ABSTRACT
PURPOSE: Genetic cancer risk assessment (GCRA) has become increasingly important in clinical cancer care. Almost all published information on genetic risk assessment has come from academic institutions. However, a majority of patients with cancer are seen in the community practice setting. METHODS: We describe the evolution of a community oncology practice GCRA clinic. RESULTS: Over a 10-year period, 445 patients were seen for a possible genetic cancer syndrome. This included 325 patients with family history of breast or ovarian cancer, 92 patients with family history of colorectal cancer or polyposis, and 28 families with another familial cancer predisposition. Fifty-three unique families with a genetic mutation were identified. CONCLUSION: A GCRA clinic can be incorporated into an oncology practice setting and can enhance the standard of care for the entire community. We present data reflecting a 10-year experience with such a clinic and provide recommendations for establishing a successful one.
ABSTRACT
BACKGROUND: Opsoclonus-myoclonus syndrome and breast carcinoma were initially described as neurologic and oncologic accompaniments of antineuronal nuclear autoantibody type 2 (ANNA-2, also known as anti-Ri). However, the neurologic spectrum of ANNA-2 autoimmunity is broader, includes a syndrome of jaw dystonia and laryngospasm, and can be accompanied by lung carcinoma. OBJECTIVE: To describe clinically (with a video) ANNA-2-associated jaw dystonia and laryngospasm, its pathologic correlates, and therapeutic outcomes. DESIGN: Retrospective case series with prospective clinical follow-up. SETTING: Mayo Clinic's Neuroimmunology Laboratory, Rochester, Minnesota. PATIENTS: Consecutive patients with ANNA-2 seropositivity identified since January 1, 1990. MAIN OUTCOME METHODS: Clinical (in 9 patients) and neuropathologic (in 2 patients) findings were reviewed. RESULTS: Of 48 patients with ANNA-2 seropositivity, 9 (19%) had multifocal neurologic manifestations that included jaw dystonia and laryngospasm. Among 6 patients with jaw dystonia, 5 had severely impaired nutrition, causing profound weight loss. Five patients had documented laryngospasm, which contributed to 1 patient's death. Neuropathologic examination revealed diffuse infiltration by CD8(+) T lymphocytes, with axonal loss and gliosis in brainstem and descending spinal cord tracts. Some patients improved symptomatically after immunosuppressant or cytotoxic therapies; 1 patient improved after treatment with botulinum toxin. One patient who underwent tracheostomy because of recurrent laryngospasm was alive and well longer than 3 years after symptom onset. CONCLUSIONS: Jaw dystonia and laryngospasm are common accompaniments of ANNA-2 autoimmunity and are associated with significant morbidity. We propose that selective damage to antigen-containing inhibitory fibers innervating bulbar motor nuclei by CD8(+) T lymphocytes (histopathologically observed infiltrating brainstem reticular formation) is the proximal cause of this syndrome. Early and aggressive therapy offers the prospect of neurologic improvement or stabilization.
