This case is part of our ongoing Genetic Testing Challenges in Oncology series, which examines how gaps in genetic testing and communication can delay accurate diagnoses. In this case, a shaky variant classification led to eight years of unnecessary cancer surveillance before a genetic counselor finally uncovered the truth.
A Diagnosis Built on Thin Evidence
A gastrointestinal physician referred a 25-year-old woman for genetic counseling because her medical records showed a history of Peutz-Jeghers syndrome (PJS), a rare inherited disorder that significantly raises the risk of colorectal, pancreatic, gastric, and breast cancers.
Years earlier, a lab that advertised comprehensive medical genetics services had diagnosed the patient with PJS at age 17. Specifically, the lab’s medical director based that diagnosis on her lip hyperpigmentation and three apparent “PJS-type” polyps noted on a colonoscopy report. The lab then tested her for STK11 variants and classified the variant it detected as a variant of uncertain significance “likely to be pathogenic.” However, the genetic counselor later found that this classification rested on thin evidence. As a result, eight years of unnecessary, invasive, and costly surveillance followed.
A Second Look Unravels the Misdiagnosis
When the referring genetic counselor reviewed the case, she found that the patient’s colonoscopy report actually described benign, non-PJS-type polyps. In addition, the patient had no family history of PJS, and a second reputable lab had already classified the same STK11 variant as benign.
Indeed, a search of ClinVar turned up 11 entries from various labs, the earliest dating back to 2015, all categorizing the variant as benign or likely benign. Ultimately, the genetic counselor reversed the misdiagnosis, and as a result, the patient was relieved to no longer face a lifetime of invasive cancer screenings she never needed.
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