A 33 year old female was diagnosed with endocrine carcinoma of the pancreas. No information regarding medical history was reported by the patient.

A CAT scan of the pancreas demonstrated a hyperdense oval lesion with a central hypodense area having a maximum diameter of about 2cm. This was at first was compatible with an endocrine type primitive productive process.

Based on these results, a further series of diagnostic tests were carried out (CAT scan of brain, ultrasound of neck and upper abdomen with contrast medium, an ultrasound of thyroid/parathyroid, full abdomen and upper abdomen, CAT scan of abdomen). These tests showed various pathological abnormalities listed below.

These abnormalities can be summarized as follows:

-       A pancreatic formation of approximately 2cm, with a hypointense NMR signal, which with contrast medium showed an increased intensity of the signal in the arterial phase and a slight central dishomogeneity.

-       An oval formation of approximately 1.5cm located outside the pancreas between the head of the pancreas and the left renal vein, in proximity to the outlet to the vena cava. Both of these lesions were interpreted as small hypervascularized expansive formations.

-       An increase in thickness of stomach walls with accentuated plicae.

-       A lymph node of about 2cm, in proximity with the head of the pancreas.

-       In the brain, a hypo-intense oval area of approximately 4-5mm located at the intersection between the anterior and posterior hypophysis, suspected to be a hypophysis microadenoma.

-       In the neck, 3 hyperplastic parathyroids were identified caudally to the thyroid on the right, and on the left 2 hyperplastic parathyroids were shown near the esophagus immediately behind the laryngeal nerve.

-       Right renal cyst.

A surgical procedure was carried out to remove the growth in the pancreas by intra-aortocaval retropancreatic lymphadenectomy.

Histology tests on the surgical samples listed below showed the following:

-       No neoplasia in intra-aortocaval retroduodenal lymph nodes.

-       Nodule on the large omentum: No neoplasia in lymph node.

-       No neoplasia in lymph node at inferior margin of tail of pancreas.

-       Neoplasia at head of pancreas, suspected insulinoma (oval nodule of 3 x 2.5cm). Clearly differentiated lymph node metastasis of endocrine carcinoma.

-       No neoplasia in lymph node along left gastric artery.

-       Neoplasia of tail of pancreas, suspected gastrinoma. Clearly differentiated endocrine carcinoma.

Another surgical procedure of distal pancreatectomy was carried out with removal of tail and part of body of pancreas and total splenectomy. The histology test showed the following:

No neoplasia in Tripod lymph node. No neoplasia in hepatic peduncle lymph nodes. Surgical sample (spleen and pancreas): Clearly differentiated multiple endocrine benign tumors.

A further surgical procedure of parathyroidectomy was carried out and the results of the histology test were as follows:

Right inferior parathyroid adenoma: Thyroid macrofollicular adenoma.

Whole body scintigraphy showed an irregular image of trace hyper-accumulation in the right paramedian anterior epigastric area, suggesting a lesion expressing somatostatin receptors in apparent slight progression.

The complete abdominal CAT scan showed a partly calcified hyperdense formation in the pancreas, near the mesenteric vein, having an estimated dimension of 11 mm, indicative of base pathology localization. These results were subsequently confirmed by an ultrasound.

The results of the whole body scintigraphy were as follows: Results were substantially the same as the previous follow-up and were compatible with the presence of a pancreatic lesion expressing somatostatin receptors and suspected repetitive abdominal lesions.

The results of the parathyroid scintigraphy were as follows: Results were compatible with the presence of hyper-functioning parathyroid tissue.

The results of the whole body scintigraphy with immune and receptor traces confirmed the presence of a suspected recurrence of neuroendocrine heteroplasia in the pancreas. The results also showed areas expressing somatostatin receptors in the abdomen (epigastric region with localization at the head of the pancreas and in the left paracolic and homolateral paraumbilical regions) and parathyroid.

The patient reports that she is currently completely asymptomatic.

 It appears that the patient has multiple endocrine neoplasia Type I (MEN-I). She has parathyroid adenomas, pancreatic insulinoma/ gastrinoma, and suggestion of pituitary adenoma on CT of the brain. The family history is not given which would be of interest since this is an autosomal dominant disease; however, if there is no family history, the patient may represent the index case of this disease.

Hyperparathyroidism is the most common manifestation of MEN-I. We do not have information on calcium levels and parathyroidism levels; but, the patient is currently asymptomatic. There is a high rate of recurrent hyperparathyroidism after apparently successful subtotal parathyroidectomy in patients with MEN-I and it appears from imaging studies that the patient may have recurrent hyperparathyroidism at this time. 

 

Pituitary adenomas develop in approximately 15 -20% of patients with MEN-I screened with CT or MRI. The most common type of adenoma in MEN-I is a prolactinoma. Since the patient is currently asymptomatic, with no signs of enlarged adenoma, there is no clinical indication for intervention with respect to the suspected pituitary adenoma at this time. 

 

There is an effective treatment for hyperparathyroidism and pituitary disease in MEN-1; the life-threatening manifestation of MEN-1 is the malignancy of pancreatic islet cell tumors. Pancreatic islet cell tumors in MEN-1 often synthesize multiple hormones as seen with this patient. Patients do not always have clinical symptoms due to the fact that many of these tumors may be defective in their hormone processing apparatus or have an inefficient secretory mechanism.  

MEN-I-related gastrinoma tumors are multifocal, often small and easily overlooked, making surgical removal largely unsuccessful. The risk of death from malignant spread of MEN-1-associated gastrinoma appears to be less than that for isolated gastrinoma. Local lymph node metastases are common. Insulinomas in MEN-1 are also small, multiple, and associated with the simultaneous presence of other islet cell tumors.

Although the patient is asymptomatic at this time, unfortunately, a recent Octreoscan indicates evidence of recurrent disease in the pancreas and metastatic disease in abdominal lymph nodes. There is also evidence of hyperfunctioning parathyroid tissue.

 

With respect to medical treatment, I recommend checking calcium and parathyroid hormone levels to determine the extent of hyperparathyroidism. Surgical intervention for hyperparathyroidism is not warranted again at this time. Medications such as estrogen plus progestin, bisphosphonates, and raloxifene inhibit bone resorption and can increase bone density and lower serum calcium concentrations in patients with hyperparathyroidism. Other medications, such as calcimimetics or vitamin D analogues suppress parathyroid hormone release, or counteract hyperparathyroidism effects at the level of PTH receptors.

 

With respect to the metastatic islet cell tumor, I recommend testing baseline gastrin and insulin. It appears that the patient's disease has been progressing over the past year. Because of her disease progression, I recommend treating with Octreotide LAR (sandostatin) monthly and increasing the dose as tolerated. Gastrin and insulin levels should be checked at 3 month intervals to determine response to treatment. If the patient’s disease progresses while on Octreotide LAR, a chemotherapy combination of platinum and etoposide would be recommended. Enrollment in a clinical trial, if available, would also be appropriate. 

It is difficult to make estimates regarding prognosis as this largely depends upon her response to therapy. The patient may have a very favorable response to Octreotide and her disease may be manageable for quite some time.