In two subsequent publications (Jones, 1938 ; Jones et al., 1950) a follow-up of he family was conducted in stages, during which two further siblings were added to the series as the family increased and developed. In one case the lesion involved one side of the mandible only, and in the other the changes were minimal and radiographic only.
It was in 1938 that Jones stated: "the full round cheeks and upward cast of the eyes give the children a peculiar grotesque, cherubic appearance. If one wished to designate the disorder by a short descriptive name, the word cherubism might be coined and would seem very appropriate."
Although few subsequent observers have stressed the upturned eyes upon which it was chiefly founded, the pseudonym has persisted, perhaps as much for its romantice aura as for its non-commital quality.
Mention was made (Jones, 1938) of a male patient of Dr. P. J. Yhomas of Savannah, Georgia, who at the age of 11 years showed the characteristic radiological and photographic appearances of this condition, and gave a postive family history of the disorder having affected five generations in an unbroken line; in all, nine members of the family (two female and seven male) had developed the characteristic faces in childhood.
Miller (1947) briefly reported the case of a man of 18 years suffering from fibrous hypertrophy of both jaws, whose mother had been similarly affected. The account is inadequate, and no biochemical or radiographic evidence is submitted, but it seems likely that the condition at least closely resembled that considered here.
Caffey and Williams (1951), to a careful and detailed consideration of all then existing knowledge of the subject, added five new cases (three children and two adults) from two families, and gave the best available description of radiographic appearances of childhood and adult forms of the disease.
Waldron (1951) reported the incidence of bilateral giant-cell tumours of the mandibular angles and ascending rami in two sisters, first appearing at the ages of 5 and 7 years, and the subsequent appearance in the daughter of one of these patients, of similar lesions in the mandible at the age of two and a half years, and in both maxillary tuberosities two years later.
Talley (1952) reported the case of a child showing characteristic clinical and radiographic changes in the mandible, whose mother also showed the typical radiographic appearances of mandibular fibrous dysplasia, depite a wholly negative history and normal clinical appearance.
Bruce et al. (1953) reported four children with cherubism occurring in three families; in one family where two children were affected the family history was negative: in another the mother had suffered from jaw swellings in early life, and in the third family the father and paternal grandfather gave a history of tumours of the mandible in childhood.
Brannin and Christensen (1954) reported bilateral giant-cell tumours of the mandible in a brother and sister aged 7 and 10 years old. The parents were unaffected.
By now the syndrome had become sufficiently established for children with the characteristics of cherubism to be reported as such, despite the total absence of any history of familial incidence in parents or siblings: single instances were reported by McDonald and Shafer (1955) and Hogan and Liebner (1957), and two cases by Small and Young (1958).
Finally, Riley et al. (1956) reported the case of a child with major involvement of both jaws, whose father and paternal uncle both showed persistent changes in the mandible on X-ray, thereby bringing the detailed accounts of cherubism in childhood to a total of twenty-three cases.
Although the patient's sister (aged 7) and parents were unaffected, the maternal grandmother (aged 69) gave a history of being similarly affected as a child, and presented certain radiographic changes in her mandible suggestive of the adult form of this lesion.
Case 1.-J.R., male, born 14th May 1950. This patient was first seen in 1955 at the age of 5 years, with the sole complaint from the parents of painless, progressive, and disfiguring enlargement of the lower face and jaws.
History.-The patient had been born as a full-term normal delivery, with a birth weight of 9 lb. 6 oz., following an uneventful pregnancy.
The infant was breast-fed, gained weight normally, and showed no abnormalities whatever until about the age of two years. Thus a photograph at the age of 15 months showed normal facial appearance, but a later photograph at 2 years 5 months shows already established symmetrical and bilateral swellings of the lower face. This enlargement had continued in gradually progressive fashion throughout the subsequent years.
Eruption of teeth began at the age of 10 months, and thereafter proceeded normally.
There had latterly become established a slight blurring of speech, but there was no dysphagia or respiratory embarrassment.
Family history.-Siblings: one sister, aged 7 years, normal. Parents: father, aged 35 years, and four siblings, all normal; mother, aged 32 years, and one sibling, both normal. Grandparents: paternal, both normal; maternal, father normal. Mother, see case 2 below.
Physical Examination.-The patient was a well-built, sturdy, and active boy, intelligent and mentally alert.
There was massive symmetrical enlargement of both maxillae and both sides of the mandible, lending a somewhat pugnacious aspect to the face.
The skin and subcutaneous tissues appeared of normal texture and thickness, and there was no sclera visible below the iris of the eye, and indeed the palpebral fissures appeared narrowed by the subjacent swelling.
The mandible was enlarged in all dimensions, and showed on its outer aspect multiple lobulations of 1 to 4 cm. diameter, smooth and ill-defined, bony hard and not tender, and covered intra-orally by normal mucosa.
Smaller and rather more discrete lobulations, also smooth and bony hard , were easily palpable through the overlying cheeks on the anterior surface of both maxillae, being more marked on the left.
The alveolus of both jaws was considerably broadened and flattened, especially in the symphyseal region of the mandible where on the lingual aspect a bony platform projected backwards into the floor of the mouth at the level of the genial tubercles, for a distance of 2 cm. The maxillae, in addition to alveolar expansion, showed an acutely vaulted, narrow V-shaped, hard palate.
The teeth were tilted and in poor occlusion; anteriorly a gap of 1 cm. separated the incisal margins of the upper and lower incisors.
No teeth were missing in the deciduous dentition, and there was no alteration in the size or shape of the teeth.
The submandibular lymph nodes showed bilateral, firm, smooth, non-tender, discrete, mobile enlargement of moderate degree.
No cutaneous pigmentation or other congenital abnormailty was present elsewhere on the body; there was no clinical evidence of endocrine disturbance.
No abnormality was found on clinical examination of the chest, abdomen, cardiovascular, or central nervous systems.
Laboratory Investigations.-The serum calcium, phosphorus, and alkaline phosphatase were estimated on three separate occasions over a period of two years, with the following results: serum calcium 9.3, 9, and 11.4 mg. per cent.; serum phosphorus 5.1, 4.5, and 5 mg. per cent.; serum alkaline phosphatase 22.1, 15.5, and 16 units (Jenner and Kay).
Hb 12.3 g. per cent. Red blood cells 4,900,000 per c.mm. White blood cells 6,000 per c.mm. Differential white blood cell count showed a slight lymphocytosis: polymorphs 41 per cent., eosinophils 2 per cent., basophils nil, lymphocytes 51 per cent., monocytes 6 per cent. Erythrocyte sedimentation rate 6mm. per hour. Serum proteins: total=5.9 g. per cent.; albumin 3.7 g. per cent.; globulin 2.2 g. per cent.
Blood urea 23 mg. per cent.
Wasserman reaction and Kahn both were negative.
Urine investigation showed no abnormality.
Radiology.-There was considerable expansion of the whole of the mandible (in a vertical as well as horizontal dimesnion) which showed multiple, well-circumscribed, radiolucent areas separated by denser trabeculae, giving an appearance suggesting multilocular cyst formation. Only the mandibular condyles were not involved. The coronoid processes were rudimentary and the mandibular notch almost abolished. The cortex, though irregularly expanded and considerably thinned to give a lobulated outline, appeared intact.
Both maxillae showed similar multilocular areas of rarefaction throughout their extent, with apparent complete obliteration of the maxillary sinuses, and some upward displacement of the medial part of the infra-orbital margin on each side.
The developing permanent teeth were in most cases considerably displace from normal position, Calcification of the permanent teeth follicles appeared normally advanced except in the case of the second premolars and second molars, of whose calcification there was no evidence.
X-ray of the chest disclosed peculiar cyst-like changes in the anterior ends of all ribs on both sides.
X-ray of the remaining skeleton showed no abnormality.
Biopsy. of the mandible was obtained at the first stage of operative treatment (see below), and showed that most of the section consisted of connective tissue, made up of numerous spindle-shaped and uniformly stained cells, and intercellular collagen fibres distributed in interlacing bundles and whorls. Numbers of thin-walled and dilated capillaries were present. There was no evidence of mitoses or inflammatory round-cell infiltration.
In this matrix of cellular fibrous tissue, two other elements occurred in isolated scattered areas: irregular trabeculae of immature bone, and sparse collections of multinucleated cells of the osteoclast type.
Treatment.-Operative treament was undertaken (Mr W. Hynes) because the facial appearance was causing worry to both child and parents. The mandible was reduced on its bucco-labial aspect as well as its lower border, through intra-oral incisions, in two stages, at the age of 6 years.
The cortex was found to be sclerotic and substantial, requiring the use of chisel and osteotome; the subcortical tissue was vascular, of reddish colour, and rubbery consistence where it was not traversed by strands of bone.
A satisfactory reduction was obtained, but the mandible was inadvertently fractured during the second operation. Great difficulty was encountered in immobilising the fragments, the often ectopic and deciduous teeth providing an inadequate foundation for splints, and the fibrous nature of the mandible rendering internal fixation impossible. Despite subsequent bone graft, union of the fracture remains fibrous, though function is good.
Follow-up.-Subsequent repeated X-rays taken at the age of 8 years showed that the pathological process continues to progress. This is especially marked in the maxillae where cystiform expansion is more marked and has now invaded the zygomatic bones on each side. A recent photograph shows the broad, expanded maxillary alveolus and acutely vaulted hard palate. Intra-oral radiographs show that the second molars and pre-molars are still not evident as calcified shadows, with the single exception of one maxillary second premolar, where half of the crown is now visible.
X-rays of the skull and jaws of the patient's mother, father and sister were all normal.
Case 2.-E.T., aged 69, maternal grandmother of Case 1.
History.-Facial appearances were quite normal at birth, but swelling of the lower face was noticed at the age of 3 to 4 years. This increased steadily throughout her schooldays, but became less noticeable after the age of 20 years. The condition thereafter steadily improved until middle age was reached. A photograph at the age of 29 years still suggested rounded prominence of mandibular angles and symphysis.
Portions of the right and anterior mandible were excised at operations, at the ages of 17 years and 30 years, in attempts to improve facial contour.
Family History.-Both parents and siblings (seven sisters, three brothers) were all normal, as were the son and daughter (the latter being the mother of Case 1).
On Examination.-Facial appearances were unremarkable, and the patient was edentulous.
The upper jaw was normal, but the mandible showed rounded, smooth, bony-hard prominences overlying the outer aspects of the body of the molar regions on each side and the lingual aspect of the symphysis mentis.
Radiology.-The maxilla appeared normal. The mandible showed expansion of the horizontal rami and symphysis, with ill-defined but widespread areas of irregular patchy sclerosis. There was no evidence of cyst formation. Many areas suggested the classical ground-glass appearance, as a result of the small, tightly compressed trabecular pattern.
The jaw and face lesions are the only clinical abnormalities present.
The progressive swelling of the lower face, with marked increase in fullness of cheeks and jaws, is common to almost all descriptions and is due to enlargement and expansion of the underlying bony structures, the skin and subcutaneous tissue being normal.
The "upward turning of the eyes revealing white line of sclera beneath" (Jones, 1933), presumably due to stretching of the facial skin over the expanded bones, was not observed in the child reported here and is rarely encountered in other case reports.
The lower facial swelling is contributed to by the bilateral chronic enlargement of the submandibular lymph nodes. These are firm, smooth, discrete, mobile, painless and enlarged to a size of 2 to 4 cm. diameter. Although Bruce et al. (1953) in reporting four children aged 5 to 9 and a half years, found enlarged lymph nodes in only one case, they have been present in all other juvenile cases reported, though never in adults. This accorded with the observation (Jones et al., 1950) that the lymph nodes begin to regress after 5 years and become impalpable at the age of 11 to 12 years.
The upper cervical lymphadenopathy appears only after the facial swelling, sometimes after an interval as long as two years (Jones, 1938).
No case of spontaneous pathological fracture of the jaw has been reported.
Alveolar enlargement is marked, causing often a narrow V-shaped vault to the hard palate (Jones, 1938), and a lingual extension of the anterior mandible sometimes causing backward displacement of the tongue (Hogan and Liebner, 1957). The overlying mucosa is normal.
Almost all reports stress that the deciduous teeth are irregular, misplaced, missing, or malformed, and become loose and are lost early. This applies especially to the mandible, the maxillary dentition being little affected. Some permanent molar teeth are usually absent, and deciduous teeth may show resorption of roots by tumour tissue (Bruce et al., 1953).
Though it is usual for both sides of both jaws to be affected, this is not invariable. Thus five cases have been recorded as having no maxillary involvement and unilateral involvement of the mandible occurred in one case (Jones et al., 1950) and in one of the ancestors of Dr Thomas' patient.
Functional disability is rare, the swellings being painless and jaw movements free. One negro boy, however, is reported as suffering from limitation of jaw movement, unintelligible speech, and significant respiratory embarrassment (Caffey and Williams, 1951), and another as having speech difficulties of lesser degree (McDonald and Shafer, 1955).
In three children, in addition to the jaw enlargement, there was present a soft tissue epulis of the alveolus of giant-cell type, and resembling histologically biopsies taken from the adjacent bony lesions; of these, two were situated in the anterior mandible and the third in the maxilla (McDonald and Shafer, 1955; Small and Young, 1958).
Only three children have hitherto been reported where radiological examination disclosed a skeletal abnormality elsewhere than in the jaws. One of these merely showed an incidental coxa plana of hip (Caffey and Williams, 1951), but the others each showed a localised area of rarefaction in a humerus, biopsy of which presented the histological appearances of fibrous dysplasia in one case (Bruce et als., 1953) and giant-cell tumour in the other (Brannin and Christensen, 1953); in each case the associated jaw lesion was of similar structure.
The rib lesions reported here, though not biopsied, may be reasonably assumed to resemble in character the jaw changes. Though not previously described in the context of cherubism, Schlumberger (1946 a) found that of his sixty-seven cases of monostotic fibrous dysplasia, twenty-nine showed involvement of a rib only. It might appear that skeletal involvement outside the skull in cherubism may be more widespread than earlier reports suggested.
There is now general agreement that the child is normal at birth, and that the pathological process begins at the age of 1 to 2 years, showing maximal expansion of the jaws at 2 to 4 years and thereafter progressing more slowly. At puberty an absolute decrease in the size of the jaws may be suspected, the maxillary lesions regressing much more quickly than those in the mandible. Slow but progressive improvement follows, and by middle age there is no striking facial abnormality.
Radiology.-Good evidence that the jaws are normal at birth is afforded by two cases having received incidental jaw radiography at the age of 4 days and 2 years, before the clinical onset of the condition (Jones, 1938; Caffey and Williams, 1951); in each case radiological appearances were normal.
X-rays show clearly that the facial enlargement is the result of bone changes. The mandible shows well-defined multilocular areas of diminished density, often so extensive that only a few irregular bony septa can be seen. The cortex is reduced to a mere expanded shell of irregular contour. Only the condylar processes are spared, and the coronoid processes may be so expanded that they appear stunted and the mandibular notch absent. The process usually begins and is most marked in the mandibular angles and coronoid processes, but sometimes only the anterior mandible may be affected (Talley, 1952).
The effect of the lesion on permanent tooth development may be manifested by delayed eruption of first molars, and absence of second molars (Brannin and Christensen, 1954); it is interestingly demonstrated in the case reported here, where calcification was normally advanced only in those permanent teeth whose calcification had commenced before clinical onset of the disease at 2 years. In those teeth commencing calcification after this time, i.e., second premolars and second molars which would normally begin to calcify at 2 to 3 years (Kronfield, 1939), there was no evidence of their presence at the age of 5 years, and only one hypocalcified example at the age of 8 years.
The maxillae are enlarged and show usually a uniform and diffuse rarefaction encroaching upon the maxillary sinuses to a greater or lesser degree (Caffey and Williams, 1951). The process seems to begin in the tuberosities, which alone may be affected (Bruce et al., 1953). Multilocular pseudocystic change in the maxilla has, however, occurred (McDonald and Shafer, 1955; Small and Young, 1958) though not of such advanced degree as in the case reported here, and not previously involving the zygomatic bones.
All the other skull bones are normal, and the changes so frequently found in the cranial vault or base in the non-familial forms of polyostotic fibrous-dysplasia (Windholz, 1947) have never been described.
In the adult, the maxillae are normal and the multilocular rarefactions of the mandible have become replaced by a moderate irregular sclerosis, often having a granular or ground-glass appearance, due to an increase in the number of trabeculae present. The coronoid process is often blunt, and the mandibular notch shallow. It is evident that between childhood and adult forms, progressive calcification of the rarefied areas has occurred, the bony septa have increase in density, and new cortical bone has been laid down.
Biochemistry.-Normal serum calcium and phosphorus levels serve to eliminate hyperparathyroidism from consideration. Inconstant rises of serum calcium have occurred (Jones et al., 1950; Talley, 1952). The serum alkaline phosphatase may show a moderate rise, as it may in any condition in which osteoblastic activity is present, whether the net condition is destructive of bone or the reverse; the normal level in children is in any case higher than in adults.
Pathology.-On exploration, the tumour tissue is found to be reddish or red-grey in colour, of firm but resilient consistence, and often gritty from contained bone particles. No clear line of demarcation separates the tumour tissue from adjacent bone, or from mucoperiosteum where the cortex has been destroyed. Usually no cystic spaces are present, and the multilocular appearances on X-ray are due to the radiolucent tumour tissue.
Histologically the original bone is always replaced by a cellular fibrous tissue, containing usually trabeculae of woven bone, and often collections of giant cells resembling osteoclasts. Reports vary as to whether all are present in the same lesion, and difficulties of interpretation have resulted from divergent views on the significance of the osteoclast. Consequently cases of cherubism have been variously designated as "familial multilocular cystic disease of the jaws," "familial fibrous dysplasia of the jaws," "familial fibrous swellings of the jaws," "famililial bilateral giant-cell tumours of the jaw," "familial intra-osseous fibrous swelling of the jaws," "disseminated juvenile fibrous dysplasia of the jaws," and "familial osseous dysplasia of the jaws".
Sections showing a fibroblast-collagen stroma, usually with scattered aggregations of giant cells, and even without bone or osteoid formation, have usually been interpreted as a fibrous dysplasia of bone (Jones et al., 1950; Caffey and Williams, 1951; McDonald and Shafer, 1955; Hogan and Liebner, 1957). However, Jaffe, reviewing sections from a case of cherubism (Bruce et al., 1953) denied the interpretation of fibrous dysplasia on the grounds that there was no evidence of metaplastic ossification present: such a view is difficult to correlate with the experience of Small and Young (1958), who failed to discover metaplastic bone formation in a mandibular lesion at initial exploration, but found it present in a recurrence at the same site two years later.
Where, however, giant cells predominate and are scattered throughout the stroma, Waldron (1951) has maintained a histological diagnosis of giant-cell tumour, a view also taken by Brannin and Christensen (1954).
Further support of this interpretation has been lent by Thoma (1954) who, in reviewing the slides of the three original cases of cherubism (Jones et al., 1950), now believes them to represent benign giant-cell tumour.
A reorientation of views on giant-cell tumours of the jaws has in recent years followed upon the revival by Jaffe (1953) of some earlier theories of Mallory and Konjetzny on the significance of the osteoclast.
This has established the "giant-cell reparative granuloma" as a separate clinico-pathological entity. This is a localised bony swelling of the jaws, occurring usually in the female at the age of 10 to 25 years, and showing histologically a fibroblastic stroma, sometimes with spicules of newly formed osteoid or bone, and always with sparse collections of giant cells which occur in relation to areas of haemorrhage. It is regarded not as a true neoplasm but merely as a local reparative reaction to an unknown injury, and does not recur after local removal. Scarff and Thomson (1958) differentiate it from true giant-cell tumour by the evidence of new bone formation, the scarcity of giant cells, and the latter's phagocytic properties.
Having now had the opportunity of inspecting the slides from ten cases of cherubism, Waldron (1957) maintains that this condition is due to neither fibrous dysplasia nor true giant-cell tumour, but represents the reparative giant-cell granuloma described above. This view has gained recent support (Small and Young, 1958).
The nature of the submandibular lymphadenopathy has caused some conjecture. Jones (1933) reported the biopsy of such a node as showing "fibrous overgrowth and endothelial cell proliferation of the sinuses." It must appear more reasonable to regard this as a non-specific hyperplasia secondary to a persistent low-grade infective focus in the affected jaws, rather than to assume that the basic pathological process affects primarily not only the bones of the jaws but also the stroma of the lymph nodes. This is supported by the relatively late appearance of the lymph node swelling; also, the purely local lymph node involvement would be otherwise difficult to explain. In most cases evident sources of oral infection are not lacking.
Treatment.-The treatment of jaw fibrous dysplasias "demands surgical judgement rather than technical skill, and should be conservative" (Wass, 1952).
Local curettage of the worst affected areas in childhood, with good immediate results but some recurrence has been done (Bruce et al., 1953; Brannin and Christensen, 1954; Small and Young, 1958).
However, it is probably true to say that a majority of authoritative opinion is against operative interference in childhood, unless severe respiratory embarrassment, marked speech impairment, or considerable emotional disturbance forces the hand of the surgeon. Operation during the active phase of the disease is prone to be followed by rapid recurrence, possibly due to the stimulus of surgical trauma applied to an already overactive tissue (Cahn, 1952).
Simple paring down of the overgrown bone, following an intra-oral approach and the raising of mucoperiosteal flaps, gives very satisfactory results if done when all growth of the lesion has stopped (Jones et al., 1950).
No inhibition of fibrous tissue formation followed the use of massive doses of ACTH in an extensive case of mandibular fibrous dysplasia in a child of 7 years (Lewin, 1955).
Radiotherapy is best avoided as having little or no effect on the rate of tumour growth, and possibly producing later disfiguring telangiectases of skin (Wass, 1952).
Aetiology.-As with many diseases that rarely progress to autopsy, this is not established.
Jones (1933) suggested that the jaw lesion resulted from "an anomalous development of dental structures," being related to multiple dentigerous cysts, and has maintained this view to the end despite the defection of his co-authors to the ranks of those believing it to represent a fibrous dysplasia of bone (Jones et al., 1950). That dental cysts may be transmitted on a hereditary basis is beyond doubt (Thoma and Blumenthal, 1946), and it is tempting to associate the partial supression of dentition with the multilocular radiographic appearances.
However, Thoma (1954) does not favour such a theory, and no histological evidence of association with the enamel organ has ever been established; it is, moreover, accepted that the teeth may remain unerupted in any type of bone dystrophy.
Latent hyperparathyroidism has often been considered as a cause, but convincing metabolic evidence of parathyroid dysfunction is lacking.
Hogan and Liebner (1957) have suggested that the condition may represent a benign neoplasm, and that the spontaneous remission at puberty may be brought about by hormonal changes. However, though hormone-dependent growths are well recognised, the familial incidence would be peculiar behaviour on the part of a neoplasm.
Fibrous dysplasia was originally conceived as an aberration of bone-forming mesoderm (Jaffe, 1946). though Schlumberger (1946 a) has suggested that it may represent a non-specific abnormal reaction to trauma. Those protagonists of the interpretation of the lesions of cherubism as representing a reparative giant-cell granuloma have reintroduced trauma in childhood as a cause. However, injury has not been an exciting cause in any case reported to date, and the multiple tumour sites involved in the case reported here, and others, must render such an explanation unlikely.
An attractive and unifying concept of histogenesis of fibro-osseous lesions of the jaws has gained ground in recent years. Schlumberger (1946 b) suggested that pure fibroma, fibrous osteoma, osteofibroma, and ossifying fibroma are all variants of fibrous dysplasia, a view now supported by Jaffe (1953), while Smith and Zalveta (1952) go even further in regarding osteoma of the skull bones as the end result of fibrous dysplasia. It may therefore be conceived that all fibro-osseous swellings of the jaws are not true neoplasms, but merely aberrations of ossification in membrane, producing fibrous dysplastic lesions which whether localised or diffuse may vary from a fibroma at one extreme to an osteoma at the other. The significance of the osteoclast, so often present, is speculative. Whether or not giant cells indistinguishable from it are to be found in the vicinity of organising haemorrhages (Jaffe, 1953), there is general agreement that the osteoclast may be found wherever bone resorption occurs; in such fibro-osseous tumours its presence may thus merely indicate an active phase of bone resorption.
Such a concept, though not susceptible of proof, is possibly more appealing to the clinician (Wass, 1952) than to the morbid histologist (Sicher and Weinmann, 1954).
It must be assumed that the hereditary element in cherubism arises as a spontaneous mutation of the germ cell. Waldron (1951) quotes the opinion of a geneticist that the mutation is of dominant type, so that half the offspring of any of the affected persons may develop the anomaly; in fact, almost every reported case discloses the existence of some normal siblings in each instance.
The familial incidence of the disease is the greatest single barrier to explaining cherubism as a fibrous dysplasia of bone, for it does not occur in any other example of the latter. Possibly an inherited predisposition on which some subsequent factor (traumatic, infective, hormonal) becomes superimposed, may prove an ultimate explanation.
A summary is given of all previously reported cases.
The clinical features, radiographic, pathological, and biochemical aspects of the disease are discussed, and treatment is considered.
After a consideration of theories of histogenesis and aetiology, the disease is regarded as fibrous dysplasia, this term being used in its wider interpretation.
I wish to thank Mr W. Hynes and Mr G. H. Rayner for permission to report Case 1, who was under their care. I am also indebted to Dr T. Lodge, Consultant Radiologist, and Dr J. L. Edwards, Consultant Pathologist, both of the Royal Hospital, Sheffield, for allowing access to X-rays and slides.