Case Letter

Phacomatosis Cesioflammea in Association With von Recklinghausen Disease (Neurofibromatosis Type I)

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Practice Points

  • Phacomatosis cesioflammea can be associated with neurofibromatosis type I.
  • The port-wine stain component of phacomatosis cesioflammea may develop nodularity in long-standing cases.
  • The Nd:YAG laser is beneficial for treating blue spots of phacomatosis cesioflammea.



To the Editor:

Vascular lesions associated with melanocytic nevi were first described by Ota et al1 in 1947 and given the name phacomatosis pigmentovascularis. In 2005, Happle2 reclassified phacomatosis pigmentovascularis into 3 well-defined types: (1) phacomatosis cesioflammea: blue spots (caesius means bluish gray in Latin) and nevus flammeus; (2) phacomatosis spilorosea: nevus spilus coexisting with a pale pink telangiectatic nevus; and (3) phacomatosis cesiomarmorata: blue spots and cutis marmorata telangiectatica congenita. In 2011 Joshi et al3 described a case of a 31-year-old woman who had a port-wine stain in association with neurofibromatosis type I (NF-1). We present a case of phacomatosis cesioflammea in association with NF-1.

A 20-year-old woman presented to our outpatient section with a bluish black birthmark on the left side of the face since birth with the onset of multiple painless flesh-colored nodules on the trunk and arms of 1 year’s duration. She reported having occasional pruritus over the nodular lesions. Cutaneous examination showed multiple well-defined café au lait macules (0.5–3.0 cm) with regular margins. Multiple flesh-colored nodules were evident on the upper arms (Figure 1) and trunk. The nodules were firm in consistency and showed buttonholing phenomenon with some of the lesions demonstrating bag-of-worms consistency on palpation. Both palms showed multiple brownish frecklelike macules (Figure 2). A single bluish patch extended from the left ala of the nose to the sideburns. Adjoining the bluish patch was a subtle, ill-defined, nonblanchable red patch extending from the lower margin of the bluish patch to the mandibular ridge (Figure 3). Ocular examination showed melanosis bulbi of the left sclera and a few iris hamartomas (Lisch nodules) in both eyes. A biopsy of the skin nodule was obtained under local anesthesia after obtaining the patient’s informed consent; the specimen was fixed in 10% buffered formalin. A hematoxylin and eosin–stained section showed a well-circumscribed nonencapsulated tumor in the dermis composed of loosely spaced spindle cells and wavy collagenous strands (Figure 4). Routine hemogram and blood biochemistry including urinalysis were within reference range. Radiologic examination of the long bones was unremarkable. Our patient had 3 of 6 criteria defined by the National Institutes of Health for diagnosis of NF-1.4 On clinicopathological correlation we made a diagnosis of phacomatosis cesioflammea in association with NF-1. We have reassured the patient about the benign nature of vascular nevus. She was informed that the skin nodules could increase in size during pregnancy and to regularly follow-up with an eye specialist if any visual abnormalities occur.

Figure 1. Cutaneous neurofibromas (molluscum fibrosa)(black arrows) on the left upper arm.

Figure 2. Multiple brownish frecklelike macules on both palmar surfaces.

Figure 3. Evidence of twin spotting with pigmentary nevus (nevus of Ota) along with adjoining vascular nevus (nevus flammeus, port-wine stain).

Figure 4. Histopathology of a neurofibroma showing proliferation of spindle cells with elongated wavy nuclei (H&E, original magnification ×10).

The term phacomatosis is applied to genetically determined disorders of tissue derived from ectodermal origin (eg, skin, central nervous system, eyes) and commonly includes NF-1, tuberous sclerosis, and von Hippel-Lindau syndrome. Neurofibromatosis type I was first described by German pathologist Friedrich Daniel von Recklinghausen.5 Phacomatosis pigmentovascularis has been defined as the association of vascular nevus with a pigmentary nevus. Its pathogenesis can be explained by the twin spotting phenomenon.6 Twin spots are paired patches of mutant tissue that differ from each other and from the surrounding normal background skin. They can occur as 2 clinical types: allelic and nonallelic twin spotting. Our patient had nonallelic twin spots for 2 nevoid conditions: vascular (nevus flammeus) and pigmentary (nevus of Ota). Nevus of Ota was distributed in the V2 segment (maxillary nerve) of the fifth cranial nerve along with classical melanosis bulbi, which is considered a characteristic clinical feature of nevus of Ota (nevus cesius).7 Nevus flammeus (port-wine stain) is a vascular malformation presenting with flat lesions that persists throughout a patient’s life. The phenomenon of twin spotting, or didymosis (didymos means twin in Greek), has been proposed for co-occurrence of vascular and pigmented nevi.8 The association of NF-1 along with phacomatosis cesioflammea (a twin spot) could be explained from mosaicism of tissues derived from neuroectodermal and mesenchymal elements. Neurofibromatosis type I can occur as a mosaic disorder due to either postzygotic germ line or somatic mutations in the NF1 gene located on the proximal long arm of chromosome 17.9 Irrespective of the mutational event, a mosaic patient has a mixture of cells, some have normal copies of a particular gene and others have an abnormal copy of the same gene. Somatic mutation can lead to segmental (localized), generalized, or gonadal mosaicism. Somatic mutations occurring early during embryonic development produce generalized mosaicism, and generalized mosaics clinically appear similar to nonmosaic NF-1 cases.10,11 However, due to a lack of adequate facilities for mutation analysis and financial constraints, we were unable to confirm our case as generalized somatic mosaic for NF1 gene.

Several morphologic abnormalities have been reported with phacomatosis cesioflammea. Wu et al12 reported a single case of phacomatosis cesioflammea associated with pectus excavatum in a 9-month-old infant. Shields et al13 suggested that a thorough ocular examination on a periodic basis is essential to rule out melanoma of ocular tissues in patients with nevus flammeus and ocular melanosis.

Phacomatosis cesioflammea can occur in association with NF-1. The exact incidence of association is not known. The nevoid condition can be treated with appropriate lasers.

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