# Recurrent anti-TIF1γ-positive dermatomyositis coexisting with postoperative parotid lymphoepithelial carcinoma: a case report with pathogenesis analysis

## TL;DR

A rare case of dermatomyositis linked to a parotid tumor shows complex immune responses and genetic factors, highlighting the need for long-term care.

## Contribution

A novel case report linking anti-TIF1γ-positive dermatomyositis with postoperative parotid lymphoepithelial carcinoma and EBV-driven immune dysregulation.

## Key findings

- DM recurred after successful cancer treatment, indicating persistent immune dysfunction.
- PBMC analysis showed active B-cells and reduced cytotoxic cells during DM recurrence.
- Germline mutations in immune genes, including CR2, may contribute to EBV-related B-cell activation.

## Abstract

Anti-TIF1γ-positive dermatomyositis (DM) is a classic paraneoplastic syndrome in adults, but its coexisting with lymphoepithelial carcinoma (LEC) of the parotid gland is exceptionally rare. This rarity poses significant challenges for clinical management.

To report a unique case of parotid LEC emerging three years after a diagnosis of anti-TIF1γ-positive DM, followed by a post-oncologic DM recurrence. We aimed to investigate the underlying immunopathogenesis through peripheral blood mononuclear cell (PBMC) analysis and genetic profiling.

A 28-year-old male presented with anti-TIF1γ-positive DM. Three years later, he developed parotid LEC, with Epstein-Barr virus (EBV) detected in both tumor tissue and serology. He was treated with surgical resection and adjuvant therapy, achieving a near-complete oncologic response. However, DM recurred eight months after the cancer diagnosis. Initial cyclophosphamide treatment was effective, but its withdrawal led to relapse; subsequent therapies with methotrexate and tofacitinib provided minimal benefit.

PBMC analysis during the DM recurrence revealed a highly active B-cell population and a reduction in cytotoxic cells. This B-cell expansion subsequently decreased 10 months later, suggesting a delayed effect of the documented EBV activation. Germline genotyping identified a panel of deleterious germline mutations in immune regulation genes, including a variant in CR2 (rs367567954), which encodes a receptor for EBV on B cells and may contribute to their aberrant activation.

This case illustrates that refractory anti-TIF1γ-DM can persist even after the associated malignancy is well controlled and underscore the need for long-term vigilance and personalized management strategies in paraneoplastic DM.