Download Report

SPITZ NEVUS
Daryl J. Sulit, MD
Spitz nevi were first described by Sophie
Spitz in 1948.1 She originally called these lesions
“benign juvenile melanoma”. Sophie Spitz was able
to identify and describe a separate class of benign
melanocytic neoplasms in children that were
previously diagnosed and treated as malignant
melanoma.2 Prior to Spitz’s landmark paper, the
predominant opinion among the medical community
was that all suspicious pigmented lesions in children,
such as benign juvenile melanoma, be removed prior
to adulthood in order to prevent possible malignant
transformation.2,3 Today, “Spitz nevus” is the more
commonly used term for benign juvenile melanoma
because it is also encountered in adults and the term
“melanoma” carries a negative connotation.4 Other
synonyms for the Spitz nevus include Spitz tumor,
juvenile melanoma, spindle cell and epithelioid
nevus, and nevus of large spindle and/or epithelioid
cells.3,5
EPIDEMIOLOGY
Spitz nevi are relatively uncommon. Herreid
et al.6 approximates the incidence of Spitz nevi to be
7 per 100,000 people. Spitz nevi are found more
frequently in children and adolescents, but can occur
in adults. In Weedon et al.7, 69% of the 211 cases of
Spitz nevi occurred in patients less than 20 years old.
The incidence of Spitz nevi steadily decreases with
increasing age. One study3 found 28.5 % of its 200
cases of Spitz nevi were in patients older than 30
years old, but only 8.5% were older than 45. Spitz
nevi occur predominantly in the Caucasian population, and slightly more often in females.4,8
Dr. Sulit is a staff Navy flight surgeon from the Naval
Branch Medical Clinic, Marine Corps Air Station, Beaufort,
South Carolina.
The opinions expressed herein are those of the author and
do not reflect the policies or positions of the U.S. Navy, U.S.
Department of Defense, or any of its other branches.
DEFINING THE CLASSIC SPITZ NEVUS
A Spitz nevus can arise de novo or in
association with an existing melanocytic nevus. The
lesions can be asymptomatic or have a history of
rapid, but limited growth. Grossly, classical Spitz
nevi are well circumscribed, symmetrical, small to
medium sized firm papules (approximately 3-10
mm), with smooth discrete borders and a uniform
color, which is typically pink or flesh colored.9 Size
is typically less than 6 mm.7 Spitz nevi can occur in
various shapes, such as flat and polypoid. In a study
of 211 cases of Spitz nevi, 19% were described as
flat or uneven, 24% as polypoid, and 57% as plateau
or elevated.7 Spitz nevi usually are found on the
face, neck, or lower extremities (Figures 1, 2, and 3),
but can occur anywhere on the body.7,9
Histologically, the classical Spitz nevus
consists of large spindle and/or epithelioid melanocytes arrayed as epidermal nests grouped in a vertical orientation (the so called “bunches of bananas”
or “raining down pattern”), with clefting artifact at
the perimeter (Figures 4, 5, 6, and 7). The nests are
fairly uniform, nonconfluent, and evenly spaced.
There is little or no pagetoid spread pattern. Epidermal changes include acanthosis, hypergranulosis,
and hyperkeratosis. The intradermal pattern displays
maturation, with single-file or single unit arrays
descending to the base. Eosinophilic Kamino bodies
are frequently found along the dermoepidermal
junction. Kamino bodies are globular clusters which
represent apoptotic, degenerative melanocytes
(Figures 8 and 9). They stain positive with both
periodic acid-Schiff and trichrome. At the dermal
base, there is no mitoses, no pushing deep margins,
and lack of significant pleomorphism. Little or no
melanin is present.4,9,10
The differential diagnosis of the Spitz nevus
includes pyogenic granuloma, mastocytoma, juvenile xanthogranuloma, warts, melanocytic nevi, and
malignant melanoma.
DermatologyReview.com Journal ©, June 2005
1
SPITZ NEVUS – SULIT
DIFFERENTIATING SPITZ NEVI FROM
MELANOMA
Melanoma is a major part of the differential
diagnosis of the Spitz nevus. As stated before, the
Spitz nevus typically has a benign nature.1,3,11 But
melanoma is potentially fatal. Therefore, making a
correct diagnosis can be a matter of life and death
for a patient. Fortunately, there are specific gross
and histological guidelines to help differentiate the
classic benign Spitz nevus from malignant melanoma.9,10
In contrast to the classic Spitz nevus,
melanoma is typically greater than 6 mm,
asymmetrical, and poorly demarcated. Nests are
variable in size, shape, orientation, and there is
absence of Kamino bodies. There is pagetoid spread
into epidermis. The intradermal pattern shows lack
of maturation, high mitotic rate at the base, and
pushing deep margins into the dermal base or
subcutis. Cellular type is variable, often with heavy
pigmentation or irregularly scattered pigmented
cells. Epidermal changes are minimal. Other
suspicious findings include ulceration and highAge is another useful clue in the diagnosis of
Spitz nevus versus malignant melanoma. In Herreid
et al.6, the data of Spitz nevi and melanoma cases
submitted to the Yale Dermatopathology Laboratory
from May 1990 – June 1994 was analyzed. The age
range of 177 Spitz nevi cases was 6 months to 72
years of age, with an average age of 21 years. The
age range of 625 melanoma cases was 18 years to 94
years of age, with an average age of 56 years. The
study showed a ratio of Spitz nevi to melanoma
Figure 1: Spitz nevus on the leg of a child. Photograph courtesy of
Dr. Eve Lowenstein.
grade nuclear atypia.9.10
greater than 60:1 in individuals less than 20 years
old. Conversely, in individuals greater than 50 years
old, the ratio of Spitz nevi to melanoma was less
than 1:60. The age where equal numbers of Spitz
nevi and melanoma cases were found was 27 years.
This study demonstrates that the Spitz nevus is more
likely to occur in children and adolescents, and
melanoma is more likely to occur in adulthood,
especially in middle age and the later years.
Figures 2 and 3: Clinical and dermatoscope pictures of a classical Spitz nevus on a child. Photographs courtesy of Dr. Mark Blair.
DermatologyReview.com Journal ©, June 2005
2
SPITZ NEVUS – SULIT
Figures 4, 5, 6, and 7: Histological pictures of Spitz nevi. Photographs courtesy of Drs. Jennifer O’Neill and Samar Shami.
Though the risk is very small, melanoma can
occur in children and clinicians should be aware of
this fact. There are several case reports that
document the rare occurrence of malignant melanoma in children.8,12-17 One study states the risk of
melanoma before the age of 15 years is approximately 1 per million.15 Therefore, when clinicians
encounter a case of Spitz nevus in a child, it is most
likely a Spitz nevus; but they should consider the
possibility of melanoma in the back of their minds,
especially if it has atypical features. Conversely, if a
physician encounters a case of Spitz nevus in an
elderly patient, they should be suspicious of such a
diagnosis because it is rare in elderly patients and
further tests and examinations should be done to rule
out melanoma.
DermatologyReview.com Journal ©, June 2005
3
SPITZ NEVUS – SULIT
Figures 8 and 9: Histological pictures of eosinophilic, globular-shaped Kamino bodies. Photographs courtesy of Dr. Samar Shami.
PROBLEMS DIFFERENTIATING SPITZ NEVI
FROM MELANOMA
Despite gross and histological guidelines and
factors such as age, sometimes it is difficult to
distinguish Spitz nevi from melanoma, even for
experienced dermatologists and dermatopathologists.
The major problem is histological overlap with Spitz
nevi and malignant melanoma. Many authorities
have emphasized that there is no single discriminating factor for Spitz nevi and melanoma
because virtually every trait of Spitz nevi has been
described in melanoma.2,10,14,18-20 Multiple studies
have concluded that there was variability among
experts on the analysis of melanocytic nevi and
melanoma lesions and the final diagnosis was
subjective.5,18 Differentiation is further complicated
in Spitz nevi with atypical features such as large
size, ulceration, involvement of subcutaneous fat,
and increased mitotic activity.21
Some experts try to explain this phenomenon
by theorizing that both Spitz nevi and melanoma
exist along a continuum with the classic benign Spitz
nevus at one end of the spectrum and the aggressive
malignant melanoma at the opposite end, with a
diverse range of atypical lesions with features of
both in between.4,10,12,13,21 They contend this theory
is supported by case reports of metastasizing and
malignant lesions with Spitz-like characteristics.19
Others refute this claim and view the unequivocal
Spitz nevus as clinically benign and totally unrelated
to melanoma.11 They point out that many of these
case reports of malignant melanomas with Spitz-like
features do not fit the diagnosis of unequivocal Spitz
nevus.11 Regardless of which view is taken, the lack
of consensus among expert dermatologists and
dermatopathologists on discriminating Spitz nevi
and melanoma lesions cannot be ignored.5,18
Given the limitations of gross and histological analysis in discriminating benign Spitz nevi
and atypical Spitz nevi from malignant melanoma,
many investigators are researching other tools and
techniques that may help enhance diagnostic accuracy. Promising genetic analysis techniques include
comparative genomic hybridization (CGH) and
florescent in situ hybridization (FISH).22 In one
study22, researchers compared Spitz nevi and
primary cutaneous melanoma using CGH and FISH
and discovered clear differences. In the study, Spitz
nevi were found to have no chromosomal aberrations
or gains in chromosome 11p or 7q21-qter. In comDermatologyReview.com Journal ©, June 2005
4
SPITZ NEVUS – SULIT
parison, primary cutaneous melanomas had frequent
chromosomal deletions of chromosomal 9p, 10q, 6q,
8p and gains of chromosomes 7, 8, 6p, and 1q.22,23
Immunohistochemistry is another potential tool for
improving diagnostic accuracy.
Examples of
promising immunohistochemical markers include
antibody MIB-124-26, bcl-227, and anti-S100A628.
Studies have shown that most melanomas are
immunoreactive to MIB-1 and bcl-2, whereas Spitz
nevi are not.24-27 Recently, anti-S100A6 protein was
also shown to be a potential immunohistochemical
marker to differentiate a Spitz nevus versus
melanoma.28 Investigators found strong, uniform,
and diffuse S100A6 protein expression in the
junctional and dermal components of all 42 Spitz
nevi it studied versus weak and patchy S100A6
protein expression found mainly in the dermal
component of 35 out of 105 melanoma specimens it
studied. Anti-S100A6 is different from anti-S100.
Anti-S100 is sensitive in detecting melanocytes, but
it lacks specificity because it is found in many other
cell types and their associated tumors. Anti-S100A6
is more specific because it is restricted to a specific
subclass of normal cell types and certain cancer cell
lines.28 Although these techniques show exceptional
potential, further research will be required to prove
their reliability.
MANAGEMENT OF SPITZ NEVI
There is controversy regarding the treatment
of a classic Spitz nevus. Some authors recommend
conservative treatment because a Spitz nevus is
benign. They state the Spitz nevus may be removed
or left alone.3 Others agree, but would add that if
there are atypical features found on the Spitz nevus,
then complete excision with clinical follow-up is
appropriate.11,20,29 Other authors4 are more aggressive and recommend complete excision with clear
margins of all Spitz nevi, unequivocal or not,
because Spitz nevi have histological overlap with
malignant melanoma and recurrent lesions may
present with pseudomelanomatous changes30, which
makes differentiation more difficult later. They
conclude the benefits of complete excision outweigh
the risks of partial treatment.4 Regardless of which
treatment plan is chosen, regular follow-up with a
dermatologist is highly recommended to look for
Spitz nevus changes or recurrences after surgical
excision.
ACKNOWLEDGEMENTS
The author would like to thank Drs. Jeffrey Ellis and Gina
Taylor for their support in writing this article. Appreciation is
also extended to Drs. Eve Lowenstein, Mark Blair, Jennifer
O’Neill, and Samar Shami for providing clinical, dermatoscope, and histological pictures of Spitz nevi.
REFERENCES
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
Spitz S. Melanomas of childhood. Am J Pathol. 1948;24:
591-609.
Spatz A, Barnhill RL. The Spitz tumor 50 years later:
revisiting a landmark contribution and unresolved
controversy. J Am Acad Dermatol. 1999 Feb;40(2 Pt
1):223-8.
Paniago-Pereira C, Maize JC, Ackerman AB. Nevus of
large spindle and/or epithelioid cells (Spitz's nevus). Arch
Dermatol. 1978 Dec;114(12):1811-23.
Casso EM, Grin-Jorgensen CM, Grant-Kels JM. Spitz
nevi. J Am Acad Dermatol. 1992 Dec;27(6 Pt 1):901-13.
Barnhill RL, Argenyi ZB, From L, et al. Atypical Spitz
nevi/tumors: lack of consensus for diagnosis,
discrimination from melanoma, and prediction of outcome.
Hum Pathol. 1999 May;30(5):513-20.
Herreid PA, Shapiro PE. Age distribution of Spitz nevus vs
malignant melanoma. Arch Dermatol. 1996 Mar;132(3):
352-3.
Weedon D, Little JH. Spindle and epithelioid cell nevi in
children and adults. A review of 211 cases of the Spitz
nevus. Cancer. 1977 Jul;40(1):217-25.
Bader JL, Li FP, Olmstead PM, et al. Childhood malignant
melanoma. Incidence and etiology. Am J Pediatr Hematol
Oncol. 1985 Winter;7(4):341-5.
Elder DE, Murphy GF: Atlas of Tumor Pathology.
Melanocytic Tumors of the Skin. Washington, DC, Armed
Forced Institute of Pathology, 1990, pp40-57.
Piepkorn M. On the nature of histologic observations: the
case of the Spitz nevus. J Am Acad Dermatol. 1995 Feb;
32(2 Pt 1):248-54.
Shapiro PE. Spitz nevi. J Am Acad Dermatol. 1993 Oct;
29(4):667-8.
Barnhill RL. Childhood melanoma. Semin Diagn Pathol.
1998 Aug;15(3):189-94.
Barnhill RL, Flotte TJ, Fleischli M, et al. Cutaneous
melanoma and atypical Spitz tumors in childhood. Cancer.
1995 Nov 15;76(10):1833-45.
Crotty KA, McCarthy SW, Palmer AA, et al. Malignant
melanoma in childhood: a clinicopathologic study of 13
cases and comparison with Spitz nevi. World J Surg. 1992
Mar-Apr;16(2):179-85.
DermatologyReview.com Journal ©, June 2005
5
SPITZ NEVUS – SULIT
15. Handfield-Jones SE, Smith NP. Malignant melanoma in
childhood. Br J Dermatol. 1996 Apr;134(4):607-16.
16. Lerman RI, Murray D, O'Hara JM, et al. Malignant melanoma of childhood. A clinicopathologic study and a report
of 12 cases. Cancer. 1970 Feb;25(2):436-49.
17. Melnik MK, Urdaneta LF, Al-Jurf AS, et al. Malignant
melanoma in childhood and adolescence. Am Surg. 1986
Mar;52(3):142-7.
18. Farmer ER, Gonin R, Hanna MP. Discordance in the histopathologic diagnosis of melanoma and melanocytic nevi
between expert pathologists. Hum Pathol. 1996 Jun;27(6):
528-31.
19. Smith KJ, Barrett TL, Skelton HG 3rd, et al. Spindle cell
and epithelioid cell nevi with atypia and metastasis
(malignant Spitz nevus). Am J Surg Pathol. 1989 Nov;
13(11):931-9.
20. Shimek CM, Golitz LE. The golden anniversary of the
Spitz nevus. Arch Dermatol. 1999 Mar;135(3):333-5.
21. Spatz A, Calonje E, Handfield-Jones S, et al. Spitz tumors
in children: a grading system for risk stratification. Arch
Dermatol. 1999 Mar;135(3):282-5.
22. Bastian BC, Wesselmann U, Pinkel D, et al. Molecular
cytogenetic analysis of Spitz nevi shows clear differences
to melanoma. J Invest Dermatol. 1999 Dec;113(6):1065-9.
23. Bastian BC, LeBoit PE, Hamm H, et al. Chromosomal
gains and losses in primary cutaneous melanomas detected
by comparative genomic hybridization. Cancer Res. 1998
May 15;58(10):2170-5.
24. Bergman R, Malkin L, Sabo E, et al. 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 Mar;
44(3):500-4.
25. Li LX, Crotty KA, McCarthy SW, et al. A zonal
comparison of MIB1-Ki67 immunoreactivity in benign
and malignant melanocytic lesions. Am J Dermatopathol.
2000 Dec;22(6):489-95.
26. McNutt NS, Urmacher C, Hakimian J, et al. Nevoid
malignant melanoma: morphologic patterns and immunohistochemical reactivity. J Cutan Pathol. 1995 Dec;22(6):
502-17.
27. Kanter-Lewensohn L, Hedblad MA, Wejde J, et al.
Immunohistochemical markers for distinguishing Spitz
nevi from malignant melanomas. Mod Pathol. 1997 Sep;
10(9):917-20.
28. Ribé A, McNutt NS. S100A6 Protein Expression is
Different in Spitz Nevi and Melanomas. Mod Pathol. 2003
May;16(5):505-11.
29. Kaye VN, Dehner LP. Spindle and epithelioid cell nevus
(Spitz nevus). Natural history following biopsy. Arch
Dermatol. 1990 Dec;126(12):1581-3.
30. Omura EF, Kheir SM. Recurrent Spitz's nevus. Am J
Dermatopathol. 1984 Summer;6 Suppl:207-12.
DermatologyReview.com Journal ©, June 2005
6