Pancreatic Pathology Online

Neoplasms of the Endocrine  Pancreas

Dr Sampurna Roy MD           July 2016

 

Benign and malignant tumours of the pancreatic islets are common enough to be encountered occasionally during a lifetime in a busy medical practice.

These tumours secrete large amounts of potent hormones that lead to physiologic disturbances that are responsible for distinctive clinical syndromes.

Before considering islet cell tumours a brief discussion of the development and function of normal islets will serve to set this group of intriguing tumours in perspective.

Neuroendocrine tumours of pancreas are not common (prevalence rate of less than 1 per 1000,000 population) but, because of the good prognosis and often early presentation, relative to pancreatic adenocarcinoma,  they are disproportionately represented in tumour resection specimens of pancreas (14% of cases).

In most published series approximately 70-80% of neuroendocrine tumors are categorized as functional- i.e. , they secrete a recognized hormone causing a distinct hormonal syndrome.

Insulinomas are the most common functional pancreatic endocrine tumors.

In decreasing order of frequency the other encountered functional tumours include gastrinoma, vipoma, glucagonoma, and somatostatinoma.

Functional tumours tend to present at an earlier age than non-functional ones.

The latter usually present with symptoms such as obstruction, or as abdominal masses or as incidental  findings on CT examinations, etc.

Diagnosis: Neuroendocrine tumours can usually be readily diagnosed on hematoxylin and eosin staining.

A variety of histological patterns can be seen (trabecular, solid, acinar) but these patterns bear no relationship to the hormonal status of the tumour or its malignant potential.

Immunocytochemistry can be used to show neuroendocrine differentiation (Chromogranin A , PGP 9.5 , synaptophysin)  as well as the presence of pancreatic hormones (insulin, glucagons, somatostatin and pancreatic polypeptide) and gastrin.

Many tumours on the analysis will be shows to be multi-hormonal, although cells producing the hormone causing the syndrome are liable to predominate.

Some tumors will be shows to contain hormones such as pancreatic polypeptide or somatostatin in the absence of any obvious hormonal clinical syndrome.

By convention, these tumours are classified as non-functional.

The main differential diagnosis of a non-functional pancreatic neuroendocrine tumour is solid and cystic tumour of the pancreas which tends to present in young women as a large, symptomatic abdominal mass arising in the pancreas.

When resected this lesion often shows areas of necrosis (a rare finding even in malignant pancreatic neuroendocrine tumours) and a careful search will usually show areas of the tumour in which a definite papillary pattern can be demonstrated.

This, coupled with negative immunocytochemical findings for neuroendocrine markers, should allow the correct diagnosis to be made.

It is not unusual to find difficulty in demonstrating the  relevant hormone immunocytochemically in a functional pancreatic neuroendocrine tumour.

The cells in many tumours are relatively "incontinent", such that while they may secrete large quantities of hormone they may store relatively little.

Immunocytochemistry detects stored prohormone within cells of relatively little staining of the relevant hormone may be seen.

In situ hybridization for hormonal messenger RNA is a possible way round this problem since it reflects the rate of hormonal synthesis rather than quantity of hormone stored within a cell.

A preliminary study of insulinoma has confirmed that in-situ hybridization may indeed be more sensitive than immunocytochemistry in defining functional tumours.

Benign or malignant?  The two definite criteria of malignancy in pancreatic endocrine neoplasms are invasion of adjacent organs and the presence of metastases.

However, these features are only present to 30-50% of resected tumours which subsequently prove to be malignant.

Have recent studies advanced our ability to predict the behavior of tumours which, at the time of surgery appear to be confined to the pancreas?

Since over 90% of insulinomas are benign this question is not often raised when these tumors are encountered.

Among the remainder, the presence of an intrapancreatic invasive growth pattern, the demonstration of nuclear pleomorphism, aneuploidy or cytoplasmic alfa-HCG all fail to act as prognostic predictors.

Progesterone receptor is present more commonly in benign tumours but the difference is insufficiently clear cut to be of diagnostic use.

Two Italian studies have shown that measures of tumour proliferation give the best predictive value of subsequent behavior.

In Pelosiís study,  the actual survival of all patients with a Ki-67 proliferative index greater than 5% was zero within 7 years, where as in those with a lower index more than 80% survival longer than 10 years.

Similar findings were demonstrated in the non-functioning pancreatic endocrine tumours studied by La Rossa, although here the cut-off Ki-67 proliferative index was 2%. 

Other criteria found to be statistical significant prognostic value in the latter study were the presence of tumour thrombi within capsular blood vessels, perineural space infiltration and a tumour size greater than 4 cms.

As Ki-67 can now be immunostained on routinely fixed tissues these observations should be applicable to clinical use.

Pancreatic Endocrine Tumours:

-Islet Cell Tumours

-Alpha Cell Tumours (Glucagonomas)

-Beta Cell Tumours (Insulinomas)

-Somatostatinoma

-VIPomas

-Pancreatic Polypeptide-Secreting Tumours

-Enterochromaffin Cell (Carcinoid) Tumours

-Pancreatic Gastrinoma

-Corticotropinoma (Ectopic ACTH syndrome)

-Parathyrinoma

-Multiple Endocrine Neoplasia (MEN) Syndrome

 

Further reading:

WHO 2010 classification of pancreatic endocrine tumors. Is the new always better than the old?

WHO 2004 criteria and CK19 are reliable prognostic markers in pancreatic endocrine tumors.

Prognostic and immunohistochemical validation of the capella classification of pancreatic neuroendocrine tumours: an analysis of 82 sporadic cases.

Pancreatic endocrine tumors: an update.

Update on pancreatic endocrine tumors.

Neuroendocrine pancreatic tumors: guidelines for management and update.

Pancreatic endocrine neoplasms: a current update on genetics and imaging.

Pancreatic endocrine tumors: clinical manifestations and predictive factors associated with survival.

Rare functioning pancreatic endocrine tumors.

Predictive factors associated with long-term survival in patients with neuroendocrine tumors of the pancreas.

Prognostic factors in pancreatic endocrine neoplasms: an analysis of 136 cases with a proposal for low-grade and intermediate-grade groups.

Review of the clinical, histological, and molecular aspects of pancreatic endocrine neoplasms.

Pancreatic neuroendocrine tumors: clinical features, diagnosis and medical treatment: advances.

 

 

Dr Sampurna Roy  MD

Consultant  Histopathologist (Kolkata - India)


 

 

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