Furthermore, Takahashi et al suggested the inclusion of a ��clinically malignant group�� to include patients with peritoneal dissemination, metastasis, and invasion into adjacent organs or tumor rupture [19]. It is conceivable that patients within this Nilotinib chemical structure group have overtly malignant tumors that do not need be included into any risk classification system. In this context, it should be emphasized that tumors within this ��clinically malignant group�� may lack histological features of overt malignancy and instead show a bland histology [20]. A recent proposal by Joensuu used the NIH system as a base to include in addition to the tumor size and mitotic count the presence of tumor rupture as a high risk factor irrespective of size and mitotic count [8].

Further modification in the Joensuu’s criteria was the removal of non -gastric tumors in the NIH intermediate category to be placed into the high risk group, a step that reflect the influence of the AFIP system. Also, the ��forgotten�� tumors with exactly 5 mitoses have been included accordingly in the Joensuu’s revised NIH risk system. Other features remained as in the original NIH scheme. The problematic mitosis counting: technical notes Counting mitotic figures represents a highly significant issue in surgical pathology practice. The mitotic rates are often necessary, either for primary assessment of malignancy (particularly in soft tissue tumors), for grading malignant neoplasms (sarcomas and some carcinomas) or both. To date, there are no standardized data concerning the appropriate methods for mitotic counting in GIST.

In our experience with referral materials, General pathologists tend to over-count mitoses, most likely because of the common sprinkling of irregular-shaped lymphocytes and other inflammatory cells between tumor cells and presence of apoptotic bodies in GIST (Agaimy, unpublished data). Generally, GISTs show a low to moderate mitotic activity distributed throughout the tumor. However, there exists a subset of GIST with a high intratumoral heterogeneity leading to a great discrepancy in mitotic rates based on the area used for this purpose [21]. The three major questions: where to count, how to count and how large the 50 HPFs area should be, are still open. In the studies from the pre KIT era, Franquemont et a I examined five sets of 10 HPFs and the highest number of unequivocal mitotic figures in one set was used as the final mitotic count [11].

The calculated 50 HPFs area in their studies corresponded to 7.95 mm2. Review of the recent literature revealed remarkable variation in the methods used to count mitosis in GIST, even by the same investigators. Miettinen et al counted mitoses in consecutive 50 HPFs from the most mitotically Brefeldin_A active area or the most cellular area, or until >100 mitoses were found [7]. Other authors counted in randomly selected 50 HPFs [15].