Differentiating osteopoikilosis from osteoblastic metastasesPublished on Rheumatology Network(http://www.rheumatologynetwork.com)

Differentiating osteopoikilosis from osteoblastic metastasesJuly 27, 2008 | Imaging in Rheumatology [1]By David J. Kolessar, MD [2] and Clayton Austin Everline, MD [3]

ABSTRACT: Osteopoikilosis is a rare, benign osteosclerotic dysplasia that predominantly involves theappendicular skeleton. Radiographic findings are diagnostic, and the disease often is discoveredincidentally on x-ray films. The importance of recognizing osteopoikilosis lies in differentiating it fromosteoblastic metastases. The cause is unclear. Patients typically are asymptomatic. Diagnosticfindings include the appearance of numerous small,well-defined, spheroid sclerotic foci. Becauseevidence suggests an association with skeletal and dermatological changes, evaluation forcoexisting pathological conditions may be warranted. The differential diagnosis for a patient who hasradiographic characteristics similar to those of osteopoikilosis includes osteoblastic metastases,mastocytosis, tuberous sclerosis, melorheostosis, and osteopathia striata. (J Musculoskel Med.2008;25:387-389)

ABSTRACT: Osteopoikilosis is a rare, benign osteosclerotic dysplasia that predominantly involves theappendicular skeleton. Radiographic findings are diagnostic, and the disease often is discoveredincidentally on x-ray films. The importance of recognizing osteopoikilosis lies in differentiating it fromosteoblastic metastases. The cause is unclear. Patients typically are asymptomatic. Diagnosticfindings include the appearance of numerous small, well-defined, spheroid sclerotic foci. Becauseevidence suggests an association with skeletal and dermatological changes, evaluation forcoexisting pathological conditions may be warranted. The differential diagnosis for a patient who hasradiographic characteristics similar to those of osteopoikilosis includes osteoblastic metastases,mastocytosis, tuberous sclerosis, melorheostosis, and osteopathia striata. (J MusculoskelMed. 2008;25:387-389)

Osteopoikilosis, which literally means "spotted bones," is a rare, benign osteosclerotic dysplasia thatwas first described in the early 20th century.1-5 The disease, seen in men and women of all ages,predominantly involves the appendicular skeleton. It occurs most often in bones of the hands andfeet, although lesions are seen scattered around larger joints.3,5,6 The pathogenesis is unknown,although mutations in the LEMD3 gene may be the cause.7,8

Radiographic findings are diagnostic, and the disease often is discovered incidentally on x-ray films.Medical evaluation may be important, however, because there may be coexisting developmental orpathological conditions.9The importance of recognizing osteopoikilosis lies in differentiating it from osteoblastic metastases.2Gaining a better understanding of the disease may alleviate both patient and physician anxiety. Inaddition, having knowledge of this radiographic entity may minimize unnecessary testing andmedical costs. In this article, we describe the epidemiology of osteopoikilosis, the history andphysical examination, radiographic characteristics, the histology, associations with skeletal anddermatological changes, and the differential diagnosis.Incidence, epidemiology, causesThe incidence of osteopoikilosis is estimated at 1 in 50,000; the disease is seen in up to 6 per100,000 radiographs.3,10 This benign skeletal dysplasia has no age or sex predilection.Osteopoikilosis usually is discovered in patients aged 15 to 60 years, but fetal and geriatric caseshave been reported. The cause of osteopoikilosis is unclear. The disease probably is transmitted inan autosomal dominant fashion, although sporadic forms are documented.5,9,11-13 The pathogenesisis thought to involve perturbation of collagen regulation or failure to form trabeculae along the linesof stress.5,10 Evidence suggests a relationship with other osteosclerotic skeletal disorders, especiallyosteopathia striata and melorheostosis.4,13

History and physical examinationPatients with osteopoikilosis typically are asymptomatic, although 15% to 20% report mild articularpain and joint effusion.5,11,14 Overt external physical findings otherwise are absent. Whether the mildsymptoms are related to osteopoikilosis or to the inciting injury that led to the indication forradiography is uncertain.5,9,11 Because the condition is thought to be without symptoms, discovery byradiographic examination most often is incidental.

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Differentiating osteopoikilosis from osteoblastic metastasesPublished on Rheumatology Network(http://www.rheumatologynetwork.com)

Radiographic characteristicsFindings diagnostic of osteopoikilosis include the appearance of numerous small, well-defined,spheroid sclerotic foci—usually ranging from 2 to 10 mm—clustered in periarticular regions(Figure).3,5,9 These well-delineated opacities most often are seen in the small bones of the hands(carpus) and feet (tarsus).5

Figure – Radiographic findings diagnostic of osteopoikilosis include the appearance of numeroussmall, well-defined, spheroid sclerotic foci clustered in periarticular regions in the shoulder (A), ankle(B), and pelvis (C).

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Differentiating osteopoikilosis from osteoblastic metastasesPublished on Rheumatology Network(http://www.rheumatologynetwork.com)

In the epiphyses of tubular bones, the foci rarely contact the subchondral bone plate. Themetaphyseal lesions may be located eccentrically, abutting the endosteal cortical surface.4The chief distribution of lesions in the pelvis is found about the acetabulum; this distribution appearsto be related to the orientation of trabecular bone.15 The long axes of the sclerotic foci parallel thelong axes of the bones involved.3The scapula may show involvement around the glenoid. The skull, mandible, clavicles, sternum, ribs,and spine usually are not affected.4On serial radiographs, the radio-opaque areas may increase or decrease in size, remain the same, oreven disappear.4,13 Once growth plate closure occurs, however, the lesions usually do not change insize or appearance.3HistologyThe histology of the lesions consists of thickened trabeculae of lamellar osseous tissue that containshaversian systems lying within the cancellous structure; they probably represent foci of bone thatdid not become cancellous during growth and differentiation.2,10 The condensation of cancellous bonein osteopoikilosis consists of a peripheral area of trabeculae in which osteocytes are scant and thereare no osteoblasts or osteoclasts (both are present in the central core of irregular trabeculae). Theprecise origin of these abnormal areas remains debatable, but they appear to represent foci ofderanged differentiation in cancellous bone.9AssociationsOsteopoikilosis is a benign condition, but considerable evidence suggests an association withskeletal and dermatological changes.5,13 Therefore, evaluation for coexisting pathological conditionsmay be warranted.In an association known as Buschke-Ollendorf syndrome (osteopoikilosis and dermatofibrosislenticularis disseminata),3,5,10 there is a tendency toward keloid formation. In addition, pea-sizedfibrous skin papules accompany the bone lesions in 25% of cases; these papules usually are widelydistributed over the patient's trunk and extremities.16

Osteopoikilosis also has been associated with scleroderma, syndactyly, dwarfism, endocrineabnormalities, cleft palate, dystocia, spinal stenosis, and tuberous sclerosis.4,5,17 Another associatedcondition is mixed sclerosing bone dysplasia, a rare triad of benign bone disorders—osteopoikilosis,osteopathia striata, and melorheostosis—that occur in concert.3,17

Differential diagnosis The differential diagnosis for a patient who has radiographic characteristics similar to those ofosteopoikilosis includes osteoblastic metastases, mastocytosis, tuberous sclerosis, melorheostosis,and osteopathia striata.3,5 However, these other conditions have additional distinguishing physicalfindings on clinical examination. The discriminating radiographic features should help support thediagnosis of osteopoikilosis.Radionuclide bone scanning may play a critical role in differentiating osteopoikilosis from primary ormetastatic bone disease. In osteopoikilosis, the bone scan result usually is somewhat normal.Although an abnormal result does not rule out osteopoikilosis, bone scanning has been used todifferentiate the process from metastatic bone disease.2,5,11,14 The bone scan of a patient withmetastatic disease usually reveals increased uptake at the lesion (hot spot). If multiple sites areinvolved, an asymmetrical distribution may be expected throughout the skeleton.2,4,9,11,12

Mastocytosis and tuberous sclerosis have bone lesions that are symmetrical, uniform, andwell-defined with a predilection for metaphyseal and epiphyseal areas; all are less striking than thosein osteopoikilosis.4 In melorheostosis, there is thickening along the endosteal and periosteal bonethat has been described as having a "candle dripping" appearance, which helps differentiate thepathology from osteopoikilosis.3 Osteopathia striata (Voorhoeve disease) is a benign disordercharacterized by longitudinal dense striations in affected bones that is thought to be a variant ofosteopoikilosis.3,4,15 This condition often is asymptomatic and, like osteopoikilosis, is discovered byaccident. 3 Another bone disorder, Paget disease, may be distinguished from osteopoikilosis withradionuclide scanning; it also has radiographic differences. References:

References

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Differentiating osteopoikilosis from osteoblastic metastasesPublished on Rheumatology Network(http://www.rheumatologynetwork.com)

1. 1. Benli IT, Akalin S, Boysan E, et al. Epidemiological, clinical and radiological aspects ofosteopoikilosis. J Bone Joint Surg. 1992;74B:504-506.

2. 2. Tong EC, Samii M, Tchang F. Bone imaging as an aid for the diagnosis of osteopoikilosis. Clin Nucl Med. 1988;13:816-819.

3. 3. McLennan MK. Radiology rounds: osteopoikilosis. Can Fam Physician. 1999;45:2315,2318-2320.

4. 4. Niwayama G. Enostosis, hyperstosis, and periostitis. In: Resnick D, ed. Diagnosis of Boneand Joint Disorders. Philadelphia: WB Saunders; 1988:4084-4088.

5. 5. Borman P, Ozoran K, Aydog S, Coçskun S. Osteopoikilosis: report of a clinical case andreview of literature. Joint Bone Spine. 2002;69:230-233.

6. 6. Gunal I, Seber S, Basaran N, et al. Dacryocystitis associated with osteopoikilosis. ClinGenet. 1993;44:211-213.

7. 7. Hellemans J, Preobrazhenska O, Willaert A, et al. Lossof-function mutations in LEMD3 resultin osteopoikilosis, Buschke-Ollendorff syndrome and melorheostosis. Nat Genet.2004;36:1213-1218.

8. 8. Mumm S, Wenkert D, Zhang X, et al. Deactivating germline mutations in LEMD3 causeosteopoikilosis and Buschke-Ollendorff syndrome, but not sporadic melorheostosis. J BoneMiner Res. 2007;22:243-250.

9. 9. Havitçioglu H, Günal I, Göçen S. Synovial chondromatosis associated withosteopoikilosis—a case report. Acta Orthop Scand. 1998;69:649-650.

10. 10. Drouin CA, Grenon H. The association of Buschke-Ollendorf syndrome and nail-patellasyndrome. J Am Acad Dermatol. 2002;46:621-625.

11. 11. Mungovan JA, Tung GA, Lambiase RE, et al. Tc-99m MDP uptake in osteopoikilosis. ClinNucl Med. 1994;19:6-8.

12. 12. Whyte MP, Murphy WA, Siegel BA. 99mTc-pyrophosphate bone imaging in osteopoikilosis,osteopathia striata, and melorheostosis. Radiology. 1978;127:439-443.

13. 13. Chigira M, Kato K, Mashio K, Shinozaki T. Symmetry of bone lesions in osteopoikilosis:report of 4 cases. Acta Orthop Scand. 1991;62:495-496.

14. 14. Wadhwa SS, Mansberg R. Abnormal bone scan in osteopoikilosis. Clin Nucl Med.1999;24:71-72.

15. 15. Lagier R, Mbakop A, Bigler A. Osteopoikilosis: a radiological and pathological study. Skeletal Radiol. 1984;11:161-168.

16. 16. Albertini JG, Maroon M, Tyler WB. Widespread pea-sized papules and gooseflesh plaquesin a 44-year-old woman. Arch Dermatol. 2000;136:1055-1060.

17. 17. Butkus CE, Michels VV, Lindor NM, Cooney WP 3rd. Melorheostosis in a patient withfamilial osteopoikilosis. Am J Med Genet. 1997;72:43-46.

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