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Estimation of the volume-weighted mean nuclear volume discriminates Spitz's nevi from nodular malignant melanomas.

BACKGROUND: Spitz's nevi are benign melanocytic skin tumors that are usually differentiated from nodular malignant melanomas by histopathologic criteria. Often, however, the architectural pattern and cytologic features of Spitz's nevi and nodular melanomas are similar. Hence, Spitz's nevi may be confused with nodular malignant melanomas at the histopathologic level. EXPERIMENTAL DESIGN: The determination of volume-weighted mean nuclear volume (Vv) uses a technique that permits an unbiased and efficient estimation of nuclear volumes in tissues. In this study, Vv was determined in 13 Spitz's nevi and 14 nodular malignant melanomas to investigate whether this stereologic approach may be of use in the differentiation of these two tumors. Vv was determined by computer-assisted image analysis (IBAS 20, Kontron, Germany) on Feulgen-stained sections using stereologic estimation of the Vv. RESULTS: The Vv (+/- SD) of Spitz's nevi was 491.6 micron3 (SD +/- 175.1), whereas nodular malignant melanomas exhibit a significantly higher (p < 0.001) Vv of 775.2 micron3 (SD +/- 205.4). This difference was even more pronounced when the deeper portions of the lesions (Spitz's nevi: 443.1 micron3, SD +/- 142.4; nodular malignant melanomas: 864.1, SD +/- 169.6) were investigated. In addition, we found that in relation to the depth of the lesions the mean Vv decreased in Spitz's nevi, whereas it increased in nodular melanomas. CONCLUSIONS: We found that (i) nodular malignant melanomas reveal a larger Vv than Spitz's nevi in general, and (ii) in contrast to malignant melanomas, the Vv of nevomelanocytes in Spitz's nevi decreases in the deeper portions of the dermis. Thus, Vv may be regarded as a helpful tool for the differential diagnosis of Spitz's nevi and nodular malignant melanomas.

Cell Nucleus↗

Incidence of new and changed nevi and melanomas detected using baseline images and dermoscopy in patients at high risk for melanoma.

OBJECTIVE: To determine the incidence of new, changed, and regressed nevi and melanomas in a cohort of patients at high risk for melanoma using baseline total body photography and dermatoscopy. DESIGN: Cohort study of patients at high risk for melanoma who underwent baseline cutaneous photography between January 1, 1992, and December 31, 1997, and had at least 1 follow-up visit by December 31, 1998. SETTING: Private practice rooms of 1 dermatologist in conjunction with a public hospital-based, multidisciplinary melanoma clinic in Victoria, Australia. PATIENTS: A total of 309 patients who had at least 1 of the following risk factors for melanoma: personal history, family history, 100 or more nevi, or 4 or more dysplastic nevi. MAIN OUTCOME MEASURES: Number of new, changed, and regressed nevi and melanomas detected and excised during the study interval. RESULTS: The incidence of new, changed, and regressed nevi decreased with increasing age (P<.001), whereas the incidence of melanomas increased (P = .05). The number of dysplastic nevi at baseline was positively associated with the incidence of changed nevi (P<.001) and melanomas (P = .03). The use of baseline photography and dermatoscopy was associated with low biopsy rates and early detection of melanomas. The development of melanoma in association with a preexisting nevus was not directly correlated with a change in a preexisting lesion monitored by baseline photography. CONCLUSIONS: Nevi are dynamic, and only a small percentage of all new and changed melanocytic lesions are melanomas. Patients younger than 50 years had a lower incidence of melanomas and a higher rate of new, changed, and regressed nevi when compared with patients older than 50 years. A new or changed pigmented lesion is more likely to be a melanoma in patients older than 50 years.

Adolescent↗

Absence of change in choroidal nevi across 5 years in an older population.

OBJECTIVE: To determine the proportion of choroidal nevi that were previously identified in a population cross section and that showed evidence of growth or progression during a 5-year period. METHODS: The Blue Mountains Eye Study was a cohort study of residents 49 years and older living in an area west of Sydney, Australia. Retinal photographs were used to identify choroidal nevi. Repeat photographs were obtained 5 years later and graded side-by-side to ascertain clinical growth or progression of all identified nevi. The greatest diameter and surface area of each nevus were measured. Nevus growth was defined as an increase in size of at least 33%. RESULTS: There were 160 choroidal nevi identified in the 128 subjects with nevi who participated in both eye examinations. Only 1 nevus (0.6%) exhibited clinical growth during the 5 years. No nevi developed other indicators of progression, such as subretinal fluid or orange pigment accumulation. CONCLUSIONS: Findings from this study indicate that benign nevi in older persons rarely progress. Regular eye examinations may be unnecessary for clearly defined small nonsuspicious choroidal nevi. This information could relieve patient anxiety and reduce costs associated with regular monitoring of nevi.

Aged↗

Count of benign melanocytic nevi as a major indicator of risk for nonfamilial nodular and superficial spreading melanoma.

A study of 207 consecutive white patients older than 18 years of age with nonfamilial nodular and superficial spreading melanoma and 295 controls was conducted in southeast France. Controls were recruited in a public health center. They were matched for sex and age to the overall population older than 18 years of age according to the last census. Melanocytic nevi were counted over the entire body, and data on sun exposure and skin type were collected. A multiple logistic model was used to determine the variables best predicting the risk of melanoma. In order of entry into the model, these variables were number of nevi from 5 to less than 10 mm (N5/10), outdoor leisure per year, frequency of sunburn in the last years, depth of suntan, number of nevi less than 5 mm in diameter (N1/5), age, social level, and hair color. Nevi counts were shown to be indispensable to the construction of a good predictive model for nonfamilial melanoma. After adjustment, estimated relative risks for nonfamilial melanoma rose with increasing number of N1/5, N5/10, and clinically atypical nevi (CAN) on the whole body. Compared with baseline groups the presence of more than 120 N1/5 was associated with a RR of 19.6, the presence of at least five N5/10 with a RR of 10, and the presence of more than one CAN with a RR of 2.77. The number of nevi on the buttocks seemed to be a strong risk factor of melanoma and may provide a simple technique for mass screening. The association between CAN and nonfamilial melanoma could be explained largely by the association between this tumor and the number of large nevi (greater than or equal to 5 mm). It is suggested that when using number of nevi as risk markers, their size might be more important than the other features of clinical atypia. Phenotypic traits and sun exposure, on the one hand, and number of nevi, on the other, seem to be independent risk factors. On the basis of nevus count alone, high-risk subgroups can be identified, which represent only a small part of the overall population older than 18 years of age and from which a large proportion nonfamilial melanoma would theoretically derive.

Adult↗

The density of melanocytic nevi correlates with constitutional variables and history of sunburns: a prevalence study among Italian schoolchildren.

In several studies from northern Europe, north America and Australia, melanocytic nevi are correlated with pigmentary traits and with intense sun exposure in a way similar to malignant melanoma. However, it is unclear if these data can be extrapolated to populations in other geographic locations and with different prevalent phenotypes. Our study was conducted among schoolchildren aged 13-14 years in 16 Italian cities. The parents of 3,127 children of a total of 3,160 (99%) consented to our study. A structured questionnaire was used to collect information about sun exposure and lifetime history of sunburns. Children were also examined by trained dermatologists to assess pigmentary traits and to make a count of melanocytic nevi. The median nevus density was higher among boys than girls. Areas that are usually chronically exposed to the sun exhibited a higher density of nevi compared to intermittently and rarely exposed areas. A higher density of nevi was found in children with lighter skin, blond hair and blue eyes. Red-haired children had a remarkably lower nevus density compared to the other color categories. The density of nevi increased with an increased number of reported episodes of sunburns. The results concerning nevi >/=6 mm in diameter paralleled those obtained for the total nevus density. However, at variance with total nevus density, a significant relation was also observed between larger nevi and freckling. Our study confirms that, in Italian schoolchildren, there is a relation between pigmentary traits, history of sunburns and the density of melanocytic nevi. Melanocytic nevi and malignant melanoma share a similar risk factor profile.

Adolescent↗

Loss of heterozygosity and microsatellite instability in acquired melanocytic nevi: towards a molecular definition of the dysplastic nevus.

Acquired melanocytic nevi may show signs of histological dysplasia, and epidemiological studies have demonstrated that dysplastic melanocytic nevi (DMN) are associated with an elevated melanoma risk. Nevertheless, the concept of DMN as precursors of melanoma has remained a concept, in view of the difficulty of establishing unambiguous cytological and histological criteria for DMN. Recent molecular data suggest that genetic instability is more frequent in DMN than in benign acquired melanocytic nevi. We have analyzed 54 benign melanocytic nevi and 6 DMN for loss of heterozygosity (LOH) at microsatellite markers D9S171, IFNA, D9S270, D9S265. LOH at one or more loci was detected in 17 out of 54 benign nevi and in 4 out of 6 DMN. LOH was demonstrated at 26 out of 103 amplified and informative microsatellites in benign nevi and at 6 out of 11 microsatellites in DMN. In addition, 6 benign nevi and 6 DMN were microdissected in 4-15 regions per lesion and analyzed for LOH and microsatellite instability (MSI) at D9S162 and D14S53. Both LOH and MSI were detected more frequently in dysplastic nevi (LOH frequency 0.61 vs 0.18; MSI frequency 0.27 vs 0.05). These results confirm that genetic instability is more prevalent in DMN than in benign acquired melanocytic nevi. Therefore, DMN might be defined as a monoclonal and genetically unstable, but limited, melanocytic proliferation that distinguishes this entity from the benign nevus and from malignant melanoma.

Chromosomes, Human, Pair 9↗

[Nevocytic nevi associated elastic fibers hyperplasia: a type of "twin nevus"].

BACKGROUND: In common intradermal or compound nevi, nevocytes may be associated with other kinds of cells, tissues or lesions. In rare cases, they are associated with notable hyperplasia of the elastic fibers. CASE-REPORTS AND RESULTS: In 11 nevi (10 intradermal or compound nevi and 1 blue nevus), we observed striking hyperplasia of the elastic fibers strictly limited to the nevi, with normal aspect of the elastic fibers in the surrounding reticular dermis. These fibers were thicker than normal elastic fibers and showed tight connexions with nevus cells. This hyperplasia was not clinically relevant. It was correlated neither with the age and sex of patients nor with the site of the excised nevi. It was seen in 0.1% of excised nevi. DISCUSSION: Hyperplasia of elastic fibers in some common nevi is a curiosity which may be classified together with other vascular, nervous, epithelial or connective twin lesions occasionally associated with the nevocytic nevi. It has to be added to the list of so-called "twin nevi".

Adolescent↗

Number of melanocytic nevi as a major risk factor for malignant melanoma.

A study of 121 melanoma patients and 139 control subjects from the University of California, San Francisco clinics was conducted among whites to examine the relationship between number of melanocytic nevi and cutaneous melanoma. Nevi that measured 2 mm or more in diameter were counted over the body by a dermatologist and a dermatology fellow. The average number of nondysplastic melanocytic nevi that were 2 mm or greater in diameter was 97 for melanoma patients and 36 for control subjects (p less than 0.001). Relative risks were 1.6 (p = 0.43) for 11 to 25 nevi, 4.4 (p = 0.01) for 26 to 50 nevi, 5.4 (p = 0.008) for 51 to 100 nevi, and 9.8 (p = 0.001) for more than 100 nondysplastic melanocytic nevi. Relative risks were 3.8 (p = 0.001) for 1 to 5 dysplastic nevi and 6.3 (p = 0.003) for 6 or more of these lesions. Report of blistering sunburns or of a previous skin cancer and having red or blond hair at the age of 20 were also independently associated with an increased risk of cutaneous melanoma. If confirmed in larger studies, the results presented on number of nevi and melanoma risk suggest a readily identifiable melanoma-prone group that could be followed to detect early malignant melanoma.

Dysplastic Nevus Syndrome↗

Effect of oral isotretinoin on dysplastic nevi.

We previously reported a favorable histologic response of dysplastic nevi to topical tretinoin in three patients. To investigate the anticancer and cancer preventive effects of retinoids we have examined the effect of systemic isotretinoin on dysplastic nevi. After confirmatory baseline biopsies, eleven patients with the dysplastic nevus syndrome were treated with oral isotretinoin, 40 mg twice a day for 4 months. At completion of therapy, at least three previously identified and photographed clinically typical dysplastic nevi were rephotographed and removed for histologic evaluation. Eight patients completed the full course of medication. There were no clinical changes in the dysplastic nevi in these patients. Posttherapy biopsy specimens in six volunteers revealed most of the remaining lesions to be dysplastic nevi. The majority of lesions biopsied in two subjects showed normal, benign nevi only. This proportion of clinically typical dysplastic nevi that prove to be normal nevi histologically (28%) is not significantly different from that reported by others. Oral isotretinoin does not appear to have a significant biologic effect on the clinical or histologic appearance of dysplastic nevi in the treatment schedule employed.

Administration, Oral↗

Widespread eruptive dermal and atypical melanocytic nevi in association with chronic myelocytic leukemia: case report and review of the literature.

Eruptive nevi have been associated with local skin trauma and immunosuppression, and atypical eruptive nevi preceding melanoma have been reported in immunocompromised transplant patients. We describe a 25-year-old man with widespread eruptive atypical and dermal melanocytic nevi in association with chronic myelocytic leukemia. Our patient's disease differs from earlier reports of eruptive nevi because his nevi appeared before induction chemotherapy. Eruptive nevi may have been a prodrome to leukemia in this patient. His nevi were histologically similar to eruptive atypical nevi observed in AIDS patients and may imply a link between systemic immunosuppression and melanocyte proliferation. We suggest that patients in whom eruptive nevi develop in association with immunosuppression should be carefully observed for the development of melanoma skin cancer.

Adult↗

Number and size of nevi are influenced by different sun exposure components: implications for the etiology of cutaneous melanoma (Belgium, Germany, France, Italy).

OBJECTIVE: The solar wavelength involved in melanoma occurrence remains unknown. Sunburns and latitude gradient are indicators of greater exposure to the ultraviolet B radiation. We examined the associations between the components of holiday sun exposure with numbers of small (2-4.9 mm) and large nevi (> or = 5 mm) in young children. METHODS: Information about each holiday period from birth to interview was recorded from parents of 628 6-7-year-old children in four European countries. Sun exposure was characterized using four different components: cumulative duration of holidays, number of holiday periods, sunburn episodes and latitude gradient between habitual living place and holiday places. RESULTS: Individual susceptibility to sunlight, cumulative duration and number of holiday periods were moderately associated with increasing number of small but not of large nevi. The number of small nevi together with sunburn history and latitude gradient were strong predictors of large nevi number. In contrast, sunburn history and latitude gradient were not associated with small nevi. CONCLUSIONS: Exposure to high doses of ultraviolet B radiation would be implicated in the formation of large nevi, while solar radiation other than the ultraviolet B could be implicated in the development of small nevi in children. Given that numbers of large nevi are strong predictors of melanoma in children and adolescents, these results agree with the hypothesis that high ultraviolet B doses are needed for melanoma occurrence, but probably not for nevi formation.

Belgium↗

Congenital melanocytic nevi frequently harbor NRAS mutations but no BRAF mutations.

Most melanocytic nevi develop on sun-exposed skin during childhood and adolescence and commonly harbor BRAF mutations or, less frequently, NRAS mutations. A small subset of nevi is present at birth, and therefore must develop independently of UV light. To assess whether these nevi have a different mutation spectrum than those that develop on sun-exposed skin, we determined the BRAF and NRAS mutation frequencies in 32 truly congenital nevi. We found no BRAF mutations, but 81% (26/32) harbored mutations in NRAS. Consistently, seven of 10 (70%) proliferating nodules that developed early in life in congenital nevi showed mutations in NRAS. A separate set of nevi that displayed histological features frequently found in nevi present at birth ("congenital pattern nevi") but lacked a definitive history of presence at birth showed an inverse mutation pattern with common BRAF mutations (20/28 or 71%) and less frequent NRAS mutations (7/28 or 25%). Thus, nevi that develop in utero are genetically distinct from those that develop later, and histopathologic criteria alone are unable to reliably distinguish the two groups. The results are consistent with the finding in melanoma that BRAF mutations are uncommon in neoplasms that develop in the absence of sun-exposure.

Adolescent↗

BRAF mutations are common somatic events in melanocytic nevi.

We determined mutations in the BRAF, N-ras, and CDKN2A genes in 27 histologically diverse melanocytic nevi and corresponding surrounding tissues from 17 individuals. Mutations in the BRAF and N-ras gene were found in 22 nevi (81%) from 16 individuals (94%). The predominant BRAF mutation T1799A (V600E) was detected in 18 nevi; 1 nevus had a novel A1781G (D594V) mutation in the same gene and 3 nevi had mutations in codon 61 of the N-ras gene. In 4 individuals both nevi carried a BRAF mutation, whereas in 2 other individuals 1 nevus showed a BRAF mutation and the second nevus had an N-ras mutation. In 2 individuals normal skin distant from nevi showed a BRAF mutation. No mutations were detected in the CDKN2A gene. The mutations in the BRAF and N-ras genes, in this study, were not associated with histologic type, location, skin type, size, or numbers of nevi. Our results suggest that mutations in the BRAF gene and to some extent in the N-ras gene represent early somatic events that occur in melanocytic nevi. We hypothesize the dual effect of solar ultraviolet irradiation on melanoma, through mutagenesis and by increasing the number of melanocytic nevi, many of which carry a BRAF or N-ras mutation.

Adult↗

Correlation between clinical atypia and histologic dysplasia in acquired melanocytic nevi.

BACKGROUND: The validity of clinical and histologic criteria in identifying dysplastic nevi is controversial. Recognition of the dysplastic nevus as a distinct clinicopathologic entity requires demonstration of significant agreement between clinical atypia and histologic dysplasia. OBJECTIVE: We attempted to determine the correlation between clinical atypia and histologic dysplasia in acquired melanocytic nevi and to evaluate the sensitivity and specificity of clinical criteria for dysplastic nevi when compared with histopathologic features. METHODS: A total of 940 acquired melanocytic nevi 3 mm in diameter or larger were selected by initially choosing clinically unequivocal dysplastic and nondysplastic nevi and then, from these, histologically unequivocal dysplastic and nondysplastic lesions. The level of concordance between clinical atypia and histologic dysplasia was estimated by kappa statistics. RESULTS: Nevi were classified as clinically dysplastic (n = 499) or nondysplastic (n = 441). On the basis of histologic features, 739 were classified as dysplastic and 201 as nondysplastic. Agreement between clinical atypia and histologic dysplasia was found in 432 nevi, that is, a sensitivity of 58.4% (3-5 mm = 27.2%, >5 mm = 69.8%). Agreement between clinical and histologic criteria on the absence of dysplasia was found in 134 nevi, a specificity of 66.6% (3-5 mm = 92.4%, >5 mm = 47.9%). The kappa value was 0.17 (3-5 mm = 0.14, >5 mm = 0.10). CONCLUSION: The limited sensitivity and specificity together with the negligible kappa value indicate a poor agreement between clinical and histologic diagnoses of dysplastic nevus. The dysplastic nevus cannot be considered a distinct clinicopathologic entity because histologic dysplasia is found in a range of nevi that may or may not show clinical atypia.

Adult↗

Prevalence of melanocytic nevi and freckles in young Israeli males. Correlation with melanoma incidence in Jewish migrants: demographic and host factors.

The role of host and environmental factors in the pathogenesis of multiple melanocytic nevi, atypical nevi, and freckles was studied in 1989 in a random sample of 3,040 Israeli males aged 17 years. Multiple melanocytic nevi were significantly associated with family history of melanoma or multiple melanocytic nevi (odds ratio (OR) = 15.0), fair or lightly pigmented skin color (OR = 2.7 and 2.3, respectively), and affiliation to the high or heterogenous melanoma risk group, determined by the incidence rates of melanoma in Jewish migrants from corresponding origin (OR = 3.1 and 2.1, respectively). An environment-related effect may account for the increased multiple melanocytic nevi risk among second- (OR = 8.2) compared with first-generation, native-born recruits (OR = 3.0) from the high melanoma risk group whose families had been living in Israel the longest. Atypical nevi were associated with fair (OR = 6.1) and lightly pigmented (OR = 3.5) skin color, high and moderate sunburn susceptibility (OR = 4.7 and 2.5, respectively), and family history of melanoma or multiple melanocytic nevi (OR = 4.7). Freckles were significantly associated with sun-sensitive phenotype, family history of melanoma or multiple melanocytic nevi (OR = 1.5). Conservative (OR = 1.9) or nonreligious status (OR = 1.9), and high (OR = 2.4) or heterogenous melanoma risk groups (OR = 1.8). These findings indicate that environmental factors may modify the occurrence of multiple melanocytic nevi and freckles in genetically susceptible ethnic groups.

Adolescent↗

Expression of Melan-A and Ki-67 in desmoplastic melanoma and desmoplastic nevi.

BACKGROUND: Desmoplastic melanoma (DMM) is an uncommon melanoma variant with a distinct morphology, including a prominent spindle cell component with fibrosis, as well as a distinct immunohistochemical profile. Histologically, the spindle cell component of DMM can be confused with sclerotic/desmoplastic nevi, nonpigmented blue nevi, scar, and neural tumors. The histological distinction between sclerotic/desmoplastic/blue nevi and DMM using standard light microscopic techniques can be exceedingly subtle. Therefore, we investigated whether immunohistochemical staining for Melan-A and Ki-67 expression can be used to discriminate these lesions, distinguishing between epithelioid and spindle cell compartments of the lesions. DESIGN: Fifty cases of DMM and 13 cases of sclerotic/desmoplastic/blue nevi were identified. Standard immunohistochemical techniques were used with antibodies towards HMB-45, Melan-A (A103), and Ki-67; 43 of 50 DMM cases were available for staining with Melan-A, 42 of 50 for HMB-45, and 31 of 50 cases were stained with Ki-67. All 13 nevi were stained for Melan-A and 8 for Ki-67. Immunoreactivity to Ki-67 antibody was scored as 0 to 5%, 6 to 10%, 11 to 30%, or greater than 30% positive tumor cells. RESULTS: Only 3 of 43 and 3 of 42 of spindle cell compartments of DMMs were positive for Melan-A and HMB-45, respectively. Focal staining of epithelioid cells in the junctional component or superficial dermis was observed in 33% (14/43). In contrast, 100% of the 13 nevi were strongly positive for Melan-A (P < 0.001). Seventeen melanomas (55%) were 0 to 5% positive for Ki-67, five (16%) fell into the 6 to 10% category, three (10%) were between 11 and 30%, and six (19%) were at least focally greater than 30% positive. All 8 nevi (100%) had less than 5% positive cells for Ki-67 (P = 0.02), with only 2 cases having more than 2% positive cells. CONCLUSION: The sclerotic/desmoplastic and hypopigmented blue nevi were uniformly positive for Melan-A, while the vast majority of DMM were negative in their spindle cell compartments. Melan-A is very useful in distinguishing between DMM and sclerotic nevi. Ki-67 appears to be an inconsistent marker for DMM. However, a high labeling index (over 5%) may be used as a clue in diagnosing DMM.

Antigens, Neoplasm↗

Expression of melanocyte differentiation antigens and ki-67 in nodal nevi and comparison of ki-67 expression with metastatic melanoma.

Nodal nevi represent a potential diagnostic pitfall in the analysis of lymph nodes. They may be confused with metastatic melanoma or carcinoma. Although several morphologic guidelines exist for the recognition of nodal nevi, on occasion immunohistochemical studies may be helpful for diagnosis, especially when melanocytes extend into the lymph node parenchyma. To learn more about the immunohistochemical profile of nodal nevi we examined 15 nodal nevi for the expression of S-100 protein, gp100 (HMB-45), Melan-A/MART-1 (A103), and tyrosinase (T311), and we studied the expression of Ki-67 (MIB-1) in nodal nevi and 40 melanoma metastases (35 lymph node and five cutaneous metastases). All nodal nevi were homogeneously immunoreactive for S-100 protein, tyrosinase, and Melan-A/MART-1. Two nodal nevi were focally positive for gp100. Fourteen of 15 nodal nevi were completely negative for Ki-67. One large cellular nodal nevus showed nuclear labeling in <0.2% of melanocytes. All metastases showed MIB-1 labeling. However, the percentage of labeled tumor cells varied widely, ranging from 2% to 80%. These results demonstrate that MIB-1 and HMB-45 are helpful reagents for the distinction of nodal nevi from melanoma. Immunohistochemistry for S-100 protein, Melan-A/MART-1, or tyrosinase facilitates the recognition of melanocytes but does not distinguish between nodal nevus and metastatic melanoma.

Adult↗

The T1796A mutation of the BRAF gene is absent in Spitz nevi.

BACKGROUND: BRAF, a serine/threonine kinase, is a component of the retrovirus-associated sequence (RAS)-RAF-extracellular-regulated protein kinase (ERK)-MAP kinase signal transduction pathway mediating signals from RAS to ERK. The T1796A single point mutation in exon 15 of the BRAF gene has recently been reported in a high percentage of malignant melanomas and benign melanocytic lesions such as congenital nevi, compound nevi, intradermal nevi and dysplastic nevi. The T1796A mutation has been shown to promote cell proliferation. METHODS: We screened 21 Spitz nevi and six spitzoid malignant melanomas for the presence of the T1796A BRAF mutation. RESULTS: The T1796A BRAF mutation could not be detected in any of the 21 Spitz nevi but was present in two of the six spitzoid malignant melanomas. CONCLUSIONS: Our results, in conjunction with data from a previous investigation, suggest that the melanocytic proliferation of Spitz nevi might be induced by components of the RAS-RAF-ERK-MAP kinase pathway different from BRAF, possibly combined with other genetic aberrations. The lack of the T1796A BRAF mutation might be of practical importance in distinguishing Spitz nevi from other melanocytic lesions simulating Spitz nevi as a part of a future complex diagnostic assay.

Base Sequence↗