Page 91 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

70 PART I The Biology and Pathogenesis of Cancer

of low-grade canine MCTs found that 23% of margin outcomes Many tumor-specific studies have been performed with the
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changed according to the sectioning technique. The most com- goal of correlating surgical margins to clinical outcome. For canine
MCTs a number of studies have reported positive associations
mon method of trimming for routine specimens is the cross-sec-
VetBooks.ir tioning or radial method. The mass is bisected along its short axis, between histologically complete margins and improved clinical out-
88,103,104
Complete excision of canine STSs also has proven
after which each remaining half is bisected along its long axis,
comes.
creating quarter sections. This method is perpendicular section- beneficial; dogs with incomplete margins have been reported as 10.5
ing and facilitates numeric quantification of the deep and four times more likely to experience local recurrence. 22,26 Incomplete
circumferential (lateral) margins. The overall amount of margin margins also have been linked to local recurrence of canine SCCs of
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tissue evaluated is minimal, and this method may be particularly the digit, 105 nasal planum, 106 and oral cavity 107,108 ; MLOs ; and
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problematic for tumors with irregular geometry or discontinu- malignant canine mammary tumors. Excisional status has been
ous growth patterns (i.e., microsatellites). Additional techniques linked to survival time in canine noncutaneous HSA. 57
that can increase the overall percentage of margin tissue evaluated Although the histologic margin status is an important clinical
include parallel, modified (a combination of parallel and cross- consideration, incompletely excised malignancies do not always
1
sectioning), and tangential sectioning. Tangential sectioning recur, even after protracted follow-up periods. This is illustrated
(sections taken parallel to the surgical edge) captures a greater per- in canine low-grade STSs, 22,109 canine cutaneous MCTs, and sub-
centage of the margin but can generate only a dichotomous mar- cutaneous MCTs. 110,111 Conversely, some neoplasms with highly
gin outcome (i.e., tumor cells present versus not present). Shaved invasive and/or metastatic phenotypes have a recurrence potential
margins taken from the tumor bed might bypass some limitations that is not necessarily related to complete histologic margin sta-
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associated with examination of the excised specimen. Shavings tus. Recurrence is especially well recognized in feline ISSs, likely
from the tumor bed may be submitted in addition to the excised because of the tumor’s infiltrative nature and pattern; one study of
mass but should be submitted in a separate, appropriately labeled 13 recurrent tumors had only one that was histologically incom-
container. Möhs surgical technique is the most comprehensive plete. 112 For canine oral malignant melanoma, the survival impli-
histologic margin evaluation, but it is not widely available in a cations of excisional status are also ambiguous. 113 High-grade
veterinary surgical setting. 95 canine MCTs have a significant risk of local recurrence that is not
Reporting of the histologic surgical margins should be clear, con- associated with margin width. 114 Biologic factors that contribute
cise, and thorough, furnishing the clinician with essential informa- to the potential for recurrence may include molecular signatures,
tion needed to make informed decisions and recommendations for field cancerization, tumor heterogeneity, and overall changes in
further management. Reporting should include (1) a description the tumoral and peritumoral microenvironment. 87,115,116
of the neoplastic cells closest to the surgical edge (e.g., individual Histologic margin interpretation fundamentally centers on a
cells, nests of cells, cells at the periphery of the mass itself); (2) an morphologic, light microscopic interpretation by a trained ana-
objective measurement of the HTFM (precluded for tangentially tomic pathologist. By definition this requires accurate identification
trimmed sections); and (3) a description of the tissue constituents of cells at the “leading front” of the neoplasm and recognition of
(e.g., adipose tissue, dense connective tissue, muscle) and the qual- the surgical edge (ideally identified by the presence of ink). Some
ity of these constituents (e.g., normal, necrotic, inflamed), because degree of variation in margin measurement is expected. One study
different tissue types provide variable barriers against invasion of canine MCTs found a median standard deviation of almost 2 mm
and infiltration of neoplastic cells. 1,96,97 Vague terminology, such in circumferential MCT measurements. Although this difference
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as clean, dirty, close, or narrow, should be avoided because these may not be relevant in wide excisions, marginal excisions are espe-
are subjective terms that introduce interpretative variability. Even cially prone to interpretive differences, particularly if the margins are
90
though a pathologist might use complete excision to communicate a classified as dichotomous variable (i.e., complete or incomplete).
HTFM greater than 0 mm, this terminology introduces ambiguity Sometimes differentiating between inflammatory or reactive and
by virtue of the fact that minimally adequate margins are poorly neoplastic cells can be challenging, as with the edges of canine
defined for most veterinary oncologic specimens. 87 MCTs, granulation tissue in STSs, and carcinoma cells undergo-
Of note, a quantified histologic surgical margin may be signifi- ing epithelial-mesenchymal transition. The pathologist’s approach
87
cantly less than a gross surgical margin. Margin measurements are to margin evaluation, and subsequent clinical interpretation, might
influenced by architectural changes that begin at excision (inher- also take into account growth patterns at the invasive front, which
ent postexcisional tissue retraction) and end with sectioning and differ between tumor types. In one study of low-grade canine
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mounting of paraffin-embedded tissue onto the slide. Cadaveric MCTs and low/intermediate-grade canine STSs, circumferential
canine skin undergoes a notable physical tissue length reduction and deep infiltration was 4 mm or 2 mm, respectively, from the
(“shrinkage”) immediately after excision, approximately 14% for subgross tumor edge. Asymmetric invasion has been associated
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circumferential measurements. Myofibril contraction and tis- with a greater likelihood of incomplete excisions in canine MCTs. 78
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sue elasticity account for much of this effect. This same process Collective data suggest that the adequacy of excision, and sub-
98
may result in increased tissue thickness, which can be influenced sequent indications for possible adjuvant therapy, should not rest
by tissue composition. Tissue shrinkage also is affected by for- solely on the histologic margin status. Assessment of the likeli-
99
malin fixation, and the degree of shrinkage varies relative to the hood of recurrence should be interpreted in parallel with a num-
tissue type. 99–101 For cutaneous biopsy specimens, shrinkage can ber of other variables, including tumor lineage, histologic grade
be up to 30%. 99,100 Specimens may also undergo considerable where applicable, frequency of MFs, growth pattern, trimming
tissue distortion during fixation, and this distortion may affect technique, and margin composition.
the observed HTFM. 87,98 In one study the reduction between
the in vivo grossly normal surgical margin and the HTFM, once Ancillary Diagnostics
microscopic tumor infiltration had been taken into account, was
reported to be as much as 30 mm and 24 mm in canine MCTs Most oncologic cases in human medicine can be diagnosed by
5
and STSs, respectively. 102 light microscopy using hematoxylin and eosin (H&E) stains.