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Spitz nevus/tumor in children: Diagnosis and management

Spitz nevus/tumor in children: Diagnosis and management
Literature review current through: Aug 2023.
This topic last updated: Nov 16, 2021.

INTRODUCTION AND TERMINOLOGY — Spitz nevus (or Spitz tumor) is an uncommon, melanocytic lesion composed of large, epithelioid and/or spindled cells that presents as a well-circumscribed, dome-shaped, pink-red or brown papule, most commonly located on the face or lower extremities (picture 1A). It predominantly occurs in children but may also develop in adults:

Spitz nevus was initially described by Dr. Sophie Spitz in 1948 as a childhood melanocytic proliferation, with histologic features indistinguishable from melanoma but with a favorable outcome, and was termed "juvenile melanoma" [1].

The term "spitzoid proliferation" generally refers to lesions with the typical, spindle and epithelioid cell morphology. These lesions are thought to occur on a clinical spectrum, ranging from benign Spitz nevus to atypical Spitz tumor and Spitz melanoma.

The typical, benign Spitz nevus is often clinically recognized and, if biopsied, may be termed "Spitz nevus," "spindle and epithelioid cell nevus," or "pigmented spindle cell nevus of Reed" by the pathologist.

The World Health Organization (WHO) 2018 classification of melanoma designates melanocytic lesions that harbor characteristic molecular features, such as tyrosine kinase or serine/threonine kinase fusions (ALK, BRAF, MET, NTRK1/3, MAP3K8, RET, and ROS1) or HRAS hotspot mutations in a mutually exclusive pattern, as "Spitz neoplasms" (table 1) [2]. Whereas initial reports identified such mutations in Spitz melanomas, they are now regarded as a diagnostic feature for all types of Spitz tumors, including benign Spitz nevi (55 percent), atypical Spitz tumors (56 percent), and Spitz melanomas (39 percent) [3].

This topic will discuss the diagnosis and management of Spitz nevus and spitzoid proliferations in children. The classification and histopathologic and molecular diagnosis of Spitz nevus and atypical Spitz tumors are discussed in more detail separately. BAP1-inactivated melanocytic tumors and melanoma in children are also discussed separately.

(See "Spitz nevus and atypical Spitz tumors".)

(See "BAP1-inactivated melanocytic tumors".)

(See "Melanoma in children".)

EPIDEMIOLOGY — The incidence of spitzoid proliferations is unknown. Typical, benign Spitz tumors are most often identified in patients of 10 to 20 years of age [4], though they can occur in children of any age [5,6]. Spitzoid proliferations are rare in adults.

Data are lacking on the risk factors for spitzoid proliferations. The risk factors for conventional melanoma (eg, ultraviolet [UV] radiation exposure; light skin phenotype; high number of typical nevi; atypical nevi; large, congenital nevi; and genetic predisposition) do not appear to be relevant for Spitz tumors. (See "Melanoma: Epidemiology and risk factors".)

CLINICAL PRESENTATION AND COURSE — The clinical presentation of Spitz proliferations in children is very distinctive (figure 1):

Typical, benign Spitz nevi appear as a solitary, pink-red or reddish-brown papule or dome-shaped nodule (picture 1A-B) or dark brown to black macule or papule (picture 2A-B) usually 5 to 6 mm in diameter. They usually have regular, raised borders and are most often located on the face or extremities.

Characteristically, there is a history of a sudden appearance of these lesions, followed by a period of rapid growth over a few months, and then by a stable phase.

A small subset of spitzoid proliferations (atypical Spitz nevi) have atypical clinical features, such as larger size (>10 mm), irregular borders, ulceration, and history of continued growth.

Very rarely, Spitz nevi may occur as multiple lesions in a localized area (agminated Spitz nevi) or in multiple body areas (eruptive, disseminated Spitz nevi) [7].

Over time (months to years), most Spitz nevi appear to involute or acquire clinical and dermoscopic features of common, acquired nevi [8-10], with the rest remaining stable.

DERMOSCOPIC FEATURES — Dermoscopy is an important support for the clinical diagnosis of spitzoid lesions and is generally well tolerated by children. Among 175 dermatologists reporting their management experiences with Spitz nevi, 80 percent recommended routine use of dermoscopy for these lesions [11].

The dermoscopic features of Spitz nevi are well characterized and show three main patterns [12]:

Starburst pattern (51 percent; pigmented Spitz nevus, Reed's nevus)

Regularly distributed, dotted vessels (19 percent; nonpigmented Spitz nevus)

Globular pattern with reticular depigmentation (17 percent; pigmented Spitz nevus)

The distribution of these features is usually symmetric in benign Spitz nevi. In contrast, atypical Spitz tumors often show an atypical or multicomponent pattern suggestive of spitzoid melanoma [12].

In a case series of 52 pediatric melanomas, the dermoscopic pattern most frequently observed in nonpigmented spitzoid melanomas was a "vascular, pink, Spitz-like" pattern including shiny, white structures and atypical vessels. In contrast, pigmented spitzoid melanomas often showed a "pigmented, Reed-like" pattern, including black, dark brown, and blue-gray shades; dark blotches; and peripheral streaks [13].

DIAGNOSIS — The diagnosis of typical Spitz nevus in children is made clinically in many cases. Lesions with atypical clinical and dermoscopic features and changing lesions should be biopsied and examined by a dermatopathologist with experience in the diagnosis of difficult, melanocytic tumors.

Clinical diagnosis — The diagnosis of Spitz nevi can often be made clinically with the recognition of the typical clinical features, onset, and clinical course (see 'Clinical presentation and course' above), in conjunction with supportive findings on dermoscopy (see 'Dermoscopic features' above):

Pink-red or reddish-brown papule or dome-shaped nodule (picture 1A-B) or a dark brown to black macule or papule (picture 2A-B)

Sudden onset

Rapid growth over a few months

Stabilization

Starburst or globular pattern or symmetrically distributed, dotted vessels on dermoscopy

The diagnosis may be challenging in a child presenting with a new, pink-red or brown papule associated with atypical clinical features and course (eg, larger size, recent or irregular growth or change over time, symptoms of itch or pain, history of bleeding or trauma). Such features are suggestive of an atypical spitzoid proliferation or melanoma [14,15].

A close interval follow-up of one to three months will allow for the detection of clinical changes that prompt an excisional biopsy for definitive diagnosis. There are several reasons to elect close clinical follow-up over excisional biopsy, including the overall benignity of the vast majority of lesions; cost, scar risk, and stress associated with surgical excision; likelihood of the recognized evolution or abnormality over a short time duration for lesions that are concerning; and patient age and tolerance of procedure, along with risk of general anesthesia if required to safely perform a procedure [16,17].

When to biopsy — Biopsy is warranted for lesions that have atypical clinical and/or dermoscopic features or show growth or changes between close interval follow-up visits. Biopsy should be planned to remove the entire lesion (excisional biopsy), with particular attention to sampling the entire base of the lesion, as information such as overall architecture and features inherent to the base of the lesion are critical to determine whether a lesion is histologically representing a benign or malignant diagnosis. Ideally, biopsy should include the subcutaneous fat and a small rim of normal-appearing skin surrounding the lesion. This author suggests a 3 mm margin of normal-appearing skin.

Histopathologic diagnosis — For clinically challenging spitzoid proliferations that require biopsy, the histopathologic diagnosis will determine the management approach. The differentiation of an atypical Spitz tumor from a malignant Spitz melanoma is essential to avoid overtreatment and one of the most challenging issues in dermatopathology. Some dermatopathologists incorporate terms to indicate the uncertainty associated with the diagnosis of ambiguous, melanocytic lesions, such as "melanocytic lesion of uncertain malignant potential" or "spitzoid melanoma of childhood."

The histopathologic features of typical Spitz nevi, atypical Spitz nevi, and spitzoid melanoma are summarized in the table (table 2) and discussed in detail elsewhere. (See "Spitz nevus and atypical Spitz tumors", section on 'Histopathology'.)

Molecular tests — With increased efforts to develop ancillary molecular tools, studies have allowed for better molecular understanding of Spitz nevi, atypical Spitz tumors, and Spitz melanoma. However, it is important to acknowledge that ancillary testing has not been validated in the pediatric population, is not approved for use, and is often costly. While useful for characterizing pediatric melanoma subtypes prospectively, the same molecular tools have not effectively distinguished between atypical Spitz tumors and spitzoid melanomas [18].

Molecular tests are not required to render a histopathologic diagnosis of Spitz nevus. For atypical spitzoid proliferations, the distinction from melanoma can be exceedingly challenging and often requires expert dermatopathologist consultation. Histopathology remains the gold standard for melanoma diagnosis in the pediatric population, though we encourage additional testing, as feasible, to provide additional information in conjunction with expert dermatopathologist consultation. At the author's institutions, histopathology and immunohistochemistry remain the gold standard for diagnosis in the majority of pediatric spitzoid proliferations; in the case of discordant diagnosis, molecular studies are sought for additional input:

Mutational analysis and whole exome sequencing – Spitz tumors and Spitz melanoma harbor HRAS mutations or kinase fusions [2]. Molecular tests to identify these mutations may designate a lesion as "Spitz" versus "non-Spitz" but do not provide information on the malignancy of the tumor, as such mutations are identified in banal Spitz nevi, atypical Spitz tumors, and Spitz melanomas [3].

A less costly approach may be to explore the presence of NRAS (G12, Q61) and BRAF (V600) mutations, which are not present in Spitz tumors and may designate a melanoma or other atypical, pigmented lesion with spitzoid features. (See "Spitz nevus and atypical Spitz tumors", section on 'Mutational analysis' and "Spitz nevus and atypical Spitz tumors", section on 'Next-generation DNA and RNA sequencing'.)

Fluorescence in situ hybridization – Historically, as part of the diagnostic work-up for challenging, pediatric, pigmented lesions, fluorescence in situ hybridization (FISH) testing was performed to provide support for the diagnosis of malignancy. For adult tumors, studies have established that the most valuable probe targets 9p21. Since the 9p21 locus is responsible for expression of p16, immunohistochemistry staining for p16 expression provides similar valuable data. Homozygous loss of 9p21 yields no p16 expression, noted by lack of p16 staining on immunohistochemistry [19].

Several studies utilizing various probes have explored the role of FISH for the diagnosis of atypical Spitz tumors or spitzoid melanomas, and data suggest that this tool is less reliable for pediatric tumors:

FISH analysis of 50 pediatric, atypical Spitz tumors found that the four-probe FISH technique was not able to distinguish Spitz nevi from atypical Spitz tumors [20].

In a nonpediatric cohort, homozygous deletion of 9p21 was associated with aggressive behavior of atypical spitzoid proliferations [21]. However, in a pediatric series of atypical spitzoid proliferations and spitzoid melanomas, most tumors with homozygous deletions in 9p21 had a favorable prognosis [22].

Preferentially expressed antigen in melanoma – Another ancillary test that has performed poorly for spitzoid proliferations is preferentially expressed antigen in melanoma (PRAME), a noninvasive tool that was developed to distinguish malignant melanoma from benign, pigmented lesions [23]. In a study of PRAME on 35 spitzoid lesions (not a pediatric-specific cohort), PRAME was expressed in 1 of 2 spitzoid melanomas, 1 of 13 atypical Spitz tumors, and 1 of 20 Spitz nevi [24].

TERT promoter mutations – Conventional adult melanomas may harbor promoter mutations in the TERT (telomerase reverse transcriptase) gene. In a study of spitzoid melanomas (n = 33) and atypical Spitz tumors (n = 23), there were four patients (two adults and two adolescents) with TERT promoter mutations. All died from metastatic disease, while no patients who lacked this mutation died [25].

DIFFERENTIAL DIAGNOSIS — The differential diagnosis of Spitz nevi and atypical Spitz tumors in children includes a variety of benign, cutaneous lesions, both melanocytic and nonmelanocytic (eg, compound nevus, blue nevus, pyogenic granuloma, hemangioma, solitary mastocytoma, juvenile xanthogranuloma). Whereas these lesions are easily identified on histopathology, the differentiation of an atypical spitzoid proliferation from melanoma is one of the most difficult problems in dermatopathology. (See "Spitz nevus and atypical Spitz tumors", section on 'Differential diagnosis'.)

MANAGEMENT

Approach — The approach to the management of Spitz nevus or tumor in the pediatric population is distinguished from the approach to spitzoid lesions in adults. In children, Spitz nevi are of benign nature in most cases and have a favorable outcome [5]. For these lesions, a conservative approach may be appropriate. Spitzoid lesions with atypical clinical and dermoscopic features have a high risk of representing melanoma, especially in adolescents and young adults [26]. These lesions should be excised for histopathologic examination. Our approach to the management of Spitz nevus and spitzoid lesions in children is illustrated in the algorithm (algorithm 1).

Due to the diagnostic ambiguity of some spitzoid tumors and the overlapping features with melanoma, consultation with dermatopathologists experienced in the diagnosis of these tumors is the most important step of management, from which further care will follow.

Children with typical Spitz nevi — For most children with typical Spitz nevi without any acutely concerning features, we suggest clinical and dermoscopic monitoring every three to six months without biopsy or excision (algorithm 1). Clinical and dermoscopic images are stored in the medical record for future comparison.

The decision of monitoring and return frequency versus biopsy or excision is very dependent on the clinical situation, parental or caregiver input, and patient input as well:

If the typical Spitz nevus is noted incidentally on examination with no indication of evolution, a three to six-month follow-up is considered appropriate by most experts. Some recommend dermoscopic follow-up for Spitz nevi in children under age 12 years every three to six months until stability is achieved or for the first two to three years, before extending to annual follow-up [27,28].

If the typical Spitz nevus or a clinical change prompted the visit, the option to perform an excisional biopsy versus returning for close clinical follow-up in three months (including an option to call if the lesion changes in the interim) is discussed with the patient's parent or caregiver or the patient themself. Generally, an acutely concerning change will be noted within that time frame and will prompt an excisional biopsy.

For a biopsy-proven, typical Spitz nevus that lacks atypical or dysplastic features, the excision site may be monitored without re-excision for clear margins of any size. If margins are positive, a discussion of monitoring versus re-excision is reasonable, particularly if the child is young or otherwise unable to tolerate additional surgery. The option to monitor the surgical site is common among clinicians caring for patients with Spitz nevi. In the author's practice, the site is monitored regularly every 6 to 12 months for the first few years [11].

Any gross appearance of pigment within the scar noted in a follow-up visit should prompt re-excision at that time, as recurrence with atypia of an incompletely biopsied Spitz nevus has been reported [5], and the scar may obscure the detection of possible, future, concerning changes.

Children with atypical Spitz nevi/tumors

Surgical excision — For children with atypical Spitz tumors or Spitz nevi with biopsy-proven, atypical or dysplastic features, we suggest complete surgical excision (algorithm 1). Some authors recommend complete excision without a designated margin size, while others recommend a 5 mm margin (particularly in the circumstance of atypical features that are graded as severely dysplastic).

In cases where specific margins are not feasible due to the small size of a child or the anatomy of a small location (eg, an ear), this author recommends discussion with the parents/caregivers and surgeon, with a joint decision on the appropriate excision size and follow-up plan to monitor for recurrence.

For lesions excised with positive margins, re-excision is recommended to attain clear margins. This is very important to reduce the risk of recurrence or of concerning changes that may be obscured by the scar.

Sentinel lymph node biopsy — Sentinel lymph node biopsy (SLNB) is not recommended for atypical Spitz tumors. In the past, SLNB was pursued for patients with atypical Spitz tumors or ambiguous tumors, and a positive SLNB would prompt a reclassification of the original lesion as a melanoma. However, studies have not demonstrated a prognostic or therapeutic benefit for SLNB in patients with atypical Spitz tumors [29,30].

In a systematic review including 541 patients with atypical Spitz tumors (303 of whom underwent SLNB), the survival rate among 119 patients with positive SLNB and 238 patients who were treated with wide excision alone were similar (99 and 98 percent, respectively) after an average follow-up time of 59 months [29]. Moreover, 4 of 119 patients (4 percent) with positive SLNB and 11 of 238 patients (5 percent) treated with wide excision alone had regional recurrence during follow-up.

PROGNOSIS — In general, children and adolescents with Spitz nevi and atypical Spitz tumors have good clinical outcomes:

Two retrospective studies of biopsy-proven spitzoid neoplasms in pediatric patients did not identify a fatal case in a total of 888 lesions [5,6]. In one study, 25 of 595 patients had more than one biopsy-proven spitzoid proliferation [5].

A multicenter study of fatal pediatric melanoma patients failed to identify a fatal case of Spitz melanoma in prepubertal patients [31]. This finding is particularly reassuring for patients presenting in childhood with a challenging tumor for which the differential diagnosis between atypical Spitz tumor and Spitz melanoma is difficult.

FOLLOW-UP — Patients with Spitz tumors may have an increased risk of developing a melanoma. In a single-institution study, 6 of 144 patients with a diagnosis of Spitz nevus or atypical Spitz tumor followed up for a median of nine years developed an invasive melanoma, corresponding to an eightfold excess risk compared with the age- and sex-matched general population [32]. Therefore, it is helpful to monitor the skin after the diagnosis with regular total body skin examinations. The frequency of skin evaluations may vary depending upon the presence of other nevi and risk factors. We usually see patients with a history of atypical Spitz tumors and many nevi every six months and see patients with few nevi and a remote history of Spitz nevus once a year.

PREVENTION — Ultraviolet (UV) protection is generally recommended to mitigate the risk of developing melanoma. Although the genetic alterations of Spitz tumors do not implicate UV radiation as an inciting factor, interventions to reduce individual sun exposure are recommended for patients with Spitz nevi, as they are at increased risk for melanoma [32].

Pediatric patients are generally counseled to adopt "safe sun" habits, including prevention of sunburns by minimizing sun exposure at peak hours (10 AM to 4 PM); wearing sun-protective clothing; wearing mineral sunscreen containing zinc oxide and titanium dioxide, which are not absorbed by the skin; and reapplying sunscreen as needed to avoid sunburns. Additionally, indoor tanning is discouraged. (See "Selection of sunscreen and sun-protective measures".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Melanoma screening, prevention, diagnosis, and management".)

SUMMARY AND RECOMMENDATIONS

Definition and terminology – Spitz nevus (or Spitz tumor) is an uncommon, melanocytic lesion occurring predominantly in children. It presents as a well-circumscribed, dome-shaped, pink-red or brown papule, most commonly located on the face or lower extremities (picture 1A). (See 'Introduction and terminology' above.)

Clinical presentation – Typical, benign Spitz nevi appear as a solitary, pink-red or reddish-brown papule or dome-shaped nodule (picture 1A-B) or dark brown to black macule or papule (picture 2A-B) usually 5 to 6 mm in diameter, with a history of sudden appearance, rapid growth over months, and then stabilization. Atypical Spitz nevi have atypical clinical features, such as larger size (>10 mm), irregular borders, ulceration, and a history of continued growth. (See 'Clinical presentation and course' above.)

Diagnosis – The typical Spitz nevus is, in many cases, diagnosed based on characteristic clinical and dermoscopic features. Spitzoid tumors with atypical clinical and dermoscopic features require biopsy for diagnosis, due to their resemblance with melanoma. It is critical to have histopathologic confirmation of the diagnosis by dermatopathologists with experience in classifying these tumors, as their management is distinct from that of Spitz melanoma. In particular, for tumors with high-grade atypia, a definitive diagnosis may require expert consultation. (See 'Diagnosis' above.)

Molecular tests may identify fusions or mutations that define a lesion as a Spitz tumor but do not distinguish among Spitz nevus, atypical Spitz tumor, or Spitz melanoma. Ancillary tests have not been validated in the pediatric population and should be interpreted with caution. (See 'Molecular tests' above.)

Management (algorithm 1):

For pediatric patients with typical, benign-appearing Spitz nevi, we suggest clinical monitoring rather than surgical excision (Grade 2C). Excision is indicated if concerning clinical and/or dermoscopic changes are noted during monitoring. (See 'Children with typical Spitz nevi' above.)

For pediatric patients with atypical Spitz nevi or Spitz tumors, we suggest surgical excision (Grade 2C). It is important to sample the lesion completely and ensure that histopathology is reviewed by a dermatopathologist experienced in the diagnosis of these tumors. Atypical Spitz tumors with insufficient or positive margins should be re-excised. (See 'Children with atypical Spitz nevi/tumors' above.)

Sentinel lymph node biopsy (SLNB) is not recommended for atypical Spitz tumors. (See 'Sentinel lymph node biopsy' above.)

Prognosis and follow-up – In general, children and adolescents with Spitz nevi and atypical Spitz tumors have good clinical outcomes. However, because they may have an increased risk of developing a melanoma, regular total body skin examinations are recommended following a diagnosis of Spitz tumor. (See 'Prognosis' above and 'Follow-up' above.)

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References

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