Gastrointestinal mesenchymal and stromal tumours GISTs

— spindle cells, epithelioid cells, skeinoid collagen fibres. Note also that extraintestinal mesenteric or retroperitoneal lesions can occur.

Myogenic: 10%—desmin/h-caldesmon/smooth muscle actin positive and c-kit negative. True leiomyoma or leiomyosarcoma.

Neural: 2-5%—S100/synaptophysin positive and c-kit negative. Schwannoma, neurofibroma (can be associated with von Recklinghausen's disease/MEN syndrome and GISTs elsewhere in the gut).

Stromal: CD34 and CD117 (c-kit:tyrosine kinase receptor) positive, with absent or incomplete myogenic/neural differentiation. Putative precur sors are the interstitial cells of Cajal, which are gut pacemaker cells located in the deep submucosa and myenteric plexus. Note that there can be marked heterogeneity and focal expression of antigens. In general, antigen positivity is CD117 (95%), CD34 (70-85%), smooth muscle actin (20-40%), h-caldesmon (60-80%) and nestin (90-100%). C-kit-negative GISTs may be identified by positive protein kinase c theta and PDGFR. Note that other malignant tumours can also be c-kit positive, e.g. seminoma, melanoma and some metastatic carcinomas, e.g. breast, ovary, colorectal, small cell carcinoma. GANT is now regarded as a variant of GIST and assessed accordingly.

Malignancy relates to: size (>2-5 cm), cellularity, atypia, cell type (epithelioid is worse than spindle cell), necrosis, margins and mitoses. Prognosis (approximately 50% 5-year survival) is also stage dependent.

DNA ploidy, Ki-67 proliferation indices (>10%), overexpression of p53, loss of CD34 and CD117 immunoexpression and morphometry also correlate with these parameters.

Lesions are NIH categorized as being very low, low, intermediate or high metastatic risk on the basis of size and mitoses (see Table 2.2).

Prognosis in gastrointestinal stromal tumours is dependent on patient age, tumour size (>5cm), tumour site and mitotic activity. A robust criterion in stomach tumours is >5 mitoses/50hpfs, but mid- and hindgut lesions are more aggressive (even if <5cm diameter and mitotic counts are low) than foregut tumours. Behaviour can also be unpredictable, with clinicopathological factors at best being only broadly indicative, and the terminology "gastrointestinal stromal tumour of uncertain malignant potential" is useful. With an established diagnosis of sarcoma histologi-cal grading is not a reliable index of metastatic potential and tumour size is a better indicator. So much so that a proposed TNM staging system is pT1 <5 cm diameter, pT2 >5 cm diameter. Metastases are commonly to peritoneum, liver, pancreas, retroperitoneum and lungs. Metastatic disease responds well to STI 57I (Glivec, Imatinib) agent giving several disease-free years, but usually therapeutic escape occurs with recurrent peritoneal disease. This may relate to new acquired genetic mutations in the tumour cells.

0 0

Post a comment