CAP TODAY Pathology/Laboratory Medicine/Laboratory Management
Julia Keefe, MB(ASCP)CM
Abigail Finer, MS, LCGC
Andrea Pannone
Jochen K. Lennerz, MD, PhD
September 2023—What happens when an oncologist cannot confidently determine what type of genetic test to order for their patient? Where can a provider turn if they do not know whether a genetic variant is clinically actionable? As genetic testing becomes a more integral part of personalized medicine and health care in general, there is a growing need to bridge the gap between those skilled in molecular diagnostics and those on the patient-facing side of care. In response to this need, the Center for Integrated Diagnostics (CID), a high-complexity molecular diagnostics laboratory at Massachusetts General Hospital, created its Consultation Service.
The CID Consultation Service was launched in late 2021 with the goal of streamlining a series of recurrent practice-related questions about high-complexity molecular diagnostic cases.
Since its launch, the service has received more than 500 requests, which can be attributed to its accessible platform. Providers can submit a consultation request by using the service’s electronic health record form, which links each request to the patient’s medical chart. In addition to using the EHR form, providers and their patients can contact the Consultation Service via email or phone.
The Consultation Service is a multidisciplinary team consisting of board-certified molecular genetic pathologists, a medical technologist, and a certified genetic counselor. A surgical pathologist, radiologist, and/or oncologist may supplement the team depending on the question. Each member of the service team brings a unique perspective to every case. Attending pathologists specialize in a variety of domains, and each week one attending is on service and provides their unique expertise to the team. The high-complexity medical technologist has a deep understanding of the technical aspects of molecular testing and interacts with attending pathologists to help interpret test results. As the CID’s genetic counselor, one of the authors (A.F.) synthesizes the patient’s medical and family history along with insights from attending pathologists, medical technologists, clinical databases, and relevant literature to produce a comprehensive case report.
The genetic counselor’s role within the service differs from that of many of her peers who see patients in clinic. Classically, clinical genetic counselors often provide services within the scope of hereditary disease. The genetic counselor on the CID Consultation Service focuses on somatic genetic testing in the field of oncology. While also working closely with physicians to provide personalized patient care, the genetic counselor works directly within the laboratory as opposed to a clinic. Essentially, she serves as a liaison between the molecular genetics professionals within the laboratory and the physicians on the clinical side of care.
Although the genetic counselor works within the laboratory, her responsibilities differ from those of a traditional commercial laboratory genetic counselor. While genetic counselors in laboratories typically use highly specific skills such as variant interpretation, the Consultation Service counselor plays a variety of roles as she works through the most complex cases the laboratory receives. In addition to her variant interpretation services, she performs in-depth reviews of each patient’s medical history to provide comprehensive recommendations on clinical actionability and future testing. In this setting, a genetic counselor ensures that patients receive high-quality test result interpretations and relevant clinical recommendations.
Common inquiries and a consult case. From next-generation sequencing assays to PCR-based small molecular testing to FISH, the Center for Integrated Diagnostics, with its Consultation Service, is a one-stop shop for genetic testing related to personalized medicine and cancer care. However, the comprehensive test menu (49 in-house tests currently and numerous send-out tests) generates an extensive list of questions from a variety of providers.
To date, almost one-third of the questions submitted to the Consultation Service are about whether a variant with a high variant allele frequency (VAF) is germline or somatic in origin. When a variant has a high VAF, providers often wonder if further germline testing is warranted. The answer to this question depends on many factors such as the variant classification (variant of unknown significance, pathogenic variant, likely benign, etc.) and the patient’s health and family history.
Some providers are interested in the clinical management implications of genetic test results.
In fact, one in five inquiries is related to the clinical actionability of a genetic variant. For instance, if a molecular test reveals that a patient’s tumor harbors a specific variant, providers can contact the Consultation Service to learn about personalized treatment options or connect with trial staff or both.
The most frequent and captivating consultation cases are inquiries about the relatedness of tumors and the primary site that might be unknown; these discussions often happen in tumor boards. Solving these questions ad hoc can be particularly challenging. To illuminate this aspect of the Consultation Service, we share a complex tumor origin case.
In 2022, a female patient with a history of neuroendocrine carcinoma was diagnosed with endometrioid carcinoma of the ovary. Upon this diagnosis, the patient’s oncologist contacted the Consultation Service to determine the origin of the endometrioid carcinoma. The oncologist asked whether the two carcinomas had similar molecular features and came from the same neoplastic process or if they had evolved separately. Molecular testing identified an ESR1::AKAP12 fusion in the endometrioid ovarian carcinoma that was not present in the neuroendocrine carcinoma; however, both tumors shared six other genetic variants. Additional testing revealed that aside from the six variants the tumors shared, the endometrial cancer contained two unique variants while the neuroendocrine carcinoma contained one unique variant.
Since the molecular profiles of each tumor were not identical, the Consultation Service opted to perform additional genetic testing on normal tissue to gauge whether the shared variants were germline or somatic. The test on the normal tissue detected five of the six variants present in both tumors. The results from normal tissue testing suggested that the five shared variants were germline and thereby specific to the patient (rather than a shared phenomenon of the tumors). After comparing the variants across the tumors and the normal tissue, the team found that one pathogenic TP53 variant was present in both tumor types but not the normal tissue.
Ultimately, with this new data comparing both cancers to the normal tissue, the team concluded that the two tumors were distantly related and that a clonal divergence event occurred early in the cancer’s development.
The genetic counselor was responsible for the initial draft of a comprehensive report on the case that summarized each detail from the patient’s medical history and the test result interpretations for each variant found in each tissue. Since the overarching goal of the Consultation Service is to improve the quality of patient care through personalized medicine, the report included recommendations on clinical actionability. The service advised the patient’s oncologist to consider CDK4/6 inhibitors as they can effectively target ESR1 gene fusions, which were present in the endometrioid ovarian carcinoma.
Financial impact. In addition to guiding testing and treatment decisions, the Consultation Service works with hospital billing staff to mitigate medical costs for the laboratory and patients. To date the service has received and processed numerous billing-related questions and helped draft more than 20 appeal letters to payers.
Incorrect test orders waste the laboratory’s resources, and insurance denials cause stress for patients. Thus, the Consultation Service helped develop a triaging workflow that ensures that each patient receives the most appropriate tests, coupled with prior authorization, management of billing questions, or both. To further educate providers on the appropriate context for each test, the team also created a test order tip sheet, which provides suggested order sets for a variety of cancer types and syndromes.
Before the service was created, attending pathologists provided their expertise to other providers informally—via email, for example. The attending pathologists often spent a substantial amount of time helping them with complex cases, but their input was not necessarily documented in the medical record nor were they compensated for their work. According to the consultation reports, a pathologist’s time spent on consultation case reviews can range from five minutes to three hours depending on the complexity of the case. Pathologists in the Center for Integrated Diagnostics can now use the 2022 pathology clinical consultation CPT codes to track and bill for the time they spend on each case. The most common CPT code used for CID consult billing is code 80505, which represents 41 to 60 minutes of comprehensive medical record review and high-level medical decision-making.
Patient perspective. The Consultation Service saves time and money and reduces stress for patients, providers, and attending pathologists. It also brings a patient-centered perspective to laboratory work that high-complexity technologists may not otherwise experience. The team is now in the initial stages of developing a patient-facing clinic at MGH, which will focus on somatic cancer testing and molecular diagnostics within the scope of personalized care. This will provide an additional layer of patient service that entails direct patient interaction.
As genetic testing and genetic counseling become more common in all areas of health care, we expect to see growth of multidisciplinary teams that synthesize information from high-complexity tests. Other clinical molecular diagnostics laboratories could use a platform similar to the Consultation Service as a blueprint for developing their own service. The successful implementation and expansion of the Consultation Service demonstrates the benefits of increasing collaboration between genetics and nongenetics providers within the scope of high-complexity testing. The breadth and success of our service underscore the value of integrating genetic counseling into the laboratory space.
Julia Keefe is a medical laboratory technologist, Abigail Finer is a genetic counselor, Andrea Pannone is a medical laboratory technologist, and Dr. Lennerz is medical director—all in the Center for Integrated Diagnostics, Department of Pathology, Massachusetts General Hospital.