An 8-month-old girl with an unremarkable prenatal and birth history presented with a giant red nodular lesion on her left shoulder. The lesion first appeared at 7 weeks of age as a solitary, small vascular-appearing red papule, not exceeding 1 cm. Two dermatologists diagnosed it as an infantile hemangioma with no systemic involvement. No treatment was initiated due to its location, lack of ulceration, and small size. The parents were advised to monitor the lesion, anticipating typical growth and spontaneous regression.

At 8 months of age, the infant was brought to the emergency department with fever and lethargy. Routine blood tests revealed pancytopenia and elevated C-reactive protein levels. A peripheral blood smear showed a few blast cells (Fig. 1b), leading to admission for severe neutropenic fever.

During hospitalization, the lesion on the left shoulder had grown to 16 cm (Fig. 1a). Examination revealed a highly erythematous, giant nodular lesion that was firm on palpation with overlying ulceration. No bruit or thrill was detected on auscultation, and Doppler ultrasound showed no vascular malformation. Bone marrow and skin biopsies were performed under general anesthesia.

The skin biopsy revealed perivascular atypical large lymphoid cells infiltrating the dermis (Figure 2a), and immunohistochemistry confirmed B cells via positive terminal deoxynucleotidyl transferase (TdT) and CD20 markers (Fig. 2b). The bone marrow biopsy confirmed acute B-cell lymphoblastic leukemia. The diagnosis of leukemia cutis secondary to B-ALL was established. The patient was promptly started on induction chemotherapy (vincristine,dexamethasone, asparaginase, and doxorubicin), and the skin lesion drastically regressed in size after the first cycle (Fig. 2c), demonstrating a positive response to treatment.