Pancreatic solid pseudopapillary tumor (SPTP) is a rare low-grade malignancy predominantly affecting young females, with a male-to-female ratio of 1:10. Although SPTP generally exhibits indolent behavior, recurrence or metastasis occurs in less than 5% of cases. Notably, SPTP pathogenesis is strongly linked to somatic mutations in exon 3 of the CTNNB1 (catenin Beta 1) gene, leading to nuclear accumulation of β-catenin and constitutive activation of the Wnt/β-catenin signaling pathway.

Aggressive fibromatosis (AF), a monoclonal myofibroblastic proliferation with locally invasive growth but no metastatic potential, shares a similar molecular hallmark: over 85% of AF cases harbor CTNNB1 mutations or APC gene alterations, resulting in dysregulated Wnt/β-catenin signaling. While AF has been sporadically reported following surgeries for gastrointestinal malignancies (e.g., colorectal and gastric cancers), its association with SPTP remains undocumented. Current literature hypothesizes that surgical trauma and β-catenin pathway activation may synergistically drive AF development, yet direct clinicopathological evidence is lacking.

Here, we present the first case of retroperitoneal AF arising 3 years after curative resection of SPTP. Both tumors demonstrated β-catenin nuclear positivity, suggesting a shared oncogenic mechanism. This case provides critical clinical support for the hypothesized link between Wnt/β-catenin dysregulation, surgical intervention, and AF pathogenesis, while highlighting challenges in postoperative surveillance and management of rare secondary tumors.

Solid pseudopapillary tumor of the pancreas (SPTP) is a rare low-grade malignant pancreatic tumor (1)with a significant female predisposition, a male-to-female incidence ratio of about 1∶10 (2)Some patients have few obvious clinical symptoms, and serological tests lack sensitive tumor markers. Very few SPTP will develop recurrence or metastasis (3).

The etiology and pathogenesis of SPTP are still unclear, and it is believed that the occurrence of SPTP may be closely related to β-catenin gene mutations (2, 4, 5). In recent years, it has been found that almost all SPTP have somatic mutations in exon 3 of the CTNNB1 gene encoding β-catenin protein, which leads to nuclear translocation of β-catenin, allowing β-catenin to escape cytoplasmic phosphorylation and abnormally accumulate in the nucleus, forming a β-catenin- T cell binding factor (Tcf)/lymphoid enhancer binding factor (lef) complex by binding to Tcf/lef and activating transcription factors, which further activates the transcription of multiple oncogenes (e.g., c-myc and cyclin D1) (6). Also, because β-catenin is the main regulatory molecule of the Wnt signal transduction pathway, this allows the Wnt/β-catenin signaling pathway to be activated, leading to the development of tumors (7–10)

AF, also known as desmoid tumors (DTs) and ligamentous tumors (DF), is a rare tumor characterized by monoclonal proliferation of myofibroblasts in muscles, tendons, and ligaments (11). The disease is morphologically benign but has a biological behavior of low malignancy, infiltrative growth, and a tendency to recur locally but not metastasize. In 2006, the new WHO pathology and genetics classification of soft tissue and bone tumors defines them as junctional tumors of the soft tissues, also known as mesenchymal tumors. In 2013, the World Health Organization classified them as locally invasive nonmetastatic mesenchymal cell tumor group. Its incidence is low and few clinical cases have been reported.

The pathogenesis of AF is still not fully understood, and studies have shown that activation of the Wnt/β-catenin/APC signaling pathway caused by mutations in the oncogenes APC and β-catenin (12, 13) plays an important role in the development of AF (14–18). Mutations in exon 3 of the CTNNB1 gene, which encodes a serine- and threonine-containing β-catenin sequence, are detected in 87% of AF tumors (19, 20). These mutations dephosphorylate β-catenin, which in a stable state, is not broken down by the proteasome, and can enter the nucleus and accumulate inside it, where it acts on the Tcf/lef family of transcription factors and other specific target genes such as cellular-myelocytomatosis viral oncogene (c-MYC), Matrix metalloproteinase-7 (MMP7), neural cell adhesion molecule (Nr-CAM), cyclin D1 and Cyclooxygenase-2 (COX-2) to promote cell proliferation. The accumulation of these genes in the nucleus is stimulated, which in turn activates the transcription of the target genes, thus promoting the proliferation of tumor cells. Meanwhile, elevated levels of free β-catenin in the cytoplasm play an important role in wound healing and fibroproliferative disorders and AF development (21, 22).

A few sporadic AFs and AFs associated with FAP have mutations in the APC gene, which is mutually exclusive with the CTNNB1 gene, but also acts through the Wnt/β-catenin/APC signaling pathway by inhibiting β-catenin dephosphorylation. Thus, familial adenomatous polyposis is a risk factor for aggressive fibromatosis (23–25).

And in this case report, the patient with a new onset of aggressive fibromatosis was found more than 3 years after pancreatic caudal resection for SPTP. The tumor was located in the left adrenal region - near the left renal hilum, and it occurred close to the pancreatic dissection and was considered to be of retroperitoneal origin. The author’s review of the literature revealed that there are no reports of the same in the literature. Only one similar report was found by Navin and Mafficini et al. (26, 27), describing three cases of new invasive fibromatosis after surgical resection in patients with pancreatic cancer. The common features between these articles and this case report are: all were pancreatic tumors; all were open pancreatic body tail + splenectomy (some were also combined with gallbladder and other organs resection). However, the new irregular solid soft tissue mass discovered in this case report is located near the edge of the pancreatic incision and has been confirmed by pathology to be invasive fibromatosis, while the mass discovered by Navin et al. is located in the mesentery or the epiploon retrocavity. In addition, Eric S Weiss et al. reported a case of a 63-year-old white male who underwent pylorus preserving pancreatectomy for insulinoma. After surgery, he developed aggressive fibromatosis and underwent further surgical resection, including distal pancreatectomy and total splenectomy, with only a 6cm portion of the neck and proximal body of the pancreas preserved (28). Shahab Shayesteh et al. reported a 66-year-old male with a history of colon cancer metastasis who underwent sigmoidectomy and wedge resection of the liver. Three years after surgery, a CT scan revealed new low-density lesions with unclear boundaries in the body of the pancreas. Initially, colon cancer metastasis was considered, but the puncture biopsy results ruled out this possibility. To further clarify the condition, the patient underwent distal pancreatectomy and splenectomy, and the intraoperative pathological results confirmed the diagnosis of invasive fibroadenoma of the pancreas (29).

The relationship between pancreatic adenocarcinoma and invasive fibromatosis was mentioned in this literature as unclear. Considering that the new occurrence of AF after resection of pancreatic adenocarcinoma in three cases was not entirely coincidental, researchers analyzed the similarities in pathogenesis between pancreatic cancer and invasive fibromatosis, and found that all of them were related to the specific expression of the β-catenin pathway (30, 31). Besides, the pathogenesis of pancreatic solid pseudo-papillary neoplasia is also associated with it, so this case report can provide another piece of evidence in favor of the conjecture of this literature.

In other literature reports, colorectal cancer (32, 33), gastric cancer (34, 35) gastrointestinal mesenchymal stromal tumors (36)and other malignant diseases have been reported to be complicated with invasive fibroblastoma after surgery, and although these cases did not mention whether the first tumor expressed β-catenin, the authors reviewed the relevant literature to show that β-catenin has a very high positive expression in gastric cancer (37), colorectal cancer (38)and gastrointestinal mesenchymal tumors (39)and has a certain role in the development of this tumor and the proliferation and invasion of cancer cells. The authors reviewed the relevant literature, which showed that β-catenin was highly expressed in gastric cancer (37), colorectal cancer (38), and gastrointestinal mesenchymal stromal tumor (39), and it had a certain role in the development of the tumor and the proliferation and invasion and metastasis of the cancer cells (40–42). However, neurofibromatosis may also be associated with surgery or trauma, and surgical trauma is a predisposing factor for most abdominal and extra-abdominal aggressive fibromatosis (43). The incidence of postoperative complications of invasive fibroma after laparoscopic colectomy has been reported to be significantly smaller than that of open colectomy (44), implying that less surgical stimulation may reduce the incidence of postoperative invasive fibroma. However, cases of neurofibromatosis following surgery are very rare, and given this low number compared to the number of intra-abdominal surgeries performed each day, the relatively small impact of surgical trauma, and the fact that the majority of primary tumors have specific expression of the β-catenin pathway, the Wnt/β-catenin/APC pathway can be considered a potential etiology (20, 45).

We report a case of a SPTP that developed a new aggressive fibromatosis in its adjacent location 2 years after resection. The pathogenesis of these two tumors remains incompletely defined, and the current literature suggests that both are closely related to activation of the Wnt/β-catenin/APC signaling pathway. Here, the author ventured to speculate on the relationship between the specific expression of β-catenin pathway in intra-abdominal primary tumors and the images of surgery and the occurrence of invasive fibromatosis in the postoperative period, which could provide an interesting speculation for the clinic although there were not enough samples for further study. Meanwhile, the author put forward his opinion on the treatment of intra-abdominal type of invasive fibromatosis, which should be R0 resection as far as possible while preserving the functionality of the organ. If R0 resection is not achievable, postoperative chemotherapy can be added to achieve a similar effect (46). For patients with no obvious symptoms, with adequate notification, they can be regularly reviewed and treated with endocrine therapy and/or NSAIDs; if the tumor invades and compresses the surrounding organs/vessels, producing serious symptoms, and patients who need to have their tumor size reduced as soon as possible can choose radiotherapy, chemotherapy or targeted therapy. Considering the good prognosis of the disease, patients with radical resection and palliative treatment can achieve long-term survival.