FNAC diagnosis of pancreatic somatostatinoma
Somatostatinomas are rare neuroendocrine tumors arising from the pluripotent D-cells of the gastrointestinal tract. The classic somatostatinoma syndrome of hyperglycemia, cholelithiasis, steatorrhea and hypochlorhydria is present in a small proportion of patients presenting with somatostatinoma. We report a case of metastatic somatostatinoma of the pancreas diagnosed by fine needle aspiration cytology (FNAC) of liver and confirmed by histopathological examination and raised somatostatin levels. Because the FNAC was performed from the liver, hepatoma and other metastatic small round cell tumors also had to be ruled out. The importance of correlating with the computed tomography (CT) findings and clinical picture is emphasized in the following case report.
A 63-year-old female patient presented with complaints of pain in the lower abdomen, passing foul-smelling greasy stools, indigestion, nausea, weight loss of over four kilograms in the last six months and malaise. She was a known diabetic for the past two years and was on treatment. However, fasting blood sugar level on hospital visit was raised to 240 mg/dl. Duodenoscopy showed antral gastritis. Ultrasonography (USG) revealed cholelithiasis with a large calcified growth occupying the porta hepatis and the left upper quadrant, with an ill-defined soft tissue component. Triple-phase CT of the abdomen and pelvis showed liver of normal size with multiple calcified enhancing lesions in both lobes, the largest measuring 8 × 7 cm. The stomach wall and omentum were thickened with calcific deposits. The pancreas showed a calcified growth measuring 11 × 7 cm, occupying the neck, body and tail. The splenic vein was thrombosed. CT diagnosis of calcified malignant mass with multiple secondaries was given. Routine laboratory parameters were within normal limits.
USG-guided FNAC with a 23-gauge lumbar puncture needle was performed from the left lobe of the liver. Two smears each were stained with Leishman and hematoxylin and eosin stains. The remaining material was submitted for cell block. Smears were highly cellular and showed cells arranged in loosely cohesive groups, acini, rosettes and singly scattered [Figure 1]. Cells were plasmacytoid with small to medium-sized eccentrically placed nuclei and a moderate amount of eosinophilic granular cytoplasm [Figure 1-inset]. The nuclei showed salt and pepper chromatin with micronucleoli. Thin-walled blood vessels were seen with tumor cells attached to the walls of the blood vessels forming a palisading pattern. No necrosis or mitosis was seen. Cell block showed cells arranged predominantly in clusters and in an acinar pattern.
Correlating cytological features with CT scan findings and clinical picture of somatostatinoma syndrome, the possibility of a metastatic pancreatic somatostatinoma was suggested.
In view of extensive metastasis, surgery was not advised and thus ERCP (endoscopic retrograde cholangiopancreatography) -guided biopsy of the pancreatic mass was sent for histopathological examination. The sections showed small, relatively uniform cuboidal cells with abundant cytoplasm and centrally located oval nuclei showing indistinct nucleoli arranged in acinar and solid patterns. No pancreatic tissue was seen [Figure 2]. The serum chromogranin A level was high. The tissue chromogranin A was positive [Figure 2, inset]. Because of the nonavailability of antibody directed against tissue somatostatin, serum somatostatin levels were estimated, which were markedly elevated (10 ng/ml, the normal being 10–22 pg/ml). The patient was put on monthly injections of sandostatin followed by chemotherapy and is doing well after two years of follow-up.
Somatostatinomas are rare endocrine tumors comprising around 1% of all gastroentero-pancreatic endocrine neoplasms. Since the first two case reports of somatostatinoma in 1977, approximately 200 cases have been reported in the medical and surgical literature till date. The mean age of patients diagnosed with somatostatinoma is 54 years, with a range of 30–84 years. Seventy percent of the somatostatinomas occur in the pancreas and the remaining occur in other sites of the gastrointestinal tract, mainly in the duodenum and particularly in the ampulla. In the pancreas, the most common site is the pancreatic head, with size ranging from 3 to 11 cm. Three-fourth of them metastasize to the liver by the time the tumor is diagnosed. Somatostatinoma syndrome refers to presence of somatostatinoma with accompanying clinical symptoms of diabetes mellitus, cholelithiasis, steatorrhea and hypochlorhydria due to ectopically released somatostatin. In the present case, the patient had somatostatinoma syndrome. In a recent review, somatostatinoma syndrome was seen in only 11% of the cases presenting with somatostatinoma. It almost exclusively occurs only in tumors of pancreatic origin. Most of these symptoms arise due to inhibition of other endocrine cells in the pancreas by somatostatin. More commonly, patients complain of nonspecific symptoms, such as vague abdominal pain, weight loss or a change in bowel habits.
The cytological features of somatostatinomas are like those of other pancreatic endocrine neoplasms, except that it commonly forms acinar structures, more commonly seen in somatostatinomas arising in the duodenum, and often has cells with abundant fine granular cytoplasm. Because FNAC was performed from the liver mass, hepatic adenocarcinoma had to be ruled out. Lack of large polygonal cells, eccentrically placed nucleus instead of central placement, no intranuclear inclusions or bile pigment ruled out hepatic adenocarcinoma. Also, the nuclei had salt and pepper chromatin with micronucleoli instead of macronucleoli as seen in hepatic adenocarcinoma. Serum alpha feto-protein was within normal limits. Further, lymphoma, metastatic stomach carcinoid and metastatic small cell carcinoma of the lung were ruled out due to uniformity of tumor cells, lack of mitosis and necrosis. Plasmacytoma was ruled out due to lack of dyscohesive round cells, granular cytoplasm, Russell bodies and Dutcher bodies.
Pancreatic somatostatinomas also shares cytological similarities with acinar cell carcinoma and solid pseudopapillary tumor. Cells in acinar cell carcinoma resemble their normal counterpart with many naked nuclei in the background. Cells are monomorphic with granular cytoplasm and prominent nucleoli. In solid pseudopapillary tumor, papillary fragments are seen with central fibrovascular core and nuclei showing grooves. Cytoplasm is absent or scanty. Background may show necrosis, histiocytes and foreign body giant cells. Also, all these are negative for chromogranin.
Another intriguing factor about the present case was the presence of extensive calcification, which could be due to slow growth of the tumor.
If the tumor is surgically not resectable, chemotherapeutic drugs and somatostatin analog octreotide are given.
FNAC diagnosis of somatostatinoma has been rarely reported. We report this case because of its rarity and also to emphasize the correlation with clinical and radiological findings.
Source of Support: Nil
Conflict of Interest: None declared.
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