Neurotized congenital melanocytic nevus resembling a pigmented neurofibroma.

Neurotized congenital melanocytic nevus and pigmented neurofibroma (PNF) are close mimics and pose a clinicopathological challenge. We present a case of pigmented hypertrichotic plaque over lumbosacral region and discuss the differential diagnosis and its clinical, histopathological and immunohistochemistry features which may aid in differentiation. We highlight the difficulties faced in differentiating neurotized congenital melanocytic nevus from pigmented neurofibroma.

What was known?

Neurotized congenital melanocytic nevus and pigmented neurofibroma (PNF) are close mimics.

Introduction

Neurotized congenital melanocytic nevus and pigmented neurofibroma (PNF) are close mimics and pose a clinicopathological challenge.[1] Pigmented neurofibroma is a rare neurofibroma with melanin-laden pigment cells which accounts for less than 1% of neurofibromas.[1] We present a case of pigmented hypertrichotic plaque over lumbosacral region and discuss its differential diagnosis, clinical, histopathological and immunohistochemistry features.

Case Report

A 55-year-old male presented with a solitary growth over lumbosacral area present since birth and associated with radiating pain over lower back onto bilateral posterior thighs (right > left) for past 6 months. There was no family history of similar skin disorder. Cutaneous examination revealed a single, band like, nontender, hyperpigmented, verrucous soft plaque of size 7 × 5 cm over lumbosacral area in the midline [Figure 1]. Surface of the plaque showed hypertrichosis and a few soft nodules with size ranging from 0.5 × 0.5 cm to 2 × 2.5 cm. There was no bag of worms feel on palpation. There was a single café-au-lait macule of size 3 × 1 cm present to the left side of the plaque and a satellite nevus on the right side. Clinical examination revealed no other abnormality. Lisch nodules in iris were not seen on slit lamp examination. A skin biopsy was taken from the plaque and nodule and sent for histopathological examination. Magnetic resonance imaging study of pelvis and lumbosacral region did not reveal any abnormal findings. Histopathology of the skin biopsy specimen revealed an unremarkable epidermis with a zone of uninvolved dermis and a lesion extending mostly from mid-dermis up to the subcutaneous tissue. The upper portion of the lesion showed large nests of nevus cells in mid-dermis [Figure 2], some containing melanin pigment and an occasional small nest of nevus cells in upper dermis without any junctional activity. There was progressive maturation of these nests of cells into spindle-shaped cells with wavy nuclei resembling a neurofibroma in the lower part of the lesion extending from the dermis to subcutis. Interspersed and merging imperceptibly within these spindled cells were small nerve twigs, some of which had oval and lamellated appearance similar to tactile bodies [Figure 3] indicating neural differentiation. On immunohistochemistry, S100 [Figures 4 and 5] and HMB 45 [Figure 6] stained the nests of nevus cells, spindled cells and the neural component; Melan A [Figure 7] stained the nevus cells as well as the spindled cells but not the neural component; neuron-specific enolase [Figure 8] and CD57 [Figure 9] stained only the neural component; CD 34 highlighted the blood vessels and stromal cells only [Figure 10] and glial fibrillary acid protein (GFAP) was negative. Thus, we arrived at the diagnosis of congenital melanocytic nevus with extensive neurotization resembling a pigmented neurofibroma

Figure 1

Band like hyperpigmented, verrucous, hypertrichotic plaque with a nodular surface in the lumbosacral area in midline. A solitary café-au-lait macule can be made out on the left side of the plaque and a satellite nevus on the right side

Figure 2

Nests of nevus cells containing melanin pigment in dermis showing maturation into spindle-shaped cells (H and E ×40)

Figure 3

Neural differentiation in the spindle cell component with presence of oval structures, resembling tactile bodies (inset) (H and E, ×100)

Figure 4

On immunohistochemistry, both nests of nevus cells and neural component stained with S100 (S100, ×40)

Figure 5

On immunohistochemistry, tactile bodies are seen stained with S100 (S100, ×100)

Figure 6

On immunohistochemistry, both nests of nevus cells and neural component stained with HMB 45 (HMB 45, ×100)

Figure 7

On immunohistochemistry Melan A stained nests of nevus cells and (inset) spindle cells but not the tactile bodies (Melan A, ×100)

Figure 8

On immunohistochemistry, only neural elements stained with neuron-specific enolase (NSE, ×100)

Figure 9

On immunohistochemistry, CD 57 stained only the neural component (CD 57, x200)

Figure 10

On immunohistochemistry, CD 34 stained only the blood vessels and stromal cells (CD 34, ×400)

Discussion

Pigmented hypertrichotic plaque over lumbosacral region posed a clinicopathological challenge to us. Our clinical differential diagnoses were congenital melanocytic nevus (CMN) and PNF Clincal, histopathological and immunohistochemistry features which may aid in their differentiation along with the features of our case are listed in Table 1.[123] Melanocytic nevus and neurofibromas have a common origin, i.e. neural crest derived stem cells. Skin lesions appearing in midline of back include subcutaneous lipoma, dermal sinuses, hypertrichosis, capillary hemangiomas, lumbosacral congenital scars and atretic meningoceles, which are considered markers of occult spinal dysraphism (OSD) and are present in 70% cases of OSD.[4] These markers of OSD are predominantly seen in lumbosacral area.[4] There was no evidence of spinal dysraphism in our case.

Table 1

Clinical and histopathologic differentiation of congenital melanocytic nevus and pigmented neurofibromas from its close mimics

PNF, CMN, neurotized melanocytic nevus, neurocristic hamartoma (NCH), Becker's nevus, Bednar tumors and cellular blue nevi are close mimcs.[567] Even though both PNF and CMN present as hyperpigmented, hypertrichotic plaque but CMN lacks the bag of worms feeling on palpation which may be present in PNF. The other features of neurofibromatosis like café-au-lait macules, intertriginous freckling may be helpful in diagnosing PNF but may not always be present. Satellite nevi may be seen in a case of CMN.[1] On histopathology, there is prominent clustering of nests or cords of melanocytes in CMN unlike PNF. Spindled cells with peripheral nerve sheath differentiation including Wagner-Meissner corpuscle like bodies and junctional and/or dermal melanocytosis may be visible in both CMN and PNF. But, prominent abnormal nerve structures and plexiform foci are seen in PNF not in CMN. Further differentiation can be done by immunohistochemistry when S-100 would stain both PNF and CMN, like in our case, while antibodies to Leu-7, Glial fibrillary acidic protein (GFAP), factor XIIIA and myelin basic protein would stain PNF but not the neurotized melanocytic nevus.[189] NCH lesions have a predilection for the scalp with focal alopecia and are usually not found on the trunk.[3] On histopathology, NCH reveal dermal melanocytes and neuroid structures with Schwannian differentiation. On immunohistochemistry, CD34 stains the stromal cells throughout the NCH lesion which differentiates it from its other close mimics including blue nevi, which has prominent nevomelanocytic component and absence of Wagner-Meissner corpuscle like bodies.[3] However, our case showed nevus cells with a progressive maturation into spindle cells and differentiation into neuroid structures and hence a diagnosis of neurotized congenital melanocytic nevus was made. Although differentiation of CMN and PNF is difficult due to sometimes overlap of clinic-pathological features, Becker's nevus can also form a differential diagnosis especially in a brown hypertrichotic plaque. Becker's nevus is usually acquired and on histopathology would show increased melanocytes at the basal layer and increased melanophages in papillary dermis, while in PNF, melanocytes are present not only in increased numbers in basal layer but also in papillary dermis and scattered throughout in the neurofibroma in reticular dermis and subcutis.[6] There is no prominent clustering of nests or cords of melanocytes in Becker's nevus unlike CMN. Bednar tumors are storiform neurofibromas, a pigmented variant of dermatofibrosarcoma protuberans (DFSP) which are characterized by storiform arrangement of spindles cells admixed with melanin containing dendritic cell.[7] Non-pigmented spindle cells of Bednar tumor don’t stain with S-100 thus differentiating from CMN and PNF.[7]

Conclusion

The differentiation of pigmented neurofibroma and neurotized congenital melanocytic nevus may pose a clinicopathological challenge and immunohistochemistry serves as a very useful aid in their differentiation.

What is new?

Immunohistochemistry especially Melan-A serves as a very useful aid in differentiation of neurotized congenital melanocytic nevus and pigmented neurofibroma.