Of Ducks and Tumours

Daniel Nava Rodrigues, Clinical Research Fellow in the Experimental Cancer Medicine Team.

Some of you might have heard this piece of medical humour. It goes something like this:

An internist, a surgeon and a pathologist decided to go duck hunting together. Pretty soon a bird appeared on the horizon.

The internist watched it carefully as it came over and said, "Gentlemen, observe the colourful plumage, the quacking call and the web feet trailing behind."

As the bird disappeared out of range he said, "Based on my observation, I would venture that we have seen a duck, but further tests may be necessary before we decide on a course of action."

The other doctors looked blankly at him, but there was a slight sneer from the surgeon. It wasn't long until another bird appeared. They waited until it came closer and then the surgeon leaped to his feet with his gun. BLAM!

Feathers and pieces of feet, blood, guts and bill exploded overhead and a sorry-looking carcass fell. The surgeon turned to the pathologist and said, "Hey boy, would you mind running over, getting that bird and telling me if it was a duck?"

I guess it’s a good thing the joke ends there because a true pathologist would never use a term as prosaic as “duck” and would rather call the poor bird a mallard, mandarin or a red-breasted merganser. As a pathologist however, I do think there is another possible punch-line… Let’s get to that later.

Pathology is at the centre of cancer diagnosis. With all the advances of modern imaging modalities, one could count on the fingers of one hand the clinical contexts where a surgeon would be willing to operate or oncologist start radio- or chemotherapy without a pathologist looking at a tumour in the eye and reporting as cancer. When tough decisions that could lead to mutilation or death are to be made, when push comes to shove, doctors have St. Thomas’s attitude: seeing is believing.

There are good reasons why pathologists are trusted to make these crucial decisions and the main one is that it works. Careful examination of cells and tissues has been informing clinical decisions for over a century now and, in at least one instance, old school morphological analysis has helped change the natural history of cancer. In 1928, Georgios Papanikolaous introduced a simple technique, the Pap smear, which allowed for the screening of cervical cancer (a type of uterine cancer now known to be strongly associated with infection by certain types of human papillomavirus). It basically consisted of collecting cells shed from the vaginal and cervical mucosa, placing them on a slide, staining them with different dyes and then analysing them under a microscope. Cancer cells, or cells on their way to becoming cancer, look different from their healthy counterparts. By detecting these abnormal cells, or atypical cells in pathology jargon, early in the course of the disease, tumours were discovered at earlier stages and were easier to treat. The massive screening program using the Pap smear in the UK, launched in 1988, has lead to a 70% drop in mortality rates since 1979! Quite impressive I would say…

When perused under a microscope, malignant and pre-malignant tissues show a number of features. Tumours aren’t arranged in an orderly fashion like benign tissues and the cells making them up have weird appearances being too big, too small, or too odd-shaped (among other disturbing patterns). There is something visibly wrong about these cells and at times one can spot one of the most peculiar traits of cancer cells: their propensity to divide at unusually high rates. Cell division is essential for the development and survival of multicellular organisms such as ours. It allows us to grow, heal wounds and renew tissue. This tightly regulated process happens under specific conditions determined by the interaction between cells, between cells and their surroundings and between cells and the organism as a whole through signalling hormones and other circulating substances. When cancer ensues, however, regulation goes out the window.

Cancer is not one disease and this term encompasses diverse conditions with clinical behaviours ranging from indolent to swiftly lethal. Despite the differences, these ailments share one common denominator: all result from dysfunctional DNA. This star of biomolecules, so popular that most are aware of its applications in forensic science and in parenthood determination, contains the recipe for building all life on earth, from bacteria to blue whales to human cells. What’s the connection between DNA and cancer after all? Well, among the many terabytes of information contained in it, including some less relevant to life like eye colour, are detailed instructions on cellular behaviour including when to divide and when to stay put. Genes, which can be loosely defined as a functional stretch of DNA, are the words in the recipe.

There has never been a more exciting time to be a pathologist involved with cancer research. Integrating morphology and genetics is challenging and incredibly exciting. There’s so much to be learnt! The fast pace of technology makes DNA deciphering quicker and cheaper by the hour, and laboratory techniques and microscopy have advanced to the point that pathologists can actually look at segments of DNA inside the cell! Still, some people get carried away: in 2001 a commentary in Nature Medicinecompared conventional tumour histopathology to the rituals of primitive tribesmen who, when faced with critical decision making, would examine bags of animal bone or study mammalian entrails. I find this notion laughable. Morphology will always be important. The last thing medicine needs is a pathologist who would come out of that duck hunt and issue the following report: “Specimen is a bird presenting with flattened beak and webbed feet, consistent with the diagnosis of 'duck'. However, differentials include goose and swan. Awaiting genetic test results for definite diagnosis.”

Image: Henry Thomas Alken (1825), "Duck Shooting", from the Google Art Project / Wikimedia Commons