(P 172) GIST WITH ATYPICAL MORPHOLOGY INITIALLY MISDIAGNOSED-THE IMPORTANCE OF BROAD IMMUNOCHEMISTRY-A CASE REPORT

Objective: Gastrointestinal stromal tumor (GIST) is a rare gastrointestinal tumor but the most common mesenchymal tumor in the gastrointestinal tract. Most GISTs occur in the stomach or small intestine but sometimes they occur in the mesentery, retroperitoneum, or omentum.

The immunohistochemically (IHC) analysis represents, in addition of morphological findings, the basis for the diagnosis of GISTs. Morphologically the tumor is often of spindle cell type (70%) but there are cases with epitheloid GISTs (10-20%) and mixed morphology (10%). IHC shows positivity for CD117 and /or the marker DOG 1 in 90-95% of GISTs. If the ICH is not typical the diagnosis may be verified by mutation analysis. Activating KIT-mutations are found in 75% of GISTs, most common in exon 11 (66%) and exon 9 (6%), rarely in exon 13, 17 and 8. 10% of GISTs harbor PDGFRA-mutations.

We describe a case where the morphology of the tumor did not show common findings for GIST, and therefore initially no further GIST specific IHC-analysis were performed. The case was referred for genetic analysis.

Preliminary diagnosis was an unclassified sarcoma, but the patient’s condition deteriorated during treatment with chemotherapy. Further analysis found a mutation in KIT exon 11. The patient’s treatment was successfully changed to imatinib.

Methods: A 65-year-old woman was diagnosed with multiple tumors in the abdomen in January 2024, described as peritoneal carcinosis. No obvious primary tumor in the body, including the gastrointestinal tract, was found. Biopsies were taken from the tumors. The histopathology showed a tumor with small epitheloid cells and a myxoid stroma, and GIST was not initially a suspected diagnosis. Unfortunately, therefore IHC for CD117, DOG1 or CD34 was not made (tables with IHC done will be added). Preliminary diagnosis based on morphology and IHC was an unclassified sarcoma. Material was sent to a sarcoma center for genetic analysis.

The patient was not in a condition allowing treatment with anthracyclines, and was started on oral treatment with trofosfamide - etoposide in March 2024. After 6 weeks, there was a clinical and radiologic progression.

Results: During treatment with chemotherapy the results of mutation analysis arrived, showing a mutation in KIT exon 11. There was no material left for further IHC, and because the patient had severe symptoms there was no time to take new biopsies. KIT gene mutations can rarely be seen in other malignancies than GIST, such as acute myeloid leukemia (AML), natural killer/T-cell lymphoma and seminoma. In this case, however, GIST was the most likely diagnosis.

The patient underwent a FDG PET-CT and the same day started treatment with tyrosine kinase inhibitor imatinib 400 mg/day. The PET showed high metabolic activity in 2 tumors in the upper abdomen and low activity in the biggest tumor. The patient three weeks later underwent a new FDG PET-CT for assessment of early treatment response. The PET showed obvious decreased metabolic activity, and the largest tumor showed signs of regression in size. (figures will be added) The patient was also showing clinically good response to the treatment.

Conclusion: Not all GISTs have the standard morphological structures of spindle like cells and this case shows the importance of ICH for the GIST diagnosis. In this case the patient was initially misdiagnosed and treated with chemotherapy.

With a morphological suspicion of sarcoma in the abdomen, staining for CD117 and DOG1 should be done even if the histopathology is not typical for GIST, and no primary GI -tumor has been discovered. In doubtful cases also mutational analysis is recommended. KIT mutations in exon 11 is in 90% of cases seen in GISTs and not commonly seen in other tumors.