Middle-aged Woman With Myriad Growths
CASE: A 46-year-old woman presents to the emergency department (ED) with pain in the left hand after an injury. Radiographs obtained in the ED are normal.
On physical examination, however, multiple “nodule-like” lesions are observed on the patient’s face (shown here) and body. Similar lesions are present on the face and the body of her daughter. The patient states that she has undergone an extensive investigation; a biopsy performed by a dermatologist confirmed the diagnosis.
What do you suspect the biopsy results revealed?
A. McCune-Albright syndrome
B. Von Recklinghausen disease
C. Bloom syndrome
D. LEOPARD syndrome
(Answer on next page.)
ANSWER: B, von Recklinghausen disease (neurofibromatosis type 1)
This patient has von Recklinghausen disease, which is also known as neurofibromatosis type 1.
NEUROFIBROMATOSIS
Neurofibromatosis is an autosomal dominant disorder that may affect the nervous system, bone, soft tissues, and skin. There are 2 types of neurofibromatosis:
•Type 1, which is referred to as peripheral neurofibromatosis and is the most common subtype—accounting for about 90% of all cases.
•Type 2, which is referred to as central neurofibromatosis because it is associated with bilateral acoustic neuromas (cranial nerve VIII) that often lead to hearing loss.
Neurofibromatosis affects all races and ethnicities equally. Because the trait is autosomal dominant, males and females are affected equally as well.
At least 2 of the following 7 criteria are required to make a clinical diagnosis:
•Six or more café-au-lait spots (hyperpigmented macules).
•Axillary or inguinal freckles.
•Two or more typical neurofibromas.
•Optic nerve glioma.
•First-degree relative with neurofibromatosis.
•Two or more iris hamartomas (Lisch nodules).
•Skeletal abnormalities, such as sphenoid dysplasia or thinning of the cortex of the long bones of the body (eg, bones of the leg, potentially resulting in bowing of the legs).
Because there is no cure for the condition itself, the only therapy for patients with neurofibromatosis is a program by a team of specialists to manage symptoms or complications. Surgery may be needed when the tumors compress organs or other structures. Cancerous growths develop in fewer than 10% of persons with neurofibromatosis; in these cases, chemotherapy may be successful.1-3
McCUNE-ALBRIGHT SYNDROME
McCune-Albright syndrome is a genetic disease that affects the bones and pigmentation of the skin. It is caused by mutations in the GNAS1 gene. The abnormal gene is present in a fraction, but not all, of the patient’s cells (mosaicism). This disease is not inherited. It is caused by a DNA mutation that occurs in the uterus while the fetus is developing. Symptoms include bone fractures, deformities of the facial bones, gigantism, and irregular and large patchy café-au-lait spots (especially on the back.) There is no specific treatment for McCune-Albright syndrome; however, drugs that block estrogen production, such as testolactone, have been tried with some success.4
BLOOM SYNDROME
Bloom syndrome (congenital telangiectatic erythema) is a rare autosomal recessive disorder characterized by telangiectases and photosensitivity, growth deficiency of prenatal onset, variable degrees of immunodeficiency, and increased susceptibility to neoplasms of many sites and types. Cutaneous findings in Bloom syndrome include telangiectatic erythema, which appears as macules or plaques in a butterfly distribution on the face and other photodistributed areas; scleral telangiectases; cheilitis with crusting or bleeding; and café-au-lait macules with adjacent hypopigmented areas. Bloom syndrome has no specific treatment; however, avoidance of sun exposure and use of sunscreens can help prevent some of the cutaneous changes associated with photosensitivity.5
LEOPARD SYNDROME
Molecular studies have demonstrated that LEOPARD syndrome and Noonan syndrome are allelic disorders caused by different missense mutations in PTPN11, a gene encoding the protein tyrosine phosphatase SHP-2 located at band 12q24.1. Lentigines are the most prominent manifestation of the LEOPARD syndrome and are present in more than 90% of affected patients; however, an absence of the feature does not exclude the diagnosis. On careful examination, other cutaneous abnormalities may be detected, such as axillary freckling, café-au-lait spots, and localized hypopigmentation. Although cryosurgery and laser treatment may be beneficial for isolated lentigines, these procedures may be time-consuming because of the large number of lentigines. For some patients, treatment with tretinoin cream and hydroquinone cream may be helpful.6
1. Barone J. USMLE Step 1 Lecture Notes: Pathology. New York: Kaplan Inc.; 2008:57.
2. Rubin R, Strayer DS. Rubin’s Pathology: Clinicopathologic Foundation of Medicine. 5th ed. Baltimore, Md: Wolters Kluwer Health: Lippincott Williams & Wilkins; 2008:201-203.
3. Torpy JM, Burke AE, Glass RM. Neurofibromatosis. JAMA. 2009;302(19):2170.
4. Garibaldi L. Disorders of pubertal development. In: Kliegman RM, Behrman RE, Jenson HB, Stanton BF, eds. Nelson Textbook of Pediatrics. 18th ed. Philadelphia, Pa: Saunders Elsevier; 2007:chap 563.
5. Gretzula JC, Hevia O, Weber PJ. Bloom’s syndrome. J Am Acad Dermatol. 1987;17(3):479-488.
6. Tong KL, Ding ZP, Chua T. Leopard syndrome. Singapore Med J. 2001;42(7):328-331.