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Hygroscopic Sonographically Detectable Clips Form Characteristic Modern Pathology (2018) 31, 62–67 62 © 2018 USCAP, Inc All rights reserved 0893-3952/18 $32.00 Hygroscopic sonographically detectable clips form characteristic breast and lymph node pseudocysts Moshe Carmon1, Sofia Zilber2, David Gekhtman3, Oded Olsha1, Tal Hadar1 and Eliahu Golomb2 1Breast Health Unit, Shaare Zedek Medical Center, Hebrew University, Jerusalem, Israel; 2Department of Pathology, Shaare Zedek Medical Center, Hebrew University, Jerusalem, Israel and 3Department of Breast Imaging, Shaare Zedek Medical Center, Hebrew University, Jerusalem, Israel The use of hygroscopic sonographically detectable clips (HSDCs) has dramatically increased during the last years, especially in breast cancer patients who undergo neoadjuvant chemotherapy. The aims of this study are to define the appearance of HSDC sites in histopathological specimens, and to enable pathologists to recognize these sites and differentiate them from other lesions. We examined 124 breast cancer specimens in which the application of HSDCs was documented, 88 breast tissues and 36 lymph nodes, and analyzed the appearance of the clip site in these tissues. The clip site was clearly detected histologically in 79/88 (90%) of the breast specimens and in 29/36 (81%) of lymph node specimens. In most of the specimens, the HSDC site had a specific characteristic appearance of a pseudocyst, lined by layers of epithelioid histiocytes, sometimes with pseudopapillary formation, and with minimal or no fibrosis. This was the appearance in 69 of the breast specimens and in 23 of the lymph node specimens. In other specimens, scarring, scattered foamy macrophages and abundant siderophages were the predominant findings, as usually found in sites of other clips. As non-palpable breast lesions become more frequent, clips play a major role in the treatment of breast cancer, making them an important component of the communication among radiologists, surgeons, pathologists, and oncologists. HSDCs in tissues have a characteristic appearance with an epithelioid component. Pathologists should be able to recognize this finding, differentiate it from other breast lesions and include it in the pathology report. Modern Pathology (2018) 31, 62–67; doi:10.1038/modpathol.2017.96; published online 11 August 2017 Increased availability of screening for breast cancer for neoadjuvant therapy, or in cases in which the and compliance to screening, as well as improved biopsy procedure itself removes the lesion or sensitivity of modern screening tools, have led to a reduces its visibility.6 Such clips may also help high rate of detection of very small breast tumors.1 identify axillary nodes that had metastases prior to Such small cancers may be completely removed by neoadjuvant treatment. This is specifically important percutaneous sampling.2 Improved anti-cancer drugs in centers that practice sentinel lymph node biopsy 7–9 and patient selection for neoadjuvant treatment for involved nodes following chemotherapy. increase the rate of complete radiological and Ultrasound performed by clinicians is rapidly pathological response of breast cancers.3 To prevent expanding in many medical fields such as anesthesia loss of tumor location in such instances, marker for delivering nerve blocks, trauma medicine for quick emergency room evaluation, and in breast metal clips are often used in breast cancer surgery cancer surgery.10,11 Intraoperative ultrasound in over the last two decades.4,5 Markers are commonly breast conserving surgery has been shown to reduce used for inconspicuous lesions, for tumors planned the rate of re-operations.12–14 With this background, a wide variety of ultrasound visible tissue localiza- Correspondence: Dr M Carmon, MD, Breast Health Unit, Shaare tion marker clips have been designed. The avail- Zedek Medical Center, Hebrew University, 12 Beyth St., POB ability of such clips offered sonographic targeting as 3235, Jerusalem 91031, Israel. E-mail: [email protected] a faster and less expensive alternative to stereotaxis, Received 6 May 2017; revised 11 June 2017; accepted 18 June with less patient discomfort and without exposure to 2017; published online 11 August 2017 ionizing radiation.6 The use of sonographically www.modernpathology.org Pseudocysts formed by hygroscopic clips M Carmon et al 63 visible clips in conjunction with intraoperative especially in presence of additional, benign ultrasound often obviates the need for pre-operative findings.14 With the increased use of neoadjuvant localization procedures.15 therapy, and the high rates of complete response to Many types of sonograpically detectable clips it, clips become the target site of breast and lymph (SDCs) from different manufacturers have become node surgical procedures. It is imperative that the available in the last decade.16 A thorough compara- pathologist recognizes and describes the appearance tive analysis of their main features, composition, of a clip site in the tissue in this setting. size, and sonographic visibility, with pictures of the Tissue response to breast biopsy site marking different clips and their sonographic tissue appear- devices has been described in 2005, and was found ance, has been published by Seow et al.6 The main to be dependent on the type of devices used. 17 The types of SDCs include: (1) clips made of metal only aim of the present study is to define and characterize (titanium, to avail MRI compatibility): Ultraclip II the appearance of HSDC sites in breast and lymph MR (CR Bard, Tempe, AZ, USA) and CeleroMark node histopathological specimens. For this purpose, (Hologic, Marlborough, MA, USA). (2) clips without we reviewed our database for cases with documen- metal: with carbon-coated zirconium oxide: BiomarC ted use of HSDCs between 2014 and 2016 in our (Carbon Medical Technologies, St Paul, MN, USA). Breast Service unit, and analyzed the histopatholo- (3) Clips with a combination of a hygroscopic gical specimens of the patients who underwent organic material and metal, in which the fluids HSDC placement. We found that HSDC sites tend accumulated by the hygroscopic substance provide to show pseudocysts lined by epithelioid histiocytes sonographic visibility. Most SDCs in the current in breast and lymph node tissue. practice belong to the latter type. They include SDCs with non-absorbable material, such as Ultraclip II PVA, with polyvinyl alcohol (Bard) and clips with Materials and methods hygroscopic bio-absorbable organic material, includ- Institutional Review Board authorization was ing V Mark (Angiotech Pharmaceuticals, Vancouver, obtained to perform this study, and informed BC, Canada); Gel Mark Ultra (stainless steel+gel, consent was waived. Bard ); SecurMark (Hologic), and Hydromark (Mam- To identify pathological specimens with hygro- motome, Cincinnati, OH, USA). The selection of the scopic clips, we reviewed the prospective database clip to be used depends on regulatory approval in 17 of our breast surgery service, the surgical reports, specific countries, economic parameters, local and the gross pathology reports of 1260 surgical service considerations, and the personal preferences procedures performed in our breast service between and experience of the radiologists and surgeons. In our 2014 and 2016. This screening led to the finding of center we have used the hygroscopic Hydromark clip 124 breast cancer surgical specimens in which the (Mammotome). According to information from the introduction of HSDCs was documented: 88 breast manufacturer, the global annual use of the hydromark tissue specimens and 36 lymph node specimens. The clip exceeds 200 000 units. Like most widely used time period between the clip placement and the clips, it contains a metal and hygroscopic gel organic resection procedure varied from 1 day to 7 months. component. The metal size of this clip is ~ 2 mm. We The sonographically detectable clip used was the previously found that it is sonographically visible for 9 HydroMARK clip (Mammotome). at least 6 months after placement, tends not to be Hematoxylin and eosin (H&E) stained slides were displaced with time and enables good cross-modality examined in all cases. The cellular components, communication. The degradability of its hygroscopic degree of inflammation, fibrosis, neovascularization, component may be an additional advantage if the and presence of birefringent foreign material were lesion does not have to be removed. analyzed in all cases. The availability of MRI-compatible metal and hygroscopic SDCs (HSDCs) enables a significant facilitation of cross-modality correlation. Lesions Results seen by MRI only or mammography only become accessible to removal by the use of intraoperative The histologic detection rate and appearance of ultrasound if they contain an SDC.6 The presence of HSDCs in breast and lymph node tissue is summar- SDC can help in the localization by the surgeon, ized in Table 1. The clip site was clearly detected Table 1 Detection and appearance of the sonographically detectable clip Hydromark (Mammotome) in breast and lymph node tissue Pseudocyst—minimal Pseudocyst— Foreign body reaction Fibrosis, hemorrhage, and Clip site not Tissue or no fibrosis prominent fibrosis without pseudocyst hemosiderin deposition found Breast 69 4 2 4 9 Lymph node 23 3 3 7 7 Modern Pathology (2018) 31, 62–67 Pseudocysts formed by hygroscopic clips 64 M Carmon et al histologically in 79/88 (90%) of the breast specimens and in 29/36 (81%) of the lymph node specimens. In most of the specimens, the HSDC site had a specific characteristic appearance of a
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