Non-intestinal type adenocarcinoma (non-ITAC)

by Jason Wasserman MD PhD FRCPC
March 20, 2022

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What is non-intestinal-type adenocarcinoma?

Non-intestinal-type adenocarcinoma (non-ITAC) is a type of cancer. The tumour starts from the tissue that lines the inside of the nasal cavity or the paranasal sinuses such as the ethmoid or maxillary sinus. Pathologists divide non-ITAC into two grades, high and low, with high-grade tumours being associated with more aggressive behaviour and worse overall outcome.

What causes non-intestinal-type adenocarcinoma?

At present, doctors do not know what causes non-ITAC. Rare tumours have been associated with human papillomavirus (HPV) but this virus is not believed to cause most non-ITACs.

How do pathologists make this diagnosis?

The diagnosis of non-ITAC is usually made after a small sample of tissue is removed in a procedure called a biopsy. The diagnosis can also be made after the entire tumour is removed in a procedure called a resection. The tissue is then sent to a pathologist who examines it under a microscope.

How do pathologists determine the tumour grade for non-intestinal-type adenocarcinoma?

Pathologists divide non-ITAC into two grades, high and low, based on the way the tumour looks when examined under the microscope. Low-grade tumours are made up of medium-sized cells that contain a specialized type of protein called mucin. The tumour cells often connect together to form round structures called glands or long finger-like projections called papillae. The glands may be arranged in a back-to-back manner that pathologists describe as cribriform. Dividing cells called mitotic figures and a type of cell death called necrosis are rarely seen in low-grade non-ITAC.

This picture shows a low-grade non-intestinal type adenocarcinoma

High-grade tumours are often made up of larger more abnormal-looking cells that contain less mucin than low-grade tumours. Pathologists use the word atypical to describe abnormal-looking cells. The tumour cells are often connected together into large groups that pathologists describe as a solid pattern of growth. Unlike low-grade tumours, dividing tumour cells called mitotic figures and a type of cell death called necrosis are commonly seen.

This picture shows a high-grade non-intestinal type adenocarcinoma

What other tests are performed to confirm the diagnosis?

Your pathologists may perform a test called immunohistochemistry to confirm the diagnosis. When performed, the tumour cells in non-ITAC are usually positive for specialized proteins called cytokeratins including CK7. Very rarely the tumour cells may be positive for proteins normally seen in the gastrointestinal tract such as CK20. High-grade non-ITACs may produce proteins made by neuroendocrine cells such as chromogranin and synaptophysin.

What does perineural invasion mean?

Nerves are like long wires made up of groups of cells called neurons. Nerves transmit information (such as temperature, pressure, and pain) between your brain and your body. Perineural invasion is a term pathologists use to describe cancer cells attached to a nerve.

Perineural invasion is important because cancer cells that have attached to a nerve can use the nerve to travel into tissue outside of the original tumour. For this reason, perineural invasion is associated with a higher risk that the tumour will come back in the same area of the body (local recurrence) after treatment.

What does lymphovascular invasion mean?

Blood moves around the body through long thin tubes called blood vessels. Another type of fluid called lymph contains waste and immune cells that move around the body through lymphatic channels. Cancer cells can use blood vessels and lymphatics to travel away from the tumour to other parts of the body. The movement of cancer cells from the tumour to another part of the body is called metastasis.

Before cancer cells can metastasize, they need to enter a blood vessel or lymphatic. This is called lymphovascular invasion. Seeing lymphovascular invasion increases the risk that cancer cells will be found in a lymph node or a distant part of the body such as the lungs.

What is a margin?

A margin is any tissue that was cut by the surgeon in order to remove the tumour from your body. Whenever possible, surgeons will try to cut tissue outside of the tumour to reduce the risk that any cancer cells will be left behind after the tumour is removed.

A negative margin means there were no cancer cells at the very edge of the cut tissue. A margin is considered positive when there are cancer cells at the very edge of the cut tissue. A positive margin is associated with a higher risk that the tumour will grow back (recur) in the same site after treatment.

Because these tumours are often removed in multiple pieces, your pathologist may not be able to reliably assess the margins of the tumour. For that reason, most pathology reports for non-intestinal type adenocarcinoma do not have information about margins.

What are lymph nodes?

Lymph nodes are small immune organs located throughout the body. Cancer cells can travel from the tumour to a lymph node through lymphatic channels located in and around the tumour (see Lymphovascular invasion above). The movement of cancer cells from the tumour to a lymph node is called metastasis.

Lymph nodes from the neck are sometimes removed at the same time as the main tumour in a procedure called a neck dissection. The lymph nodes removed usually come from different areas of the neck and each area is called a level. The levels in the neck include 1, 2, 3, 4, and 5. Your pathology report will often describe how many lymph nodes were seen in each level sent for examination. Lymph nodes on the same side as the tumour are called ipsilateral while those on the opposite side of the tumour are called contralateral.

Your pathologist will carefully examine each lymph node for cancer cells. Lymph nodes that contain cancer cells are often called positive while those that do not contain any cancer cells are called negative. Most reports include the total number of lymph nodes examined and the number, if any, that contain cancer cells. The number of lymph nodes that contain cancer cells and their location in the body is used to determine the nodal stage (see Pathologic stage below).

What is a tumour deposit?

A group of cancer cells inside of a lymph node is called a tumour deposit. If a tumour deposit is found, your pathologist will measure the deposit and the largest tumour deposit found will be described in your report. Larger tumour deposits are associated with a worse prognosis. The size of the largest tumour deposit is also used to determine the nodal stage (see Pathologic stage below).

How do pathologists determine the pathologic stage (pTNM) for non-intestinal-type adenocarcinoma?

​The pathologic stage for non-intestinal type adenocarcinoma is based on the TNM staging system, an internationally recognized system originally created by the American Joint Committee on Cancer. This system uses information about the primary tumour (pT), lymph nodes (pN), and distant metastatic disease (pM)  to determine the complete pathologic stage (pTNM). Your pathologist will examine the tissue submitted and give each part a number. In general, a higher number means more advanced disease and a worse prognosis.

Tumour stage (pT) for tumours that start in the nasal cavity or ethmoid sinus

These tumours are given a tumour stage between 1 and 4. The tumour stage is based on how far the tumour has spread outside of the nasal cavity or ethmoid sinus.

• T1 – The tumour is limited to the nasal cavity or ethmoid sinus. It has not extended into the surrounding bones.
• T2 – The tumour has spread out of the nasal cavity or ethmoid sinus.
• T3 – The tumour has spread into the wall or floor of the orbit (the cavity that holds the eye), maxillary sinus, palate (the roof of the mouth), or cribriform plate (an area at the top of the nasal cavity).
• T4 – The tumour has spread to the eye, skin of the nose or cheek, cranial cavity (the space that holds the brain), pterygoid plates (bones at the bottom of the cranial cavity), sphenoid or frontal sinuses.

Tumour stage (pT) for tumours that start in the maxillary sinus

These tumours are given a tumour stage between 1 and 4. The tumour stage is based on how far the tumour has spread outside of the maxillary sinus.

• T1 – The tumour is limited to the maxillary sinus. It has not extended into the surrounding bones.
• T2 – The tumour has spread out of the nasal cavity or ethmoid sinus.
• T3 – The tumour has spread into the bone at the back of the maxillary sinus, subcutaneous tissues, floor or wall of the orbit (the cavity that holds the eye), pterygoid fossa, or ethmoid sinuses.
• T4 – The tumour has spread to the eye, skin of the nose or cheek, cranial cavity (the space that holds the brain), pterygoid plates (bones at the bottom of the cranial cavity), sphenoid or frontal sinuses.

Nodal stage (pN) for tumours that start in the nasal cavity or paranasal sinuses

These tumours are given a nodal stage between 0 and 3 based on the following three features:

1. The number of lymph nodes that contain cancer cells.
2. The size of the tumour deposit.
3. Whether the lymph nodes with cancer cells are on the same side (ipsilateral) or the opposite side (contralateral) of the tumour.

The nodal stage will be higher if any of the tumour deposits are larger than 3 cm, more than one lymph node contains cancer cells, cancer cells are found in lymph nodes on both sides of the neck, and if any of the lymph nodes show extranodal extension.

If no cancer cells are found in any of the lymph nodes examined, the nodal stage is N0. If no lymph nodes are submitted for pathological examination, the nodal cannot be determined and the stage is listed as NX.

Metastatic stage (pM) for non-intestinal type adenocarcinoma

Non-intestinal type adenocarcinoma is given a metastasis stage (pM) of 0 or 1 based on the presence of cancer cells at a distant site in the body (for example the lungs). The metastatic stage can only be determined if tissue from a distant site is submitted for pathological examination. Because this tissue is rarely present, the metastasis stage cannot be determined and is listed as MX.