Paroxysmal Nocturnal Hemoglobinuria (PNH) constitutes a rare bone marrow failure syndrome characterized by hemolytic anemia, thrombotic events (TEs), and bone marrow aplasia of variable degrees. Thrombosis is one of the major clinical manifestations of the disease, affecting up to 40% of individuals with PNH. Venous thrombosis is more prevalent, affecting mainly unusual sites, such as intrabdominal and hepatic veins. TEs might be the first clinical manifestation of PNH. Complement activation, endothelial dysfunction, hemolysis, impaired bioavailability of nitric oxide, and activation of platelets and neutrophils are implicated in the pathogenesis of TEs in PNH patients. Moreover, a vicious cycle involving the coagulation cascade, complement system, and inflammation cytokines, such as interleukin-6, is established. Complement inhibitors, such as eculizumab and ravulizumab (C5 inhibitors), have revolutionized the care of patients with PNH. C5 inhibitors should be initiated in patients with PNH and thrombosis, while they constitute a great prophylactic measure for TEs in those individuals. Anticoagulants, such as warfarin and low-molecular-weight heparin, and, in selected cases, direct oral anticoagulants (DOACs) should be used in combination with C5 inhibitors in patients who develop TEs. Novel complement inhibitors are considered an alternative treatment option, especially for those who develop extravascular or breakthrough hemolysis when terminal inhibitors are administered.

Extramedullary Involvement (EMI) in Multiple Myeloma (MM) is a rare but aggressive entity that usually occurs in advanced or relapsed cases of MM. Although otologic manifestations aren’t frequent, they may mimic common inflammatory or neoplastic pathologies and could be a diagnostic challenge for the clinician. Case presentation: A 65-year-old woman with a history of Relapsed Refractory Multiple Myeloma (RRMM) presented at our outpatient Otolaryngology department with a four-month history of right-sided aural fullness and a minor episode of watery otorrhea. Otoscopy revealed an abnormal tympanic membrane lesion, and audiological evaluation showed moderate conductive hearing loss. The rest of the examination was normal. A Computed Tomography (CT) scan showed a soft-tissue mass occupying the tympanic membrane with associated temporal bone erosion. The history of RRMM and otoscopic and CT findings were indicative of EMI. After multidisciplinary consultation with a hematologist and radiologist, systemic therapy for relapsed disease was initiated, with consideration of adjunctive radiotherapy. However, the clinical course of the patient deteriorated and she eventually died due to her multiple comorbidities. Conclusions: EMI of the tympanic membrane is a rare entity, among the few reported cases with otologic involvement and it remains a diagnostic “challenge” because it resembles many other otologic conditions. Careful analysis of imaging findings in combination with the patient’s medical history is the key to accurate diagnosis. Early recognition is necessary to guide appropriate management, avoid unnecessary surgical intervention, and enable timely initiation of systemic therapy