| disease | Pancreatic Polypeptide Tumor |
| alias | Ppoma, Pancreatic Polypeptidoma |
Pancreatic Polypeptidoma (Ppoma) is one of the gastrointestinal endocrine tumors, primarily occurring in pancreatic endocrine cells that contain Pancreatic Polypeptide (PP). It is extremely rare clinically, with fewer than 20 reported cases to date according to incomplete statistics. No literature has been reported domestically.
bubble_chart Pathological Changes
Most pancreatic polypeptide tumors are located in the pancreas, with the head of the pancreas being the most common site, followed by the body and tail. A small number of tumors are found in extra-pancreatic organs. Based on a review of 16 reported cases, 13 tumors (81%) originated in the pancreas, including 8 in the head, 3 in the tail, and 1 each in the neck and body. The remaining 3 cases (19%) were located in the stomach, duodenum, and liver, respectively. Most tumors are solitary, with sizes ranging from 1 to 15 cm, while a few are multifocal and scattered throughout the pancreas.
The majority of these tumors are malignant. For example, Tomita reported 3 cases, 2 of which were malignant. However, benign tumors or cases with only PP cell hyperplasia also occur. The liver is the most common site of metastasis for malignant tumors, but metastases to the lungs, brain, and bones (rare for other endocrine tumors, except glucagonomas) have also been observed. Immunohistochemical studies using various gastrointestinal hormone antisera show the highest levels of pancreatic polypeptide (PP), while other gastrointestinal hormones are negative or weakly positive. Measurements of PP in tumor tissues reveal extremely high concentrations, up to 196.5 μg/g wet tissue, whereas other gastrointestinal hormones are present in minimal amounts or are undetectable. Electron microscopy demonstrates that the granules in tumor cells are morphologically consistent with PP granules.
bubble_chart Clinical ManifestationsThe clinical manifestations of pancreatic polypeptide tumors are not strongly linked to the physiological effects of their excessive secretion of pancreatic polypeptide. It was previously believed that pancreatic polypeptide tumors lacked specific clinical symptoms and signs. However, with the gradual increase in reported cases in recent years, some clinical characteristics of pancreatic polypeptide tumors have been recognized.
1. The more common clinical manifestations of this disease include abdominal pain, weight loss, diarrhea, hepatomegaly, abdominal masses, skin erythema, ascites, etc. These manifestations are related to tumor malignancy, compression, and metastasis. The difference between skin erythema in pancreatic polypeptide tumors and the migratory necrolytic erythema seen in glucagonoma patients lies in the fact that the former often presents with scales on the erythema surface and symptoms of cutaneous pruritus. The erythema typically affects the face, hands, chest, abdomen, and perineum. After surgery or chemotherapy, when serum pancreatic polypeptide levels decrease, the erythema can disappear.
2. Pancreatic polypeptide tumors are closely associated with multiple endocrine neoplasia (MEN-I) and may appear as part of MEN-I. Among the 16 cases reported in the literature, 4 cases fell into this category, with patients exhibiting hyperparathyroidism and a family history.
3. Some pancreatic polypeptide tumor patients may also present with WDHA-like symptoms. However, in these patients, the levels of vasoactive intestinal peptide (VIP) in plasma and tumor tissues are normal.
bubble_chart Auxiliary Examination
2. Examinations such as B-ultrasound, CT, MRI, intraoperative ultrasound, and selective abdominal stirred pulse angiography.
3. Percutaneous transhepatic portal vein catheterization for blood sampling (PTPC) and selective stirred pulse injection of methylene blue (SAMBI). The authors reported a case of a 72-year-old male patient with a sexually transmitted disease who complained of abdominal pain. CT revealed a space-occupying lesion in the pancreatic tail, and stirred pulse angiography showed a 2 cm tumor vascular staining focus in the pancreatic tail. Serum radioimmunoassay results indicated elevated levels of both glucagon and pancreatic polypeptide. Subsequently, percutaneous transhepatic hepatic vein catheterization and selective splenic stirred pulse catheterization were performed. A stimulant (5 ml of 10% calcium gluconate) was injected into the splenic stirred pulse, and blood samples were drawn from the hepatic vein before injection and at 30, 60, 90, 120, and 180 seconds after injection to measure glucagon and pancreatic polypeptide levels. The results showed a 500% increase in pancreatic polypeptide compared to the baseline value, while glucagon levels remained unchanged after calcium injection. During surgery, after completing the exploration, 2 ml of sterilized methylene blue was injected through the splenic stirred pulse catheter. The spleen and the body and tail of the pancreas immediately turned blue; after 2 minutes, the staining faded in all areas except for the 2 cm nodule in the pancreatic tail, which remained blue. A distal pancreatectomy was performed. Immunohistochemical examination of the tumor tissue confirmed the presence of abundant pancreatic polypeptide.
1. The clinical diagnosis of this disease is quite challenging. Due to the rarity of clinical symptoms in pancreatic polypeptide tumors, they are often difficult to detect. Especially since other functional endocrine tumors may sometimes secrete small amounts of pancreatic polypeptide and cause corresponding symptoms, leading to confusion with this disease. When a patient presents with the aforementioned clinical manifestations and a significant increase in serum pancreatic polypeptide, the possibility of this disease should be suspected.
2. Using radioimmunoassay to measure plasma pancreatic polypeptide levels, if the baseline PP level is normal, a protein meal or secretin can be used for a stimulation test. A significant increase in PP also aids in the diagnosis of this disease.
3. Examinations such as B-ultrasound, CT, MRI, and selective abdominal angiography help determine the location, number of tumors, and the presence of metastases, but they cannot provide a qualitative diagnosis. Intraoperative ultrasound can assist in detecting small, deeply located occult lesions. Immunohistochemical methods to measure hormones in the tumor show a significant increase in pancreatic polypeptide content in the tumor tissue, with little or no other pancreatic endocrine hormones, which is one of the key diagnostic criteria for this disease.
4. Fedorak reported that combining percutaneous transhepatic portal vein catheterization (PTPC) with selective angiography and methylene blue injection (SAMBI) can aid in the qualitative and localization diagnosis of this disease.
bubble_chart Treatment Measures
1. Surgical Treatment
Surgical intervention is the primary treatment for this disease, especially for early-stage, isolated tumors, where surgical resection should be prioritized.
(1) For tumors located in the body or tail of the pancreas, superficial and solitary lesions may undergo enucleation; for deeper or multifocal lesions, resection of the pancreatic body and tail is recommended.
(2) For tumors in the pancreatic head, an 80% pancreatectomy combined with tumor resection may be performed. If the tumor is large and pancreatectomy alone is difficult, pancreaticoduodenectomy can also be considered.
(3) For patients with large tumor volumes, advanced disease, or metastasis, debulking surgery can still provide symptomatic relief.
2. Chemotherapy
For patients with advanced-stage tumor diseases, chemotherapy may be administered, with streptozotocin being the drug of choice. In one report, two patients with pancreatic polypeptide-secreting tumors were treated with streptozotocin, one of whom survived for three and a half years. Octreotide acetate can broadly inhibit the secretion of pancreatic polypeptide in functional endocrine tumors, with an efficacy rate of up to 90%. Chemotherapy can lead to symptom relief or partial remission, as well as a reduction or even normalization of serum pancreatic polypeptide levels.
