This 58-year-old male with a clinical history of Li-Fraumeni Syndrome was initially found to have a polypoid lesion in the distal greater curvature of the stomach. Biopsy of this lesion showed an atypical smooth muscle neoplasm, consistent with leiomyosarcoma (LMS). A chest CT scan revealed a well-circumscribed lung nodule. Core needle biopsy of the lung nodule was consistent with metastatic leiomyosarcoma. The patient underwent a lobectomy, which corroborated the biopsy findings. Molecular studies performed on the gastric biopsy revealed a TP53 variant with an allelic frequency close to 50%. Molecular studies performed on peripheral blood confirmed a germline TP53 variant: p.R158H. This mutation is considered likely oncogenic and has been described previously in colorectal adenocarcinomas, high-grade gliomas, and leiomyosarcoma. Endoscopic ultrasound revealed multiple pancreatic, well-circumscribed nodules. Cytology of the pancreatic nodules revealed a high-grade spindle cell neoplasm with positivity for desmin. In this context, the findings were interpreted as metastatic leiomyosarcoma in the context of Li Fraumeni syndrome [3,4].

Soft tissue sarcomas are the second most frequent type of neoplasms after breast cancer in patients with Li Fraumeni syndrome. In these patients, LMS is one of the five most common sarcomas [5]. LMS is a malignant mesenchymal neoplasm with smooth muscle differentiation that most frequently occurs in the uterus, retroperitoneum and gastrointestinal (GI) tract. [6]. Gastrointestinal LMS most commonly arises in the small intestine, followed by the colorectum, stomach, and esophagus, and most frequently presents in adults in the sixth decade of life, except for gastric primaries, with a median age of diagnosis at 37 years [6,7].

Overall, metastases constitute 2-5% of pancreatic tumors and are usually associated with widespread systemic disease, except in metastatic renal cell carcinoma where the pancreas may be the only site affected. Kidney (34-41%), lung (14-15%), colon (7-10%), melanoma (7-9%), and breast carcinomas (6-9%) are the most frequent primary sites. There are no definitive endoscopic ultrasound features indicative of metastasis; however, metastatic foci are characterized by nodules with well-defined ultrasonographic borders [8-11].

Besides carcinomas, high-grade mesenchymal tumors may also metastasize to the pancreas. Reports include synovial sarcoma, solitary fibrous tumor, undifferentiated pleomorphic sarcoma, osteosarcoma, mesenchymal chondrosarcoma, myxofibrosarcoma, myxoid liposarcoma, rhabdomyosarcoma, phyllodes tumor and leiomyosarcoma [12-15].

The pancreas may also be involved by low-grade spindled cell lesions like GISTs, schwannoma, desmoid-type fibromatosis, inflammatory myofibroblastic tumor, and low-grade fibromyxoid sarcoma [16-18].

In patients without a clinical history indicative of possible metastatic disease, the differential diagnosis of pancreatic spindle cell lesions is vast, and attention to cytomorphology clues and ancillary studies are necessary for accurate diagnosis.