Nonkeratinizing squamous cell carcinoma (NKSCC)


Nonkeratinizing squamous cell carcinoma (NKSCC) is a type of cancer made up of squamous cells that have not undergone a process called keratinization. Squamous cells are normally flat cells found on the surface of your skin and in the lining of many internal areas such as the mouth, throat, lungs, cervix, and anal canal. Keratinization is a natural process in which these cells produce a tough protein called keratin, making them stronger and more resistant to damage. In NKSCC, cancer cells do not produce significant amounts of keratin, causing them to appear differently under a microscope.

Nonkeratinizing squamous cell carcinoma is commonly found in specific areas of the body, including the tonsils, base of the tongue, soft palate, nasal cavity and sinuses (collectively known as the sinonasal tract), lungs, cervix, and anal canal. When NKSCC occurs in the nasopharynx (the area behind your nasal passages), it’s also known as nasopharyngeal carcinoma.

What are the symptoms of nonkeratinizing squamous cell carcinoma?

Symptoms of NKSCC vary depending on where the tumor develops:

  • Oropharynx (tonsils, tongue base, soft palate): Persistent sore throat, trouble swallowing, ear pain, or a lump in the neck.

  • Nasopharynx: Nasal congestion, frequent nosebleeds, hearing loss, ear pain, or neck swelling.

  • Sinonasal tract: Blocked or congested nose, frequent nosebleeds, facial pain, swelling around the eyes, or persistent sinus infections.

  • Lungs: Persistent cough, difficulty breathing, chest pain, coughing up blood, or unexplained weight loss.

  • Cervix: Irregular vaginal bleeding, discomfort or pain during intercourse, or unusual discharge.

  • Anal canal: Bleeding, pain, discomfort, or a lump around the anus.

What causes nonkeratinizing squamous cell carcinoma?

The cause of NKSCC usually depends on the part of the body where the cancer starts:

  • Human papillomavirus (HPV) infection causes most cases of NKSCC in the oropharynx, cervix, and anal canal.

  • Epstein-Barr virus (EBV) infection is strongly linked to NKSCC in the nasopharynx.

  • Tobacco smoking is associated with most NKSCC cases involving the lungs.

  • Exposure to harmful substances or chronic irritation may contribute to NKSCC in the sinonasal tract.

In many cases, viral infections such as HPV or EBV lead to long-term changes in squamous cells, eventually causing cancer to develop.

How is this diagnosis made?

The diagnosis of NKSCC is made after examining a tissue sample under a microscope, usually obtained through a biopsy. A biopsy is a procedure where a doctor removes a small piece of tissue from the suspicious area. A pathologist, a doctor specialized in diagnosing disease by examining cells and tissues, carefully analyzes the biopsy sample to look for characteristic features of NKSCC, such as the appearance and arrangement of cells, and the absence of keratinization.

What additional tests may be performed to confirm the diagnosis?

In addition to examining cells under the microscope, pathologists often perform specialized tests to confirm the diagnosis of NKSCC. These tests typically include:

  • Immunohistochemistry (IHC): IHC is a test used to identify proteins unique to squamous cells or related to specific viral infections, such as HPV or EBV. For example, the protein p16 is frequently detected in HPV-related tumors.

  • In situ hybridization (ISH): ISH is a test that specifically looks for viral genetic material, such as EBV or HPV DNA/RNA, within tumor cells.

  • Polymerase chain reaction (PCR): PCR is a test that detects the genetic presence of viruses such as HPV or EBV, providing further confirmation and important details for treatment decisions.

These additional tests not only confirm the diagnosis but also help guide treatment by identifying the exact cause of the cancer.

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