Spitz Lesions: Clinical Outcomes
Overview
The management of Spitz-type lesions in clinical practice has been a subject of debate due to the limited information available on their long-term clinical outcomes. Some medical centers opt for a conservative and observational approach, while others recommend further surgery and extended follow-up. The objective of this study was to investigate the extended clinical outcomes of various Spitz-type lesions, including classic Spitz and Spitzoid nevi, atypical Spitz tumors (ASTs), and Spitzoid melanomas. The aim was to gather evidence that could guide a unified management approach for these lesions.
The study conducted a retrospective cohort review of patients aged 18 years and older, who had received a histopathological diagnosis containing the term ‘Spitz’ between 1991 and 2020 at Addenbrooke’s Hospital. The assessment included examining results from sentinel lymph node biopsy (SLNB), rates of wide local excision (WLE), occurrences of metastases, and fatality rates.
The study identified 126 patients with Spitz-type proliferations and available follow-up data, with a mean age of 35.9 years. Among these patients, there were 86 cases (68.3%) of classic Spitz or Spitzoid nevi, 12 cases (9.5%) of ASTs, 27 cases (21.4%) of Spitzoid malignant melanomas, and one case (0.8%) of melanoma that arose in a previously excised Spitz nevus. Notably, SLNB findings were positive in three out of seven patients with classic Spitz or Spitzoid nevi, but none of the 10 individuals with ASTs and Spitzoid melanomas had positive SLNB results. Additionally, four patients with classic Spitz or Spitzoid nevi developed invasive non-Spitz melanoma. After a median follow-up period of 46 months, ranging from 1 to 304 months, only one patient with a Spitzoid melanoma developed distant metastases, and no deaths were observed.
The study findings indicate that Spitz-type lesions are rarely associated with mortality or distant metastasis. However, classic Spitz or Spitzoid nevi may slightly increase the risk of developing non-Spitz-type malignant melanoma. These results suggest that aggressive surgical management, such as SLNB and WLE, may not be necessary for Spitz-type lesions, but continued surveillance is advisable to monitor for potential development of malignant melanoma in the future.
Introduction
Spitz-type lesions are skin growths that can manifest as well-defined papules or nodules, exhibiting a range of colors from nonpigmented to pink, red, or deeply pigmented, appearing dark or brown. These lesions can develop anywhere on the body but are commonly found on the lower extremities. They typically occur before a person reaches their third or fourth decade of life. Spitz-type proliferations encompass a spectrum of lesions, including benign Spitz nevi, which can further be categorized into Classic Spitz Nevi (CSN) and Spitzoid nevi, at one end, and Spitzoid melanomas at the other end. However, the malignant potential of atypical Spitz tumors (ASTs), which fall in between, remains uncertain and controversial. Establishing a consistent relationship between histopathological features and clinical outcomes has proven elusive, resulting in significant uncertainty surrounding the management of Spitz-type lesions.
Despite the availability of evidence-based guidelines for managing Spitz-type lesions based on dermoscopic properties, the application of these guidelines in clinical practice varies among countries. In the United Kingdom (UK), for example, the National Institute of Clinical Excellence (NICE) has determined that there is insufficient and low-quality evidence regarding the diagnostic reliability and value of dermoscopy, sentinel lymph node biopsy (SLNB), and histological assessment. Consequently, there are no specific guidelines defining the use of these diagnostic modalities in the UK. For tumors excised and found to be ASTs, NICE recommends heavy involvement of a specialist multidisciplinary team (MDT) and advises treating all Spitzoid tumors of uncertain malignant potential as melanomas, acknowledging that some may be overtreated. This lack of definitive universal guidance and the reliance on MDT input contribute to the current heterogeneity of management strategies.
The benefits of establishing unified management guidance for Spitz-type lesions are substantial. Such guidance would ensure that patients receive consistent and evidence-based care and follow-up across different healthcare centers and physicians. It would also reduce uncertainty among healthcare practitioners, enabling them to approach patient care with confidence and allocate resources more effectively.
The absence of consensus in managing Spitz-type lesions can be attributed to the limited evidence available regarding the clinical features and outcomes of affected patients. While several case series have explored patient outcomes after SLNB for atypical Spitzoid tumors, these studies are constrained by small sample sizes. Only two large-scale studies have addressed this topic, both originating from the same institution, with one focusing on a pediatric cohort. Consequently, their findings may not be readily generalizable to populations with differing demographic characteristics.
To address these gaps in knowledge, this study aimed to replicate and expand upon previous findings by conducting a retrospective cohort study. The study focused on assessing the clinical features and outcomes of adult patients diagnosed with Spitz-type lesions at Addenbrooke’s Hospital in Cambridge from January 1991 to December 2020. The goal is to provide additional evidence that supports a more unified approach to managing Spitz-type lesions, addressing the existing uncertainties and heterogeneity in clinical practice.
Methods
The study conducted a thorough search within the database of the Department of Pathology at Addenbrooke’s Hospital, focusing on records from 1990 to 2020. The search criteria involved the term ‘Spitz,’ aiming to identify relevant cases with at least a 5-year follow-up window. This comprehensive search yielded a total of 304 pathology reports generated during the specified timeframe, where the term ‘Spitz’ appeared in various sections, including clinical diagnosis, final pathology diagnosis, or pathology notes and comments.
To ensure the inclusion of unique cases and eliminate duplicates or re-excised specimens, the researchers carefully filtered the records, ultimately identifying 207 distinct cases from different individuals. Subsequently, they embarked on a retrospective review of the electronic medical records associated with these index cases to assess their clinical outcomes.
Among these 207 individual cases, 126 had a confirmed diagnosis of a ‘Spitz’ lesion after the age of 18 and had follow-up information available. The researchers verified demographic details, including birth dates and diagnosis dates, through the electronic medical records. Additionally, they corroborated information regarding sentinel lymph node biopsy (SLNB) and wide local excision (WLE) procedures and examined reports related to non-Spitz-type melanomas.
Since distinguishing between atypical Spitz tumors (ASTs) and malignant melanomas can be challenging, many pathology reports indicated efforts to seek further histopathological opinions through multidisciplinary team (MDT) consultations. Molecular analyses, including techniques such as fluorescence in-situ hybridization, immunohistochemical staining, and next-generation DNA sequencing, were also performed to identify classic melanoma biomarkers such as BRAF and ALK upregulation, as well as p16 and BAP-1 loss. The final diagnoses, based on the collective insights from MDT meetings and molecular assessments, were used to categorize cases for the study’s analysis.
Statistical Analysis
In the study, multivariate logistic regression models were employed to examine the relationships between the type of proliferation and several clinical parameters of interest. These parameters included age, sex, and the anatomical location of the lesions. The analysis was conducted separately for both detailed and grouped categorizations of the lesions’ anatomical locations, which encompassed acral sites, sun-protected areas, and the head and neck region.
For all statistical analyses, a significance level of 0.05 was considered as the threshold for statistical significance. The researchers utilized RStudio software to perform these analyses, ensuring rigorous statistical assessment and evaluation of the data in a medically rigorous manner.
Result
The study examined baseline patient demographics and tumor characteristics in a cohort of individuals with Spitz-type lesions. Among the 126 confirmed cases, 95 occurred in women, and 31 in men, with the majority (65.9%) identifying as white. The average age at diagnosis was approximately 35.74 years, ranging from 18 to 71 years. The median follow-up period for the cohort was 46 months, ranging from 1 to 304 months.
Of these cases, 47.6% were classic Spitz nevi (CSN) or Spitzoid naevi, 9.5% were atypical Spitz tumors (ASTs), 21.4% were Spitzoid melanomas, and 0.8% was a melanoma arising in a previously excised Spitz naevus. The majority of lesions (70%) were located in acral regions, with the thigh/leg being the most common site (34.9%).
The study also revealed that younger age was associated with CSNs/Spitzoid naevi, while older age was associated with Spitzoid melanomas. No statistically significant association was found between patient sex and the anatomical location of the lesion.
Among the patients with ASTs, sentinel lymph node biopsies (SLNBs) were performed on seven individuals, with two cases showing microscopic nodal involvement. Wide local excisions (WLEs) were carried out in all 12 AST cases. While 10 instances showed residual lesions in the excised tissue, no deaths or distant metastases were observed.
In addition, the study identified three cases of invasive melanomas and one melanoma in situ in patients with Spitz-type lesions. All of these melanomas were preceded by CSNs or Spitzoid naevi. Furthermore, there were 34 cases of Spitz-related melanomas, of which 16 underwent SLNB. Two cases had positive SLNB results, with one patient experiencing disease recurrence and undergoing multiple treatments. WLEs were performed in 21 of the 34 individuals with Spitz-related melanomas, and none showed evidence of malignant cells in the tissue samples. Overall, most patients with these lesions were alive without signs of disease at their last follow-up.
Conclusion
This retrospective cohort study focused on 126 adult patients diagnosed with Spitz-type tumors to investigate their long-term clinical outcomes. The cohort included various types of Spitz lesions, including classic Spitz nevi (CSN), Spitzoid naevi, atypical Spitz tumors (ASTs), Spitzoid melanomas, and a melanoma arising in a previously excised Spitzoid naevus.
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