Multiple Endocrine Neoplasia Type 1 Clinical Presentation

  • Author: Thomas N Darling, MD, PhD; Chief Editor: Dirk M Elston, MD   more...
 
Updated: Mar 7, 2012
 

History

Cutaneous tumors in multiple endocrine neoplasia type 1 (MEN1) are of long duration and generally grow slowly or not at all. This permanence helps differentiate these lesions from inflammatory skin lesions.

Ask patients with the cutaneous abnormalities seen in MEN1 about symptoms of hormone hypersecretion. Ask patients if any family members have similar skin lesions or endocrine tumors. Ask if any family members have tuberous sclerosis.

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Physical

In multiple endocrine neoplasia type 1 (MEN1), angiofibromas are telangiectatic, skin-colored, pink or light-brown papules that are 1-4 mm in diameter, as shown in the image below. Approximately 2-50 lesions may be present. They are mostly located on the central part of the face. In separate studies, angiofibromas were reported in 5%, 8%, 22%, 43%, 64%, and 88% of patients with MEN1.[3, 5, 15, 17, 18, 19]

A 27-year-old man has telangiectatic, red papules A 27-year-old man has telangiectatic, red papules on the nose, the nasolabial fold, and the upper lip. Histologic examination of one of these lesions confirmed the clinical diagnosis of angiofibroma. In addition to multiple facial angiofibromas, this patient has multiple collagenomas and gingival papules, as well as hyperparathyroidism and a positive family history for multiple endocrine neoplasia type 1.

Angiofibromas in patients with MEN1 tend to be smaller in size and less numerous than angiofibromas in patients with tuberous sclerosis. In addition, angiofibromas in MEN1 are common on the upper lip and vermillion border of the lip, whereas angiofibromas in tuberous sclerosis tend to spare the upper lip. The age at onset of angiofibromas is later in MEN1 than in tuberous sclerosis; typically, they occur in the second decade and later in life in MEN1 compared with the first decade of life in tuberous sclerosis.[20] Patients with MEN1 do not exhibit several findings described in tuberous sclerosis, including the forehead plaque, multiple periungual fibromas, and pitting of the teeth.

Collagenomas are skin-colored to slightly hypopigmented, firm, round to oval papules that are 0.2-2 cm in diameter, as shown in the images below. Multiple smaller lesions and/or a few larger lesions may be observed. They are mostly located on the upper part of the trunk and on the neck. They have been reported in 0-72% of patients with MEN1, with 83-91% of patients with collagenomas having multiple lesions.[3, 5, 18, 21, 22]

The shoulder of a 65-year-old man shows multiple fThe shoulder of a 65-year-old man shows multiple firm, skin-colored to slightly hypopigmented papules. Biopsy results of the largest lesion revealed collagenoma. Endocrinologic features of multiple endocrine neoplasia type 1 in this patient are hyperparathyroidism and Zollinger-Ellison syndrome. Note that the photograph was taken with side lighting to accentuate the lesions. A close-up view of a large collagenoma on the shouA close-up view of a large collagenoma on the shoulder of a 65-year-old man shows multiple firm, skin-colored to slightly hypopigmented papules. Endocrinologic features of multiple endocrine neoplasia type 1 in this patient are hyperparathyroidism and Zollinger-Ellison syndrome.

Lipomas are soft, compressible, subcutaneous nodules that are generally 0.5-5 cm in diameter, as shown in the image below. They are solitary or multiple, and they occur on the trunk, the extremities, and the scalp. Lipomas have been reported in 3-34% of patients with MEN1.[3, 5, 18]

A 39-year-old woman with multiple endocrine neoplaA 39-year-old woman with multiple endocrine neoplasia type 1 has a soft nodule on the forehead that is consistent with lipoma. Lipomas in patients with multiple endocrine neoplasia type 1 can be single or multiple, and they are sometimes large.

Additional skin findings include café au lait macules; hypopigmented macules, including confettilike hypopigmented macules; gingival papules (see image below); and solitary periungual fibroma.

On the attached gingiva of a 27-year-old man with On the attached gingiva of a 27-year-old man with multiple endocrine neoplasia type 1, a few small, whitish papules are present. Gingival papules are a rare and subtle finding in multiple endocrine neoplasia type 1. In addition to multiple facial angiofibromas, this patient has multiple collagenomas, hyperparathyroidism, and a positive family history for multiple endocrine neoplasia type 1.

Solitary hypopigmented macules or café au lait macules are common in the general population and should not be used as markers for MEN1.

Multiple hypopigmented macules or confettilike hypopigmented macules are more commonly observed in persons with tuberous sclerosis but have been observed in patients with MEN1.

Similarly, gingival papules are typically associated with tuberous sclerosis and Cowden syndrome, but they have also been observed in 2 patients with MEN1.[3]

Café au lait macules numbering 3 or less have been seen in patients with MEN1. Six or more café au lait macules indicates neurofibromatosis.

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Causes

See Pathophysiology.

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Contributor Information and Disclosures
Author

Thomas N Darling, MD, PhD  Director of Dermatologic Research, Associate Professor of Dermatology, Department of Dermatology, Uniformed Services University of the Health Sciences

Thomas N Darling, MD, PhD is a member of the following medical societies: American Academy of Dermatology and Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Specialty Editor Board

Terry L Barrett, MD  Clinical Professor of Dermatology and Pathology, University of Texas Southwestern School of Medicine; Director, ProPath Dermatopathology, Dallas, Texas

Terry L Barrett, MD is a member of the following medical societies: American Academy of Dermatology, American Dermatological Association, American Medical Association, American Society of Dermatopathology, College of American Pathologists, and United States and Canadian Academy of Pathology

Disclosure: Nothing to disclose.

Richard P Vinson, MD  Assistant Clinical Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine; Consulting Staff, Mountain View Dermatology, PA

Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Association of Military Dermatologists, Texas Dermatological Society, and Texas Medical Association

Disclosure: Nothing to disclose.

Lester F Libow, MD  Dermatopathologist, South Texas Dermatopathology Laboratory

Lester F Libow, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, and Texas Medical Association

Disclosure: Nothing to disclose.

Catherine M Quirk, MD  Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania

Catherine M Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD  Director, Ackerman Academy of Dermatopathology, New York

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

References

  1. Brandi ML, Gagel RF, Angeli A, et al. Guidelines for diagnosis and therapy of MEN type 1 and type 2. J Clin Endocrinol Metab. Dec 2001;86(12):5658-71. [Medline].

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  3. Darling TN, Skarulis MC, Steinberg SM, Marx SJ, Spiegel AM, Turner M. Multiple facial angiofibromas and collagenomas in patients with multiple endocrine neoplasia type 1. Arch Dermatol. Jul 1997;133(7):853-7. [Medline].

  4. Zeller S, Marx SJ, Lungu AO, Cowen EW, Turner ML. Multiple angiofibromas and collagenomas in a 45-year-old man with recurrent nephrolithiasis, fatigue, and vision loss. J Am Acad Dermatol. Aug 2009;61(2):319-22. [Medline].

  5. Asgharian B, Turner ML, Gibril F, Entsuah LK, Serrano J, Jensen RT. Cutaneous tumors in patients with multiple endocrine neoplasm type 1 (MEN1) and gastrinomas: prospective study of frequency and development of criteria with high sensitivity and specificity for MEN1. J Clin Endocrinol Metab. Nov 2004;89(11):5328-36. [Medline].

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  10. Canaff L, Vanbellinghen JF, Kaji H, Goltzman D, Hendy GN. Impaired transforming growth factor-beta (TGF-ß) transcriptional activity and cell proliferation control of a menin in-frame deletion mutant associated with multiple endocrine neoplasia type 1 (MEN1). J Biol Chem. Jan 24 2012;[Medline].

  11. Pack S, Turner ML, Zhuang Z, et al. Cutaneous tumors in patients with multiple endocrine neoplasia type 1 show allelic deletion of the MEN1 gene. J Invest Dermatol. Apr 1998;110(4):438-40. [Medline].

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  13. Rusconi D, Valtorta E, Rodeschini O, Giardino D, Lorenzo I, Predieri B, et al. Combined characterization of a pituitary adenoma and a subcutaneous lipoma in a MEN1 patient with a whole gene deletion. Cancer Genet. Jun 2011;204(6):309-15. [Medline].

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  15. Sakurai A, Hashizume K, Fukushima Y. Facial angiofibroma as an initial manifestation in multiple endocrine neoplasia type 1. Intern Med. 2008;47(11):1067-8. [Medline].

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  25. Weiss ET, Geronemus RG. New technique using combined pulsed dye laser and fractional resurfacing for treating facial angiofibromas in tuberous sclerosis. Lasers Surg Med. Jul 2010;42(5):357-60. [Medline].

 
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A 27-year-old man has telangiectatic, red papules on the nose, the nasolabial fold, and the upper lip. Histologic examination of one of these lesions confirmed the clinical diagnosis of angiofibroma. In addition to multiple facial angiofibromas, this patient has multiple collagenomas and gingival papules, as well as hyperparathyroidism and a positive family history for multiple endocrine neoplasia type 1.
The shoulder of a 65-year-old man shows multiple firm, skin-colored to slightly hypopigmented papules. Biopsy results of the largest lesion revealed collagenoma. Endocrinologic features of multiple endocrine neoplasia type 1 in this patient are hyperparathyroidism and Zollinger-Ellison syndrome. Note that the photograph was taken with side lighting to accentuate the lesions.
A close-up view of a large collagenoma on the shoulder of a 65-year-old man shows multiple firm, skin-colored to slightly hypopigmented papules. Endocrinologic features of multiple endocrine neoplasia type 1 in this patient are hyperparathyroidism and Zollinger-Ellison syndrome.
A 39-year-old woman with multiple endocrine neoplasia type 1 has a soft nodule on the forehead that is consistent with lipoma. Lipomas in patients with multiple endocrine neoplasia type 1 can be single or multiple, and they are sometimes large.
On the attached gingiva of a 27-year-old man with multiple endocrine neoplasia type 1, a few small, whitish papules are present. Gingival papules are a rare and subtle finding in multiple endocrine neoplasia type 1. In addition to multiple facial angiofibromas, this patient has multiple collagenomas, hyperparathyroidism, and a positive family history for multiple endocrine neoplasia type 1.
Light microscopic evaluation of a section of an angiofibroma shows prominent vessels and concentric rings of collagen around vessels and adnexal structures (hematoxylin and eosin, original magnification X100). These findings are indistinguishable from those observed in angiofibromas in patients with tuberous sclerosis.
Histologic examination of a collagenoma reveals dense, thick collagen in the reticular dermis (hematoxylin and eosin, original magnification X40). An elastic stain showed reduced elastic fibers (not shown). Biopsy samples of collagenomas can be mistaken for healthy skin unless an elliptical excision containing surrounding healthy skin is obtained for comparison. The contrast with healthy skin accentuates the thickened dermis and collagen alterations seen in collagenomas.
 
 
 
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