Long-standing or significant effects of the NCB procedure on perilesional tissue, beyond that of hemorrhage, organizing fat necrosis and subsequent scarring, are usually not apparent in imaging studies. In 24 patients studied by Kaye et al. (6), follow-up mammography performed 6 months after stereotactic 14-gauge biopsy revealed no mammographically detectable architectural distortion attributable to the procedure. In two instances, there were fewer calcifications in postbiopsy mammograms, and a 6-mm fibroadenoma contained a 3-mm defect. Lamm and Jackman (7) reported the formation of a “small” (mean size: 8 mm) mammographic density in 6 to 8 months at the biopsy site when larger (11-gauge) needles were utilized. These as well as multiple recent reports indicate that in general the performance of NCBs does not inflict notable effect on subsequent radiographic (including ultrasound, mammographic, and MRI) studies.

Nonetheless, procedural trauma-induced changes in and around the NCB site can affect the histopathologic interpretation of the subsequently performed excisional biopsy—an observation noted more than two decades ago (8,9). Evidence of previous NCB track (or, less accurately, tract), for example, hemorrhage, granulation tissue formation, and fibroplasia, should be sought in excisional biopsies, as evidence that the target lesion has been sampled (8,9). The presence of fresh blood or of hemosiderin within the lumina of glands in the vicinity of the target lesion as well as in lesional glands is a frequent manifestation of prior needling procedures, including needle-localizing techniques (Fig. 25.1). Fragments of epidermis may be dislodged into breast tissue by the needle if a cutaneous incision was not made before inserting the needle. An epidermal inclusion cyst may form from the displaced skin epithelium (10) (Fig. 25.2). Considerable diagnostic difficulties can ensue as a result of displacement of neoplastic or non-neoplastic epithelium along the healing biopsy track (vide infra) (11,12).

The healing NCB site initially develops granulation tissue (i.e., proliferating fibroblasts and capillaries amid inflammatory cells), and eventually forms a scar. The maturity of the scar depends on the time period that has elapsed between the initial NCB and the subsequent excisional procedure. In some cases, the reactive process displays exuberant myofibroblastic or histiocytic hyperplasia with mitotic activity (13) to a degree that it forms a “pseudotumor” (14) or appears “pseudosarcomatous”

(15). Association with a healing biopsy track and comparative histopathologic review with findings in the NCB can be helpful in rendering the appropriate diagnoses.

It is now routine practice to place a clip at the site of a targeted lesion after the performance of a NCB. Clip placement primarily serves to localize the site of the lesion by spatially guiding the subsequent surgical procedure and helps optimize the volume of tissue excised. Clips also serve to mark a malignant neoplasm prior to neoadjuvant chemotherapy, indicate the edges of extensive carcinoma, and facilitate radiologic follow-up of presumed benign lesions. Clips can be placed to mark targets sampled via biopsies that are stereotactic, sonographic, or MRI-guided, and multiple clips of different shapes or sizes can mark several targets sampled either synchronously or metachronously (16,17,18,19). The finding of the clip during gross examination of an excisional biopsy specimen ensures, at a minimum, that the vicinity of the lesion that was previously sampled by NCB has been removed. In mastectomy specimens, the clip can be particularly helpful in directing tissue sampling.

A wide variety of clips are commercially available, including those that are composed principally of stainless steel, ceramic, or titanium (Fig. 25.3). Clips have to be removed at the time of gross pathologic evaluation to enable complete inspection of the specimen, document its presence, and ensure that the subsequently prepared tissue block does not inadvertently contain the clip. The latter could potentially damage the microtome during sectioning of the tissue block and also compromise the quality of histologic sections. Minute sharp hooks serve to anchor the clip into the soft tissues, and the removal of clips at the time of gross pathologic examination can inflict physical injury on the pathologist.

Diligent efforts at the time of gross examination may be required to find the clip within the specimen. These efforts include serial “thin” (approximately 2 mm) sectioning and specimen radiography. Rarely, despite a concerted effort, the clip cannot be found in the excisional biopsy or mastectomy, and the most likely explanation is loss incurred either through the intraoperative use of a suction device with a 4-mm aperture (most clips span 2-3 mm) or through careless specimen procurement, transport, and handling (20,21).

Various types of bioresorbable embedding material such as bovine collagen (Avitene), polylactic acid/polyglycolic acid pellets, starch pellets, polyglycolic acid pads, polyethelene-glycol hydrogel, etc. are inserted along with the clip at the biopsy site to prevent displacement (“migration”) of the clip and improve hemostasis by filling of the newly created cavity. Each embedding material has a distinctive histologic appearance (Fig. 25.4), and some of these may be mistaken by the uninitiated for amyloid, osteoid, or other foreign material (22,23). Although these materials do not typically elicit a reactive inflammatory reaction, occasionally a prominent reaction might be evident.

Tissue disruption may result in displacement of lesional epithelial cells into the healing needle track and into stroma in the lesional area. This can produce a pattern that simulates invasive carcinoma (2,24,25) (Figs. 25.5 and 25.6). Youngson et al. (8,9) were among the first to report finding displaced epithelium in excisional biopsies of breast with various types of lesions after the performance of NCBs. The average interval between the needling procedure and excisional biopsy was 10 days. Fragments of benign or malignant epithelium were present within lymphovascular channels in seven cases, six of which also had stromal displacement. One of these women, who had extensive intraductal carcinoma associated with stromal
displacement and lymphovascular tumor emboli in the breast, also had clusters of carcinoma cells in the subcapsular sinuses of two axillary lymph nodes. Hoorntje et al. (26) reported finding displaced carcinoma cells in 11 of 22 (50%) needle tracts after 14-gauge needle biopsy procedures. Prospectively, these authors found displaced carcinoma in 7 or 11 (64%) needle tracks examined 7 to 35 days (median interval, 25 days) after 14-gauge needle biopsy.

Displacement of benign or carcinomatous epithelium is suggested by the finding of scattered, isolated, clusters of epithelium in iatrogenically created minuscule cystic spaces within the healing biopsy track—generally in a linear distribution. Depending upon the time elapsed since the procedure, the displaced epithelium is accompanied by hemorrhage, hemosiderin-laden macrophages, fat necrosis, an inflammatory cell infiltrate or granulation tissue, and scarring (Fig. 25.7). Displaced epithelium that is not in the immediate vicinity of the biopsy site may not be accompanied by any significant degree of stromal reaction. This may lead to the mistaken diagnosis of invasive carcinoma even in a benign lesion. It is not unusual to find fragments of displaced epithelium within lumina of benign glands. Rarely, portions of intraductal carcinoma that is entirely dislodged into the lumen of an atrophic duct may simulate lymphatic invasion.

Immunostains for confirming the presence of epithelial displacement can be helpful if myoepithelial cells can be demonstrated via p63, p40, myosin, etc. around the extralesional epithelial cells (Fig. 25.8). Coincidentally, it must be possible to immunohistochemically detect myoepithelial cells in the target lesion sampled by the NCB. Myoepithelial cells are almost certainly present if the primary lesion is benign (e.g., papillary ductal hyperplasia and intraductal papilloma), but they can also be found in in situ carcinomas. Failure to find myoepithelial cells in association with the extralesional
epithelium is not by itself diagnostic of invasive carcinoma, even if the target lesion contains myoepithelial cells, because displaced epithelial cells derived from a benign lesion may not adhere to myoepithelial cells. When p63-positive cells can be demonstrated as evidence of epithelial displacement, they are usually associated with a minor proportion of the displaced epithelial clusters. Epithelial displacement can be difficult to distinguish from invasive carcinoma and also lymphovascular channel involvement (Fig. 25.9) when intraductal carcinoma is present and epithelial clusters are devoid of myoepithelial cells.