Basic cancer biology

To begin to understand Cancer of Unknown Primary (CUP) one needs to understand first that:

  • The human body is composed of billions of cells. These cells are genetically programmed to do various things throughout our lifetime. We need new cells to replace worn out cells that die in a regular cycle.

Cancer with an unknown starting point is referred to in many different ways but, increasingly, as Cancer of Unknown Primary (CUP). Other terms include: Carcinoma of Unknown Primary, Metastatic Malignancy of Unknown Origin, Tumour of Unknown Origin, Occult Primary Malignancy. (Occult meaning hidden from the Latin Occultus.)

  • If (the DNA in) a cell becomes faulty it can start growing uncontrollably and form a tumour (literally 'swelling' but in the Cancer context the word is used to denote abnormal growth of tissue).
  • If the tumour is abnormal it is known as "malignant"; if it is not cancerous it is known as "benign". (The word 'lesion' is sometimes used. Lesions are caused by any process that damages tissues. A cancerous tumour is an example of a lesion.)
  • A benign tumour does not spread within the body but an untreated, malignant tumour is likely to metastasise or spread (see cancer spread).
  • Early diagnosis is important. However, a tumour may not be apparent and the symptoms may not be recognised by the patient or doctor.

CUP - a summary definition

CUP - where the origin of the cancer cannot be determined in assessment before treatment and sometimes remains hidden - probably accounts for about 5% of cancer diagnoses; but this figure depends on how CUP is defined. Most CUP definitions are of metastatic carcinoma of unknown primary where the primary is not detectable.

  • Clinical presentations are usually non specific  and often involve metastasis in more than one organ.
  • Usually, the most important step in diagnosis is the biopsy because this allows a general cancer categorisation of carcinoma, sarcoma, lymphoma or melanoma. Our focus is on carcinoma where further definitions are needed to achieve effective treatment.
  • Some further classifications are usually possible from the biopsy sample which will help determine likely treatment. But in the case of CUP, the cells have lost their unique features in the cancer spread. This makes identifying the original cancer cells (the target of chemotherapy) difficult.
  • Because carcinoma of unknown primary may originate in any epithelial cells in the body, and CUP biology is not understood (other than that the primary stays small or disappears yet spreads - metastasises - unpredictably) it is a challenging diagnosis for the cancer doctor as well as the patient.
  • There are few standard treatments, because the cancer is likely to be different for every patient, with widely different outcomes.
  • Improving genetic, pathological and radiological techniques will reduce the incidence of CUP in the future.

Message board

NICE are developing the first Clinical Guideline for the treatment and management of CUP covering the NHS in England, Wales and Northern Ireland. This will be operational in the Summer of 2010.

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