"Rare" cancers experts

Is it an oxymoron to have an expert in rare cancers? In oncology, cancers that arise in unusual sites or of unusual origins do occur. Sometimes, they have been described as "rare as hen's teeth". If these cancers occur infrequently, then it would be very hard for a person to have seen enough to be an expert in such a cancer.

There are 2 situations where the cancer might be rare. The first is where the cell of origin of the cancer is rare. An example that comes to mind would be the different types of non-Hodgkin's lymphoma (NHL) described in the World Health Organization (refer to table) classification. With better scientific analytical techniques, such as antibodies (immunohistochemistry), genetic analysis, we now have many different types of NHL. The commonest histologic type is diffuse large B-cell lymphoma, accounting for approximately 25 percent of NHL cases. However, some non-Hodgkin's lymphomas would be considered rare. These are sometimes not suspected or the laboratory had not used the specific tests to differentiate them.

Another category of rarer cancers arise from the connective soft tissues of the body. Connective tissues includes various cell types, such as fat cells, cells lining joints, muscle cells, fibrous tissues, nerves and blood vessels that can turn cancerous. These types of malignancies are termed sarcomas and may include liposarcoma, synovial sarcoma, leiomyosarcoma, rhabdomyosarcoma, fibrosarcoma, primitive neuroectodermal tumor and angiosarcoma etc. Sarcomas are not common and are not in the top 10 cancers in Singapore. Some sarcomas are more sensitive to chemotherapy than others and it would be helpful to differentiate them. Specific targeted therapy is now available for a particular type called gastrointestinal stromal cell tumour (GIST) which provides excellent response just by taking oral medication.

Unusual presentation of some cancers

The second situation arises when we cannot tell where the cancer had arisen from. As a group, a cancer where the primary is not obvious happens about 4 to 5% of the time. These cancers may not be really rare; they just show up in unusual sites of the body where we do not expect them to be. For example, prostate cancer frequently spreads to the bones (the most common metastatic site) but in rare situations the cancer can spread to the liver. This sometimes causes a diagnostic dilemma when it is not suspected. In the end, a careful evaluation and a biopsy may be needed as the treatment may be very different. A blood test called prostatic specific antigen (PSA) and testing for this on biopsy specimen can diagnose the problem if suspected. I had a patient with multiple small nodules in the lung suggestive of cancer or tuberculosis. A CT scan and blood tests were not able to reveal where the primary cancer was. Having seen several specialists and undergoing procedures like bronchoscopy and tests for tuberculosis, she was not able to confirm that this is cancer. This poses several problems - namely, the treatment to administer, the prognosis (even if it is cancer) and the medical insurance might not reimburse without a clear diagnosis! In the end, the patient had a video-assisted thorascopic surgical biopsy done. With immunohistochemical techniques, the pathologists were able to identify that this is primary lung cancer and she is assessed for a clinical trial. Therefore, in some situations, direct methods to examine the tumour tissue, which may sometimes involve invasive procedures, may provide a rapid and clearer answer than multiple indirect approaches.

The general principle to follow in management then is to get adequate tissue of the tumour for evaluation. Traditionally, pathologists look at the architecture of the tumours under the microscope. Cancer cells under the microscope look like just cancer cells and will not declare their origins although experienced pathologists are often able to give us a diagnosis or hint of origin. This would also depend on the quantity and quality of the tumour tissue available. Immunohistochemistry using antibodies to “tag” receptors on the cells improves the discrimination of the cancers. New generation technologies exploring the genes expressed by the tumours, analysing the chromosomes and DNA, electron microscopy and so on have also added to the armamentarium for diagnosis.

Treatment is individually decided. For rare tumours, there is usually little medical literature to guide therapy. Experience in treating cancers and approaching such a situation is invaluable in management. Various combinations of surgery, radiotherapy, chemotherapy, hormonal therapy or targeted therapy may sometimes be employed.

If we approach unusual cancers systematically with some of these principles, we will be able to then achieve the best oncological care for patients!

Rare cancer case

Case example
This patient had an unusual adenoid cystic carcinoma of the eye which had spread to the bones. He had a good response to chemotherapy with resolution of cancer activity in the bone on PET/CT scan.

"Rare" cancers experts

Unusual presentation of some cancers

WHO classification of the non-Hodgkin's lymphomas (subclassified according to clinical aggressiveness)