Q&A with Christine Ko, MD

The Dermatologist spoke with Christine Ko, MD, professor of dermatology and pathology at Yale School of Medicine, about her research on the pathology of squamous cell carcinoma and pseudocancers.

Dr Ko

Christine Ko, MD, is a professor of dermatology and pathology at Yale School of Medicine in New Haven, CT, where she primarily works in the division of dermatopathology. Dr Ko received her Bachelor of Arts at Princeton University and medical degree at New York University School of Medicine. She completed an internship and a postdoctoral fellowship at the University of California, Los Angeles, and completed her residency in dermatology at the University of California, Irvine. 

Outside of the clinic, where she treats patients with skin cancer as well as a variety of dermatologic conditions, such as psoriasis and autoimmune diseases, she studies the pathology and diagnoses of squamous cell carcinoma (SCC) and keratocanthomas. She spoke with The Dermatologist about her latest research on SCC and keratocanthomas, as well as the difficulties of treating SCCs on the lower leg.

Q. Could you briefly describe your current research projects? 

A. My current projects focus on clinical-pathologic correlation, visual recognition, and SCC vs mimics. Specifically, I am interested in optimizing diagnoses, through documenting histopathologic findings for a particular clinical presentation/disease, in understanding how we make diagnoses and avoid diagnostic error, and in discriminating cancer from pseudocancer. 

Q. What are some gaps in the research of nonmelanoma skin cancer that you think should be addressed?

A. Currently, it is better known that there is subjectivity in the diagnosis of atypia/dysplasia in melanocytic lesions. However, it is less well-known that there is subjectivity in the diagnosis of squamous epithelial cancer. For example, how do we best tell the difference between a thick actinic keratosis and a SCC in situ? How best to differentiate a reactive proliferation (eg, hypertrophic lichen planus) from SCC?

Q. What are the next steps to address the gaps in differentiating SCC from other conditions? 

A. We need better tools to be able to know what truly constitutes cancer in keratinocytes. We know that growth of the skin (hyperplasia) can be reactive and mimic well-differentiated SCC. Oftentimes, there are microscopic clues that point in the direction of reactive pseudocancers. However, sometimes it is very difficult to distinguish a mimicker from a SCC. In the case of some keratoacanthomas in the growth stage, only spontaneous regression definitively tells you that the lesion was a keratoacanthoma rather than SCC. It would be great to have a biomarker that predicts behavior early on, before waiting for regression, or, in the case of cancer, metastasis. 

Q. What are some of the challenges for diagnosing and treating SCC?

A. I believe that squamous lesions on sun-damaged skin of the leg are overdiagnosed, leading to overtreatment and morbidity. I would like to see more of these lesions treated less aggressively, particularly if we can continue to refine the differences between squamous lesions on the leg and SCC at other body sites. 

Q. Could you elaborate how SCCs on the legs differ from other parts of the body? Does the location of SCC affect treatment options for patients?

A. The legs seem to be a particular site that is prone to “growing” nodular lesions that can have histopathologic similarity to well-differentiated SCC. We have studied these lesions, and some of them do seem more akin to keratoacanthoma, a tumor that was originally described as a benign lesion that mimics SCC but spontaneously regresses. Nodular lesions on the legs do not necessarily seem to regress on their own, so I am not sure they are truly keratoacanthoma. 

However, the leg has thin skin that is difficult to close up into a neat line after an excision and does not heal well. Excision can lead to large ulcers, infections, poor wound healing, and unsightly scars. Our dermatologic surgeons are familiar with these lesions on the legs and often treat more conservatively, with good response. Conservative treatments include intralesional medications, such as intralesional methotrexate, triamcinolone acetonide (Kenalog), oral acitretin (Soriatane), or shave removal with cautery of the base.

Q. Is this an area that you are addressing in your work? 

A. Yes, we are continuing to study these lesions and other types of SCC with the “pie-in-the-sky” goal of finding a biomarker to definitely distinguish more aggressive SCC from indolent mimickers.