Spitz nevus and atypical spitzoid neoplasm

Spitz nevus (SN) and Spitzoid malignant melanoma (SMM) represent benign and malignant counterparts at both ends of the spectrum of Spitzoid lesions. Atypical Spitzoid neoplasm (ASN) is a poorly defined and characterized category of melanocytic tumors with histologic features of both benign Spitz nevi and malignant melanomas. The group of ASN represents a mixture of Spitz nevi with atypical features and Spitzoid melanomas. However, at the current moment in time, histopathologists are not capable of differentiating between the 2 in some cases and are forced to place them in this ambiguous category, where the behavior of these lesions cannot be predicted with certainty. Because this group encompasses both benign and malignant lesions, and perhaps also a separate category of melanocytic tumors that behave better than conventional melanomas, some of these neoplasms can metastasize and kill patients, whereas others have no metastatic potential, and yet others might only metastasize to regional lymph nodes. Although diagnostic accuracy has improved over the years, many of these lesions remain controversial, and there is still poor interobserver agreement in classifying problematic Spitzoid lesions among experienced dermatopathologists. The objective of this review article is to summarize the most relevant information about SN and ASNs. At this time histologic examination remains the golden standard for diagnosing these melanocytic neoplasms. We therefore concentrate on the histopathologic, clinical, and dermoscopic aspects of these lesions. We also review the most recent advances in immunohistochemical and molecular diagnostics as well as discuss the controversies and dilemma regarding whether to consider sentinel lymph node biopsy for diagnostically ambiguous melanocytic neoplasms.     

Pigmented spindle cell nevus and pigmented Spitz nevus--clinical and histopathological study on pigmented Spitz nevus, and its differentiation from early melanoma by fluorescence method and measurement of 5-S-CD level in the lesion

On the basis of clinical and histopathological studies on 17 patients who had been diagnosed as having pigmented Spitz nevus (PSN), pigmented spindle cell nevus (PSCN) was surmised to be a type of pigmented Spitz nevus. In order to distinguish pigmented spindle cell nevus and pigmented Spitz nevus from early melanoma, 5 PSCN cases and 12 PSN cases were analyzed by the fine-needle aspiration fluorescence method, touch fluorescence method and measurement of the 5-S-CD level in the lesion. With the touch fluorescence method, fluorescent tumor cells were detected in one case of PSN. With the fine-needle aspiration fluorescence method, fluorescent tumor cells were detected in one PSCN case and 2 PSN cases. In comparison with fluorescent melanoma cells, the detected fluorescent tumor cells were smaller in size and number and resembled melanocytes. The 5-S-CD level in the lesion was 50 ng/mg or less in all cases, whereas the level in melanoma is known to be a high 100 ng/mg or more. In the final analysis, measurement of the 5-S-CD level in the lesion was concluded to have the greatest utility for differential diagnosis of pigmented spindle cell nevus and pigmented Spitz nevus from early melanoma.     

结缔组织增生性Spitz痣和色素性梭形细胞痣临床及组织病理学特征

目的:分析结缔组织增生性Spitz痣和色索性梭形细胞痣的临床及组织病理学特点.方法:回顾性分析确诊的8例结缔组织增生性Spitz痣和9例色素性梭形细胞痣患者的临床和组织病理学特征.结果:结缔组织增生性Spitz痣表现为梭形或上皮样痣细胞增生并伴有显著的胶原硬化和均质化,色素性梭形细胞痣表现为真、表皮交界处梭形细胞增生并伴有纤细的色素颗粒沉积.结论:结缔组织增生性Spitz痣和色素性梭形细胞痣是Spitz痣中较少见的特殊类型.其中色素性梭形细胞痣需要与黑素瘤相鉴别.     

Morphologic changes of a pigmented Spitz nevus assessed by dermoscopy

Pigmented Spitz nevus may simulate cutaneous melanoma clinically and histopathologically. In an effort to characterize Spitz nevi using dermoscopy, we documented the dermoscopic features of a single pigmented Spitz nevus over a 6-month period. A 3-year-old boy had a brownish black papule, 3 mm in diameter, on the dorsum of the first finger of his left hand, clinically diagnosed as a Reed nevus. Two follow-up examinations were performed after 3 and 6 months, when the lesion finally was excised for histopathologic examination. Dermoscopically, a globular pattern was recognized during the initial examination, whereas a starburst pattern was identified 3 months later. After 6 months, a variation of the starburst pattern was still detectable. Based on our observation, the globular and the starburst patterns might be considered different morphologic expressions corresponding to the evolutionary phases of pigmented Spitz nevi.     

Spitz Nevus: A Rare Lesion of the Oral Cavity

Pigmented mucosal lesions represent a group of rare entities with different etiopathogenetic origins, histopathologic features, dermoscopic appearances, and clinical course. Solitary pigmented lesions of melanocytic origin are uncommon in the oral mucosa, and intraoral occurrence of Spitz nevus is very rare. Here we present a case of Spitz nevus occurring on the hard palate of a 26‐month‐old boy.     

Nevo de Spitz y otros tumores spitzoides en la infancia. Parte 1: aspectos clínicos,histológicos e inmunohistoquímicos

A Spitz nevus is a melanocytic neoplasm of epithelioid and/or spindle cells that usually appears in childhood. These lesions are by nature benign, but their features can sometimes make them difficult to distinguish from melanomas. Spitzoid melanocytic lesions have been grouped into 3 types in recent decades: Spitz nevi, atypical Spitz tumors, and spitzoid melanomas. Atypical Spitz tumors are spitzoid melanocytic proliferations that have atypical histopathologic features that are insufficient to support a diagnosis of melanoma. The malignant potential of these lesions is at present uncertain. This review examines the clinical, dermoscopic, and histopathologic features of this group of lesions.     

Spitz样肿瘤320例临床及组织病理分析

【摘要】 目的 总结Spitz样肿瘤的临床及组织病理特征。方法 回顾2005年1月至2020年1月西京皮肤医院确诊的320例Spitz样肿瘤患者的临床及病理资料。结果 320例患者中,男141例,女179例,年龄0 ~ 65（12.5 ± 11.7）岁,病程1个月至30年;其中,Spitz痣307例,不典型Spitz肿瘤（AST）8例,Spitz痣样黑素瘤（SM）5例。皮损多为单发,可见于头面部、躯干和四肢,边界均清楚。307例Spitz痣皮损以黑色（132例,43.0%）和红色（108例,35.1%）为主,多数色素均匀（262例,85.3%）且表面平滑（272例,88.6%）。Spitz痣存在特殊临床亚型,11例 （3.6%）发生在斑痣上,11例 （3.6%）呈簇发性,6例（2.0%）播散性,7例（2.3%）结节性,1例（0.3%）为瘢痕疙瘩样。Spitz痣特征性病理表现包括表皮内痣细胞呈Paget样扩散（123例,40.1%）,真表皮交界处出现Kamino小体（74例,24.1%）,痣细胞呈水平带状（177例,57.8%）及楔形分布（118例,38.4%）,痣细胞巢周围出现裂隙（177例,57.8%）,可见生理性核分裂象（117例,38.1%）,核染色质均细腻。根据特殊组织病理表现,Spitz痣又分为色素性上皮样Spitz痣（9例,2.9%）、结缔组织增生性Spitz痣（13例,4.2%）、血管瘤样Spitz痣（8例,2.6%）、疣状Spitz痣（12例,3.9%）、黏液样Spitz痣（10例,3.3%）、晕痣样Spitz痣（4例,1.3%） 等。4例AST皮损为黑色,7例色素均匀,3例皮损表面粗糙;特征病理表现包括细胞均有轻度至中度的异型性,均可见核分裂象（7例为2 ~ 6个/mm2）,5例核染色质粗糙。3例SM皮损呈红色,4例色素不均匀,3例表面粗糙;特征病理表现包括黑素细胞呈Paget样扩散（3例）,瘤细胞呈无极性浸润性生长且均未见成熟现象,均有明显异型性,并可见病理性核分裂象（3例, > 6个/mm2）,核染色质均粗糙且核膜明显着色。结论 Spitz样肿瘤的临床及组织病理表现具有特征性,Spitz痣的临床及病理亚型繁多,AST同时具有Spitz痣和黑素瘤的临床及组织学特征。     

Spitz Nevi and Other Spitzoid Neoplasms in Children: Overview of Incidence Data and Diagnostic Criteria

Spitz nevi are benign melanocytic neoplasms characterized by epithelioid or spindle melanocytes or both. In some rare cases their presentation overlaps with the clinical and histopathologic features of malignant melanoma, so a differential diagnosis can be difficult to make. Intermediate forms between Spitz nevi and malignant melanoma, with unpredictable behavior, have been called atypical Spitz tumors. A literature search was performed to review the clinical, dermoscopic, genetic, and histopathologic aspects of spitzoid tumors. Spitz nevi mainly occur in children, with no predilection for sex, and in young women. Common sites are the head and lower arms, where Spitz nevi present as pink nodules or hyperpigmented plaques. Spitzoid lesions may have diverse dermoscopic patterns: vascular, starburst, globular, atypical, reticular, negative homogeneous, or targetoid. The management of spitzoid lesions can be invasive or conservative; surgical excision is usually reserved for those with doubtful features, whereas clinical and dermoscopic follow‐up is preferred for typical pediatric Spitz nevi. The role of sentinel lymph node biopsy in atypical Spitz tumors is debated. Immunohistochemistry and new molecular techniques such as comparative genomic hybridization, polymerase chain reaction, and fluorescence in situ hybridization offer new diagnostic perspectives, investigating genetic alterations that are specific for malignant melanoma or for Spitz nevi.     

Dermoscopic classification of atypical melanocytic nevi (Clark nevi).

OBJECTIVES: To create a dermoscopic classification of atypical melanocytic nevi (Clark nevi) and to investigate whether individuals bear a predominant type. DESIGN: Digital dermoscopic images of Clark nevi were classified according to structural features, ie, reticular, globular, or homogeneous patterns or combinations of these types. The nevi were also characterized as central hypopigmented or hyperpigmented, eccentric peripheral hypopigmented or hyperpigmented, or multifocal hypopigmented or hyperpigmented. SETTING: Two pigmented skin lesion clinics. PATIENTS: We examined 829 Clark nevi on 23 individuals. MAIN OUTCOME MEASURE: A reliable dermoscopic classification of Clark nevi and frequency of different dermoscopic types. RESULTS: Using the dermoscopic classification, the 829 Clark nevi were classified as follows: 221 (26.7%) as reticular, 167 (20.1%) as reticular-homogeneous, 148 (17.9%) as globular-homogeneous, 112 (13.5%) as reticular-globular, 89 (10.7%) as homogeneous, 84 (10.1%) as globular, and 8 (1.0%) as unclassified. Most individuals were prone to a predominant type of Clark nevus. Seven individuals (30%) showed a single type of Clark nevus in more than 50% of their nevi and 5 (22%) in more than 40% of their nevi. CONCLUSIONS: The proposed dermoscopic classification of Clark nevi is easily applicable and allows a detailed characterization of the different dermoscopic types of Clark nevi. Knowledge of these dermoscopic types should reduce unnecessary surgery for benign melanocytic lesions. Exact classification of the different types of Clark nevi is a necessary prerequisite for further clinical, dermoscopic, and histopathologic studies, which will give new insights in the biology of acquired melanocytic nevi.     

The many faces of blue nevus: a clinicopathologic study

BACKGROUND: In recent years, several histopathologic variants of blue nevus have been identified, whose clinical and dermoscopic correlates need further clarification. METHODS: A comparative evaluation of histopathologic and dermoscopic features was carried out on 52 melanocytic proliferations belonging to the morphologic spectrum of blue nevus. RESULTS: On dermoscopy, all lesions showed a homogeneous, structureless pigment pattern, with a curious variety of colors (blue, white-blue, black, brown, and polychromatic). Histopathologically, the majority of blue lesions were common blue nevi (11/19); the majority of white-blue lesions were 'hypochromic' (sclerotic, hypomelanotic, and amelanotic) blue nevi (17/22); all the black lesions were 'compound' blue nevi (2/2); the majority of brown lesions were combined blue nevi (3/4); the unusual polychromatic dermoscopic appearance was often associated with a histopathologic diagnosis of deep penetrating nevus (2/5). CONCLUSION: A dermoscopic-pathologic approach now allows us to identify 'blue' (common) blue nevi, 'white' (hypochromic) blue nevi, 'black' (compound) blue nevi, 'brown' (combined) blue nevi, and 'polychromatic' (deep penetrating) blue nevi. A better recognition of the many dermoscopic faces of blue nevi is expected to give a morphologic guideline for the clinical management of these lesions.     

Multiple skin metastases of malignant melanoma with unusual clinical and histopathologic features in an immunosuppressed patient

Immunosuppressive regimens may have significant impact on the number of pigmented lesions and the clinical appearance of nevi. Whether immunosuppression can also influence the clinical and histopathologic appearance of malignant melanocytic lesions is still a matter of debate. A patient was immunosuppressed because of heart and bone marrow transplantation. A clinically inconspicuous mole was removed from the left flank and was considered to be a papillomatous nevus. After 1 year, the patient developed multiple pigmented lesions over the entire body, which presented clinically as benign papillomatous nevi and histologically as atypical Spitz nevi. Three months later melanoma metastases were removed from the patient's left axilla, which finally resulted in the death of the patient. Thus, in retrospect, the eruptive pigmented lesions have to be considered as cutaneous melanoma metastases. The atypical clinical and histopathologic appearance of the melanocytic lesions as well as the course of disease may have been influenced by the immunosuppression.     

Dermoscopic features of combined melanocytic nevi

In order to investigate the possible role of dermoscopy in the non-invasive classification of combined nevi, we analyzed dermoscopic features of a series of combined nevi consecutively excised. Two dermatologists expert in dermoscopy retrospectively evaluated all images based on the presence of dermoscopic findings to analyze which epiluminescence microscopy features were more frequently associated with each type of combined nevus. Dermoscopy may provide useful information in the non-invasive diagnosis of combined nevi, allowing a conservative management, but this may be limited to combined nevi including a blue nevus component. Conversely, combined nevi including a Spitz nevus component may be difficult to classify even by dermoscopy, thus requiring careful monitoring or surgical excision.     

Morphologic changes of acquired melanocytic nevi with eccentric foci of hyperpigmentation ("Bolognia sign") assessed by dermoscopy

BACKGROUND: Melanocytic nevi with eccentric foci of hyperpigmentation ("Bolognia sign") can be considered as a melanoma-simulating type of acquired melanocytic nevus. We report on the morphologic changes of this type of melanocytic nevus over a 39-month period of dermoscopic follow-up. OBSERVATIONS: A 5-year-old girl had a 4-mm brown papule with a peripheral blue-black area on her right upper arm. The eccentric focus of the hyperpigmentation corresponded dermoscopically to a blue-gray area of pigmentation associated with irregular brown-black globules or dots and partially with a superficial black network. After 39 months, a globular type of acquired melanocytic nevus was detectable, which clinically and dermoscopically appeared to be completely benign. A nearly identical situation was observed in 5 other melanocytic nevi, underlining the involution of the pigmented foci in these nevi. The histopathologic diagnoses of 2 lesions were consistent with a compound type of acquired melanocytic nevus with eccentric foci of hyperpigmentation. CONCLUSIONS: Dermoscopy allows identification of a morphologic pathway of modifications, probably typical for this type of melanocytic nevus in children, and therefore enables avoidance of surgical excision with attendant hypertrophic scarring in children. Conversely, in adults, when dermoscopic follow-up of melanocytic nevi reveals eccentric foci of hyperpigmentation, surgical excision of the lesion is indicated.     

Reed nevus (pigmented spindle-cell nevus): a report of three cases with distinct dermoscopic patterns

Reed nevus or pigmented spindle-cell nevus may mimic cutaneous melanoma; however, its dermoscopic and histopathological characteristics are different. This case report describes three patients with distinct clinical, dermoscopic and histopathological presentations, which were correlated to enable a differential diagnosis to be made between melanoma and Spitz nevus.     

Epidermolysis bullosa nevus: an exception to the clinical and dermoscopic criteria for melanoma

BACKGROUND: Large acquired melanocytic nevi that occur in patients with epidermolysis bullosa (EB), referred to as EB nevi, may pose a diagnostic challenge because of their clinical and dermoscopic resemblance to melanoma. These unconventional melanocytic nevi have been encountered in all categories of hereditary EB, most of them in childhood. Although some of the reported cases have an alarming clinical appearance that is indistinguishable from melanoma, long-term follow-up has confirmed the benign nature of these rarely encountered melanocytic lesions. The histopathologic patterns of these nevi range from a banal congenital pattern to the problematic persistent pseudomelanoma pattern. OBSERVATION: We describe the clinical, dermoscopic, and histopathologic features of a large EB nevus in a toddler. Clinically, the lesion was markedly asymmetrical and irregularly pigmented with foci of stippled pigmentation and scarring, which easily fulfilled the ABCD criteria for melanoma. Accordingly, a false-positive score resulted when dermoscopy was performed. Histopathologically, a pattern of persistent melanocytic neoplasm was observed. In the following 18 months, dynamic changes of the lesion included near-complete disappearance of the pigment, which was replaced by scar, milia, and areas of healing ulcers. CONCLUSION: Epidermolysis bullosa nevi are dynamic melanocytic lesions that may simulate melanoma.     

Spitz nevus: follow-up study of 8 cases of childhood starburst type and proposal for management

Spitz nevus is an uncommon, benign melanocytic neoplasm that shares many clinical and histological features with melanoma. It presents clinical ambiguity that makes the diagnosis and management of the patient difficult. We present our experience in the management of Spitz nevus by rigorous dermoscopic long-term follow-up of 8 Spitz nevi in patients younger than 12 years. Dermoscopic images, acquired every 6 months, show evolution and modifications of these lesions. The aim of this paper is to better understand the long-term modifications of nevi with starburst pattern to avoid surgical excision of these lesions in the pediatric age group.     

Use of DAPI cytofluorometric analysis of cellular DNA content to differentiate Spitz nevus from malignant melanoma

Cellular DNA content was measured for the purpose of differentiating Spitz nevus from malignant melanoma using the cytofluorometric technique. DNA was stained by 4',6-diamidino-2-phenylindole, and measured by microfluorometer. Among 20 Spitz nevi examined, 18 of them showed a diploid DNA distribution histographic pattern similar to that of acquired pigmented nevi. The other two Spitz nevi had a few polyploid cells with the major population of cells containing diploid DNA content. In contrast, all malignant melanomas showed an aneuploid DNA distribution histographic pattern. The DNA index values of cells from Spitz nevi distributed in the similar range to that of acquired pigmented nevi and separated from those of malignant melanomas distributed in a much higher range. Our results suggest that cytofluorometric analysis of cellular DNA content reflects the biologic behavior more sensitively than do conventional clinical or histologic criteria, and that it serves as a useful aid for the differentiation of Spitz nevus from malignant melanoma.     

Linear arrangement of multiple deep penetrating nevi: report of first case and review of literature

BACKGROUND: Deep penetrating nevus is a recently described variant of melanocytic nevi with clinical and histopathological features that may be confused with malignant melanoma, blue nevus, pigmented Spitz nevus, or congenital melanocytic nevus. We report a case with linear arrangement of multiple deep penetrating nevi. To our knowledge, such presentation has never been reported in the literature. OBSERVATIONS: We describe a patient with multiple darkly pigmented lesions in the right periauricular area, above and behind the ear. The histopathological features of these lesions were consistent with deep penetrating nevus. CONCLUSIONS: To our knowledge, this is the first report of linear arrangement of multiple deep penetrating nevi. We consider this case a unique presentation of deep penetrating nevus.     

Spitz nevus is relatively frequent in adults: a clinico-pathologic study of 247 cases related to patient's age

Spitz nevus is a clinico-pathologic entity that can cause diagnostic concern, particularly in adults. Many studies have been performed to establish reliable histologic criteria, in the attempt to differentiate this lesion from melanoma. A series of 247 Spitz nevi, 6 of which were formerly classified as melanomas, were reviewed for clinical and histopathological parameters. Patients older than 20 comprised 66% of cases, with a predominance of women. The lower extremity was more affected in females of any age, whereas the trunk was more frequently involved in men over 40. Histopathologic examination showed the following differences among Spitz nevi related to age: acanthosis, parakeratosis, pagetoid infiltration, and Kamino bodies were more frequent in young people, whereas multinucleated melanocytes were more frequent in adults. The latter also had lesions that were less pigmented, with less maturation and more desmoplasia. At a mean follow-up of 94 months (range 52-172), recurrence at the site of biopsy or metastases were absent. In our study, a greater proportion of Spitz nevi occurred in adults than in previous series. Moreover, the relative incidence of Spitz nevus compared with melanoma in our population was higher than in other studies. Histopathologic criteria elaborated to diagnose Spitz nevus, applied to our cases, appeared reliable, allowing a correct diagnosis, even in adults.