Spitz melanoma of childhood: a review compendium and terminology clarification

Childhood melanoma, while rare, represents the most prevalent form of skin cancer among pediatric populations. Among its various subtypes, Spitz tumors are of particular interest due to their distinct histological features and unique molecular pathways. These tumors are categorized into three primary groups: Spitz nevi, Spitz melanocytomas (also known as atypical Spitz tumors), and Spitz melanomas. Pediatric melanomas, predominantly Spitzoid in nature, differ from the conventional melanomas seen in adults, which are less common in children. The diagnostic challenge posed by Spitzoid melanomas, due to their histological similarities with benign lesions and other types of melanoma, underscores the need for precise classification and diagnosis.

Clinical Presentation and Challenges

Spitz melanomas typically present as rapidly growing lesions, often exceeding 10 mm in diameter. These tumors are more common in certain anatomical regions, such as the head, neck, shoulders, and extremities. Pediatric cases often involve younger patients, particularly those with specific genetic fusions associated with Spitz melanoma. The differential diagnosis is complicated by the overlap in clinical features between Spitz melanomas and benign Spitz nevi or atypical Spitz tumors. Accurate diagnosis is critical, as these tumors can exhibit a wide range of behaviors, from benign to highly aggressive.

Histopathological Features

The histopathological examination of Spitz melanomas involves assessing architectural and cytological characteristics. These tumors often extend into the deep dermis and subcutis, displaying a proliferating bulbous deep edge. While some symmetry may be present, it is less pronounced than in benign Spitz nevi. Key features indicative of Spitz melanoma include a high degree of cytological atypia, frequent mitotic figures, and atypical mitoses. Ulceration and consumption of the epidermis by atypical melanocytes are additional diagnostic markers. Different genetic fusions in Spitz tumors are associated with specific histological patterns, such as spindle-shaped melanocytes in ALK-rearranged tumors and desmoplastic stroma in HRAS-mutated tumors.

Diagnostic Tools and Immunohistochemistry

Immunohistochemistry is a crucial tool in the evaluation of Spitz melanomas, aiding in differentiating these tumors from other melanocytic lesions. Common markers include SOX10, S100, MITF, tyrosinase, and Melan A. The absence of p16 staining is particularly indicative of Spitz melanoma. Given the lack of a definitive single marker, a comprehensive panel of immunohistochemical tests is recommended to guide further investigations.

Genetic Landscape and Prognosis

Spitz melanomas exhibit distinct genetic alterations compared to conventional melanomas. Notably, the BRAF V600 mutation common in conventional melanoma is absent in Spitz melanomas. Instead, HRAS mutations and increased 11p copy numbers are characteristic of Spitz tumors. Other genetic features include kinase fusions, which can be divided into tyrosine kinase fusions (e.g., ROS1, RET, MET, ALK, NTRK1, NTRK3) and serine-threonine kinase fusions (e.g., BRAF, MAP3K8). The presence of these fusions can help in classifying the tumor and predicting its behavior. For instance, the TERT promoter mutation is associated with a higher risk of metastasis. Advanced molecular techniques such as FISH or chromosomal microarrays are utilized to detect specific chromosomal abnormalities, aiding in the diagnosis and prognostication of these tumors.

Clinical Course and Management

The clinical course of Spitz melanoma in children is generally favorable, with most cases exhibiting indolent behavior. However, there are exceptions, and some cases can present with more aggressive features, necessitating careful clinical and pathological evaluation. The management of Spitz melanoma includes surgical excision, often supplemented by sentinel lymph node biopsy to assess the extent of disease spread. Given the complexity of diagnosing Spitz melanoma, a multidisciplinary approach involving dermatopathologists, oncologists, and surgeons is essential for optimal patient management.

Discussion and Future Directions

The diagnostic challenge of Spitz melanoma lies in distinguishing it from benign Spitz nevi and other melanomas. The evolving understanding of its molecular and genetic landscape is paving the way for more precise diagnostic criteria and treatment strategies. Future research should focus on refining these criteria and exploring targeted therapies based on the unique genetic alterations in Spitz melanomas. Additionally, there is a need for standardized terminology and classification to reduce confusion among clinicians and pathologists.

Conclusions

In conclusion, Spitz melanoma in childhood presents unique diagnostic and clinical challenges. The tumor's behavior ranges from benign to potentially aggressive, necessitating a comprehensive diagnostic approach that includes histopathological examination, immunohistochemistry, and genetic testing. The proposed term "Spitz melanoma of childhood" encompasses the diverse presentations and genetic profiles of these tumors. As molecular diagnostics and understanding of the tumor's biology advance, more accurate and tailored treatment options will likely emerge, improving outcomes for pediatric patients. The limited quantity of biopsied material, especially in young children, underscores the importance of thorough initial and follow-up evaluations to ensure accurate diagnosis and management.

Full text

https://www.xiahepublishing.com/2771-165X/JCTP-2023-00023

The study was recently published in the Journal of Clinical and Translational Pathology.

Journal of Clinical and Translational Pathology (JCTP) is the official scientific journal of the Chinese American Pathologists Association (CAPA). It publishes high quality peer-reviewed original research, reviews, perspectives, commentaries, and letters that are pertinent to clinical and translational pathology, including but not limited to anatomic pathology and clinical pathology. Basic scientific research on pathogenesis of diseases as well as application of pathology-related diagnostic techniques or methodologies also fit the scope of the JCTP.

Follow us on X: @xiahepublishing

Follow us on LinkedIn:  Xia & He Publishing Inc.