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Dermatopathology: Practical & Conceptual

October – December 2010 | Volume 16, No. 4

What is the lesion and what is the syndrome (XII)?

González-Beato, María José

Introduction

Some cutaneous lesions may be the first manifestation of a syndrome of which the patient is unaware. For this reason, it is only if the pathologist, many times the first to encounter these lesions, knows about the associations between these lesions and syndromes, that they can alert to the need for more extensive investigation. When these underlying diseases are inherited, an early diagnosis benefits other family members as well.

In a series of articles, some of these skin markers of syndromes are described, and the underlying condition they can alert to is addressed. Previous articles of the series have already commented on the relationship between multiple tricholemmomas with Cowden’s syndrome, [1] multiple odontogenic keratocysts with nevoid basal-cell carcinoma syndrome, [2] tufted angioma with Kasabach-Merritt syndrome, [3] multiple fibrofolliculomas/trichodiscomas with Birt-Hogg-Dubé syndrome, [4] multiple fibrous papules of the face with tuberous sclerosis, [5] clear-cell syringomas with diabetes mellitus, [6] sebaceous adenoma/carcinoma with Muir-Torre syndrome, [7] multiple pilomatricomas with myotonic dystrophy, [8] myxomas with Carney’s complex, [9] dermal clumps of basophilic distorted elastic fibers with pseudoxanthoma elasticum, [10] and that between numerous mucosal neuromas with multiple endocrine neoplasia type 2B (MEN2B). [11]

The lesion

The following lesion, shown in two photographs, was located on the chest of a 14-year-old female (Figs. 1A-B).

Figs. 1A and B

What is the lesion? When multiple, what is the syndrome?

Answer

The diagnosis of the pictured lesion is connective tissue nevus of elastic type. Numerous elastic type connective tissue nevi are diagnostic of Buschke-Ollendorff syndrome.

Comment

Connective tissue nevi are circumscribed hamartomas of the dermal extracellular matrix in which its components-collagen, elastic fibers, and glycosaminoglycans—are present in abnormal amounts. Depending on the component that is mostly involved, they are classified as collagen type (collagenoma and shagreen patch), elastic type (elastoma) and proteoglycan type (nodules in Hunter’s syndrome). [12]

The elastic type connective tissue nevus is also called elastoma, elastic nevus, juvenile elastoma, nevus elasticus and connective tissue nevus of Lewandowsky type. It presents as an asymptomatic flesh-colored or yellowish papule, plaque or nodule, normally on the trunk and limbs (Fig. 2). Microscopically, the dermis is usually normal in hematoxylin and eosin-stained sections, but stains for elastic tissue show coarse, clumped and interlacing elastic fibers in the mid and lower dermis. Occasionally, they are accompanied by thickening of collagen bundles or increase in acid mucopolysaccharides. The epidermis may be slightly wavy. [13] A morphometric analysis showed a 4- to 5-fold increase in elastic fibers, together with an increase in their diameter. [14]

Fig. 2

This plaque is made up of the confluence of multiple yellowish papules. The biopsy (the scar can be noticed in the middle of the lesion) revealed an elastic type connective tissue nevus.

Connective tissue nevi of elastic type can be single or numerous when part of Buschke-Ollendorff syndrome. [15] Buschke-Ollendorff syndrome was described it 1928 as the association of disseminated connective tissue nevi and osteopoikilosis. [16] It is a rare condition with an incidence of 1:20,000. [17] It is an autosomal dominant inherited disease with high penetrance and highly variable expressivity in affected individuals, to the point that some may manifest either the skin or the skeletal alterations independently. Recently, LEM domain-containing 3 (LEMD3) gene mutations have been detected as responsible for this syndrome in most of the cases. [18,19] This gene is thought to be involved in elastin production from fibroblasts, and therefore in connective tissue and bone morphogenesis. Melorheostosis (a more severe bone disease characterized by ectopic bone formation on the periosteal and endosteal surface of the long bones) appears to be allelic with this syndrome and the concurrence of the two has been reported. [18]

Buschke-Ollendorff syndrome presents with osteopoikilosis and multiple connective tissue nevi. Osteopoikilosis is defined as spots of increased bone density on radiographs affecting predominantly the spongiosa of epiphyses and metaphyses of long bones, the pelvis, and the bones of the hands and feet. Osteopoikilosis is usually symmetrical, asymptomatic, and often detected incidentally. [15] Cutaneous manifestations of the syndrome are usually detectable at childhood and puberty. [20] They are connective tissue nevi, normally of elastic type (juvenile elastoma), and only occasionally of collagen type (dermatofibrosis lenticularis disseminata). These lesions gradually increase in size and number and spread over the trunk and extremities. They can spread symmetrically as white or yellowish papules, or form larger asymmetrical yellowish nodules that eventually coalesce in plaques. Variability in lesions is very common on different family members and even among lesions of the same patient. [15]

Although some other conditions have been associated to Buschke-Ollendorff syndrome, they are probably incidental. The syndrome is benign and it requires no specific treatment. However, knowledge of this syndrome is important to avoid suspicion of more complicated diseases and consequent worries or expenses. Cutaneous lesions of Buschke-Ollendorff disease could be misdiagnosed, for example, as those of tuberous sclerosis and pseudoxanthoma elasticum, and the skeletal changes with osteoblastic bone metastases. [15]

Summary

Background: Some skin lesions, usually when multiple, are clues to certain syndromes and sometimes the first manifestation of them. Knowing about these relationships supposes an earlier diagnosis of the underlying disease. When the condition is inherited, other family members can also get diagnosed. Objectives: To make the associations between several cutaneous lesions and some syndromes familiar to the reader. Patients/Methods: Microscopic photographs of a connective tissue nevus of elastic type are shown and are followed by a quiz about the underlying condition. Results: Multiple elastic type connective tissue nevi are diagnostic of Buschke-Ollendorff syndrome. Conclusions: Buschke-Ollendorff syndrome is characterized by the association of multiple elastic tissue nevi with osteopoikilosis. Although this syndrome is asymptomatic and benign, it is important to be aware of it in order to not suspect other more complex diseases.

Dr. Beato is dermatopathologist at La Paz University Hospital in Madrid, Spain. This article was reviewed by Almut Böer, M.D. Contact author via e-mail: mgbeato@yahoo.com .

References

1. González-Beato MJ. Quiz. What is the lesion and what is the syndrome (I)? Dermatopathology: Practical & Conceptual,2008;14(1):13. Available at: http://www.derm101.com.

2. González-Beato MJ. Quiz. What is the lesion and what is the syndrome (II)? Dermatopathology: Practical & Conceptual,2008;14(2):16. Available at: http://www.derm101.com.

3. González-Beato MJ. Quiz. What is the lesion and what is the syndrome (III)? Dermatopathology: Practical & Conceptual,2008;14(3):12. Available at: http://www.derm101.com.

4. González-Beato MJ. Quiz. What is the lesion and what is the syndrome (IV)? Dermatopathology: Practical & Conceptual, 2008;14(4):17. Available at: http://www.derm101.com.

5. González-Beato MJ. Quiz. What is the lesion and what is the syndrome (V)? Dermatopathology: Practical & Conceptual,2009;15(1):10. Available at: http://www.derm101.com.

6. González-Beato MJ. Quiz. What is the lesion and what is the syndrome (VI)? Dermatopathology: Practical & Conceptual,2009;15(2):11. Available at: http://www.derm101.com.

7. González-Beato MJ. Quiz. What is the lesion and what is the syndrome (VII)? Dermatopathology: Practical & Conceptual,2009;15(3):7. Available at: http://www.derm101.com.

8. González-Beato MJ. Quiz. What is the lesion and what is the syndrome (VIII)? Dermatopathology: Practical & Conceptual,2009;15(4):11. Available at: http://www.derm101.com.

9. Beato MJ. Quiz. What is the lesion and what is the syndrome (IX)? Dermatopathology: Practical & Conceptual,2010;16(1):12. Available at: http://www.derm101.com.

10. Beato MJ. Quiz. What is the lesion and what is the syndrome (X)? Dermatopathology: Practical & Conceptual, 2010;16(2):12. Available at: http://www.derm101.com.

11. Beato MJ. Quiz. What is the lesion and what is the syndrome (XI)? Dermatopathology: Practical & Conceptual, 2010;16(10):12. Available at: http://www.derm101.com.

12. Weedon D. Disorders of collagen. In: Weedon D, ed. Weedon’s Skin Pathology, 3rd ed. London: Churchill Livingstone, 2010:317.

13. Weedon D. Disorders of collagen. In: Weedon D, ed. Weedon’s Skin Pathology, 3rd ed. London: Churchill Livingstone, 2010:333-334.

14. Ghomrasseni S, Dridi M, Bonnefoix M, et al. Morphometric analysis of elastic skin fibres from patients with: cutis laxa, anetoderma, pseudoxanthoma elasticum, and Buschke-Ollendorff and Williams-Beuren syndrome. J Eur Acad Dermatol Venereol. 2001; 15: 305-311.

15. Kawamura A, Ochiai T, Tan-Kinoshita M, et al. Buschke-Ollendorff syndrome: three generations in a Japanese family. Pediatr Dermatol. 2005;22:133-137.

16. Buschke A, Ollendorff H. Ein Fall von dermatofibrosis lenticularis disseminate und osteopatha condensans disseminata. Dermatol Wochenschr. 1928;86:257-262.

17. Schena D, Germi L, Zamperetti MR, et al. Buschke-Ollendorff syndrome. Int J Dermatol. 2008;47:1159-1161.

18. 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;36:1213-1218.

19. Yadegari M, Whyte MP, Mumm S, et al. Buschke-Ollendorff syndrome: absence of LEMD3 mutation in an affected family. Arch Dermatol. 2010;146:63-68.

20. Woodrow SL, Pope FM, Handfield-Jones SE. The Buschke-Ollendorff syndrome presenting as familial elastic tissue naevi. Br J Dermatol. 2001;144:890-893.