Dermatology: Practical and Conceptual Editorial | Dermatol Pract Concept 2015;5(1):6 45 DERMATOLOGY PRACTICAL & CONCEPTUAL www.derm101.com Introduction The clinicopathologic classification, diagnosis, and manage- ment of Spitzoid melanocytic lesions is one of the most prob- lematic topics in dermato-oncology and dermatopathology. After earlier anecdotal reports [1,2], the controversial history of these controversial lesions began in 1948 when Sophie Spitz described 13 cases of what she called “juvenile mela- noma,” underlining its presumably good prognosis because only one case of her series had proven fatal [3]. During the following forty years, however, the entity described by Sophie Spitz was thought to be completely benign, with metastasiz- ing cases being intuitively considered as cases of melanomas simulating Spitz nevus (Spitzoid melanoma) [4]. In 1989, Smith and co-worker described the so-called “Spitz nevus with atypia and metastasis” or “malignant Spitz nevus,” i.e., a kind of lesion showing histopathologic features not enough for a diagnosis of malignancy, yet capable of nodal metastasis, usually with no further dissemination [5]. This apparently contradictory concept was then set forth by Barnhill with the diagnostic category of “metastasizing Spitz tumor” [6], or “atypical Spitz nevus/tumor” [7]. To date, while some opinion leaders maintain that there are only two diagnostic categories (nevus and melanoma) and that every “abnormal” behavior is simply a diagnostic mistake [8], some others suggest that Spitzoid lesions are indeed a “morpho-biologic spectrum” of lesions ranging from benignity to full-blown malignancy [9], and sharing a peculiar genetic profile, with chromosome rearrangements involving kinase fusions [10]. Intermediate lesions within such a spectrum eventually show: i) an equivocal histomorphology, featuring a diagnostic agreement among experts which is consistently lower than for “conventional” (non-Spitzoid) melanocytic neo- plasms [7,11]; ii) peculiar clinical features and behavior with a relatively high incidence in prepubescent patients [12] and a higher incidence of regional (sentinel) node involvement [13] but a better prognosis than “conventional” (non-Spitzoid) melanoma of the same thickness/stage [14] (possible low- grade malignancies [11]). Hypopigmented atypical Spitzoid neoplasms (atypical Spitz nevi, atypical Spitz tumors, Spitzoid melanoma): a clinicopathological update Gerardo Ferrara1, Stefano Cavicchini2, Maria Teresa Corradin3 1 Department of Oncology, Anatomic Pathology Unit, Gaetano Rummo Hospital, Benevento, Italy 2 Dermatology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore, Milan, Italy 3 Department of Dermatology, Santa Maria degli Angeli Hospital, Pordonenone, Italy Key words: Spitz nevus, Spitz tumors, Spitz melanoma, dermoscopy, histopathology Citation: Ferrara G, Cavicchini S, Corradin MT. Hypopigmented atypical Spitzoid neoplasms (atypical Spitz nevi, atypical Spitz tumors, Spitzoid melanoma): a clinicopathological update. Dermatol Pract Concept 2015;5(1):6. doi: 10.5826/dpc.050106 Received: September 2, 2014; Accepted: October 5, 2014; Published: January 30, 2015 Copyright: ©2015 Ferrara et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: None. Competing interests: The authors have no conflicts of interest to disclose. All authors have contributed significantly to this publication. Corresponding author: Gerardo Ferrara, MD, Department of Oncology, Anatomic Pathology Unit, Gaetano Rummo Hospital, Via dell’Angelo 1, I-82100 Benevento, Italy. Email: gerardo.ferrara@libero.it 46 Editorial | Dermatol Pract Concept 2015;5(1):6 We have already pointed out that dermoscopy seems to allow clinicians to increasingly identify and excise pigmented spindle cell Spitz nevus and Reed nevus (which are basically the same clinicopathological entity), to such an extent that the brown-black plaque-like “variant” is surprisingly becom- ing the most common (and therefore “typical”) Spitz nevus encountered in clinico-dermoscopic-pathologic studies [15- 17]. The present paper will focus on the clinicopathological features of papulonodular hypopigmented Spitzoid lesions, which are “atypical” with a much greater frequency than their plaque-like heavily pigmented counterpart [16,17]. The proposed classification systems for Spitzoid neoplasms The dermatopathologist’s mission is to provide an accurate, specific, and comprehensive diagnosis, thereby enabling the clinician to estimate the prognosis and develop the optimal plan of treatment and follow up for any single patient. There is little doubt that the simple designation “benign” vs “malignant” provides the clinician with all of the necessary information for the patients’ care. A. Bernard Ackerman taught us that each pigmented lesion may have only three diagnoses: “melanoma,” “nevus” or “I don’t know,” with the “I don’t know” cases to be referred to an expert who will be finally able to place them into either of the first two entities. According to this view, the adjective “atypical” is redundant and useless, because any Spitz nevus is “atypical” by definition; nevertheless, it can be differentiated from its malignant simulator (i.e., Spitzoid melanoma) according to a well defined set of histologic criteria; every Spitzoid (and non-Spitzoid) melanocytic proliferation behaves as either a benign or a malignant neoplasm which we can be unable to correctly categorize simply because our brain can fail to cor- rectly apply the diagnostic criteria [8]. A.B. Ackerman’s approach delivers a clear-cut message to the clinicians; nevertheless, it carries at least two major problems, which are still waiting to be overcome. The first problem is purely morphologic: by assuming that Spitz nevus is a simulator of melanoma (Spitz nevus as a pseudo- malignancy) and that melanoma resembling Spitz nevus is a simulator of its simulator (Spitzoid melanoma as a pseudo- pseudomalignancy), it is not surprising that the diagnosis of such lesions is a quandary even among experts who may be indeed unable to place an “I don’t know” lesion into a either “nevus” or “melanoma” category [7,11,18]. The second problem with A.B. Ackerman’s approach is biological. A tutorial held in Graz, Austria, in 2008 evaluated 57 melanocytic tumors of uncertain malignant potential, 35 of which being thick Spitzoid neoplasms: a panel of expert was unable to differentiate cases with favourable and unfa- vourable behaviour on morphologic grounds; therefore, it was concluded that the cases were all malignant, albeit clearly different from “conventional” melanoma because of a great thickness associated with a relatively low metastatic rate [18]. Because of all these uncertainties and under medicolegal pressure, a dichotomic “benign vs malignant” approach unavoidably leads to a frequent overdiagnosis of melanoma or, else, to the cautious suggestion of a management as per melanoma for lesions that, even if malignant, are biologically different from “conventional” melanoma. These reasons led Barnhill to set forth a three-tiered clas- sification system by assuming an “intermediate” category (“atypical Spitz nevus/tumor”) between Spitz nevus and melanoma [6,7]. Within Barnhill’s “intermediate” category, the risk of malignancy of each lesion was considered as alleg- edly proportional to its “deviance” from the conventional stereotype of the Spitz nevus. As an extreme consequence of this view, in 2006 Barnhill proposed that every Spitzoid lesion could be actually clas- sified “intermediate” and thereby designated as “tumor” (without or with atypical features) [19]: more explicitly, all Spitzoid lesions could be virtually “non-benign,” with the new dichotomic approach thus being “tumor vs melanoma.” The message to the clinician, which stems from Barnhill’s approach is that basically all Spitzoid lesions represent a harmful occurrence, and in our opinion, this is too much. In keeping with the concept of Spitzoid neoplasms as a morpho-biological spectrum, we have adopted a four-tiered classification system proposed by Da Forno [20] and encom- passing: i) Spitz nevus; ii) atypical Spitz nevus; iii) (atypical) Spitz tumor; iv) Spitzoid melanoma [17]. The histopathologic criteria for the differential diagnosis between the two “inter- mediate” categories of the spectrum—atypical Spitz nevus and Spitz tumor—are provided in Table 1. Briefly, a Spitz tumor is—by definition—“tumorigenic,” i.e., it is character- ized by a nodular silhouette made by confluent sheets of cells in the dermis without intervening collagen, and/or (non- traumatic) ulceration, and/or relevant mitotic activity [17]. The decision-making process following a diagnosis based on our classification system is itemized in the “Guidelines for management” section. An algorithm for the clinical diagnosis of Spitzoid neoplasms It is commonly said that Spitz nevus can show all the “local” dermoscopic features of melanoma, but in a more or less tidy fashion [15,17]. The occurrence of an atypical (melanoma- like) dermoscopic pattern in Spitz nevus is also possible. However, the relationship between dermoscopic and histo- pathologic atypia is not absolute, inasmuch as dermoscopi- cally atypical lesions are not necessarily histopathologically atypical as well; conversely, it is well known that amelanotic Editorial | Dermatol Pract Concept 2015;5(1):6 47 melanoma can show a tidy (“Spitz nevus-like”) dermoscopic appearance [21]. Since a fully reliable clinico-dermoscopic distinction between Spitz nevus and melanoma is not possible, surgi- cal excision is warranted for all lesions with Spitzoid fea- tures. There is, however, a remarkable exception to this rule: since in pre-puberty Spitz nevus is relatively common [12] whereas melanoma is exceedingly rare [22], a Spitzoid lesion in patients younger than 12 years can be managed conser- vatively unless it stands as atypical on clinical and/or on dermoscopic grounds, either at the baseline or during follow up [12]. For the above, the clinical evaluation of such lesions can be accomplished according to the following algorithm: 1. Recognition of a Spitzoid melanocytic lesion on dermos- copy: this is enough to warrant surgical excision after puberty. 2. Recognition of atypical clinicodermoscopic features in a Spitzoid melanocytic lesion: this is the threshold for surgi- cal excision in prepubescent patients. 3. Recognition of atypical clinicodermoscopic features dur- ing follow up of a Spitzoid melanocytic lesion in prepu- bescent patients. The following sections will focus on hypopigmented Spitzoid lesions; nevertheless, the above-specified algorithm must be implemented for all Spitzoid lesions, irrespective of the amount of their pigmentation. Recognition of a hypopigmented Spitzoid lesion A hypopigmented Spitzoid melanocytic neoplasm can be typi- fied by at least one of the following: 1. Homogeneous pink color: sometimes associated with a brownish hue or remnant(s) of brown pigmentation. 2. Dotted vascular pattern: short capillary loops visible as pinpoint dots, best appreciated with non-contact dermos- copy. 3. “Starburst” vascular pattern: long centrifugal capillary loops visible as regular lines radiating toward the periph- ery of the lesion, easier to be observed with non-contact dermoscopy. 4. Reticular depigmentation: a grid of whitish areas delineat- ing pink (homogeneous or “dotted”) areas representing the holes of the net. 5. Chrystalline (chrysalis-like) structures (with polarized dermoscopy only): a variation on the theme of reticular depigmentation, featuring white shiny parallel or orthogo- nal or disordered linear streaks or short lines which can be seen only with polarized light dermoscopy. These features can consistently help the clinical differ- ential diagnosis with hypopigmented Clark nevus, pyogenic granuloma, juvenile xanthogranuloma, molluscum contagio- sum, and viral wart. Any single above-listed feature can be seen also in mela- noma. Symmetric and plaque-like or slightly raised (dome- TABLE 1. Proposed histopathologic criteria for the differential diagnosis be- tween atypical Spitz nevus and Spitz tumor (Copyright: ©2015 Ferrara et al.) Microscopic features Atypical Spitz nevus Atypical Spitz tumor Size 7-10 mm >10 mm Tumorigenicity (nodule) - + Asymmetry Superficial Deep +/- superficial Sharp circumscription, intraepidermal +/- +/- Sharp circumscription, lateral dermal - -/+ Sharp circumscription, deep dermal - +/++ Epidermal atrophy -/+ +/++ Ulceration - -/+ Large dermal nests Superficial Deep +/- superficial Dermal sheets of cells - +/++ Deep extension - + Melanin in the depth - -/+ Cytologic atypia Focal (‘random’) Widespread Maturation + - Mitotic figures Few Numerous and/or close to the base 48 Editorial | Dermatol Pract Concept 2015;5(1):6 TABLE 2. Histomorphologic criteria for metastasizing atypical Spitz nevi/tumors (Urso, 2005 [23]) with their clinico-dermoscop- ic correlates (Copyright: ©2015 Ferrara et al.) Histopathologic Features Clinico-Dermoscopic Correlates Expansile dermal nodule (Large) nodule Deep extension (Large) nodule Deep mitoses Nodule Abundant melanin in depth Gray-blue or pink color Great nuclear pleomorphism No correlate Asymmetry Asymmetry (when superficial) Necrosis No correlate Epidermal atrophy Prominent vascular pattern, ulceration Cells within the lymph vessels No correlate shaped) cutaneous lesions showing these dermoscopic features in a tidy fashion are most commonly Spitz nevi; never- theless, a histopathologically atypical Spitzoid proliferation can be dermo- scopically quite tidy and symmetric (Figure 1), thereby underlining once again the need to excise all lesions with Spitzoid features after puberty. Recognition of atypical clinico dermoscopic features in a Spitzoid melanocytic lesion This topic is of paramount importance in prepubescent patients. In 2005, Urso [23] performed a review of 19 papers reporting 62 Spitzoid neoplasms show- Figure 1. A lesion of the right thigh in a 22-year-old woman. The lesion is clinically (A, inset) reddish and sharply circumscribed; on dermoscopy (A) its main feature is reticular depigmen- tation, which is associated with regularly distributed light brown dots/globules. Overall, the lesion is very symmetric. Nevertheless, it is slightly atypical histopathologically. The silhou- ette is dome-shaped, with a sharp lateral circumscription (B) but also with a central exag- gerated confluence of nests within the superficial dermis (C) at this level, cytomorphology is very bland and monomorphic, with no mitotic figure (D). Histopathological diagnosis: Spitz nevus according to Ackerman’s classification [8]; Spitz tumor with atypical features accord- ing to Barnhill’s classification, 2006 [19]. Our histopathological diagnosis was atypical com- pound Spitz nevus and a narrow re-excision was advised. (Copyright: ©2015 Ferrara et al.) ing an aggressive biological behavior in spite of histopathologic features not enough for a diagnosis of clear-cut malignancy. Nine criteria were thus found to be predictive of metastatic potential: notably, such criteria were not the very same as for “conventional” melanoma and, most important, they had to be used in a completely different manner, because even the presence of one criterion could be virtually incom- patible with benignity. Urso’s [23] crite- ria are listed in Table 2, along with their expected clinico-dermoscopic counter- part. By accepting Urso’s approach [23], atypical (possibly malignant) Spitzoid neoplasms are most often: A. Large, commonly >7 mm in diameter; B. Nodular: more or less irregularly raised, palpable, firm, sometimes polypoid and/or ulcerated; C. Hypo-amelanotic: pink-reddish in color, with a nondescript or, else, with a prominent and/or polymor- phous vascular pattern. The above listed features have been sum- marized in the clinicopathologic defini- tion “red Spitz tumors,” as opposite to the “blue Spitz tumors” [12], the latter histopathologically corresponding to epi- thelioid (Spitzoid) proliferations inter- mingled with heavily pigmented den- dritic melanocytes (so-called “pigmented epithelioid melanocytomas” [24]). The two cases of red Spitz tumors shown in Figure 2 demonstrate that such lesions sometimes disclose unspecific dermo- scopic features with a clinical picture which is, however, definitely worrisome. The unique banal cutaneous lesion, which cannot be differentiated from a red Spitz tumor on the basis of der- moscopy, is pyogenic granuloma: this is the reason why always submit to his- topathologic examination the curetted material of any pyogenic granuloma look-alike lesion. The quality of the vas- cular pattern is of paramount impor- tance for the differential diagnosis of “red Spitz tumors” from more common and banal lesions, such as viral warts (Figure 3) and molluscum contagiosum (Figure 4). In our experience, a diagno- Editorial | Dermatol Pract Concept 2015;5(1):6 49 Figure 3. A dome-shaped red lesion with a light verrucous surface (A) located on the back in a 7-year-old girl. Dermoscopy (B) suggests that the lesion is probably not a vi- ral wart, because of the presence of a thick reticular depigmentation surrounding linear irregular vessels; some small white scales and a peripheral light brown symmetric pig- mentation are visible as well. Histopatho- logically, the lesion is very atypical, with an asymmetric involvement of the epidermis (C, arrow) and a deep dermal component made by epitheloid (spitzoid) cells with a confluent pleomorphomism and a larger size than the overlying melanocytes (D). Histopathologi- cal diagnosis: Spitzoid melanoma, according to Ackerman’s classification [8]; Spitz tumor with atypical features, according to Banhill’s classification, 2006 [19]. Our histopathologi- cal diagnosis was (atypical) Spitz tumor. In this case, a sentinel node biopsy disclosed few parenchymal aggregates of pleomorphic melanocytes; no completion lymph node dissection was performed. The patient is alive with no evi- dence of disease after six years. (Copyright: ©2015 Ferrara et al.) sis of Spitz nevus in the presence of a polymorphous vascular pattern must be made only under a compelling histo- pathological evidence of benignity; we have also suggested that when a given Spitzoid lesion is histopathologically atypical but its “grading” is uncertain, the presence of a highly atypical vas- cular pattern could point toward its management as a “tumor” instead of an “atypical nevus” [17]. Recognition of atypical clinico dermoscopic features during follow- up of a Spitzoid melanocytic lesion in prepubescent patients. Dermoscopic monitoring of Spitzoid proliferations can be recommended only for plaque-like or dome-shaped dermoscopically symmetric lesions before puberty [12]: the suggested pro- tocol is based on clinico-dermoscopic controls every three to six months [25]. A completely benign hypopigmented lesion is expected to enlarge, even very rapidly but always very symmetrically, and then to slowly involute, either completely [26] or up to a “dermal nevus-like” homogeneous light brown pattern [27,28]. Abnormal dermo- Figure 2. Two examples of “red tumors” which are not easily recognizable as “Spit- zoid” on clinicodermoscopic grounds. On the top, a multinodular polypoid neoplasm of the external ear (A) in a 9-year-old boy. The neoplasm is dermoscopically typified by a prominent ad atypical vascular pat- tern (diffuse reddish areas, dotted vessels, peripheral thick linear irregular vessels); a few light brown areas are also visible and can dermoscopically suggest that this highly atypical lesion is melanocytic (B). On the bottom, a raised multinodular pink-reddish lesion of the buttock (C) in an 11-year-old boy; dermoscopy (D) shows whitish-pink lobules with a polymorphous vascular pat- tern (diffuse pink-red areas, thin and elon- gated linear-irregular vessels, hairpin ves- sels), peripheral white globules, and light brown structureless areas. Also in this case dermoscopy discloses remnants of pigmenta- tion, which are not clinically evident and, again, can suggest that the lesion is melanocytic. In both cases our histopathological diagnosis was (atypical) Spitz tumor. (Copyright: ©2015 Ferrara et al.) 50 Editorial | Dermatol Pract Concept 2015;5(1):6 scopic digital follow up findings (an example is given in Figure 5) include: A. Asymmetric growth B. Nodular/polypoid growth C. Ulceration D. Increased atypia in the vascular pattern. Any of the above features warrant immediate surgical excision. Spitzoid melanoma: a clinicopathological reassessment While adult Spitzoid melanoma is often clinically and der- moscopically indistingiuishable from “conventional” mela- noma, pediatric Spitzoid melanoma shows very peculiar clinicopathologic features. Histopathologically, it differs from atypical Spitz nevus or Spitz tumor by showing a non-Spitzoid cytomorphologic clone arising in the context of a Spitzoid lesion. Such a highly unusual occurrence can be detected even clinically and dermoscopically. In Figure 6 the “clone” is the red nodule with a nondescript vascular pattern; the nodule was initially treated as per pyogenic granuloma, but histopathologically disclosed a highly atypical proliferation of pleomorphic epithelioid cells. On the excision specimen, the “shoulder” of the neoplasm disclosed a bland morphology, featuring monomorphic spindle cells, probably representing a benign background (Spitz nevus) in which Spitzoid melanoma had been developing. Based on the very few exceptional cases we have seen, pediatric Spitzoid melanoma is a malignancy Figure 4. A melanocytic neoplasm removed from the forearm of a 10-yr-old girl. Clini- cally (A) the lesion is firm red nodule with a central depression. Dermoscopically (B), a central yellow crust could resemble the umbilication of a molluscum contagiosum; however, vessels around the crust are atypi- cal; in addition there is a peripheral reddish area with dotted vessels which suggest that the lesion is melanocytic. Histopathologi- cally the neoplasm is strikingly cellular and focally eroded with large dermal sheets of cells (C); several mitotic figures (D; arrows) are detected in the mid-dermal component. Histopathological diagnosis: melanoma ac- cording to Ackerman’s classification [8]; Spitz tumor with atypical features according to Barnhill’s classification, 2006 [19]. Our histopathological diagnosis was (atypical) Spitz tumor. Histologic images kindly pro- vided by Prof. Raffaele Gianotti, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy. (Copyright: ©2015 Ferrara et al.) Figure 5. Dermoscopic digital monitoring of a red lesion of the arm in a melanocytic lesion of the leg in a 5-year-old girl. At the baseline (A), the lesion is typified by a quite symmetri- cal ‘starburst’ vascular pattern associated with a reticula depigmentation; rare coiled vessels are also present. After 17 months (B), there is evidence of early nodular growth in the cen- tral area, which appears homogeneous pink- ish-red with some dotted vessels and thin lin- ear vessels. A brownish peripheral hue is also evident. Histopathologically, the silhouette is nodular (C), with wide areas of epidermal atrophy (D) and crops of dermal mitotic fig- ures (E; arrows). Histopathological diagnosis: melanoma according to Ackerman’s classifica- tion [8]; Spitz tumor with atypical features ac- cording to Barnhill’s classification, 2006 [19]. Our histopathologic diagnosis was (atypical) Spitz tumor. (Copyright: ©2015 Ferrara et al.) Editorial | Dermatol Pract Concept 2015;5(1):6 51 arising in the background of a Spitz nevus [17], just like already suggested for melanoma arising in Spitz tumor [29]. Guidelines for management Surgical excision is recommended for all lesions with Spitzoid dermoscopic features detected after puberty. Before puberty, plaque-like or dome-shaped dermoscopically symmetric lesions with Spitzoid features can undergo dermoscopic digital monitoring [12]. Large (>1cm), nodular, ulcerated, rapidly growing/changing, or otherwise atypical Spitz nevi of the childhood must be excised. The management of patients with a histopathologic diagnosis of atypical Spitz nevus and Spitz tumor should be decided with a multidisciplinary approach and on an informed consent basis. A narrow re-excision can be consid- ered for atypical Spitz nevi and must be recommended for all incompletely excised lesions, as well as for Spitz tumors. The opportunity of a sentinel node biopsy for Spitz tumors should be evaluated case by case. The decision must be made by preliminarily considering that in Spitz tumors the pres- ence of isolated tumor cells in the sentinel node is not an unequivocal sign of malignancy [30,31] and is not an indica- tion to completion lymphadenectomy, based on the ambiguity of the primary. It must be also underlined that, in a recent meta-analysis, 98-99% of young patients with Spitz tumors had no evidence of disease after a median follow-up of 59 months, regardless the sentinel node positivity [14]; therefore, the diagnostic and prognostic information given by a positive sentinel node in young patients seems to be negligible. If this is true, an echotomographic monitoring of the regional nodes (and an echotomography-guided fine needle aspiration biopsy cytology) can even replace sentinel node biopsy, because it allows to efficiently detect massive replace- ment of the node(s) by neoplastic cells, thereby addressing selected patients to election lymphadenectomy [31]. Such a fol- low up protocol is probably the best choice in patients younger than 10 years, especially for lesions located in the head/neck area, a region in which surgical procedures are aesthetically relevant and are hampered by a sizable failure rate [32]. The prognosis of Spitz tumors is age-dependent [33]. Adult patients, who are expected to be at greater risk, could be managed more aggressively. The risk stratification for atypical Spitzoid melanocytic proliferations has been recently addressed with the use of a new four-probe fluorescence in- situ hybridization (FISH) assay for 6p25 (RREB1), 11q13 (CCND1), 9p21 (CDKN2a), and 8q24 (MYC) [34]. The following categories have been individuated: i) Spitzoid mela- noma with homozygous 9p21 deletion (high risk); ii) Spitzoid melanoma with 6p25 and/or11q13 gain (intermediate to high risk); iii) atypical Spitz tumor with isolated 6q23 deletion (low risk); iv) atypical Spitz tumor with no FISH abnormality (low to very low risk). So far, the number of investigated cases is too low to validate the above-detailed risk stratification system. However, the use of FISH techniques for prognos- tic—rather than for diagnostic—purposes seems to be a very promising tool. In adult patients, cases of Spitz tumor with homozygous deletion of 9p21, best evaluated using a dual color FISH test targeting CDKN2a (SpectrumOrange) and Cep9 (SpectrumGreen), might be managed as per melanoma. Figure 6. An atypical neoplasm of the face in an 11-year-old girl. Dermoscopically (A) the lesion is biphasic: a flat portion shows reticu- lar depigmentation along with structureless and globular brown areas; a nodular area discloses a non-descript vascular pattern, fea- turing a diffuse reddish area. The lesion was clinically diagnosed as a pyogenic granuloma associated with a Spitz nevus. For aesthetic reasons, the nodular portion was thus curet- ted. Histopathologically, the nodule showed a widespread derma atrophy (B) with large sheets of epithelioid cells at the junction (C); cytomorphologically, dermal melanocytes were epithelioid but devoid of true ‘Spitzoid’ features (D). The excision specimen showed a bland junctional proliferation of spindle cells (E), which were clearly different from epithelioid melanocytes of the previously curetted nodule (F). Histopathological diag- nosis: melanoma according to Ackerman’s classification [8]; Spitzoid melanoma according to Barnhill’s classification, 2006 [19]. Our histopathological diagnosis was pediatric Spitzoid melanoma (melanoma over a Spitz nevus). The dermoscopic differential diagnosis between pyogenic granuloma and nodular melanoma is virtually impossible; nevertheless, histopathologically we have never seen a pyogenic granuloma associated with a melanocytic nevus. (Copy- right: ©2015 Ferrara et al.) 52 Editorial | Dermatol Pract Concept 2015;5(1):6 The suggested management for both pediatric-type and adult-type Spitzoid melanoma is obviously the same as for “conventional” melanoma. Conclusions The introduction of dermoscopy has significantly changed the clinical diorama of Spitzoid lesions. Since there are still many controversial points in the histopathologic categorization of these lesions, clinicopathologic correlation must be the main- stay for their diagnosis and proper management. References 1. Darier FJ, Civatte A. Naevus ou naevo-carcinoma chez on nouris- son? Bull Soc Franc Dermatol Syphilol 1910;21:61–3. 2. Pack GT. Pre-pubertal melanoma of the skin. Surg Gynecol Obstet 1948;86:374-75. 3. Spitz S. Melanoma of childhood. Am J Pathol 1948;24:591-609. 4. Kernen JA, Ackerman LV. Spindle cell nevi and epithelioid cell nevi (so-called juvenile melanomas) in children and adults: a clinicopathologic study of 27 cases. Cancer 1960;13:612-25. 5. Smith KJ, Barrett TL, Skelton HG 3rd, Lupton GP, Graham JH. Spindle cell and epithelioid cell nevi with atypia and metastasis (malignant Spitz nevus). Am J Surg Pathol 1989;13:931-39. 6. Barnhill RL, Flotte TJ, Fleischli M, Perez-Atayde A. Cutane- ous melanoma and atypical Spitz tumors in children. Cancer 1995;76:1833-45. 7. Barnhill RL, Argenyi ZB, From L, et al. Atypical Spitz nevi/tumor: lack of consensus for diagnosis, discrimination from melanoma, and prediction of outcome. Hum Pathol 1999;30:513-20. 8. Mones JM, Ackerman AB. “Atypical” Spitz’s nevus, “Malignant” Spitz’s nevus, and “Metastasizing” Spitz’s nevus: a critique in historical perspective of three concepts flawed fatally. Am J Der- matopathol 2004;26:310-33. 9. Casso EM, Grin-Jorgensen CM, Grant-Kels JM. Spitz nevi. J Am Acad Dermatol 1992;27:901-13. 10. Wiesner T, He J, Yelensky R, et al. Kinase fusions are frequent in Spitz tumors and spitzoid melanomas. Nat Commun 2014;5:3116. 11. Ferrara G, De Vanna A. F1000Prime Recommendation of Gerami P et al’s Histomorphologic assessment and interob- server diagnostic reproducibility of atypical spitzoid melano- cytic neoplasms with long-term follow-up. Am J Surg Pathol 2014, 38(7):934-40, 15 Jul 2014. Website. F1000Prime.com. doi: 10.3410/f.718306130.793497130. F1000Prime.com/71830 6130#eval793497130 12. Ferrara G, Zalaudek I, Savarese I, Scalvenzi M, Argenziano G. Pediatric atypical spitzoid neoplasms. A review with emphasis on ‘red’ (‘Spitz’) tumors and ‘blue’ (‘Blitz’) tumors. Dermatology 2010;220:306-10. 13. Ludgate MW, Fullen DR, Lee J, et al. The atypical Spitz tumor of uncertain biologic potential: a series of 67 patients from a single institution. Cancer 2009;115:631. 14. Lallas A, Kyrgidis A, Ferrara G, et al. Atypical Spitz tumours and sentinel lymph node biopsy: a systematic review. Lancet Oncol 2014;15:e178. 15. Ferrara G, Argenziano G, Soyer HP, et al. The spectrum of Spitz nevi: a clinicopathologic study of 83 cases. Arch Dermatol 2005;141;1381-87. 16. Ferrara G, Zalaudek I, Argenziano G. Spitz nevus: an evolving clinicopathologic concept. Am J Dermatopathol. 2010;32:410-14. 17. Ferrara G, Gianotti R, Cavicchini S, et al. Spitz nevus, Spitz tu- mor, and Spitzoid melanoma: a comprehensive clinicopathologic overview. Dermatol Clin 2013;31:589-98. 18. Cerroni L, Barnhill R, Elder D, et al. Melanocytic tumors of un- certain malignant potential: results of a tutorial held at the XXIX Symposium of the International Society of Dermatopathology in Graz, October 2008. Am J Surg Pathol 2010;34:314-26. 19. Barnhill RL. The spitzoid lesion: the importance of atypical vari- ants and risk assessment. Am J Dermatopathol 2006;28:75-83. 20. Da Forno PD, Fletcher A, Pringle JY, Saldanha GS. Understanding spitzoid tumours: new insights from molecular pathology. Br J Dermatol 2008;158:4-14. 21. Pizzichetta MA, Talamini R, Stanganelli I, et al. Amelanotic/ hypomelanotic melanoma: clinical and dermoscopic features. Br J Dermatol 2004;150:1117-24. 22. Moscarella E, Zalaudek I, Cerroni L, et al. Excised melanocytic lesions in children and adolescents—a 10-year survey. Br J Der- matol 2012;167;368-73. 23. Urso C. A new perspective for Spitz tumors? Am J Dermatopathol 2005;27:364-65. 24. Zembowicz A, Scolyer RA. Nevus/melanocytoma/melanoma: an emerging paradigm for classification of melanocytic neoplasms? Arch Pathol Lab Med 2011;135:300-6. 25. Brunetti B, Nino M, Sammarco E, Scalvenzi M. Spitz naevus: a proposal for management. J Eur Acad Dermatol Venereol 2005;19:391. 26. Argenziano G, Zalaudek I, Ferrara G, Lorenzoni A, Soyer HP. Involution: the natural evolution of pigmented Spitz and Reed nevi? Arch Dermatol 2007;143:549-51. 27. Ferrara G, Moscarella E, Giorgio CM, Argenziano G. Spitz nevus and its variants. In: Soyer HP, Argenziano G, Hoffmann- Wellenhof R, Johr R (eds). Color Atlas of Melanocytic Lesions of the Skin. Berlin-Heidelberg: Springer-Verlag 2007:151-163. 28. Scalvenzi M, Francia MG, Palmisano F, Costa C. Long term clini- cal and dermoscopic follow-up of a child with a Spitz nevus. Open J Ped 2012;2:253-6. 29. Magro CM, Yaniv S, Mihm MC. The superficial atypical Spitz tumor and malignant melanoma of the superficial spreading type arising in association with the superficial atypical Spitz tumor: a distinct form of dysplastic Spitzoid nevomelanocytic proliferation. J Am Acad Dermatol 2009;60:814-23. 30. LeBoit PE. What do these cells prove? Am J Dermatopathol 2003;25:355-6. 31. Ferrara G, Errico ME, Donofrio V, Zalaudek I, Argenziano G. Melanocytic tumors of uncertain malignant potential in child- hood: do we really need sentinel node biopsy? J Cutan Pathol 2012;39:1049-51. 32. Jones EL, Jones TS, Pearlman NW, et al. Long-term follow-up and survival of patients following a recurrence of melanoma after a negative sentinel node biopsy result. JAMA Surg 2013; 16:1-6. 33. Pol-Rodriguez M, Lee S, Silvers DN, Celebi JT. Influence of age on survival in childhood spitzoid melanoma. Cancer 2007;109:1579- 83. 34. Gerami P, Scolyer RA, Xu X, et al. Risk assessment for atypi- cal spitzoid melanocytic neoplasms using FISH to identify chromosomal copy number aberrations. Am J Surg Pathol 2013;37:676-84. http://www.ncbi.nlm.nih.gov/pubmed?term=Pizzichetta%20MA%5BAuthor%5D&cauthor=true&cauthor_uid=15214897 http://www.ncbi.nlm.nih.gov/pubmed?term=Talamini%20R%5BAuthor%5D&cauthor=true&cauthor_uid=15214897 http://www.ncbi.nlm.nih.gov/pubmed?term=Stanganelli%20I%5BAuthor%5D&cauthor=true&cauthor_uid=15214897 http://www.ncbi.nlm.nih.gov/pubmed/22428965 http://www.ncbi.nlm.nih.gov/pubmed/22428965 http://www.ncbi.nlm.nih.gov/pubmed/23388126 http://www.ncbi.nlm.nih.gov/pubmed/23388126 http://www.ncbi.nlm.nih.gov/pubmed/23388126