Practice Essentials

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.

Etiology

The cause of connective tissue nevi is unknown.

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.

Signs and symptoms

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

Familial cutaneous collagenoma (FCC): Multiple, indurated cutaneous papulonodules that vary in size are located over the upper two thirds of the back (see the image below).

Familial cutaneous collagenoma.
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Shagreen patch: Flesh-colored plaques of variable size are located singularly or asymmetrically in limited numbers in the lumbosacral area. Note the image below.

Shagreen patch.
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Eruptive collagenoma: Multiple cutaneous papulonodules are located on the extremities, the lower part of the trunk, and the ears. Eruptive collagenoma has been described in rare association with Down syndrome.^[2]
Isolated collagenoma: This condition is characterized by cutaneous papulonodules, sometimes in a zosteriform pattern. Note the image below.

Collagenoma
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Plantar cerebriform collagenoma: This condition is characterized by cerebriform plaques on the palms and the soles and is often associated with Proteus syndrome.^{[3, 4, 5]}
Fibroblastic connective tissue nevus (FCTN): First described in 2012, FCTN is a mesenchymal lesion with a rare incidence. Nevi consist of CD34-positive fibroblasts. The lesion is typically asymptomatic and slow-growing.^[6]
Buschke-Ollendorf elastomas: Lesions consist of minimally elevated and firm nodules that may be grouped together in one or several plaques, or they may be widely disseminated. They vary in size from 0.5-8 cm in diameter, and they may have a wrinkled, pigskin appearance. The most common areas of involvement include the abdomen, the back, the buttocks, the arms, and the thighs. Nevi are asymmetric and occur on the lower part of the trunk and the extremities.
Nevus anelasticans: These small, yellowish, perifollicular papules lack elastic fibers. They are located on the chest.
Juvenile elastoma: Numerous nodules are present on the lower part of the trunk and the anterior aspects of the thighs.
Nevus elasticus: Lesions are similar to those of juvenile elastoma.
Nevus mucinosis (Hunter syndrome): Symmetric, small, firm papules that are located on the arms, on the chest, and over the scapular region give the skin a pebbled appearance. Hunter syndrome involves multiple organ systems, including severe CNS impairment (eg, mental retardation, deafness, progressive neurologic disease), coronary heart disease, hepatosplenomegaly, and respiratory disease. It is also associated with coarse facial features.

Diagnostics

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.

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.

Also see Histologic Findings.

Management

A biopsy may be indicated for diagnostic purposes. One case report has described a linear nodular collagenoma treated successfully with intralesional triamcinolone.^[7]

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.

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,^[8]also called MAN1, which encodes an inner nuclear membrane protein.

Epidemiology

The prevalence of connective tissue nevus is rare worldwide.

No racial predilection has been reported for connective tissue nevi.

No sexual predilection is described for connective tissue nevus.

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.

Clinical Presentation

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. [QxMD MEDLINE Link].
Kato Y, Yamamoto T. Eruptive collagenoma in a juvenile patient with Down syndrome. An Bras Dermatol. 2022 Sep-Oct. 97 (5):687-688. [QxMD MEDLINE Link]. [Full Text].
Modlin EW, Slavotinek AM, Darling TN, et al. Late-onset Proteus syndrome with cerebriform connective tissue nevus and subsequent development of intraductal papilloma. Am J Med Genet A. 2022 Sep. 188 (9):2766-2771. [QxMD MEDLINE Link].
Arredondo Montero J, Bronte Anaut M, López-Gutiérrez JC. Proteus Syndrome: Case Report with Anatomopathological Correlation. Fetal Pediatr Pathol. 2022 Oct. 41 (5):861-864. [QxMD MEDLINE Link].
Friedrich RE. Phenotype and Surgical Treatment in a Case of Proteus Syndrome With Craniofacial and Oral Findings. In Vivo. 2021 May-Jun. 35 (3):1583-1594. [QxMD MEDLINE Link]. [Full Text].
de Feraudy S, Fletcher CD. Fibroblastic connective tissue nevus: a rare cutaneous lesion analyzed in a series of 25 cases. Am J Surg Pathol. 2012 Oct. 36 (10):1509-15. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Xia Y, Darling TN. Rapidly growing collagenomas in multiple endocrine neoplasia type I. J Am Acad Dermatol. 2007 May. 56(5):877-80. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Lara-Valencia P, Ybo A, Coter A. Fibroblastic Connective Tissue Nevus Mimicking Lipoma on Ultrasound: Case Report and Brief Review. Dermatopathology (Basel). 2022 Jan 17. 9 (1):32-34. [QxMD MEDLINE Link]. [Full Text].
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. [QxMD MEDLINE Link].

Media Gallery

Familial cutaneous collagenoma.
Shagreen patch.
Collagenoma

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Author

Steven Brett Sloan, MD Professor, Department of Dermatology, University of Connecticut School of Medicine; Residency Program Director, Connecticut Veterans Affairs Healthcare System

Steven Brett Sloan, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, Association of Military Dermatologists

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

Specialty Editor Board

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, Texas Medical Association, Association of Military Dermatologists, Texas Dermatological Society

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

Paul Krusinski, MD is a member of the following medical societies: American Academy of Dermatology, American College of Physicians, Society for Investigative Dermatology

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

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

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

Daniel J Hogan, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Contact Dermatitis Society, Canadian Dermatology Association

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.