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Sophie Spitz, M.D. described this nevus in 1948 as a benign juvenile melanoma. This unfortunate appellation has remained in the minds of many physicians who treat this benign, yet histologically alarming nevus. It usually occurs in children and young adults presenting as a raised flesh-colored or pink-red nodule. It is common on the face, trunk, and extremities. Occasionally, multiple clustered (agminate) or disseminated lesions can occur.

The pathologist is faced with the sometimes daunting task of distinguishing the Spitz nevus from a melanoma. If isolated histologic fields are examined out of context, the diagnosis of melanoma may be difficult if not impossible to exclude. As in every diagnosis, the entire lesion must be evaluated histologically. The difficulty lies in the fact that the melanocytes comprising the Spitz nevus are atypical. The melanocytes vary from spindled to epithelioid. Unlike melanomas, Spitz nevi are symmetrical and show maturation (diminution of the size of the cells) as the melanocytes descend into the underlying dermis. Additional criteria include the lack of mitotic figures deep in the dermal melanocytes and junctional cleavage. There is no magic formula to establish the diagnosis and there is occasional disagreement even amongst expert dermatopathologists. Cases of Spitz nevi metastasizing are probably misdiagnosed melanomas. These experiences have left some clinicians wary of the ability of pathologists to make a distinction between the Spitz nevi and melanoma. As a rule, a pathologist should always think thrice before diagnosing a Spitz nevi in an adult over 40 years of age.

SYNONYMS Spindled and epithelioid cell nevus
AGE RANGE-MEDIAN J Am Acad Dermatol 1993;29:667-778
May occur at any age but 50% or more are <20 years



Molecular cytogenetic analysis of Spitz nevi shows clear differences to melanoma.

Bastian BC, Wesselmann U, Pinkel D, Leboit PE.

Cancer Genetics Program, Cancer Center, University of California San Francisco, 94143-0808, USA.

J Invest Dermatol 1999 Dec;113(6):1065-9 Abstract quote

Spitz nevus is a benign neoplasm of melanocytes that can be difficult or impossible to distinguish from melanoma by clinical and histopathologic examination.

We studied genomic DNA from 17 Spitz nevi by comparative genomic hybridization (CGH).

Thirteen lesions showed no chromosomal aberrations, three cases had a gain involving the entire p-arm of chromosome 11, and one case showed a gain of chromosome 7q21-qter. Fluorescence in situ hybridization (FISH) on lesional tissue with a probe for the p-arm of chromosome 11 showed 6-10 p-arm signals per nucleus in those cases with a CGH-detected gain of chromosome 11p. One case with a normal CGH profile also showed increased copy number of 11p by FISH.

Thus, the majority of Spitz nevi have a normal chromosomal complement at the level of CGH resolution; however some may contain gains, with 11p apparently being the most frequently involved location. These findings differ significantly from the previously reported changes in primary cutaneous melanoma, which show frequent deletions of chromosomes 9p (82%), 10q (63%), 6q (28%), and 8p (22%), as well as gains of chromosomes 7 (50%), 8 (34%), 6p (28%), 1q (25%) by CGH analysis.

These clear differences in the location and frequencies of chromosomal aberrations in Spitz nevi and primary cutaneous melanomas could represent a basis for developing adjunctive techniques for refining accuracy in the difficult differential diagnosis of spitzoid melanocytic neoplasms.

Differentiation between Spitz nevi and malignant melanomas by interphase fluorescence in situ hybridization.

Wettengel GV, Draeger J, Kiesewetter F, Schell H, Neubauer S, Gebhart E.

Institute of Human Genetics, University of Erlangen-Nuremberg, D-91054 Erlangen, Germany.

Int J Oncol 1999 Jun;14(6):1177-83 Abstract quote

Spitz nevi are benign melanocytic neoplasias which have distinct pathological features that make the pathological differential diagnosis from malignant melanomas extremely difficult. The Spitz nevi may be misdiagnosed as malignant melanoma and vice versa.

Therefore, interphase fluorescence in situ hybridization (I-FISH) was used for a possible discrimination between Spitz nevi and malignant melanomas on the basis of numerical aberrations of the chromosome complement in interphase nuclei of thin sections.

Previous studies had shown changes in malignant melanomas which were not found at the same level in normal tissue or benign tumors. Thin sections of archival paraffin material from 42 Spitz nevi with different histological type and grade of anomaly were subjected to FISH-analyses using commercially available biotinylated and/or digoxigenated alphoid DNA probes of chromosomes 1, 6, 7, 9, 17 and 18, which were applied in combinations in a two- or three-color-FISH. Unaffected epithelial areas from the same sections served as. The obtained data were compared with those collected previously from thin sections of malignant melanomas prepared in the same way. Due to the sometimes limited nevus area investigated, the number of evaluable nuclei was lower than expected from previous experiences with malignant melanomas.

Therefore, only 20 nevi could be reliably evaluated. The comparison of the group of Spitz nevi with the group of controls did not show any significant difference regarding chromosomes 1, 6, 7, 9 and 17 (Wilcoxon test). The method used to detect chromosomal loss or gain in the individual Spitz nevi demonstrated only two nevi (one of the spindle cell type with a low to middle grade of anomaly, the other of the epitheloid cell type with a middle grade of anomaly) with a gain of chromosome 7 and chromosome 17, respectively. So, with respect to the histological type and grade of anomaly, no numerical aberrations could be detected in Spitz nevi.

The comparison of the group of Spitz nevi with subgroups of malignant melanomas (metastatic, non-metastatic, melanomas with a thickness <1.5 mm and melanomas with a thickness >2. 0 mm) and with the whole group of malignant melanomas showed significant differences concerning chromosome 9 (Mann-Whitney U test), signal indices, which were higher in the melanomas than in the Spitz nevi.

Regarding chromosomes 6, 7 and 17 no significant differences could be shown, although a trend of gain in melanomas and of loss in Spitz nevi was observed of these chromosomes.

Chromosomal abnormalities of 11p with amplification

Am J Pathol 2000;157:967-972

Confirmed by FISH analysis in small subset of Spitz nevi (11.8%) (12/102)
These tumors were associated with the following:

Increased thickness
Larger diameter
Predominantly intradermal
Florid desmoplastic stromal reaction
Larger and more pleomorphic cells
Infiltrative growth (often single cells) between the collagen bundles at their base

Spitz Nevi Display Allelic Deletions

Inja Bogdan, MD; Günther Burg, MD; Roland Böni, MD

Arch Dermatol. 2001;137:1417-1420 Abstract quote

Spitz nevi are acquired benign melanocytic lesions that occur in childhood and adolescence. Histologically, they resemble malignant melanoma and were first termed benign juvenile melanoma. Several studies have attempted the difficult task of establishing diagnostic criteria to differentiate between Spitz nevi and malignant melanoma.

To elucidate sets of diagnostic criteria for differentiation between the 2 lesions.

We aimed to search for allelic deletions in Spitz nevi and to evaluate whether loss of heterozygosity (LOH) or microsatellite instability (MSI) would be a valuable diagnostic tool to differentiate between Spitz nevi and malignant melanoma.

Two areas within each of 5 lesions were microdissected, and LOH and MSI were evaluated at chromosomes 6q (using polymorphic DNA marker D6S305), 9p21 (D9S171, IFNA, D9S265, and D9S270), 10q (D10S185), and 14q (D14S53).

Five Swiss patients with Spitz nevi.


Main Outcome Measure
Allelic deletions may serve as a diagnostic tool to distinguish Spitz nevi from melanoma. Results All lesions were informative, displaying LOH or MSI with at least one marker. No LOHs were found at 14q. At 6q, MSI was found in 2 dissected areas from the same lesion; the remaining lesions were noninformative. Loss of heterozygosity was found in 2 of 6 areas at D9S171, 2 of 6 at IFNA, 3 of 6 at D9S270, 3 of 4 at D9S265, and 1 of 4 at D10S185. Microsatellite instability was found in 1 of 4 areas at D9S265.

With the markers used in our study, Spitz nevi display LOH and MSI similar to those in melanoma. Analysis of LOH or MSI is therefore not a suitable diagnostic tool in distinguishing Spitz nevi from melanoma.

J Cutan Pathol 1997;24:219-222
Probably does not play a signficant role found in equal numbers in Spitz nevi, melanocytic nevi, and melanoma
In general, no significant difference with melanoma
Cyclin D1

Am J Dermatopathol 1999;21:115-120
Strongly expressed in superficial cells but not in the deeper cells

In contrast, melanomas have overexpression


Am J Dermatopathol 1995;17:547-550
Show weak staining except in rapidly growing lesions
Strong staining favors melanoma



Eruptive widespread Spitz nevi: can pregnancy be a stimulating factor?

Onsun N, Saracoglu S, Demirkesen C, Kural YB, Atilganoglu U.

Dermatology Department of Vakif Gureba Training Hospital, Istanbul, Turkey.

J Am Acad Dermatol 1999 May;40(5 Pt 2):866-7 Abstract quote

Spitz nevus is most commonly a benign solitary lesion. Agminated or disseminated Spitz nevi represent an uncommon manifestation of this nevus.

We report an unusual case of Spitz nevi arising and disseminating during pregnancy.



Successful differentiation of Spitz naevus from malignant melanoma by microfluorometric analysis of cellular DNA content.

Otsuka F, Chi HI, Umebayashi Y.

Department of Dermatology, University of Tsukuba, Japan.

Clin Exp Dermatol 1993 Sep;18(5):421-4 Abstract quote

Two cases of presumed Spitz naevus, whose diagnosis on clinical and histological grounds was uncertain, were examined for cellular DNA content using the technique of DAPI-DNA microfluorometry.

They were compared with 20 cases, respectively, of clinically and histologically confirmed, Spitz naevus, malignant melanoma and acquired pigmented naevus. The two Spitz naevi showed a diploid pattern in a distribution histogram of cellular DNA content. The pattern was similar to that of confirmed Spitz naevi and of acquired pigmented naevi but different from the aneuploid pattern of malignant melanomas. DNA index values of the two cases were within the range of confirmed Spitz naevi and different from those of malignant melanomas.

The DAPI-DNA microfluorometric method thus provided confirmatory evidence for the diagnosis of Spitz naevus. The method appears to reflect sensitively the biological behaviour of tumour cells, and is a useful aid to the diagnosis of uncertain Spitz naevi.

Flow Cytometry J Cutan Pathol 1990;17:342-347
Large cells are usually hyperdiploid
Image Analysis

J Invest Dermatol 1987;88:753-757
Increased DNA content in large cells which in some cases overlap with melanoma

Predominance of diploid cells near the base of a Spitz nevus but a predominance of hyperdiploid cells near the base of most melanomas

Measurement of the maturation parameter by using computer-assisted interactive image analysis may be helpful in the differential diagnosis between compound Spitz nevus and malignant melanoma.

Bergman R, Sabo E, Schafer I.

Department of Dermatology, Rambam Medical Center, Haifa, Israel.

Am J Dermatopathol 1996 Dec;18(6):567-70 Abstract quote

The so-called maturation parameter (MP) (that is, the ratio of the mean nuclear areas in the deep portion and in the superficial portion of a tumor) was measured and calculated using a computer-assisted interactive image analysis system in 29 compound Spitz nevi (SNs) and 37 primary invasive cutaneous malignant melanomas (MMs), of which 16 and 14 lesions, respectively, measured up to 1 mm in Breslow thickness (that is, thin).

The MPs of the SNs and MMs were found to be 0.37-0.89 (mean +/- SD, 0.64 +/- 0.1) and 0.81-1.16 (mean +/- SD, 0.96 +/- 0.1), respectively (p < 0.001). The MPs of the subgroups of thin SNs and MMs were 0.56-0.87 (mean +/- SD, 0.67 +/- 0.1) and 0.86-1.10 (mean +/- SD, 0.98 +/- 0.1), respectively (p < 0.001). Most of the SNs and MMs had MP values of < 0.81 and > 0.89, respectively. This pattern of distribution prevailed in the subgroup of thin lesions. Thus, the previously shown difference in MPs between SN and MM for thicker lesions (> or = 1.0 mm) was demonstrated in this study in thin lesions (< or = 1.0 mm) as well.

Although a relatively small area of overlap in MP values exists between compound SNs and MMs, including the thin ones, below this area the lower the MP value the more likely the diagnosis is SN, and vice versa.

Comparitive genomic hybridization

Science 1992;258:818-821
J Invest Dermatol 1999;113:1065-1069

Majority of Spitz nevi do show a normal pattern. However, about 25% have an amplification of 11p, an abnormality which does not occur in melanomas

Need to perform on relatively thicker lesions and ones that lack a significant lymphocytic infiltrate which have a normal DNA component

DNA in situ hybridization as a diagnostic tool in the discrimination of melanoma and Spitz naevus.

De Wit PE, Kerstens HM, Poddighe PJ, Van Muijen GN, Ruiter DJ.

Department of Pathology, University Hospital Nijmegen, The Netherlands.

J Pathol 1994 Jul;173(3):227-33 Abstract quote

As the clinical and histological differential diagnosis between Spitz naevus and cutaneous melanoma may be very difficult, we have investigated whether DNA in situ hybridization maybe helpful in resolving this problem.

To this end, routinely-processed paraffin sections of 15 typical Spitz naevi, 15 typical nodular melanomas, and five cases originally misdiagnosed as Spitz naevi but which later metastasized and were reclassified as melanoma were analysed using a method previously described (De Wit et al., J Invest Dermatol 1992; 98: 450-458).

Microscopical semi-quantitative evaluation revealed that the number of nuclei with supernumerary aberrations of the centromere region of chromosome 1, suggestive of aneuploidy, was significantly different in Spitz naevi and nodular melanoma. The mean number of aberrant nuclei per high power field was 0.41 and 4.01, respectively (P = 0.0001). On applying the results of the typical lesions to the equivocal, originally misdiagnosed lesions, three out of five could be identified as melanoma.

These results suggest that the application of DNA in situ hybridization may contribute to the positive identification of histologically equivocal pigmented lesions. The advantages of this technique are that it is cheap, requires little tissue, and can be applied on routinely-processed paraffin sections.

Morphological features of Spitz naevus as observed by digital videomicroscopy.

Pellacani G, Cesinaro AM, Seidenari S.

Department of Dermatology, University of Modena, Italy.

Acta Derm Venereol 2000 Mar-Apr;80(2):117-21 Abstract quote

A characteristic epiluminescence pattern of pigmented epithelioid and/or spindle cell naevus, or Spitz naevus, has been described previously.

The aim of this study was (i) to evaluate the characteristic morphological features both of pigmented and non-pigmented epithelioid and/or spindle cell naevi observed employing a videomicroscope, (ii) to identify their histopathological correlates and (iii) to assess the improvement in diagnostic accuracy for epithelioid and/or spindle cell naevi obtained by means of this new instrumental device. Clinical, videomicroscopic and histopathological diagnoses were performed on 26 epithelioid and/or spindle cell naevi. Moreover, the videomicroscopic pattern of each lesion was described using appropriate morphological parameters.

Based on their morphological aspect detected by digital videomicroscopy, epithelioid and/or spindle cell naevi can be subdivided into three main groups: (i) darkly pigmented lesions, (ii) red or light brown ESC naevi, and (iii) lesions with dark or brown areas on a light-brown background. Whereas most epithelioid and/or spindle cell naevi of the spindle cell type belonged to the morphological group I and group 3, most epithelioid cell lesions appeared as red or light-brown coloured naevi. Finally, instrumental observation by means of a videomicroscope enabled an improvement in diagnostic accuracy with respect to the naked eye observation, with an increase in sensitivity from 15% to 58%.



Clinical review of 247 case records of Spitz nevus (epithelioid cell and/or spindle cell nevus).

Dal Pozzo V, Benelli C, Restano L, Gianotti R, Cesana BM.

Institute of Dermatologic Sciences, University of Milan, Italy

Dermatology 1997;194(1):20-5 Abstract quote

BACKGROUND: Spitz nevus has clinically been described as a dome-shaped usually nonpigmented papular or nodular lesion variable in color from pink to red. OBJECTIVES: To give an exhaustive description of the clinical features of the Spitz nevus from a large series of 247 patients.

METHODS: A retrospective analysis of the clinical features of 247 Spitz nevi excised from 1974 to 1993 has been performed. We evaluated the following features: age, sex, anatomical location, clinical and histopathologic features; descriptive statistics were calculated and relationships among the above variables were assessed.

RESULTS: Most lesions were pigmented (71.7%), located on the lower extremities (43.3%), more frequent in the first decade (55.8%) and in females (57.9%). The nonpigmented type was more frequent in the head or neck region, whereas the pigmented types were more frequent on the lower extremities. Besides, these types showed different histopathologic features: the spindle cells usually predominated in the flat pigmented type, whereas dome-shaped types were usually composed of both spindle and epithelioid cells.

CONCLUSIONS: In our patients, the pigmented Spitz nevi were more common than the nonpigmented ones; furthermore pigmented and nonpigmented Spitz nevi showed different anatomical locations and different histopathologic features.

Agminated Spitz nevi Clusters of papules sometimes within a cafe au lait macule

Agminated Spitz nevi occurring within a congenital speckled lentiginous nevus.

Aloi F, Tomasini C, Pippione M.

Department of Dermatology, University of Turin, Italy.

Am J Dermatopathol 1995 Dec;17(6):594-8 Abstract quote

A 40-year-old woman had a speckled lentiginous nevus on her thigh since birth. During her first pregnancy, additional papules and nodules appeared within the preexisting hyperpigmented area, histologic examination of which showed features of both junctional and compound Spitz's nevi accompanied by simple lentigolike changes.

In this particular case, speckled lentiginous nevus may have constituted a particular environment for the production of multiple Spitz nevi.

Agminated intradermal Spitz nevi arising on an unusual speckled lentiginous nevus with localized lentiginosis: a continuum?

Betti R, Inselvini E, Palvarini M, Crosti C.

Clinica Dermatologica IV, Osp. S. Paolo, Milan, Italy.

Am J Dermatopathol 1997 Oct;19(5):524-7 Abstract quote

We report an 18-year-old boy with a congenital pigmented lesion measuring 2 x 6 cm on his right thigh.

About a third of the lesion was composed of numerous lentiginous macules superimposed on histologically normal and clinically nontan skin; in the remainder of the lesion, several macules and papules with histologic features of junctional and compound nevi were superimposed on clinically normal skin, which had a lentiginous pattern histologically. Some years later, eruptive intradermal Spitz nevi developed at one corner of the lesion. The combined clinical and histological features of the lesion fulfill descriptions for both segmental lentiginosis and an unusual variant of speckled lentiginous nevus.

Our case points out the limitations of using strict diagnostic criteria to define speckled lentiginous nevus and offers an opportunity to consider the natural history of the lesion as a continuum from lentigines to melanocytic nevi. Moreover, the presence of eruptive intradermal Spitz nevi arising within the area of speckled lentiginous nevus lacking a distinct tan background, suggests the possibility that the entire area of the lesion per se constitutes an environment where development of nevi is enhanced.

Eruptive Am J Dermatopathol 1987;9:520-527
May occur after an inciting event such as sunburn or whooping cough


GENERAL Dermatopathol: Practical and Conceptual 1999;5:9-13
Hum Pathol 1998;29:1105-1112
One must apply strict histologic criteria to ensure that the diagnosis of Spitz nevi do not overlap with other diseases including melanoma
Earliest changes
Relatively even distribution of melanocytes along the dermoepidermal junction
Monomorphous cytology of the large melanocytes
Abundant eosinophilic cytoplasm
Many multinucleated melanocytes
Clefts between melanocytes and neighboring keratinocytes
Slight epidermal hyperplasia overlying the melanocytic proliferation
Later changes

Gently domed contour
Irregular epidermal hyperplasia, with jagged rete ridges, a thickened granular layer, and thickened compact cornified layer
Kamino bodies
Clefts around nests of melanocytes and between melanocytes within each nest
Sharp lateral circumscription-usually ends with a nest rather than with single cells
Nests of melanocytes predominate over single melanocytes at the junction
Few single melanocytes are present above the basal layer, usually in the center of the lesion

Nests within the papillary dermis are usually the same size or smaller than those at the junction and often do not extend within the dermis to the same width as the junctional nests

There may be dense lymphocytic infiltrates with junctional and early compound Spitz nevi

Nucleoli are brightly eosinophilic in the upper part of the lesion but in the deeper reticular dermis, the nuclei should have bluish hue, unlike melanomas-in addition, if these nucleoli are about the size of an erythrocyte and are bright red, a melanoma should be considered

Fully Developed changes

Wedge shaped with a domed surface with melanocytes extending into the reticular dermis
Maturation of melanocytes as melanocytes descend deeper in the dermis in the form of:
Diminution in the sizes of aggregates of cells
Decreases in the sizes of the cells themselves
Loss of cytoplasmic volume with diminished pigmentation
Decrease in nucleolar size

NOTE: If the aggregations of cells near the base of a Spitz nevus are large, a melanoma should be considered

Intradermal Spitz nevus

Like most melanocytic nevi, Spitz nevi become intradermal neoplasms characterized by:
Wedge shape with apex in the deep dermis
Discrete nests of melanocytes throughout the lesion
Nests at each level of the dermis are approximately the same size, with cells of the same pigmentation and cytologic appearance
Thick collagen bundles throughout the neoplasm, not focal

Eventually resembles a dermatofibroma, histologically

Kamino bodies

Am J Dermatopathol 1979;1:319-324
Dull pink globules found in many Spitz nevi

Not brightly eosinophilic as dyskeratotic cells and had scalloped borders

Stain with PAS with diastase digestion

Composed of basement membrane material (laminin and collagen type IV)
EM shows filaments which may represent debris from necrotic melanocytes and keratinocytes

  Am J Dermatopathol 1998;20:551-554
TUNEL revealed no evidence for apoptosis
Suprabasilar scatter of single cells usually occurring in the center of the nevus and not at the edges

Angiomatoid Spitz nevus: a distinct variant of desmoplastic Spitz nevus with prominent vasculature.

Diaz-Cascajo C, Borghi S, Weyers W.

Center for Dermatopathology, Freiburg, Germany.

Am J Dermatopathol 2000 Apr;22(2):135-9 Abstract quote

Five cases of a distinctive variant of desmoplastic Spitz nevus are reported. To the best of our knowledge, this tumor has never been described previously.

Clinically, it presents itself as a solitary papule on the extremities of young adults. Microscopically, it shows predominance of solitary melanocytes with epithelioid appearance over cell nests. They are embedded in a prominent fibrous stroma with many densely arranged, small blood vessels with plump endothelia not seen in other Spitz nevi.

Because of its resemblance to a vascular tumor, the name angiomatoid Spitz nevus is proposed for this lesion. Absence of recurrences or metastases after complete excision in all cases supports the benign nature of the tumor.


Atypical Spitz nevi/tumors: lack of consensus for diagnosis, discrimination from melanoma, and prediction of outcome.

Barnhill RL, Argenyi ZB, From L, Glass LF, Maize JC, Mihm MC Jr, Rabkin MS, Ronan SG, White WL, Piepkorn M.

Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Hum Pathol 1999 May;30(5):513-20 Abstract quote

The biological nature of Spitz nevi/tumors and their diagnostic distinction from, or relationship to, melanoma remain unresolved issues.

In this report, a series of 30 melanocytic lesions removed from 28 patients, including atypical Spitz nevi/tumors and metastasizing Spitzoid tumors/melanomas, were evaluated by a panel of dermatopathologists to evaluate interobserver diagnostic concordance and to assess the prognostic power of histological criteria.

For inclusion in the study, each lesion had to display some criteria for the Spitz nevus, and in addition one of the following was required: (1) definitive clinical outcome such as metastasis or death of disease, or (2) long-term follow-up if the patient remained disease free.

Each lesion was reviewed independently and blinded as to the clinical data by 10 pathologists, who categorized them as (1) typical Spitz nevus/tumor, (2) atypical Spitz nevus/tumor, (3) melanoma, (4) tumor with unknown biological potential, or (5) other melanocytic lesion. There was limited discussion of criteria before the review.

Evaluation of 17 Spitzoid lesions yielded no clear consensus as to diagnosis; in only one case did six or more pathologists agree on a single category, regardless of clinical outcome. Notably, however, some lesions that proved fatal were categorized by most observers as either Spitz nevi or atypical Spitz tumors. Conversely, seven or more pathologists scored 13 lesions as melanoma.

These results illustrate (1) substantial diagnostic difficulties posed by many Spitz tumors, especially those with atypical features, even among experts, and (2) the lack of objective criteria for their distinction from melanoma and for gauging their malignant potential. Nevertheless, our observations do suggest that a biological relationship exists between the Spitz nevus/tumor and melanoma.

Am J Dermatopathol 1985;7:61S-78S
Spitz nevus is combined with other forms of melanocytic nevi including:
Congenital type
Blue nevus

Congenital spitz nevus.

Harris MN, Hurwitz RM, Buckel LJ, Gray HR.

Dermatopathology Laboratory, Inc., Indianapolis, Indiana 46260, USA.

Dermatol Surg 2000 Oct;26(10):931-5 Abstract quote

BACKGROUND: Congenital Spitz nevus has been reported previously in the literature, but the histopathologic features have not been examined in detail.

OBJECTIVE: To histologically examine and report on congenital Spitz nevus.

METHOD: We examined 10 clinically submitted congenital melanocytic nevi that were histopathologically identified as congenital Spitz nevi and compared them to the characteristics seen in acquired Spitz nevus and superficial congenital melanocytic nevus.

RESULTS: Of the 10 congenital Spitz nevi, 9 were compound and 1 was dermal. Two showed features of combined Spitz nevus (Spitz and blue). Six cases showed all 16 listed characteristics of acquired Spitz nevus, with two cases having 15 and two cases having 14 characteristics. Of the superficial congenital melanocytic nevus characteristics, all except three cases had all 12 attributes. The one dermal lesion had all the characteristics of the acquired Spitz nevus and all but one of the characteristics of the superficial congenital melanocytic nevus in regards to intradermal findings.

CONCLUSIONS: Congenital Spitz nevi are true congenital lesions, with histopathologic features of both acquired Spitz nevus and superficial congenital melanocytic nevus.


Desmoplastic nevus: a distinct histologic variant of mixed spindle cell and epithelioid cell nevus.

Barr RJ, Morales RV, Graham JH.

Cancer 1980 Aug 1;46(3):557-64 Abstract quote

From a series of 75 cases of mixed spindle cell and epithelioid cell nevi, 14 were designated as desmoplastic nevi. Junctional activity, theque formation, and pigmentation were uncommon features. As a result, desmoplastic nevi may be confused with a variety of fibrohistiocytic lesions.

Well defined intranuclear invaginations of cytoplasm occurred in 12 cases, and were helpful in differentiating desmoplastic nevi from these lesions.

Desmoplastic malignant melanoma must also be considered in the microscopic differential diagnosis, but distinguishing features of desmoplastic melanoma include the presence of preexisting lentiginous melanoma, and necrosis of tumor cells and collagen.

Desmoplastic nevus was compared to the ordinary variants of mixed spindle cell and eipthelioid cell nevus in an attempt to define etiologic factors responsible for a desmoplastic reaction. No satisfactory explanation could be found since the clinical variables examined were not statistically different.

Cancer 1980;46:557-564
Histopathology 1992;20:207-211

Some have used this term to describe lesions with intradermal Spitz features and prominent collagen bundles

A key is the presence of a wedge shaped infiltrate with apex pointing in reticular dermis
Clefts are present between melanocytes in superficial dermis and thickened collagen bundles separate small nests
Melanocytes at the base are positioned singly or in small discrete aggregations, an important differential point with melanomas which tend to lack this dispersal with descent


Spitz's nevi with halo reaction: a histopathologic study of 17 cases.

Harvell JD, Meehan SA, LeBoit PE.

Department of Pathology, University of California, San Francisco, School of Medicine, 94143-0506, USA..

J Cutan Pathol 1997 Nov;24(10):611-9 Abstract quote

Halo reactions to melanocytic nevi are a well-recognized phenomenon. In contrast, halo reactions to Spitz's nevi have been reported only infrequently. Halo reactions may cause misdiagnosis of an otherwise benign nevus as melanoma because inflammatory cells sometimes obscure the architectural features of the underlying nevus, and may induce cytologic atypia. For Spitz's nevus where the distinction between malignancy and benignancy is already challenging, halo reactions compound the problem.

We describe 17 examples of Spitz's nevus with halo reaction, and compare their immunohistochemical features with those of "ordinary" halo nevi. Only 2 of 17 lesions demonstrated clinically apparent halos. Clinical follow-up was available for 12 of 17 cases. None of the 12 has persisted at the biopsy site or metastasized after an average 3.6-year follow-up period. Junctional, compound, intradermal, and combined types of Spitz's nevi were represented. All were characterized by symmetrical lymphocytic infiltrates which permeated the full thickness of the nevus, including junctional nests. Combined Spitz's nevi constituted more than one-half of examples in this series (9/17 cases). The combined Spitz's nevus included a combination of Spitz's nevus with either an ordinary (common, banal) nevus or a superficial congenital type nevus. In these combined Spitz's nevi, the lymphocytic response was often directed exclusively to the Spitz's nevic component.

Important distinguishing features from malignant melanoma arising in a pre-existing nevus included symmetry and lateral circumscription of the spitzoid component, no large expansile-appearing aggregates of melanocytes, a decrease in size of nests with increasing dermal depth, a lack of mitotic figures among melanocytes at the base, and a symmetrical and diffusely permeative lymphocytic response. Although the combined Spitz's nevus with halo reaction sometimes appeared asymmetrical at scanning magnification, each component of the combination was symmetrical, when examined independently. Probably because of reactive atypia, nuclear maturation with progressive descent into the dermis was sometimes absent.

There were no obvious differences in immunohistochemical staining patterns among 4 Spitz's nevi with halo reaction, 5 regressing melanomas, and 5 benign halo nevi when stained with antibodies to S100, HMB-45, OPD4, CD8, TIA-1, CD1a, CD68, and Ki-67.

Scatter of melanocytes above the basal layer
Related to increased epidermopoiesis, secondary to such varied insults as ultraviolet light and trauma
If a scale crust, parakeratosis, or hemorrhage and fibrin are identified, especially with deeper levels, it may be inferred that this is focal phenomenon

Pagetoid Spitz nevus. Intraepidermal Spitz tumor with prominent pagetoid spread.

Busam KJ, Barnhill RL.

Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.

Am J Surg Pathol 1995 Sep;19(9):1061-7 Abstract quote

A distinctive variant of melanocytic growth pattern is described, which appears to be related to Spitz nevus and is characterized by a mainly intraepidermal proliferation of large epithelioid melanocytes with a predominantly pagetoid distribution.

This melanocytic lesion appears clinically as a small (< 0.4 cm) pigmented macule in young patients. Histologically, this lesion needs to be distinguished primarily from in situ or microinvasive malignant melanoma with pagetoid spread.

Features favoring nevus over melanoma include small size, circumscription, symmetry, even distribution of cells, and lack of marked cytologic atypia.

See file.

Plexiform spitz nevus: an intradermal spitz nevus with plexiform growth pattern.

Spatz A, Peterse S, Fletcher CD, Barnhill RL.

Department of Pathology, Institut Gustave-Roussy, Villejuif, France.

Am J Dermatopathol 1999 Dec;21(6):542-6 Abstract quote

Two cases of a distinctive variant of Spitz (spindle and epithelioid cell) nevus are described.

One lesion developed on the lower leg of a 17-year-old boy and the other lesion on the back of a 52-year-old man.

The microscopic appearance was characterized by a plexiform arrangement of bundles and lobules of enlarged spindle to epithelioid melanocytes throughout the superficial and deep dermis. Intraepidermal melanocytic proliferation was unappreciated. Some lobules were circumscribed by a thin rim of compressed fibrous tissue. In both cases a myxoid stroma was present. The cells had abundant eosinophilic cytoplasm with well-defined borders. The nuclei were enlarged, consistently ovoid and vesicular, with small nucleoli. Both cases contained scattered multinucleate giant cells similar to those observed in classical form of Spitz nevi. No melanin pigment was detectable by light microscopy. No mitoses were observed in one case and a rare mitosis was present in the other. Tumor cells were strongly immunoreactive for S-100, but not for HMB-45, desmin, and actin.

The differential diagnosis of this distinctive tumor includes desmoplastic/neurotropic melanoma, plexiform spindle cell nevus, cellular blue nevus, plexiform neurofibroma, and cellular neurothekeoma.

The designation of "plexiform Spitz nevus" is chosen to emphasize its distinctive plexiform growth pattern.


Polypoid Spitz naevus: the benign counterpart of polypoid malignant melanoma.

Fabrizi G, Massi G.

Department of Dermatology, *Department of Pathology, Catholic University Medical School, Largo F. Vito, 1, 0168 Rome, Italy.

Br J Dermatol 2000 Jan;142(1):128-32 Abstract quote

Polypoid malignant melanoma is a peculiar morphological variant of melanoma with a distinct exophytic pattern of growth. This form of melanoma is usually very thick and the prognosis is accordingly poor.

We present here a previously undescribed form of Spitz naevus which had a similar polypoid exophytic silhouette and marked cytological atypia. Despite these close morphological similarities, polypoid Spitz naevus evolves in a completely benign manner.

Morphologically, polypoid Spitz naevus can be distinguished from polypoid melanoma by the absence of mitoses and by the prominent stromal reaction throughout the lesion.

Recurrent Spitz nevus

Arch Dematol 1990;126:1582-1583
Lesions that have been interrupted by surgery are no longer symmetrical and may display considerable pagetoid scatter of single melanocytes

There may be nodular aggregations of melanocytes adjacent to a zone of scar

Single melanocytes may be positioned between thickened collagen bundles in dermis beneath the scar

Recurrent Spitz's nevus.

Omura EF, Kheir SM.

Am J Dermatopathol 1984 Summer;6 Suppl:207-12 Abstract quote

A recurrence of a spindle- and epithelioid-cell nevus following partial removal is described.

Clinical and histologic photographs of the original and recurrent lesion and an immunohistochemical stain (S-100) which highlights melanocytic cells and their pattern of growth are included. This nodular recurrence of a Spitz's nevus is contrasted with macular recurrence of ordinary melanocytic nevi that may follow partial removal by shaves.

It is presented in order to promote recognition and prevent misdiagnosis of such a recurrence as a malignant melanoma.



C-fos protein expression in Spitz nevi, common melanocytic nevi, and malignant melanomas.

Bergman R, Kerner H, Manov L, Friedman-Birnbaum R.

Department of Dermatology, Rambam Medical Centre, and the Bruce Rappaport Faculty of Medicine, Technion-Israel of Technology, Haifa.

Am J Dermatopathol 1998 Jun;20(3):262-5 Abstract quote

The expression of c-fos protein was studied in formalin-fixed, paraffin-embedded sections of 11 compound Spitz nevi (SNs), 16 ordinary compound melanocytic nevi (MNs), and 17 malignant melanomas (MMs) using monoclonal antibody MAB1283 and an immunoperoxidase technique.

Eleven (100%) SNs, 15 (94%) MNs, and 16 (94%) MMs showed positive reactions in some of the tumor cells (p = nonsignificant). In the majority of the tumors the staining was located in nuclei and graded as moderate to strong in intensity. The percentages of positively stained cells did not differentiate the three types of tumor, although they were higher in the melanocytic nevi. Most of the lesions with a significant dermal component did not show stratification of staining with progressive descent into the dermis. Positive staining for c-fos was also frequently found in the normal skin constituents within and adjacent to the melanocytic tumors.

In conclusion, the pattern of expression of c-fos in routinely processed specimens does not differentiate between SNs, MNs, and MMs.


Cyclin D1 overexpression in Spitz nevi: an immunohistochemical study.

Nagasaka T, Lai R, Medeiros LJ, Brynes RK, McCourty A, Harada T, Saddik M.

Division of Pathology, Nagoya University Hospital, Japan.

Am J Dermatopathol 1999 Apr;21(2):115-20 Abstract quote

The morphologic distinction between Spitz nevus and malignant melanoma can be difficult. Because cyclin D1 has been reported to be overexpressed in malignant melanomas, but not in common acquired nevi, we hypothesized that cyclin D1 might be a useful marker to distinguish Spitz nevi from malignant melanoma.

Thus, we assessed for cyclin D1 expression in 11 Spitz nevi (10 compound and 1 intradermal) and 9 malignant melanomas (4 Clark stages I-III and 5 Clark stages IV-V) using an immunohistochemical method and routinely fixed and processed tissues. The cyclin D1 results were arbitrarily divided into three groups: 0% to 10%, >10% to 25%, and >25%. We confirmed the observations reported previously by others that cyclin D1 is expressed in malignant melanomas but not in common acquired nevi. Unexpectedly, a relatively high number of cyclin D1-positive cells (i.e., >10%) was also found in all cases of Spitz nevus. However, unlike malignant melanoma, the cyclin D1 positivity in Spitz nevi was present in a zonal pattern. In other words, the number of cyclin D1-positive cells decreased as the lesion extended more deeply, with the number of positive cells in the reticular dermis being less than that in the papillary dermis. Fluorescence in situ hybridization methods were used to assess amplification of 11q13, the locus harboring the cyclin D1 gene, in four cases of Spitz nevus; all were disomic.

Using the antibody MIB-1, we compared cyclin D1 expression to the proliferation rate in Spitz nevi. Despite the high cyclin D1 positivity, all Spitz nevi had a relatively low number of MIB-1-positive cells (mean=3.2%), which was significantly lower than that of malignant melanomas (mean=15.3%) (p < 0.001).

Thus, unlike malignant melanoma, there appears to be a dissociation between cyclin D1 overexpression and cell proliferation in Spitz nevi.

J Pathol 1990;161:41-45
More weakly expressed in Spitz nevus cells rather than melanoma
J Cutan Pathol 1995;22:502-517
Am J Surg Pathol 1999;23:786-794
Am J Dermatopathol 1995;17:542-546
Usually just marks the uppermost cells of Spitz nevus unlike the diffuse expression by neoplastic melanocytes deep in the dermis

The pattern of HMB-45 antibody staining in compound Spitz nevi.

Bergman R, Dromi R, Trau H, Cohen I, Lichtig C.

Department of Dermatology, Rambam Medical Center.

Am J Dermatopathol 1995 Dec;17(6):542-6 Abstrac quote

We studied the staining pattern of HMB-45 antibody in 29 compound Spitz nevi (SNs) of the epithelioid cell variety, 17 of which showed extension of nevus cells into the reticular dermis (i.e., "deep"); 20 ordinary compound nevi (CNs), all with a deep dermal component; and 22 primary cutaneous invasive malignant melanomas (MMs) (excluding the desmoplastic and spindle cell types), 12 of which extended into Clark level IV or V. Of the 29 SNs, eight (28%) stained negatively; five (17%), including two deep SNs, stained in the epidermal component only; and 16 (55%), including 10 deep SNs, stained in both the epidermal and dermal components.

Of the latter 10 deep SNs, eight stained in the upper dermis only, and in the remaining two lesions, a smaller number of positively stained nevus cells were detectable in the lower dermis as well; these two SNs were not atypical histologically. Of the 20 CNs, four (20%) stained negatively, two (10%) stained in the epidermal component only, and 14 (70%) stained in the epidermal component and the upper dermis only. Of the 22 MMs, one stained negatively, and 21 (95%) stained positively in both the epidermal and dermal components. The pattern was variable in frequency of both staining and distribution, but showed no stratification.

We conclude that the majority of our positively stained deep compound SNs showed a stratified pattern of HMB-45 staining, similar to ordinary CNs and different from MMs, and that this pattern might be used as an adjunct in the histopathologic differential diagnosis of compound SN and MM, in the proper clinicopathological context.

MIB-1 monoclonal antibody to determine proliferative activity of Ki-67 antigen as an adjunct to the histopathologic differential diagnosis of Spitz nevi

J Am Acad Dermatol 2001;44:500-4

Twenty-five compound SNs, 27 MMs, and 26 compound nondysplastic melanocytic nevi (MNs) were immunostained with the MIB-1 antibody.

Results: The mean counts of MIB-1-stained tumor cells of the epidermal and dermal components, both alone and together, were significantly lower in SNs and MNs than in MMs (P < .0001). The dermal counts showed the best discriminating power. In addition, the mean dermal/epidermal count ratios for MIB-1 in SNs and MNs (0.25 and 0.23, respectively) were significantly lower than the corresponding ratio (0.94) in MMs (P < .0001).

Conclusion: MIB-1-stained tumor cell counts, especially of the dermal component, and dermal/epidermal MIB-1 count ratios may be helpful as an adjunct to the histopathologic differential diagnosis of SN.

Mod Pathol 1997;10:917-920
Am J Dermatopathol 1993;15:311-314
Proliferation rate is lower as compared to melanoma with 75% of cases having proliferation rate of <2% and only 2% of melanomas having this low a proliferation rate

PCNA may overestimate the number of proliferating cells because of its long half life and also shows a striking increase in proliferating cells over conventional nevi with a small overlap with melanoma

Immunohistochemical study of p53 protein expression in Spitz nevus as compared with other melanocytic lesions.

Bergman R, Shemer A, Levy R, Friedman-Birnbaum R, Trau H, Lichtig C.

Department of Dermatology, Rambam Medical Center, Haifa, Israel.

Am J Dermatopathol 1995 Dec;17(6):547-50 Abstract quote

The accumulation of p53 protein was studied immunohistochemically on paraffin-embedded sections of 26 Spitz nevi (SNs), 26 primary invasive cutaneous malignant melanomas (MMs), 20 metastases of MM, and 17 ordinary compound nevi (CNs), using monoclonal antibody BP53-12.

Positive reactivity was detected in some of the tumor cells in seven (35%) metastatic MMs, all exhibiting strong nuclear staining; eight (31%) primary MMs, of which seven showed strong nuclear staining; two (7%) SNs, of which only one showed strong nuclear staining; and none of the CNs. The frequencies of the positively stained lesions in general, and the strongly positively stained lesions in particular, in the MM and metastatic MM groups were each statistically significantly higher than the respective frequencies in the SN and CN groups.

We believe that the immunohistochemical detection of p53 protein with the use of monoclonal antibodies such as BP53-12 on paraffin sections, especially when strong nuclear reactivity is demonstrated, may prove to be an adjunctive tool in the histopathologic differentiation of MM from SN.


Malignant melanoma

Most of the key differential points are covered in the histology outline

In general, the following histologic features should make one question the diagnosis:
Cells with abundant pale or dusty melanin cytoplasmic pigmentation pattern
Cells with very large eosinophilic nucleoli
Uniformly hyperchromatic nuclei

In addition, there are other points which should be mentioned, especially in light of cases of metastasizing Spitz nevi

Desmoplastic melanoma Differ from intradermal Spitz by the following:
Long fascicles of spindled cells resembling nerve fascicles
Nodular collections of lymphocytes at margin between reticular dermis and subcutis or between fibrotic subcutaneous septa and lobules
Perineural invasion at a distance form main partof the neoplasm

Nuclear pseudoinclusions in melanocytic naevi and melanomas.

Rose DS.

Department of Histopathology, University College, London Medical School.

J Clin Pathol 1995 Jul;48(7):676-7 Abstract quote

Melanocytes in melanocytic naevi and melanomas can display great variation. The presence of nuclear pseudoinclusions (NPI) is said to be useful in the histological and cytological differential diagnosis of malignant melanoma.

The prevalence and characteristics of NPI in a series of 493 naevi and 50 melanomas are described. NPI were found in 31% of adult naevi, 30% of congenital naevi from children, 42% of Spitz naevi, 20% of dysplastic naevi, and 56% of melanomas.

The presence of NPI is not a reliable criterion for differentiating melanoma from benign melanocytic lesions, although it is useful in distinguishing melanocytic from non-melanocytic tumours.

Spitz naevi misdiagnosed histologically as melanoma: prevalence and clinical profile.

Orchard DC, Dowling JP, Kelly JW.

Victorian Melanoma Service, Alfred Health Care Group, Prahran, Australia.

Australas J Dermatol 1997 Feb;38(1):12-4 Abstract quote

A Spitz naevus is a benign melanocytic tumour that may histologically resemble a malignant melanoma. Data was retrospectively gathered from patients who attended the Victorian Melanoma Service to determine the prevalence of Spitz naevi pathologically misdiagnosed as melanoma. Assessment of the clinical characteristics of these patients was also performed and compared to those with correctly diagnosed melanoma.

It was found that 6.5% of all melanomas referred were in fact Spitz naevi and that Spitz naevi represented the majority of pathologically misdiagnosed melanomas. The Spitz naevi were more likely to be on the lower extremities and were no average, considerably smaller than the melanomas. Patients with Spitz naevi were more likely to be younger, female, have fewer dysplastic naevi and have brown eyes. One hundred per cent of the Spitz naevi were brought to the attention of the initial doctor by the patient compared to 72% of the melanomas.

This study concludes that Spitz naevi that are pathologically misdiagnosed as melanomas retain the clinical characteristics of other Spitz naevi and that greater clinicopathological communication may reduce the frequency of diagnostic error.

Silhouette symmetry: an unsupportable histologic criterion for distinguishing Spitz nevi and compound nevi from malignant melanoma.

Okun MR.

Dermatopathology Foundation, Canton, Mass 02021, USA.

Arch Pathol Lab Med 1997 Jan;121(1):48-53 Abstract quote

BACKGROUND: In 1989, Ackerman proposed that pattern analysis can be a more accurate method of evaluating neoplasms than assessment of nuclear morphology. He stated that malignant melanomas tend to be asymmetrical, and benign melanocytic neoplasms tend to be symmetrical.

METHODS: We examined a series of typical Spitz nevi, compound nevi, and malignant melanomas with the loupe and with higher magnifications. We also considered pattern analysis from the standpoint of solid geometry.

RESULTS: The ratio of symmetrical to asymmetrical lesions (visualized in histologic sections) in malignant melanomas approximated that of Spitz nevi and compound nevi. The configuration seen in sections does not necessarily reflect the three-dimensional configuration of a lesion. Lesions with three-dimensional reflective symmetry cannot be shown to have this property in sections unless cuts are made perpendicular to the plane of symmetry, which is an impossibility.

CONCLUSIONS: The presence or absence of symmetry in sections of neoplasms must be considered coincidental or focal. Using symmetry as a criterion to distinguish malignant melanomas from Spitz nevi and compound nevi is without validity on both theoretical and empirical grounds.

A combined variant of Spitz's nevi. How to differentiate them from malignant melanomas.

Rogers GS, Advani H, Ackerman AB.

Department of Dermatology, New York University Medical Center, New York.

Am J Dermatopathol 1985;7 Suppl:61-78 Abstract quote

In the past several years we have studied 22 lesions of what we believe are combined variants of Spitz's nevi.

Almost all of the patients were young adults. These combined melanocytic nevi have the architectural pattern of benign lesions, i.e., they are relatively symmetrical and well circumscribed. Each was characterized by the presence of at least two populations of nevus cells, one relatively banal with small nuclei and scant cytoplasm, the other with large nuclei and abundant cytoplasm. The latter are indistinguishable from cuboidal (epithelioid) cells of Spitz's nevus. The banal and the large nevus cells were intermingled in some of the lesions, but were segregated in others.

Because these combined nevi differ from conventional Spitz's nevi and because the large nevus cells often fail to show maturation with progressive descent into the dermis, they are commonly misdiagnosed histologically as malignant melanomas.

Spitz nevus versus spitzoid malignant melanoma: an evaluation of the current distinguishing histopathologic criteria.

Walsh N, Crotty K, Palmer A, McCarthy S.

Department of Anatomical Pathology, Royal Prince Alfred Hospital and the University of Sydney, Australia.

Hum Pathol 1998 Oct;29(10):1105-12 Abstract quote

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 dermatopathologists 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 evaluated 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.


PROGNOSIS Benign if accurate histopathologic criteria are applied
GRADING SYSTEMS Some authors have advocated a grading system to assess atypical Spitz nevi in children and adolescents
  Taken from Basitan BC, etal. Am J Pathol 2000;157:967-972
Parameter Score
Age (Years)  
Diameter (mm)  
Involvement of subcutaneous fat  
Mitotic activity (mm2)  

This grading system is by no means universally accepted but is reproduced here as an example of a system that some pathologists have utilized to stratify Spitz nevi into atypical categories

Using this system, the risk for metastasis is as follows:
0-2 Low risk
3-4 Intermediate risk
5-11 High risk


Spitz tumors in children: a grading system for risk stratification.

Spatz A, Calonje E, Handfield-Jones S, Barnhill RL.

Department of Pathology, Institut Gustave-Roussy, Villejuif, France.

Arch Dermatol 1999 Mar;135(3):282-5 Abstract quote

OBJECTIVE: To describe a grading system for risk stratification of atypical Spitz tumors in children and adolescents. In some circumstances, unequivocal distinction between Spitz nevus and melanoma is practically impossible. It is likely that these lesions for which we lack specific diagnostic criteria represent a broad histological continuum extending from benign to malignant tumors. Therefore, we propose that Spitz tumors be categorized into low-, intermediate-, or high-risk categories based on the accumulation of abnormal features.

DESIGN: Retrospective study.

SETTINGS: Institutional practice.

PATIENTS: We present 30 cases of atypical Spitz tumors in patients younger than 18 years evaluated for at least 3 years or in whom a metastatic event developed during this period. I


MAIN OUTCOME MEASURE: The grading system was formulated after data collection.

RESULTS: Among the parameters studied, only diagnosis at age greater than 10 years, diameter of the lesion greater than 10 mm, presence of ulceration, involvement of the subcutaneous fat (level V), and mitotic activity of at least 6/mm2 carried a likelihood ratio greater than 1.50 and were therefore used for the grading system.

CONCLUSION: The application of an objective grading system, such as the one described herein for the first time, is the first step in providing useful information for the management of atypical Spitz tumors.


Quantification of vascularity in nodular melanoma and Spitz's nevus.

Binder M, Steiner A, Mossbacher U, Hunegnaw M, Wolff K, Pehamberger H.

Department of Dermatology, University of Vienna Medical School, Austria.

J Cutan Pathol 1997 May;24(5):272-7 Abstract quote

Spitz's nevi are acquired benign melanocytic skin tumors. Usually they are differentiated from nodular melanoma by clinical and histopathological criteria. Since Spitz's nevi are one of the most common simulators of nodular melanomas their bizarre histopathology may cause diagnostic confusion and make it difficult to differentiate these two melanocytic tumors. One of the histologic features shared by Spitz's nevus and nodular melanoma is prominent vascularity. The ability of malignant melanoma to induce angiogenesis is well established whereas benign melanocytic tumors do not have a prominent overall vascularity.

The purpose of this study was to find out whether the degree of vascularity of nodular melanomas differs significantly from that of benign Spitz's nevi. In this study the number of microvessels and the vessel area were determined in 23 Spitz's nevi and 16 nodular melanomas. The number of microvessels and the vessel area were determined on Ulex Europaeus agglutinin I-stained sections by computer-assisted image analysis. Two methods of measurement were used, namely systematic and selective sampling. Measurement of the whole tumor specimen (systematic sampling) revealed a vessel count of 10.83/field (SD +/-5.97) for Spitz's nevi whereas nodular melanomas exhibited a significantly lower (p=0.04) vessel count of 6.44/field (SD +/-3.85). This difference was even more pronounced when the vessel area (Spitz's nevi: 17.85x10-4mm2, SD +/-10.32; nodular melanomas: 7.88x10-4mm2, SD +/-5.23) was investigated (p < 0.001). The difference in vessel area and vessel count was insignificant for areas exhibiting the greatest vascularity (selective sampling).

Measurement of vessel count and vessel area lead us to conclude that Spitz's nevi have a significantly higher vascularity than do nodular melanomas.

Our results thus indicate that angiogenesis in these pigmented lesions is not correlated with malignancy.

RECURRENCE Arch Dematol 1990;126:1582-1583
Rare-see histology outline

Arch Dermatol 1979;115:1416-1420
Am J Surg Pathol 1989;13:931-939
Am J Surg Pathol 1990;14:53-68
Hum Pathol 1999;30:513-520
Arch Dermatol 1999;135:282-285

These cases that are cited have been diagnosed as:
Malignant Spitz nevus
Metastasizing Spitz nevi
Atypical Spitz nevi
Spindle cell and epithelioid cell nevi with atypia and metastases
Minimal deviation melanoma-Spitz nevus type

If one examines these papers, the majority of these cases utilize diagnostic criteria which differ from those of conventional Spitz nevi including:
Extension into subcutis
Sheets of melanocytes rather than discrete nests
Confluence of melanocytes disposed as nests with markedly irregular shapes
Sheets of melanocytes and cells with gigantic nucleoli
Presence of mitotic figures in melanocytes deep in the dermis
Plasma cells around nearby vessels

In addition, one article cited several clinical and histologic features that may predict malignant behavior:
Age >10 years
Lesional diameter >1.0 cm
Extension into subcutis
Mitotic rate of >6/mm2

All of the cases cited, however, did share some histologic similarity with Spitz nevi including a vertically oriented silhouette, sharp lateral circumscription, irregular epidermal hyperplasia, and clefts between melanocytes and epidermis

Even Sophie Spitz described a case in her original series which metastasized. In review, this case was present in a child and histologically extended into the subcutaneous fat of the foot. In retrospect, this case was probably a melanoma, especially if strict modern histologic criteria are utilized

If a Spitz nevus metastasizes, the correct diagnosis is malignant melanoma and not a metastasizing Spitz nevus. A Spitz nevus, in spite of cases which may be difficult to diagnose, is still a benign neoplasm


One caveat should be mentioned regarding lymph node metastasis of melanocytic neoplasms

In examining lymph nodes which drain the lesional skin, there may be occasional subcapsular nests of melanocytes. These may be benign and represent:
Normal migration of benign melanocytes, presumably a embryonic migration
Normal draining of benign melanocytes, especially from a congenital nevus

Only if the lymph node is nearly totally replaced by melanocytes can a diagnosis of metastastic melanoma be made with confidence

Sentinel Lymph Node Biopsy in Patients With Diagnostically Controversial Spitzoid Melanocytic Tumors

Christina M. Lohmann, M.D. ; Daniel G. Coit, M.D. ; Mary S. Brady, M.D. ; Marianne Berwick, Ph.D. ; Klaus J. Busam, M.D.

From the Departments of Pathology (C.M.L., K.J.B.), Surgery (D.G.C., M.S.B.), and Epidemiology and Biostatistics (M.B.), Memorial Sloan-Kettering Cancer Center, New York, NY, U.S.A.

Am J Surg Pathol 2002;26:47-55 Abstract quote

Melanomas can be difficult to diagnose histologically if they deviate in their growth pattern or cytology only minimally from a nevus. On occasion, even experts on melanocytic lesions may not reach a consensus on whether a lesion is a benign but unusual nevus or a malignant melanoma mimicking a nevus. This diagnostic dilemma is particularly well known for the distinction of Spitz nevus from melanoma. Diagnostic uncertainty and disagreement among consultant pathologists lead to confusion about the prognosis and clinical management of patients.

In this study we present the clinical and pathologic findings of 10 patients with diagnostically controversial melanocytic tumors, who underwent sentinel lymph node biopsy. In all of these cases, the diagnostic controversy among experts was between Spitz nevus and melanoma. Seven patients were female, and three were male, ranging in age from 7 to 46 years (mean 21 years). Histologic examination of the sentinel lymph nodes revealed tumor deposits in the lymph node parenchyma in 5 of 10 patients. Among patients with positive sentinel lymph nodes, two had satellite nodules and one showed additional tumor deposits in three nonsentinel regional lymph nodes. All patients are alive and free of disease with a follow-up of 10–54 months (mean 34 months).

Our study illustrates the role of a sentinel lymph node biopsy in the evaluation of patients with diagnostically controversial melanocytic tumors. Although the presence of metastatic tumor deposits in the sentinel lymph node supports the diagnosis of malignant melanoma, further studies are needed to determine the prognostic significance of the sentinel lymph node findings in such patients.


There is great controversy regarding adequate treatment for a Spitz nevus. Although this is definitely a benign proliferation of melanocytes, there may be hesitation on the part of both the dermatologist or treating physician to accept the diagnosis as well as the pathologist/dermatopathologist in making the diagnosis

At the very least, the diagnosis should be made only if most of the lesion is visualized and if the biopsy is a superficial shave or punch biopsy which does not completely or nearly completely visualize the entire lesion, a re-excision should be recommended

Having said that, if an experienced dermatopathologist or pathologist makes the diagnosis on an adequate excision, a reexcision is not necessary.

From a practical standpoint, a reexcision may be reasonable even if the diagnosis is confident. This is because if a Spitz nevus were to recur in a previously biopsied area, the distortion and treatment related atypia may make an accurate diagnosis very difficult, keeping in mind that Spitz nevi are already histologically atypical

J Am Acad Dermatol 1999;40:223-228
Adv Dermatol 2000;16:81-110.

Commonly Used Terms

Kamino bodies-Coalescent eosinophilic globules usually located at the dermal-epidermal junction.

Pigmented spindle cell nevus

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