A Perivascular Epithelioid Cell Tumor in the Ascending Colon: A Rare Case Involving a Patient With Tuberous Sclerosis.

A 33-year-old woman began experiencing back pain two years before presentation for treatment. She had no known family history of TSC. Subsequently, her primary care physician ordered a contrast-enhanced CT examination, which revealed a 90-mm mass in the right lower pole of her kidney. After detailed evaluations, she was diagnosed with renal angiomyolipoma and subsequently underwent arterial embolization. Thereafter, CT of the head revealed a subependymal nodule. Based on these findings and clinical diagnostic criteria, the patient was diagnosed with TSC. Despite this case meeting the diagnostic criteria for TSC, the patient refused genetic testing. An abdominal CT performed at the initial visit identified a mass in the ascending colon. A follow-up CT performed six months after arterial embolization for the renal tumor showed no significant change in size or appearance. A subsequent colonoscopy revealed an elevated submucosal tumor-like lesion in the same region. A boring biopsy was performed, but histopathological examination revealed only normal mucosa, and the sample was classified as Group 1. Given the lesion’s characteristics and size (40 mm), surgical intervention was considered a relative indication for suspected submucosal tumors of the colon. Subsequently, the patient was referred to our department for surgical management. Her medical history included uterine myoma and endometriosis, and the blood test results did not indicate elevated tumor markers. A colonoscopy confirmed the presence of a submucosal tumor-like mass in the ascending colon (Figure 1 ). A submucosal tumor-like elevation in the ascending colon (arrowheads) is observed. Imaging of the colon with Gastrografin revealed a shadow defect in the ascending colon opposite to the ileocecal valve (Figure 2 ). Contrast-enhanced abdominal CT showed a 40-mm tumor in the ascending colon with early contrast enhancement (Figure 3 ). A filling defect in the ascending colon was observed on gastrointestinal Gastrografin radiography. (a) Transverse computed tomography shows a tumor circumferentially involving the right wall of the ascending colon (arrowhead). (b) Coronal computed tomography reveals a 40-mm tumor extending along the craniocaudal axis in the ascending colon (arrowhead), with early contrast enhancement suggesting hypervascularity. Subsequently, laparoscopic ileocecal resection was performed six months after the first visit, and a white tumor protruding from the wall of the ascending colon was observed (Figure  4a ). In the resected specimen, a submucosal tumor-like elevation was noted in the ascending colon, while the mucosa remained intact (Figure 4b ). (a) A whitish tumor protruding extramurally was observed in the ascending colon (dashed circle). (b) In the resected specimen, a submucosal tumor-like elevation was noted in the ascending colon, while the mucosa remained intact (dashed circle). The histopathological examination revealed a complex network of spindle-shaped cells (Figure 5a ). The immunostaining results were as follows: smooth muscle actin, positive (Figure 5b ); desmin, positive (Figure 5c ); c-kit, negative (Figure 5d ); S100 protein, negative; and HMB-45, positive (Figure 5e ). The Ki-67 labeling index was 2% to 3%, indicating a low proliferation rate, and the features were not suggestive of high-grade malignancy. Therefore, a PEComa was diagnosed. The postoperative course was uneventful, and the patient did not experience any complications. The patient was discharged on postoperative Day 7. Additionally, the patient has been followed for three years postoperatively without any recurrence or progression of the disease. (a) Hematoxylin and eosin (HE) staining indicating a complex array of spindle-shaped cells, (b) positive staining for smooth muscle actin, (c) positive staining for desmin, (d) negative staining for c-kit, and (e) positive staining for human melanoma black (HMB)-45.

Perivascular epithelioid cell tumors (PEComas) comprise a group of rare mesenchymal tumors such as angiomyolipomas of the kidney and liver, clear-cell "sugar" tumors of the lungs and extrapulmonary sites, and lymphangioleiomyomatosis, which is associated with tuberous sclerosis (TSC) [ 1 ]. These tumors are characterized by cells associated with blood vessel walls and exhibit epithelioid morphology. Although PEComas can appear in various organs, their occurrence as primary tumors in the gastrointestinal tract is rare. This report describes a unique case of a PEComa in the ascending colon associated with TSC. This case is significant because it contributes to the limited body of knowledge regarding gastrointestinal PEComas and emphasizes the need for awareness of this rare diagnosis among patients with TSC who present with gastrointestinal symptoms. This study aims to provide insights regarding the clinical, radiological, and pathological characteristics of PEComas in the gastrointestinal tract to enhance the understanding of these rare tumors.

PEComas are rare mesenchymal tumors that occur in various organs, including the kidneys, lungs, and uterus, and originate from perivascular epithelial cells [ 1 ]. In 1996, Zamboni et al. proposed the term “PEComa” for pancreatic tumors that are closely associated with blood vessels and contain epithelial cells that exhibit smooth muscle and melanocyte differentiation [ 2 ]. Since then, PEComas have been identified at nearly all anatomical sites encompassing visceral and somatic soft tissues and, although rare, bones [ 3 ]. Patients with TSC often present with angiomyolipomas or lymphangioleiomyomatosis; however, PEComas in the gastrointestinal tract are uncommon [ 4 ]. Clinically, PEComas may manifest as abdominal pain, melena, obstruction, weight loss, and anemia; however, some cases may be asymptomatic [ 1 ]. A PEComa is a rare mesenchymal tumor with distinctive characteristics that are observed during imaging. Contrast-enhanced CT typically shows PEComas with uniform contrast enhancement outlining the mass with a well-defined border. Magnetic resonance imaging often shows these lesions as hypointense to isointense on T1-weighted images, and they have a heterogeneous hyperintense pattern on T2-weighted images. However, the features of PEComas observed with CT and magnetic resonance imaging are generally non-specific; therefore, determining a definitive diagnosis based on these imaging modalities alone is challenging. This was exemplified by our case involving a patient with TSC and a mass in the ascending colon that was incidentally discovered on a CT image despite an asymptomatic presentation. This underscores the importance of considering the clinical context and additional diagnostic methods when evaluating potential cases of PEComas. We searched PubMed using the keywords “PEComa” and “gastrointestinal tract” and found 20 case reports involving 11 female and nine male patients with a median age of 40.5 years (range, 12-71 years) [ 4 - 23 ] (Table 1 ). The most common anatomical site of involvement was the colon (10 patients; 50%). Tumors were observed in the small intestine in four patients (20%); two cases occurred in the ileum and one occurred in the duodenum. The preoperative diagnosis is difficult and often confirmed by the postoperative pathology examination results. For this case, the pathology examination results included epithelial-like cells and spindle-shaped cells encompassing the blood vessels. Immunohistological results typically indicate positive malignant melanoma-related markers (HMB-45 and Melan-A) and muscle lineage markers. Although these tumors are generally benign, some studies have defined malignancy as a tumor diameter larger than 5 cm, an infiltrative tendency, nuclear atypia, high cell density, more than one mitotic figure per 50 high-power fields, necrosis, and vascular invasion. There is no established definitive treatment for PEComas; however, surgical resection is considered the most effective treatment approach. mTOR inhibitors (e.g., sirolimus, everolimus) and immune checkpoint inhibitors (e.g., pembrolizumab) are also considered for cases with malignant findings; however, evidence supporting their effectiveness remains limited [ 24 - 26 ]. IHC: immunohistochemistry, HMB-45: human melanoma black 45; SMA: smooth muscle actin, NR: not recorded, NER: no evidence of recurrence

This case emphasizes the need to consider PEComas when patients present with TSC and gastrointestinal symptoms. An accurate diagnosis often requires both imaging and histopathological analyses because the preoperative identification of these tumors is difficult. Although surgical resection is the main treatment, chemotherapy and immunotherapy are considered for malignant cases. These valuable insights enhance the limited knowledge of gastrointestinal PEComas, thus improving their future diagnosis and management.