(A577) Melanoma in a Patient with Septo-optic Dysplasia: A Case Report

Introduction: Here, we present the case of a 44-year-old Caucasian male with septo-optic dysplasia (SOD) who was diagnosed with pT3b melanoma, a combination not previously documented. SOD is a rare congenital disorder arising from environmental and genetic factors, characterized by a triad of midline structural defects: optic nerve hypoplasia, agenesis of the corpus callosum/septum pellucidum, and hypoplasia of the hypothalamic-pituitary axis. Various transcription factors have been implicated in its pathogenesis, such as HESX1, SOX2, SOX3, and OTX2.

Methods: Our patient was diagnosed with SOD at age 19-20 via MRI and hormonal blood testing, requiring prednisone and levothyroxine therapy. At the time of presentation to our clinic in 2024, he reported a dark mole on his left lateral neck that was present for several years and recently started to scab. Family history was significant for melanoma in his father. Biopsy confirmed the presence of melanoma, with a depth of invasion of 2.1 mm. Following this, he underwent a wide local excision and sentinel lymph node biopsy, both of which were negative for additional malignancy.

Results: Several factors warrant consideration here. SOX2, implicated in SOD, may also play a role in melanoma. Studies have shown that its upregulation is associated with increased tumorigenesis and invasion, while reduced activity correlates with lower long-term tumor viability. Of note, strong SOX2 expression is crucial for normal neural development, with mutations that reduce expression (like those seen in SOD) leading to pituitary hypoplasia and other defects. This baseline reduction in SOX2 activity in neural/neural crest cell-derived tissues could have decreased the metastatic potential/aggressiveness of our patient's tumor. Conversely, the patient’s very fair skin (a risk factor for melanoma) may be a consequence of diminished melanocyte-stimulating hormone from his panhypopituitarism.

Conclusions: This unique interplay of genetic and physiological factors contributing to the pathogenesis of this patient’s melanoma highlights a case that has not been previously described in the literature.