The Appendix That Wasn't: Myeloid Sarcoma Unmasked as Acute Appendicitis in Post-Transplant Relapsed Myelodysplastic Syndrome

Introduction

Myeloid sarcoma (MS) is a rare extramedullary AML-related tumor (~2/million incidence). It may arise de novo, with concurrent AML/MDS, or as relapse — including post-allogeneic HSCT. GI involvement occurs in 7–11% of cases (ileum most common); appendiceal MS mimicking acute appendicitis is extraordinarily rare (<20 reported cases worldwide). Histologic overlap with non-Hodgkin lymphoma drives misdiagnosis rates up to 47%. Extramedullary relapse accounts for 5–12% of post-HSCT relapses (~70% isolated).

Case Presentation

A 75-year-old woman with prior treatment with vidaza/venetoclax, HFrEF, hypothyroidism, hypertension, and recent multifocal pneumonia/bronchiolitis obliterans on antifungal prophylaxis with high-grade MDS (MDS-IB2, complex karyotype, IPSS-M Very High Risk), relapsed 3 months after matched-unrelated-donor allo-HSCT (10% chimerism on a 2025 marrow biopsy). Presented in 2026 with acute abdominal pain, nausea, vomiting, and diarrhea. Labs showed leukocytosis (22,000/µL, 11% blasts), elevated LDH, and mild hyperuricemia. CT showed findings consistent with acute appendicitis, and she underwent laparoscopic appendectomy with intraoperative findings of acute appendicitis.

Surgical pathology revealed an unexpected diagnosis of myeloid sarcoma of the appendix, representing progression of her MDS to AML with monocytic differentiation post-HSCT. Histology showed a dense atypical mononuclear infiltrate with myeloblastic morphology across the appendiceal wall. Immunohistochemistry was positive for CD33, CD43, CD117 (dim), CD163, CD68, and CD34, and negative for CD15/CD56 — confirming myeloid lineage.

Discussion

Appendiceal MS is among the rarest MS presentations; this appears to be one of the first reported cases combining appendiceal MS, acute appendicitis presentation, and relapsed post-HSCT MDS. Proposed mechanisms include aberrant leukemic stem cell homing (CXCR4/CCR5, MMPs, EMT pathways) and reduced graft-versus-leukemia effect from reduced-intensity conditioning. The case highlights the risk of missing MS without routine histopathology, even in classic surgical presentations.

Conclusion

This case showed extremely rare appendiceal MS masquerading as acute appendicitis in relapsed post-HSCT MDS. Key takeaways is to always maintain broad differentials in immunocompromised patients with abdominal emergencies; always pursue routine pathology on resected specimens in hematologic malignancy patients; and engage hematology-oncology early, as pathology may redirect the entire treatment course.