Veterinary Surgical Oncology. Группа авторов

from one surgical site to another.

      Defining and Evaluating Surgical Margins

      The evaluation of surgical margins of an excised specimen is an essential component to appropriate care in a cancer patient. A surgical margin denotes a tissue plane established at the time of surgical excision, the tissue beyond which remains in the patient. Excised masses should be submitted in their entirety for evaluation of the completeness of excision. The surgeon should indicate the margins with ink or some other method prior to placing the specimen in formalin to aid the pathologist in identifying the actual surgical margin. Because the larger tumor specimen is trimmed by a technician to fit on a microscope slide, the pathologist may not be oriented as to what represents a surgical margin versus a sectioning “margin.” Tissue ink on the surgical margin allows there to be orientation throughout sectioning. The ink is present throughout the processing of the tumor specimen and is visible on the slide. If tumor cells are seen at the inked margin under the microscope, the surgical margin is by definition “dirty” or incomplete.

There is considerable confusion and controversy surrounding the issue of appropriate surgical margins and clinical decision‐making when histologically incomplete margins are obtained. Prior dogma has suggested that an overly generous margin is likely to be curative. In order to ensure a good oncological outcome, surgical oncologists have been trained to be as aggressive as possible. While it is well‐accepted that aggressive surgical margins tend to lead to better local control, this is not true in every case. Even extensive, complete surgical margins do not always lead to a cure. Local recurrence and/or metastasis may occur despite a histologically complete margin. Mounting evidence in the human sarcoma literature seems to suggest that a planned and executed “widest” surgical margin has not resulted in sufficient improvements in disease‐free intervals to justify the morbidity incurred with such resections. This opinion among human surgeons is confounded by the routine use of adjuvant radiation therapy in traditionally difficult‐to‐resect tumors such as extremity sarcomas. In veterinary medicine, adjuvant radiation therapy may not be available or affordable. As we know from experience and from the veterinary literature, not every patient with a histologically positive margin will experience recurrence. To confound things further, different malignancies and grades of malignancy (mast cell tumor vs. soft tissue sarcoma, low grade vs. high grade) may require specific and separate guidelines for margin planning.

      Veterinary surgical oncology has traditionally followed the adage that for most malignant solid tumors, a 2–3 cm surgical margin and an additional tissue plane deep is the desired intraoperative goal to achieve wide excision, and is most likely to result in a histologically clean excision. Nonetheless, many surgical oncologists bend these “rules” based on tumor‐specific evidence in the literature and personal experience. Examples of this include using proportional margins in mast cell tumor resection (Pratschke et al. 2013) or less generous margins for specific anatomic areas, where 2–3 cm could result in undesirable functional morbidity (e.g. head and neck, spinal column). Many, based on experience, feel comfortable with smaller margins in specific tumor types (anal sac tumors, thyroid tumors, low‐grade sarcomas) and in some cases, this is supported in the veterinary literature by findings of no difference in local recurrence between one “width of margin” and a lesser one. However, the minimum safe distance necessary to reduce the chance of local recurrence is currently unknown. Regardless of what is actually performed in the operating room, most of the published literature agrees that a histologic margin free of tumor cells is considered the best predictor of improved local recurrence.

      Varying Definitions of “Margin”

      There are several considerations that make the comparison of evidence in the literature and subsequent adjustment of surgical planning difficult. There are distinct and widely different concepts of what constitutes the definition of a “margin” and how the quality or magnitude of margins are reported. Margins may refer to: (i) the intraoperative margin (i.e. the normal tissue margin as measured in situ between palpable tumor and the planned incision), (ii) the width of normal tissue beyond palpable tumor and the resected edges as measured after resection and before fixation, (iii) the measured width of tissue beyond the palpable tumor after fixation, and (iv) the measured width of normal tissue between the nearest microscopic tumor cell and the resected edge as seen by a pathologist on the slide. Each of the above margin assessment methods represents very different measurements, yet it is rare for veterinary journal articles to report which of these margin assessment methods is being used or even the magnitude of the resected margin beyond a description of “wide,” “marginal,” or “incomplete.” A recent study (Terry et al. 2017) showed that there was significant difference in the measured grossly normal surgical margins following sarcoma removal after resection compared to the planned intraoperative excision margin. Therefore, surgeon intent (wide or marginal) should not be considered an acceptable means of reporting margins obtained. In addition, these same authors noted that comparison of subgross evaluation of tumor‐free margins, once sectioned and placed on a slide, was not at all comparable to the magnitude of the pathologist‐reported histological tumor‐free margin.

      In human medicine, there has been a shift in margin assessment schemes from a traditional Enneking‐style margin assessment (intralesional, marginal, wide, or radical) to either a distance method (reporting the minimum distance between the nearest observed tumor cell and the inked surgical margin) or a qualitative method, where resected specimens are classified as R0 (no tumor at the inked edge), R1 (microscopic tumor at the inked edge), and R2 (residual gross disease left in patient). This highlights the important difference between surgical margins in situ versus histologic margins. Recent reports comparing the distance method to the qualitative method indicate that with osteosarcoma the distance method in combination with tumor response to chemotherapy (>90% or <90%) was the best predictor of local recurrence (Cates 2017). Conversely, in soft tissue sarcomas of the extremity, the qualitative assessment was most predictive and the distance method was not (Harati et al. 2017). It is likely, therefore, that different methods of margin assessment will have differing prognostic significance in veterinary surgical oncology.

      The Influence of Sectioning

Despite histopathology universally being used to assess the completeness of surgical margins, the methods of sectioning to evaluate the completeness of margins may vary. The most common method is to perform four complete radial sections. These represent cranial, caudal, dorsal, and ventral portions of the submitted specimen. Unless the surgeon uses tissue ink to identify the surgical margin, it may be difficult for the pathologist to determine whether any one of these sections represents a surgical margin or a trimming artifact. Tissue inking improves the likelihood that the standard sections evaluated do indeed represent true surgical margins; however, in the case of radial sectioning, the area of margin examined represents only a small percentage of the actual surgical margin surface. Several reports document the fact that with more sections, there is a higher likelihood of finding a positive margin. Comprehensive margin evaluation of a 1 cm cutaneous malignancy is estimated to require greater than 4000 sections, making this an impractical means of assessing margin completeness. Tangential sectioning is an alternative method to evaluate surgical margins. Tangential sections are taken parallel to the inked edge, and represent a potentially more sensitive method to detect residual tumor at the margin because they evaluate a greater percentage of the total margin. In humans, significant differences were noted in margin reporting outcomes when tangential sectioning was compared with radial methods. The disadvantage to tangential sectioning is that it does not allow for quantification of the histologically tumor‐free distance and lacks contextual reference to the primary tumor. In one recently reported study in the veterinary literature (Dores et al. 2018), tangential sections detected a significantly higher proportion of positive margins as compared with radial sections in resected mast cell tumors. In this study, radial sections incorrectly classified 50% of the margins as being complete. Surgical oncologists should therefore understand the histologic margin status is influenced not only by the adequacy of excision but also by the method of margin assessment.

      Future Directions

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