Squamous cell carcinomas are traditionally graded into well-, moderately, and poorly differentiated SCC. The criteria for grading are: the degree of differentiation, nuclear pleomorphism and mitotic activity. Well-differentiated SCCs closely resemble normal squamous epithelium and contain varying proportions of large, differentiated keratinocyte-like squamous cells, and small basal-type cells, which are usually located at the periphery of the tumour islands. There are intercellular bridges and usually full keratinisation; mitoses are scanty (Fig. 1.13a). Moderately differentiated SCCs exhibit more nuclear pleomorphism and more mitoses, including abnormal mitoses; there is usually less keratini-sation (Fig. 1.13b). In poorly differentiated SCCs, basal-type cells predominate, with a high mitotic rate, including abnormal mitoses, barely discernible intercellular bridges and minimal, if any, keratinisation (Fig. 1.13c). Although keratinisation is more likely to be present in well- or moderately differentiated SCCs, it should not be considered an important histological criterion for grading SCCs.

Tumour growth at the invasive front (tumour-host interface) shows an expansive pattern, an infiltrative pattern, or both. An expansive growth pattern is characterised by large tumour islands with well-defined pushing margins, whereas an infiltrative pattern is characterised by small scattered irregular cords or single tumour cells, with poorly defined infiltrating margins. It has been demonstrated that the growth pattern at the invasive front has prognostic implications: an infiltrative pattern is associated with a more aggressive course and poorer prognosis than an expansive pattern [57, 58, 76, 382].

Invasive SCCs are almost always associated with a des-moplastic stromal reaction, which consists of proliferation of myofibroblasts, excessive deposition of extracellular matrix and neovascularisation [63, 94, 221]. In our experience, desmoplastic stromal reaction is present only in invasive SCCs and never in SILs, regardless of their grade, and may be considered as an additional marker of invasion [395, 396].

Desmoplastic stromal reaction tends to be pronounced in well- and moderately differentiated SCCs and weak or absent in poorly differentiated SCCs and in lympho epithelial carcinomas. The intensity of desmo-plasia is inversely related to the density of stromal lym-phocytic infiltration. In SCCs with marked desmopla-

sia, lymphocytic infiltration is focal and scarce, while intense lymphocytic infiltration is found in SCCs with little or no desmoplasia.

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