Department of Pathology, University of Oklahoma Health Sciences Center

NeuroTest Sample Question #30 Next question Previous question

Answer:  B (Plexiform Neurofibroma) Level of difficulty: 1 NeuroTest NeuroLearn NeuroHelp

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Discussion: 

• Pathology: This photo was obtained from a parotid gland mass from a patient with neurofibromatosis 1. The salient pathologic changes in this case is the round bundles of mesenchymal tissue that appears to be neoplastic. These bundles are well separated from some epithelial component in the same picture. At high magnification, the tumor cells appear spindle and admixed with some myxomatous substance. So, the diagnoses of adenoid cystic carcinoma, mucoepidermoid carcinoma, epithelial-myoepithelial carcinoma are incorrect since they contain epithelial components that can be easily seen. Schwannoma is an unlikely diagnosis for the lack of palisading arrangement of the cells. Also, schwannoma does not arrange in this type of well demarcated bundles. The histopathology, in fact, is classic for plexiform neurofibroma. 

• Neurofibromatosis 1: NF1 is known as the true von Recklinghausen's disease and it is about 10 times more common than neurofibromatosis 2 (NF2). It is a pleiotropic congenital multiple dysplasia syndrome. The cardinal feature is multifocal focal hyperplasia and neoplasia in the supportive tissue throughout the nervous system. These include neurofibroma of the peripheral nervous system and glioma of the central nervous system, particular astrocytoma of the optic nerve hypothalamic pathway. Plexiform neurofibroma as illustrated in this case has a particularly strong association with NF1. Lesions in the skin, bone, and eye are also common in NF1 patients.  Malignant transformation of neurofibroma in NF1 patients is far more common than in non-NF1 patients. NF1 patients also carry an ncreased risk of other malignancies. They have a 200 fold increase in risk in development of chronic myelomonocytic leukemia (CML). Increased risk for other malignancies include adenocarcinoma of the ampulla of Vater, melanoma, non-Hodgkin's lymphoma and lymphoblastic leukemia. Genetics: NF1 is transmitted in an autosomal dominant triat, about 50% of the cases are sporadiac and arise as new mutations. In familial cases, the expressivity of NF1 is extremely variable but the penetrance is 100%. No convincing genotype-phenotype correlations have been established. Neurofibromin is the gene involved. It is large protein located under the plasma membrane. The neurofibrominb gene is a classic tumor suppressor gene and is located on 17q11.2, encodes neurofibromin. Deletion of the entire gene, deletion of single- and multiple-exons, and small deletion comprised about 50% of all the mutation. The deletion can be bigger than the gene and therefore other potential genes can also be deleted. The rest includes insertion and point mutations. Point mutations that have been identified do not cluster in hot spots.

Comment: KarMing-Fung@ouhsc.edu