Spitz, Reed, and Spitzoid Lesions

01The classical dermoscopic patterns of Spitz/Reed nevi are starburst, globular, homogeneous, atypical (multicomponent), and reticular. The starburst pattern (peripheral pigmented streaks or large globules arranged radially in symmetric crown around a darker center) is the dermoscopic signature of pigmented spindle cell nevus (Reed nevus), histopathologically corresponding to confluent junctional nests of heavily pigmented spindle melanocytes. The globular pattern is typical of non-pigmented or lightly pigmented Spitz nevus, with brown to black globules scattered throughout. The homogeneous pattern shows structureless brown-black or red-brown coloration. The atypical multicomponent pattern shows multiple structures asymmetrically distributed and is the high-risk variant.

02Vascular Spitz (atypical pink Spitz, classic Spitz nevus without pigment) is the non-pigmented form, presenting in children and young adults as a rapidly growing pink papule. Dermoscopy shows pink homogeneous areas with regular dotted or coiled (corkscrew) vessels arranged in a symmetric pattern, sometimes with white reticular depigmentation (negative network). The differential against amelanotic Spitzoid melanoma is the central challenge: any asymmetric vascular spitzoid lesion in an adult should be excised, while the same morphology in a young child with strict symmetry may be monitored short-term.

03The IDS management algorithm (Lallas BJD 2017, building on prior Argenziano series) stratifies Spitz/Reed nevi by age, symmetry, and pattern. In children under 12 with classic symmetric starburst or globular Spitz, monitoring with sequential digital dermoscopy at 3-month intervals is acceptable, with excision triggered only by asymmetric change. In patients aged 12 or older, or any patient with asymmetric or multicomponent pattern, excision is recommended because the dermoscopic features that distinguish benign Spitz from spitzoid melanoma in adults are unreliable. Asymmetric pigmented spindle cell tumors at any age are excised. Vascular Spitz is excised in any patient over 12.

04Spitzoid melanoma red flags include adult onset, asymmetry of pattern and color, multiple colors (especially blue-grey peppering or blue-white veil), irregular streaks (asymmetric, not in a starburst configuration), and atypical polymorphic vessels. The absence of these does not exclude melanoma, but their presence in a spitzoid lesion is a strong excision indication. Pediatric melanoma is rare but real: about 2% of all melanomas occur in patients under 20, and spitzoid lesions are the most common pediatric melanoma morphology.

05Atypical Spitz tumor (AST) is a controversial intermediate category in histopathology, defined by combinations of size over 1 cm, depth into the reticular dermis or subcutis, mitoses below the surface, asymmetry, and other ambiguous features that prevent clear classification as nevus or melanoma. The Spitz tumor of uncertain malignant potential (STUMP) terminology is similar. Genomic studies (CGH, FISH for 6p25 RREB1 amplification or 11q13 CCND1 amplification) and now fusion testing inform classification but do not always resolve uncertainty. Most ASTs are excised with clear margins and patients are followed clinically; some centers offer sentinel lymph node biopsy for ASTs over 5 mm thick or with concerning features, although the prognostic value is debated.

06BAP-1 inactivated Spitz nevus (also called BAP-1 inactivated melanocytoma, BAP-omas, or atypical Spitz tumor with BAP-1 loss) is a distinct entity defined by combined BRAF V600E mutation and BAP-1 (BRCA1-associated protein 1) loss. Clinically, lesions are skin-colored to pink, dome-shaped, well-circumscribed papules, often multiple, on any body site. Histopathology shows spindle and epithelioid melanocytes, often without pigmentation, and immunohistochemistry confirms BAP-1 nuclear loss. Multiple BAP-omas can be sporadic or part of BAP-1 tumor predisposition syndrome (germline BAP-1 mutations), which carries increased risk of cutaneous and uveal melanoma, mesothelioma, renal cell carcinoma, and other cancers. Recognition mandates germline genetic testing in patients with multiple lesions or family history.

07Kinase fusions and targeted therapy implications have reshaped Spitz nomenclature. Recurrent fusions involving NTRK1, NTRK3, ALK, ROS-1, RET, MET, BRAF, and NTRK2 occur in roughly half of Spitz neoplasms, are mutually exclusive, and define molecular subgroups with characteristic morphologies. NTRK1 fusion Spitz tumors are typically deeply pigmented and spindled. ALK fusion Spitz tumors are often polypoid and amelanotic. ROS-1 fusion lesions overlap morphologically with epithelioid cell histiocytoma. The therapeutic implication is that fusion-positive spitzoid melanomas may respond to TRK inhibitors (larotrectinib, entrectinib for NTRK fusions), ALK inhibitors (crizotinib, alectinib for ALK fusions), or other tyrosine kinase inhibitors, opening targeted therapy avenues for unresectable or metastatic disease.

08The spitzoid lesion management workflow reflects this molecular understanding. Any spitzoid lesion in an adult, any asymmetric spitzoid lesion at any age, vascular Spitz over age 12, and any concerning AST should be excised with clear margins. Molecular workup (FISH, CGH, fusion panels, BAP-1 immunohistochemistry) is reserved for histopathologically equivocal cases and for guiding therapy in confirmed melanoma. Genetic counseling is offered for multiple BAP-omas. Fusion testing is increasingly standard for atypical and malignant spitzoid lesions because of targeted therapy implications.

09Practical caveats include the recognition that small (under 6 mm) symmetric Reed nevi in young patients are common and stable, that asymmetric starburst is rare in children but increasingly suspect in adults, that vascular spitzoid melanoma can present without pigment-network features and rely entirely on vascular morphology, and that AST classification varies between dermatopathologists with significant interobserver disagreement. The conservative approach (excise rather than monitor) is often the correct one outside of pediatric symmetric Reed nevi.