Clinicopathologic Analysis of Undifferentiated Carcinoma of the Pancreas With Osteoclast-Like Giant Cells

Objective To investigate the clinicopathological features, differential diagnosis, and prognosis of undifferentiated carcinoma of the pancreas with osteoclastic giant cells (UCOGCP). Methods The clinical histomorphological features and immunohistochemical results of 20 patients of UCOGCP were collected and analyzed. Sanger sequencing was performed on 3 tumor components to assess KRAS gene mutations. Results The 20 patients ranged in age from 52 to 84 years, with a mean age of 62.8 years. The cohort included 12 male patients and 8 female patients. Of the 20 specimens, 9 were pancreaticoduodenectomy specimens, 7 were distal pancreatectomy specimens, and 4 were pancreatic puncture biopsy specimens. Tumor maximum diameters ranged from 1.2 to 11 cm. Microscopically, the tumor was composed of multinucleated giant cells with bland, uniform cytology, and mononuclear cells with significant nuclear atypia. The multinucleated giant cells were large, with abundant eosinophilic cytoplasm, containing several to dozens of uniformly distributed nuclei that exhibited fine chromatin and small, clear nucleoli. The mononuclear cells were round or short spindle-shaped, scattered, with a moderate amount of eosinophilic cytoplasm and marked nuclear atypia, characterized by heterochromatin, active mitotic figures, and easily identifiable pathological mitoses. Both multinucleated giant cells and mononuclear cells expressed vimentin. Multinucleated giant cells expressed CD68, leukocyte common antigen (LCA/C45), and MAC387 and showed a low Ki-67 proliferation index (<10%). Mononuclear cells showed aberrant p53 expression (suggestive of a mutant pattern) and a high Ki-67 proliferation index (>60%). They consistently expressed at least one epithelial marker, including keratin pan, EMA, CAM5.2, keratin 7, keratin 8/18, keratin 19, or keratin 20. Mononuclear cells were negative for S100 protein, Melan A, and HMB45. Molecular pathological analysis revealed KRAS gene mutations in all specimens. Conclusion Undifferentiated carcinoma of the pancreas with osteoclastic giant cell is a rare clinical entity with histomorphological features resembling those of malignant giant cell tumors of bone and soft tissue. It can be distinguished from pleomorphic giant cell carcinoma and pancreatic adenosarcoma through immunohistochemistry and molecular testing. Radical surgical resection remains the optimal treatment for patients with UCOGCP.