Role of pathologists in governing the management of malignancies

 Role of pathologists in governing the management of malignancies 

Older than civilization itself, cancer has debilitated individuals and crippled lives. With advancements in science, society and the economy, our response to malignancies has evolved. The role of the pathologist - in a medical team, with representation from diverse specialisations, in the deliverance of this response - is not only prime but blossoming.

 

Whereas radiographic and clinical tests can only suppose the presence of a malignancy, the pathologists’ array of tests can not only confirm but characterise it. This is important, as characterisation using histopathological techniques is essential for deciding the modality of therapy. For instance, small cell and non-small cell lung cancers, have drastically different treatment regimens.

 

Further, with genetic bases being assigned to neoplasia, the role of the pathologist extends beyond the cellular level. The presence or absence of key cellular molecules can be ascertained using immunohistochemistry. For instance, the excessive presence of Estrogenic Receptors in the nucleus of malignant breast cells would warrant therapy with anti-estrogenic drugs such as tamoxifen. Yet another way the pathologist can check for drug targets is through flow cytometry analysis in the case of lymphoreticular malignancy. The detection of CD markers can fuel the addition of a monoclonal antibody directed against those markers in the therapeutic regimen.

In the case of certain haematological malignancies, the pathologist’s ideation is paramount. Take, for instance, promyelocytic leukaemia, which is diagnosed using the detection of a fusion gene – ‘PML-RARA’; and can be treated, to an excellent degree, using tretinoin. Similarly, the detection of ‘BCR-ABL’, another fusion gene, in cases of chronic myeloid leukaemia, allows for therapy using drugs such as Imatinib which target the fusion product. 

 

The role of the pathologist doesn’t end here. They must, at periodic intervals, check for any alteration in the ‘omic’ environment of a tumour, which would confer upon it, resistance to drugs. The advent of liquid biopsies, methods to check for cell-free DNA and subject it to PCR analysis, obviates the need for excessive biopsies and makes checking for drug resistance practical. The detection of residual disease post chemotherapy using the quantification of genes using PCR is still another responsibility of the pathologist.

 

Frontiers in the field of molecular genetics have revolutionised the way cancer biology and therapy are understood. Next-Generation Sequencing, for instance, can detect ‘profiles’ of genetic damage and identify otherwise undetectable lesions. For instance, any cancer with involvement of the DNA mismatch repair apparatus, regardless of microscopic appearance, can be treated with immune checkpoint inhibitors. Monitoring of the neoantigen burden can further guide therapy. Analysis of neoplastic RNA and epigenomes can help us more intimately track tumour biology and possibly even design ‘personalised’ therapeutic regimens. 

 

With the rapid integration of healthcare and technology, it is evident that pathology will no longer be a laboratory science. Ultimately, a malignancy is an alteration in the biology of cells and can best be treated by those who study cells – pathologists.