Page 87 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

66 PART I The Biology and Pathogenesis of Cancer

TABLE 3.3 Tumors That Tend to Defy the Typical of regions to be evaluated should be considered moving forward.
Paradigm of Mitotic Figures and Expected Regions with the highest mitotic activity, whether at the invasive
edge or elsewhere, may be the most representative of the GF.
VetBooks.ir High Mitotic Figures Low Mitotic Figures but Typically evaluating and reporting MFs certainly will be beneficial, the
Biologic Aggressiveness
Although efforts to improve standardization in methods for
but Typically Benign Malignant authors highlight that (1) applying such terminology or tech-
niques to previously published studies may cause confusion and
Histiocytoma, Acanthomatous ameloblastoma, Adrenocorti- perhaps more inaccuracy; and (2) reporting of MFs is an estimate
trichoblastoma cal carcinoma, Chondrosarcoma, Hepato- of biologic activity and is only one parameter of cell prolifera-
cellular carcinoma, High/low fibrosarcoma tion (reflective only of M-phase), as other evaluable proliferation
of the canine oral cavity, Islet cell (β-cell) indices (e.g., Ki67, PCNA, AgNORs) exist. The broader histo-
carcinoma, Malignant melanoma, Thyroid pathologic picture still should be considered, as should all tumor-
follicular cell carcinoma
associated clinical parameters, including stage of disease, in the
management of the cancer patient.

Lymph Node Metastasis
MFs. MFs represent cell division and thus provide information
about the growth fraction (GF) of a neoplastic mass. Through Histopathologic evidence of LN metastasis is a feature of malig-
numerous studies, the presence of MFs in neoplastic tissue has nancy, a negative prognostic indicator, and has a profound effect
proven to be a prognostic indicator of biologic behavior, either as on the therapeutic plan. When LN “metastasis” is reported on a
an independent variable or as one factor in a grading scheme con- biopsy report, it is important the clinician recognize that this is
sidered with other phenotypically observable histopathologic fea- the pathologist’s interpretation based on histopathologic features
tures (e.g., cell differentiation, nuclear features, necrosis). 9,21–30 observed. To that end, no firmly established nor standardized his-
In general, a higher number of MFs typically reflects a higher GF tologic criteria for LN metastasis in veterinary medicine exists,
and increased potential for biologic aggressiveness; however, mul- although recent attempts to establish a foundation have been
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tiple exceptions exist (Table 3.3). Additionally, when the relevance made. Ultimately, if a neoplastic cell population has colonized a
of MFs for a specific tumor type has not been proven scientifically, tissue distant from its primary site, is forming a new mass lesion
caution is advised in simply extrapolating an interpretation of bio- at that site, and is effacing and replacing the normal tissue architec-
logic behavior based on “high” or “low” “numbers of MFs. ture, these are irrefutable histopathologic features of overt metas-
The terminology used in histopathology reports and published tasis. Similar findings in LN tissue are unequivocally supportive of
veterinary studies to quantitatively report MFs (e.g., MFs, mitotic metastasis. However, alternative findings may consist solely of indi-
index, mitotic rate, mitotic activity, number of mitoses, mitotic vidualized/isolated tumor cells (ITCs) or small aggregates of tumor
count) has lacked standardization, as has the method of acquisi- cells in sinusoids and/or parenchyma, and these may be sparsely
tion. This can create confusion as to how to interpret the pathol- or frequently present. Without standardized histologic criteria
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ogy report and can complicate accurate comparison of data across for metastasis, these types of histologic findings can result in inter-
studies. Additionally, even if the methodology is similar, micro- pathologist variability in interpretation and reporting of metastasis.
scopes can have variable lenses and magnifying components that For this reason (1) the clinician should be cognizant of the
affect the field of view (FOV) such that the area of tissue visualized histopathologic description of the LN on the pathology report,
at 400× magnification of one microscope may differ from that especially if the diagnosis itself states LN metastasis; and (2) out-
of another. Moreover, the advent and ever-increasing presence of side of overt histopathologic evidence of metastasis as described
digital pathology has introduced yet another variable with which previously, the pathologist should try to reserve an interpretive
to consider the FOV and total area of tissue evaluated, especially diagnosis (e.g., LN metastasis, no evidence of metastasis) and
as it relates to previous studies and data acquired via traditional instead work to provide a descriptive diagnosis (e.g., rare isolated
microscopic evaluation. tumor cells are noted in the subcapsular sinus). Clinicians may
An effort to standardize terminology and the FOV, regardless find this frustrating and may not know how to interpret these
of the instrument or technology used, recently has been intro- descriptive findings, but until further research is pursued, the sig-
31
duced. It has been proposed that the profession use the term nificance of these findings or the expected biologic behavior of
2
“mitotic count” and that a standardized area of 2.37 mm be the the tumor simply remains unknown. In human medicine, evalu-
total area evaluated (this is most commonly acquired by evaluating ation for LN metastasis typically is reported as negative, ITCs,
10 fields with a 40× objective, 22 field number ocular, and no tube micrometastases, or macrometastases; however, the clinical and
lens); the number of fields viewed may vary, depending on equip- prognostic significance of ITCs and micrometastases is still under
ment. The region of the tissue examined is yet another variable in investigation. 35–39
need of standardization. Examples of various region approaches in To improve the sensitivity of identification of nodal metas-
the literature are consecutive regions, regions of highest mitotic tasis, perioperative or intraoperative evaluation for the sentinel
activity, regions at the invasive edge, and random fields. 21,24,32,33 LN (SLN) is becoming more commonplace in veterinary medi-
40
The authors believe that daily diagnostic application by patholo- cine (Chapter 9). The pathologist also can improve sensitivity
gists should replicate the study-specific methods when a published by using IHC (e.g., cytokeratin for carcinomas) or histochemical
grading scheme or published MF value as an independent variable stains (e.g., toluidine blue for metachromatic granules in MCTs).
is applied. The clinician should be familiar with the study-specific This can aid in the identification of aberrant nodal cells and/
methodologies from which MFs and associated prognostic conclu- or improve the efficiency by which these cells are detected visu-
sions were drawn and should be aware of how the number of MFs ally. 34,41 Serial sectioning or multilevel sectioning can also improve
reported on the pathology report were obtained. Standardization detection sensitivity of metastasis by increasing the overall amount