Challenges in Diagnostic Cytomorphology

Gathering more information from smaller samples

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When it comes to the initial observation and diagnosis of potentially fatal diseases such as cancer, the biopsy has traditionally been the go-to approach for taking the first samples. The problem with this, of course, is that biopsies and other architectural diagnostic examinations that involve removing tissue tend to be more invasive regardless of whether or not there's a known problem. The concept of cytomorphology takes the information usually obtained through excision-based procedures and produces it using significantly smaller sample sizes - even down to a group of cells.

In a recent interview with ADVANCE, Kristen A. Atkins, MD, director of residency training and associate professor of pathology at the University of Virginia School of Medicine, discussed the benefits and obstacles surrounding cytomorphology and the impact the practice stands to make on the healthcare industry. Not only is it less invasive for the patient, but the results are available more quickly after a sample is taken, allowing the physician to determine a diagnosis and treat accordingly without having to wait for results. For the medical professionals administering the test, the process is fairly simple and can be applied to several areas of the body.

"I think that many of my colleagues and I were attracted to cytology because we can stay very diverse in our interests," said Atkins. "We apply diagnostic rules to different body sites, but it's still the same thought process that we are going through."

Rather than having to remove an entire pieces of tissue for analysis, cytomorphology involves the use of a needle, which Atkins described as being smaller than one used to draw blood, to collect cell samples. By collecting small samples of cells as opposed to excising whole portions of tissue in a biopsy and utilizing new technology, equipment and techniques to examine the cells, the test helps clinicians diagnose a potential problem with relatively little sample sizes.

"With respect to cervical cancer, cytologists could find not only cancer, but pre-cancerous regions," continued Atkins. "And that's what you want to do is find the precursors, because if you can treat the precursors, then they won't become invasive cancer."

Of course, one of the most obvious limitations of cytomorphology is the possibility that not enough information will be made available given such a small sample size. According to Atkins, without an architectural sample, the test sometimes can lead a pathologist in the general direction of a diagnosis, but simply not have enough cytologic features to point to a definitive answer. Even in the event of an inconclusive sample, she also noted the importance of the test as a baseline, preliminary measure.

"Sometimes you just don't have enough cells. So, that if you need to do a lot of tests, like immunochemistry or molecular tests, you may not have enough just from this procedure. However, it's a really good way to start," explained Atkins. "So, because the procedure is so minimally invasive, if you end up needing to do a bigger biopsy, it hasn't been a huge expense nor a huge burden to the patient most the time."

The practice of cytomorphology developed and came into its own as a distinct part of pathology following its role in the diagnosis of cervical squamous cell carcinoma roughly 50 years ago. Scientists found that, by studying the cells and observing them under a microscope (the Pap smear), the cancerous cells could be found and even prevented. Beyond that, the procedure extended to areas all over the body, most notably areas that were more hard-to-reach with punch biopsy such as lung cancers, where excision can be difficult for both the physician and the patient.

"If a patient with a palpable mass is very anxious about the reason, I can do a fine needle aspiration, look at it immediately and if it's good news convey that benign diagnosis. That it is great," said Atkins. "But it's equally important when somebody's anxious and it ends up being something malignant because then they can start the plans and even start treatment. They don't have to wait two or three days for an answer."

Like many other areas of the healthcare field, molecular diagnostics have made a substantial impact in cytology. Given the ease-of-testing and speed in which results can be produced and analyzed, the combination of cytomorphology and molecular diagnostic approaches has expanded the potential for results. Now, clinicians can analyze the genetic makeup of cancer cells and tumors to determine characteristics such as how effective chemotherapy would be or how susceptible a patient might be to other cancer types.

Moving forward, the ability to rely on the individual cells gathered in altogether smaller sample sizes for increasingly precise diagnostic purposes stands to change the way we view specimen collection. Atkins commented that all diagnostic tests have their benefits and limitations. Despite being an older testing option compared to methodologies like genetic sequencing, however, cytomorphology continues to evolve and improve, adapting and growing with newer assays and technologies.

Michael Jones is on staff at ADVANCE.


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