A 33-year-old woman was admitted to an external hospital because of recurrent abdominal pain, flush attacks and diarrhea. CT revealed enlarged paraaortic lymph nodes, but no primary tumor. On exploratory laparotomy a tumor in the head of the pancreas was found and was thought to be a pancreatic ductal adenocarcinoma. This tumor was deemed inoperable because of the involvement of the mesenteric vessels and the paraaortic lymph nodes. Therefore only a lymph node biopsy was obtained. Histological investigation of the biopsy specimen revealed a lymph node metastasis (peripancreatic) of a highly differentiated neuroendocrine carcinoma that stained positive for chromogranin A and synaptophysin (Figure and ). There was no expression of insulin, glucagon, somatostatin, or pancreatic polypeptide. The somatostatin receptor SSTR2 showed distinct membranous expression (Figure ). The tumor cells were only supported by small stromal tissue bands. A [68Ga]DOTA-1-Nal3-octreotide (NOC) PET/CT was performed to evaluate the somatostatin receptor status. Chromogranin A and serotonin serum levels were normal at all times. Finally, the patient was diagnosed as having a highly differentiated neuroendocrine pancreatic carcinoma, stage IV. Biotherapy with a somatostatin analogue failed. The patient still complained about flushes and diarrhea.
Figure 1 Histological images. A: Lymph node metastasis of a high differentiated neuroendocrine carcinoma of the pancreas showing a trabecular pattern (HE, × 120); B The cells are positive for synaptophysin (× 120); C: High membranous expression (more ...)
As the patient resolutely refused any chemotherapy, but was willing to undergo radioreceptor therapy, two cycles of PRRT were administered intravenously. The first cycle, administering 6000 MBq (162.1 mCi) [90
] octreotate) was given in February 2007 and the second one, injecting 4500 MBq (121.6 mCi), in June 2007. To prevent nephrotoxicity, an amino acid infusion based on the protocol of Jamar et al[7
] was used. Kidney function was measured by 99m
Tc-DTPA using the single sample plasma clearance method for GFR calculation. 99m
Tc-MAG3 was used for dynamic renal scintigraphy and for determination of the tubular extraction rate (TER). The blood profile and routine laboratory parameters (electrolytes, liver function tests, creatinine, BUN etc
.) were checked prior to therapy and then every month.
Mild grade 1 anemia and erythrocytopenia were noted as the only side effects. There was no other hematotoxicity or nephrotoxicity.
After 2 cycles the abdominal lymph node metastases had regressed significantly and PET/CT using [68Ga]DOTA-NOC and 18F-FDG ([18F]fluor-2-deoxy-glucose) performed in October 2007 indicated that the patient was operable. After every PRRT cycle a partial remission (EORTC criteria 1999) was detected (Figure and ).
Figure 2 Gallium-68 DOTA-NOC PET-CT in the follow up. A: Octreotide scan prior to PRRT-1, Gallium-68 DOTA NOC PET-CT and prior operation, showing multiple paraaortal lymph nodes next to the pancreas head; B: 3 mo after PRRT-1; C: 5 mo after PRRT-2 showing consistently (more ...)
In November 2007, a pylorus-preserving pancreatoduodenectomy (Traverso-Longmire) was performed with en bloc resection of parts of the jejunum and its mesenterium and lymph nodes (Figure ). The operation specimen revealed a tumor in the head of the pancreas that was more than 2 cm in diameter and had metastasized to one mesenteric lymph node. Histologically, the endocrine tumor formed a trabecular pattern. The cell structures were embedded in well developed hyaline connective tissue, some parts of which were myxomatous. In the myxomatous area there were aggregates of CD68 positive macrophages that were occasionally positive for iron (Figure ). The tumor tissue infiltrated the surrounding pancreatic and interstitial tissue and also showed perineural infiltration. Immunohistologically, about 5%-10% of the tumor cells expressed glucagon or somatostatin and were negative for insulin, serotonin and pancreatic polypeptide. The somatostatin receptor SSTR2 showed a distinct membranous staining pattern in all tumor cells. The lymph node was filled with tumor tissue. The final stage was ypT2 pN1 pM1(LYM) G3 R0 L0 V0[8
]. The patient left the hospital 19 d after the operation. Six, twelve and eighteen months later a [68
Ga]DOTA NOC PET/CT revealed a complete remission (Figure ).
The pancreatic tumor with lymph node metastases (peripancreatic and one distal mesenteric lymph node metastasis) after pylorus-preserving duodenopancreatectomy and mesenteric lymphadenectomy en bloc.