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Background
Congenital nevi are melanocytic nevi present at birth. They are probably best recognized as the large bathing suit nevi that may cover large portions of the body. Giant congenital nevi are usually larger than 6 cm on the trunk, 9 cm on the scalp in an infant, or greater than 20 cm in its largest diameter in an adult. The management of these larger lesions is controversial. The outline below highlights some of the approaches. Neurocutaneous melanosis is the presence of neurologic symptoms and an increased number of melanocytes within the central nervous system associated with large cutaneous nevi or multiple smaller nevi. CNS melanocytes are usually found in the anterior temporal lobes, cerebellum, thalami, and base of the frontal lobe.
OUTLINE
DISEASE ASSOCIATIONS CHARACTERIZATION ASSOCIATED FINDING WITH GIANT CONGENITAL MELANOCYTIC NEVI Loss of subcutaneous fat
Limb hypoplasiaRhabdomyosarcoma
Liposarcoma
Neuroblastoma
Primitive neuroectodermal tumors
Mixed malignant neoplasmsVascular
Supernumerary digits
Ear deformities
Preauricular appendages
Cryptorchidism
Club feetNeuroectodermal neoplasms arising in congenital nevi.
Jerdan MS, Cohen BA, Smith RR, Hood AF.
Department of Dermatology, Johns Hopkins University and Hospital, Baltimore, Maryland.
Am J Dermatopathol 1985;7 Suppl:41-8 Abstract quote
Congenital giant nevi of neuroectodermal origin are composed predominantly of melanocytes and occasional neural elements. Neoplasms arising in such nevi may be morphologically heterogeneous with variable clinical behavior.
We report the case of a female infant born with multiple pigmented nevi, including a giant hairy nevus of bathing trunk distribution in which arose a large pedunculated mass involving the sacral region, buttocks, perineum, and left thigh. Within this neoplasm, mixtures of neural crest-derived tissues having both melanocytic (nevus) cell and neural supportive (neuroid of Schwannian) cell differentiation were identified. The neural differentiation, which was seen in the dermis and subcutaneous tissue, had a neurofibromatous appearance and demonstrated multiple pseudomeissnerian corpuscles. In addition, at 16 months of age the child developed a malignant melanoma in the flank region of this congenital giant nevus.
The morphologic pluripotentiality of the primitive neural crest derivatives in congenital nevi has only recently been elucidated. These lesions should be regarded as neuroectodermal neoplasms and subclassified according to their differentiating histologic characteristics because prognosis and management are influenced by morphologic determinants.
LYMPH NODES Nevus cells in lymph nodes: an association with congenital cutaneous nevi.
Fontaine D, Parkhill W, Greer W, Walsh N.
Departments of Pathology (D.F., W.G., N.W.) and Surgery (W.P.), Queen Elizabeth II Health Sciences Center and Dalhousie University, Halifax, Nova Scotia, Canada.
Am J Dermatopathol 2002 Feb;24(1):1-5 Abstract quote It is known that collections of nevus cells can occur in the collagenous framework of lymph nodes excised for a variety of reasons. These can be difficult to distinguish from nodal deposits of metastatic cancer but attention to cytologic detail, the distribution of the cells, and their immunohistochemical profile usually lead to a satisfactory conclusion. From another perspective, the mechanism by which nevus cells are deposited in lymph nodes has been a source of interest and controversy. Theories in this regard include embolic transfer of cells from cutaneous nevi to corresponding regional nodes and an aberration in the embryologic migration of melanocytes in utero. There have been tentative indications in the literature of a potential link between the presence of nevus cells in lymph nodes and cutaneous nevi in corresponding catchment areas of skin.
In the course of evaluating sentinel lymph nodes from patients with melanoma, we noted a significant association between the presence of nodal nevi and cutaneous nevi in corresponding regional zones of skin (Fischer's exact test, p = 0.021). The link with cutaneous nevi of congenital type was even stronger (Fischer's exact test, p = 0.008).
This consolidates previous sporadic reports of such an association and through further scrutiny may help shed light on the mechanism by which nodal and congenital cutaneous nevi are linked.
RHABDOMYOSARCOMA
Rhabdomyosarcoma arising in a congenital melanocytic nevus.Hoang MP, Sinkre P, Albores-Saavedra J.
Division of Anatomic Pathology, University of Texas Southwestern Medical Center, Dallas, Texas
Am J Dermatopathol 2002 Feb;24(1):26-9 Abstract quote A variety of malignancies have been reported to arise within congenital melanocytic nevi, most commonly malignant melanoma, but rarely rhabdomyosarcoma, liposarcoma, and malignant peripheral nerve sheath tumor as well. There have been only three documented cases of rhabdomyosarcoma arising within congenital melanocytic nevi: two embryonal rhabdomyosarcomas and one mixed liposarcoma and rhabdomyosarcoma. One of these cases was also associated with neurocutaneous melanosis.
We report a fourth case of rhabdomyosarcoma originating from a congenital melanocytic nevus. A 4-year-old girl presented with a large ulcerated nodule that developed within a hairy congenital nevus on her left gluteal and sacral regions. Her parents refused postoperative adjuvant therapy, and she died 13 months after surgical excision. Histologic sections showed a lesion with two distinct components. There was an expansile proliferation of pleomorphic cells within a fibromyxoid stroma. The neoplastic cells were spindled, and some had abundant eosinophilic globular cytoplasm with occasional cross-striations characteristic of rhabdomyoblasts. They strongly expressed desmin and myoglobin and were negative for S-100 protein and HMB-45. The tumor merged with an adjacent congenital melanocytic nevus characterized by a proliferation of uniform nonatypical melanocytes.
The finding of both rhabdomyoblastic and melanocytic differentiation within the same lesion lends support to the hypothesis of their derivation from common pluripotential stem cells or neural crest cells.
CHARACTERIZATION RADIOLOGIC Central nervous system imaging and congenital melanocytic naevi.
Kinsler VA, Aylett SE, Coley SC, Chong WK, Atherton DJ.
Department of Dermatology, Great Ormond Street Hospital for Children NHS Trust, Great Ormond Street, London WC1N 3JH, UK.
Arch Dis Child 2001 Feb;84(2):152-5 Abstract quote
AIM: To establish the prevalence of central nervous system (CNS) abnormalities on magnetic resonance imaging (MRI) in a population of children with congenital melanocytic naevi (CMN) over the head and/or spine, and to compare this with clinical findings.
METHODS: Forty three patients identified from outpatient clinics underwent MRI of the brain and/or spine. These were reported by a paediatric radiologist and findings compared with the clinical picture.
RESULTS: Nine patients had abnormal clinical neurology, seven had abnormal findings on MRI, and six had both abnormal clinical and radiological findings. Only three of the abnormal MRIs showed features of intracranial melanosis. Three others showed structural brain abnormalities: one choroid plexus papilloma, one cerebellar astrocytoma, and one posterior fossa arachnoid cyst; the first two of these have not previously been described in association with CMN. The last abnormal MRI showed equivocal changes requiring reimaging.
CONCLUSIONS: The prevalence of radiological CNS abnormality in this group of children was 7/43. Six of these developed abnormal clinical neurological signs within the first 18 months of life, but two did not do so until after the MRI. Two of the CNS lesions were operable; for this reason we support the routine use of early MRI in this group.
LABORATORY MARKERS Hypercalcemia in a patient with malignant melanoma arising in congenital giant pigmented nevus. A case of increased serum level of parathyroid hormone-related protein.
Matsui T, Kageshita T, Ishihara T, Tomiguchi S, Takahashi M, Ono T.
Department of Dermatology, Kumamoto University School of Medicine, Japan.
Dermatology 1998;197(1):65-8 Abstract quote
We describe a 43-year-old Japanese female who developed hypercalcemia associated with malignant melanoma.
The patient underwent three resections of tumors on her groin and buttock secondary to a bathing trunk congenital nevus, and the histopathological findings showed benign congenital nevi. At the age of 42 years, she developed a malignant melanoma under the giant pigmented nevus in her groin. Fourteen months after the diagnosis of melanoma, she developed metastases to the lung, para-aortic lymph nodes and bones accompanied by hypercalcemia resulting from a remarkable increase in the serum level of parathyroid hormone-related protein (PTHrP). The patient died from acute renal and respiratory failure.
In addition, we analyzed serum levels of calcium and PTHrP in 19 patients with advanced malignant melanoma. Seven patients had hypercalcemia, and 3 had increased serum levels of PTHrP.
The use of digital dermoscopy for the follow-up of congenital nevi: a pilot study.
Braun RP, Calza AM, Krischer J, Saurat JH.
Pigmented Skin Lesion Unit, Department of Dermatology, University Hospital Geneva, Geneva, Switzerland.
Pediatr Dermatol 2001 Jul-Aug;18(4):277-81 Abstract quote
One of the main problems in the management of congenital nevi is the potential risk for malignant transformation and the resulting need for follow-up examination. Dermoscopy is a noninvasive technique that has been shown to be useful for the follow-up of benign melanocytic skin lesions as well as the early diagnosis of malignant melanoma. Therefore we thought to use the digital dermoscopy (DD) technique for the follow-up of congenital nevi.
For documentation purposes we registered an overview, and the following standardized dermoscopic images of every lesion: representative architectural pattern, border of the lesion, and regions of "special interest." In all instances the examination with digital dermoscopy was well tolerated by the patients and the integration of the parents to the "live" examination on the computer screen was appreciated. The follow-up was easy to perform with these standardized documents.
We showed the feasibility of follow-up of congenital nevi using digital dermoscopy. Furthermore, we identified three different patterns as well as some typical structures seen in congenital nevi by DD.
GROSS APPEARANCE/
CLINICAL VARIANTSCHARACTERIZATION GENERAL NEUROCUTANEOUS MELANOSIS Hydrocephalus
Macrocephaly
Increasing head circumference
Bulging fontanelle
Seizures
Developmental delayHeadache
Vomiting
Failure to thrive
Weakness
Gait abnormalities
Bladder or bowel dysfunction
Departments of *Pathology ‡Dermatology §Pediatrics, Yale University School of Medicine, New Haven, CT †Department of Pathology, Cook Childrenʼs Medical Center, Fort Worth, TX.
Neurocutaneous melanosis, better referred to as neurocutaneous melanocytosis (NCM), is a rare congenital disorder occurring in childhood characterized by proliferation of melanocytes in the central nervous system (CNS), associated with large congenital melanocytic nevi. The phenotype of the CNS lesions varies, ranging from that of a benign, nevuslike lesion, to one of an aggressive-looking, atypical cell proliferation; however, specific diagnostic criteria allow the distinction from CNS metastasis of a primary skin melanoma. NCM can present with severe neurologic manifestations, and usually has a relentless clinical progression whence neurologic symptoms appear.
Dissemination to the peritoneal surface by ventriculo-peritoneal shunting has been exceptionally observed, and we describe 2 cases of such occurrence, one of which was associated with a "bulky perineal nevocytoma" with complex cytogenetic rearrangements. This "metastatic" spreading supports an aggressive phenotype, able to seed and establish new colonies, although only after facilitated translocation of the proliferating cells through the shunt conduit; the aggressiveness of these lesions in our cases is further supported by the histopathologic features and clinical course.
The biologic features of NCM cells merit further exploration, as they may shed light on a much more frequent neoplastic neurocristopathy, namely, malignant melanoma.
- Large or multiple congenital melanocytic nevi: occurrence of neurocutaneous melanocytosis in 1008 persons.
Bett BJ.
Nevus Network, West Salem, Ohio, USA.
J Am Acad Dermatol. 2006 May;54(5):767-77. Epub 2006 Feb 2. Abstract quote
BACKGROUND: There is a dearth of information regarding the occurrence of neurocutaneous melanocytosis (NCM) in a large cohort of persons with large congenital melanocytic nevi (LMCN) or multiple congenital melanocytic nevi (MCMN).
OBJECTIVE: The purpose of this article is to report occurrence of NCM and other complications in 1008 persons having LCMN or MCMN.
METHODS: Evaluation of information obtained from a database of persons with LCMN or MCMN voluntarily submitted by the affected persons to a nevus support group, the Nevus Network.
RESULTS: Of those with truncal LCMN, 6.8% developed significant complications, 4.8% developed symptomatic NCM, and 2.3% died from either benign or malignant NCM or cutaneous melanoma. Of the 4.8% of persons with a truncal nevus who developed symptomatic NCM, 34% died. Of those with head or extremity LCMN, 0.8% developed symptomatic NCM, and, to date, none have died from any cause. Of the small number with MCMN without a giant nevus, 71% developed symptomatic NCM, and 41% died of it.
LIMITATIONS: Attending physician confirmation of submitted information was unavailable.
CONCLUSIONS: LCMN of the trunk were associated with a relatively low occurrence of medical complications and death in our group, considering the large nevomelanocytic burden present. If symptomatic NCM developed in those with truncal nevi, the occurrence of death rose to a third. LCMN of the head or extremity were associated with minimal medical complications and no deaths. In contrast, most of the rare persons (N = 17) with MCMN developed symptomatic NCM, and more than a third died.
- Asymptomatic neurocutaneous melanocytosis in patients with large congenital melanocytic nevi: a study of cases from an Internet-based registry.
Agero AL, Benvenuto-Andrade C, Dusza SW, Halpern AC, Marghoob AA.
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10022, USA.
J Am Acad Dermatol. 2005 Dec;53(6):959-65. Epub 2005 Oct 7. Abstract quote
BACKGROUND: Recent retrospective studies using magnetic resonance imaging (MRI) to screen for neurocutaneous melanocytosis (NCM) among neurologically asymptomatic children with large congenital melanocytic nevi (LCMN) report high prevalence (23-30%) of asymptomatic NCM. We sought to determine prevalence of asymptomatic NCM, and current application of MRI as a screening tool.
METHODS: Patients with LCMN from an Internet-based registry answered a questionnaire regarding NCM status.
RESULTS: Of 379 patients with LCMN, 26 reportedly had NCM, with 17 reporting neurologic symptoms. Of 186 patients undergoing MRI, 9 reported abnormal findings without neurologic symptoms (4.8%); 80% had LCMN on the posterior axis, whereas 55% had more than 20 satellite nevi.
LIMITATIONS: Study data rely on the registry members' self-reported findings and are limited by lack of independent data verification.
CONCLUSION: Asymptomatic NCM (determined by MRI) may not be common, with much lower prevalence (4.8%) than previously reported. MRI is widely used for screening patients at risk for NCM, such as patients with LCMN involving the posterior axis and greater than 20 satellite nevi.
Number of satellite nevi as a correlate for neurocutaneous melanocytosis in patients with large congenital melanocytic nevi.
Marghoob AA, Dusza S, Oliveria S, Halpern AC.
Dermatology Section, Memorial Sloan-Kettering Cancer Center, New York, NY.
Arch Dermatol. 2004 Feb;140(2):171-5. Abstract quote
BACKGROUND: Patients with large congenital melanocytic nevi (LCMN) are at risk for neurocutaneous melanocytosis (NCM). Patients with LCMN on the posterior axis or in conjunction with many satellite melanocytic nevi seem to represent subgroups at greatest risk.
OBJECTIVE: To determine the relationship between LCMN location, number of satellite nevi, and risk of NCM.
DESIGN: Descriptive survey study.
SETTING: An Internet Web-based registry of patients with LCMN, maintained by a nevus support group (Nevus Outreach Inc).
PARTICIPANTS: Individuals with LCMN or their guardians visiting the Nevus Outreach Web site were provided the opportunity to complete the questionnaire.
OUTCOME MEASURES: Location of LCMN, number of satellite nevi, and NCM as assessed by patient self-report.
RESULTS: A total of 379 patients with LCMN were evaluated, 26 of whom had NCM. A significantly higher percentage of patients with NCM had their LCMN on the posterior axis compared with patients without NCM (96% and 70%, respectively). Patients with NCM had significantly more satellite melanocytic nevi compared with non-NCM patients (median, 68.5 and 18, respectively). Furthermore, patients with LCMN and more than 20 satellites had a 5.1-fold (95% confidence interval, 1.9-14.0) increased risk for NCM compared with LCMN patients with 20 or fewer satellites. Logistic regression analysis, controlling for age, sex, number of satellite nevi, and LCMN location, identified number of satellite nevi as the only significant risk factor for NCM.
CONCLUSIONS: The presence of large numbers of satellite nevi is the most important risk factor for NCM in patients with LCMN. Although location of the LCMN on the posterior axis was a moderate risk factor for NCM in univariate analysis, the strength of the relationship was attenuated in the multivariate analysis.Giant congenital nevus and chronic progressive ascending hemiparesis (Mills syndrome). Report of a case.
Frisoni GB, Gasparotti R, Di Monda V.
Clinica Neurologica, Universita di Brescia.
Ital J Neurol Sci 1992 Apr;13(3):259-63 Abstract quote
We describe the case of a 20 year old boy with a giant congenital nevus who developed a chronic progressive ascending hemiparesis. The association of the pigmented lesion with a focal neurological deficit is pathognomonic for neurocutaneous melanosis complicated by a leptomeningeal melanoma. MR imaging at 1.5 tesla ruled out such a possibility and showed a small aspecific pontine lesion along the route of the corticospinal tract.
We discuss possible etiologies.
Giant congenital melanocytic nevi: brain magnetic resonance findings in neurologically asymptomatic children.
Frieden IJ, Williams ML, Barkovich AJ.
Department of Dermatology, University of California, School of Medicine, San Francisco.
J Am Acad Dermatol 1994 Sep;31(3 Pt 1):423-9 Abstract quote
BACKGROUND: Patients with giant or multiple congenital melanocytic nevi occasionally have leptomeningeal melanocytosis, also called neurocutaneous melanosis (NCM). Patients with symptomatic NCM usually have signs or symptoms of increased intracranial pressure and have a poor prognosis. Magnetic resonance (MR) imaging is sensitive in detecting melanin; several recent reports have described the MR findings in neurocutaneous melanosis.
OBJECTIVE: The aim of this study is to review the brain MR findings and their potential significance in a group of neurologically asymptomatic children with giant congenital melanocytic nevi at risk for the development of NCM.
METHODS: Retrospective review of patient charts and MR studies was performed.
RESULTS: Nine of the 20 patients evaluated had MR abnormalities: six had focal areas of high signal on T1-weighted images, strongly suggestive of melanosis, in one or multiple areas of the brain including the temporal lobes, cerebellum, pons, and medulla. One had a middle cranial fossa arachnoid cyst; another had a Chiari type I malformation of the brain. In one patient a crescentic enhancement over the right parietal region, probably from perinatal trauma, was absent on repeat MR 6 months later. In no case was thickening of the leptomeninges or spinal abnormalities noted.
CONCLUSIONS: NCM may be much more common than previously suspected in patients with giant congenital melanocytic nevi. The most common finding on MR appears to be T1 shortening in the cerebellum, temporal lobes, pons, and medulla, rather than evidence of leptomeningeal thickening. These findings may have implications for management of patients with giant CMN.
Neurocutaneous melanosis: clinical features of large congenital melanocytic nevi in patients with manifest central nervous system melanosis.
DeDavid M, Orlow SJ, Provost N, Marghoob AA, Rao BK, Wasti Q, Huang CL, Kopf AW, Bart RS.
Ronald O. Pereiman Department of Dermatology, New York University School of Medicine, New York, USA.
J Am Acad Dermatol 1996 Oct;35(4):529-38 Abstract quote
BACKGROUND: Patients with a large congenital melanocytic nevus (LCMN) may have associated leptomeningeal melanocytosis with or without central nervous system (CNS) melanomas. These patients are considered to have neurocutaneous melanosis, a disorder that, when symptomatic or otherwise manifest neurologically, carries a poor prognosis even in the absence of malignancy.
OBJECTIVE: Our purpose was to identify typical clinical features in patients who have manifest CNS melanosis in association with LCMN.
METHODS: The records of 117 patients with LCMN in the New York University Registry of LCMN and the reports of 172 cases of LCMN in the world literature were included for features that might signal a high risk for the development of manifest CNS involvement.
RESULTS: Of the 289 patients with LCMN, 33 had manifest CNS melanosis. In all 33 in whom symptomatic neurocutaneous melanosis was diagnosed, the LCMNs were present in a posterior axial location on the head, neck, back, and/or buttocks. "Satellite" nevi were known to be present in 31 of the 33 patients.
CONCLUSION: Patients with LCMN in a posterior axial location, especially when associated with "satellite" melanocytic nevi, are at greater risk for the development of manifest neurocutaneous melanosis than patients with LCMN limited to the extremities or those who are lacking satellite nevi.
MR imaging of symptomatic neurocutaneous melanosis in children.
Byrd SE, Darling CF, Tomita T, Chou P, de Leon GA, Radkowski MA.
Division of Neuroimaging, Department of Radiology, Children's Memorial Hospital and Northwestern Medical School, 2300 Children's Plaza, Chicago, IL 60614, USA
Pediatr Radiol 1997 Jan;27(1):39-44 Abstract quote
Neurocutaneous melanosis is a syndrome consisting of cutaneous nevi and melanocytosis of the leptomeninges.
Over a 5-year period (1989-1994) we evaluated with MR imaging the central nervous system of five children with a confirmed histologic diagnosis of neurocutaneous melanosis. The children ranged in age from 7 to 10 years and consisted of two girls and three boys. They all had multiple pigmented skin lesions (cutaneous nevi) and presented with seizures, signs of raised intracranial pressure, cranial nerve palsies and/or myelopathy. The MR studies were performed with T1-weighted, T2-weighted and T1-weighted post-gadolinium images of the brain in addition to T1-weighted post-gadolinium images of the entire spine.
The MR findings in all the children consisted of marked, diffuse enhancement of thickened leptomeninges surrounding the brain and spinal cord which was only demonstrated on the post-gadolinium T1-weighted images and mild to moderate hydrocephalus.
We present our MR findings and compare these findings with other imaging findings in the literature. Our findings represent part of a spectrum of imaging abnormalities seen in patients with neurocutaneous melanosis.
Large congenital melanocytic nevi and the risk for development of malignant melanoma and neurocutaneous melanocytosis.
Bittencourt FV, Marghoob AA, Kopf AW, Koenig KL, Bart RS. Ronald O. Perelman
Department of Dermatology, New York University School of Medicine, New York, New York 10016, USA.
Pediatrics 2000 Oct;106(4):736-41 Abstract quote
OBJECTIVE: To determine the risk for developing malignant melanoma and neurocutaneous melanocytosis (NCM) in patients with large congenital melanocytic nevi.
DESIGN: Follow-up data suitable for calculations were available on 160 patients in the New York University Registry of Large Congenital Melanocytic Nevi who had been free of known melanomas or NCM when entered into the Registry. The cumulative 5-year life-table risks for developing melanoma and NCM were calculated. The relative risk for developing melanoma, using a control general population reference group, was determined.
RESULTS: The 160 patients (median age at entry: 14 months) were followed prospectively for an average of 5.5 years. Three extracutaneous melanomas developed: 2 were in the central nervous system (CNS) and 1 was retroperitoneal. The 5-year cumulative life-table risk for developing melanoma was 2.3% (95% confidence interval [CI]:.8-6.6) and the relative risk was 101 (95% CI: 21-296). No melanoma occurred within a large congenital melanocytic nevus. Four patients developed manifest NCM, 2 with CNS melanomas. The 5-year cumulative life-table risk for developing NCM was 2.5% (95% CI:.8-7.2). Ten patients were excluded from the calculations because of preexisting disease on entry into the Registry: 5 with manifest NCM and 5 with melanomas (3 in large congenital melanocytic nevi, 1 in nonnevus skin, and 1 unknown primary).
CONCLUSIONS: Patients with large congenital melanocytic nevi are at increased risk for developing melanomas. There is also a significant increased risk for developing NCM. The high incidence of CNS involvement may influence decisions concerning treatment of the large congenital melanocytic nevi.
Neurocutaneous melanosis: a case of primary intracranial melanoma with metastasis.
Arunkumar MJ, Ranjan A, Jacob M, Rajshekhar V.
Christian Medical College and Hospital, Vellore, India.
Clin Oncol (R Coll Radiol) 2001;13(1):52-4 Abstract quote
Neurocutaneous melanosis is a rare disorder characterized by the presence of large or multiple congenital melanocytic naevi and benign or malignant pigment cell tumours of the leptomeninges. Distant metastasis is unusual in primary leptomeningeal/intracranial melanomas.
We present the case history of an adult male who had multiple primary intracranial melanomas associated with neurocutaneous melanosis (naevus of Ota) in the ophthalmic division of the left trigeminal nerve. Excision of the intracranial tumours was carried out in two stages, but the patient died 2 days after the second operation.
Autopsy showed multiple metastatic deposits in the liver. Symptoms and signs of raised intracranial pressure, the presence of Ota's naevus, and a dural-based mass or masses should alert the treating physician to suspect a primary leptomeningeal/intracranial melanoma.
Giant congenital melanocytic nevi: the significance of neurocutaneous melanosis in neurologically asymptomatic children.
Foster RD, Williams ML, Barkovich AJ, Hoffman WY, Mathes SJ, Frieden IJ.
Division of Plastic and Reconstructive Surgery, Department of Dermatology, , University of California, San Francisco, USA.
Plast Reconstr Surg 2001 Apr 1;107(4):933-41 Abstract quote
Patients with a giant congenital melanocytic nevus can develop melanotic tumors characterized by central nervous system involvement, termed leptomeningeal melanocytosis or neurocutaneous melanosis. Although symptomatic neurocutaneous melanosis is rare, we previously reported distinct magnetic resonance (MR) findings of T1 shortening, strongly suggestive of neurocutaneous melanosis, in 30 percent (6 of 20) of children with giant congenital melanocytic nevi who presented initially without neurological symptoms.
The purpose of this study was to determine the incidence of neurocutaneous melanosis in high-risk patients and its long-term clinical significance.Magnetic resonance imaging was recommended for all 46 patients with "at-risk" giant congenital melanocytic nevi involving the skin overlying the dorsal spine or scalp. The clinical histories and follow-up of these patients were evaluated by retrospective chart review. Forty-two underwent MR imaging of the brain and 11 underwent additional MR scanning of the spinal cord. Abnormalities were identified in 14 of 43 MR studies, and 23 percent (n = 10) had T1 shortening indicative of melanotic rests within the brain or meninges. None had associated masses or leptomeningeal thickening. The most common areas of involvement in these 10 included the amygdala (n = 8), cerebellum (n = 5), and pons (n = 3). In the group of 11 patients with spinal MR scans, a tethered spinal cord was demonstrated in one. Additional abnormalities were detected by MR scanning, including a middle cranial fossa arachnoid cyst, a Chiari type I malformation, and a crescentic enhancement that subsequently resolved.
Clinical follow-up averaging 5 years (range, 2 to 8 years) revealed that only one of the 46 patients evaluated developed neurological symptoms, manifested as developmental delay, hypotonia, and questionable seizures but no other signs of neurocutaneous melanosis. No patient has developed a cutaneous or central nervous system melanoma. Magnetic resonance findings of neurocutaneous melanosis are relatively common, even in asymptomatic children with giant congenital melanocytic nevi.
Although these findings suggest an increased lifetime risk of central nervous system melanoma, they do not signify the eventual development of symptomatic neurocutaneous melanosis during childhood.
VARIANTS ATROPHY Lower and upper extremity atrophy associated with a giant congenital melanocytic nevus.
Itin PH, Lautenschlager S.
Department of Dermatology, University of Basel, Switzerland.
Pediatr Dermatol 1998 Jul-Aug;15(4):287-9 Abstract quote
Giant congenital melanocytic nevi (GCMN) may be associated with a variety of malformations. Recently, atrophy of the underlying extremity was reported for the first time.
We observed two patients with GCMN on the extremities with marked atrophy of the underlying tissue without functional impairment. According to the definition of hamartoma, it seems possible that one component of tissue has decreased. Dermatologists treating patients with such nevi in the first weeks of life with dermabrasion, laser, or curettage need to know that the natural course of GCMN may lead to atrophy and that this does not necessarily result from the treatment regimen.
SCLERODERMOID REACTION Giant congenital nevus with progressive sclerodermoid reaction in a newborn.
Pattee SF, Hansen RC, Bangert JL, Joganic EF.
Section of Dermatology, University of Arizona College of Medicine, Tucson, Arizona, USA.
Pediatr Dermatol 2001 Jul-Aug;18(4):320-4 Abstract quote
Giant congenital melanocytic nevi are a rare occurrence in the pediatric population. The risk of malignant transformation associated with these lesions has been well established; however, the management strategies for giant congenital nevi remain controversial.
We report an unusual sclerodermoid reaction in a giant congenital nevus in a 6-week-old Caucasian girl. Given its abnormal clinical appearance, the entire lesion was excised. The histology was consistent with an atypical compound/sclerosing spindle and epithelioid cell congenital nevus. No evidence of malignant change was seen histologically. The incidence of malignant transformation in giant congenital nevi has been difficult to calculate.
Review of the literature yields an incidence of between 4 and 9%, favoring surgical excision of these lesions where possible. Atypical presentations of giant congenital nevi are rare, and we have found no other reported cases with a stromal change similar to that seen in our patient. We hypothesize that this change may represent an atypical host reaction to the nevus cells.
SPECKLED LENTIGINOUS NEVUS Speckled lentiginous nevus: within the spectrum of congenital melanocytic nevi.
Schaffer JV, Orlow SJ, Lazova R, Bolognia JL.
Department of Dermatology, Yale University School of Medicine, 333 Cedar St, New Haven, CT 06520, USA.
Arch Dermatol 2001 Feb;137(2):172-8 Abstract quote
BACKGROUND: Currently, there is disagreement as to whether speckled lentiginous nevi (nevi spili) are congenital or acquired pigmented lesions. Part of this controversy is related to the natural history of these lesions that often present at birth as hyperpigmented patches and then take several years to reach their more readily recognized spotted form. Arguments in favor of speckled lentiginous nevi as a subtype of congenital nevi include the following observations: multiple reports of lesions present at birth or noted soon thereafter; patterns of distribution reflecting embryonic development; hamartomatous behavior with various types of nevi (eg, junctional nevi, blue nevi, and Spitz nevi) presenting in the same lesion over time; and histologic features of congenital melanocytic nevi within the spots. Herein we present additional evidence for the congenital nature of speckled lentiginous nevi.
OBSERVATIONS: Ten patients are described with congenital pigmented lesions that had the clinical appearance of speckled lentiginous nevi in whole or in part. These lesions either evolved and acquired an appearance more suggestive of "classic" congenital nevi, or they existed as "hybrid" lesions with portions appearing as classic congenital nevi adjacent to or admixed with portions appearing as speckled lentiginous nevi. On histologic examination, biopsy specimens from the spots within these lesions showed features of congenital melanocytic nevi.
CONCLUSIONS: These 10 cases, along with the arguments outlined above, provide strong support for the hypothesis that speckled lentiginous nevi are a subtype of congenital melanocytic nevi.
HISTOLOGICAL TYPES CHARACTERIZATION GENERAL
- Congenital melanocytic nevi: clinical and histopathologic features, risk of melanoma, and clinical management.
Tannous ZS, Mihm MC Jr, Sober AJ, Duncan LM.
Dermatopathology Unit, Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
J Am Acad Dermatol. 2005 Feb;52(2):197-203. Abstract quote
Congenital melanocytic nevi occur in approximately 1% of newborns and are usually classified according to their size. Giant congenital melanocytic nevi are most simply defined as melanocytic nevi that are greater than 20 cm in largest dimension; whereas small congenital nevi are defined as melanocytic nevi less that 1.5 cm in largest dimension.
Congenital nevi can exhibit distinctive histologic features that can help in differentiating them from common acquired nevi. Giant congenital melanocytic nevi are associated with an increased risk of the development of melanoma. On the other hand, there is evidence of an increased melanoma risk in patients with small congenital nevi. Nevertheless, the risk of malignant transformation in small congenital nevi and the lifetime melanoma risk in patients with small congenital nevi remain controversial. In large part due to inconsistency in the reported literature describing patients with congenital melanocytic nevi, the risk of melanoma in these patients remains unclear and consistent guidelines for clinical management do not exist.
We review the literature and comment on the course of management for these patients at the Massachusetts General Hospital Pigmented Lesion Clinic.Lack of clinical-pathological correlation in the diagnosis of congenital naevi.
Cribier BJ, Santinelli F, Grosshans E.
Laboratoire d'Histopathologie Cutanee, Clinique Dermatologique des H opitaux Universitaires de Strasbourg, France.
Br J Dermatol 1999 Dec;141(6):1004-9 Abstract quote
Congenital naevocellular naevi (CNN) have classical histological criteria that are thought to allow distinction from acquired naevi. These criteria are mainly the horizontal distribution of melanocytes, forming 'Indian files', and a prominent adnexotropism.
In order to check whether the previously described criteria were reliable, we analysed 1349 unselected consecutive cases of naevocellular naevi excised in children under 16 years, during a 54-month period. The slides were analysed in order to determine by histological analysis only if they could be classified as CNN. These results were then compared with the clinical files, in which only the most reliable data from parental and/or medical observations were included. Of the 1349 naevi, 659 had the typical histological criteria of CNN, 32 of them being deep CNN, characterized by massive involvement of the lower dermis and hypodermis. The comparison with clinical data showed that 32 naevi with the histological criteria of congenital naevi were actually acquired, and that 179 naevi present at birth did not fulfil these criteria. This study shows that the classic histological criteria are not absolutely specific and are poorly sensitive as 36% of naevi present at birth lacked the classic criteria. The most specific criteria of true CNN were the involvement of eccrine glands and presence of melanocytes in the septae. In the case of deep CNN which corresponded to large or very large naevi, the clinicopathological correlation was 100%. Deep CNN could easily be distinguished from superficial CNN and often exhibited many histological changes consistent with a complex hamartoma, such as presence of brown fat tissue, abnormal vessels and numerous large terminal follicles.
In conclusion, our study suggests that it is not possible to predict, by histological analysis alone, that a naevus was present at birth, except in deep CNN which are likely to be a separate entity among all congenital naevi. Studies dealing with congenital naevus-associated melanoma should take into account the lack of sensitivity of these criteria.
VARIANTS EPITHELIOID CELLS
Congenital giant melanocytic nevus with pigmented epithelioid cells: a variant of epithelioid blue nevus.Martinez-Barba E, Polo-Garcia LA, Ferri-Niguez B, Ruiz-Macia JA, Kutzner H, Requena L.
Department of Pathology, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain.
Am J Dermatopathol 2002 Feb;24(1):30-5 Abstract quote Epithelioid-cell blue nevus is an unusual cytologic variant of blue nevus that has been recently described mostly in patients with Carney complex, although the lesion may also appear in patients with no evidence of Carney complex. This variant of blue nevus is composed of melanin laden large polygonal epithelioid melanocytes situated within the dermis. The neoplastic cells show no maturation with progressive descent and, in contrast with the usual stromal changes in blue nevi, epithelioid-cell blue nevus exhibits no dermal fibrosis.
This report describes a congenital giant melanocytic nevus with pigmented epithelioid cells located on the back of a 2-year-old male. The lesion was present at birth and the patient had no evidence of Carney complex.
Histopathologically, the lesion consisted of a large and entirely intradermal melanocytic nevus composed of heavily pigmented epithelioid melanocytes involving the full-thickness of dermis, but extending also to the subcutaneous fat and underlying soft tissues. Immunohistochemically, epithelioid neoplastic melanocytes expressed immunoreactivity for S-100 protein, HMB-45, Melan-A, NK1C3, and microphthalmia transcription factor (MiTF) antibodies. MIB-1 cellular proliferation marker was expressed in the nuclei of only a few scattered epithelioid melanocytes.
This report demonstrates that epithelioid-cell blue nevus is a distinctive histopathologic variant of blue nevus that may also appear as a giant congenital melanocytic nevus.
HYPOPLASIA OF SUBCUTANEOUS FAT Giant congenital melanocytic nevus with underlying hypoplasia of the subcutaneous fat.
Caradona SA, Skidmore R, Gupta A, Bush CH, Ford MJ.
Department of Dermatology, University of Florida College of Medicine, Gainesville, USA.
Pediatr Dermatol 2000 Sep-Oct;17(5):387-90 Abstract quote
A 17-week-old boy with a giant congenital melanocytic nevus (GCMN) of the left lower extremity was noted to have a reduction in circumference of the left lower extremity relative to the contralateral side. The skin overlying the GCMN was persistently warm when compared with the surrounding and contralateral skin. Comparative plain radiography, ultrasonography, and magnetic resonance imaging showed fat hypoplasia of the left lower extremity, with bone and muscle appearing unaffected. The possible role of cytokines produced by the nevus in fat hypoplasia in GCMN is discussed.
LYMPH NODES Melanocytic lesions in lymph nodes associated with congenital naevus.
Hara K.
First Department of Pathology, Aichi Medical University, Japan.
Histopathology 1993 Nov;23(5):445-51 Abstract quote
Two cases of melanocytic lesions in lymph node associated with congenital naevus are presented.
The first was a 30-year-old man with a nodular melanoma arising in a small congenital naevus. The second was a 2-year-old male infant with a giant congenital naevus. In both cases, naevus cell aggregates were observed in the capsule, trabeculae, perisinusoidal areas and lymphatic vessels surrounding the nodes. In the first case, clusters of large atypical melanocytes were present amongst naevus cell aggregates in the perisinusoidal areas as well as in the lymphoid parenchyma. Between the naevus cells and large atypical melanocytes, transitional forms were observed which supports the idea that the presence of large atypical melanocytes is indicative of benign naevus cells. In the second case, marginal sinuses were packed with clusters of large melanin-rich cells. Immunohistochemically, these cells were S-100 protein negative, but ultrastructural studies proved them to be melanocytes. They were considered indicative of spread of benign naevus cells via lymphatic vessels.
Arrested migration of naevus cells during embryogenesis and benign spread of naevus cells are possible explanations for the histogenesis of naevus cell aggregates in lymph nodes associated with congenital naevus.
PROLIFERATIVE NODULES
- Proliferative nodules with balloon-cell change in a large congenital melanocytic nevus.
McGowan JW, Smith MK, Ryan M, Hood AF.
Department of Dermatology, Eastern Virginia Medical School, Norfolk, VA 23507, USA.
J Cutan Pathol. 2006 Mar;33(3):253-5. Abstract quote
The balloon-cell nevus was first described over 100 years ago. Since then, balloon-cell changes of melanocytes have been noted in numerous tumors, including melanoma, blue nevus, and Spitz nevus. Whether these changes reflect cellular deterioration or proliferative changes is a matter of debate.
We report a case in which balloon-cell changes were found within proliferative nodules occurring in a large congenital melanocytic nevus.Proliferative Nodules in Congenital Melanocytic Nevi: A Clinicopathologic and Immunohistochemical Analysis.
Herron MD, Vanderhooft SL, Smock K, Zhou H, Leachman SA, Coffin C.
*Department of Dermatology, University of Utah School of Medicine, daggerDepartment of Pathology, Primary Children's Medical Center and University of Utah School of Medicine, and double daggerHuntsman Cancer Institute, Salt Lake City, UT.
Am J Surg Pathol. 2004 Aug;28(8):1017-1025. Abstract quote
Congenital melanocytic nevi (CMN) occur in 1% to 2% of newborns, and the risk of malignant melanoma is increased in patients with large CMN. Appearance at birth or later of a nodular or hyperpigmented area within a CMN simulates malignant melanoma and prompts biopsy. Although their clinical and pathologic features seem ominous, proliferative nodules (PNs) typically are benign and may regress, although atypical features cause greater concern.
Here we report clinical and pathologic findings with outcome in 10 children who had multiple biopsies of large CMN with PNs. We reviewed 78 separate samples from the 10 patients and classified the 60 PNs according to published criteria. A subset of 30 samples containing both the CMN and a PNs was analyzed for immunohistochemical reactivity for melanocytic (S-100 protein, HMB45, melan-A), lymphocytic (CD45), cell-cycle/proliferative (Mib-1, p16, p21, p27, c-Myc), apoptotic (p53, Bax, c-kit, CD95), and anti-apoptotic (bcl-2) markers. Both CMN and PNs had similar expression of melanocytic, lymphocytic, and most cell-cycle/proliferative and apoptotic markers, including Mib-1, p16, p21, p27, c-Myc, Bax, CD95, and bcl-2. A greater proportion of PNs than CMN were reactive for p53 (67% vs. 30%, P < 0.0098) and c-kit (97% vs. 3%, P < 0.0001). p53 and p21 expression in CMN and all types of PNs were inversely correlated. When ordinary and atypical PNs were compared, the atypical PNs more frequently expressed p53, Mib-1, Bax, and bcl-2, but less frequently expressed p21.
The c-kit expression in nearly all PNs and its absence in nearly all CMN is potentially useful for recognition of PN, suggests a delayed melanocytic maturation process in proliferative nodules, and may be likely indicative of their benign nature. p53 reactivity in concert with a lack of p21 up-regulation by immunohistochemistry suggests that a p53 mutation may be present in PN, although the immunohistochemical findings alone cannot exclude possible overexpression of wild-type p53. Regressive, involutional, or maturational changes were observed in sequential samples from 4 patients. No patient developed malignant melanoma or another melanocytic nevus-associated malignancy during the follow-up period.
These findings underscore the similarities between PNs and the underlying CMN and suggest that maturational, proliferative, and apoptotic processes are involved in their clinical evolution.
Cellular nodules in congenital pattern nevi.
Xu X, Bellucci KS, Elenitsas R, Elder DE.
Departments of Pathology and Laboratory Medicine, and Department of Dermatology, Hospital of the University of Pennsylvania, Philadelphia, USA.
J Cutan Pathol. 2004 Feb;31(2):153-9 Abstract quote.
BACKGROUND: The diagnosis of 'cellular dermal nodule in melanocytic nevi' is challenging, as it can simulate invasive and tumorigenic melanoma. Because cellular nodules are presumed benign, it is essential to differentiate them from true malignant melanoma arising within a nevus, which portends a poor prognosis. Although presumed benign, to date, no published long-term follow-up studies have proved the benignity of this lesion.
METHODS: To better understand the clinical behavior and histological features of these lesions, we present a clinical pathological study of a cohort of 26 cases, for which we obtained clinical follow up by chart review and questionnaires.
RESULTS: Clinical follow up was obtained on 16 out of 26 patients (61.5%) and ranged from 12 to 132 months (average 62.3 months). The cellular nodules in congenital pattern nevi, reported here, had an invariably benign clinical course.
CONCLUSIONS: Features useful in differentiating cellular nodule from melanoma include: (1) lack of high-grade uniform cellular atypia; (2) lack of necrosis within the nodule; (3) rarity of mitoses; (4) evidence of maturation in the form of blending or transitional forms between the cells in the nodule and the adjacent nevus cells; (5) lack of pagetoid spread into the overlying epidermis; and (6) no destructive expansile growth. The difference between cellular nodule and melanoma arising from nevus can be very subtle, and it is important to emphasize that these lesions must be assessed on an individual case-by-case basis.
Neonatal giant congenital nevi with proliferative nodules: a clinicopathologic study and literature review of neonatal melanoma.
Leech SN, Bell H, Leonard N, Jones SL, Geurin D, McKee PH, Lawrence CM.
Department of Dermatology, Royal Victoria Infirmary, Queen Victoria Infirmary, Newcastle upon Tyne, England.
Arch Dermatol. 2004 Jan;140(1):83-8 Abstract quote
BACKGROUND: Review of the literature reveals that congenital malignant melanoma is an exceptionally rare occurrence and has a generally poor prognosis when it does occur. However, benign proliferative melanocytic lesions are known to occur within giant congenital nevi (GCN). This entity is not well recognized and can be confused clinically and histologically with malignant change.
OBSERVATIONS: We report 2 cases of GCN in neonates demonstrating benign proliferating nodules present at birth. An initial diagnosis of malignant melanoma was assumed in both cases. Careful histologic analysis, however, revealed these lesions to be benign, as did long-term follow-up of 3.5 years, with both patients remaining well with no evidence of melanoma. Review of the literature suggests that there are 2 clinical patterns of these benign nodules arising within GCNs: small (<1 cm) and large (>1 cm) dermal nodules with varying histologic patterns that we have attempted to categorize.
CONCLUSIONS: Our cases illustrate the difficulty in accurate diagnosis of melanocytic lesions in the neonate. We recommend caution in making a diagnosis of malignant melanoma and highlight the possibility that benign lesions can be mistaken for melanoma in this age group. We encourage the acquisition of fixed histologic specimens for accurate diagnosis of melanocytic lesions.
DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES NEUROCRISTIC HAMARTOMA
Department of Surgery, University of Virginia, Charlottesville, VA, USA.
Neurocristic hamartomas (NCH) are rare pigmented skin lesions based in the deep subcutaneous tissues that may be either congenital or acquired. The clinical importance of these lesions is the potential for misdiagnosis and the development of malignant melanomas over a poorly described time course. Histological pleomorphism precludes meaningful random biopsies as a means of cancer surveillance.
We present the case of an extensive NCH in a 67-year-old man, with a reported duration of greater than 50 years and no current clinical or histological indication of malignancy. Incisional biopsies of nodular areas showed bland-appearing pigmented cells that extended into subcutaneous adipose tissue and skeletal muscle. The specimens contained numerous clusters of differing configurations and cell types. Positron emission tomography (PET) scanning was used as an adjunct to physical examination in follow up. A PET-avid mass was detected but proved to be a banal nodular melanocytic proliferation within the NCH.
In conclusion, NCH may be characterized by extensive deep tissue involvement in the absence of overt malignancy. The possible development of malignant melanoma in such lesions warrants close surveillance.
PROGNOSIS AND TREATMENT CHARACTERIZATION PROGNOSTIC FACTORS GENERAL-RISK OF MELANOMA
Large or multiple congenital melanocytic nevi: occurrence of cutaneous melanoma in 1008 persons.
Bett BJ.
J Am Acad Dermatol. 2005 May;52(5):793-7. Abstract quote
BACKGROUND: There is a dearth of information regarding the occurrence of cutaneous melanoma in a large cohort of persons with large congenital melanocytic nevi (LCMN) or multiple congenital melanocytic nevi (MCMN).
OBJECTIVE: The purpose of this article is to report our experience with 1008 persons having LCMN and MCMN.
METHODS: Information was evaluated that was obtained from a database of persons with LCMN or MCMN voluntarily submitted by the affected persons to a nevus support group, the Nevus Network.
RESULTS: Of those with garment LCMN, 2.9% developed cutaneous melanoma associated with 0.8% deaths. Of those with LCMN on the head or extremity, 0.3% developed cutaneous melanoma associated with no deaths to date. Of the small number with MCMN without a giant nevus, 6.7% developed cutaneous melanoma.
LIMITATIONS: Attending physician confirmation of submitted information was unavailable. Conclusions LCMN and MCMN were associated with a low occurrence of cutaneous melanoma in our group.J Am Acad Dermatol 1997;36:409-416
Arch Dermatol 1996;132:170-175
Pediatrics 2000;106:736-741Lifetime risk for melanoma estimated between 4.5-10%
5 year cumulative risk of 2.3% and relative risk of 101If melanoma develops, >50% develop <5 years and 70% by age 10
Greater risk occurring on the axial site (head, neck, and/or trunk)
No reports of melanomas arising in nevi restricted to an extremity or within congenital satellite neviNeoplasms arising in congenital giant nevi: morphologic study of seven cases and a review of the literature.
Hendrickson MR, Ross JC.
Am J Surg Pathol 1981 Mar;5(2):109-35 Abstract quote
Congenital giant nevi are complex cutaneous malformations composed of melanocytic and occasionally neural supportive elements. Malignant neoplasms arising in this setting are not uncommon, and their histologic appearances often differ significantly from the typical pattern of malignant melanoma.
We report six patients with neoplasms arising in congenital giant nevi and one patient with a neoplasm arising in an extensive congenital blue nevus, and present a description of the neoplastic patterns encountered. These patterns include 1) poorly differentiated small round cell cancer, 2) malignant cellular blue nevus, 3) spindle-cell malignant tumor with lamellar cell (pseudomeissnerian) differentiation, 4) so-called minimal deviation melanoma, 5) heterologous malignant mesenchymal differentiation including rhabdomyosarcoma and liposarcoma, and 6) undifferentiated spindle cell cancer.
We have reviewed the literature in order to address the question of frequency of malignant transformation in congenital giant nevi, the reported experience with the morphology of these cancers, and the histogenesis of these sometimes complex neoplasms as it is illuminated by our current understanding of the embryology of the neural crest.
Giant congenital nevus and malignant melanoma.
Hori Y, Nakayama J, Okamoto M, Nagae S, Taniguchi S, Takayama O, Oohara K.
Department of Dermatology, Kyushu University, Faculty of Medicine, Fukuoka, Japan.
J Invest Dermatol 1989 May;92(5 Suppl):310S-314S Abstract quote
Frequency of malignant transformation arising in giant congenital nevi is considered to be 4%-5%. More than a half of the patients in which malignant melanoma developed in giant congenital nevi were under the age of 10.
It may be hypothesized that dermabrasion of giant congenital nevus may provoke malignant transformation. Some of the cell groups in giant congenital nevus are potentially malignant. Some groups of nevus cells were larger in size than those of other portions of nevus. Electron microscopic observation revealed that nuclei of these larger nevus cells were significantly indented, and melanization of melanosomes was irregular. Coexistence of alpha-like actin with beta- and gamma-actins in giant congenital nevus cells and disappearance of alpha-like actin in malignant melanoma cells were noted.
Large congenital melanocytic nevi and the risk for the development of malignant melanoma. A prospective study.
Marghoob AA, Schoenbach SP, Kopf AW, Orlow SJ, Nossa R, Bart RS.
Department of Dermatology, State University of New York at Stony Brook, USA.
Arch Dermatol 1996 Feb;132(2):170-5 Abstract quote
BACKGROUND AND DESIGN: Patients with large congenital melanocytic nevi have been described to have an increased risk for the development of malignant melanoma (MM). Ninety-two patients with large congenital melanocytic nevi were followed up prospectively for the development of MM. Matched individuals from the general population served as control subjects.
RESULTS: Ninety-two patients (median age, 3 years) were followed up prospectively for an average of 5.4 years. In three patients (3%), MM developed in extracutaneous sites. The cumulative 5-year life-table risk for the development of MM was calculated to be 4.5% (95% confidence interval, 0% to 9.3%). In individuals in the general US population, matched for age, sex, and length of follow-up to the 92 study patients, 0.013 would be expected to develop MM. The standardized morbidity ratio (adjusted relative risk) was calculated to be 239, which was highly significant (P < .001).
CONCLUSIONS: Patients with large congenital melanocytic nevi are at a significantly increased risk for the development of MM and should be kept under continuous surveillance for the development of cutaneous as well as noncutaneous primary MM.
Cutaneous melanoma risk and phenotypic changes in large congenital nevi: a follow-up study of 46 patients.
Egan CL, Oliveria SA, Elenitsas R, Hanson J, Halpern AC.
Department of Dermatology, University of Pennsylvania Medical Center, Philadelphia, USA.
J Am Acad Dermatol 1998 Dec;39(6):923-32 Abstract quote
BACKGROUND: Large congenital melanocytic nevi may undergo malignant transformation. Few prospective studies have evaluated the incidence of melanoma in large congenital nevi or have described how their phenotypic characteristics change over time.
OBJECTIVE: We attempted to ascertain the incidence of cutaneous melanoma in a cohort of patients with large congenital nevi and to evaluate the frequency and nature of several morphologic changes over time.
METHODS: Forty-six patients with large congenital nevi were prospectively followed up in our Pigmented Lesion Group. Large congenital nevi were defined as those occurring at birth and comprising 5% body surface area or greater in infants, children, and preadolescents and more than 20 cm in adolescents and adults. Information was obtained on location, satellitosis, changes in color and nodularity, and incidence of melanoma. The most atypical histologic findings from those who underwent biopsy were also noted. Standardized morbidity ratios (SMR) and 5-year cumulative risk were calculated and presented with corresponding 95% confidence intervals (CI).
RESULTS: Twenty-four male and 22 female patients (age range, 7 days to 36.7 years; mean, 8.4 years) with large congenital nevi were followed up prospectively for a total of 335 person-years (range, 0.17 to 17.5 person-years; mean, 7.3 person-years). Two patients (4.3%) experienced 3 cutaneous melanomas that originated in their primary congenital nevi. We found one case of neurocutaneous melanosis. No satellite, extremity, or extracutaneous melanomas were detected. The majority of nevi in our cohort were located on the posterior trunk, were accompanied by multiple satellite congenital nevi, and became lighter over time. In the 27 patients who underwent biopsies, the most atypical histologic findings included melanoma, atypical melanocytic dysplasia, neurocristic dysplasia, atypical neural crest hamartomas, atypical spindle cell tumors, and congenital nevi with dysplasia. The SMR comparing observed-to-expected melanoma incidence was 148 (95% CI 18, 535; P = .0002) indicating a substantially increased risk of melanoma in patients with large congenital nevi. The cumulative 5-year risk of cutaneous melanoma was 5.7% (95% CI 0%, 13.5%).
CONCLUSION: Our findings are consistent with the previously observed increased risk for the occurrence of cutaneous melanoma in patients with large congenital nevi. Although the number of patients with melanoma in this study is small, our observations and those of previous studies suggest that location and age correlates with melanoma risk. The majority of large congenital nevi are located on the trunk and may undergo several clinical changes as these patients age. Additional prospective studies are needed to gain more insight into the natural history and optimal management of large congenital nevi.
Large congenital melanocytic nevi and the risk for development of malignant melanoma and neurocutaneous melanocytosis.
Bittencourt FV, Marghoob AA, Kopf AW, Koenig KL, Bart RS. Ronald O. Perelman
Department of Dermatology, New York University School of Medicine, New York, New York 10016,
Pediatrics 2000 Oct;106(4):736-41 Abstract quote
OBJECTIVE: To determine the risk for developing malignant melanoma and neurocutaneous melanocytosis (NCM) in patients with large congenital melanocytic nevi.
DESIGN: Follow-up data suitable for calculations were available on 160 patients in the New York University Registry of Large Congenital Melanocytic Nevi who had been free of known melanomas or NCM when entered into the Registry. The cumulative 5-year life-table risks for developing melanoma and NCM were calculated. The relative risk for developing melanoma, using a control general population reference group, was determined.
RESULTS: The 160 patients (median age at entry: 14 months) were followed prospectively for an average of 5.5 years. Three extracutaneous melanomas developed: 2 were in the central nervous system (CNS) and 1 was retroperitoneal. The 5-year cumulative life-table risk for developing melanoma was 2.3% (95% confidence interval [CI]:.8-6.6) and the relative risk was 101 (95% CI: 21-296). No melanoma occurred within a large congenital melanocytic nevus. Four patients developed manifest NCM, 2 with CNS melanomas. The 5-year cumulative life-table risk for developing NCM was 2.5% (95% CI:.8-7.2). Ten patients were excluded from the calculations because of preexisting disease on entry into the Registry: 5 with manifest NCM and 5 with melanomas (3 in large congenital melanocytic nevi, 1 in nonnevus skin, and 1 unknown primary).
CONCLUSIONS: Patients with large congenital melanocytic nevi are at increased risk for developing melanomas. There is also a significant increased risk for developing NCM. The high incidence of CNS involvement may influence decisions concerning treatment of the large congenital melanocytic nevi.
Small congenital nevi associated with melanoma: case reports and considerations.
Betti R, Inselvini E, Vergani R, Crosti C.
Clinica Dermatologica IV, Universita degli Studi di Milano, Ospedale San Paolo, Milan, Italy.
J Dermatol 2000 Sep;27(9):583-90 Abstract quote
Melanocytic nevi, both congenital and acquired, are considered to be precursors of melanomas. Data about the malignant potential of these nevi are conflicting, particularly with reference to the nevus of the smallest size. Patients with preexisting melanocytic nevi (both congenital and acquired) have risks of developing melanoma that differ from those of subjects without them.
The purpose of this study was to verify the presence of melanoma in preexisting nevi both congenital (congenital nevus associated melanoma) (CNAM) and acquired (ANAM). In particular, we investigated melanomas associated with small congenital nevi (SCN). A cohort of 190 patients with primary melanomas was studied. Congenital nevi were called "small" (SCN) when their diameters were less than 1.5 cm. Epiluminescence microscopy (ELM) was performed to further improve the clinical diagnosis and to observe the more subtle changes in the preexisting nevi. Forty of the 190 cases of melanoma were associated with preexisting nevi; of these, 15 had congenital features with a CNAM largest diameter of 1.5 cm. These 15 cases were melanomas of the superficial type with a mean tumor thickness lower than that of ANAM (0.33 vs 1.50). There were no differences between the locations of CNAM and other melanomas. Male patients were significantly more affected. ELM microscopy permitted us to detect the early malignant changes in nevi and thus to improve our diagnosis.
A high percentage of small congenital nevi were found to be associated with melanomas. They may be considered as melanomas precursors. Because of their large number and frequency, prophylactic removal of all SCN is not feasible. However, they should be removed as soon as possible when clinical or ELM changes are observed.
Malignant melanoma in children and congenital melanocytic nevi: DNA content and cell cycle analysis by flow cytometry.
Alvarez-Mendoza A, Reyes-Esparza J, Ruiz-Maldonado R, Lopez-Corella E, Juarez-Herrera NC.
Department of Pathology, National Institute of Pediatrics, Mexico City, Mexico.
Pediatr Dev Pathol 2001 Jan-Feb;4(1):73-81 Abstract quote
Malignant melanoma (MM) in children, although a rare neoplasm, can occur within a preexisting congenital melanocytic nevus (CMN). All the potential risk factors for this phenomenon are not well known, but increases in S phase and G2 + M phase of cell cycle, DNA aneuploidy, and cell cycle abnormalities in precursor lesions might be among the risk factors.
Using paraffin-embedded tissue, we performed a retrospective analysis of DNA content, aneuploidy, and cell cycle by flow cytometry.
Two groups of patients were analyzed: 28 children with CMN who did not developed MM, and 6 patients who further developed MM. In this second group, three patients had four biopsies done before the appearance of MM and in two patients biopsies were done after the appearance of MM. All CMN not associated with MM exhibited diploid cells only, their S phase was 11.5% (+/- 3.8), and their G2 + M phase was 2.5% (+/- 2.2). Among those patients who developed MM, 3/6 had an S phase > 15.5 and a G2 + M phase > 2.3 prior to the appearance of MM. Two out of six patients had a tetraploid DNA when MM developed and died with a disseminated MM. They had an S phase > 15.5 and their G2 + M phase was > 2.5.
We propose that evaluation of DNA content and cell cycle by flow cytometry is a useful method to supplement biopsy findings in children with CMN who have lesions suspicious of developing a MM.
Giant congenital melanocytic nevi: the significance of neurocutaneous melanosis in neurologically asymptomatic children.
Foster RD, Williams ML, Barkovich AJ, Hoffman WY, Mathes SJ, Frieden IJ.
Division of Plastic and Reconstructive Surgery, Department of Dermatology, , University of California, San Francisco, USA.
Plast Reconstr Surg 2001 Apr 1;107(4):933-41 Abstract quote
Patients with a giant congenital melanocytic nevus can develop melanotic tumors characterized by central nervous system involvement, termed leptomeningeal melanocytosis or neurocutaneous melanosis. Although symptomatic neurocutaneous melanosis is rare, we previously reported distinct magnetic resonance (MR) findings of T1 shortening, strongly suggestive of neurocutaneous melanosis, in 30 percent (6 of 20) of children with giant congenital melanocytic nevi who presented initially without neurological symptoms.
The purpose of this study was to determine the incidence of neurocutaneous melanosis in high-risk patients and its long-term clinical significance.
Magnetic resonance imaging was recommended for all 46 patients with "at-risk" giant congenital melanocytic nevi involving the skin overlying the dorsal spine or scalp. The clinical histories and follow-up of these patients were evaluated by retrospective chart review. Forty-two underwent MR imaging of the brain and 11 underwent additional MR scanning of the spinal cord. Abnormalities were identified in 14 of 43 MR studies, and 23 percent (n = 10) had T1 shortening indicative of melanotic rests within the brain or meninges. None had associated masses or leptomeningeal thickening. The most common areas of involvement in these 10 included the amygdala (n = 8), cerebellum (n = 5), and pons (n = 3). In the group of 11 patients with spinal MR scans, a tethered spinal cord was demonstrated in one. Additional abnormalities were detected by MR scanning, including a middle cranial fossa arachnoid cyst, a Chiari type I malformation, and a crescentic enhancement that subsequently resolved. Clinical follow-up averaging 5 years (range, 2 to 8 years) revealed that only one of the 46 patients evaluated developed neurological symptoms, manifested as developmental delay, hypotonia, and questionable seizures but no other signs of neurocutaneous melanosis. No patient has developed a cutaneous or central nervous system melanoma. Magnetic resonance findings of neurocutaneous melanosis are relatively common, even in asymptomatic children with giant congenital melanocytic nevi.
Although these findings suggest an increased lifetime risk of central nervous system melanoma, they do not signify the eventual development of symptomatic neurocutaneous melanosis during childhood.
PREGNANCY Giant congenital melanocytic nevus with placental involvement: long-term follow-up of a case and review of the literature.
Jauniaux E, de Meeus MC, Verellen G, Lachapelle JM, Hustin J.
Histopathologic Institute of Loverval, Belgium.
Pediatr Pathol 1993 Nov-Dec;13(6):717-21 Abstract quote
We describe a case of giant congenital melanocytic nevus with placental villous involvement in an otherwise uncomplicated pregnancy. Only four similar cases have been reported in the world literature. Nevomelanocytes were found in both villous stoma and fetal capillaries.
No neonatal or maternal adverse effects were observed 5 years after diagnosis in the present case.
TREATMENT Dermabrasion of large congenital melanocytic naevi in neonates.
Bohn J, Svensson H, Aberg M.
Department of Plastic and Reconstructive Surgery, Malmo University Hospital, Malmo, Sweden.
Scand J Plast Reconstr Surg Hand Surg 2000 Dec;34(4):321-6 Abstract quote
We describe our findings in a series of 12 patients with large congenital melanocytic naevi treated with dermabrasion between the first and fourteenth week of life.
Postoperative follow-up ranged from 1-16 years. In all but two cases dermabrasion resulted in an appreciable and stable reduction of the hyperpigmentation, possibly by reducing the number of pigmented cells in the epidermis. In six of our 12 patients, reconstruction using grafts and flaps was done to improve the aesthetic result.
Seven years after dermabrasion, one patient developed a minimal deviation melanoma in the treated area, but his subsequent clinical course has been uneventful.
Giant congenital nevi: a 20-year experience and an algorithm for their management.
Gosain AK, Santoro TD, Larson DL, Gingrass RP.
Department of Plastic and Reconstructive Surgery, Medical College of Wisconsin.
Plast Reconstr Surg 2001 Sep;108(3):622-31 Abstract quote
A variety of treatment options exists for the management of giant congenital nevi. Confusion over appropriate management is compounded because not all giant congenital nevi are pigmented, and malignant potential varies between different types.
The present study sought to define factors in the presentation of giant congenital nevi that could provide an algorithm for their management, with respect to both the extent of resection and subsequent reconstructive options.
A retrospective review of all patients who presented with a congenital nevus of 20 cm2 or greater since 1980 was performed, distinguishing among nevi involving the head and neck, the torso, and the extremities.
Sixty-one patients with giant congenital nevi were evaluated (newborn to age 16 years), of which 60 nevi in 55 patients have been operated on. Giant congenital nevi having malignant potential were pigmented nevi (53 patients) and nevus sebaceus (four patients). Those not having malignant potential were verrucous epidermal nevi (three patients) and a woolly hair nevus (one patient).
Of the 60 giant congenital nevi operated on, expanded flaps were used in 25, expanded full-thickness skin grafts were used in 10, split-thickness or nonexpanded full-thickness skin grafts were used in 13, and serial excision was used in 30. After 1989, operations tended to use multimodality treatment plans, with an increased use of expanded full-thickness grafts and immediate serial tissue expansion. The use of serial excision, particularly in the extremities, also increased after 1989. Serial excision was the treatment of choice when it could be completed in two procedures or less, which occurred in more than 80 percent of cases using serial excision alone. Expanded flaps were the most common mode of reconstruction in the head and neck region and were used in 49 percent of these procedures. Serial excision was the most common form of treatment in the extremities, used in 50 percent of procedures. Tissue expansion in the extremities was infrequently used to provide an expanded flap (8 percent of procedures), whereas it was frequently used to provide expanded full-thickness skin grafts harvested from the torso (used in 31 percent of procedures).
On the basis of these data, algorithms for the extent of resection and subsequent reconstructive options for giant congenital nevi were developed. Their management should be formulated relative to pigmentation, malignant potential, and anatomic location of the respective lesions.
Curettage of giant congenital melanocytic nevi in neonates: a decade later.De Raeve LE, Roseeuw DI.
Department of Dermatology, Academic Hospital Vrije Universiteit Brussel, Brussels, Belgium
Arch Dermatol 2002 Jul;138(7):943-7 Abstract quote BACKGROUND: Currently, there is tremendous uncertainty regarding how giant congenital melanocytic nevi (GCMN) should be treated. Our approach to patients with GCMN is based on 2 main considerations: (1) obtain an acceptable cosmetic result to decrease the psychosocial inconvenience to the patient, and (2) attempt to minimize the risk of malignancy. For the past 10 years we have treated GCMN by curettage in the neonatal period. We report our experience and results.
OBSERVATIONS: Sixteen neonates with GCMN were treated by curettage between 1990 and 2000. Biopsy specimens were obtained and the patients received close clinical follow-up. In most patients cosmetic and functional results were good, and, to date, no melanoma has been observed in this series.
CONCLUSIONS: Curettage offers an adequate alternative to surgical excision when performed during the first 2 weeks of life. Patients and parents are pleased with the cosmetic and functional results and thereby suffer less from the psychosocial inconvenience caused by these lesions. Careful long-term follow-up of these children is essential to monitor final cosmetic outcome and reduce the potential for malignancy.
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Rosai J. Ackerman's Surgical Pathology. Ninth Edition. Mosby 2004.
Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 6th Edition. McGraw-Hill. 2003.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fifth Edition. Mosby Elesevier 2008
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