Pathology of Neurofibromatosis
described by von Recklinghausen in 1882.
Neurofibromas may arise in any part of the body including axilla, thigh, buttock, deep lying soft tissue, orbit, mediastinum, retroperitoneum, tongue, gastrointestinal tract.
There are 8 clinical subtypes:
NF-1: Classic von Recklinghausen's disease is inherited as an autosomal dominant trait. The responsible gene (NF1) is located in chromosome 17.
Plexiform neurofibroma is pathognomonic of NF-1.
Cafe-au-lait pigmentation (macular pigmentation) develops within the first few years of life. Multiple neurofibromas appear during childhood and adolescence after the cafe au lait spots.
Pigmented hamartoma of the iris (Lisch nodules) are present in 90% of patients. There may be skeletal abnormalities (kyphoscoliosis, bone hypertrophy, pseudoarthrosis).
Malignant transformation may occur rarely.
NF-2: Central neurofibromatosis-
Autosomal dominant disorder (alteration of a gene located in chromosome 22). Associated with acoustic neuroma and a range of neoplasms of the central nervous system.
Cutaneous schwannomas may also be present.
NF-3: Characterized by combined features of NF-1 and NF-2.
NF-4: Characterized by diffuse neurofibroma and cafe-au-lait pigmentation. Other features of NF-1 are not present.
NF-5: Segmental form of neurofibromatosis where the disease is restricted to one area of the body.
NF-6: Cafe-au-lait pigmentation is the only manifestation.
NF-7: Late onset type.
NF-8: Miscellaneous group
Neurofibromatosis type I and 2 are two genetically distinct autosomal dominant disorders. Both these lesions are characterized by the presence of tumors of the nerves.
Neurofibromatosis type 1 (von Recklinghausen disease), is characterized by three important features:
1) Multiple neural tumors involve nerve trunks in skin as well as internal organs. Three types of lesions are found: cutaneous, subcutaneous and plexiform.
The last mentioned are subcutaneous tumours that contain numerous tortuous thickened nerves.
They sometimes cause massive enlargement of a limb or other body parts.
Histologically, there is proliferation of neurites, Schwann cells, and fibroblasts, all embedded in loose myxoid stroma.
2) Cutaneous pigmentations, present in more than 90% of patients, take the form of light brown macules located over nerve trunks (café au lait spots).
3) Lisch nodules or pigmented iris hamartomas are present in almost all cases.
Several associated abnormalities are as follows
- There are skeletal lesions (bone cysts, scoliosis, and erosion of the bone surface) in 30 to 50% of patients.
- There is an increased risk of the development of other tumors, especially meningiomas, optic gliomas, and pheochromocytomas. Paraganglioma-Online
- There is a tendency towards reduced intelligence.
Loss by mutation of tumour suppressor genes underlies these conditions.
The NF-1 locus on chromosome 17 encodes neurofibromin, a protein that regulates the function of the p21 ras oncoprotein. NF-1 is a tumor-suppressor gene. The NF-2 locus on chromosome 22 also encodes a tumor-suppressor gene of unknown function
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