Connective Tissue Nevus

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Background

Connective tissue nevi are hamartomas in which one or several components of the dermis is altered. Lesions in which collagen predominates are called collagenomas; lesions in which elastin predominates are called elastomas. A nevus mucinosis is a lesion in which an alteration in the amount of dermal glycosaminoglycan is present. The name nevus mucinosis is also used for lesions in which an alteration in more than one dermal component is present.

Connective tissue nevi may be solitary or multiple, sporadic or inherited. They may occur as isolated skin lesions, or they may be associated with a number of syndromes. One report described a collagenoma that occurred on the bulbar conjunctiva.[1]

Zosteriform connective tissue nevus is considered to be a separate entity because of its distribution and histopathologic characteristics.

Pathophysiology

The cause of connective tissue nevi is unknown. However, note that osteopoikilosis with or without the skin manifestations of Buschke-Ollendorf syndrome and with or without melorheostosis can be caused by heterozygosity for loss-of-function mutations in LEMD3,[2] also called MAN1, which encodes an inner nuclear membrane protein.

Etiology

The cause of connective tissue nevi is unknown.

Epidemiology

Frequency

The prevalence of connective tissue nevus is rare worldwide.

Race

No racial predilection has been reported for connective tissue nevi.

Sex

No sexual predilection is described for connective tissue nevus.

Age

The age of onset of a connective tissue nevus depends on the type of lesion. Collagenomas and elastomas generally present during the postpubertal period. In Buschke-Ollendorf syndrome, the skin changes may be delayed until adulthood. Nevus mucinosis may present at birth, during childhood, or in adolescence.

Prognosis

Connective tissue nevi are benign lesions. However, they do not resolve spontaneously. Patients with associated syndromes have other prognostic considerations. For example, the bony lesions of Buschke-Ollendorf have no adverse effects on the patient's health. Both Hunter syndrome and tuberous sclerosis are associated with early death.

Patient Education

Patients should be informed about the bony lesions of Buschke-Ollendorf syndrome so that another physician will not incorrectly perform a workup for metastatic cancer in the future.

History

Collagenomas have been associated with multiple medical syndromes. For example, 72% of patients seen at the National Institutes of Health (NIH) for evaluation of multiple endocrine neoplasia (MEN) type 1 over a 3-year period were noted to have these lesions.[3] Shagreen patches of tuberous sclerosis are collagenomas, and collagenomas have also been associated with Down syndrome. Other diseases associated with collagenomas include chronic myelocytic leukemia, syphilis, Cowden disease,[4] Proteus syndrome,[5] and encephalocraniocutaneous lipomatosis. Note the following:

Physical Examination

Patients should receive a complete physical examination to rule out any associated conditions. Note the following:

Laboratory Studies

Laboratory studies are usually directed by signs or symptoms suggesting that the connective tissue nevus is part of an underlying syndrome. Eruptive connective tissue nevi have been associated with syphilis.

Hunter syndrome can be detected either by performing fibroblast enzyme studies or by finding mucopolysaccharides in the urine.

Imaging Studies

Radiographs of the spine should be obtained in patients with extensive musculoskeletal deformities.

In patients suspected of having Buschke-Ollendorf syndrome, radiographs of the hands, the feet, and the knees should be obtained. In patients with Buschke-Ollendorf syndrome, radiographic studies reveal round densities that are 2-10 mm in diameter in the long bones and the bones of the hands, the feet, and the pelvis.

In patients with tuberous sclerosis, imaging studies of the brain, EEG, funduscopic examination, renal ultrasound, and an echocardiogram in infancy are indicated.

Cardiac studies, such as echocardiography, are useful to evaluate for coronary heart disease secondary to mucopolysaccharide deposition.

Procedures

Perform either a punch biopsy or an incisional/excisional skin biopsy. The skin biopsy depth must include the entire dermis and may need to include adjacent healthy skin to document abnormalities in elastin, collagen, or ground substance.

Histologic Findings

In collagenoma, a disproportionate increase of dense, coarse collagen fibers, leading to dermal thickening, is observed. Storiform collagenomas have been suggested to be a possible clue to a diagnosis of Cowden disease. Scanning electron microscopy of the dermis of an eruptive collagenoma showed individualized collagen fibers forming waved compact masses and not bundles. Transmission electron microscopy also showed sparse and loose collagen fibers with different diameters in cross sections.[8]

In elastoma, the dermis has an increased number of nonfragmented, interweaving elastin fibers.

In pseudoxanthoma elasticum, elastic tissue fragmentation and calcification are observed.

Hunter syndrome is the only mucopolysaccharidosis in which significant extracellular dermal mucin is present. The fibroblasts in this condition metachromatically stain cytoplasmic material, and characteristic vacuoles are seen on electron microscopy examination.

Medical Care

A biopsy may be indicated for diagnostic purposes. One case report has described a linear nodular collagenoma treated successfully with intralesional triamcinolone.[9]

Surgical Care

Surgical excision is necessary when the patient would like the lesion removed for cosmetic reasons; however, surgery may not be advised when multiple or large lesions are present.

Consultations

For connective tissue nevi unassociated with a syndrome, no additional consultation is required. Other consultations are as follows:

Author

Steven Brett Sloan, MD, Associate Professor, Department of Dermatology, University of Connecticut School of Medicine; Residency Site Director, Connecticut Veterans Affairs Healthcare System; Assistant Clinical Professor, Yale University School of Medicine

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: American Academy of Dermatology;UpToDate;Medical Review Institute of America<br/>Received income in an amount equal to or greater than $250 from: American Academy of Dermatology; Medical Review Institute of America.

Specialty Editors

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

Disclosure: Nothing to disclose.

Paul Krusinski, MD, Director of Dermatology, Fletcher Allen Health Care; Professor, Department of Internal Medicine, University of Vermont College of Medicine

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Disclosure: Nothing to disclose.

Additional Contributors

Daniel J Hogan, MD, Clinical Professor of Internal Medicine (Dermatology), Nova Southeastern University College of Osteopathic Medicine; Investigator, Hill Top Research, Florida Research Center

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous authors, Boris Zaks, MD, and Dina D. Strachan, MD, to the development and writing of this article.

References

  1. Zarate JO, Pelayes DE, Gioino JM, Piantoni GR. [Giant cell collagenoma of the bulbar conjunctiva]. Arch Soc Esp Oftalmol. 2007 Apr. 82(4):233-5. [View Abstract]
  2. Hellemans J, Preobrazhenska O, Willaert A, et al. Loss-of-function mutations in LEMD3 result in osteopoikilosis, Buschke-Ollendorff syndrome and melorheostosis. Nat Genet. 2004 Nov. 36(11):1213-8. [View Abstract]
  3. Xia Y, Darling TN. Rapidly growing collagenomas in multiple endocrine neoplasia type I. J Am Acad Dermatol. 2007 May. 56(5):877-80. [View Abstract]
  4. Al-Daraji WI, Ramsay HM, Ali RB. Storiform collagenoma as a clue for Cowden disease or PTEN hamartoma tumour syndrome. J Clin Pathol. 2007 Jul. 60(7):840-2. [View Abstract]
  5. Twede JV, Turner JT, Biesecker LG, Darling TN. Evolution of skin lesions in Proteus syndrome. J Am Acad Dermatol. 2005 May. 52(5):834-8. [View Abstract]
  6. McClung AA, Blumberg MA, Huttenbach Y, Colome-Grimmer MI, Raimer SS. Development of collagenomas during pregnancy. J Am Acad Dermatol. 2005 Aug. 53(2 Suppl 1):S150-3. [View Abstract]
  7. Thappa DM, Singh A, Jaisankar TJ, Rao R, Ratnakar C. Pebbling of the skin: a marker of Hunter's syndrome. Pediatr Dermatol. 1998 Sep-Oct. 15(5):370-3. [View Abstract]
  8. de Almeida HL Jr, Breunig Jde A, Wolter M, de Castro LA, Rocha NM. Light and electron microscopy of eruptive collagenoma. J Cutan Pathol. 2009 Oct. 36 Suppl 1:35-8. [View Abstract]
  9. Sardana K, Bansal S, Garg VK, Khurana N. Linear nodular collagenoma--successful treatment with intralesional triamcinolone acetonide. Pediatr Dermatol. 2009 Sep-Oct. 26(5):626-8. [View Abstract]

Familial cutaneous collagenoma.

Shagreen patch.

Collagenoma

Familial cutaneous collagenoma.

Shagreen patch.

Collagenoma