Hiding beneath the surface: Paraneoplastic pemphigus as a rare presentation of follicular lymphoma Free

Introduction:

Paraneoplastic pemphigus (PNP) is a rare autoimmune mucocutaneous blistering disorder associated with underlying malignancies, most commonly non-Hodgkin lymphoma. PNP carries a poor prognosis due to life-threatening infections and pulmonary complications such as bronchiolitis obliterans (BO), which account for most deaths within one year of presentation. Fewer than twenty cases of PNP associated with follicular lymphoma have been described. We present a diagnostically and therapeutically challenging case of PNP in a patient with follicular lymphoma.

Case Presentation:

A 50-year-old man presented with several months of painful oral ulcerations. Multiple evaluations, including nondiagnostic biopsies, negative direct immunofluorescence (DIF), and unremarkable autoimmune serologies, were inconclusive. He was initially diagnosed with erosive lichen planus and had minimal improvement with topical corticosteroids. A staging CT revealed a 13 cm mesenteric mass; biopsy confirmed Grade 3A follicular lymphoma. PET/CT demonstrated Stage III disease. He initiated treatment with bendamustine and obinutuzumab and tolerated three of six planned cycles. However, oropharyngeal lesions worsened, causing severe odynophagia. High-dose systemic steroids led to near-resolution of mucosal lesions, but he developed invasive fungal pneumonia and required prolonged ICU admission. Despite antifungal therapy and radiographic improvement, his pulmonary function declined. He was diagnosed with BO by pulmonology. Follow-up PET/CT demonstrated complete lymphoma response, but mucosal lesions persisted. Esophageal biopsies revealed DIF-negative lichenoid mucositis with necrotic keratinocytes, consistent with PNP. His symptoms were refractory to IVIG but improved with topical tacrolimus. He underwent tracheostomy for ventilatory support and was eventually discharged to LTAC on palliative steroids, later transitioning to hospice care.

Discussion:

This case highlights the diagnostic difficulty of PNP, especially the lichenoid variant, which is believed to be driven by CD8+ T cell activation. This subtype often results in DIF-negative biopsies due to necrosis and may not respond to therapies targeting humoral mechanisms, such as IVIG. Up to 50% of mucosal biopsies in PNP are DIF-negative. Importantly, PNP affects respiratory epithelium in over 90% of cases and remains progressive even when the underlying malignancy responds to treatment, as demonstrated here. The observed rapid improvement with topical tacrolimus supports a T cell–mediated pathogenesis. Systemic immunosuppression akin to treatment for graft-versus-host disease has been proposed but must be weighed against infection risks—already a major cause of morbidity and mortality in this population.

Conclusion:

PNP is an exceptionally rare autoimmune manifestation of follicular lymphoma and should be considered in patients with refractory erosive mucositis and new lymphoproliferative diagnoses, even when conventional diagnostic tests are inconclusive. Prompt recognition, interdisciplinary management, and consideration of T cell–targeted therapy are essential, especially in cases with respiratory involvement. Further research into immunosuppressive strategies for lichenoid PNP is needed.