As commented in Chap. 30 in the discussion of acoustic neuroma, it is now apparent that the propensity to develop multiple schwannomas can also be inherited as a dominant trait, without the vestibular tumors characteristic of NF2. This trait maps to a genetic locus on chromosome 22 that is distinct from the one for NF2. It has been estimated that 2 to 5 percent of schwannomas requiring resection are from this disease. The diagnostic criteria are based on the presence of two of more schwannomas without vestibular nerve tumors in an individual older than age 18 years, as summarized in a thorough review by MacCollin and colleagues, and more recently by Plotkin and colleagues. Pain is the dominant problem.
Pathology of NF1 and NF2
The cutaneous tumors are characterized by a rather thin epidermis whose basal layer may or may not be pigmented. The collagen and elastin of the dermis is replaced by a loose arrangement of elongated connective tissue cells. The lack of compactness of the normal dermal collagen allows the palpable opening in the skin. The pigmented (café-au-lait) lesions contain only the normal numbers of melanocytes; the dark color of the skin is instead the result of an excess of melanosomes in the melanocytes. Some of the abnormally large melanosomes measure up to several microns in diameter.
The nerve tumors are composed of a mixture of fibroblasts and Schwann cells (except the optic nerve tumors, which contain a combination of astrocytes and fibroblasts). Predominance of one or the other of these cells in the nerve is the basis of the diagnosis of neurofibroma or schwannoma. Palisading of nuclei and sometimes encircling arrangements of cells (Verocay bodies) are features of both (see Chap. 30). Occasionally, along spinal roots or sympathetic chains, one may find a tumor made up of partially or completely differentiated nerve cells, a typical ganglioneuroma. Clusters of abnormal glia cells may be found in the brain and spinal cord, and, according to
Bielschowsky, they imply a link with tuberous sclerosis that has never been proved. Clinically and genetically, the two diseases are quite independent.
Malignant degeneration of the tumors is found in 2 to 5 percent of cases; peripherally they become sarcomas and centrally, astrocytomas or glioblastomas (Fig. 37-11).
If skin tumors and café-au-lait spots are numerous and Lisch nodules are present in the iris, the identification of the disease as type 1 neurofibromatosis offers no difficulty. A history of the illness in antecedent and collateral family members makes diagnosis even more certain. Doubt arises most frequently in patients with bilateral acoustic neuromas or other cranial or spinal neurofibromas or schwannomas with no skin lesions or only a few random ones. The tendency for these forms of NF to have few skin lesions is well known, but differentiation of type 1 from type 2 may be uncertain unless genetic studies are undertaken. Plexiform neuromas with muscle weakness because of nerve involvement and abnormalities of underlying bone may be confused with other tumors, especially in young children, who tend to have few café-au-lait spots and few cutaneous tumors. Hypertrophy of a limb requires differentiation from other developmental anomalies including Klippel-Trenaunay-Weber syndrome.