Neonatal melanoma arising in a giant congenital nevus

INTRODUCTION: Malignant melanoma arising in giant congenital nevus is a well known but rare event. CASE REPORT: A 15 day-old boy with giant congenital nevus all over the left leg was seen for a 6 mm red and bleeding nodule inside the nevus on the inner thigh. Histopathology showed spindle cell malignant melanoma. A 3 cm edge surgical excision was performed with a favorable outcome which persists 5 years later. DISCUSSION: The diagnosis of malignant melanoma is always very difficult in a child, unless metastasis occurs. Histopathologic modifications of childhood malignant melanomas are discussed. Development of malignant melanoma in giant congenital nevus would not appear to exceed 5 p. 100. Nevertheless, early surgical excision is recommended because the nevus is smaller and skin mobilization is easier at this age.     

Malignant melanoma in childhood and adolescence

In this review, the epidemiology and prognosis of malignant melanoma in childhood and adolescence (CMM) are discussed with reference to 627 patients reported in the literature. CMM accounts for only 1-2% of all melanomas, but there is the same increasing incidence as in adult melanoma. A distinction is made between congenital CMM (n = 27), CMM on giant congenital pigmented naevi (n = 69) and CMM in small pigmented lesions or de novo. The latter are identical in biological behaviour to melanomas in adults, while the CMM on giant naevi nearly always have an unfavourable outcome. Chemotherapy seems to be more effective in CMM than in adult melanomas, but prophylaxis is also the best therapy in children: early removal of congenital giant pigmented naevi and frequent monitoring, if not excision, of all congenital melanocytic lesions must be considered.     

Malignant blue nevus: a case report and molecular analysis

Malignant blue nevus is a rare melanocytic tumor that is described by some authors as a variant of malignant melanoma, whereas others regard it as a distinct entity. To our knowledge no molecular studies of this tumor have been performed, although the molecular pathogenesis of conventional melanomas has been extensively described. We present a case of malignant blue nevus that developed in a 15-cm congenital blue nevus on the back of a 41-year-old man. Subsequent regional lymph node and lung metastases developed within 1 and 29 months, respectively. We performed a molecular analysis for loss of heterozygosity on microdissected samples from the spectrum of benign to malignant blue nevus, using a panel of eight genes (MTS1, MXI1, CMM1, p53, NF1, L-myc hOGG1, and MCC), many of which are commonly associated with conventional melanomas. No loss of heterozygosity was detected, despite informativeness in seven genes. We suggest that malignant blue nevus may represent a distinct entity with a different molecular pathway to tumorigenesis than that of conventional melanomas.     

Melanoma within naevus spilus: 5 cases

BACKGROUND: Nevus spilus is defined as café-au-lait macules with dark maculopapular speckles. Histologically, it has the aspect of lentigo associated with nevocellular nevus. There are 3 types of nevus spilus: small or medium-sized (<20 cm), giant and zosteriform. Malignant transformation of nevus spilus is rare. PATIENTS AND METHODS: We analyzed the cases of 5 patients presenting melanoma within nevus spilus as well as 20 published cases. The evaluation criteria were: for nevus spilus: size, type, topography, age of onset and presence of dysplastic nevi within the nevus spilus; for melanoma: clinical aspect, histological type, thickness, level and age at diagnosis. The presence of other risk factors for melanoma was noted. RESULTS: The 14 women and 11 men had a mean age of 49 years at melanoma diagnosis. Type of nevus spilus was: small or medium-sized (15 cases), zosteriform (6 cases) and giant (4 cases). Only 3 nevi spili were<4 cm in diameter. Nevus spilus was present since birth (11 cases), childhood (7 cases), after the age of 20 years (3 cases) and was unspecified in 4 cases. Three of our five patients had other risk factors for melanoma. Two patients were presenting 2 melanomas within nevus spilus. The histological type of melanoma was not specified in 8 cases but SSM was the most common type (13 cases). Median Breslow thickness was 1.25 mm (0.27 to 8 mm) for the 19 cases in which it was specified. CONCLUSION: The following criteria appeared to be associated with risk of developing melanoma in nevus spilus patients: nevus spilus present since birth, nevus spilus over 4 cm in diameter, and giant or zosteriform nevus spilus. Development of melanoma within nevus spilus is a rare event. Consequently, guidelines for follow-up of nevus spilus cannot be defined. However, follow-up is recommended, and in particular, self-examination.     

MALIGNANT MELANOMA IN CHILDREN

Background. While significant risk factors for malignant melanoma may initially develop or are first seen in childhood, the actual occurrence of this neoplasm in prepubertal children is uncommon. Methods. A retrospective study of malignant melanoma in Puerto Ricans up to 16 years of age occurring from 1973 to 1990 was carried out by identifying those cases in the Puerto Rico Cancer Registry. Results. A total of seven cases were found consisting of three boys and four girls with ages ranging from 22 months to 16 years and comprising 0.94% of the total melanomas. In three of the seven cases, there was a history of a previously existent small congenital melanocytic nevus on the area. Three cases were Clark's level I, two level II, and in two cases with proved metastatic disease, Clark's level of invasion were not reported. Those cases with Clark's level I and II had a 100% 5-year survival. Conclusions. Although rare, malignant melanoma in children can be as aggressive as in adults. Among the known factors predisposing to malignant melanoma, three out of seven cases developed within a small congenital nevus, two of which occurred during the first decade of life. Due to the rarity of this event in our population, it appears unreasonable to excise all small congenital nevi during the first decade of life. Even for those who advocate excision of all small congenital nevi, the evidence at present suggests that such small nevi very rarely undergo malignant change before puberty and therefore a policy of observation in childhood and offering excision around the time of puberty is perfectly logical.     

A comparative study of fluorescence in malignant melanoma and nevocellular nevus using a fluorescence microscope and formalin-fixed specimens

Fluorescence in malignant melanoma cells was investigated. The specimens from 18 cases of malignant melanoma and 26 cases of nevocellular nevus, which were fixed with formalin and embedded in paraffin wax, were studied by the fluorescence microscopic method. On the fluorescence microscope, the malignant melanoma cells emitted intense fluorescence from the cytoplasm. The nevus cells with large amounts of melanin granules showed moderate fluorescence. The tumor cells of melanoma in situ and nevus cells with few melanin granules emitted little fluorescence. Not only malignant melanoma cells but also nevus cells in the formalin fixed specimens had various degrees of fluorescence. Many cases of malignant melanoma emitted intense fluorescence, but this was rarely found in nevocellular nevus. This method is also useful in differentiating melanoma from nevocellular nevus.     

Okkultes dermales Primärmelanom in kongenitalem Nävuszellnävus

Malignant melanomas normally arise at the dermoepidermal junction. Development of these tumours in deeper layers of the dermis without having contact with the junction is rare. A small congenital melanocytic nevus localized in the region of the waist band was excised because of mechanical irritation; it had not shown any changes over years. A thorough examination of the whole body did not give any clue to a malignant melanoma. Histologically a compound nevus with the typical architecture of a congenital melanocytic nevus was found. In the deeper dermis there was an isolated nodule of extremely atypical melanocytes with minimal pigmentation of melanin. S100 antigen could be demonstrated throughout the whole tumour whereas HMB45 was only found at the dermoepidermal junction. There was no marking of the tumour cells with a pancytokeratin antibody. A histological relationship between the new tumour and a mixed tumour of the left testicle, which had been excised 3 years ago, could be excluded. We did not find any metastases neither by image-aided methods nor by sentinel lymph node biopsy.     

Malignant melanoma arising in a blue nevus with features of pilar neurocristic hamartoma

A 65-year-old man presented with a history of a giant blue plaque of the parietal scalp since childhood. Biopsy revealed a cellular blue nevus. The blue nevus was observed for 10 years and thought to be unchanged until a new adjacent lesion was noted. Biopsy of the new lesion revealed metastatic malignant melanoma. A wide excision was performed of the original lesion which revealed malignant melanoma arising in a blue nevus. Areas within the blue nevus were consistent with a pilar neurocristic hamartoma, whereas other areas were consistent with a common blue nevus. Subsequent satellite metastases developed, with early metastases resembling blue nevi except for the absence of a stromal component and the presence of hyperchromatic nuclei. Later metastases were typical of metastatic melanoma. This case illustrates the uncommon evolution of malignant melanoma from a blue nevus. The histological features and relationship between melanoma, blue nevus, and pilar neurocristic hamartoma are reviewed.     

Malignant melanoma in childhood and adolescence: report of 13 cases

We reviewed all cases of malignant melanoma in children younger than 17 years of age who were evaluated at Sainte Justine Hospital, a tertiary care pediatric center, between 1980 and 2002. The medical records and histologic features of all cases were reviewed. Thirteen cases were identified, 4 boys and 9 girls. Fifty-three percent of patients were prepubescent. None of the patients had a predisposing condition (eg, giant congenital nevi, dysplastic nevus syndrome, or xeroderma pigmentosum). One patient had had chemoradiotherapy previously for an undifferentiated pleuropulmonary malignant tumor (blastoma) and another patient had Down syndrome. The most frequent reason for initial consultation was a recent increase in size of the lesion. Three patients had pyogenic granuloma-like lesions. Eighty-five percent of the observed melanomas were nodular in type. Tumor thickness ranged from 0 to 6 mm with a median and mean thickness of 2.8 and 3.2 mm, respectively. The overall 5-year survival rate was 58.8%. Lack of awareness and delay in diagnosis may lead to a higher incidence of thick and intermediate melanoma in children. Because it appears that the majority of melanomas in childhood and adolescence occur de novo, clinicians should consider this condition in the differential diagnosis of any suspect lesion in children and adolescents even without an identified predisposing factor.     

Dermal melanocytosis of the scalp associated to intracranial melanoma: malignant blue nevus, neurocutaneous melanosis, or neurocristic cutaneous hamartoma?

Intracranial invasion of cellular blue nevus is extremely rare, and its malignant transformation is even less common. The differential diagnosis includes neurocutaneous melanosis and neurocristic cutaneous hamartoma. A 50-year-old female presented with intracranial melanoma in contiguity with a congenital blue nevus on the scalp. The patient showed a wide pigmented lesion on the scalp that had grown in the last few years over the congenital blue nevus. Magnetic resonance imaging revealed an intracranial tumor lying contiguous to the nevus. Despite aggressive surgery, the tumor relapsed and the patient developed systemic metastases. We report a rare case of cellular blue nevus showing an unexpected aggressive behavior with extensive extra- and intracranial expansion and distant metastases.     

RETROLUMBAR SUBCUTANEOUS EPENDYMOMA AND GIANT BATHING-TRUNK NEVOCELLULAR NEVUS

Background. Subcutaneous ependymomas have been reported rarely in dermatologic reviews and, apparently, were never associated with other cutaneous malformations. Methods. A 60-year-old woman with a retrolumbar subcutaneous ependymoma and a giant bathing-trunk nevocellular nevus submitted to thorough dermatologic and neurologic investigation. The surgical material was extensively analyzed with light and electron microscope. The literature was reviewed. Results. The tumor fits exactly the classical prerequisites of the clinical and pathologic diagnosis. In contrast with the literature, it developed at 53 years, apparently after a trauma, within a congenital giant nevocellular nevus, at the retrolumbar level; it proved unrelated to any spinal cord alteration and so far appeared quite benign. Conclusions. The observation of a retrolumbar subcutaneous ependymoma is reported with detail; this tumor exceptionally recognized by dermatologists must be included in the differential diagnosis of lumps arising in the retro-lumbar-retrosacral area. The most peculiar feature was its development within a giant bathing-trunk nevocellular nevus; such a fascinating association of two neurectodermal defects, as far as known, is presented for the first time.     

A Malignant Melanoma Associated with a Blue Nevus of the Lip

Blue nevi are characterized by a collection of pigment-producing melanocytes in the dermis. These lesions clinically present as well demarcated cerulean-blue or bluish black colored papules or plaques that usually measure less than 1 cm in diameter. They are typically found on the dorsal surface of the hands and feet or in the head and neck region; however, they are rarely found in the oral cavity. These lesions are usually benign and stable over time. However, malignant melanomas developing in or associated with a blue nevus (which is also called malignant blue nevus) have been only rarely reported. A malignant blue nevus might develop in a common blue or cellular blue nevus, a giant congenital nevus or in a nevus of Ota, or it may be malignant from the start. Malignant blue nevi most commonly are found on the scalp. A malignant blue nevus of the lip has not been previously reported in the medical literature. We report here on a patient with a malignant melanoma associated with a blue nevus of the lip. The malignant melanoma was presumed to have developed from a blue nevus that was present on the upper lip of a 50-year-old male.     

Nerve growth and expression of receptors for nerve growth factor in tumors of melanocyte origin.

Nerve growth factor (NGF) stimulates growth and differentiation of sensory and sympathetic neurons. It is not known what role NGF plays in melanoma development, but nevus and malignant melanoma cells express NGF-receptor (NGF-R). We counted nerve fibers within melanocytic nevi, primary cutaneous melanomas, and cutaneous melanoma metastases using a monoclonal antibody (MoAb) as marker against a 200-kD glycoprotein that is expressed on human nerves. The expression of NGF-R was studied in serial cryostat sections using a MoAb against the NGF-R. Compared to normal skin, increased numbers of nerve fibers were found in 72 melanocytic nevi. In congenital nevi their number significantly increased with age. In 47 primary cutaneous melanomas the number of nerve fibers decreased in proportion to tumor thickness. In 33 cutaneous melanoma metastases no accumulation of nerve fibers was found. NGF-R was not expressed in normal skin melanocytes and in the majority of nevus cells in melanocytic nevi. Considerable numbers of NGF-R-positive nervus cells were found only in some congenital nevi and few acquired nevi with dysplastic features. By contrast, in primary and metastatic melanomas higher expression of NGF-R was observed. The increased number of nerve fibers in melanocytic nevi suggests that neurite-promoting factors are produced in situ. Production of such factors appears to be lost in malignant melanoma cells. The finding of an inverse correlation between an abundance of nerve fibers in NGF-R-poor nevi and a high expression of NGF-R in melanomas that show no evidence of nerve growth suggest a role of NGF and its receptor in malignant melanocytic tumors.     

The relationship between melanocytic nevi and malignant melanoma

In conclusion, although there are data, some quite convincingly implicating dysplastic nevi and congenital nevi (particularly "giant") as "precursors" of malignant melanomas, our ability to predict the magnitude of these associations is lacking. Thus, until additional basic and clinical research data are forthcoming, any recommendation to prophylactically remove all congenital nevi or all dysplastic nevi in order to decrease the incidence of malignant melanoma is premature. In regard to congenital nevi, evidence exists that giant (larger than 20 cm in diameter) congenital nevi may have a significant risk factor so as to warrant, when feasible, prophylactic excision of such lesions. In our opinion, no uniform recommendation can be made at this time for the management of small and medium-sized congenital nevi. Patients with familial dysplastic nevus syndrome should be followed carefully and educated concerning the early detection of malignant melanoma. Patients with sporadic dysplastic nevus syndrome deserve further study to enable us to accurately determine their risk of developing malignant melanoma.     

Malignant blue nevus with lymph node metastases

Background:  Malignant blue nevi arise within cellular blue nevi and contain atypical mitoses, necrosis, nuclear pleomorphism and prominent nucleoli. Malignant blue nevus has been described as a distinct identity, a rare form of malignant melanoma, and a misdiagnosed melanoma.
Methods:  We present a patient with metastatic malignant blue nevus and studies on the histopathologic, immunohistochemical, and molecular features of the neoplasm.
Results:  Histology showed a malignant blue nevus arising in a combined intradermal and cellular blue nevus. CD117 (c-kit) staining showed diffuse cytoplasmic expression within the cellular blue nevus, decreased staining in the malignant component, and variable positivity within the lymph node metastases. Molecular loss of heterozygosity analysis showed different allelic patterns at the hOGG-1 locus between the melanoma and control skin specimens with a varying heterozygous allelic pattern in both the benign and malignant blue nevus.
Conclusions:  Our case of malignant blue nevus with lymph node metastasis involved mutation of the hOGG-1 DNA repair gene. CD117 showed decreased staining of the primary malignant blue nevus with marked upregulation in the metastatic lesion, unlike most metastatic melanomas. Further study is needed to determine if hOGG-1 mutation or c-kit upregulation play a role in the pathogenesis of dendritic melanocytic lesions (either benign or malignant).     

Case Reports of Fatal or Metastasizing Melanoma in Children and Adolescents: A Systematic Analysis of the Literature

Childhood melanoma (ChM) is rare, with clinical and epidemiologic characteristics that differ from those of adult melanomas. The objective of the current study was to systematically identify and analyze case reports and case series of fatal and metastasizing ChM in the medical literature. ChM case reports with a fatal outcome or metastases were identified using a Medline search and subdivided into ChM developing in the absence of a congenital melanocytic nevus (ChM without CMN) and ChM associated with a CMN (ChM with CMN); 258 cases of ChM without CMN (206 cutaneous, 52 noncutaneous) were identified. In cutaneous ChM without CMN with a fatal outcome (n = 155), the mean age at diagnosis was 13.1 years (median 14 yrs). The mean Breslow index in this group was 8.5 mm for children ages 0 to 10 years and 3.7 mm for children ages 11 to 18 years. In ChM with CMN (n = 178; 112 cutaneous, 66 central nervous system [CNS]), the mean age at diagnosis was 5.8 years for cutaneous melanoma (median 3 yrs) and 5.5 years for CMN‐associated CNS melanoma (median 3 yrs). The majority of CMN‐associated cutaneous melanomas developed in small and giant CMN (vs medium and large); 53.9% of CNS melanomas developed in patients with multiple medium CMN. This study represents the largest and most complete synopsis of ChM case reports in the medical literature. Our analysis supports the view that cutaneous ChM without CMN (or associated with smaller CMN) differs in several important aspects from ChM associated with large or giant CMN.     

Cutaneous melanoma in childhood and adolescence: an analysis of 36 patients

Analysis of data of 6931 patients with cutaneous melanoma seen at the Department of Dermatology and Allergology at the Ludwig-Maximilians-University of Munich between 1977 and 1998 identified 36 patients in whom cutaneous melanomas developed during childhood or adolescence (age <18 years). Clinical courses of all patients and histopathologic characteristics of the lesions were reviewed. Seventeen patients were boys and 19 patients were girls. The median ages of the boys and girls were 15 and 16 years, respectively (range, 2-17 years). Thirty-one patients presented with nonmetastatic primary melanomas and 5 patients presented with metastatic melanoma. Forty-seven percent of the primary lesions were associated with a nevus (22% with congenital nevi and 25% with acquired nevi). Tumor thickness ranged from 0.24 to 7.0 mm, with a median of 1.29 mm (mean, 1.67 mm). All patients with primary melanomas received surgical therapy; patients with metastatic disease received chemotherapy, radiation therapy, or both. Relative 5-year survival was 87.5% for the group of patients younger than 18 years. Similar to experience in adult patients, survival strongly correlated with tumor thickness and clinical stage at the time of diagnosis. The data emphasize that a high index of suspicion for cutaneous melanoma is needed by clinicians assessing melanocytic lesions in children and adolescents for early diagnosis. Reduction of the melanoma mortality rate in children and adolescents will be achieved through identification of patients at increased risk.     

Significant melanocytic lesions in infancy, childhood, and adolescence

Malignant melanoma is diagnosed yearly in approximately 300 persons under age 20 in the United States. Relatively recent advances in dermatology include the recognition of lesions felt to be potential precursors of malignant melanoma. Small congenital melanocytic nevi, present in 1 per cent of all newborn infants, may have a small but definite potential for developing malignant melanoma. Furthermore, despite inconclusive data, many leading dermatologists now advocate removal of these small congenital lesions. Giant congenital melanocytic nevi, with their strong predilection for undergoing malignant change, are removed surgically at an early age, often in multistaged procedures. Dermabrasion, once felt to have a role in the treatment of giant congenital nevi, does not remove the malignant potential of these lesions. The dysplastic nevus syndrome, recognized in 1976, identifies individuals at increased risk for developing melanoma. Adolescents who have the dysplastic nevus syndrome or who are members of families with the syndrome require close medical supervision and patient education. The benign Spitz nevus, with its histologic similarity to malignant melanoma, continues to challenge the dermatopathologist and clinician. These lesions--the Spitz nevus, dysplastic nevus, congenital melanocytic nevus, and malignant melanoma--must all be actively considered when regarding the many other benign melanocytic lesions found in infancy, childhood, and adolescence.     

Clinical and Pathological Correlation of Malignant Melanoma

We have attempted to review virtually all forms of cutaneous and mucocutaneous melanomas. Superficial spreading, lentigo maligna and nodular melanomas have been more thoroughly investigated and documented in previous studies. Lentigo maligna melanoma appears to have a longer duration and better prognosis than SSM or NM. The overall prognosis probably correlates better with the anatomic level and thickness of invasion than with type (Clark et al. 1975, Breslow 1970, 1975). It appears that certain pitfalls exist in either method of assessing prognosis, and it is recommended that both methods be applied in evaluating a malignant melanocytic lesion when feasible. With regard to in situ melanoma or Level I melanoma, it is our experience that such lesions can achieve a 100% cure rate when completely excised. Hence, we prefer to call such lesions severely atypical melanocytic hyperplasia, and thus avoid labeling these patients with a malignant diagnosis. The most difficult histologic challenge in diagnosing a lesion of malignant melanoma is the Spitz nevus. The pathologist should never be biased by the age of the patient, for a serious mistake can arise. We have seen a case of nodular melanoma in a 13-year-old girl diagnosed as Spitz nevus only to be followed by a lymph node metastasis years later. Other examples of histologic differential diagnoses of malignant melanomas include, for example, halo nevus, soft tissue sarcoma, squamous cell carcinoma with spindle cell proliferation, Paget's disease of metastatic carcinoma, (for example, from the breast). Therefore, the approach to the diagnosis of malignant melanoma necessitates an evaluation of both clinical and pathological features. Histologic study must encompass both the pattern of growth and cellular cytologic detail for successful interpretation.     

A Case of Spitzoid Melanoma

Spitzoid melanoma is a subtype of melanoma that, clinically and histologically, resembles a Spitz nevus. Clinically, spitzoid melanomas usually evolve from amelanotic nodular lesions, growing to 1 cm or more in diameter. They often remain clinically undiagnosed because of their wide variety of clinical appearances and a lack of pigmentation. Distinguishing a Spitz nevus from a spitzoid melanoma can be extremely difficult. Features that favor the diagnosis of a spitzoid melanoma are asymmetrical shape, diameter greater than 1 cm, a lesion with a deep invasive component, and a high degree of cytologic atypia. There have been only rare reports in the literature of the presence of giant cells in malignant melanoma, and the presence of these cells may result in its misdiagnosis as a histiocytic tumor. We present a case of spitzoid melanoma on the right ankle of a 22-year-old-woman.