When you meet an oncologist, their attention is necessarily divided. It might seem rude to multi-task in the middle of an introduction, impertinent as flirting with twins. Forgive the affront but we have precious little time to learn about our dual, dueling interests: you and your Significant Other.

We come to know about you -- the inadvertent host -- through probing both verbal and physical. We study your visitor through a different kind of poking and prodding; we measure its dimensions on scans, we scour your bloodstream for signs of its presence, but most of all we scrutinize the rogue tissue itself under the microscope. In the case of a biopsy, one of our technically adept counterparts, a surgeon or an interventional radiologist, guides a needle of variable gauge into the mass for sampling, and then that sliver is sent to the pathology lab. This task demands exactitude and care because all the decisions which follow pivot upon it, as if planning a five-course meal around a single garnish.

Call us prickly but seldom do we make a diagnosis without needing to stick a needle into you first. There is an almost-nauseatingly whimsical rhyme that “if tumor is the rumor, then tissue is the issue.” I abhor the sing-song quality of that couplet but cannot deny its inherent truth: that we need to look at your cancer under high magnification before we can zoom out to see the big picture. The oncologist without the pathologist is blind, but with their guidance we can see the problem, and, hopefully, its solution.

Myths abound about a biopsy angering the cancer, as if we should be fearful of disturbing a hornet’s nest with a very pointy stick. And it is true that some caution has to be taken not to create a track that a deep cancer can follow to the surface, like a rodent burrowing upward. But overwrought concerns about exposing the cancer to the air are a vestige of the days when exploratory surgery was needed to determine the full extent of illness. In the pre-CT era, the distribution of a cancer was often unknown until the laparotomy, when the surgeon saw with their own eyes that the inner surfaces of the abdomen -- the peritoneal lining and the fatty apron of the omentum -- were studded with innumerable tumor implants. It was like turning on the lights to reveal vermin that had been scurrying and multiplying in the darkness to the point of overwhelming infestation. Having found such an irrevocable distribution of disease beyond their scalpel’s reach, they retreated, closed the patient’s wound, and told their family that the “cancer had spread.” These revelations -- grim tidings borne by masked men after disappointingly abbreviated operations -- led to the false equivalency that it was the exposure to the outside that enabled dissemination, as oxygen fuels a fire.

Few, if any patients ever meet the doctor who actually makes their diagnosis. For the most part pathologists do their essential work hunched over microscopes in laboratories where patients only enter piecemeal. Samples of their flesh are labelled with accession codes even more impersonal than the medical record number, meat twice anonymized from its source. This is truly reductive, dispassionate science, the patient’s problem distilled onto a slide and examined under precision optics. But it’s not losing the forest for the trees; rather, it’s diagnosing Dutch Elm disease from fragments of bark, all without ever stepping foot in the woods.

The tissue under investigation is sliced to a thinness that would inspire envy in the most skillful artisan of the delicatessen. But before the microtome descends to produce these ultra-wafer sections, the specimen is fixed in place, cells embedded in paraffin. In the case of cancer, they look like angry mosquitoes trapped in amber, a swarm still buzzing with lethal potency even with wings frozen mid-flight. The charcuterie par excellence is then ready for inspection by a physician who has devoted their entire career to minutiae, the cytopathologist.

We didn’t always know we were made of stars. Cosmologists had to deduce that we coalesced from the scattered debris of the Big Bang, that particles became nuclei to be fused and spewed from the furnaces of supernovae. The raw materials of our human existence could only be forged in the hottest of foundries.

We didn’t always know we were made of cells either. The fantasy of the Platonic whole blinded us to the partitioned nature of our teeming constituency: no man is an island, instead he is a vast unchartered archipelago. It wasn’t until the 17th century when Antoine van Leeuwenhoek, a Dutch cloth merchant interested in examining the quality of his fabrics, invented a whole new level of magnification that saw far more than threadcount. Through his novel lens, like Gulliver peering down upon the Lilliputians, he glimpsed a world erupting with life on a tiny scale. Our component parts were illuminated: the striated bands of muscles, the wriggling spermatozoa and the ova for which they quested.

Across the English channel, Robert Hooke was soon looming over his own scope, authoring Micrographia as the record of his “disciplined seeing.” Through the looking glass he surveyed the myriad inner chambers of a cork before finding analogous ‘little rooms’ within honeycomb, wool, sponge, and pumice stone. If Leeuwenhoek gave us the surveying equipment, it was Hooke who described the architecture; it was he who allowed us to uncover the wondrous designs of the human interior, from the palisades of the cornea to the aqueducts of the circulation. The blueprint for Amsterdam can be found in the inner ear’s semicircular canals.

Over time, the patterns became familiar enough to be catalogued, and scientists came to distinguish the body’s normal patterns from the avant garde creations of cancer as readily as art critics can segregate impressionism from cubism. You have to know the rules to appreciate them being broken, although cancer is more Pollock’s random splatter than Picasso’s analytic mosaic.

Cells usually don’t go bad overnight, but rather transgress by degrees. Like most serial killers, there are typically clues of disturbance before the spree. Hyperplasia becomes dysplasia becomes neoplasia. To use the analogy of Hooke’s rooms, first they multiply in number, then they change shape to a ‘bad formation,’ then the walls begin to topple and they encroach on neighboring properties. From the epicenter of disruption, a seismic tremor razes the landscape, allowing Candide to escape through an earthquake.

High above the mitotic catastrophe the pathologist surveys the damage. Adjacent to the beauty of a well-organized organ a malignancy looks ugly as sin, piquing a near-prurient interest. After scanning sheet upon sheet of homogeneous order, there is a certain rubber-necking attraction to aberrancy. As Charles Darwin before him, the pathologist experiences the sober joy of a man who extracts order from chaos, applying his own taxonomy to the pandemonium. Their written reports try to capture the essence of wild growth like a zoologist’s field notes on a savage beast, but there’s no domestication through description, no more than a leopard is tamed by the counting of its spots. The departure from normalcy is graded, with the most bizarre mutants so poorly differentiated as to barely resemble their harmless ancestors, like a king cobra sprung from a garden snake. Mention of abundant nucleoli conjures the image of a many-eyed monster staring out from the slide, unblinking and unnerving. Mitotic figures are enumerated to determine the tempo at which a strand of tumor DNA is unraveling from one double helix to partner again; at its most rapidly proliferative the do-si-do of replication quickens to a whirling dervish, a frantic danse macabre.

Sometimes the sight of cancer through the microscope is so breathtaking that the pathologist cannot wait for the written report to be issued. Every oncologist dreads that urgent call from their colleague in the lab announcing a new and noteworthy adversary, like the primitive grains of oats sewn by a three-pack-a-day smoker and now reaped in their lungs as small cell carcinoma. Thankfully such hot gossip is rare, and the cancer diagnosis usually arrives in cold text, stripped of feeling through transcription: invasive carcinoma.

My own dominant mass looks yawningly slow under the scope, yet is not to be underestimated. Historically, it has been. More than a century ago in Munich, a brilliant pathologist named Siegfried Oberndorfer stared down his lens at an unusual type of tumor found in the small intestine of several patients at autopsy. The growth pattern looked different under the microscope than that of a typical cancer, and at the time Dr. Oberndorfer thought the tumors were benign in their behavior, so he accordingly named them “carcinoma-like”, or karzinoide.

Over 20 years later, Dr. Oberndorfer realized that the tumors were not always benign and could invade & spread like other malignancies, but by then the Anglicized term carcinoid was well established. This has proven to be a deeply unfortunate misnomer for thousands of patients who have been told, erroneously, that this disease is "nothing to worry about." In fact, it can cause death through both liver & heart failure, not to mention a highly unpleasant symptom complex called carcinoid syndrome which involves intractable cholera-like diarrhea, wheezing, and flushing episodes that some of my female patients have vividly described as "menopausal hot flashes on steroids." Like their pancreatic brethren, neuroendocrine tumors of the gut lumen can impair quality of life while shortening its duration. They are to be ignored at the patients' peril.


While I am not a pathologist myself, I sometimes think of their work like archaeology, not the swashbuckling portrayed by Indiana Jones but rather the quiet, seldom-acknowledged dedication of an academic unearthing the truth. The fields share a painstaking attention to detail that plays out unshowily with the tiniest of tools and the utmost respect for the specimen under study.

Next week, my biggest & most troublesome neoplasm will be excavated in dramatic fashion by an expert surgeon but it is the careful, largely unsung work of the pathologists -- honing their knowledge of neuroendocrine tumors since Oberndorfer's seminal 1907 discovery -- that has paved my way to the OR.

Mark Lewis1 Comment