Concurrent Diagnosis of Follicular Lymphoma and High Grade Pancreatic Neuroendocrine Carcinoma: A Rare Dual Malignancy.

Introduction/Background/Significance: The simultaneous diagnosis of two distinct primary malignancies, known as synchronous malignancies, is rare but increasingly recognized, with reported prevalence ranging from < 1% to approximately 5%. The coexistence of neoplasms with divergent biological behavior, such as indolent follicular lymphoma (FL) and high-grade pancreatic neuroendocrine carcinoma (HGNEC) poses a significant diagnostic challenge. In such cases, initial tissue diagnosis may not fully account for the patient's clinical severity or disease extent.

We report a rare case of coexisting stage I FL and metastatic HGNEC in a previously healthy patient presenting with rapidly progressive symptoms and widespread metastases, highlighting the diagnostic complexity of synchronous dual malignancy.

Materials and Methods/Case Presentation/Objective: A 57-year-old man with no significant past medical history presented with progressive right hip and lower back pain, decreased appetite, and a 40-pound unintentional weight loss over three months. He denied fever, chills, gastrointestinal symptoms or trauma. Computed tomography (CT) abdomen/pelvis revealed a 4 cm pancreatic uncinate mass with biliary and pancreatic ductal obstruction, peripancreatic and retroperitoneal lymphadenopathy, bilateral liver lesions, osseous lesions, and pulmonary nodules, raising concern for metastatic pancreatic cancer. Brain and cervical spine imaging were unremarkable. Laboratory studies showed hypercalcemia (corrected calcium 13.4 mg/dL), elevated uric acid (9.7 mg/dL), and LDH (834 U/L). PTH was inappropriately normal (59 pg/mL) with low 25-OH vitamin D (12.6 ng/mL), low 1,25-OH vitamin D (< 8 pg/mL), and normal PTHrP. CA 19-9 (8 U/mL) and CEA (< 2.0 ng/mL) were unremarkable.

Aortocaval lymph node biopsy revealed low-grade follicular lymphoma (grade 1–2), confirmed by immunohistochemistry and flow cytometry. Given the discordance between this indolent diagnosis and the aggressive clinical presentation, a positron emission tomography (PET)-CT was performed, demonstrating hypermetabolic pancreatic mass, retroperitoneal nodes, hepatic and osseous metastases, raising suspicion for a second malignancy. Liver biopsy confirmed poorly differentiated HGNEC with Ki-67 >90%. The patient was diagnosed with coexisting stage I FL and metastatic HGNEC. He subsequently developed complications including urinary retention, lower extremity weakness, spinal and brain metastasis. Despite platinum-based chemotherapy and palliative radiation, his condition deteriorated, and he transitioned to hospice.

Results/Description/Main Outcome Measures: This case presented a diagnostic challenge where initial biopsy showing indolent FL did not explain the patient's progressive symptoms and extensive metastases. Clinical-pathologic discordance prompted further investigation, revealing a second primary malignancy: HGNEC.

The coexistence of lymphoid and neuroendocrine neoplasms is uncommon, and clinical manifestations may be dominated by either tumor or paraneoplastic phenomena. Initial anchoring to the FL diagnosis delayed identification of the more aggressive malignancy. Repeating biopsy and imaging helped uncover the true nature of disease.

Management of synchronous malignancies requires a multidisciplinary approach that considers the biology and prognosis of each tumor. Treatment should be guided by relative aggressiveness and symptom burden. Prognosis is determined by the more aggressive malignancy and the presence of synchronous diseases is associated with increased morbidity and mortality.

Conclusions: This case highlights rarity and diagnostic complexity of synchronous HGNEC and FL. It underscores the importance of repeat, site-specific biopsies when clinical presentation is discordant with initial pathology. Early multidisciplinary evaluation is essential to ensure accurate diagnosis and treatment planning.