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Multiple Endocrine Neoplasia
This is a true clinical story. For obvious privacy reasons, the names of the patients, the doctors and their titles and the institutes have been omitted.
The patient’s story
When you’re a young mom you never expect to have any serious illness.
I had felt unwell for a while so I went to my physician. He sent me for a CAT scan so I had a feeling that it might be something serious. When I was told the results I couldn’t believe it… a ‘lesion’ in my pancreas which may be affecting my hormones. Obviously I was shocked and scared. What was a ‘lesion’? How did I get it?
I was sent for more scans that showed more ‘lesions’ all over the place… in my pancreas, neck and even my brain.
The next thing I knew I was having surgery to remove the lesions in my pancreas. When the results came back I was told I had two different types of tumors: an ‘insulinoma’, as well as a ‘gastrinoma’ both of which were producing too many hormones and making me feel unwell... I started to understand what a ‘lesion’ was… cancer
Three months later I was having surgery again, this time to remove part of my pancreas and all of my spleen. More tumours were discovered… this time in the spleen. I ended up having a third operation to my neck where even more tumours were found.
Over the next 2 years, I did the best to get on with my life, but kept having more scans which showed suspicious areas spreading around both my pancreas and my ‘parathyroids’ (The gland in my neck where I’d had my third operation). I felt well so I couldn’t really understand what was going on; especially when I was told I had to’ prepare for the worst’. The explanations I was given never felt good enough so when I saw the medical Opinions website I decided to send them all my case notes to get another opinion.
My file was sent to a Professor who is the world authority on these types of tumours. She immediately identified that all these tumours are part of a syndrome called… multiple endocrine neoplasia Type I (MEN-I). She explained that it is a genetic problem that results in tumours in different, but predictable, places in the body. This illness runs in families so all my children will be checked to see if they have the gene… hopefully this will mean that if they do have it it’ll be picked up early.
She explained that further surgery doesn’t really help with my illness and that the best treatment is to have just one injection a month, with close follow up. (She also detailed exactly what needed to be done). Chemotherapy may end up being needed... But we’ll cross that hurdle if we come to it. She also said that she’d happily treat me in the future.
The following documents are the case history that the patient provided and the experts opinion in response.
Clinical information
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Send Report to: US
Diagnosis: Endocrine carcinoma of the pancreas.
The patient is a 35 year old women with no previous medical history.
In June 2001 she was sent by her primary care doctor for a CAT scan following abdominal pain. It showed a hyperdense oval lesion in tail of the pancreas within which was a central hypodense area with 2cm diameter. This was thought to be compatible with an endocrine tumour.
Based on this, a further series of diagnostic tests were carried out.
An ultrasound of the neck showed three hyperplastic parathyroids caudally to the thyroid on the right, and on the left two hyperplastic parathyroids; one retroesophageal and the other anterior to the esophagus immediately behind the laryngeal nerve.
A repeat abdominal CT scan with contrast showed several further abnormalities;
A
A further oval formation of approximately
A surgical procedure was performed removing the lesions in the pancreas and lymph nodes in the intra-aortocaval and the retropancreatic areas.
The histology showed a 3 x
The histology of the intra-aortocaval and retroduodenal lymph nodes showed no neoplasia. A nodule which was removed from the greater omentum and a lymph node along left gastric artery also revealed no neoplasia.
Following this, further surgery was performed removing both the tail and part of the body of the pancreas and all of the spleen.
The histology report showed clearly differentiated multiple endocrine benign tumours in both the body and tail of pancreas and the spleen (Ki-67 < 2%, mitosis < 2HPF).There was no neoplasia in the tripod lymph nodes or in the nodes of the hepatic peduncle.
A parathyroidectomy was carried out in the January of 2002.The histology showed a thyroid macrofollicular adenoma in the right inferior parathyroid, a parathyroid adenoma in the right inferior parathyroid and a lymph node with sinus histiocytosis in the right inferior parathyroid.
In July 2002 whole body scintigraphy was carried out showing a trace hyperaccumulation in an irregular oval image at the right paramedian anterior epigastric area, suggesting a lesion expressing somatostatin receptors in apparent progression.
An abdominal CT scan in November 2002 showed a partly calcified 11mm hyperdense formation at the head of the pancreas, in proximity to the superior mesenteric vein indicative of pathology. The next month an ultrasound was performed confirming the finding.
In August 2003 repeat whole body scintigraphy was repeated showing the pancreatic lesion expressing somatostatin receptors with further suspected abdominal lesions.
Parathyroid scintigraphy in April 2004 showed hyperfunctioning parathyroid tissue.
In May 2004 further whole body scintigraphy confirmed the recurrence of neuroendocrine heteroplasia in the pancreas. The results also showed areas expressing somatostatin receptors in the epigastric region with localization at the head of the pancreas as well as in the left paracolic region, the homolateral paraumbilical regions and the parathyroids.
The patient reports that she is currently completely asymptomatic.
Questions:
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What is the prognosis?
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What would be the most appropriate therapy, given that the scintigraphy shows a lesion identified as being receive?
The expert’s opinion
To Medical Opinion:
Thank you for the referral and the copy of the medical records for this patient. I had the opportunity to review -------- medical records:
To summarize, Ms. -------- is a 35 year old woman who was found to have a 2cm pancreatic lesion on CT of the abdomen in June 2001. This study was repeated one month later and showed the same lesion as well as a
In July 2001, Ms. --------- underwent removal of the pancreatic lesion and lymph node dissection. The pathology report revealed an insulinoma in the head of the pancreas with lymph node metastasis and a gastrinoma in the tail of the pancreas. Ms. ------- underwent surgery again in October 2001 to remove the distal pancreas and spleen. The pathology report revealed multiple benign endocrine tumors. In January 2002, Ms. -------- underwent a parathyroidectomy which revealed multiple adenomas.
In July 2002, an Octreoscan revealed uptake in the epigastric area. Two months later, a CT of the abdomen revealed a 1.1cm lesion in the head of the pancreas. The Octreoscan was repeated in August 2003 and revealed a pancreatic lesion and “suspected repetitive abdominal lesions”. In May
Ms. --------- is currently asymptomatic.
It appears as if Ms. -------- 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, Ms. -------- 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; however, we do know that Ms. -------- 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 Ms. -------- may have recurrent hyperparathyroidism at this time.
Pituitary adenomas develop in approximately 15 – 20% of patients with MEN-I when screened with CT or MRI. The most common type of pituitary adenoma in MEN-I is a prolactinoma. Since Ms. ------- is currently asymptomatic, it does not appear as if this adenoma has been enlarging or producing hormones to the extent to cause symptoms. As a result, there is no clinical indication for intervention with respect to the suspected pituitary adenoma at this time.
Effective treatment is usually available for the hyperparathyroidism and pituitary disease in MEN-1; as a result, the life-threatening manifestation of MEN-1 is the malignant potential of pancreatic islet cell tumors. Pancreatic islet cell tumors in MEN-1 often synthesize multiple hormones as has been seen with Ms. -------. Patients do not always have clinical symptoms associated with these tumors due to the fact the many of these tumors may be defective in their hormone processing apparatus or have an inefficient secretory mechanism.
Attempts at surgical cure of gastrinomas in patients with MEN-I have been unsuccessful. This is due to the fact that in MEN-I these tumors are multifocal, often very small and easily overlooked. 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, but are not necessarily associated with a poor prognosis or a high likelihood that visceral metastases will occur. Like gastrinomas, insulinomas in MEN-1 are often small, may be multiple, and may be associated with the simultaneous presence of other islet cell tumors.
Fortunately, Ms. -------- is asymptomatic at this time. Unfortunately, a recent Octreoscan indicates evidence of recurrent disease in the pancreas and apparent metastatic disease is abdominal lymph nodes. There is also evidence of hyperfunctioning parathyroid tissue.
With respect to treatment, I would recommend first checking calcium and parathyroid hormone levels to determine the extent of hyperparathyroidism. Since Ms. ------- had surgery in the past and is currently asymptomatic, surgical intervention for the hyperparathyroidism is not likely warranted again at this time. Certain medications, particularly 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 the effects of hyperparathyroidism at the level of the PTH receptor.
With respect to the presumed metastatic islet cell tumor, I would recommend first testing baseline gastrin and insulin levels if not already done. Fortunately again, Ms. ------- is asymptomatic; however, it appears as if her disease has been progressing over the past year. Because of her disease progression, I would recommend treating with Octreotide LAR (sandostatin) 20mg IM monthly and increasing the dose by 10mg monthly as tolerated. Gastrin and insulin levels should be checked in 3 month intervals to determine response to treatment. If Ms. -------’s disease progresses while on Octreotide LAR, chemotherapy would be recommended. While there is no standard of therapy, these tumors many times resemble small cell carcinoma so a combination of platinum and etoposide would be reasonable. 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. Ms. ------ may have a very favorable response to Octreotide and her disease may be manageable for quite some time.
Thank you for allowing me to participate in the care of your patient. I wish you and Ms. ------- the best.
I would be happy to see this patient in my practice if she wishes to travel to the
Thank you.
Sincerely,
Prof. --------
Oncologist
Head of Oncology Department