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Introduction

Melorheostosis is a rare mesodermal disease that af-

fects the skeleton and adjacent soft tissues. Often it isincidentally detected on plain radiographs. It was untilnow believed that only few of the patients suffer fromconcomitant chronic pain, limb swelling, soft tissuemasses, and limitations in the motion of the affectedlimb attributable to the disease. These patients usuallyshow extensive bony involvement, mostly combinedwith a soft tissue involvement including edema, hyper-pigmented skin patches, fibrosis, circumscribed andlinear scleroderma, as well as myosclerosis, myositis,and muscular atrophy. Since the disease usually occurssporadically and because of the segmental distribution

of the lesions, most authors believe that melorheostosisis not inherited but represents an embryonal metamer-ic disturbance [1, 2]. In the standard radiology and or-

thopedics literature melorheostosis ( from the Greek:melos = limb, rheos = flow) is described monotonouslyas a ªflowing hyperostosis, resembling dripping candlewax (Fig. 1) as an incidental radiographic finding.ºWe, however, assume that radiological and clinical di-versity, severity of symptoms, and degree of physicalimpairment may be generally and harshly underesti-mated.

Especially in unusual presentations doubts about thecorrectness of diagnosis may arise and thus provoke in-vasive procedures in order to obtain histologic speci-mens. Macroscopic and histologic findings are unspe-

Eur. Radiol. (2001) 11: 474±479Ó Springer-Verlag 2001 MUSCULOSKELETAL

J.Freyschmidt Melorheostosis: a review of 23 cases

Received: 2 March 2000Revised: 1 June 2000Accepted: 6 June 2000

J. FreyschmidtDepartment of Radiology,Zentralkrankenhaus St.-Jürgen-Strasse,28205 Bremen, Germany

Abstract The aim of this study wasto review clinical and radiologicalsigns of melorheostosis in a largeseries of cases. Family history, pa-tient history, clinical data and radio-logical features of 23 consecutivecases of melorheostosis were inves-tigated. Criteria for establishing thediagnosis ªmelorheostosisº weredefined. Sixteen patients (mean age34 years, equal ratio between gen-ders) had chronic pain in the affect-ed limb(s) and/or subcutaneous fi-brosis and/or various skin lesions.

Number of involved bones: onebone (n = 10); two bones (n = 4);three or more bones (n = 9). Ana-tomic distribution: upper extremity(n = 5); lower extremity (n = 16);upper and lower extremity (n = 1);sacrum (n = 1). Radiologic pattern:osteoma-like (n = 7); classic candle

wax appearance (n = 5); myositisossificans-like (n = 1); osteopathiastriata-like (n = 6); mixed pattern(n = 4). Patterns different from theappearance formerly judged to beªclassicº prevail. The standard con-cept of disease manifestation has tobe adjusted. Pathogenesis remainsunclear. The classic theory claimsthe presence of an early embryonicinfection of a sensory nerve inducingchanges in the respective sclero-tome, but we propose the concept of mosaicism as a better explanation

for the sporadic occurrence, theasymmetric ªsegmentalº patternwith variable extent of involvementand equal gender ratio of the dis-ease.

Key words Melorheostosis ´Segmental bone hyperostosis



cific, however, and generally not helpful in making theappropriate diagnosis.

We reviewed a large series of melorheostosis to try toderive clinical and radiological criteria to cover the en-

tire scope of the disease.

Materials and methods

Twenty-three cases of melorheostosis were reviewed through aperiod of 16 years. Fifteen cases came from external consultationsand 8 were incidental findings on radiographs taken from dailyroutine at our department. We evaluated the following:

1. Family history and symptoms2. Patient age and gender3. Number of involved bones4. Anatomic distribution5. Radiologic pattern

The diagnosis of melorheostosis was made on the basis of clinicaland radiologic pattern.

Diagnostic criteria for establishing the diagnosis ªmelorheos-tosisº were one of the following:

1. Typical radiologic pattern with the flowing or dripping candlewax phenomenon on the inner and/or outer surface of the in-volved bone(s)

2. In the case of an osteoma-like hyperostosis with orientation inthe long axis of the involved bone following subset of criteria:a. The lesion diameter would have to be more than 5 cm or moreb. More than one bone would have to be involved

c. Only eccentrically located lesions at or in the bone were eli-gible

d. If only one bone was involved, other signs, such as circum-scribed scleroderma or subcutaneous fibrosis above the in-volved skeleton, were mandatory to establish the diagnosis

3. Radiographic pattern with long and dense hyperostotic stria-tions near the inner side of the cortex in two or more bones, butunilateral in contrast to the typical pattern of genuine osteo-pathia striata

4. In the case of myositis ossificans neuropathica-like pattern fol-lowing subset of criteria:a. Ossifications adjacent to a joint in two or more unilateral re-

gions with or without intraosseous hyperostosisb. In contrast to classic myositis ossificans, the ossifications

would have to be nodularly arranged and not appear as struc-tured lamellar bone

c. Exclusion criteria: history of direct trauma to the region of interest and/or neurologic deficit

Diagnosis was confirmed by follow-up studies. When melorheos-tosis presented atypically (e. g., osteoma-like pattern), follow-upwas performed through a period of at least 3 years.

Plain radiographs were obtained from each patient. Additionalcomputed tomographs were taken when parosseal ossificationswould obscured underlying bone, making a reliable judgement,wether there were intraosseous ossifications as well, impossible. In

the patients with lesions in the pelvis and shoulder girdle, CT andconventional tomography, respectively, were also performed. In 2patients MRI was performed to define whether marrow edema waspresent as a possible cause of pain (see Discussion).

Bone biopsy was performed in 7 cases.

Results

Patient age and gender The mean age was 34 years (age range 7±70 years),there were 12 men and 11 women (n = 23).

Number of involved bonesIn 10 cases only was one bone involved, in 4 cases twobones, and in 9 cases three or more bones (n = 23).

Anatomic distributionSee Table 1.

Radiologic pattern and symptomsSee Table 2.

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a b

Fig.1 a, b The dripping or flowing candle wax phenomenon, witha real candle and b the fibula of a 45-year-old man

Table 1 Anatomic distribution of affected bones (23 cases)

Five upper extremity including shoulderSixteen lower extremity including pelvisOne upper and lower extremityOne sacrum (alone)

Number of involved bones: 10 1, 4 2, 9 3, or more bones



· Seven cases had an osteoma-like appearance (type A)of melorheostosis (Fig.2): 3 of 7 patients had two ormore bones of the upper extremity involved and an-

other two bones of the lower extremity (Fig.2a,b).Further 3 patients showed involvement of just onebone of the lower extremity (femur, fibula, metatar-sus), of whom 2 had an associated circumscribedscleroderma and 1 had a slight subcutaneous fibrosisabove the affected bone. All patients with involve-ment of more than one bone and 1 patient with in-volvement of a metatarsus had chronic pain.

· In 5 cases we found the classic pattern with a flowingcandle wax appearance (type B; Fig. 1 b): 1 case waslocated in the upper extremity and 4 were in thelower extremity. In 4 cases only one bone and in 1

case more than three bones were involved. Two pa-tients had a circumscribed scleroderma in the regionof the affected limb. One patient with monostoticand the patient with oligoostotic manifestation hadchronic pain in the affected limb.

· A predominant myositis ossificans-like pattern (typeC) was detected in only 1 case. The soft tissue ossifi-cations were unilateral around the hip and knee(Fig.3).

Joint movement was limited. Soft tissue masseswere palpable, and subcutaneous fibrosis and skin

hyperpigmentation at the joints were present. Thepatient had no history of trauma and no neurologicdeficit. Plain radiographs of the hip revealed two os-teoma-like lesions in the acetabulum. Furthermore,we detected a hyperostotic lesion on the dorsal innersurface of the distal femur (Fig.3 b).

· An osteopathia striata-like pattern (type D; Figs. 4, 6)was foundin 6 cases: onein the upperextremity (morethan three bones involved), and three in the lower ex-tremity (1 case with justone bone, 1 case with two and1 case with more than three bones involved). In 1 casein the upper as well as in the lower extremity, two andthree bones, respectively, were affected, and in 1 case

the melorheostotic hyperostosis was located in thesacrum.Four patients (all with more than two bones in-

volved and the patient with sacral melorheostosis)had pain in the affected limb; in 2 of them an addi-tional circumscribed scleroderma was found.

· A mixed pattern (type E; Fig.5) was detected in 4patients: 3 cases had a myositis ossificans-like patternin combination with an osteopathia striata-like pat-tern, and in 1 case an osteoma-like pattern combinedwith a myositis ossificans-like pattern was found. Allpatients with a mixed pattern had chronic pain, pal-

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Table 2 Radiologic pattern of melorheostosis (23 cases)

Pattern No. of cases

Osteoma like (A) 7Classic (B) 5Myosits ossificans like (C) 1Osteopathia striata like (D) 6Mixed (4 C + D, 1 A + C) 4

Sixteen of 23 patients had clinical symptoms (see Results)

a b c d e

Fig.2a±e The osteoma-like pattern of melorheostosis. a,b Thesame 18-year-old female with subcutaneous fibrosis and circum-scribed scleroderma of the affected femur and tibia. The patienthad had chronic pain since she was 9 years of age. The hyperostosisis located eccentrically on the medial cortex of the right femur andthe ventral cortex of the right tibia. c±e A 14-year-old boy withosteoma-like hyperostosis in the tibia, corresponding to the so-called sclerotome L4. On bone scan only a slightly increased up-take in the left tibia was seen.



pable soft tissue masses, subcutaneous fibrosis, andlimited movement of the affected limb. One patienthad a classic circumscribed scleroderma as well.

Discussion

More than 250 cases of melorheostosis have been re-ported in the literature. Campbell et al. [1], Murray andMcCredie [2], and Morris et al. [3] reported on larger

series, but the most publications have been case reportsthat focus on unusual clinical, topographic, and radio-logic manifestations. Nevertheless, in most textbooksthe disease is monotonously described as a more or lessharmless ªflowingº hyperostosis on the outer surface of the long bones, resembling flowing or dripping candlewax, for which it was originally named by Leri andJoanny [4]. The true scope of clinical and radiologicsigns and symptoms, however, appears to be muchbroader (Table 2), leading to a similarly broad differen-tial diagnosis. Our review of 23 cases of melorheostosisis proof of that and indicates that ªunusualº manifesta-tions of melorheostosis, as shown in most case reports,

seem to outweigh the classic presentation by far.Only 5 of 23 cases corresponded to the classic type of melorheostosis (type B) with the typical dripping orflowing candle wax phenomenon, following the outerrather than the inner surface of the affected tubularbone (Fig.1). The largest subgroup with 7 cases had anosteoma-like appearance (type A; Fig.2) with the hy-perostosis located either on the outer or the inner aspectof the affected bone, or both. Six cases had an osteo-pathia striata-like pattern (type D; Figs. 4, 6) and 4 casesshowed a mixed pattern with hyperostosis on or in thebone and myositis ossificans-like ossifications in the soft

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a bFig.3 a, b The predominantly myositis ossificans-like pattern of melorheostosis in a 26-year-old patient. Above the ossificationsthere was a painful subcutaneous fibrosis and we observed hyper-pigmentated skin around the hip and knee. In both joints motionwas limited

a b

Fig.4 a, b The osteopathia striata-like pattern (25-year-old man).

Note the eccentrically located dense hyperostotic striations in thedistal femur and proximal tibia (sclerotome L3). The main reasonagainst a true osteopathia striata is the eccentric arrangement of the hyperostotic striations and the fact that the hyperostosis wasonly unilateral

a b

Fig.5 a, b Mixed pattern of melorheostosis with conspicuous para-

articular myositis ossificans-like ossifications in the laterodorsalportion of the left knee, typical dripping candle wax hyperostosison and in the fibula (see Fig. 1 b), and osteoma-like ossifications inthe foot skeleton (not shown), corresponding to the so-called scle-rotomes L4/L5 (45-year-old man with long-standing chronic painand contracture in the left knee)



tissue of the affected limb (type E; Fig.5), as describedby Khurana et al. [7] and Rhys et al. [8].

The lower extremity was involved three times as of-ten as the upper extremity, 1 patient had manifestationsin the upper as well as in the lower extremity, and in 1patient there was sacral melorheostotic hyperostosis(Table 1). The latter is an extremly rare localization, as

are other parts of the spine and ribs [1, 5, 6]. It is of in-terest, for reasons of differential diagnosis, that morethan 50% of our patients (13 of 23) had an involvementof more than one bone. In 9 cases even three or morebones were affected.

Neither male nor female preponderance of the con-dition could be observed.

Sixteen of 23 patients with melorheostosis had clini-cal symptoms; these included various skin lesions, suchas circumscribed hyperpigmentation, edema, fibrosis,and circumscribed scleroderma (7 cases), as well aschronic pain (15 of 23 patients), soft tissue masses, and

limitation of joint movement by soft tissue contracture.In most cases mainly the soft tissue involvement withfibrosis and/or myositis ossificans-like ossificationsaround hip, knee, shoulder, ankle, and feet was respon-sible for the pain. All patients with severe symptomshad extensive degree of hyperostosis as well as a highnumber of affected bones. Furthermore, there seemed

to be a connection between severity of pain and extentof hyperostosis especially in the bone marrow compart-ment, perhaps due to an elevated intraosseous pressureresulting from hindered blood circulation. Two of ourpatients (1 patient with a large intraosseous osteoma-like humeral lesion, the other with tibial hyperostosis)could be relieved from pain, on a long-term basis, bycortical fenestration ± possible evidence for the as-sumption of an elevated intraosseous pressure.

The most important differential diagnosis of melorheostosis are bone tumors producing dense bone,primarily the various types of osteosarcoma. This is es-

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a

b

c

d

e

Fig.6a±e Melorheostosis in the left hemipelvis, hip and lower ex-tremity, following the so-called sclerotomes L5/S1. At presentationthe girl was 8 years old. She suffered from chronic pain in her left

hip and foot since the age of 2 years. There was an increasing de-formation of the left foot (e) and an abductional contracture of theleft femur (a) because of a massive fibrosis in the tractus iliotibialis(b). Note the hyperostotic striations in the ilium (a) and the gro-tesque hyperostotic formations in the foot (c,d)



pecially true for the osteoma-like form and some classicforms of melorheostosis. In most cases the correct diag-nosis can be made by appreciating the segmental ar-rangement of the hyperostosis following the sclerotomes

(see below); therefore, melorheostotic hyperostosis isusually eccentric in the affected bone, contrary to mostosteosarcomas. Bone destruction is missing as well.

Histopathologycan only be usedas exclusion criterionagainst osteosarcoma, because it is unspecific. The denseboneisamixtureofimmatureandmatureboneelements.Cellular atypia or anaplasia are missing. The haversiansystem may be obliterated by thickened trabeculae, andinterspersed osteoid and fibrous tissue may be observedin the marrow spaces surrounding the areas of new boneformation. Extraosseous ossifications derive from an ec-topic cartilaginous matrix with typically lamellar ossifi-cation. These features are more or less typical of reactivebone changes which confront the pathologist with ex-

treme difficulties in diagnosing melorheostosis.Furthermore, it is not possible to exclude an os-

teosarcoma in large lesions, because there may be sam-pling error due to the biopsy (see also Materials andMethods). It is much more helpful and safer to includeclinical signs and symptoms in the differential diagnosis(e.g., cutaneous changes, subcutaneous fibrosis) and toestablish the definite diagnosis synoptically.

Etiology and pathogenesis of melorheostosis ispoorly understood. The disease principally occurs spo-radically. That virtually excludes a solely inherited dis-order and makes a disturbance of embryonal metamericdifferentiation or perhaps a sequence of both seem

much more likely. Because of the ªsegmentalº distribu-tion of the melorheostotic lesions following the sclerot-omes (Figs. 4, 5, 6), Murray and McCredie [2] suggesteda pathogenesis similar to herpes zoster. Sclerotomes arezones of the skeleton supplied by individual sensoryspinal nerves. An early (embryonic) intrauterine infec-tion of the sensory bone nerves would cause neuralscarring which in turn induces segmental bone sclerosis.

Hypothetically, the frequent association with variousskin lesions with subcutaneous fibrosis and soft tissueossifications could be explained by involvement of thedermatomes and myotomes of the same sensory nerve

roots. Since the existence of sclerotomes is not yetproved, the theory seems very uncertain.On the other hand, melorheostosis may be geneti-

cally determined but so far only sporadic and not he-reditary. Translating the concept of Happle [9, 10], thedisorder could be due to the action of a lethal gene thatsurvives only in a mosaic state. The presence of themutation in the zygote leads to the embryo's death at anearly stage of development. Cells bearing the mutationwould only survive if they were intermingled with nor-mal cells ± in a mosaic state. The mosaic may arise eitherfrom a gametic half-chromatid mutation, or from anearly somatic (postzygotic) mutation. This concept wasproposed by Happle [9, 10] for better explanation of

disorders such as, for example, McCune-Albright, Klip-pel-TrØnaunay, and Proteus syndromes, and somegenodermatoses with sporadic occurrence, asymmetricor scattered distribution of the lesions, variable extentof involvement, lack of diffuse involvement of entireorgans, and equal gender ratio.

In our patients family history was not significant, thedisease extent variable, and the gender ratio equal.

The location of the postzygotic mutation remainsobscure.

Conclusion

The review of 23 cases of melorheostosis revealed amuch broader spectrum of radiographic features thanexpected. Patterns hitherto addressed as ªunusualºseem to outweigh the classic form (dripping or flowingcandle wax phenomenon) by far. Clinical signs andsymptoms may be more frequent and severe than hadbeen expected.

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References

1. Campbell CJ, Papademetriou T, Bonfi-glio M (1968) Melorheostosis: a report

of the clinical, roentgenographic, andpathological findings in fourteen cases.J Bone Joint Surg [Am] 50:1281

2. Murray RO, McCredie J (1979)Melorheostosis and the sclerotomes: aradiological correlation. Skeletal Radi-ol 4:57

3. Morris JM, Samilson RL, Corley CL(1963) Melorheostosis. Review of theliterature and report of an interestingcase with nineteen-year follow-up.J Bone Joint Surg [Am] 45:1191

4. Leri A, Joanny J (1922) Une afflictionnon decrite des os. Hyperostose ªen

couleeº sur toute la longeur d'un mem-bre ou melorheostose. Bull Mem SocHop Paris 46:1141

5. Garver P, Resnick D, Haghighi P et al.(1982) Melorheostosís of the axial skel-eton with associated fibrolipomatouslesions. Skeletal Radiol 9:41

6. Raby N, Vivian G (1988) Case report478 (Melorheostosis of the axial skele-ton with associated intrathecal lipoma).Skeletal Radiol 17:216

7. Khurana JS, Ehara S, Rosenberg AEet al. (1988) Case report 510

(Melorheostosis of ilium, femur, andadjacent soft tissues. Skeletal Radiol17:539

8. Rhys R, Davies AM, Mangham DCet al. (1998) Sclerotome distribution of melorheostosis and multicentric fibro-matosis. Skeletal Radiol 27:633

9. Happle R (1987) Lethal genes survivingby mosaicism: a possible explanationfor sporadic birth defects involving theskin. J Am Acad Dermatol 16:899

10. Happle R (1986) The McCune-Albrightsyndrome: a lethal gene surviving bymosaicism. Clin Genet 29:321

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