Don’t mix apples and oranges: Grading systems should be developed for a specific tumor type in a specific species

According to Avallone et al (2021), a grading system is “a method to quantify the putative clinical aggressiveness of a neoplasm based on specific histological features.” There are general histologic features of malignancy that can suggest relatively aggressive behavior, but not all tumors with malignant or benign histologic features behave accordingly, e.g., plasma cell tumors, and histologically low-grade behaviorally high-grade fibrosarcomas of the mandible and maxilla. In addition, a given tumor type can behave differently in different species, e.g., mast cell tumors in dogs vs in horses, and osteosarcoma in dogs vs in cats. Development of a prognostically significant grading system requires knowledge of the clinical outcome of a large number of cases in which patients of the same species have the same tumor type. 

While limited numbers of cases with clinical outcome data have led to grading systems that lump groups of tumors, e.g., canine soft tissue sarcomas, this is not ideal as different tumor types within such a group can have different biological behavior, i.e., some indolent and some aggressive. If you’re looking at a group of dissimilar things and trying to figure out the behavior of the group, it can be like the apples and oranges analogy. If apples are always malignant and oranges are always benign, based on the behavior of the group, you will reach the erroneous conclusion that apples are sometimes benign and oranges are sometimes malignant. As soft tissue sarcomas are rare in humans, accounting for 1% of all adult malignancies with at least 100 different subtypes (Fletcher 2013), soft tissue sarcomas are generally graded as a group by the French or NCI systems; however, an attempt to account for histologic types and subtypes is a component of these grading systems (Trojani 1984, Costa 1984), and there is increasing recognition for the need of subtype-specific grading systems given the heterogeneity of tumor biology (Gamboa 2020). Collaborations between investigators and their institutions can increase the numbers of cases of specific tumor types on which to base grading systems.

Because of the aforementioned differences in tumor behavior in different species, grading systems developed for a tumor type in one species should not be extrapolated to different species. Each grading system should be developed from scratch for each tumor type in each species. As many histologic parameters as possible should be assessed for prognostic value, and those with the greatest prognostic significance, interobserver concordance and ease of use incorporated in a tumor-specific and species-specific grading system. Extrapolated grading systems, even if prognostically significant, will likely not be as prognostic as a grading system specifically designed for the tumor and species in question.

The better the grading system is at predicting the clinical outcome, the more information the clinician, oncologist, surgeon and owner have to inform treatment options. In order for a grading system to be optimally prognostic, it should be developed for a specific tumor in a specific species.


1.     Avallone G, Rasotto R, Chambers JK, et al. Review of histological grading systems in veterinary medicine. Vet Pathol. 2021;58809-828. doi: 10.1177/0300985821999831
2.     Costa J, Wesley RA, Glatstein E, et al. The grading of soft tissue sarcomas. Results of a clinicohistopathologic correlation in a series of 163 cases. Cancer. 1984;53:530-541
3.     Fletcher CDM, Bridge JA, Hogendoorn P, Mertens F, eds. WHO Classification of Tumours of Soft Tissue and Bone. 4th ed. IARC WHO classification of Tumours. Vol. 5. WHO Press; 2013
4.     Gamboa AC, Gronchi A, Cardona K. Soft-tissue sarcoma in adults:An update on the current state if histologic-specific management oin an era of personalized medicine. CA Cancer J Clin. 2020;70:200-229. doi: 10.3322/caac.21605
5.     Trojani M, Contesso G, Coindre JM, et al. Soft-tissue sarcomas of adults; study of pathological prognostic variables and definition of a histopathological grading system. Int J Cancer. 1984;3337-42. doi: 10.1002/ijc.2910330108

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