Neurofibromatous neuropathy: An ultrastructural study.

Plexiform neurofibroma is pathognomonic of neurofibromatosis 1 (NF1). An NF1-associated peripheral neuropathy has been described in a small minority of NF1 patients but its histopathological features are poorly characterized. We report the case of a 46-year-old woman presenting with bilateral supraclavicular painful masses without other stigmata of NF1. MRI showed bilateral plexiform lesions extending from cervical roots to the elbows. Nerve conduction studies documented a sensory motor polyneuropathy. Morphometric analysis of sural nerve biopsy showed a preferential loss of large-caliber myelinated fibers with a g ratio of 0.515, and the presence of regeneration clusters. By electron microscopy, marked and diffuse endoneurial fibrosis with an altered relationship between Schwann cells (SC) and collagen fibrils was observed. Moreover both myelinating and non-myelinating SC were characterized by the presence of various cell degradation products. These changes suggest that, in neurofibromatous neuropathy, a widespread axonal atrophy and degeneration take place independently on the presence of tumoral infiltration, possibly due to an impairment in SC-axon cross talk. In this case, the coexistence of plexiform neurofibromas with a peripheral neuropathy strongly suggests a diagnosis of NF1 even without fulfillment of clinical criteria. We propose that in the presence of plexiform neurofibromas, electrophysiological studies should be performed also in asymptomatic patients, in order to detect the existence of a subclinical neuropathy.

Plexiform and dermal neurofibromas and pigmentation are caused by Nf1 loss in desert hedgehog-expressing cells.

Neurofibromatosis type 1 (Nf1) mutation predisposes to benign peripheral nerve (glial) tumors called neurofibromas. The point(s) in development when Nf1 loss promotes neurofibroma formation are unknown. We show that inactivation of Nf1 in the glial lineage in vitro at embryonic day 12.5 + 1, but not earlier (neural crest) or later (mature Schwann cell), results in colony-forming cells capable of multilineage differentiation. In vivo, inactivation of Nf1 using a DhhCre driver beginning at E12.5 elicits plexiform neurofibromas, dermal neurofibromas, and pigmentation. Tumor Schwann cells uniquely show biallelic Nf1 inactivation. Peripheral nerve and tumors contain transiently proliferating Schwann cells that lose axonal contact, providing insight into early neurofibroma formation. We suggest that timing of Nf1 mutation is critical for neurofibroma formation.

Microcystic pseudoglandular plexiform cutaneous neurofibroma.

Glandular structures are well documented to appear in peripheral nerve sheath tumors. These epithelial elements are usually present in malignant peripheral nerve sheath tumors although a few cases of glandular benign peripheral nerve sheath tumors have also been described, most of them being schwannomas. A neurofibroma with glands is considered to be a rare type of divergent differentiation, but a neurofibroma containing gland-like or pseudoglandular structures have not, to our knowledge, been described. We report a 33-year-old patient with a well-demarcated dermal neoplasm, composed of neoplastic Schwann cells, perineurial-like cells and fibroblasts in a matrix with collagen fibers and myxoid areas. A part of the tumor consisted of microcystic gland-like spaces lined by flat cells. These cells were either S100 positive or negative, with no epithelial membrane antigen, cytokeratin or CD31 immunostaining. Recognition of the presence of pseudoglandular elements in neurofibromas is important to distinguish them from other tumoral lesions, some of them with malignant potential.

Problemas diagnósticos en tumores del nervio periférico (I) / Diagnostic problems of peripheral nerve tumours (I)

Los tumores del nervio periférico son lesiones relativamente comunes que con frecuencia plantean problemas diagnósticos de marcada trascendencia. En la presente revisión se estudian de modo comparativo lesiones con nombres o con características morfológicas parecidas para poner en relieve los hallazgos diferenciales más significativos. En esta primera parte se revisan los siguientes diagnósticos: schwannoma convencional de tejidos blandos vs. neurofibroma intraneural; neurofibroma plexiforme vs. schwannoma plexiforme; schwannoma celular vs. tumor maligno de la vaina neural periférica (TMVNP); TMVNP vs. Melanoma, y TMVNP vs. sarcoma sinovial monofásico(AU)

Peripheral nerve tumours are relatively common and often pose important diagnostic problems. The present review makes a comparative study of lesions with similar names or morphological characteristics, highlighting the most significant findings. In this first part, the following diagnoses are considered: Conventional soft tissue schwannoma vs. intraneural neurofibroma; plexiform neurofibroma vs. plexiform schwannoma; cellular schwannoma vs. malignant peripheral neural sheath tumour (MPNST); MPNST vs. melanoma; and MPNST vs. monophasic synovial sarcoma(AU)