Case Presentation: A 60 year-old woman with a history of chronic hepatitis C without cirrhosis and schizophrenia with paranoid delusions was admitted with severe progressive bilateral burning foot pain. She had a history of intermittent alcohol use and recent homelessness. She lacked a primary care doctor and sought care for her bilateral lower extremity pain with 5 emergency department visits in the preceding months; at prior visits, her neuropathy was attributed to alcohol use.On exam, she had reduced pinprick sensation in lower extremities and loss of the bilateral Achilles and patellar reflexes. She was unable to participate in Romberg or gait assessment due to severe pain. Basic workup (A1c, B12, TSH, HIV, SPEP/UPEP/free light chains and cryoglobulins) was unrevealing. Given severity and time course, inpatient EMG was pursued, which found severe length-dependent axonal sensorimotor polyneuropathy affecting the bilateral lower extremities. Sural nerve biopsy showed severe axonal neuropathy with ongoing Wallerian degeneration and low-grade lymphoproliferative disorder– polymorphous infiltrate of small cells with associated reactive-appearing follicles and B-cell marker expression. Bone marrow pathology and flow cytometry confirmed diagnosis of marginal zone lymphoma. There was no evidence of central nervous system involvement on three lumbar punctures, and her PET/CT showed no metastases. She was treated with bendamustine as an inpatient, with a plan for HCV treatment and rituximab administration in supported living facility.
Discussion: We present a case of an unusual cause of a commonly encountered complaint, with a delayed diagnosis that was likely impacted by both cognitive and implicit bias. Length-dependent axonal sensorimotor polyneuropathy has a differential diagnosis that is familiar to hospitalists: toxic (alcohol, vincristine), metabolic (diabetes, chronic renal failure), nutritional deficiency (vitamin B12, thiamine), and endocrine (thyroid) etiologies. However, in this patient with very severe and progressive polyneuropathy as well as chronic hepatitis C, more rare etiologies including lymphoproliferative disease and vasculitis entered the differential. Extranodal marginal zone lymphoma presents with symptoms due to localized glandular epithelial disease, most commonly in the stomach mucosa, and rarely with cutaneous or nerve involvement. Diagnosis is made through morphologic, immunophenotypic, and genetic analysis of biopsy material taken from affected site. The patient’s chronic HCV likely contributed to her development of marginal zone lymphoma, given its association with chronic viral, bacterial, or autoimmune conditions.This patient’s psychosocial complexity also contributed to her delayed diagnosis. This may have been related to cognitive bias such as attribution bias—the desire to explain symptoms based on underlying patient behavior (e.g. patient’s alcohol use)– or to implicit bias, attitudes that underlie actions and decisions in an unconscious manner, faced by stigmatized groups (e.g. discounting symptoms given psychiatric disease or homelessness).
Conclusions: Marginal zone lymphoma is a rare cause of the common symptom of axonal neuropathy. Nerve biopsy should be considered in cases with rapid and severe disease progression in the absence of clear alternative etiology. Hospitalists should be mindful of not just cognitive bias but implicit bias when understanding causes of diagnostic error.