Two Contrasting Cases Show the Challenges of Treating Rare PTHrP-Secreting Pancreatic Tumors

The two cases showed strikingly different outcomes despite similar tumor grades (WHO grade 2; Ki-67: 7% and 8%). Patient 1 (age 55) achieved eight years of stable disease with multimodal therapy including somatostatin analogues, PRRT, and chemotherapy, though she developed bilateral hip osteoarthrosis from prolonged high calcium. Patient 2 (age 34) had refractory hypercalcemia that responded only partially to zoledronate, high-dose denosumab, and maximal somatostatin therapy, and she succumbed to progressive disease. Calcium levels tracked reliably with disease activity in both cases.

This is a case report of two patients with metastatic, well-differentiated PTHrP-secreting pancreatic neuroendocrine tumors treated at a single center. The authors documented treatment timelines, calcium levels, imaging results, and clinical outcomes across multiple treatment modalities.

PTHrP-secreting pancreatic neuroendocrine tumors are extremely rare, and there is no established treatment protocol. These cases provide real-world evidence on how peptide-based therapies like somatostatin analogues and PRRT perform in this context, and introduce the practical concept of using calcium as a readily available tumor marker — which could improve monitoring in similar rare cases.

Neuroendocrine tumors that secrete peptide hormones like PTHrP represent a challenging intersection of oncology and endocrinology. As peptide receptor-targeted therapies like PRRT become more widely available, understanding which patients respond — and which develop refractory metabolic complications — is critical for optimizing individualized treatment. These cases add to the limited evidence base for this rare functional syndrome and highlight the need for international collaboration.

As a two-patient case report, this provides the lowest level of clinical evidence and cannot establish generalizable treatment guidelines. The contrasting outcomes could reflect numerous unmeasured factors. Treatment decisions were made clinically rather than following a standardized protocol, making it impossible to isolate the effect of any single therapy.