Multimedia Journal of Metaverse in MEDICINE

Rectal GIST is relatively uncommon compared to other types of GIST, which typically arise from Cajal cells. These tumors most frequently occur in individuals aged 50 years, predominantly in the stomach (60%), jejunum and ileum (30%), duodenum (4-5%), rectum (4%), colon and appendix (1-2%), and esophagus (1%) [4]. Rarely, they manifest as primary extragastrointestinal tumors located near the stomach or intestines.

In the present case, preoperative pathological findings indicated positivity for CD117, CD34, DOG-1, and H-caldesmon, with negativity for S-100, focal positivity for SAM, and negativity for Desmon. These results supported a diagnosis of rectal gastrointestinal stromal tumor. However, postoperative pathology presented contrasting findings: negativity for CO117, Dog, Bcl-2 (special mess), SMA, Des, Caldsmon, CD99, S-100, GFAP, CD68, CK, and positivity for CD34 and Ki67 (+1%). These findings suggested a diagnosis of solitary fibrous cancer.

One regrettable aspect of this case was the failure to re-examine histopathology before initiating imatinib treatment. Due to the absence of pathological clues, it was impossible to determine whether the patient’s pathological changes preceded or followed imatinib administration.

To elucidate the reasons for this discrepancy, we considered the following possibilities. We first discounted any differences that could be attributed to the use of different antibody lot numbers at various time points for the two specimens or human error in the antibody blocking and washing procedures. This was because operational errors are unlikely to cause such significant differences in immune phenotype.

Next, we rejected the hypothesis that the tumor in this patient was a combination of multiple tissue types. This was based on our literature review, which indicated that two distinct cancer types originating from the same location are exceptionally rare. Additionally, even after the patient took imatinib, the GIST subgroup was infrequently eliminated. Although the MRI indicated a significant reduction in tumor size following imatinib treatment, the rectal wall thickness increased. This finding does not support the notion that GIST cells were completely eradicated by the drug.

After eight months of imatinib chemotherapy, the most plausible explanation is that the tumor’s molecular phenotype underwent changes at the mRNA level. The concept of GIST dedifferentiation was first introduced by Pauwels et al. [5] to describe the transformation of tumors from classic CD117-positive to CD117-negative GIST. This phenomenon occasionally occurs during treatment with tyrosine kinase inhibitors, either primarily or as a result of prolonged imatinib therapy. This change in both morphology and immunoprofile poses a diagnostic challenge for pathologists. Their study reported several patients with advanced GISTs who experienced complete phenotypic transformation during imatinib treatment.

We have summarized the reported cases in Table 1 [5]. Notably, the loss of CD117 was accompanied by phenotypic alterations, including epithelioid morphology and the emergence of cytokeratin or desmin expression, or both [6, 7]. Clinically, dedifferentiated GIST is typically highly invasive and unresponsive to treatment with tyrosine kinase inhibitors.

From an immunohistochemical perspective, a tumor with negative staining for both dog-1 and CD117 should be diagnosed as schwannoma if s-100 is positive or as a smooth muscle-derived tumor if SMA is positive. However, in cases where the histopathological features are compatible with GIST, but the immunohistochemical results for dog-1 and KIT are negative, and other immunohistochemical markers do not support a schwannoma or smooth muscle-derived tumor diagnosis, the diagnosis of GIST can be established if c-kit or PDGFRA gene mutations are detected. It is important to note that the absence of mutations in the c-kit and PDGFRA genes does not completely rule out the possibility of wild-type GIST.

In the present case, the preoperative pathology was typical of GIST, and the postoperative histopathological findings were consistent with GIST, ruling out schwannoma or smooth muscle-derived tumor. However, genetic testing was not performed during the treatment process, thereby leaving uncertainty regarding the presence of c-kit and PDGFRA gene mutations. Consequently, the possibility of wild-type GIST cannot be excluded. This underscores the importance of genetic testing before surgery and drug treatment to aid in accurate diagnosis and treatment planning.

Several clinical trials [8-10] have demonstrated that neoadjuvant/adjuvant imatinib mesylate treatment for locally advanced primary GIST can enhance the duration of disease-free survival (DFS) among GIST patients. Additionally, IM treatment has the ability to modify tumor size and/or density, often leading to beneficial outcomes during surgical resection.

In the present case, the patient underwent imatinib treatment for eight months prior to surgery. Although clinical symptoms improved, the tumor size did not exhibit a significant reduction. Given its proximity to the anus (only 3cm), anal preservation was not feasible, and therefore, a Miles operation was performed. In a similar case reported by [11], a patient diagnosed with a large rectal GIST received preoperative imatinib for six months. This treatment reduced the tumor diameter from 8cm to 5cm, allowing for the performance of anal sphincter-sparing surgery.

These cases highlight the importance of considering neoadjuvant/adjuvant imatinib mesylate treatment for locally advanced primary GIST, as it can potentially improve surgical outcomes and increase the chances of anal preservation. However, it is also essential to individualize treatment plans based on tumor characteristics and patient-specific factors.