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Neoplasms of Skin and Soft Tissues

Fundamental purpose of Biopsy Report

The fundamental clinically relevant facts that should be in a biopsy report and that are required to treat neoplasia are

  1. Diagnosis
  2. Prognosis
  3. Margins

Diagnosis of Neoplasia

The foundation of the naming of neoplasms is PHENOTYPE - what the neoplasms look like.

The usual phenotypes are

  1. Epithelial neoplasms
  2. Mesenchymal neoplasms
  3. Round cell neoplasms
  4. Other neoplasms including mixed tumors

 

So often, I hear the question - "What is the cell of origin?". I say - who cares. Macroscopic pathology, histopathology, electron microscopy, immunohistochemistry, in situ hybridisation, biomarkers and on and on is all about defining phenotype. Defining phenotype is the most important and accurate way of characterising a neoplasm to determine prognosis. Cytology and histopathology are the foundation of defining phenotype.

There are 2 basic theories of carcinogenesis.

  1. Somatic mutation theory. Somatic mutations are the result of genome instability. DNA mutation changes the cell so that it becomes independent and no longer under the control. A mutation in a stem cells be it embryonic or adult stem cells results in the 'new growth' that is neoplasia. This explains most neoplasms. What is the cell of origin - a stem cell!
  2. Tissue organization field theory. Alterations in interactions among cells and between cells and their extracellular matrix result in stimulation of growth promoting factors. This explains those neoplasms were there are no mutations.

 

Prognosis of Neoplasia.

The 'benign - malignant' paradyme is deeply flawed. The 'benign intermediate malignant' paradyme is a joke.

Each year I ask third year veterinary students the following question. "At what percentage of individuals with a neoplasm that is metastatic would you consider a neoplasm malignant." It began years ago with the majority suggestioning it was 10%, and this has now dropped to 1%. I have heard one extreme where a famous pathologist said 1 in a million. So the cutoff between benign and malignant is now considered to be 1% metastatic rate by veterinary students.

Neoplasms should be prognosticated based on well defined, reproducible characteristics that are tested using robust and accurate statistics. Thus metastatic rate, disease free interval and survival statistics, with and without standard of care, is the foundation of modern pathology. Multivariable and univariable statistics. A univariable Kaplan-Meier survival plot is a common graphic representation of survival. The vast majority of the neoplasms in animals have very poor statistics.

Webster JD, Dennis MM, Dervisis N, Heller J, Bacon NJ, Bergman PJ, Bienzle D, Cassali G, Castagnaro M, Cullen J, Esplin DG, Peña L, Goldschmidt MH, Hahn KA, Henry CJ, Hellmén E, Kamstock D, Kirpensteijn J, Kitchell BE, Amorim RL, Lenz SD, Lipscomb TP, McEntee M, McGill LD, McKnight CA, McManus PM, Moore AS, Moore PF, Moroff SD, Nakayama H, Northrup NC, Sarli G, Scase T, Sorenmo K, Schulman FY, Shoieb AM, Smedley RC, Spangler WL, Teske E, Thamm DH, Valli VE, Vernau W, von Euler H, Withrow SJ, Weisbrode SE, Yager J, Kiupel M. Recommended guidelines for the conduct and evaluation of prognostic studies in veterinary oncology. Vet Pathol. 2011; 48: 7-18. 

Surgical margins.

The pathologist has the obligation to provide the distance between the neoplastic cells and the closest inked surgical margin, and relationship to a fascial plane (a physical barrier to the infiltration of neoplastic cells). The best time for inking of margins is just after the surgery. The person who determines if surgical margins are adequate or appropriate is the surgeon. The pathologist cannot and should not determine if the surgical margins are 'clean' or 'complete'. The surgeon considers the diagnosis, location, ability to achieve margins, and how agressive the surgery was. When a pathologist indicates a margin is clean - dont believe it. What a pathologist sees as clean may not be adequate or appropriate.

A more detailed discussion of margins is found here.

Kamstock DA, Ehrhart EJ, Getzy DM, Bacon NJ, Rassnick KM, Moroff SD, Liu SM, Straw RC, McKnight CA, Amorim RL, Bienzle D, Cassali GD, Cullen JM, Dennis MM, Esplin DG, Foster RA, Goldschmidt MH, Gruber AD, Hellmén E, Howerth EW, Labelle P, Lenz SD, Lipscomb TP, Locke E, McGill LD, Miller MA, Mouser PJ, O'Toole D, Pool RR, Powers BE, Ramos-Vara JA, Roccabianca P, Ross AD, Sailasuta A, Sarli G, Scase TJ, Schulman FY, Shoieb AM, Singh K, Sledge D, Smedley RC, Smith KC, Spangler WL, Steficek B, Stromberg PC, Valli VE, Yager J, Kiupel M. Recommended guidelines for submission, trimming, margin evaluation, and reporting of tumor biopsy specimens in veterinary surgical pathology. Vet Pathol 2011; 48: 19-31.