Feline intestinal mast cell tumours: clinicopathological characterisation and KIT mutation analysis

Abstract

Objectives: Feline intestinal mast cell tumours (FIMCTs) are rare and reportedly characterised by poor differentiation, aggressive biological behaviour and lack of reliable therapeutic aids. KIT proto-oncogene-activating mutations have never been investigated in these tumours. This study describes the main clinicopathological and microscopic features observed in 17 FIMCTs.

Methods: Tumour degree of differentiation, proliferative activity, Kit protein expression and KIT mutations were evaluated and correlated with survival to assess their prognostic relevance.

Results: Ten tumours were located in the small intestine, two in the ileocaecocolic junction, and five in the large intestine. Survival times ranged from 3-538 days. Fifteen tumours were evaluated histologically, and there were six well-differentiated, six moderately differentiated and three poorly differentiated FIMCTs. The last showed a medium-to-large deposition of collagen tissue (P <0.001), and significantly higher mitotic and Ki67 indexes compared with more differentiated tumours (P = 0.011). On survival analysis, tumour degree of differentiation (P <0.001) and a mitotic index >2 (P = 0.022) were significantly associated with decreased survival times. Twelve cases showed Kit protein immunoexpression. The Kit pattern was membranous in five cases (33.3%), focal paranuclear in five (33.3%) and diffuse cytoplasmic in two (13.3%). Cytoplasmic Kit patterns were associated with a lesser differentiation (P = 0.015). Mutation analysis was successfully performed on 12 primary tumours and four lymph node metastases; however, no encoding mutation was detected.

Conclusions and relevance: Contrary to reports in the literature, FIMCTs seem to have an extremely variable biological behaviour. We propose a classification based on tumour degree of differentiation and proliferative activity. These findings need to be confirmed in larger series, and exploration of further genomic regions of KIT is warranted to clarify its role in the development and progression of these neoplasms.

Figure 1

Schematic representation of the strategy used for feline KIT exons 8 and 9 amplification. The position of outer and inner primers used and the length of the different PCR products obtained are reported

Figure 2

(a,b) Well-differentiated intestinal mast cell tumour. Sheets and nests of round-to-oval cells, 10–15 µm in diameter, with distinct cell borders. Cytoplasm is moderate to abundant, occasionally showing eosinophilic granules. Nuclei are round to oval, with condensed chromatin and inconspicuous nucleoli. Anisocytosis and anisokaryosis are low. Haematoxylin and eosin, (a) × 200 and (b) × 1000. (c,d) Moderately differentiated intestinal mast cell tumour. Sheets and streams of oval-to-spindle-shaped cells, 10–20 µm in diameter, with mostly distinct cell borders and moderate eosinophilic cytoplasm. Nuclei are oval shaped, with finely stippled chromatin and a small single central nucleolus visible in most cells. Anisocytosis and anisokaryosis are low to moderate. Haematoxylin and eosin (c) × 200 and (d) × 1000. (e,f) Poorly differentiated intestinal mast cell tumour. Pleomorphic, polygonal-to-spindle-shaped cells, arranged in small cords and bundles interspersed in abundant collagenous stroma. Cells are 20–40 µm in diameter, with indistinct borders and little, amphophilic cytoplasm. Nuclei are large, elongated and vesicular, with prominent nucleoli. Anisocytosis and anisokaryosis are marked. Haematoxylin and eosin (e) × 200 and (f) × 1000

Figure 3

Intestinal mast cell tumour. (a) Faint membranous positivity for Kit protein (Kit pattern 1). (b) Focal paranuclear positivity (Kit pattern 2). (c) Diffuse cytoplasmic positivity (Kit pattern 3). Kit immunostaining. Haematoxylin counterstain (× 1000)