Diagnostic and therapeutic strategies in pancreatic adenosquamous carcinoma: Molecular and clinical insights in managing metastatic disease

Abstract

Adenosquamous carcinoma of the pancreas (ASCP) is a rare and aggressive variant of pancreatic cancer, characterized by both adenocarcinoma and squamous cell carcinoma components. It presents significant diagnostic and therapeutic challenges due to its atypical histology and poor prognosis. A 72-year-old male presented with abdominal pain, lighter-colored stools, and intermittent nausea. Initial imaging revealed a complex mass in the distal pancreatic body and tail. Elevated lipase levels and subsequent endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) suggested an atypical pancreatic lesion with keratinizing squamous cells. Further investigation through fiberoptic bronchoscopy and EBUS-guided transbronchial needle aspiration (TBNA) confirmed carcinoma with squamous differentiation. Genetic testing identified KRAS G12D and PIK3CA mutations. The multidisciplinary tumor board recommended systemic chemotherapy with mFOLFIRINOX and G-CSF support. The patient underwent twelve cycles of mFOLFIRINOX with dose adjustments for thrombocytopenia and effective management of chemotherapy-related side effects. Restaging CT scans showed a decrease in tumor size and stable metastatic nodes. The patient showed a partial biochemical response with decreasing CA 19-9 levels and disease stabilization on imaging. This case demonstrates the critical role of a multidisciplinary approach in managing rare pancreatic malignancies. ASCP requires a comprehensive diagnostic and therapeutic strategy involving advanced imaging, histopathological confirmation, and personalized chemotherapy. Integrating advanced diagnostic techniques, molecular profiling, and a multidisciplinary approach is essential for improving patient outcomes and providing comprehensive care for this challenging malignancy. Addressing the psychological aspects and offering compassionate care are vital for supporting patients through their treatment journey.

Keywords: Adenosquamous carcinoma; EUS-FNB; KRAS mutation; Molecular profiling; Pancreatic cancer; mFOLFIRINOX.

Fig. 1

CT abdomen and pelvis with IV contrast (axial view) shows a complex solid-appearing mass within the distal pancreatic body and tail measuring 6.0 × 5.5 × 4.3 cm (red box), which is highly concerning for pancreatic carcinoma.

Fig. 2

CT abdomen and pelvis with IV contrast (coronal view) shows a complex solid-appearing mass within the distal pancreatic body and tail measuring 6.0 × 5.5 × 4.3 cm (red box) adjacent to the stomach.

Image A

Histology slide from fine needle aspiration (FNA) of pancreatic tail with hematoxylin and eosin stain at 20x magnification. The samples consist predominantly of keratin debris and dyskeratotic squamous cells, with no pancreatic parenchyma identified. The red arrow highlights regions of keratin debris, while the blue arrows depict areas of parakeratosis.

Fig. 3

CT chest without contrast (axial view) showing an enlarged right paratracheal lymph node measuring 2.3 × 2.0 cm.

Fig. 4

PET CT skull base to mid-thigh (coronal view) with avid mass at the tail of the pancreas measuring 6.5 cm (blue arrow) with intense hypermetabolic activity (SUV max 28.4) and metastatic precarinal lymph node (yellow arrow) measuring 2.3 cm (SUV max 9.1).

Image B

Histology slide from fine needle aspiration (FNA) of pancreatic tail with hematoxylin and eosin stain at 40x magnification. The samples consist predominantly of keratin debris and dyskeratotic squamous cells, with no pancreatic parenchyma identified. The red arrow highlights regions of keratin debris, while the blue arrows depict areas of parakeratosis.

Image C

Histology slide from ultrasound-guided transbronchial fine-needle aspiration (EBUS-TBNA) of a lymph node with hematoxylin and eosin stain at 20x magnification of carcinoma with squamous differentiation. The yellow arrows show regions of the squamous cell tumor, and the orange arrows highlight keratin and necrotic debris in the background.

Image D

Histology slide from ultrasound-guided transbronchial fine-needle aspiration (EBUS-TBNA) of a lymph node with P40 immunostaining at 20x magnification of carcinoma with squamous differentiation. This image shows positive P40 immunostaining, a highly specific prognostic marker for squamous cell carcinoma.

Image E

Histology slide from ultrasound-guided transbronchial fine-needle aspiration (EBUS-TBNA) of a lymph node with P16 immunostaining at 20x magnification of carcinoma with squamous differentiation. This image demonstrates negative P16 expression, indicating that the cancer is unlikely to be associated with human papillomavirus (HPV).

Fig. 5

CT chest, abdomen and pelvis with IV contrast (coronal view) post chemotherapy with pancreatic tail mass (red box) measuring 4.5 × 3.4 cm and questionable slight interval increase in stomach involvement.