A 29-year-old lady presented with vague, non radiating epigastric pain since four months. The general condition of patient was good. Per abdominal examination was normal.

Laboratory investigations: All routine blood investigations were normal, except a raised 24 hrs level of 5- hydroxy indol acetic acid (HIAA).

RADIOLOGICAL FINDINGS:

Ultrasonography of the abdomen showed a well-defined rounded hypoechoic lesion - two centimeter in diameter in the head of the pancreas. The pancreatic duct (PD) and the common bile duct (CBD) were normal. No calcification was noted. The rest of the pancreas was normal.

Fig. 1

Plain and contrast enhanced CT scan of the abdomen showed a well-defined isodense mass in the head of pancreas which showed homogenous enhancement after contrast administration in arterial phase and became isodense to pancreas in the portal venous phase. The mass was in close proximity to the terminal CBD and the PD was seen to be pushed posteriorly. Adjacent vessels were normal. No calcification was seen.

Fig. 2	Fig. 3
Fig. 4

Plain and contrast enhanced MRI of the abdomen confirmed the CT findings of a mass in the head of the pancreas. The mass was hypointense on T1W images and showed enhancement after gadolinium administration.

Fig. 5	Fig. 6

In view of the well-defined nature of the mass, the young age of the patient and the raised levels of 5-HIAA, a diagnosis of a carcinoid was made. The patient underwent Whipple's surgery and the excised mass was sent for histopathology study which confirmed the diagnosis.
Unfortunately the patient died on the seventh post operative day due to ARDS.

FINAL DIAGNOSIS: Carcinoid tumour of pancreatic head.

DISCUSSION:

A carcinoid tumour is one of the rare tumours of the pancreas. When compared with carcinoids at other sites, pancreatic carcinoid has specific features:
(i) Low incidence
(ii) Argyrophil stain is more likely to be positive than argentaffin stain.
(iii) Grow to larger size and
(iv) High incidence of metastases and carcinoid syndrome, resulting in an unfavorable prognosis

PATHOPHYSIOLOGY: Pancreatic carcinoids originate from the entero-chromaffin cells (Kultschitsky cells) that are usually present in the exocrine glands of pancreatic tissue and in the pancreatic islet cells which retain the capacity to secrete serotonergic derivatives. These tumors elaborate serotonin and other histamine like substances that normally are transported to the liver where they are metabolized. They frequently metastasize to regional lymph nodes and the liver. They may show calcification - whereas islet cell tumors usually do not. Metastasis is uncommon if the size is less than 1 cm.

CLASSIFICATION: According to their secretory activity, pancreatic carcinoid tumors may be biologically active or inactive. If the tumour is endorinally active and produces serotonin in significant amounts, then the patient will develop the carcinoid syndrome.

INCIDENCE: Although carcinoids are the most frequently occurring of neuro-endocrine tumors, their pancreatic localization is exceedingly rare and often "accidental" in many cases. The incidence of pancreatic carcinoid was found to be <0.5% of all carcinoids. Most of them are situated in the tail and body of the pancreas.

CLINICAL PRESENTATION: They are usually asymptomatic until metastasis occur or there is compression of the pancreatic duct and raised levels of serotonin and its metabolites in plasma and urine. The most frequent symptoms associated with pancreatic carcinoid tumours are abdominal pain and diarrhea related to intestinal hypermotility. Pancreatitis seems to be the consequence of the ductal obstruction by the tumour, Although the exact ratio of functioning versus non-functioning carcinoid tumors is not yet known, for pancreatic tumors it is estimated to be 1:10

Carcinoid syndrome occurs in a majority of patients with liver metastases and consists of the classic triad of cutaneous flushing, diarrhea and valvular heart disease. However the absence of the characteristic carcinoid syndrome does not exclude the diagnosis of carcinoid tumour even in patients with liver metastases.

INVESTIGATIONS: Pancreatic carcinoid is indistinguishable from epithelial neoplasms clinically and on imaging studies. Biopsy is essential to establish the diagnosis.

Biochemical markers:
24-hour urinary excretion of 5-hydroxy indoleacetic acid (5-HIAA): This test is helpful only when the patient has symptoms of carcinoid syndrome. The measurement of 24-hour urinary excretion of 5-HIAA is useful because it provides information of tumor secretory activity that may occasionally be missed by random plasma peptide sampling if the secretion is paroxysmal.

Chromogranin A: Chromogranin A (CgA) is a member of the chromogranin family, which is stored in the secretory granules of neuroendocrine cells. Its detection in plasma can be utilized as a general tumor marker for carcinoids even for "non-functioning" tumors. Plasma CgA levels are sensitive but nonspecific markers of carcinoid tumors because they are also elevated in other conditions. CgA concentration can be correlated with tumor burden.

RADIOLOGIC INVESTIGATION:

PLAIN RADIOGRAPH OF THE ABDOMEN: It may show curvilinear calcification in the region of the pancreatic bed. When calcification is present, it differentiates carcinoid tumour from islet cell tumours.

USG Abdomen: Sonographic findings usually demonstrate a hypoechoic mass, which may be of varying size-usually small. Calcification may or may not be present. Lymph node and liver metastases may be seen.

Endoscopic ultrasound may play an important role in the detection of pancreatic carcinoid.

CT scan : This may show a hypodense mass associated with calcification in the pancreas. Small tumors (less than 2cm in diameter) are homogeneous whereas larger tumors are heterogeneous with areas of cystic necrosis. The lesions show variable enhancement on post contrast images and may demonstrate lymph node and liver metastases.

MRI : MRI will show an hypointense mass with or without calcification in the pancreas which enhances on contrast administration. It is a very sensitive technique for the detection of liver metastases, but appears to be less sensitive for the diagnosis of extra-hepatic disease. MRI needs further evaluation before it is used as the primary modality for the diagnosis and staging of carcinoid tumor but, overall, it appears to have little advantage over CT

PET Scan: The FDG PET scan is not helpful .The administration of radioactive serotonin precursor 11C-5-HT has been shown to provide excellent tumor visualization, with high detection rates. More recently, 68 Ga coupled to Octreotide has been used as a tracer for PET imaging - also achieving high detection rate.

Angiography: It will show a highly vascular mass in the pancreas.

NUCLEAR SCAN: MRI and CT provide important means of initial localization of carcinoid tumors or their metastases; however, their detection rates and sensitivities are lower than imaging with 111In-pentetreotide scintigraphy. SRS: Somatostatin receptor scintigraphy (SRS) can be done by using MIBG, DTPA Octreoitide or 111In pentreotide (Octreoscan).The latter is the gold standard for imaging carcinoid and other neuroendocrine tumors and depends upon the presence of somatostatin receptor. This is fairly specific for neuroendocrine tumors since these receptors are present in 85-90% of all of these types of tumor. Sensitivity of this study can be enhanced by simultaneous use of SPECT.

TREATMENT:

Surgery: It is curative. Surgery is the most effective treatment for both local tumor effects and symptoms caused by the secretory agents because it removes the primary lesion.

Chemotherapy:
Conventional chemotherapeutic agents such as streptozotocin, 5-FU, doxorubicin, and cyclophosphamide are helpful. Etoposide can be used effectively either alone or in combination with cisplatin. However chemotherapy may be beneficial for selected cases of advanced tumors that do not respond to other forms of therapy.

Embolization or chemoembolisation
Selective arterial catheterization and either Embolization, or chemoembolization, is beneficial and decreases symptoms due local pressure effect and decreasing humoral output. However, the duration of palliation may be limited because of either recurrence or revascularization of lesions. Hepatic artery embolization can be used if associated liver metastasis are present.

¹³¹I-MIBG therapy More than 70% of carcinoids concentrate MIBG. The use of 131I-MIBG therapy can be considered early in an adjuvant setting after surgery to eradicate occult disease or later for treatment of disseminated disease.

Medical therapy: It is more useful in patients with carcinoid syndrome. Somatostatin analogs: Somatostatin through its physiological functions in the gastrointestinal tract inhibits the secretion of pancreatic and intestinal hormones. Somatostatin acts through high-affinity G protein-coupled membrane receptors. Examples are Octreotide and Lanreotide thermore.

New therapeutical developments:
A new so-called "universal" somatostatin analog, named SOM230 is under evaluation. Endostatin, thalidomide and angiogenesis inhibiting drugs are also under evaluation. Cryosurgery and radio frequency ablation are in developmental stages.