HISTOLOGIC MARGINS

Surgical oncology involves the surgical management of benign tumors and malignant cancers. The treatment of animals with cancer is well-established, and continues to be a growing field as improvements in preventive medicine and diets have resulted in our pets living longer and longer. Cancer is now the leading cause of death in older cats and dogs, and hence there is a need for everyone, from owners to family veterinarians to specialists, to be aware of the options available for the diagnosis and treatment of animals with benign tumors and malignant cancers. There are some important considerations when dealing with masses in animals, including preoperative biopsy, surgical margins, and histopathologic features of the tumor (such as tumor type, histologic grade, and histologic margins). 

 

HISTOPATHOLOGY AND HISTOLOGIC MARGINS

Following surgery, tumors are submitted to a laboratory for assessment by a pathologist. This histopathology is essential for the management of animals with cancer. Histopathology provides an insight into the biology of the tumor with information on tumor type, histologic grade (if appropriate depending on the type of tumor), histologic criteria (again, if appropriate, such as mitotic index for mast cell tumors and soft tissue sarcomas, lymphatic and/or vascular invasion for mammary carcinomas, etc), and histologic margins. These details provide information to determine prognosis and expected outcomes, and whether further treatments are necessary (such as either surgery or radiation therapy for local tumor control and chemotherapy for control of metastatic disease).

Histologic margins are different to surgical margins. Histologic margins are divided into complete and incomplete histologic excision. The intent of wide and radical surgical excisions is complete histologic margins where there are no tumor cells on the edge of the surgical excision. Incomplete histologic excision refers to the presence of tumor cells on the edge of the surgical excision, and this is expected for all animals treated with intralesional excision and most animals treated with marginal excision. Local tumor recurrence is significantly more common in animals with incomplete histologic excision. For instance, local tumor recurrence is 11-times more likely in dogs with incompletely excised soft tissue sarcomas compared to dogs with completely excised soft tissue sarcomas. However, incomplete excision does not equate to local tumor recurrence. For instance, only 17%-26% of incompletely excised grade II cutaneous mast cell tumors develop local tumor recurrence; and only 7% and 34% of incompletely excised grade I and II soft tissue sarcomas develop local tumor recurrence, respectively. These results highlight some of the problems with histologic assessment of the completeness of excision because histopathology provides an assessment of what tissue has been removed (and. moreover, days after surgery has been performed) rather than an assessment of whether there is residual cancerous tissue in the wound bed at the time of surgery. 

Narrow histologic margins is a frustrating term which has become entrenched in veterinary surgical oncology without any scientific evidence to support its widespread use. Narrow surgical margins refers to a complete histologic excision, but with tumor cells close to the edge of the excision. However, there is no consensus on what constitutes a narrow surgical margin with 2mm to 5mm being used in the veterinary literature. Furthermore, there is minimal to no evidence that narrow histologic excisions have a negative impact on local tumor control. To date, there has only been one study published which shows narrow histologic margins have an impact on local tumor control and this study has been widely criticized for both its design and results. In contrast, numerous studies of cutaneous mast cell tumors and soft tissue sarcomas in dogs have shown that narrow histologic margins have no prognostic significance for local tumor control. For instance, the local tumor recurrence rates in one study of 340 dogs with cutaneous mast cell tumors was 3%, 5%, and 17% for dogs with complete (> 5mm), narrow (0-5mm), and incomplete histologic excision. In another study of 73 dogs with complete histologic excision of 90 mast cell tumors, the local tumor recurrence rates were 4% and 0% for dogs with complete (> 3mm) and narrow (0-3mm) histologic excision of low-grade mast cell tumors, respectively. In another study of 109 dogs with excisional biopsies of soft tissue sarcomas, the local recurrence rates were 7%, 34%, and 75% following incomplete excision of grade I, II, and III soft tissue sarcomas, respectively; but 0% for dogs with complete histologic excision, regardless of histologic grade and narrowness of the histologic excision. However, despite all of this evidence, there is an unfounded dogma in veterinary surgical oncology that narrow histologic excisions are equivalent to incomplete histologic excision and that treatment recommendations for cats and dogs with narrow histologic excisions should be the same as an incomplete histologic excision (ie, further surgery or radiation therapy).

In contrast to veterinary surgical oncology, the R classification scheme was recommended by the American Joint Committee on Cancer (AJCC) in 1977 and has been used by the AJCC, International Union Against Cancer, and World Health Organization for nearly 40 years because of its "outstanding prognostic importance". The R classification scheme has been repeatedly validated in numerous tumor types as being a strong prognostic indicator for local tumor control. One of the advantages of the classification scheme is its simplicity:

  • R0 - No residual tumor
    • Complete histologic excision regardless of the width of the surgical margins
  • R1 - Microscopic residual tumor
    • Incomplete histologic excision
    • Satellite tumor cell populations distant to the tumor
    • Lymphatic, venous, or perineural invasion
    • Lymph node or microscopic distant metastasis
  • R2 - Macroscopic residual tumor
    • Gross residual disease
    • Macroscopic distant metastasis

The determination of adequate margins is difficult and multifactorial. A narrow histologic excision may have prognostic significance for a high-grade tumor, but not a low-grade tumor; and a narrow histologic excision may have prognostic significance for a sarcoma, but not a carcinoma. Margin assessment may also be affected by other factors such as shrinkage of samples following excision, shrinkage of samples during fixation, methods used to section tumor samples, and techniques used to assess histologic margins. Regardless, veterinary surgical oncologists should adopt (and investigate) the R classification scheme because of its simplicity and prognostic significance in human surgical oncology, and to potentially prevent the over-treatment of cats and dogs with narrow histologic excisions under the incorrect assumption that this is equivalent to an incomplete histologic excision.

 

Last updated on 6th March 2017