Mikulicz syndrome is a rare immune mediated condition characterized by tumor-like swelling, lymphoplasmacytic infiltrate and fibrosis of salivary and lacrimal glands of poorly understood etiology. Its clinical presentation in the course of treating acute leukemia can be hard to differentiate from progression of the disease. We present a challenging diagnostic case of extramedullary acute lymphoblastic leukemia (ALL) relapse in the course of blinatumumab.
Case report that aims to remember that AAL relapse can mimic any clinical picture.
A 42-year-old woman was diagnosed in May 2017 with acute pro-B lymphoblastic leukemia Ph negative, EGIL B-II. Treatment with intensive multiagent chemotherapy according to PETHEMA high risk group was started. After induction, patient achieved complete response (CR) with negative minimal residual disease (MRD). Four additional courses of chemotherapy were completed following the PETHEMA high risk schedule. First relapse occurred and salvage therapy with Fludarabine, Ara-C and Idarubicin was started achieving 2nd CR. Unfortunately, the patient relapsed three months later in the bone marrow and blinatumumab was decided. Two cycles were administered without neurological toxicities achieving CR with MRD of 0.31% and 0.11% after 1st and 2nd cycles, respectively. On 26th day of the 3rd cycle, acute swelling of both submandibular glands, swelling of right parotid gland and right monocular diplopia were observed. Cervical and cranial magnetic resonance was performed (Image 1) showing significant enlargement of the right lacrimal gland and bilateral submandibular glands. Bone marrow aspiration (BMA) showed CR with improved MRD of 0.02%. Cytological and cytometric cerebrospinal fluid analysis did not find ALL infiltration. With no evidence of disease progression and given the characteristics of the clinical and radiological picture, Mikulicz Syndrome was raised as a probable diagnostic possibility. However, a submandibular glandular tru-cut biopsy showed glandular infiltration by ALL cells. One week later, a body PET/CT found significant metabolic uptake activity in the glands, regional lymph nodes and extensive bone involvement. Then, a new BMA (performed 10 days after de previous one) demonstrated ALL massive medullar relapse.
Relapsed/refractory (R/R) ALL is a bad condition with poor survival. Isolated extramedullary ALL relapse occurs in up to 6% of ALL according to literature and is often hard to demonstrate. In our case, the picture started as neck and head glandular swelling and diplopia. In the absence of medullar disease, Mikulicz Syndrome was suspected. Mikulicz Syndrome is a rare immune chronic benign condition characterized of swelling of neck and head glands where diplopia is often the first clinical sign. It has been related with several diseases including sarcoidosis, lymphoma and acute lymphoblastic leukemia. In this scenario, a biopsy of the involved glands is strongly recommended to rule out leukemia progression. In our case, tru-cut biopsy of one of the involved glands demonstrated AAL extramedullary relapse despite absence of medullar involvement. Unfortunately, massive medullar relapse was confirmed a week later.
Mikulicz syndrome is a diagnostic challenge for clinicians. In the setting of patients with ALL under blinatumumab treatment, clinicians should rule out ALL relapse before confirming this rare condition.