Undiagnosed Clinic—Meeting the Needs of Patients With Incidental Findings

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Radiographic findings and/or abnormal laboratory values are often the first indication that a patient could have cancer. Approximately 25% of patients will have an incidental finding on imaging. Results from 1 study showed that investigators noted incidental findings in 23.6% of imaging studies. Additionally, only 64.5% of those patients had clinical follow-ups, resulting in 45.6% of patients with a clinical diagnosis based on the imaging findings.¹ Based on this information, Ochsner Health started an undiagnosed clinic to support incidental findings on imaging.

L.O. is a patient who presented to the undiagnosed clinic with an incidental finding on her imaging. She initially presented to the orthopedic clinic in March for a left distal radial fracture that occurred after falling while walking her dog. For this fracture, she required an open reduction and internal fixation in April. L.O. subsequently re-presented to the orthopedic clinic in early August for left shoulder pain after a “pop” in her shoulder. This injury was affecting her activities of daily living and was a 10/10 at its worst on the pain scale. She was sent for an MRI of the shoulder without contrast, which resulted in “MR imaging findings concerning for a marrow infiltrative process/hematologic malignancy with a nondisplaced pathologic fracture of the coracoid process.”

L.O. was referred to the undiagnosed clinic within the oncology department for further workup. She is an active 70-year-old woman who is up to date on her screenings, such as mammogram and colonoscopy. L.O.’s most recent mammogram was in May, only 2.5 months before she presented to the undiagnosed clinic in late August 2023. The mammogram showed right-sided mild skin retraction requiring additional imaging. A follow-up resulted in a Breast Imaging Reporting and Data System score of 3, “probably benign,” by the radiologist. L.O.’s most recent colonoscopy was 3 years prior, and the follow-up recommended a repeat colonoscopy in 5 years. Her family history is significant for colon and breast cancer in her father, as well as ovarian cancer and melanoma in a cousin. She had no known genetic testing completed. Her medical history includes atrial flutter, hyperlipidemia, basal cell carcinoma (right upper lip), colon polyps, and osteoporosis. She is a part-time interior designer who does not use tobacco but does have an occasional beer or glass of wine (she has limited these to avoid arrhythmias) and uses marijuana. Her only prescription medication was conjugated estrogens tablets (Premarin); however, she did take calcium and a multivitamin daily. She had previously used alendronate (Fosamax) but was not currently taking it.

During this visit, she was noted to have a 5-lb weight loss over the summer but explained that she was trying to lose weight. She also noted a fracture of her left wrist and right proximal phalanx fracture earlier in the year. These 2 fractures with her new coracoid process fractures totaled 3 fractures in 8 months. Her associated symptoms, which included left shoulder pain and gastrointestinal issues, specifically frequent bowel movements, gas, and abdominal discomfort, were being worked up by a gastroenterologist. Prior lab results demonstrated a new anemia within the past year, worked up by her internal medicine physician and not thought to be due to iron deficiency. She also had mild neutropenia earlier in the year that had resolved on the most recent labs (done within 1 month of her undiagnosed visit).

Labs and imaging were ordered given the marrow infiltrative process seen on the MRI, to rule out underlying multiple myeloma or other hematologic malignancies. A complete blood count showed normocytic anemia; results from a comprehensive metabolic panel and β2 microglobulin and immunoglobulins (IgG, IgA, IgM) levels were all within normal limits. Immunofixation electrophoresis showed no monoclonal peaks, and serum protein electrophoresis (SPEP) showed normal protein levels. A PET scan showed a “constellation of osseous findings suspicious for a hematologic malignancy. Hypermetabolic lytic lesion within the sternum. Diffuse heterogeneity of the osseous structures with mixed lytic and sclerotic appearance. Bilateral femurs and right tibia demonstrate regions of increased intramedullary attenuation demonstrating uptake slightly above background, and hypermetabolic lytic lesion within the sternum demonstrating maximum SUV [standardized uptake value] of 3.2.”

Given the unremarkable myeloma markers, but PET CT findings highly suggestive of hematologic malignancy, a bone biopsy of the sternal lesion was performed. The final pathology confirmed “metastatic carcinoma in fibrocartilaginous tissue. Malignant cells are positive for AE1/AE3, CK7, GATA3, ER, and PR (weak intensity) immunostains, and negative for CK20, CDX2, and TTF1 immunostains. HER2 immunostain is negative. The morphology and immunophenotype are compatible with metastatic carcinoma, favored to represent metastatic carcinoma of mammary origin.”

The suggestion that the sternal mass was breast cancer required MRI to further evaluate for breast malignancy. An MRI scan would not be routine imaging on this patient as her mammogram was benign in June and her PET scan did not show a definitive breast mass. L.O. had an MRI scan in October that showed “a 31 mm x 26 mm x 30 mm heterogeneous, nonmass enhancement (NME) in a regional distribution seen in the lower region of the right breast, 0.8 cm from the chest wall and 0.8 cm from the skin. The NME is remote from the nipple. The NME spans anterior to posterior extent. There is focal NME measuring 9 x 6 mm in the right breast upper outer quadrant, posterior depth 0.7 cm from the chest wall. There is rapid uptake and washout.”

L.O. was diagnosed with stage IV breast cancer with osseous involvement in October, approximately 1 month after her initial visit to the undiagnosed clinic. Notably, she went on a preplanned 10-day vacation during this time, which delayed some of the workup. She received first-line therapy with palbociclib (Ibrance) and anastrozole (Arimidex). These agents were chosen due to her gastrointestinal issues, which require lipase-protease-amylase (Creon). Her breast cancer workup will be completed with sequencing to evaluate for ESR1 and PIK3CA mutations. Additionally, the pathology department was queried for specifics regarding HER2 immunohistochemistry (0 vs 1+). L.O. was not given denosumab (Xgeva) at the time of diagnosis as she had a broken tooth that her dentist was to repair.

The new undiagnosed clinic that was started in March 2023 has provided care to many patients like L.O. The clinic uses an oncologist and oncology advanced practice provider (APP) to review a patient’s cases and determine a patient’s eligibility for the clinic. Once in the clinic, there is a thorough exam and workup that typically includes, but is not limited to, labs, imaging, biopsies, et cetera. The multidisciplinary team involved in the clinic begins with the radiologist noting incidental findings. The oncology team then relies on the interventional radiology department to perform biopsies and the pathologist for accurate pathology results. This clinic has helped patients like L.O. get timely answers on incidental findings and expedited their connecting with oncology care. The time from biopsy to an appointment with a breast medical oncologist was 13 days for L.O. (this includes the time it takes for biopsy results, on average 10-14 business days).

The undiagnosed clinic nurse practitioner (NP) managed L.O.’s care from referral to the undiagnosed clinic to hand-off to the breast oncologist. The NP contacted the orthopedic clinic for a detailed history before seeing L.O. In addition to taking a history and physical exam, the NP reviewed all labs and imaging throughout the process. As noted above, several key factors concerned the NP about a hematologic malignancy, such as a new onset baseline anemia and bone lesions seen on the PET scan. One important finding in the patient’s medical history was that her father had breast cancer. About 1 of every 100 breast cancers diagnosed in the United States is found in a man.² This is important because a family history of breast cancer, especially male breast cancer, can increase a patient’s risk for breast cancer. The “benign” findings noted on L.O.’s prior mammogram also may have increased her risk of breast cancer.

The undiagnosed clinic requires providers to be up to date on the most current evidence-based practice. The clinic also requires providers to be flexible in their thought process as the perceived diagnosis may not be accurate. Providers must adjust their approach to treatment, as seen above, when a bone biopsy is needed to obtain a definitive diagnosis. Throughout L.O.’s journey, multiple myeloma was the No. 1 most likely diagnosis, with a solid tumor (breast cancer) a distant second on the list of possible differential diagnoses, up until the bone biopsy proved otherwise. This case was a learning experience, highlighting the importance of looking at the whole patient and their family history when establishing differential diagnoses. It also required frequent changes in how to get an accurate diagnosis for the patient, as many myeloma lab results were normal and her PET scan was unremarkable for a definitive solid tumor mass. The use of MRI after a PET scan in this case was helpful, given the location of her breast tumor. The undiagnosed clinic allows APPs to be autonomous and flexible and use their knowledge to provide the latest evidence-based care for their patient population, ultimately leading to an expedited workup and diagnosis.

References

1. Lumbreras B, Donat L, Hernández-Aguado I. Incidental findings in imaging diagnostic tests: a systematic review. Br J Radiol. 2010;83(988):276-289. doi:10.1259/bjr/98067945
2. Breast cancer in men. Centers for Disease Control and Prevention. Updated July 25, 2023. https://www.cdc.gov/cancer/breast/men/index.htm#:~:text=Breast%20cancer%20is%20most%20often,is%20found%20in%20a%20man