Spitz Nevus: Background, Pathophysiology, Epidemiology


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.

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.

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. [2 Mitoses and inflammation are indicators of increased aggressiveness. [3Using single morphologic features to determine prognosis has severe limitations. 

Patient Education

Educate patients about sun protection and self-examination of the skin.

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).

Spitz nevus on the ear of a child.
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. [5]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.

 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. [1]

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.

Causes

The cause of Spitz nevi is not known.

Diagnostic Considerations

Also consider the following:

  • Melanoma
  • Epidermal nevus
  • Granulomas
  • Histiocytoma
  • Reed nevus
  • Vascular tumors

Differential Diagnoses

Imaging Studies

Dermatoscopy: A starburst pattern is observed (ie, pigmented streaks symmetrically distributed at the periphery of the lesion). [6  A 2015 multicenter study found that Spiz nevi show a multicomponent and nonspecific pattern.

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. [8910TERT promoter mutations are common among spitzoid lesions with an aggressive course, but some similar lesions with more indolent behavior have been described. [11Mutations 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. [12]

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

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).

Microphotograph (low power).

Microphotograph (low power).

Microphotograph (medium power).

Microphotograph (medium power).

Microphotograph (low power). Microphotograph (low power).

Microphotograph (medium power).

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. [14]

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. [15]

The histologic distinction between Spitz nevi and melanomas is equivocal in many cases, and pathologists often seek a second opinion. [16]

Immunohistochemistry and comparative genomic hybridization have proved helpful.[17As 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. [18]

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. [19Spitz 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. [20]

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

Surgical Care

Excision of lesions suspected of being Spitz nevi with histopathologic evaluation of the margins of the specimen is indicated. [2223Sentinel lymph node biopsy is not justified for surgical staging.

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.

Source:http://emedicine.medscape.com

 

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