Dermatology Online Journal

Bilateral segmental neurofibromatosis diagnosed during pregnancy
P Maldonado Cid¹, E Sendagorta Cudós¹, L Noguera Morel¹, M J Beato Merino²
Dermatology Online Journal 17 (5): 6

1. Department of Dermatology, Hospital Universitario La Paz, Madrid, Spain. pmaldonadocid@gmail.com
2. Department of Pathology, Hospital Universitario La Paz, Madrid, Spain

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Abstract

Bilateral segmental neurofibromatosis is a rare subtype of neurofibromatosis type 1 defined by lesions affecting a single segment of the body and crossing the midline, with no systemic involvement. We present a case diagnosed during pregnancy because of the characteristic increase in size of the lesions during this period.

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Introduction

Neurofibromatosis type 1 is a rare genetic disorder characterized by café-au-late macules, axillary freckling, multiple neurofibromas, Lisch nodules, and bone abnormalities. Bilateral segmental neurofibromatosis is an even more unusual subtype with lesions affecting a single segment of the body and crossing the midline, with no systemic involvement. It is thought to be caused by a postzygotic double coincidental mutation. We report a case of bilateral segmental neurofibromatosis diagnosed during pregnancy because the patient had noticed an increase in the size of tumors. Pregnancy outcome is usually excellent and transmission to offspring is very infrequent.

Case report

A 31-year-old female presented at 33 weeks gestation in her first pregnancy with asymptomatic cutaneous lesions on her abdomen. She had noticed skin lesions two years before, which had increased in size and turned darker during pregnancy. The patient also related that some new papules had recently appeared on her back. There was no family history of neurologic or cutaneous disorders.

Figure 1a	Figure 1b
Figure 1. Soft non-confluent brown papules bilaterally distributed (1a) on the abdomen and (1b) on the back left inferior quadrant

Figure 2
Figure 2. Hyperpigmented macules on the right side of the trunk

Physical examination showed numerous soft non-confluent light brown papules of 3 to 5 mm in diameter. The lesions were bilaterally distributed on the abdomen and on the back left inferior quadrant, showing a segmental arrangement and a sharp demarcation at the midline of the back (Figures 1a and 1b). Further examination revealed multiple discrete hyperpigmented, macules 2-4 mm in size, on the right side of her trunk, again with sharp demarcation at the midline (Figure 2). No café-au-lait spots, axillary freckling, or musculoskeletal abnormalities were present. Hair, nails, and mucous membranes were normal. On ophthalmologic examination, no Lisch nodules were found. Complete blood tests and central nervous system tomography showed no abnormalities.

Figure 3	Figure 4
Figure 3. Non-encapsulated loosely arranged lesion located in the dermis and subcutis (H&E, x2) Figure 4. Delicate fascicles of cells with a short undulated oval of spindle-shaped nucleus and scant cytoplasm, with no atypia or mitoses (H&E, x20)

A biopsy skin specimen from one of the papules was submitted for histological examination. It showed a non-encapsulated loosely arranged lesion located in the dermis and subcutis (Figure 3). The lesion was composed of delicate fascicles of cells with a short undulated oval of spindle-shaped nucleus and scant cytoplasm, with no atypia or mitoses (Figure 4). With immunohistochemical stains, these cells expressed S100 (Figure 5). The histopathological diagnosis was, therefore, neurofibroma.

Figure 5
Figure 5. Immunohistochemical stain: these cells expressed S100 (x10)

Based on the distribution of the lesions, the abscence of extracutaneous involvement, and the histopathological confirmation, diagnosis of segmental bilateral neurofibromatosis was made.

A healthy neonate was delivered at term without complications during labor. A meticulous physical examination did not reveal cutaneous lesions at birth and the child has remained healthy during a two-year follow-up period. After delivery, the mother remained stable with no noticeable enlargement of the skin tumors during the same observation period.

Discussion

Neurofibromatosis type 1 (NF1) was first described by von Recklinghausen in 1882. The major disease features include café-au-lait macules, axillary freckling, multiple neurofibromas, pigmented iris hamartomas (Lisch nodules), and bone abnormalities. Central and peripheral nervous system disorders can be associated [1, 2].

Riccardi classified NF1 into eight subtypes, of which type V is segmental neurofibromatosis (SN). It is defined as café-au-lait macules or neurofibromas in a single, unilateral segment of the body, with no crossing of the midline, no familial history, and no systemic involvement.

Considered a rare disorder, its prevalence is estimated between 0.0014 and 0.002 percent [3]. Segmental neurofibromatosis arises from a postzygotic NF1 gene mutation located on the proximal long arm of chromosome 17, which leads to mosaicism [4].

Bilateral segmental neurofibromatosis is an even rarer subtype, first described by Gamel et al. in 1931. To our knowledge, approximately 20 cases have been reported to date. This extraordinary disease is thought to be caused by double coincidental mutation [5]. Partial unilateral lentiginosis – an unusual pigmentary disorder characterized by multiple lentigines in a unilateral distribution – can be associated with neurofibromatosis, as in the case we have reported [6].

The number and size of neurofibromas in NF1 patients may increase during pregnancy. By contrast, postpartum regression may be observed. This can be explained by the presence of pregnancy steroid hormone receptors, mainly progesterone receptors in NF1 tumor cells [7]. These changes sometimes lead to the diagnosis, as it happened with our patient.

Regarding pregnancy outcome, hypertension and severe events in NF1 pregnancies have been reported and it has been hypothesized that this may be related to the number of lesions present in the patient [7].

Some authors have suggested that in absence of Lisch nodules, the risk of transmission to offspring is minimal [5]. Nevertheless, if germ cells contain the mutation, it could give rise to a child affected with NF1 or localized neurofibromatosis [4].

We have reported a clinical case showing the typical features of segmental bilateral neurofibromatosis, with the peculiarity of being diagnosed during the pregnancy period. Segmental bilateral neurofibromatosis is probably an underreported disease.

Because pregnancy outcome is usually excellent and transmission is unusual, mothers should be adequately informed of the good prognosis of this disorder. In spite of this, genetic counseling must be offered to every patient.

References

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2. Ferner RE. The neurofibromatosis. Pract Neurol. 2010;10(2):82-93. [PubMed]

3. Victor FC. Segmental neurofibromatosis. Dermatol Online J. 2005;11(4):20. [PubMed]

4. Gabhane SK, Kotwal MN, Bobhate SK. Segmental neurofibromatosis: a report of 3 cases. Indian J Dermatol. 2010;55(1):105-8. [PubMed]

5. Sezer E, Senayli A, Sezer T, Bicakci U. Segmental neurofibromatosis: report of two cases. J Dermatol. 2006;33(9):635-8. [PubMed]

6. Rao GS. Partial unilateral lentiginosis with lisch nodules: A forme fruste of segmental neurofibromatosis? Indian J Dermatol Venereol Leprol 2004;70:114-5. [PubMed]

7. Roth TM, Petty EM, Barald KF. The role of steroid hormones in the NF1 phenotype: focus on pregnancy. Am J Med Genet A. 2008;146(12):1624-33. [PubMed]

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