What Is Pancreatic Acinar Cell Carcinoma?

The pancreas is a vital organ in the digestive system, and it plays an essential role in controlling the sugar levels in the blood. Unfortunately, like many organs, the pancreas is susceptible to developing cancer.

There are two types of pancreatic cancer:

• Exocrine pancreatic cancer - cancer of the pancreas' enzyme-producing acinar cells.
• Neuroendocrine pancreatic cancer - a rare type of pancreatic cancer that develops from the hormone-producing neuroendocrine cells of the pancreas.

Exocrine cancers make up the vast majority of pancreatic cancers; however, pancreatic acinar cell carcinoma (PACC) cases are rare, making up only 1-2% of exocrine cancer cases.¹

This article will explore the following:

• What PACC is?
• Causes
• Symptoms
• Diagnosis and how the staging system works?
• Treating PACC
• Current research into PACC treatment
• Living with PACC  

Understanding the pancreas and acinar cells

Image source: OpenStax College, via Wikimedia Commons

The pancreas has both exocrine and endocrine functions. The exocrine function of the pancreas is involved in digestion. When food enters the stomach, the pancreas releases enzymes into the duodenum, a section of the small intestine. These digestive enzymes help break down food so that we can get energy.² 

The neuroendocrine function of the pancreas focuses on controlling blood sugar levels in the body. The pancreas releases hormones such as insulin and glucagon to keep blood glucose levels in a healthy range.³

Acinar cells are the cells of the pancreas that make and store the digestive enzymes. They produce three enzymes: amylase, trypsin and lipase, which allow for the digestion of carbohydrates, proteins and lipids, respectively. These enzymes are stored in an inactive form within the cells until food reaches the stomach. Signals are then sent to the pancreas to release the active forms of these enzymes into the duodenum.⁴

Development and causes of pancreatic acinar cell carcinoma

Our DNA is the collection of genes that act as blueprints for every protein in our body. Many of these genes code for proteins that regulate when our cells reproduce, how they should be maintained, checked for defects and even destroyed if defective.

However, genetic mutations can influence how the blueprints for these proteins are read.  Any change can lead to the production of faulty proteins from the mutated gene. Faults in proteins essential in cell regulation can cause cells to reproduce and evade destruction.⁵

These mutations can be passed down to every cell in its lineage, collecting mutations along the way until a cancerous cell emerges, leading to the characteristic uncontrolled cell growth or cancer.⁵

Although mutations can result from naturally occurring errors during cell reproduction, some substances and conditions can increase the chances of these mutations. These include:⁶

• Tobacco
• Obesity
• Alcohol
• Red meat
• Family genetics
• Other conditions affecting the pancreas – eg. pancreatitis, type 1 diabetes, gallstones, metabolic syndrome.

Symptoms and clinical presentation

PACC can be seen in people of any age but is most commonly seen in people in their 60s. Common symptoms include:⁷

• Weight loss
• Abdominal pain
• Back pain

A small number of people can present with other symptoms, such as: 

• Nausea/vomiting

• Black faeces (melaena)
• Weakness
• Anorexia
• Diarrhoea 
• Jaundice

Due to its rarity, there can be some challenges in diagnosing PACC as it shares some symptoms with other conditions. For example, in people with PACC, lipase levels in the blood are extremely elevated, but this is also a feature of the far more common condition pancreatitis.^7,8 

Diagnostic procedures 

If you have any features suggestive of pancreatic cancer or have a raised blood lipase level, then the doctor can advise you to undergo the following investigations:

• CT scan
• MRI scan 
• Ultrasound 

Imaging helps your doctor detect any abnormal pancreatic mass.⁹  

Your team of doctors will advise a biopsy if they find an abnormal pancreatic mass on imaging:

Microscopic image of pancreatic acinar cell carcinoma

Image source: Nephron, via Wikimedia

Microscopic examination of a biopsy sample of pancreatic mass will help to determine:

• Cell types present in neoplasm or tumour
• Size, shape and structure of tumour cells
• Presence of certain enzymes in these tumour cells
• Shape and structure of the neoplasm itself

After the confirmation of PACC, your team of doctors will assess whether the tumour is resectable or not and will plan for surgery. They will stage the pancreatic tumour to determine the likelihood of its spread to other organs and to decide which treatment will be most effective.⁷

Staging and prognosis 

Pancreatic exocrine cancers, including PACC, use a variant of the TNM system. It includes three parameters: 

• T - Size of the tumour
• N - If cancer has spread to nearby lymph nodes and how many
• M - If cancer has spread to other parts of the body (Metastasis)

Each of these characteristics have multiple categories: 

Using these characteristics, the stage of cancer can be determined. Generally, the larger the size of the tumour and the more the cancer has spread to the nodes or metastasised, the later the stage.¹⁰

The stage that PACC is diagnosed provides an idea of the patient’s prognosis. If the cancer is located within the pancreas, the median period of survival is 38 months. If the cancer has metastasised, the median survival period is 14 months. Unfortunately, in 50% of patients diagnosed with PACC, the cancer has already metastasised.¹¹ 

Furthermore, the prognosis depends on the tumour's location in the pancreas since this determines whether or not the surgeon can remove the tumour. Resectable tumours have a favourable outcome compared to those that are impossible to remove.¹¹ 

Treatment options 

Treatment of PACC includes surgery, radiotherapy, and chemotherapy. Surgery is the optimal option in treating PACC and involves the removal of the tumour. However, some tumours are inoperable due to their location in the pancreas. The tumour can sometimes invade nearby blood vessels or involve the lymph nodes, making it difficult to resect.⁷

Evaluation of PACC according to the category it falls into:⁷

• Resectable - Tumour can be removed by surgery
• Borderline resectable - Tumour may have spread to nearby blood vessels but can still be removed
• Locally advance - Tumour has spread to nearby lymph nodes or tissues and can not be entirely removed by surgery
•  Recurrent/metastatic - Tumour has metastasised and cannot be removed by surgery

In patients with resectable or borderline resectable PACC, chemotherapy and radiotherapy can be used before and after surgery to try and limit the tumour growth as well as try and prevent the tumour from returning. In locally advanced PACC, chemotherapy, radiotherapy and surgery can be conducted to slow down tumour growth. Due to the spread of the tumour in metastatic PACC patients, only chemotherapy is used.⁷ 

Ongoing research and advances 

Due to the rarity of PACC, there have been minimal numbers of studies into chemotherapies in treating the condition. Currently, the chemotherapies used in treating PACC are used to treat other pancreatic and colorectal cancers. Sadly, these chemotherapies have been found to have limited effectiveness.⁷ 

Current PACC clinical trials focus on different combinations of existing pancreatic chemotherapy.⁷ Alternatively, other trials are looking into the effectiveness of other chemotherapy drugs used for other cancers on PACC, such as the ovarian cancer drug Olaparib.¹²

Future hopes in treating PACC revolve around better understanding the genetic mutations involved in PACC. Once we have a better knowledge of them, drugs can be developed to target them and improve the outcome of PACC. .¹³

Supportive care and quality of life 

Having PACC or having a family member with the condition can be a challenging experience. Thankfully, medical care teams are in place to offer support and keep you informed and aware of the risks and benefits of each form of treatment. 

In cases that cannot be cured, pain and symptoms are managed by palliative care, so that patients can have the best quality of life possible while avoiding suffering and a prolonged death.

Palliative care includes, amongst other things:¹⁴

• Medication to help ease pain
• Surgery that can help relieve symptoms that can cause discomfort
• Providing emotional support for both patient and family, helping them come to terms with current diagnoses and what lies ahead.
• Bereavement support to families after death

Hospice care is also an option for those in palliative care, providing constant monitoring of the condition so that pain and discomfort can be limited as much as possible.¹⁴ Additionally, there are organisations such as Pancreatic Cancer UK and Pancreatic Cancer Action that offer support, advice and information to people living with or close to anyone with pancreatic cancer.

Summary

PACC is a rare form of pancreatic cancer that comes from the enzyme- producing cells of the pancreas. Its main symptoms include weight loss, abdominal pain and back pain.

Genetic mutations can cause PACC. However, alcohol, smoking, obesity, red meat and family genetics can increase the likelihood of developing PACC. Treatments for PACC include surgery, chemotherapy and radiotherapy, each with different success rates, depending on the stage and location of the tumour. Although the success rate of treatment is currently limited, ongoing research can identify new drug targets and develop chemotherapies to treat PACC.