutaneous biopsy are provided before ablation, 3 months post-ablation, and 6 months post-ablation. 3A: Pre-ablation. Mammography demonstrates a spiculated mass, before and after biopsy with satisfactory placement of a ribbon clip (yellow arrow); note mild post-biopsy changes, including a small amount of bleeding along the biopsy tract. Ultrasound-guided core biopsy of the mass (not shown) with hematoxylin and eosin staining demonstrates invasive ductal carcinoma, Nottingham Grade II of III. 3B: 1: 3-month post-ablation. Mammography demonstrates a well-centered ribbon clip within the ablation zone as well as an asymmetry at the anterior margin of the ablation zone. The asymmetry was thought to be probably benign, and therefore, short interval follow-up was recommended rather than biopsy. 2: 6-month post-ablation. Mammography demonstrates interval enlargement of the asymmetry at the anterior margin of the ablation zone, warranting tissue sampling. 3C: Tomosynthesis-guided core biopsy was performed of the asymmetry with placement of a cylinder clip (yellow arrow). 3D: Hematoxylin and eosin staining of the core specimen demonstrates fat necrosis, histiocytes and giant cells on a background of chronic inflammation and fibrosis. This benign pathology is concordant with the imaging findings. 3E: Hematoxylin and eosin staining (1-4) and ER staining (5) of the core specimen of the false- positive mammography showing expected post-ablative histological changes at 6 months post-cryoablation. 1. Fat necrosis, histocytes, and giant cells 2. Fibrosis 3. Fibrosis and chronic inflammation 4. Fat necrosis, histocytes, and giant cells 5. ER staining is negative in fibrosis (yellow arrow) and positive in benign breast lobule (black arrow). ER, estrogen receptor.

Figure 4.

74-year-old female with biopsy-proven invasive lobular carcinoma, Nottingham Grade II of III, ER/PR + HER2-, demonstrating late false-positive imaging at 48 months status post-cryoablation, consistent with fat necrosis at the margin of the ablation zone. Note, the patient had a follow-up MRI 6 months later (not shown), which demonstrated enlargement of biopsied area, subsequently undergoing repeat biopsy and again demonstrating benign fat necrosis. The following images demonstrate radiologic–pathologic correlation at various time points. 4A: Pre-ablation: MRI demonstrates an irregular enhancing mass (orange circle) on the subtracted contrast-enhanced MRI MIP image. 6-month post-ablation: MRI demonstrates minimal circumferential enhancement at the margin of the ablation zone (blue circle), consistent with expected post-ablation change. 4B: Ultrasound-guided biopsy of the initial mass (not shown) with hematoxylin and eosin staining demonstrates discohesive tumor cells infiltrating the stroma in a single file pattern (yellow arrow). The biopsy is negative for E-cadherin on immunohistochemistry (positive foci in the image are entrapped normal breast lobules [black arrow]), consistent with invasive lobular carcinoma. 4C: CT (red circle), PET (orange circle), and fused PET/CT images (not shown), obtained for evaluation of the patient’s known non-small cell lung cancer, demonstrates corresponding mild circumferential FDG-avidity in the area of the fat necrosis seen on contrast-enhanced MRI from 6-month post-ablation (blue circle). PET/CT findings are consistent with expected post-ablation change. 4D: 48-month post-ablation: PET/CT and MRI demonstrate FDG-avidity (blue circle) and focal enhancement (orange arrow), respectively, at the anterior margin of the ablation zone, which is suspicious for recurrence and warranting tissue sampling. 4E: MRI-guided core biopsy of new area of enhancement (not shown) with hematoxylin and eosin staining demonstrates with fibrosis, fat necrosis, foreign materials and giant cells, hemosiderin deposition/laden macrophages, and chronic lymphohistiocytic inflammation. The foreign material (black arrows) in this case is very impressive and surrounded by giant cells. No evidence of recurrent invasive lobular carcinoma is visualized. 4F: Lobular tumor can be very easy to miss on H&E. Therefore, immunohistochemistry for cytokeratin cocktail and estrogen receptor was performed. Any residual or recurrent tumor should be highlighted as positive and stain brown. Other than the foreign material (black arrows), all the cells in the background are light blue, indicating reactive fibroblasts and no recurrent tumor cells. FDG, fludeoxyglucose; MIP, maximal intensity projection; PET, positron emission tomography