Abstract Introduction Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) is high risk, and extramedullary relapse (EMR) is rare but ominous. Leukemia cutis (LC) is reported in a small fraction of ALL cases, and simultaneous skin, nodal and meningeal involvement is exceptional, especially in uncontrolled HIV. We report a multisite EMR that clinically mimicked opportunistic infection and required stepwise exclusion of infectious causes before confirming leukemic dissemination. Case Description A 20-year-old man with relapsed BCR-ABL1-positive B-ALL and HIV (human immunodeficiency virus) off ART (antiretroviral therapy) for 10 months was admitted to the ICU with profound pancytopenia (Hb 2.7 g/dL, platelets 9,000/mm³) and hyperleukocytosis (270,000/mm³), requiring intensive transfusion support and bleeding surveillance. A large violaceous, indurated 15-16 cm plaque on the left leg, initially tagged as cellulitis, was re-evaluated: Doppler ruled out deep-vein thrombosis and abscess; contrast MRI showed necrotic cutaneous-subcutaneous involvement without osteomyelitis or mass. Two punch biopsies revealed focal leukemic infiltration, and skin flow cytometry showed 61.3 % B-lymphoblasts, confirming leukemia cutis. Soon after, retro-ocular pain led to brain/orbit MRI, which demonstrated diffuse pachymeningeal enhancement. Because the skin biopsy mentioned luetic-like changes and the patient had advanced HIV, neurosyphilis, tuberculous meningitis and leukemic pachymeningitis were considered. Lumbar puncture showed negative cerebro-spinal fluid VDRL, meningitis/encephalitis panel, cryptococcal antigen and Mycobacterium tuberculosis PCR, so the meningeal enhancement was attributed to leukemic involvement. ART, initially withheld over concern for CNS TB (central-nervous-system tuberculosis) and IRIS (immune reconstitution inflammatory syndrome), was restarted after negative CSF studies. Persistent cervical lymphadenopathy was excised and showed partial infiltration by B-lymphoblasts (21 %) and negative mycobacterial studies, confirming nodal extramedullary relapse. Bone marrow then revealed 50 % blasts, establishing systemic relapse; ponatinib-based mini-HyperCVAD was started but interrupted by pancytopenia and multidrug-resistant infections. Discussion This case shows a rare triad: relapsed, biologically aggressive Ph+ B-ALL; multifocal extramedullary disease (skin, nodes, pachymeninges); and uncontrolled HIV with high infectious risk. That mix blurred the picture because every leukemic site looked first like an opportunistic infection and had to be ruled out as such. Management was limited by biology and by timing: ART was held to avoid CNS-IRIS while TB was excluded, then restarted after negative CSF; salvage chemo was begun but paused several times for pancytopenia, BLEE Klebsiella sepsis and lysis risk. The case underlines that, in severely immunocompromised patients with overlapping infection and malignancy, only coordinated, procedure-based, multidisciplinary care allows correct diagnosis and safe treatment. This abstract is funded by: None
Morales et al. (Fri,) studied this question.