Spitz Nevus, Spitz Tumor, and Spitzoid Melanoma: A Comprehensive Clinicopathologic Overview

Spitzoid melanoma is very rare tumour in the pediatric population, with clinical and non-uniform behaviour, different from adult melanoma [1]. It can be difficult to differentiate an atypical Spitz nevus from a Spitzoid melanoma, resulting in diagnostic problems. In addition, in our clinical case, the COVID-19pandemiccaused significant delays both in the diagnosis and in the surgical treatment of our patient.

We present the clinical case of a 4-year-old child suffering from a localized polypoid cutaneous neoformation on the dorsum of the left hand, which started immediately before the lockdown and steadily increased during the COVID-19 pandemic. After a general clinical framing, the child underwent an excisional biopsy at our Department of Plastic and Reconstructive Surgery, at the Policlinico of Foggia. Subsequently, two independent anatomic pathology groups examined the specimen. Definitive diagnosis was made only after careful genetic analysis in combination with supporting histological and immunohistochemical examinations.

This clinical case shows how during the pandemic we have been facing advanced forms of tumours, compared to the previous period and highlight show an interdisciplinary and multicenter collaboration allowed a quick diagnosis of certainty, demonstrating the utility of molecular pathology as a fundamental aid in clinical/surgical practice.

The traditional “dichotomic” (benign vs. malignant) approach to the diagnosis of melanocytic skin neoplasms is increasingly becoming less popular. Definitional features for a “gray zone” (in between the benign “white zone” and the malignant “black zone”) are as follows: (1) an “intermediate morphology,” ascribed to either deceptively bland melanomas or morphologically “atypical” but benign nevi; (2) an “intermediate biology,” referred to melanocytic tumors (“melanocytomas”) showing a high rate of regional node involvement but a very low rate of distant metastases. The histopathological report of these tumors should always reflect the diagnostic uncertainty with a “provisional diagnosis” based on the following categories: (1) atypical (junctional/compound/dermal) melanocytic nevus, for a neoplasm that is felt to be most likely benign; (2) severely atypical (junctional/thin compound/thick compound/dermal based) melanocytic proliferation for a neoplasm that is possibly/probably malignant. Recommendations about the management should be set up through a multidisciplinary team meeting.

Familial melanoma and multiple primary melanoma are suggestive of hereditary melanoma predisposition. CDKN2A is the major high-penetrance susceptibility gene to date and germline mutations are identified in 20%–40% of melanoma families, with the frequency varying between different geographical regions. A positive CDKN2A mutation status has been associated with a high number of affected family members, multiple primary melanomas, pancreatic cancer, and early age of melanoma onset. Mutations in the CDK4, BAP1, TET, POT1, ACD, TERF2IP, and MITF genes are rare, overall contributing to explain a further 10% of familial clustering of melanoma. The underlying genetic susceptibility remains indeed unexplained for half of melanoma families. Genetic testing for melanoma in clinical practice is controversial. Patients with hereditary predisposition should be counseled focusing primarily on recommendations on appropriate lifestyle, encouraging skin self-examination and regular dermatological screening. Finally, familial melanoma-associated genes have been also shown to be relevant for other cancers with implications for surveillance in mutation carriers.

Melanoma is the most common malignancy encountered during pregnancy, accounting for 31% of all malignancies diagnosed in pregnant women. In Australia, the crude incidence of pregnancy-associated melanoma increased from 37.1 per 100,000 maternities in 1994 to 51.8 per 100,000 maternities in 2008. No association between women’s parity and melanoma has been reported. Case reports with unfavorable prognosis have been published and still emerge. However, to-date reviews have not been able to conclude whether pregnancy influences the prognosis of melanoma. Within the past couple of years, two large epidemiological cohort studies have been published. The first, from the United Kingdom, reported on a significantly increased risk, while the second one, from Sweden, was not able to document such a correlation.

Melanoma is extremely rare in the pediatric age group, especially in children before puberty. It is reported to be more frequently of the nodular type and amelanotic; however, no clear-cut clinical and dermoscopic features have been described.

One important risk factor is represented by congenital nevi. Giant congenital nevi, in particular, harbor the higher risk of development of melanoma and neurocutaneous melanocytosis, requiring a multidisciplinary approach.

Controversies exist in the diagnosis and treatment of atypical Spitz tumor, a spitzoid melanocytic lesion with uncertain malignant potential.

Staging and follow-up of melanoma in children do not differ from the current practice in adults. No data are currently available about the efficacy of targeted and immunotherapy in melanoma in children. Recent evidence suggests the lack of prognostic value for sentinel lymph node biopsy in atypical Spitz tumors.

Discovery of lymph node or visceral malignant invasion by melanoma cells without clear previous history of cutaneous, ocular, or mucosal melanoma is not an uncommon situation. In such a case the four possible explanations for this phenomenon are the following: neglected or left undiagnosed primary tumor or misdiagnosed primary tumor (Hutchinson’s melanotic whitlow), fully or almost fully regressed primary tumor, metastatic spread from a visceral (occult) primary tumor (eye, sinuses, gastrointestinal tract, meninges, etc.), and hypothetical primary melanoma (in unique) of the lymph node of the affected organ.

The melanoma family encompasses tumors with different clinical characteristics and biological behavior. Several classifications have been proposed, based on clinical features, histopathologic alterations, and different anatomic locations. In the current chapter, the selected classification is clinically oriented, aiming to follow the real scenarios that clinicians are faced with in their everyday practice: (1) conventional melanoma, subclassified into melanoma of the trunk and extremities, face, acral sites, nails, and mucosa; (2) nodular melanoma; and (3) amelanotic melanoma. As a rule, melanoma is characterized by a morphologic asymmetry, which is reflected in its overall shape, border, and color distribution. These characteristics have been summarized in the ABCD clinical rule, whose introduction and dissemination among clinicians terminated the era when melanoma was diagnosed as an ulcerated or bleeding tumor. Melanomas deviating from the ABCD criteria are much more difficult to diagnose and include nodular and amelanotic tumors. Therefore, clinicians should be very careful and lower the threshold for excision when evaluating nodular or amelanotic tumors.

Dermoscopy significantly improves the diagnostic performance of clinicians, both by allowing the detection of clinically inconspicuous melanomas and by enabling the recognition of benign lesions that might look clinically worrisome, reducing, thus, the number of unnecessary excisions. The dermoscopic criteria of melanoma are a result of its asymmetric growth and vary among different subtypes of the disease. The “classic” dermoscopic criteria of melanoma are the following: atypical pigment network, irregular dots/globules, irregular streaks/pseudopods, irregular blotches, regression structures, blue-white veil, and atypical vascular pattern. In clinical practice, the majority of melanomas can be recognized by the presence of at least one of these criteria. However, dermoscopically “featureless” melanomas do exist and include very early tumors, but also nodular and amelanotic melanoma. Therefore, clinicians should be very careful when evaluating nodular and amelanotic lesions. Facial melanoma displays different dermoscopic characteristics and has to be differentiated from pigmented actinic keratosis and solar lentigo. Dermoscopy is useful also for the diagnosis of melanoma of specific anatomic sites including acral, subungual, and mucosal melanoma.

Reflectance confocal microscopy (RCM) is a new noninvasive technique that allows to rapidly explore the skin at nearly histological resolution.

Since its inception, RCM was applied mainly in the field of melanocytic lesions because melanin is the strongest source of contrast for this method.

In skin oncology, RCM stands up as an add-on test for the diagnosis of melanoma being capable of improving the specificity of a narrow-selected population of dermoscopically equivocal lesions.

For clinicopathological purposes, it is still useful to refer to the classification proposed by Clark (the United States) and McGovern (Australia) where categories are identified by the microscopic features of the intraepidermal component of the neoplasm.