Dermatology Online Journal

Segmental neurofibromatosis
Chris G Adigun MD, Jennifer Stein MD PhD
Dermatology Online Journal 17 (10): 25

Department of Dermatology, New York University, New York, New York

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Abstract

A 59-year-old man presented for evaluation and excision of non-tender, fleshy nodules that were arranged in a dermatomal distribution from the left side of the chest to the left axilla. A biopsy specimen of a nodule was consistent with a neurofibroma. Owing to the lack of other cutaneous findings, the lack of a family history of neurofibromatosis, and the dermatomal distribution of the neurofibromas, this patient met the criteria for a diagnosis of segmental neurofibromatosis (SNF) according to Riccardi’s definition of SNF and classification of neurofibromatosis. Because the patient has no complications of neurofibromatosis 1 no medical treatment is required.

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History

A 59-year-old man with a 25-year history of the gradual development of nodules on his chest and axilla has continued to develop more nodules. The lesions do not itch, burn, or bleed. They occasionally catch on clothing but are otherwise asymptomatic.

Physical examination

Figure 1

Numerous, soft, flesh-colored papules and nodules that range in size from 4 to 8 mm were arranged linearly in a dermatomal distribution from the left axillae posteriorly to the left side of the chest anteriorly. The nodules were easily manually invaginated into the skin with pressure (button-hole sign). No axillary freckles or café-au-lait macules were present.

Laboratory data

None.

Histopathology

None.

Discussion

Segmental neurofibromatosis (SNF) is a rare, atypical presentation of von Recklinghausen neurofibromatosis (NF-1) [1]. The prevalence of this disorder has been estimated to range between 0.0014 percent to 0.002 percent [2]. However, it has been proposed that this prevalence is an underestimate because of its often subtle clinical presentation [3].

Segmental neurofibromatosis was first described in 1956, when it was termed sectorial neurofibromatosis [3]. In 1977, the disorder was renamed SNF [5]. In 1982, Riccardi included SNF in his classification of neurofibromatosis to represent NF-5 and established the diagnostic criteria [6]: pigmentary abnormalities, which include café-au-lait macules and/or axillary freckles, and/or neurofibromas in a single unilateral segment of the body, with no crossing of midline; no family history of neurofibromatosis; and no systemic involvement. Segmental neurofibromatosis was then further subdivided into four subtypes: true segmental, localized with deep involvement, hereditary, and bilateral [7] to include cases that did not conform completely to these criteria.

Patients that meet the criteria for diagnosis of SNF may be further divided into four groups: those with only pigmentary abnormalities, those with only neurofibromas, those with both pigmentary abnormalities and neurofibromas, and those with isolated plexiform neurofibromas. Clinical findings develop over the same expected time course as generalized disease, with café-au-lait macules and plexiform neurofibromas developing in childhood and neurofibromas in adulthood. The most common presentation is neurofibromas alone, which most often are in a dermatomal distribution. The most commonly involved dermatomal segment is cervical, which is followed by thoracic, lumbar, and sacral being the least common. In the majority of cases that are characterized by pigmentary abnormalities, lesions tend to follow the lines of Blaschko [8]. Most cases present with unilateral disease although there are reports of bilateral disease [9].

The localized cutaneous manifestations of SNF occur as a result of a postzygotic somatic mutation in primitive neural crest cells. Recent research indicates that this postzygotic NF1 gene mutation is located on the proximal long arm of chromosome 17 and may occur in both somatic and gonadal cell lines [10]. Somatic mutations that give rise to limited disease, such as SNF, are manifestations of mosaicism. Mosaicism results from errors that occur during somatic or germ cell division, such as miscopying events during cell division; major errors occurring during mitosis, such as nondisjunction; or mitotic error at the level of DNA replication. Regardless of the mutational event, the clinical outcome is an individual with a mixture of cells, some that have normal copies of a particular gene and others that have an abnormal copy of the same gene. If the mutation occurs before tissue differentiation, the clinical phenotype will be generalized disease. Mutations that occur later in development give rise to disease that is confined to a single region. Gonadal mosaicism is responsible for instances of individuals with segmental NF having children with generalized NF [11].

Initial evaluation of these patients is directed at detecting generalized disease. Patients should receive a thorough physical examination to investigate for cutaneous findings elsewhere on the body and an ophthalmologic examination to seek Lisch nodules [12]. If lesions are found systemically or in other family members or if the patient goes on to develop systemic findings or lesions in a more generalized fashion, the initial diagnosis would need to be reevaluated. There are no specific management guidelines once a diagnosis of SNF has been established. Patients need to be initially counseled that they do not have the generalized form of NF-1 and that they have a low risk of developing any disease-related complications. Those patients considering having children should be made aware of the small risk of having a child with generalized NF1. The exact risk of this occurring is not yet defined but, based on animal studies, appears to be proportional to the percentage of body surface area involved [11].

References

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4. Crowe FW, et al. Clinical, Pathological and Genetic Study of Multiple Neurofibromatoses. Springfield, Ill: Charles C Thomas Publishers; 1956:74

5. Miller RM, Sparkes RS. Segmental neurofibromatosis. Arch Dermatol 1977; 113:837 [PubMed]

6. Riccardi VM. Early manifestations of neurofibromatosis: diagnosis and management. Compr Ther 1982; 8:35 [PubMed]

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11. Ruggieri M, Huson SM. The clinical and diagnostic implications of mosaicism in the neurofibromatoses. Neurology 2001; 56:1433 [PubMed]

12. Gabhane SK, et al. Segmental neurofibromatosis: a report of 3 cases. Indian J Dermatol 2010;55:105 [PubMed]

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