A 22-year-old man comes to the office due to occasional dull headaches that awaken him from sleep. The patient has no associated neurologic deficits. There is no history of migraines in the family. His temperature is 37.2 C (99 F), blood pressure is 140/80 mm Hg, pulse is 60/min, and respirations are 12/min. On physical examination, there are several 3- to 5-cm flat, pigmented spots on his trunk. There are also multiple, subcentimeter, soft, fleshy, cutaneous tumors located on his trunk and neck. The predominant cells forming these tumors most likely originated from which of the following structures?
Embryologic derivatives | ||
Ectoderm | Surface ectoderm |
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Neural tube |
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Neural crest |
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Mesoderm |
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Endoderm |
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*Formerly thought to be of neural crest origin. | ||
This patient has clinical features of neurofibromatosis type I (von Recklinghausen disease), an autosomal dominant neurocutaneous disorder caused by mutations in the NF1 tumor suppressor gene. Patients typically develop hyperpigmented macules (Café-au-lait spots) over the trunk soon after birth and are at increased risk of developing central nervous system neoplasms (eg, optic gliomas, pilocytic astrocytomas), which can cause elevated intracranial pressure and headache.
Cutaneous neurofibromas usually manifest during early adolescence as multiple, raised, fleshy tumors (<2 cm) that often increase in size and number with age. These are benign nerve sheath neoplasms predominantly comprised of Schwann cells, which are embryologically derived from the neural crest.
(Choice A) The endoderm gives rise to thyroid follicular cells (derived from the primitive tongue) and the epithelial linings of the gastrointestinal tract, middle ear, lungs, bladder, and most of the urethra. It also gives rise to the bulk of the liver and pancreas, as these structures form from outpouchings of the primitive gut tube.
(Choice B) The mesoderm is divided into paraxial, intermediate, and lateral sections and gives rise to muscles, bones, blood, connective tissue, dermis, and the kidneys/ureters.
(Choice D) The neural tube gives rise to neurons of the central nervous system and the neurohypophysis, retina, pineal gland, preganglionic autonomic fibers, astrocytes, and ependymal cells.
(Choice E) The notochord almost completely regresses in humans, and its only major derivative is the nucleus pulposus of the intervertebral disc. Vertebrae are derived from the paraxial mesoderm.
(Choice F) The surface ectoderm gives rise to the epidermis, lens of the eye, outer layer of the cornea, nasal and oral epithelium, and anal epithelium below the dentate line.
Educational objective:
Neurofibromatosis type I (von Recklinghausen disease) is an autosomal dominant disorder caused by mutations in the NF1 tumor suppressor gene. Patients characteristically develop numerous cutaneous neurofibromas comprised mostly of Schwann cells, which are embryologically derived from the neural crest.