Getting a toehold on subungual tumors: Aneurysmal bone cysts join the club
Aug. 26, 2016
Subungual tumors make me nervous. I realize that most are benign (subungual exostosis, osteochondroma, onycholemmal cyst, glomus tumor, pyogenic granuloma, wart, fibroma, acral fibromyxoma), however subungual malignant lesions (squamous cell carcinoma, keratoacanthoma, melanoma) occur. A delayed diagnosis can result in a profoundly adverse outcome.
Lesions may be painful or present with an overlying nail dystrophy. Certainly for common lesions such as a subungual exostosis, radiography of the affected digit should be part of the initial work-up (1). If the diagnosis is equivocal, further imaging with either a CT scan or MRI would be of value. Of course the gold standard is histologic diagnosis.
Műller et al detail the case of a 39 year-old man with a rapidly growing subungual mass of the right first toe associated with soft tissue swelling. Demineralization of the distal toe was noted on x-ray; CT and MRI scans revealed a tumor replacing the distal phalangeal bone. A biopsy confirmed the diagnosis of an aneurysmal bone cyst (ABC). FISH analysis demonstrated a USP6 rearrangement. The patient was ultimately treated surgically with an image-guided amputation of the distal phalanx and soft tissue. The authors assert that this is the first reported case of an ABC presenting as a subungual mass (2).
According to Hakim et al, “Aneurysmal bone cysts (ABCs) are fairly rare benign cystic lesions, accounting for approximately 9.1% of all bone tumours. The blood filled cysts are divided by connective tissue septa and contain a mix of osteoclasts, giant cells, and reactive woven bone. Controversy exists as to the pathogenesis of aneurysmal bone cysts. In 30% of cases a predisposing lesion can be identified, a finding that some argue suggests that aneurysmal bone cysts are a reactive process to other pathological changes, rather than a distinct tumour type. The most common pre-existing lesion is the giant cell tumour. The sites most commonly associated with ABC are the femur, tibia, humerus and fibula, although they can present in other sites.” (3)
Interestingly, the USP6 rearrangements are believed active nuclear factor kappa B, thereby causing secretion of matrix metalloproteinase, leading to osteolysis, inflammation, and vascularization, while also inhibiting bone morphogenic protein 4 (2). The receptor-activator of nuclear kappa B ligand (RANKL)-receptor-activator of nuclear kappa B (RANK) signaling axis is essential to tumor progression. Targeted RANKL inhibition with denosumab (Prolia) has been demonstrated to cause ABC shrinkage, bone reconstitution, and healing of a pathologic fracture (4). This represents a novel therapeutic option for ABCs in lieu of surgical excision or destruction.
Seth McFarlane, the versatile producer, states: “What makes me happy is just keeping my brain challenged and stimulated and on its toes.” Studying the histology and pathogenesis of ABCs would keep him elated for quite a while.
1. Russell JD, et al. Subungual exostosis. Cutis 2016; 98; 128-30.
Műller CS. First report of an aneurysmal bone cyst presenting as a subungal mass. J Cutan Pathol 2016; 43: 711-16.
2. Hakim DN, et al. Benign tumors of the bone: A review. J Bone Oncol 2015; 4: 37-41.
3. Pelle DW. Targeting receptor-activator of nuclear kappa B ligand in aneurysmal bone cysts: Verification of target and therapeutic response. Trans Res 2014; 164: 139-48.
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