Spitz Nevus

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Background

Physicians have known for almost a century that some childhood lesions histologically diagnosed as melanomas did not show malignant behavior. The terms juvenile melanoma and prepubertal melanoma were used to describe such lesions.

Several attempts were made to establish objective criteria that would clearly delineate Spitz nevi and melanomas. The controversial classification of some cases as metastasizing Spitz nevi further confounded the issue; however, such cases illustrate the difficulty of accurately distinguishing some Spitz nevi from melanoma based on histological criteria alone. Even today, no set of criteria can be used to predict the clinical outcome of atypical Spitz tumors with absolute assurance.

Pathophysiology

A Spitz nevus can arise de novo or in association with an existing melanocytic nevus. Some may be fast growing.[1]

Etiology

The cause of Spitz nevi is not known.

Epidemiology

Frequency

Exact data on incidence or prevalence are not available. Spitz nevi are estimated to represent less than 1% of all childhood melanocytic nevi.

Race

Spitz nevi have been described most frequently in fair-skinned individuals. One study reviewed 130 cases in a Hispanic population, demonstrating that Spitz nevi are not restricted to white patients.[2]

Sex

Both sexes are equally affected. Some authors describe a slight female predominance.

Age

About 50% of cases occur in children younger than 10 years; 70% of all cases are diagnosed during the first 2 decades of life.

Prognosis

The prognosis is good. Recurrences should be treated with re-excision. These lesions are clinically benign. A 2011 study reporting on 157 patients with Spitz-type melanotic lesions suggests that atypical Spitz tumors pose a minimal threat of mortality but have an increased risk of melanoma and a moderate risk of metastasis to regional nodes. Aggressive treatment is usually not needed, but monitoring for signs of relapse, as well as subsequent melanomas, is recommended.[3]  Mitoses and inflammation are indicators of increased aggressiveness.[4] Using single morphologic features to determine prognosis has severe limitations.[5]

Patient Education

Educate patients about sun protection and self-examination of the skin. For patient education materials, see the Cancer and Tumors Center.

History

After its appearance, the lesion tends to grow rapidly and may reach a size of 1 cm within 6 months. Spitz nevi tend to become static after the rapid initial growth phase; however, color changes may be observed, and bleeding and pruritus are rarely noticed (see the image below).



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Spitz nevus on the ear of a child.

Physical Examination

Single, dome-shaped, red or pigmented papules or nodules are typical. Most lesions occur on the face or legs; rare cases of oral Spitz nevi were also reported.[6] The color may vary from nonpigmented through pink to orange-red. Some lesions are pigmented, especially those found on lower extremities. Note that the rare recurrences may mimic metastatic malignant melanoma.

Misdiagnosis of Spitz nevi as melanomas and misdiagnosis of melanomas as Spitz nevi is a possibility. In one study, 6.5% of cases diagnosed clinically as melanomas were Spitz nevi. Histopathologic differentiation from melanomas is equivocal in up to 8% of cases.

Criteria that in concert strengthen the probability of the diagnosis of Spitz nevus in any given case include a young patient, a well-demarcated and symmetrical lesion, maturation and dispersion of melanocytes at its base, and the presence of epithelial hyperplasia, but no criterion is absolutely reliable.

Imaging Studies

Dermatoscopy: A starburst pattern is observed (ie, pigmented streaks symmetrically distributed at the periphery of the lesion).[7]   A 2015 multicenter study found that Spiz nevi show a multicomponent and nonspecific pattern.[8]

Other Tests

Histopathologic evaluation of a suspected Spitz nevus is indicated.

The value of including individual proliferation index and histopathological parameters (eg, Ki-67, Pi-21, fatty acid synthetase) into models of predictive probabilities is uncertain, but a panel of markers including Ki-67, HMB-45, and S100A6 can be helpful in establishing a histologic diagnosis. Ki-67 staining is usually absent in dermal nuclei of benign Spitz nevi. HMB-45 staining demonstrates a gradient, and S100A6 diffusely stains the lesion.

Analyses of mutations of BRAF, NRAS, and HRAS were promising in distinguishing Spitz nevi from melanomas, but BRAF mutations do not separate all Spitz nevi from spitzoid melanomas and other melanocytic proliferations.[9, 10, 11] TERT promoter mutations are common among spitzoid lesions with an aggressive course, but some similar lesions with more indolent behavior have been described.[12] Mutations in receptor tyrosine kinases ALK, ROS1, NTRK1, and RET have been identified, and oncogenic fusions in TRK family receptor tyrosine kinases, including NTRK3, have been found in Spitz tumors.[13]

Mass spectrometry is another promising technology in the diagnosis of Spitz tumors.[14]

Procedures

Surgical excision (generally with local anesthesia) and histopathologic evaluation of the margins of the specimen is recommended. With regard to sentinel node biopsy, a series of 12 cases with atypical Spitz nevi showed nodal micrometastases in one third of the patients, suggesting a yet not understood metastatic potential.

Histologic Findings

Most Spitz nevi are predominantly compound, although junctional and intradermal lesions are also observed. The sine qua non of the diagnosis is the presence of large and/or spindle-shaped melanocytes, usually in nests. The nests are composed of an admixture of spindle cells and/or epithelioid cells, although frequently, the spindle-shaped cells predominate (see the images below).



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Microphotograph (low power).



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Microphotograph (medium power).



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Microphotograph (low power).



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Microphotograph (medium power).

The spindle cells are usually observed in a fascicular arrangement, and typically have a vertical orientation. These cells have abundant cytoplasm and contain a vesicular nucleus with a conspicuous nucleolus. The epithelioid cells have prominent nucleoli. Tumors composed only of epithelioid cells, those that lack dispersion at the base, those that are grossly asymmetrical, those with deep mitoses, and those in older individuals are more likely to represent malignant melanoma.[15]

Striking symmetry, sharp lateral demarcation, absent (or rare) mitoses, absence of atypical mitoses, presence of eosinophilic and periodic acid-Schiff (PAS)–positive globules (Kamino bodies) and nondisruptive (single-file like) infiltration of collagen are important features indicating the diagnosis of Spitz nevi. Single-file melanocytes may also be observed in the reticular dermis located at the base of the lesion (dispersion).

Another important feature is the maturation of cellular elements toward the dermis. Pagetoid spread of the melanocytes is usually confined to the center of the lesion; when present, it can cause confusion with melanoma.

The epidermis is hyperkeratotic and acanthotic. A cleavage artifact of fixation is commonly noticed above the nests and around superficial dermal elements. Cytological features, such as oval vesicular nuclei with a single prominent nucleolus, help to differentiate Spitz nevi from melanoma.[16]

The histologic distinction between Spitz nevi and melanomas is equivocal in many cases, and pathologists often seek a second opinion.[17]

Immunohistochemistry and comparative genomic hybridization have proved helpful.[18] As specific genes related to pathogenesis and behavior are identified, next-generation sequencing and proteomics will be used increasingly to clarify the diagnosis of atypical Spitz tumors. Proteomics may be particularly important, as gene silencing may be as important as gene loss. Spitz nevi stain diffusely with S100A6, demonstrate no deep Ki-67–positive cells, and show a gradient with HMB-45 staining. Melanomas show the opposite patterns.[19]

A rare variant is the desmoplastic Spitz nevus in which the proliferating large epithelioid and/or fusiform melanocytes are embedded in a desmoplastic stroma with thick eosinophilic collagen bundles.[20] Spitz nevi showing architectural features of Clark nevi (dysplastic nevi) were also described in a small series and have been termed Spark nevi or spastic nevi. The spindle cells were oriented parallel to the epidermis with fused rete and lamellar fibroplasia.[21]

A case of a pseudogranulomatous variant (with inflammatory infiltrate mimicking a granulomatous dermatitis) was described.[22]

Surgical Care

Excision of lesions suspected of being Spitz nevi with histopathologic evaluation of the margins of the specimen is indicated.[23, 24] Sentinel lymph node biopsy is not justified for surgical staging.[25]

Consultations

Consult a plastic surgeon or head and neck surgeon if the excision requires extensive repair.

Activity

Activity is restricted only to the extent that the surgical procedure justifies.

Complications

The only complications are those that may occur after any surgical excision and repair.

Prevention

Sun protection is recommended.

Long-Term Monitoring

Regular follow-up, preferably by a dermatologist, is indicated.

What is Spitz nevus?What is the pathophysiology of Spitz nevus?What causes Spitz nevus?What is the prevalence of Spitz nevus?What are the racial predilections of Spitz nevus?What are the sexual predilections of Spitz nevus?Which age groups have the highest prevalence of Spitz nevus?What is the prognosis of Spitz nevus?What is included in patient education about Spitz nevus?Which clinical history findings are characteristic of Spitz nevus?Which physical findings are characteristic of Spitz nevus?Which conditions should be included in the differential diagnoses of Spitz nevus?What are the differential diagnoses for Spitz Nevus?What is the role of dermoscopy in the workup of Spitz nevus?What is the role of histopathologic evaluation in the diagnosis of Spitz nevus?What is the role of surgical excision in the diagnosis of Spitz nevus?Which histologic findings are characteristic of Spitz nevus?How is Spitz nevus treated?Which specialist consultations are beneficial to patients with Spitz nevus?Which activity modifications are used during the treatment of Spitz nevus?What are the possible complications of Spitz nevus?How is Spitz nevus prevented?What is included in the long-term monitoring of patients with Spitz nevus?

Author

Zoltan Trizna, MD, PhD, Private Practice

Disclosure: Nothing to disclose.

Coauthor(s)

Ronald P Rapini, MD, Professor and Chair, Department of Dermatology, The University of Texas MD Anderson Cancer Center; Distinguished Chernosky Professor and Chair of Dermatology, Professor of Pathology, University of Texas McGovern Medical School at Houston

Disclosure: Book royalties from Elsevier publishers.

Specialty Editors

Richard P Vinson, MD, Assistant Clinical Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine; Consulting Staff, Mountain View Dermatology, PA

Disclosure: Nothing to disclose.

Rosalie Elenitsas, MD, Herman Beerman Professor of Dermatology, University of Pennsylvania School of Medicine; Director, Penn Cutaneous Pathology Services, Department of Dermatology, University of Pennsylvania Health System

Disclosure: Received royalty from Lippincott Williams Wilkins for textbook editor.

Chief Editor

Dirk M Elston, MD, Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Disclosure: Nothing to disclose.

Additional Contributors

Maureen B Poh-Fitzpatrick, MD, Professor Emerita of Dermatology and Special Lecturer, Columbia University College of Physicians and Surgeons

Disclosure: Nothing to disclose.

References

  1. Pedrazini MC, Montalli VAM, Souza EM. The Fast Clinical Evolution of a Spitz Nevus: Three-Year Follow-Up of a Child. Rev Paul Pediatr. 2017 Oct-Dec. 35 (4):476-479. [View Abstract]
  2. Berlingeri-Ramos AC, Morales-Burgos A, Sánchez JL, Nogales EM. Spitz Nevus in a Hispanic Population: A Clinicopathological Study of 130 Cases. Am J Dermatopathol. 2010 Jan 22. [View Abstract]
  3. Sepehr A, Chao E, Trefrey B, et al. Long-term Outcome of Spitz-Type Melanocytic Tumors. Arch Dermatol. 2011 Oct. 147(10):1173-9. [View Abstract]
  4. Luo S, Sepehr A, Tsao H. Spitz nevi and other Spitzoid lesions part I. Background and diagnoses. J Am Acad Dermatol. 2011 Dec. 65(6):1073-84. [View Abstract]
  5. Massi D, Tomasini C, Senetta R, Paglierani M, Salvianti F, Errico ME, et al. Atypical Spitz tumors in patients younger than 18 years. J Am Acad Dermatol. 2015 Jan. 72(1):37-46. [View Abstract]
  6. Li CC, Harrist TJ, Noonan VL, Woo SB. Intraoral Spitz nevus: case report and literature review. Oral Surg Oral Med Oral Pathol Oral Radiol. 2013 Oct 16. [View Abstract]
  7. Rossiello L, Zalaudek I, Ferrara G, Docimo G, Giorgio CM, Argenziano G. Melanoacanthoma simulating pigmented spitz nevus: an unusual dermoscopy pitfall. Dermatol Surg. 2006 May. 32(5):735-7. [View Abstract]
  8. Moscarella E, Lallas A, Kyrgidis A, Ferrara G, Longo C, Scalvenzi M, et al. Clinical and dermoscopic features of atypical Spitz tumors: A multicenter, retrospective, case-control study. J Am Acad Dermatol. 2015 Nov. 73 (5):777-84. [View Abstract]
  9. Fullen DR, Poynter JN, Lowe L, et al. BRAF and NRAS mutations in spitzoid melanocytic lesions. Mod Pathol. 2006 Oct. 19(10):1324-32. [View Abstract]
  10. Gill M, Cohen J, Renwick N, Mones JM, Silvers DN, Celebi JT. Genetic similarities between Spitz nevus and Spitzoid melanoma in children. Cancer. 2004 Dec 1. 101(11):2636-40. [View Abstract]
  11. van Dijk MC, Bernsen MR, Ruiter DJ. Analysis of mutations in B-RAF, N-RAS, and H-RAS genes in the differential diagnosis of Spitz nevus and spitzoid melanoma. Am J Surg Pathol. 2005 Sep. 29(9):1145-51. [View Abstract]
  12. Requena C, Heidenreich B, Kumar R, Nagore E. TERT promoter mutations are not always associated with poor prognosis in atypical spitzoid tumors. Pigment Cell Melanoma Res. 2017 Mar. 30 (2):265-268. [View Abstract]
  13. Yeh I, Tee MK, Botton T, Shain AH, Sparatta AJ, Gagnon A, et al. NTRK3 kinase fusions in Spitz tumours. J Pathol. 2016 Nov. 240 (3):282-290. [View Abstract]
  14. Lazova R, Seeley EH, Kutzner H, et al. Imaging mass spectrometry assists in the classification of diagnostically challenging atypical Spitzoid neoplasms. J Am Acad Dermatol. 2016 Dec. 75 (6):1176-1186.e4. [View Abstract]
  15. Da Forno PD, Fletcher A, Pringle JH, Saldanha GS. Understanding spitzoid tumours: new insights from molecular pathology. Br J Dermatol. 2008 Jan. 158(1):4-14. [View Abstract]
  16. Valdebran M, Elbendary A, Chaitanya Arudra SK, Torres KM, Elattar I, Elston DM. Nuclear and cytoplasmic features in the diagnosis of banal nevi, Spitz nevi, and melanoma. J Am Acad Dermatol. 2016 Nov. 75 (5):1032-1037.e8. [View Abstract]
  17. Zhao G, Lee KC, Peacock S, Reisch LM, Knezevich SR, Elder DE, et al. The utilization of spitz-related nomenclature in the histological interpretation of cutaneous melanocytic lesions by practicing pathologists: results from the M-Path study. J Cutan Pathol. 2017 Jan. 44 (1):5-14. [View Abstract]
  18. Cho-Vega JH. A diagnostic algorithm for atypical spitzoid tumors: guidelines for immunohistochemical and molecular assessment. Mod Pathol. 2016 Jul. 29 (7):656-70. [View Abstract]
  19. Egberts F, Kaehler KC, Brasch J, Schwarz T, Cerroni L, Hauschild A. Multiple skin metastases of malignant melanoma with unusual clinical and histopathologic features in an immunosuppressed patient. J Am Acad Dermatol. 2008 May. 58(5):880-4. [View Abstract]
  20. Nojavan H, Cribier B, Mehregan DR. [Desmoplastic Spitz nevus: a histopathological review and comparison with desmoplastic melanoma]. Ann Dermatol Venereol. 2009 Oct. 136(10):689-95. [View Abstract]
  21. Ko CJ, McNiff JM, Glusac EJ. Melanocytic nevi with features of Spitz nevi and Clark's/dysplastic nevi ("Spark's" nevi). J Cutan Pathol. 2009 Oct. 36(10):1063-8. [View Abstract]
  22. Sabater Marco V, Escutia Muñoz B, Morera Faet A, Roig MM, Botella Estrada R. Pseudogranulomatous Spitz nevus: a variant of Spitz nevus with heavy inflammatory infiltrate mimicking a granulomatous dermatitis. J Cutan Pathol. 2012 Sep 18. [View Abstract]
  23. Gelbard SN, Tripp JM, Marghoob AA, et al. Management of Spitz nevi: a survey of dermatologists in the United States. J Am Acad Dermatol. 2002 Aug. 47(2):224-30. [View Abstract]
  24. Murphy ME, Boyer JD, Stashower ME, Zitelli JA. The surgical management of Spitz nevi. Dermatol Surg. 2002 Nov. 28(11):1065-9; discussion 1069. [View Abstract]
  25. Caracò C, Mozzillo N, Di Monta G, Botti G, Anniciello AM, Marone U, et al. Sentinel lymph node biopsy in atypical Spitz nevi: is it useful?. Eur J Surg Oncol. 2012 Oct. 38(10):932-5. [View Abstract]
  26. Rapini RP. Spitz nevus or melanoma?. Semin Cutan Med Surg. 1999 Mar. 18(1):56-63. [View Abstract]

Spitz nevus on the ear of a child.

Microphotograph (low power).

Microphotograph (medium power).

Microphotograph (low power).

Microphotograph (medium power).

Spitz nevus on the ear of a child.

Microphotograph (low power).

Microphotograph (medium power).

Microphotograph (low power).

Microphotograph (medium power).