Case Presentation: A 23-year-old man presents with progressively debilitating headaches since a fall 1 year ago. Headaches were worsening, exacerbated by exercise and lying flat, and localized to the occipital region. He had been taking finasteride and topical minoxidil for 3 years to treat chronic alopecia. After 3-6 months of use, two cystic, nontender, mobile skin lesions appeared along the frontal and occipital hairline which subsequently drained fluid. A third painful cystic lesion occurred later at the left frontal scalp. All lesions self resolved and a small nodule remained. He also had multiple head injuries from playing football for 17 years. No recent weight loss, dyspnea, or other skin changes. Exam revealed a subcentimeter solid, nontender, nonmobile nodule at the left frontal scalp. Head CT showed a 2.5 x 2.5 cm lytic left frontal bone lesion with an epidural soft tissue component that was concerning for an eosinophilic granuloma. MRI brain confirmed this finding and whole body PET-CT showed uptake only at cranial site. Skull biopsy confirmed the diagnosis of Langerhans cell histiocytosis (LCH) with BRAF V600E mutation. He plans to undergo neoadjuvant radiation therapy followed by surgical resection for treatment.

Discussion: Our case adds to the literature an unusual presentation of LCH that only involved the skull and was associated with debilitating headaches, chronic head injury, and alopecia. Head imaging indications for headaches include acute neurologic deficit, systemic signs, age >50, positional nature, post-traumatic onset, and changes in headache quality.1 Our patient’s history of worsening headaches exacerbated by positional changes appropriately triggered a head CT, leading to his diagnosis of LCH, a rare histiocytic neoplastic disorder that affects only 1-2 adults and 5-9 children per million.2,3 While 55% of kids have just one organ system affected, only 15-20% of adults have single-site disease.4,5 In adults, the most common sites are the bones, skin, lungs, and pituitary gland.3 Our patient’s history of repeated head injury and alopecia have been postulated as potential links.2,6,7,8 Additionally, his long-term use of finasteride, a regulator in the myeloid derived suppressor cells, and topical minoxidil on the involved scalp area brings to question if these are potential associations, especially given the cystic skin changes after minoxidil’s start.9 BRAF inhibitors are potential treatment options when a BRAF V600E mutation is present; though cases with persistently positive cfBRAF V600E can have higher reactivation rates after drug discontinuation.10

Conclusions: Given LCH’s rarity and variability in clinical manifestations, it is important to highlight new presentations that can add to our understanding. This is a unique presentation of left frontal calvarial LCH discovered on imaging done for debilitating headaches that were associated with recurrent head injuries and chronic alopecia. It highlights the importance of obtaining neuroimaging for headaches when red flag signs or symptoms are present.1 Without proper head imaging, misdiagnosis and delays in treatment may happen. A thorough history, including review of medications, and physical examination are crucial for a timely workup and diagnosis. The patient’s use of finasteride and topical minoxidil shows areas for future investigations of links to LCH.