The current study presents the case of a 35-year-old pregnant woman with a history of superficial spreading melanoma on the scalp. The primary tumor showed ulceration, vertical growth phase, Clark's level IV (18) and a Breslow thickness of 1.1 mm (19). Initial treatment consisted of an excisional biopsy with narrow resection margins (May 2021). Despite medical recommendations, a radical re-excision of the tumor bed and sentinel lymph node biopsy were not performed, mainly due to circumstances related to the SARS-CoV-2 pandemic.

At the follow-up in January 2023, a whole-body ¹⁸F-FDG PET/CT revealed a non-specific pulmonary nodule in the left anterior segment (S3) of the lung, without evidence of MTS. The melanoma was staged as IIA (T2bN0M0) according to the American Joint Committee on Cancer system (20). Systemic treatment was not indicated, and routine surveillance was continued.

In January 2024, ~3 years later, the patient presented to the Academician Ladislav Dérer Hospital (University Hospital Bratislava; Bratislava, Slovakia) at 24+2 weeks of gestation with a brief episode of expressive aphasia that resolved within 15 min. Upon admission, the neurological examination was normal.

A non-contrast low-dose CT scan of the brain revealed an intra-axial lesion in the left temporal lobe, with perifocal edema (Fig. 1A). The following day, non-contrast 3T brain MRI identified six supratentorial lesions. A total of four lesions showed radiological features consistent with MTS (Fig. 2Aa-Ad), while two small cortical hyperintensities on fluid-attenuated inversion recovery sequences were atypical but suspicious for metastatic disease (Fig. 2Ae and Af).

For systemic staging, whole-body (WB)-MRI with diffusion-weighted imaging demonstrated a small solid lesion in the left upper lung lobe (Fig. 3A). High-resolution CT confirmed a lobulated nodule in the left S3 region (Fig. 3B). Retrospective comparison with a CT scan from January 2023, showed interval growth of 12 mm (Fig. 3C). No uterine or placental involvement was detected using WB-MRI (Fig. 3D).

After multidisciplinary counseling and obtaining informed consent, a pro-fetus strategy was adopted. Due to symptomatic peritumoral edema from brain MTS, the patient received intravenous dexamethasone (4 mg every 8 h for 12 doses; total, 48 mg), followed by oral methylprednisolone (16 mg every 8 h), which was gradually reduced and discontinued after 6 weeks.

Preoperative MRI mapping with diffusion tensor imaging and functional MRI showed the largest left temporal MTS abutting eloquent language and motor areas (Fig. 3E-G). In January 2024, an awake craniotomy with resection of the left middle temporal gyrus MTS was performed (Fig. 2Ba). Histopathological analysis of formalin-fixed and paraffin-embedded samples confirmed metastatic melanoma (Fig. S1) (21). Immunohistochemistry demonstrated the following results: Cytokeratin AE1/3(−), S100(+), SOX10(+), melan-A(+), HMB-45(+), preferentially expressed antigen in melanoma(+), with a Ki-67 proliferation index up to 30% (Fig. S1) (22,23). Molecular testing detected a BRAF V600E mutation using the CE-IVD certified PNAClamp^™ BRAF Mutation Detection Kit (HLP Panagene Co., Ltd.), performed according to the manufacturer's instructions. No epileptiform activity was observed on preoperative electroencephalography or intraoperative electrocorticography.

Due to interval progression, a second craniotomy was undertaken in January 2024, to resect the right superior frontal gyrus MTS (Figs. 1B and 2Bb). Both procedures were uneventful. The patient and fetus remained clinically stable without neurological deficit, and the patient was discharged to close outpatient surveillance in February 2024.

A follow-up MRI in February 2024 demonstrated progression of brain MTS (Fig. 2Bc and Bd) and the emergence of a new unresectable left hippocampal MTS, with perifocal edema (Fig. 2Be). At 30+1 weeks' gestation, the patient was counseled regarding three potential management strategies: i) Induction of preterm delivery to permit systemic therapy; ii) initiation of systemic therapy during pregnancy; or iii) a conservative watch-and-wait approach.

A multidisciplinary board, chaired by the hospital director and including an oncologist, neonatologist, gynecologist, neurosurgeon, neurologist and clinical psychologist, reviewed the case. Counseling addressed maternal neurological risks, potential teratogenicity of targeted therapy, expected neonatal outcomes at different gestational ages, the rationale for delaying vs. expediting delivery and the scope of fetal surveillance. The patient was given >24 h to reflect on the information and had the opportunity to consult with their husband and family.

After providing informed consent, the patient elected to continue the pregnancy and initiate systemic targeted therapy. In February 2024, oral dabrafenib (150 mg twice daily) and trametinib (2 mg once daily) were commenced (Fig. 1).

A subsequent MRI in March 2024 demonstrated favorable postoperative changes (Fig. 2Ca and Cb), along with a marked reduction in brain MTS volume compared with that in February 2024 (Fig. 2Cc-Ce).

To allow for fetal maturation, delivery was planned for ~34 weeks' gestation. Oncological therapy was interrupted 3 days beforehand, and intramuscular dexamethasone (6 mg every 12 h; four doses) was administered for fetal lung maturation.

In March 2024 (33+6 weeks), the patient experienced a focal impaired consciousness seizure, necessitating an urgent cesarean section. A eutrophic premature male neonate was delivered, weighing 2,030 g and measuring 46 cm, with Apgar scores of 9/9/9 (24). The patient resumed targeted oncological therapy postoperatively and was started on levetiracetam, titrated to 500 mg twice daily, for seizure control.

At birth, the neonate exhibited delayed cranial ossification with widely open anterior and posterior fontanelles and a broad sagittal suture. Cutaneous findings included fragile vasculature with dark discoloration, most pronounced in the cubital veins, and several isolated dark gray macules (4–5 mm in diameter).

The neonate developed respiratory insufficiency requiring admission to the neonatal intensive care unit (NICU) and continuous positive airway pressure support. Transient hypotension was managed with intravenous crystalloids. Progression to respiratory distress syndrome necessitated surfactant replacement and 6 days of mechanical ventilation. Pulmonary hypertension was treated with inhaled nitric oxide and vasopressors. Cranial ultrasound revealed a grade I intraventricular hemorrhage and stage I hypoxic-ischemic encephalopathy. No congenital malformations were identified. Histological examination of the placenta and umbilical cord showed no evidence of metastatic disease (Fig. S1). The neonate was discharged 27 days after birth.

The child has been followed up at the National Institute of Children's Diseases (Bratislava, Slovakia). Neurodevelopmental assessment at 11 months of chronological age (corrected age, 9 months) included standardized testing with the Bayley Scales of Infant and Toddler Development, Fourth Edition (Bayley-4) (25) for cognitive, communication and motor domains, and the Bayley-III (26) for social-emotional behavior. Cognitive function (37th percentile), communication (50th percentile) and motor function (73rd percentile) were all within the average range (16th-84th percentile) for corrected age, while social-emotional behavior was in the higher-average range (75th percentile). Repeated screening with the S-PMV test (Slovakian, Skríning psychomotorického vývoja) was also normal. At the latest follow-up (May 2025), growth and psychomotor development were within normal limits.

The patient's targeted therapy with D + T was terminated after 7 weeks (April 2024) due to pyrexia and fatigue. The patient was subsequently transitioned to combined immune checkpoint inhibitor therapy as second-line treatment (Fig. 1). The concurrent regimen of ipilimumab (3 mg per kg) and nivolumab (1 mg per kg) was administered intravenously every 3 weeks for four doses, followed by maintenance nivolumab (240 mg) every 2 weeks.

In May 2024, the patient experienced a second epileptic seizure of the focal to bilateral tonic-clonic type, and the levetiracetam dosage was increased to 750 mg twice daily. As of May 2025, the patient remains on maintenance nivolumab therapy with partial disease remission and no evidence of treatment-related toxicity (Fig. 2Da-De).

Cognitive function remained intact, with a Montreal Cognitive Assessment (27) score of 30 out of 30. Quality of life, assessed with the Patient-Weighted Quality of Life in Epilepsy Inventory (version 2) (28), was 70.6 out of 100. Psychological evaluation revealed moderate anxiety, with a Generalized Anxiety Disorder-7 (29) score of 8 out of 21 and mild depressive symptoms, with a Patient Health Questionnaire-9 (30) score of 9 out of 27, without suicidal ideation.

The patient remains under regular oncological follow-up, receiving maintenance nivolumab every 2 weeks and under neurological surveillance every 3 months. The partial remission response could be durable as demonstrated in the CheckMate 204 study (12); however, long-term vigilance is warranted.