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The current classification of Spitz neoplasms in the World Health Organization (WHO), Fourth Edition defines Spitz neoplasms as melanocytic proliferations with characteristic Spitz morphology and a Spitz-associated genomic fusion or HRAS mutation. In contrast, melanocytic neoplasms with BRAF mutations are considered typical of common acquired nevi, dysplastic nevi, and melanomas from intermittent sun-damaged skin. However, increased utilization of ancillary testing methods such as BRAFV600E immunohistochemistry and sequencing studies have made apparent a subgroup of benign-grade and intermediate-grade melanocytic neoplasms with Spitzoid morphology that harbor BRAFV600E mutations. We refer to these cases as BRAF mutated and morphologically Spitzoid (BAMS) nevi and tumors. Two experienced dermatopathologists reviewed a series of 36 BAMS nevi/tumors. Cases in which a diagnosis of melanoma was favored were excluded. The histomorphologic, clinical, and molecular findings were assessed by immunohistochemistry, fluorescence in situ hybridization, and next-generation sequencing using validated gene panels. Characteristics of BAMS nevi/tumors were compared with a control set of Spitz tumors with previously reported fusion proteins. BAMS nevi/tumors had a decreased proportion of Kamino bodies (P=0.03) and a higher proportion of cytoplasmic pigmentation (P

Angiomatoid Spitz nevus (ASN) is a rare histological variant of Spitz nevus (SN) that is characterized by prominent blood vessel proliferation around the intradermal melanocytes of SN. In contrast, SN may have pagetoid components, which are characterized by epidermal proliferation of single melanocytes. However, cases of ASN with predominant pagetoid melanocytic proliferation in the epidermis have not been reported. Here, we report a case of ASN with surrounding pagetoid melanocytic proliferation without formation of tumor nests in the epidermis in the plantar region. A 12-year-old girl presented with a bright red nodule surrounded by a brown macule on the sole of her right foot. Histologically, the nodule showed tumor nests in the dermis, composed of spindle or epithelioid melanocytes containing abundant cytoplasm and large nuclei. Around the nests, numerous blood vessels were seen. In the overlying epidermis of the nodule, numerous eosinophilic Kamino bodies were found along the dermal-epidermal interface. In the macule, proliferation of oval melanocytes was present as single-cell units in the epidermis. Theses melanocytes had abundant cytoplasm with large nuclei, which were larger than those of the surrounding keratinocytes. From these findings, a diagnosis of ASN with surrounding pagetoid melanocytic proliferation was made. Vascular endothelial growth factor and fibroblast growth factor 2 were strongly expressed in the melanocytes as well as in the endothelial cells in our case. Therefore, angiogenic factors produced by the melanocytes of SN might have played important roles in the surrounding angiogenesis of this case.

Background Spitz nevi are benign melanocytic neoplasms that typically present as rapidly growing solitary lesions on the head, neck, or lower extremities. Very rare reports have been described in African Americans. Methods A single-institution 29-year retrospective review of African American patients diagnosed with Spitz nevi was thoroughly analyzed in order to characterize these rare clinical and histopathologic presentations. Results Eleven African Americans with spitzoid lesions were identified. Seven (64%) cases were in pediatric patients and nine (82%) were in females. Most lesions were hyperpigmented (73%) and elevated (82%). Six (55%) were compound Spitz nevi, three (27%) were dermal Spitz nevi, and two (18%) were junctional Spitz nevi. Two lesions had more than one atypical feature. Histopathologically, common features were symmetry, sharp circumscription, pagetoid spread (55%) with most being centrally, predominance of epithelioid cells (64%), Kamino bodies (45%), slight pigmentation (46%), maturation of dermal component with depth, and lack of subcutaneous fat involvement or ulceration. Excision was performed on all patients and there were no recurrences although follow-up was limited. Conclusion Awareness of the possibility and various presentations of Spitz nevi in African Americans will help prevent misdiagnosis.

The histopathologic differentiation between Spitz nevus and melanoma is of particular interest in routine diagnostic procedures of melanocytic tumors. Atypical Spitz nevi are sometimes difficult to distinguish from melanoma. There is still no single criterion that ensures a distinction of melanoma and atypical Spitz nevus. The aim of this study was to reevaluate established and new criteria to differentiate Spitz nevus from melanoma more reliably. We analyzed 25 melanomas with a Breslow index ≥ 1 mm and 18 classical compound Spitz nevi concerning their histopathologic, immunohistochemical and molecular genetic characteristics. Moreover, clinical follow-up data for 5 years were collected. We found statistically significant differences between Spitz nevus and melanoma for the following features: pagetoid spread, atypia, maturation, elastosis, Kamino bodies, p16 expression, and the staining pattern of HMB45. BRAF was positive in 7/21 melanomas and in 1/14 Spitz nevi. Fluorescence in situ hybridization confirmed the histopathologic diagnosis in 36/37 cases. The established clinical, histopathologic, and immunohistochemical criteria to differentiate Spitz nevus and melanoma could be reproduced in our collective. Especially, the expression of p16, BRAF analysis and fluorescence in situ hybridization proved to be helpful tools to improve the differentiation of Spitz nevus and melanoma in our study. Nevertheless, there is-until now-no reliable histopathologic and immunohistochemical parameter which can discriminate Spitz nevus and melanoma with absolute certainty.

A 23-year-old female presented with a reddish-brown dome-shaped hyperkeratotic nodule of 11 × 10 mm on the left lower leg. Dermoscopic examination demonstrated a prominent whitish scaly area with ring-like appearance, pinkish-white structureless areas, a few milia-like cysts, dotted and glomerular vessels, and light brown globules. The lesion was completely excised under the diagnosis of verruca vulgaris or dermatofibroma. Histopathological examination revealed a well-circumscribed symmetric lesion with hyperkeratosis, acanthosis, and pseudohorn cysts. The lesion was composed of spindle-shaped and epithelioid melanocytes with large cytoplasm arranged in confluent nests surrounded by stromal fibrosis. Mitotic figures and Kamino bodies were absent. Moderate proliferation of capillaries was found in the papillary dermis. Immunohistochemical staining with melan-A or S-100 was positive for tumor cells, but the staining with HMB-45 was negative. Melan-A staining was weaker in the deeply situated cells than in the superficial ones, which is known as stratification. Finally, we made a diagnosis of verrucous Spitz nevus based on these findings. We should have been aware of the entity of verrucous Spitz nevus as a variant of Spitz nevus and its dermoscopic features in order to reach a correct diagnosis before excision.

The present study aimed to determine the prevalence of Kamino bodies in Reed nevus, since most studies to date show conflicting data on this issue. This was a retrospective observational study, in which the histopathology of 19 Reed nevus lesions were reviewed. The slides were stained by hematoxylin and eosin and periodic acid-Schiff, with a special focus placed on the identification of Kamino bodies. Some clinical data were also collected. The median patient age was 12 years (range of 2 to 58). The women to men ratio was 5:4. Lesions were located on different parts of the body. Kamino bodies were found in eleven lesions (57.89%). five showed pigmented Kamino bodies (26.31%), four non-pigmented Kamino bodies (21,05%), and 2 (10.52%) had both. Kamino bodies, pigmented or not, are a common histological finding in Reed nevus and may well represent a good marker to differentiate these from malignant melanomas.

Spitz nevus is an infrequent, usually acquired melanocytic nevus composed of epithelioid and/or spindle melanocytes that can occasionally be confused with melanoma. Currently, there are no immunohistochemical markers or molecular biology techniques that can be used to make an entirely safe diagnosis of Spitz nevus or melanoma in problematic cases. A retrospective study has been carried out that included all the cases diagnosed as Spitz nevus from our files. Follow-up information of the patients was unavailable. Three hundred forty-nine cases of unequivocal Spitz nevi were included, and their clinical and histopathological parameters were reviewed. One hundred and forty patients (40%) were 15 years old or younger, with a male to female ratio of 1:1. In patients older than 15 years, there was an evident predominance of women, with a male to female ratio of around 1:3. Spitz nevus was most commonly located on the lower extremities, followed by the trunk in both children and adults. Despite the fact that the head and neck were the third most common location in children, it was a much more frequent location in children than in adults. The constitution by epithelioid and/or spindled cells was the only histopathological finding present in 100% of cases. The other pathological findings studied were, from more to less frequent: maturation (72%), inflammatory infiltrate (70%), epidermal hyperplasia (66%), melanin (50%), telangiectasias (40%), Kamino bodies (34%), desmoplastic stroma (26%), mitosis (23%), pagetoid extension (13%), and hyalinization of the stroma (8%). Hyalinization was the only histopathological parameter that was statistically more frequent in adults than in children.

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.

Spitz nevus is a benign melanocytic lesion and also one of the main differential diagnosis of melanoma. A descriptive and retrospective study of surgical specimens from patients with a diagnosis of Spitz nevus was conducted at two institutions in Niterói - RJ. 32 cases were analyzed. The most frequent histological subtype was compound (60 %), with a predominance of epithelioid cells (17 cases - 53%). Pagetoid spread was observed in 21 cases (68%). Maturation of melanocytes was present in 13 cases (81%). Kamino bodies were found in eight cases (25%). Atypical melanocytes were present in 18 cases (56%). Mitoses were present in 11 cases (34%). Detailed knowledge of the classical form of Spitz nevi is essential for the differential diagnosis with melanoma. However, no single criterium is definitive in the differential diagnosis between Spitz nevus and melanoma.

Spitz naevus is a benign melanocytic lesion that shares many histological features with melanoma. While Spitz naevi characteristically occur in children and young adults and melanomas in the middle-aged and elderly, either tumour can occur in patients of any age. In many cases, the histopathological diagnosis of Spitz naevus is straightforward, particularly in small lesions displaying many or all of the typical histological features and occurring in young patients. Tumours that deviate from the classic description, however, cause difficulties in diagnosis. In this review, we highlight histopathological features of Spitz naevi and those that may be useful in distinguishing Spitz naevi from melanomas. We find that the presence of good symmetry, Kamino bodies, and uniformity of cell nests or sheets from side-to-side favours a Spitz naevus. The presence of abnormal mitoses, a dermal mitotic rate of >2/mm2, and mitotic figures within 0.25 mm of the deep border of the lesion favours a melanoma. Immunohistochemical stains for HMB45 and Ki67 sometimes provide additional useful information. Despite this, in some cases it may not be possible to give an unequivocal diagnosis. Recommendations for the reporting of such cases are provided. New techniques have also demonstrated chromosomal, molecular and genetic differences between Spitz naevi and melanomas. This report highlights these new data and speculates on their possible future role in the diagnosis of borderline lesions.

Eosinophilic globules are commonly found in Spitz nevi and can be of help in the differential diagnosis with melanoma. Despite their use as a diagnostic marker, there are conflicting concepts concerning the mechanism of the formation of these globules. Because pyknotic nuclei are often present in the cells surrounding the globules, many believe that apoptotic cell death of keratinocytes and melanocytes is an important mechanism in their formation. We studied nine Spitz nevi containing 21 eosinophilic globules for apoptotic cell death around and within Kamino bodies using the TUNEL method (TdT-mediated dUTP-x nick end-labeling method). In none of the cases were positive cells seen in the vicinity of the globules. Single apoptotic cells were found only sporadically in the melanocytes of the neoplasms (one to four per section) and were scattered throughout the entire lesion. The absence of apoptosis-specific labeled cells in the vicinity of eosinophilic globules and the rare occurrence of positive stained cells in other parts of the tumors makes apoptotic cell death unlikely to be relevant in the formation of eosinophilic globules.

Of 57 reviewed cases of malignant melanoma in teenagers, 51 had a minimum follow-up of 5 years. The histological and some clinical features of the 51 cases were compared for diagnostic and prognostic significance with those of 19 Spitz naevi and 10 other benign naevi using the SPSS-X computer program. The overall crude survival was 71% (males 64%, females 81%). Five patients with regional metastases survived more than 5 years, three of these more than 10 years. The main statistically significant features associated with a poor prognosis were Breslow thickness, diameter of ulcer, abnormal mitoses, pushing dermal borders and marginal (deep) mitoses. In comparison with Spitz naevi, features favouring malignancy were Breslow thickness, fine dusty cytoplasmic melanin pigment, marginal or abnormal mitoses, epithelioid intra-epidermal melanocytes below parakeratosis, dermal nests larger than junctional nests and the mitotic rate in the papillary dermis. Features favouring a benign lesion were diffuse maturation, spindle cells, spindle nuclei and Kamino bodies, especially if numerous or clustered. In comparison with the atypical benign naevi, significant features favouring malignancy were marginal or abnormal mitoses, single cell epidermal invasion below parakeratosis, large nuclei and irregular nuclei.

Spitz nevus is an uncommon melanocytic nevus distinctive by its epithelioid and spindled melanocytes. Many studies have attempted to characterize Spitz nevus, but none of them in a Hispanic population. Our aim is to characterize the clinical and histopathological presentation of the Spitz nevus in a Hispanic population. A retrospective study was carried out from our files that included those cases histopathologically diagnosed as Spitz nevus. A blinded examination was performed to evaluate the histopathological characteristics of 130 lesions. The demographics of the patients, the anatomic location, and the accuracy of the clinical diagnosis were analyzed. Eighty-one females and 49 males (ratio of 1.7:1) were included in the study. The mean age was 18.8 years. Overall, the most common location was the lower extremities (41%), followed by the upper extremities (27%), trunk (16%), and head and neck (16%). The nevi followed a similar anatomic distribution in females and males. The lesions were clinically diagnosed with accuracy in 20% of the cases and characterized as a pigmented papule in 42% of the cases. Upon histopathological evaluation, most nevi exhibited symmetry (84%), were well circumscribed (91%), and exhibited epidermal hyperplasia (69%). The junctional type was seen in 42% of the cases, the compound type in 38%, and the dermal type in 20%. Sixty-eight percent of nevi were mostly composed of epithelioid melanocytes, the spindled-shaped melanocytes predominated in 17% of cases, and 12% were composed of both epithelioid and spindled-shaped melanocytes. Multinucleated melanocytes were seen in 7% of nevi, mostly in the epithelioid Spitz nevus (67%). Abundant melanin was observed in 51 cases, from which the most common variant was the classic Spitz nevi. The typical dull eosinophilic globules (Kamino bodies) were observed in a minority of the cases (11%), mostly in the classic Spitz nevus. The most common variant was the classic Spitz nevus (65%), followed by the dermal Spitz nevus (15%). In conclusion, Spitz nevus in a Hispanic population most commonly presents as a pigmented papule on the lower extremities irrespective of sex and age. It is characterized by a melanocytic proliferation most commonly composed of nested epithelioid melanocytes in a junctional or compound arrangement, with the presence of abundant melanin.

Background Spitz nevi are benign melanocytic tumors, sometimes misdiagnosed as malignant melanoma (MM). Objective We sought identification of characteristic in vivo microscopic features of Spitz nevi, their histopathologic correlates, and diagnostic usefulness. Methods Forty Spitz nevi were studied by in vivo confocal microscopy and dermatoscopy, evaluating histopathologic correlates, and compared with 40 MMs and 40 Clark nevi. Results Some histologic aspects characteristic for Spitz nevus diagnosis were correlated with confocal features, comprising some that can be useful for atypical Spitz nevus classification. The most striking features for differentiating Spitz nevi from MMs were the presence of sharp border cut-off, junctional nests, and melanophages. Limitations No correlates were found for other aspects, such as Kamino bodies, hyperkeratosis, acanthosis, mitoses, and maturation with depth. The impossibility of exploring deeper aspects hampered an accurate distinction from MMs in some cases. Conclusion Confocal and dermatoscopic examination enabled the identification of different Spitz categories with different histologic substrates.

A 6-year-old girl was seen for a mole that had been present for 2 years on the extensor surface of her left knee. It had darkened in color and increased in size during the preceding 6 months. Physical examination revealeda symmetrical 4-mm brown-black nodule with slight variegation of color (figure I ) . The lesion was excised. Histopathologic examination showed an acanthotic epidermis with epithelioid melanocytes forming nests of various sizes and minor variation in nuclear size and chromatin pattern. Focal Kamino bodies, rare mitoses, telangiectasias, and scattered melanophages were also identified in the specimen (figures 2 and 3). The lesion appeared to be completely excised with a narrow lateral margin. Initially, both malignant melanoma and Spitz nevus were considered by the pathologist. After a second opinion was obtained, a diagnosis of pigmented Spitz nevus was made.

Because of the well-known difficulty in distinguishing between Spitz nevi and spitzoid malignant melanomas at the microscopic level, the critical importance of this task notwithstanding, expert dermato pathologists across the world have strenuously endeavored to identify histopathologic criteria that would assist microscopists in this effort. Many reports itemizing such criteria are extant. The objective of the current study was to determine which of these criteria serve as the most consistent discriminators. Using a population of 11 spitzoid melanomas and 12 Spitz nevi, we evaulated six sets of criteria purported to be helpful in differentiating between these entities. Overall, we found that six features had significant distinguishing capacity, namely, (1) Kamino bodies, (2) a brisk mitotic rate, (3) mitoses close to the base of the lesion, (4) abnormal mitoses, (5) symmetry, and (6) uniformity of nests from side to side. It is noteworthy that the first three of these rank among the six criteria itemized repeatedly in 50% or more of the sets of criteria evaluated.

A 22-year-old man presented with a pigmented lesion on the glans penis, which had occurred 6 years previously and had been slowly growing in size. Physical examination showed a dome-shaped dark brown nodule, 9 mm in diameter, with a pinkish erythema in the centre of the glans penis (Fig. 1). An excision biopsy was made, and histological examination of a magnified portion of the upper dermis revealed spindle cells grouped within demarcated nests and epithelioid cells grouped within poorly demarcated nests (Fig. 2). The tumour cells were relatively uniform in size and showed no atypia. Eosinophilic globules at the dermal – epidermal junction, Kamino bodies, were observed. Immunohistochemical analysis demonstrated that the cytoplasm of the tumour cells was positive for S-100 protein, but not for HMB-45 (Dako Cytomation, Kyoto, Japan). Only 0.2% of tumour cells were positive for Ki-67 (MIB-1, Dako Cytomation) and proliferating cell nuclear antigen (PC10, Dako Cytomation). These findings strongly suggested that the tumour was a Spitz naevus (1). Over the 2 years and 5 months since the excision, there has been no sign of any recurrence.

A 21-year-old student of sports science presented with a 12-month history of a painful nodule on the sole of her left foot, which severely constrained her sporting activities. She was otherwise well. On examination there was a bluish pink 7-mm nodule on the arch of her left foot (Fig. 1). It was firm, exquisitely tender and she walked with a slight limp. The lesion was curetted and sent for histological diagnosis. The specimen showed a symmetrical wedge-shaped compound melanocytic lesion reaching the margins of the biopsy. The overlying epidermis was acanthotic and hyperkeratotic. Junctional nests were present and there was clefting between them and the epidermis (Fig. 2). Near the nests were eosinophilic globules (Kamino bodies) and pigment-laden macrophages. The lesion consisted of a mixture of large spindle and epithelioid cells with abundant eosinophilic cytoplasm and plump nuclei with prominent nucleoli. There were a few mitoses but none was atypical. Single epithelioid melanocytes were present deep within the lesion (outlier cells) and there was maturation with depth in the dermis. The histological features were those of Spitz naevus. There was significant reduction in the severity of her pain after curettage but the pain subsequently recurred. In view of this and possible incomplete excision, the scar was re-excised with a narrow margin. Histology confirmed complete excision of the residual naevus. Her symptoms have since subsided.

An 11 -year-old black girl presented with a nodule at the tip of the left thumb that eroded the underlying tip of the distal phalanx. The tumor was composed of junctional nests and uniform atypical spindle melanocytes that formed broad fascicles and diffusely permeated the dermis. Scattered collections of Kamino bodies were present. A single enlarged left axillary lymph node was noted 9 months after the initial presentation. The lymph node measured 7 × 4.5 × 2.5 cm and was replaced by metastatic tumor composed of fascicles of spindle melanocytes. Immunohistochemical examination demonstrated immunoreactivity for SI 00, HMB45, and Leu 7, and ultrastructural examination revealed the presence of premelanosomes in the primary and metastatic tumors. Now, more than 10 years since her initial presentation, the patient is well with no further manifestation of the disease.

A 25-year-old man presented with a 1-year history of a small nodule on the right cheek. The nodule presented as an illdefined, reddish lesion, with a diameter of 5 mm (Figure 1). The nodule was excised and subjected to pathological examination, which revealed pleomorphic spindle and epithelioid cells infiltrating dermal collagen bundles. These cells showed discernible downward maturation (Figure 2). Microscopic examination under a high-power field showed nuclear enlargement, pleomorphism, and indistinct mitotic figures. Foci of Kamino bodies and scattered melanin deposition were detected in the papillary dermis. Immunohistochemical analysis showed that the tumor cells had increased cytoplasmic expression of anti-melan-A, HMB-45, and CD68, and that these cells were negative for the expression of CD34 and epithelial membrane antigen (Figure 2). Immunoreactivity to Ki-67 antibody was scored as less than 2% positive cells. Total excision of the lesion was then performed, and no recurrence was noted during follow-ups at our clinic approximately half a year later.