Neurochirurgia 20 (1977), 189-199 © Georg Thieme Verlag Stuttgart
Cranial Eosinophilic Granuloma C. Arseni, L. Dánáila, Al. Constantinescu
Summary Investigations were carried out on 27 cases of cranial eosinophilic granuloma: 16 males (59%) and 11 females (41%). The mean age was 25 years, the extremes being 2 years and 65 years. The location in 21 cases (80 %) was exclusively in the calvarium (9 frontal, 8 parietal, three occipital and 1 temporal), orbital in two cases, fronto-orbital one case, base of the skull in the left parasellar region one case, left frontal subdural with chronic subdural haematoma one case and one case left occipital and petrosal bone. All the cases were diagnosed histologically. In 18 cases the tumour was removed at operation. Recurrences occurred in four of these cases (15 %), three of whom died (11-5 %). Four of the patients received steroid therapy and four steroid therapy combined with X-ray therapy. The evolution was favourable in all these cases. Key words: Cranial tumour - eosinophilic granuloma - subdural haematoma.
Zusammenfassung Es wurden Untersuchungen durchgeführt in 27 Fällen von kranialen eosinophilen Granulomen: 16 Männer (59 %) und 11 Frauen (41 %). Das Durchschnittsalter betrug 25 Jahre, die Extremwerte lagen bei 2 und bei 65 Jahren. Die Lokalisation war in 21 Fällen (80 %) ausnahmslos im Bereich des Schädeldaches (9 frontal, 8 parietal, 3 occipital und 1 temporal), orbital in 2 Fällen, frontoorbital in einem Fall, im Bereich der Schädelbasis links parasellär in einem Fall, links frontal subdural mit chronischem subduralen Hämatom in einem Fall und schließlich ein Fall links occipital und im Bereich des Felsenbeines. Alle Fälle wurden histologisch diagnostiziert. In 18 Fällen wurde die Geschwulst chirurgisch entfernt, davon traten Rezidive in 4 Fällen (15 %) auf, drei von diesen starben (11,5 %). 4 der Patienten erhielten Kortikoide allein und 4 erhielten Kortikoide in Kombination mit einer Röntgenbestrahlung. Der Verlauf war in all diesen Fällen günstig.
Following the details related by Schairer (1938) concerning eosinophilic granuloma, Lichtenstein and ]affé (1940) mentioned three different cases, communicated previously, and discussed one of their own cases. Otani and Ehrlich. (1940), with reference to seven cases, were the first to use the term eosinophilic granuloma. Layani and Aschkenzy (1948) emphasized the diagnostic value of biopsy puncture of the tumour. Lightwood et al. (1955) reported on 16 cases. Casan (1956), in his doctor's thesis, gathered 150 cases published in the special literature. Jelsma (1959) had six patients and Efremov and Beruciashvili (1960) seven patients. Oberman (1961) published comments on 40 cases, and Turpin et al. (1965) on 63 cases apart from his own patients. Racikov's study (1966) included 30 such cases, studied especially from the viewpoint of pain symptoms. Isolated cases were published by Green (1942), Raaf (1945), Thaunhauser (1947), Farin et al. (1958), Beier et al. (1963), etc. The present study includes 27 cases of eosinophilic granuloma of the skull, referred to our clinic between 1935 and 1976.
Discussion of the cases Sex. Of the 27 cases 16 (59 %) were males and 11 (41 %) females. Jelsma (1959) reports an equal distribution of the sexes, the same as Tönnis and Schettles (1967), whereas Lichtenstein and Jaffé (1940) maintain that the male sex is predominantly affected (75 % ) . Age. The age of our patients ranged between 2 and 65 years, being in the mean 25 years. From Table 1 it may be seen that the incidence was higher under the age of 40 (21
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Clinic of Neurosurgery, Bucharest •— Romania
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C. Arseni, L. Dänäilä, Al. Constantinescu
Age
1-5
6-10
11-20
21-30
M
0
2
6
3
F
3
0
1
0
5
2
0
11
Total
3
2
7
3
7
4
1
27
cases) and the occurrence rare after the age of 50 years. Most of Jelsma's patients were in early adult life. Tönnis et al. (1967) asserted that the disease chiefly affects individuals under the age of 20 years. Localization. The skull is prevalently affected by eosinophilic granuloma, being involved according to Gerlach (1974) in two thirds of the cases. The calvarium was exclusively affected in 21 (80 °/o) of the 27 cases: eight parietal, of which one recurred in the frontal area and opposite parietal area (in a mirror), nine frontal, of which one with a double frontal and parietotemporal lesion on the same side, three occipital and one temporal; two orbital localisations (one 44 year-old patient presented, one month after extirpation of a tumour in the infero-external angle of the left orbit, signs of compression of the brain, due to extension of the tumour intracranially in the left fronto-temporal area; he died five weeks later), one unilateral fronto-orbital eosinophilic granuloma appeared on the opposite side and extended after two months to the calvarium, 10th rib, hip bone and femur, one case at the base of the left parasellar area, one case in which the external third and base of the left petrous bone were affected but which also presented a left occipital eosinophil granuloma about the size of half a walnut, and an exceptionally rare case of left frontal subdural location with a chronic subdural haematoma. Among the multiple but also primary locations of eosinophilic granuloma, other parts of the skeleton may also be invaded:
2
31-40
41-50
2
over 50
Total
1
16
ribs, spinal column (we had two cases in which the spine alone was affected), hip-bone, proximal parts of the bones of the extremities and mandible Jelsma considered that the lesion occurred most frequently in the parietal area but did not find multiple lesions in his patients. Northfield (1962) considers that eosinophilic granuloma may be single or multiple and the skull is more frequently affected than the pelvis, long bones, scapula and phalanges. Lesions of the soft tissues and internal organs (skin, kidneys, gastrointestinal tract, lungs, liver, brain, etc.) have also been described in isolated cases. Bingas (1974) maintains that eosinophilic granuloma affects especially the temporoparietal region, then the orbital and less frequently the petrosal, sellar and sphenoid areas. In 60 % of the cases the lesions are solitary, but multiple lesions may affect the skull, ribs, pelvis, upper and lower jaw and metaphysis of the long bones.
Pathological
anatomy
Gross examination. The tumour varies in size from a cherry to an apple. After detaching the scalp which the tumour does not infiltrate, a purplish capsule appears which discharges a greyish-yellow semifluid substance. The yellowish colour is due to lipoid necrosis and the grey to haemorrhagic foci. Rarely the tumour takes on (in the fronto-orbital locations) a yellowish-red, fatty consistence. The external layer of the dura is always invaded. The tumour seldom extends through
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Table 1
the dura with intracranial involvement, as in the case of orbital lesions. Microscopy. The diagnosis is not difficult. All the cases were checked by microscopic examination, either after local biopsy or surgical removal of the tumour. There was a foamy appearance, with large mononuclears, a dense network of reticulin fibres in which different types of cells were interspersed: eosinophil granulocytes distributed in clusters, myelocytes, lymphocytes, plasma and giant cells. During recovery, reorganising connective tissue may be seen, with prevalent fibrous changes of varying degree and even imperfect osteogenesis. In general, the disease is characterized histologically by multiple granulomas and a great number of eosinophils. According to Paillas (cited by Arseni and Marinesca 1969) eosinophil granulomas develop in four phases (also encountered in Hand-Schüller-Christian disease), the histologic aspect depending on the age of the lesion: (1) proliferative hyperplastic phase with reticulo-histiocytes, abundant eosinophils and necrotic, haemorrhagic foci; (2) granulomatous phase with hyperplasia and proliferation of newly formed vessels, granulomatous and reticular cells, histiocytes, considerable eosinophilic infiltration, necrosis and incipient lipoid phagocytosis, multinucleate giant cells in the vicinity of the haemorrhagic and necrosed areas; (3) xanthomatous phase with the presence of foam cells, either isolated or in nests, marking lipoid overloading, a diminution of eosinophils and the beginning of remission; (4) fibrous phase that precedes ossification and cicatrisation, leading to spontaneous recovery or healing after irradiation and steroid therapy. This subdivision into four phases of development is purely theoretical, since the characteristics of the four phases may often be encountered in the same section.
191
Pathogenesis. Eosinophil granuloma was intitially considered to be a form of HandSchiiller-Christian disease (Engelbreth-Holm et al. 1944). In view of the benign character of the disease and its predominant cranial localisation this idea was opposed by ¡Viertens and Ullerich (1954), who regarded it as a separate entity. Schuster and Flynn (1954) inclined towards an infectious origin of the disease, and Otani et al. (1940) believed that either infection or trauma may be the causative agent. According to Jalsma (1959) the cause is not known, but various authors have associated it with xanthomatosis. There is, however, a marked difference between the symptoms, age incidence and cranial form of the two diseases. Rossenbeck (1957) showed that there is still debate concerning the distinction between eosinophilic granuloma and HandSchüller-Christian disease, their possible relationship being in turn denied or sustained. Knighton and Fox (1956) thought it to be a primary disease of the reticulo-endothelial system. Efremov et al. (1960) showed that it was one of the least elucidated diseases of the reticulo-endothelial system. Siwe (cited by Oberman) considered eosinophil granuloma a local reaction to injury of the reticulo-endothelial system of the bone, without any tendency to generalisation. Jaffe and Lichtenstein (1944) established a relationship between eosinophil granuloma, Letterer-Siwe disease and Schiiller-Christian disease. Lichtenstein (1953) grouped together, under the name of "histiocytosis Y", eosinophil granuloma, Hand-Schüller-Christian disease and Abt-Letterer-Siwe disease, with various intermediate or transitional forms. He proposed this generic term in order to suggest the continuity of the three diseases belonging to the reticulo-endotheliosis group, representing different variants of the same pathological process, initially characterized cytologically by the presence of a large number of histiocytes, with a different clinical picture and evolution, related pathological
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Cranial Eosinophilie Granuloma
C. Arseni, L. Dänäilä, AI. Constantinescu
substrate (granuloma), histologic characteristics proper to each disease and an unpredictable prognosis. This unitary concept of the three diseases was not readily accepted and was initially opposed even by Lichtenstein himself, only to be accepted subsequently by most authors (Lahey 1962). A few sustained the opinion of Otani et al. who only recognize involvement of the reticulo-endothelial system as a common factor of the three diseases. Age and the initial location of the morbid process appear to play a decisive role in determining one or other clinical form of histiocytosis. Northfield (1962) asserts that eosinophilic granuloma is related to Letterer-Siwe and Hand-Schüller-Christian diseases and may also be associated with purpura (Swann and Williams 1953). Many authors consider it as an established Letterer-Siwe disease, being a different phase of one and the same pathological process of the reticolo-endothelial system. Today, it is generally agreed that eosinophilic granuloma may be considered as a benign type of histiocytosis X, with an exaggerated development of the reticulo-endothelial elements, whereas Abt-Letterer-Siwe disease is a malignant form (Bingas 1974). The evolution of Hand-Schüller-Christian disease stands between these two extremes. Owing to the obscure pathogenesis of these diseases, many terms have been used as synonyms for eosinophilic granuloma or histiocytosis X, such as: myeloma with eosinophilic cells, solitary granuloma of the bone [Otani and Erlich 1940), histiocytic granuloma, benign granuloma, destructive granuloma of the bone, eosinophilic reticuloma, benign reticulosis of the bones, reticuloma of the spinal cord (Knochenmark-Retikulom), granular reticulosis (Schuknecbt et al. 1948), eosinophilic granulo-reticuloma (Burkhardtand Fischer 1970), histiocytic reticulo-endotheliosis (Lightwood et al. 1955), idiopathic histiocytosis (Oberman 1961), reticulo-endo-
thelial granuloma, systemic or primary granulomatosis, eosinophilic xanthomatous granuloma, histiocytic granulomatous disease (Turpin et al. 1955). We fully agree with Gerlach's opinion (1974) according to which the term eosinophilic granuloma appears to be the most satisfactory. Symptoms. Onset. During the incipient phase when the morbid process develops only intradiploically, the disease is asymptomatic, as proven by a patient admitted to the Clinic for spasmodic torticollis. X-ray of the skull, performed for another purpose showed in the parietal region a small eosinophilic granuloma, that was completely symptomless. The most frequent presenting symptom however is pain, of which 12 patients complained (44-4 °/o). Initially, a local soreness developed, the patient complaining that the place was tender when he combed his hair, or washed or put a hat on, although nothing could be palpated locally. The lesion at first shows a tendency to grow through the outer table of the skull (phase II), invading the pericranium and even the muscles, and only subsequently infiltrating the dura (phase III). The pain then becomes more intense and spreads towards the periphery of the lesion, taking on the aspect of hemicrania or attacks of migraine, accompanied by nausea, vomiting, sometimes fever, a poor general condition, insomnia, irritability, that become more and more frequent until the headaches become permanent. In this phase the tumour develops and can be palpated. In phase III when the lesion affects the meninges the pains are intense, diffuse, continuous but superficial, not in the form of internal pressure as in raised intracranial pressure. In 2 cases the pains became persistent after a local injury. In one of these two patients, with an orbital lesion, the onset was marked by hemicrania on the side of the lesion, accompanied by nausea, vomiting and ptosis that disappeared between the attacks. Three months after the onset of the migraine, these
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Cranial Eosinophilie Granuloma
One patient came to hospital because of a feeling of numbness of the head on the side of the lesion. In the patient with eosinophilic granuloma at the base of the left parasellar area the onset was marked by diplopia and ptosis. A 31-year-old patient, was operated on for a chronic left frontal subdural haematoma; the small fleck found proved to be an eosinophilic granuloma, which came as a surprise to us. The patient, after suffering a slight head injury, had been complaining for five weeks before admission, of diffuse headaches, right hemiparesis and speech disturbances. The interval elapsing between the first symptom and admission was on average nine months, with extremes of five days and four years. Nine of the 27 patients (33-3 °/o) had 13 Neurochirurgia 20,6
suffered an injury at the site where the eosinophilic granuloma developed. On admission, 16 of the 21 cases with an eosinophilic granuloma of the calvarium presented a visible localised swelling and only five had pain. The cranial tumour was never larger than an apple and generally smaller, doughy, resistent, rarely fluctuating, painless in four cases and tender in the others, non-pulsatile, adherent to the deep structures but not to the skin; a slight underlying shelf-like edge, smaller than the extent of the tumour, could sometimes be palpated. One of the two cases with an orbital lesion presented ptosis, exophthalmos, paresis of the common and external oculomotor nerve, mydriasis, blindness, pallor of the disk and intense pain in the left eyeball, on the side of the lesion located in the infero-external angle of the orbit. The other presented palpebral oedema and ptosis, slight exophthalmos, restricted outward movement of the globe of the eye, visible tumour in the outer third of the left orbital margin and local pains. The eosinophilic granuloma was located in the upper and outer angle of the left orbit. The patient with a fronto-orbital location was admitted in 1960, at the age of two years; she had been suffering from fever for three weeks, then a tumour developed in the outer half of the left orbital margin, which became enlarged in the cold. On admission, the tumour measuring 1-2 cm, was soft, painful and accompanied by exophthalmos and downward displacement of the eyeball. Through a left frontal flap an eosinophilic granuloma was removed. It had not extended through the dura but had eroded the frontal bone, orbital margin and part of the orbital roof. The child was well until January 1961, when the granuloma recurred and was extirpated. A month later a similar tumour developed on the right side, with exophthalmos and slight downward displacement of the eyeball. Through a right frontal flap the tumour removed. The child felt better for two months, but fever again developed, with
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symptoms became permanent and were accompanied by slight exophthalmos. In this phase, a diagnosis of ophthalmologic migraine and then of trigeminal neuralgia was made. In the other case, two months after the injury on the outer third of the supraorbital arch, a tumour developed. This was the second most frequent presenting symptom, observed in nine cases (33-3 °/o). In two of these cases it was accompanied by diabetes insipidus, and one patient presented general epileptic seizures and ambulatory automatism. In one case a localised depression appeared three weeks after appearance of the tumour. In five cases the tumour developed after local trauma. However, pains do not always appear in the second phase when the tumour has extended outwards beyond the bone. This was the case in three patients who had no pains at first. In three children the onset was febrile; in two the tumour appeared shortly after the fever and meningeal reaction and the third suffered for about two years from headaches and a subfebrile state without any apparent cause until a small painless tumour developed in the occipital region. Another patient was admitted because of a slightly punched-out area on the skull.
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C. Arseni, L. Dânàxla, Al. Constantinescu
diabetes insipidus, enlargement of rhe liver and spleen, pale skin, loss of weight, bilateral ptosis and slight psychomotor agitation. The X-ray revealed an occipital and two parietal round osteolytic areas measuring 1 cm in diameter, one on the tenth rib, ilium and upper third of the femur on the right side. The other investigations revealed increased ESR, leucocytosis with eosinophilia, anaemia, anisocytosis and anisochromia. The sternal puncture showed marked lymphocytic hyperplasia, hypoplasia of the red cells, shift to the left of both series, especially the red one. No Hand-Schüller-Christian cells were found. The child was taken home and died a week later. A left parasellar location at the base of the skull was found in an 18-year-old patient, who developed diplopia and left-sided ptosis two months before his admission on December 29, 1971. The presenting signs were paresis of the left oculomotor nerve, moderate exophthalmos and diplopia. The X-ray showed destruction of the sella turcica and sphenoid sinus Arteriography showed unfolding of the left carotid siphon and scintigraphy with 90Tc a left para- and retrosellar zone of moderate hyperactivity. Through a left temporal craniotomy a grey parasellar tumour was partly extirpated. The histological examination showed it to be an eosinophilic granuloma. After a short period of remission, hypoaesthesia of the left trigeminal 1st and 2nd divisions, optic atrophy, left blindness and diabetes insipidus developed. Lindlar
(1970) postulated that the endocrine disturbances were brought about by a reticulo-granuloma of the hypothalamus. A month later the patient was again operated on, and a recurrent tumour was partly removed; she died on the third day after the operation. A four-year-old little girl presented with a petrosal lesion. She had been suffering for the last three months from pains in the left ear, left suppurative otitis and a painless, soft tumour, about the size of half a walnut, which appeared in the left occipital region two months before her admission on August 2, 1954. The X-ray showed occipital lysis, with a maplike aspect extending further than soft tumour, and in the outer third and basal region of the left petrous bone, an area of destruction measuring 1-6 cm. The occipital tumour, an eosinophilic granuloma, was extirpated and the petrosal granuloma healed spontaneously, without cortisone or X-ray therapy. The patient subsequently became an employee of our Hospital and was followed up for a further 22 years. She still feels quite well. According to Kormann (1964) location in the petrous bone may produce the GradenigoLannois syndrome, with paralysis of the abducens and trigeminal nerves, headache and cerebellar signs, when the lesion is in the internal half of the petrosal bone; in the external half it may produce suppurative otitis and mastoiditis. Ancillary examinations. The most important is the X-ray examination, which may re-
Fig. 1: (a) Round, parietal osteolysis, (b) Long, angular parieto-temporal osteolysis, (c) Round, frontal osteolysis with central sequestrum.
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194
Cranial Eosinophilic Granuloma
acteristic of eosinophilic granuloma. The differential diagnosis has to be established from osteomyelitis, sarcoma, metastases, plasmacytoma, meningioma, tuberculous osteoma,
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veal a round (fig. la), oval or long angulate (fig. lb) osteolytic area, as a rule empty and only exceptionally with a central sequestrum ( % lc). Initially, the lesion is intradiploic (fig. 2a) and asymptomatic and may only be discovered casually. In the second phase the tumour destroys the outer table and extends outwards (fig. 2b), as revealed by tangential Xray views. In the third phase the tumour also invades the inner table (fig. 2c) and reaches the dura. Most patients are admitted to hospital at this stage. The lesion may be single as in fig. 1, double (fig. 3) or multiple, taking on a map-like aspect, with irregular contour due to the agglomeration of many cavities (fig. 4a, b, c, d). It contrasts with the neighbouring normal bone, is not decalcified and shows no endosteal or periosteal perifocal reaction. A postoperative recurrence may occur, either on the opposite side or in other bones of the head or body, as in the child with a fronto-orbital location. These lytic areas are fairly sharply demarcated, with absent or hazy reactive changes, not resembling dermoid or epidermoid tumours, as demonstrated by Arseni, Dänäilä and Constantinescu (1975).
195
In general, the X-ray is characterized by circumscribed lysis of the bone without surrounding sclerosis; this is actually of diagnostic value in youthful subjects. When the base of the skull or the orbit is involved, the radiological diagnosis is more difficult, and tangential views or tomographs alone may reveal the existence of an osteolytic process. Jelstna describes an irregular, punched-out area of decreased density, without any sunburst appearance on tangential views as in haemangioma. For Févre (1957) the radiographic image of a depressible swelling is characteristic. Leger (1947) proposed the term of "mottled porosity". During the process of recovery the lesion is surrounded by a fine area of sclerosis of the bone, suggesting reaction of the neighbouring tissue. The X-ray image is not, however, char13*
Fig. 2: (a) Tangential X-ray in phase I: the lesion is intradiploic. (b) Tangential X-ray in phase II: the tumour has destroyed the outer table and extrudes, (c) Tangential X-ray in phase III: the tumour has now also destroyed the inner table of the skull.
C. Arseni, L. Dänäilä, Al. Constantinescu graphy, scintigraphy, pneumoencephalography, electroencephalography and examination of the cerebrospinal fluid are as rule normal. Blood tests performed in 22 cases only revealed eosinophilia in eight cases. In three of these cases lymphocytosis was also present, in four anaemia (two anisocytosis and anisochromia) and in four cases elevated ESR values. These tests were normal in the other 14 patients. Sternal puncture performed in four cases, only revealed anomalies in the case of fronto-orbital tumour, described above.
Fig. 3: Bilateral frontal osteolysis.
and parieto-temporal
osteomyeloma, solitary myeloma, syphilis, etc. The other ancillary examinations - arterio-
Electrophoresis performed in one case showed 0-7680/o proteins (Kingsley method), 1/4 albumin/globulin ratio, 5-91 °/o albumins, 6-75 alpha-globulins, 9-50 alpha 2 -globulins, 10-80 beta-globulins, 13-85 gamma-globulins.
Fig. 4: Map-like appearance: (a) Recurrent eosino philic granuloma, initially parietal then extending frontally (b) and subsequently parietally on the o pposite side (c), with recurrence towards the occipital area.
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Walthard and Zuppinger (1949) explain the essential eosinophilic nature of the granuloma by the migration of the eosinophils to the affected area. François et al. (1963) found increased ESR, gamma-globulins, alpha 2 -glycoproteins and lipoproteins. Mertens and Ullerich (1954) reported on an abnormal Thorn test in one case. Treatment. Surgical removal of the tumour was performed in 19 cases. Three of these patients died (granuloma of the base of the skull, recurrent orbito-frontal granuloma and orbital tumour that subsequently extended intracranially in the temporal region) after recurrence and renewed surgical intervention. In a 39-year-old patient (fig. 4) who had been suffering for three years from a small left parietal tumour the size of a hazelnut, the tumour had disappeared leaving a punchedout area in the bone. Six months before admission diabetes insipidus set in and the tumour again developed rapidly, measuring 2-0 cm in November 1968 when he was operated on. Four months later there was a recurrence of the left parietal tumour, which was extirpated. Two months after the second operation a left frontal tumour, the size of a plum, and a right parietal tumour, the size of an egg, developed, and were removed on August 30, 1969. In 1970, a right parieto-occipital tumour reached the size of an egg and was extirpated on February 6, 1971. X-ray therapy and cortisone were administered and the patient has remained quite well up to the present. The diabetes insipidus treated with pitressin showed marked improvement. Such cases should be treated, we believe, from the very beginning by a combined attack operation, X-rays, steroid therapy). In four cases of small eosinophilic granulomas, that were not visible or palpable and only caused local pains, X-ray and steroid therapy were employed, arresting the evolution of the tumour. In general, when the tumour bulges under the scalp and is clearly visible, operation followed by cranioplasty is
197
recommended. The bone is resected by sharp dissection down to the healthy tissue and the dura curetted but not removed. De Sa (1959) doubts the effectiveness of irradiation and steroid therapy after operation. The lesion rarely regresses spontaneously. Cortisone alone or combined with X-ray therapy may only be applied in phase I and II, and necessitates constant surveillance of the patients. Waltbard and Zuppinger (1949) obtained good results with X-ray therapy in an inoperable case. Contradictory reports have been published concerning the value of corticosteroids and cytostatic agents. In general the evolution of eosinophilic granuloma is favourable and benign, although alarming symptoms, recurrences and death may occur. As a rule the duration is of months, seldom lasting years. Recurrences developed in four cases (15 °/o). There were three deaths (ll°/o).The prognosis depends on the initial location of the pathological process and the patient's age. The cases of solitary, isolated lesions of the bone have a good prognosis and recovery may occur spontaneously.
Conclusions - Eosinophilic granuloma more frequently affects the frontal and parietal bone and more rarely the occipital bone and orbit. - A single esosinophilic granuloma was found in 85 % of the cases, and multiple lesions in 15 %. - An eosinophilic granuloma of the calvarium develops in three phases: phase I intradiploic, phase II when the tumour develops outwards destroying the outer table of the skull and phase III when the morbid process extends inwards, destroying the inner table and invading the dura, but rarely extending beyond it. - The precise diagnosis can only be established by microscopic examination of the specimen removed surgically or by biopsy puncture. Notwithstanding, owing to the pro-
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Cranial Eosinophilie Granuloma
C. Arseni, L. Danäilä, AI. Constantinescu
gress of radiology and clinical experience and observation, a clinical diagnosis may also be established. - There is no characteristic X-ray image of eosinophilic granuloma. - Eosinophilic granuloma may be considered a precancerous state that may run a malignant course in a small number of cases. - Eosinophilic granuloma may be solitary, with recovery after operation, X-ray or steroidtherapy, or it may relapse, taking on a malignant character as in four of our cases (base of the skull, orbital, fronto-orbital and cranial) with a fatal outcome in 3 cases.
- The best results were obtained by radical surgery, excising up to the healthy bone tissue, with cranioplasty at the same session. - Treatment with cortisone or combined with X-ray therapy may give good results in phases I and II, but necessitates constant surveillance of the patients. Recurrences occurred in four cases (15 °/o). There were three deaths (11 °/o). - The prognosis depended upon the initial site of the morbid process, the patient's age and number of lesions. The solitary, isolated lesions had a good prognosis, with spontaneous recovery.
Literature Arsent, C, L. Danaila, Al. Constantinescu: Cranial and orbital epidermoid tumours. J. Neurosurg. Sei. 19 (1975) 3, 139-151 Arsent, C, V. Marinescu: Granulomul eozinofil al oaselor craniului (Probleme de clínica ci diagnostic in Histiocitoza X) Viata medícala 22 (1969) 1521-1530 Beier, R. F., G. L. Thatchen, E. M. Lahey: Treatment of reticuloendotheliosis with Vinblastine Sulfate. J. Pediat. 63 (1963) 4, 1087-1092 Bingas, B.: Tumours of the base of the skull in Vinken, J. P. and G. W. Bruyn: Handbook of clinical Neurology Vol. 17 Part II North-Holland Publishing Company - Amsterdam American Elsevier Publishing, Ca, INC. New York (1974) 175-176 Bodian, M.: Survey of the pathological features of HandSchùîîer syndrome, Letterer-Siwe disease and eosinophilic granuloma of bone. Proc. roy. Soc. Med. 48 (1955) 713-715 Burkhardt, L., H. Fischer: Pathologische Anatomie des Schädels. In: Lubarsch, O., F. Henke, R. Rössle and UchIinger, eds: Handbuch der speziellen pathologischen Anatomie und Histologie Vol. IX/7 Berlin-GÖttingen-Heidelberg. Springer (1970) 250-344 Castro Freiré L, (De), J. Delfim: Granulome osseux eosinophile et son rapport avec le syndrome de Hand-SchüllerChristian. Amatus 3 (1944) 522-532 Cassan, ].: Des granulomes eosinophiles des os. Thèse (1956) 121 De Sa, J. V.: Eosinophilie granuloma of the temporal bone. Arch. Otolaryny 70 (1959) 593-596 Efremov, A. V., L. Z. Beruceaçv'tli: Eozinofilnaia granulema kostei cerepa. Vopr. Neirohir. 2 (1960) 47-51 Engelbreth-Holm, J., G. Teilum, B. Christensen: Le granulome eosinophile de l'os (maladie de Schüller-Christian). Acta med. scand. 118 (1944) 292-312 Farin, M. J. Rotem: Eosinophilie granuloma. Acta orthop. Scand. 28 (1958) 12, 121-130 Fevre, M.: Le granulome eosinophile des os et son diagnostic radiologique. Rev. Prat. (Paris) 7 (1957) 20, 2214-2223 François, R., M. Lekieffre, J. P. Cécile: Le granulome eosinophile de l'orbite. A propos de deux observations. J. Radiol. Electrol. 44 (1963) 842-848 Gerlach, ].: Tumours of the cranial vault. In: Vinken, J. P. and G. W. Bruyn: Clinical Neurology. North-Holland Publishing Company. Vol. 17 (1974) 116-117 Green, $7. T., G. Färber: Eosinophilic or solitary granuloma of bone. J. Bone Joint. Surg. 24 (1942) 499-526
Jaffe, H. t., L. Lichtenstein: Granulome eosinophile de l'os; une affection intéressant un ou de nombreux os, mais limitée apparemment au squelette et représentant l'expression clinique la plus bénigne d'une histiocytose inflammatoire particulière comprenant également la maladie de Letterer-Siwe et le syndrome de SchüllerChristian. Arch. Path. 37 (1944) 99-118 }elsma, F.: Primary tumors of the calvaria Charles C. Thomas Springfield USA (1959) 3-116 Knighton, R. S., J. de W. Fox: Diagnosis and treatment of eosinophilic granuloma of skull. J. A.M. A. 162 (1956) 1294-1297 Kormann, G.: Ein eosinophiles Granulom in der Felsenbeinspitze. Beitr. Neurochir. 8 (1964) 221-223 Lahey, E. M.: Prognosis in reticuloendotheliosis in children. J. Pediat 60 (1962) 5, 664-671 Layani, F., A. Aschkenazy: L'histiocytome éosinophilique des os, dit »granulome eosinophile«. Ses liens de parenté avec la maladie de Schüller-Christian. Intérêt diagnostique de la ponction tumorale. B. M. Soc. Méd. Hôp. Paris 64 (1948) 391-396 Le Besnerais, Y., R. Messimy: Un cas de granulome lipoidique crânien isolé. Neuro-chirurgie 5 (1959) 326 Leger, L.: Le granulome eosinophile des os. Presse méd. 57 (1947) 648-649 Lichtenstein, L., H. L. Jaffe: Eosinophilic granuloma of bone. Am. J. Path. 4 (1940) 595-604 Lichtenstein, L.: Histicytosis X. Integration of eosinophilic granuloma of bone "Letterer-Siwes diseases" and "Schüller-Christian disease" as related manifestations of a single nosological entity. Arch. Path. I (1953) 84-102 Lightwood, R.t N. Bodian, J. Sutcliffe: Discussion: eosinophilic granuloma. Letterer-Siwe disease, Hand-SchüllerChristian disease: Histocystic type of reticulo-endotheliosis. Proc. roy. Soc. Med. 48 (1955) 711-720 Lindlar, F.: Histiozytose des Zentralnervensystems und der Lungen. Dtsch. med. Wschr. 95 (1970) 2075-2078 Mertens, H. G., K. Ullerich: Die neurologische und ophthalmologische Klinik des eosinophilen Knochengranuloms. Nervenarzt 25 (1954) 97-104 Northfield, D, W. C: Intracranial tumours, in: Recent Advances in Neurology and Neuropsychiatry (by) Brain and Strauss. Seventh ed. Churchill, London (1962) 71-72 Oberman, A. H.: Idiopathic histocytosis. A Clinical pathological study of 40 cases and review of the literature on eosinophilic granuloma of bone, Hand-Schüller-
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198
199 and eosinophilic granuloma of the skuli. Ann. Otol. (St. Louis 57 (1948) 643-676 Shuster, B. H., T. F. Flynn: Eosinophilic granuloma of frontal bones, report of case. Arch. Otolarvng. 60 (1954) 501-504 Swain, G. ]. M. Williams: Eosinophilic granuloma of bone. J. Neurosurg. 10 (1953) 185-186 Thaunhauser, G. ].: Eosinophilic granuloma of bone. J. A, M. A. 134 (1947) 1437-1438 Tönnis, W., G. Schettler: Das eosinophile Granulom der Orbita. Dtsch. Z. Nervenheilk. 192 (1967) 193-208 Turpin, R., P. Veron, L. Bosquet, R. Gorin, B. Caille, C. Lafora, B. Rouston, } . Cruveiller: Maladie granulomateuse Histiocytaire (Histiocytose X). Sem. Hôp. Paris 1 (1965) 5-23 Walthard, B., A. Zuppinger: Das eosinophile Granulom des Knochens. Schweiz, med. Wschr. 79 (1949) 618-623 Prof. Dr. C. Arseni, Clinic of Neurosurgery, Bucharest/Romania
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Christian disease and Letterer-Siwe disease. Pediatrics. 2 (1961) 307-327 Otani, S., J. Ehrlich: Solitary granuloma of bone simulating primary neoplasm. Am. J. Path. 4 (1940) 479-490 Kaaf, _/..- Eosinophilic granuloma of the skull. West J. Surg. (1945) 53-54 Racikov, B. M.: O variantah bolevogo sindoma pri eozinofilnoi granúleme kostei cerepa. Jurnal. Nevropat i Psihiatrii 5 (1966) 671-674 Rossenbeck, H. G..- Chronische disseminierte histiocytosis X mit eosinophilen Granulomen in der Schädelkaiotte, im Zwischenhirn - mit Diabetes insipidus - und in den Lungen. Frankfurt Z. Path. 77 (1967) 67-82 Schah er, £..- Über eine eigenartige Erkrankung des kindlichen Schädels (Osteomyelitis mit eosinophiler Reaktion). Zbb. allg. Path. 71 (1938) 113-117 Schuknecht, H. F., Terlman: Hand-Schüller-Christian-Disease
Cranial Eosinophilic Granuloma C. Arseni, L. Dánáila, Al. Constantinescu
Summary Investigations were carried out on 27 cases of cranial eosinophilic granuloma: 16 males (59%) and 11 females (41%). The mean age was 25 years, the extremes being 2 years and 65 years. The location in 21 cases (80 %) was exclusively in the calvarium (9 frontal, 8 parietal, three occipital and 1 temporal), orbital in two cases, fronto-orbital one case, base of the skull in the left parasellar region one case, left frontal subdural with chronic subdural haematoma one case and one case left occipital and petrosal bone. All the cases were diagnosed histologically. In 18 cases the tumour was removed at operation. Recurrences occurred in four of these cases (15 %), three of whom died (11-5 %). Four of the patients received steroid therapy and four steroid therapy combined with X-ray therapy. The evolution was favourable in all these cases. Key words: Cranial tumour - eosinophilic granuloma - subdural haematoma.
Zusammenfassung Es wurden Untersuchungen durchgeführt in 27 Fällen von kranialen eosinophilen Granulomen: 16 Männer (59 %) und 11 Frauen (41 %). Das Durchschnittsalter betrug 25 Jahre, die Extremwerte lagen bei 2 und bei 65 Jahren. Die Lokalisation war in 21 Fällen (80 %) ausnahmslos im Bereich des Schädeldaches (9 frontal, 8 parietal, 3 occipital und 1 temporal), orbital in 2 Fällen, frontoorbital in einem Fall, im Bereich der Schädelbasis links parasellär in einem Fall, links frontal subdural mit chronischem subduralen Hämatom in einem Fall und schließlich ein Fall links occipital und im Bereich des Felsenbeines. Alle Fälle wurden histologisch diagnostiziert. In 18 Fällen wurde die Geschwulst chirurgisch entfernt, davon traten Rezidive in 4 Fällen (15 %) auf, drei von diesen starben (11,5 %). 4 der Patienten erhielten Kortikoide allein und 4 erhielten Kortikoide in Kombination mit einer Röntgenbestrahlung. Der Verlauf war in all diesen Fällen günstig.
Following the details related by Schairer (1938) concerning eosinophilic granuloma, Lichtenstein and ]affé (1940) mentioned three different cases, communicated previously, and discussed one of their own cases. Otani and Ehrlich. (1940), with reference to seven cases, were the first to use the term eosinophilic granuloma. Layani and Aschkenzy (1948) emphasized the diagnostic value of biopsy puncture of the tumour. Lightwood et al. (1955) reported on 16 cases. Casan (1956), in his doctor's thesis, gathered 150 cases published in the special literature. Jelsma (1959) had six patients and Efremov and Beruciashvili (1960) seven patients. Oberman (1961) published comments on 40 cases, and Turpin et al. (1965) on 63 cases apart from his own patients. Racikov's study (1966) included 30 such cases, studied especially from the viewpoint of pain symptoms. Isolated cases were published by Green (1942), Raaf (1945), Thaunhauser (1947), Farin et al. (1958), Beier et al. (1963), etc. The present study includes 27 cases of eosinophilic granuloma of the skull, referred to our clinic between 1935 and 1976.
Discussion of the cases Sex. Of the 27 cases 16 (59 %) were males and 11 (41 %) females. Jelsma (1959) reports an equal distribution of the sexes, the same as Tönnis and Schettles (1967), whereas Lichtenstein and Jaffé (1940) maintain that the male sex is predominantly affected (75 % ) . Age. The age of our patients ranged between 2 and 65 years, being in the mean 25 years. From Table 1 it may be seen that the incidence was higher under the age of 40 (21
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Clinic of Neurosurgery, Bucharest •— Romania
190
C. Arseni, L. Dänäilä, Al. Constantinescu
Age
1-5
6-10
11-20
21-30
M
0
2
6
3
F
3
0
1
0
5
2
0
11
Total
3
2
7
3
7
4
1
27
cases) and the occurrence rare after the age of 50 years. Most of Jelsma's patients were in early adult life. Tönnis et al. (1967) asserted that the disease chiefly affects individuals under the age of 20 years. Localization. The skull is prevalently affected by eosinophilic granuloma, being involved according to Gerlach (1974) in two thirds of the cases. The calvarium was exclusively affected in 21 (80 °/o) of the 27 cases: eight parietal, of which one recurred in the frontal area and opposite parietal area (in a mirror), nine frontal, of which one with a double frontal and parietotemporal lesion on the same side, three occipital and one temporal; two orbital localisations (one 44 year-old patient presented, one month after extirpation of a tumour in the infero-external angle of the left orbit, signs of compression of the brain, due to extension of the tumour intracranially in the left fronto-temporal area; he died five weeks later), one unilateral fronto-orbital eosinophilic granuloma appeared on the opposite side and extended after two months to the calvarium, 10th rib, hip bone and femur, one case at the base of the left parasellar area, one case in which the external third and base of the left petrous bone were affected but which also presented a left occipital eosinophil granuloma about the size of half a walnut, and an exceptionally rare case of left frontal subdural location with a chronic subdural haematoma. Among the multiple but also primary locations of eosinophilic granuloma, other parts of the skeleton may also be invaded:
2
31-40
41-50
2
over 50
Total
1
16
ribs, spinal column (we had two cases in which the spine alone was affected), hip-bone, proximal parts of the bones of the extremities and mandible Jelsma considered that the lesion occurred most frequently in the parietal area but did not find multiple lesions in his patients. Northfield (1962) considers that eosinophilic granuloma may be single or multiple and the skull is more frequently affected than the pelvis, long bones, scapula and phalanges. Lesions of the soft tissues and internal organs (skin, kidneys, gastrointestinal tract, lungs, liver, brain, etc.) have also been described in isolated cases. Bingas (1974) maintains that eosinophilic granuloma affects especially the temporoparietal region, then the orbital and less frequently the petrosal, sellar and sphenoid areas. In 60 % of the cases the lesions are solitary, but multiple lesions may affect the skull, ribs, pelvis, upper and lower jaw and metaphysis of the long bones.
Pathological
anatomy
Gross examination. The tumour varies in size from a cherry to an apple. After detaching the scalp which the tumour does not infiltrate, a purplish capsule appears which discharges a greyish-yellow semifluid substance. The yellowish colour is due to lipoid necrosis and the grey to haemorrhagic foci. Rarely the tumour takes on (in the fronto-orbital locations) a yellowish-red, fatty consistence. The external layer of the dura is always invaded. The tumour seldom extends through
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Table 1
the dura with intracranial involvement, as in the case of orbital lesions. Microscopy. The diagnosis is not difficult. All the cases were checked by microscopic examination, either after local biopsy or surgical removal of the tumour. There was a foamy appearance, with large mononuclears, a dense network of reticulin fibres in which different types of cells were interspersed: eosinophil granulocytes distributed in clusters, myelocytes, lymphocytes, plasma and giant cells. During recovery, reorganising connective tissue may be seen, with prevalent fibrous changes of varying degree and even imperfect osteogenesis. In general, the disease is characterized histologically by multiple granulomas and a great number of eosinophils. According to Paillas (cited by Arseni and Marinesca 1969) eosinophil granulomas develop in four phases (also encountered in Hand-Schüller-Christian disease), the histologic aspect depending on the age of the lesion: (1) proliferative hyperplastic phase with reticulo-histiocytes, abundant eosinophils and necrotic, haemorrhagic foci; (2) granulomatous phase with hyperplasia and proliferation of newly formed vessels, granulomatous and reticular cells, histiocytes, considerable eosinophilic infiltration, necrosis and incipient lipoid phagocytosis, multinucleate giant cells in the vicinity of the haemorrhagic and necrosed areas; (3) xanthomatous phase with the presence of foam cells, either isolated or in nests, marking lipoid overloading, a diminution of eosinophils and the beginning of remission; (4) fibrous phase that precedes ossification and cicatrisation, leading to spontaneous recovery or healing after irradiation and steroid therapy. This subdivision into four phases of development is purely theoretical, since the characteristics of the four phases may often be encountered in the same section.
191
Pathogenesis. Eosinophil granuloma was intitially considered to be a form of HandSchiiller-Christian disease (Engelbreth-Holm et al. 1944). In view of the benign character of the disease and its predominant cranial localisation this idea was opposed by ¡Viertens and Ullerich (1954), who regarded it as a separate entity. Schuster and Flynn (1954) inclined towards an infectious origin of the disease, and Otani et al. (1940) believed that either infection or trauma may be the causative agent. According to Jalsma (1959) the cause is not known, but various authors have associated it with xanthomatosis. There is, however, a marked difference between the symptoms, age incidence and cranial form of the two diseases. Rossenbeck (1957) showed that there is still debate concerning the distinction between eosinophilic granuloma and HandSchüller-Christian disease, their possible relationship being in turn denied or sustained. Knighton and Fox (1956) thought it to be a primary disease of the reticulo-endothelial system. Efremov et al. (1960) showed that it was one of the least elucidated diseases of the reticulo-endothelial system. Siwe (cited by Oberman) considered eosinophil granuloma a local reaction to injury of the reticulo-endothelial system of the bone, without any tendency to generalisation. Jaffe and Lichtenstein (1944) established a relationship between eosinophil granuloma, Letterer-Siwe disease and Schiiller-Christian disease. Lichtenstein (1953) grouped together, under the name of "histiocytosis Y", eosinophil granuloma, Hand-Schüller-Christian disease and Abt-Letterer-Siwe disease, with various intermediate or transitional forms. He proposed this generic term in order to suggest the continuity of the three diseases belonging to the reticulo-endotheliosis group, representing different variants of the same pathological process, initially characterized cytologically by the presence of a large number of histiocytes, with a different clinical picture and evolution, related pathological
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Cranial Eosinophilie Granuloma
C. Arseni, L. Dänäilä, AI. Constantinescu
substrate (granuloma), histologic characteristics proper to each disease and an unpredictable prognosis. This unitary concept of the three diseases was not readily accepted and was initially opposed even by Lichtenstein himself, only to be accepted subsequently by most authors (Lahey 1962). A few sustained the opinion of Otani et al. who only recognize involvement of the reticulo-endothelial system as a common factor of the three diseases. Age and the initial location of the morbid process appear to play a decisive role in determining one or other clinical form of histiocytosis. Northfield (1962) asserts that eosinophilic granuloma is related to Letterer-Siwe and Hand-Schüller-Christian diseases and may also be associated with purpura (Swann and Williams 1953). Many authors consider it as an established Letterer-Siwe disease, being a different phase of one and the same pathological process of the reticolo-endothelial system. Today, it is generally agreed that eosinophilic granuloma may be considered as a benign type of histiocytosis X, with an exaggerated development of the reticulo-endothelial elements, whereas Abt-Letterer-Siwe disease is a malignant form (Bingas 1974). The evolution of Hand-Schüller-Christian disease stands between these two extremes. Owing to the obscure pathogenesis of these diseases, many terms have been used as synonyms for eosinophilic granuloma or histiocytosis X, such as: myeloma with eosinophilic cells, solitary granuloma of the bone [Otani and Erlich 1940), histiocytic granuloma, benign granuloma, destructive granuloma of the bone, eosinophilic reticuloma, benign reticulosis of the bones, reticuloma of the spinal cord (Knochenmark-Retikulom), granular reticulosis (Schuknecbt et al. 1948), eosinophilic granulo-reticuloma (Burkhardtand Fischer 1970), histiocytic reticulo-endotheliosis (Lightwood et al. 1955), idiopathic histiocytosis (Oberman 1961), reticulo-endo-
thelial granuloma, systemic or primary granulomatosis, eosinophilic xanthomatous granuloma, histiocytic granulomatous disease (Turpin et al. 1955). We fully agree with Gerlach's opinion (1974) according to which the term eosinophilic granuloma appears to be the most satisfactory. Symptoms. Onset. During the incipient phase when the morbid process develops only intradiploically, the disease is asymptomatic, as proven by a patient admitted to the Clinic for spasmodic torticollis. X-ray of the skull, performed for another purpose showed in the parietal region a small eosinophilic granuloma, that was completely symptomless. The most frequent presenting symptom however is pain, of which 12 patients complained (44-4 °/o). Initially, a local soreness developed, the patient complaining that the place was tender when he combed his hair, or washed or put a hat on, although nothing could be palpated locally. The lesion at first shows a tendency to grow through the outer table of the skull (phase II), invading the pericranium and even the muscles, and only subsequently infiltrating the dura (phase III). The pain then becomes more intense and spreads towards the periphery of the lesion, taking on the aspect of hemicrania or attacks of migraine, accompanied by nausea, vomiting, sometimes fever, a poor general condition, insomnia, irritability, that become more and more frequent until the headaches become permanent. In this phase the tumour develops and can be palpated. In phase III when the lesion affects the meninges the pains are intense, diffuse, continuous but superficial, not in the form of internal pressure as in raised intracranial pressure. In 2 cases the pains became persistent after a local injury. In one of these two patients, with an orbital lesion, the onset was marked by hemicrania on the side of the lesion, accompanied by nausea, vomiting and ptosis that disappeared between the attacks. Three months after the onset of the migraine, these
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Cranial Eosinophilie Granuloma
One patient came to hospital because of a feeling of numbness of the head on the side of the lesion. In the patient with eosinophilic granuloma at the base of the left parasellar area the onset was marked by diplopia and ptosis. A 31-year-old patient, was operated on for a chronic left frontal subdural haematoma; the small fleck found proved to be an eosinophilic granuloma, which came as a surprise to us. The patient, after suffering a slight head injury, had been complaining for five weeks before admission, of diffuse headaches, right hemiparesis and speech disturbances. The interval elapsing between the first symptom and admission was on average nine months, with extremes of five days and four years. Nine of the 27 patients (33-3 °/o) had 13 Neurochirurgia 20,6
suffered an injury at the site where the eosinophilic granuloma developed. On admission, 16 of the 21 cases with an eosinophilic granuloma of the calvarium presented a visible localised swelling and only five had pain. The cranial tumour was never larger than an apple and generally smaller, doughy, resistent, rarely fluctuating, painless in four cases and tender in the others, non-pulsatile, adherent to the deep structures but not to the skin; a slight underlying shelf-like edge, smaller than the extent of the tumour, could sometimes be palpated. One of the two cases with an orbital lesion presented ptosis, exophthalmos, paresis of the common and external oculomotor nerve, mydriasis, blindness, pallor of the disk and intense pain in the left eyeball, on the side of the lesion located in the infero-external angle of the orbit. The other presented palpebral oedema and ptosis, slight exophthalmos, restricted outward movement of the globe of the eye, visible tumour in the outer third of the left orbital margin and local pains. The eosinophilic granuloma was located in the upper and outer angle of the left orbit. The patient with a fronto-orbital location was admitted in 1960, at the age of two years; she had been suffering from fever for three weeks, then a tumour developed in the outer half of the left orbital margin, which became enlarged in the cold. On admission, the tumour measuring 1-2 cm, was soft, painful and accompanied by exophthalmos and downward displacement of the eyeball. Through a left frontal flap an eosinophilic granuloma was removed. It had not extended through the dura but had eroded the frontal bone, orbital margin and part of the orbital roof. The child was well until January 1961, when the granuloma recurred and was extirpated. A month later a similar tumour developed on the right side, with exophthalmos and slight downward displacement of the eyeball. Through a right frontal flap the tumour removed. The child felt better for two months, but fever again developed, with
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symptoms became permanent and were accompanied by slight exophthalmos. In this phase, a diagnosis of ophthalmologic migraine and then of trigeminal neuralgia was made. In the other case, two months after the injury on the outer third of the supraorbital arch, a tumour developed. This was the second most frequent presenting symptom, observed in nine cases (33-3 °/o). In two of these cases it was accompanied by diabetes insipidus, and one patient presented general epileptic seizures and ambulatory automatism. In one case a localised depression appeared three weeks after appearance of the tumour. In five cases the tumour developed after local trauma. However, pains do not always appear in the second phase when the tumour has extended outwards beyond the bone. This was the case in three patients who had no pains at first. In three children the onset was febrile; in two the tumour appeared shortly after the fever and meningeal reaction and the third suffered for about two years from headaches and a subfebrile state without any apparent cause until a small painless tumour developed in the occipital region. Another patient was admitted because of a slightly punched-out area on the skull.
193
C. Arseni, L. Dânàxla, Al. Constantinescu
diabetes insipidus, enlargement of rhe liver and spleen, pale skin, loss of weight, bilateral ptosis and slight psychomotor agitation. The X-ray revealed an occipital and two parietal round osteolytic areas measuring 1 cm in diameter, one on the tenth rib, ilium and upper third of the femur on the right side. The other investigations revealed increased ESR, leucocytosis with eosinophilia, anaemia, anisocytosis and anisochromia. The sternal puncture showed marked lymphocytic hyperplasia, hypoplasia of the red cells, shift to the left of both series, especially the red one. No Hand-Schüller-Christian cells were found. The child was taken home and died a week later. A left parasellar location at the base of the skull was found in an 18-year-old patient, who developed diplopia and left-sided ptosis two months before his admission on December 29, 1971. The presenting signs were paresis of the left oculomotor nerve, moderate exophthalmos and diplopia. The X-ray showed destruction of the sella turcica and sphenoid sinus Arteriography showed unfolding of the left carotid siphon and scintigraphy with 90Tc a left para- and retrosellar zone of moderate hyperactivity. Through a left temporal craniotomy a grey parasellar tumour was partly extirpated. The histological examination showed it to be an eosinophilic granuloma. After a short period of remission, hypoaesthesia of the left trigeminal 1st and 2nd divisions, optic atrophy, left blindness and diabetes insipidus developed. Lindlar
(1970) postulated that the endocrine disturbances were brought about by a reticulo-granuloma of the hypothalamus. A month later the patient was again operated on, and a recurrent tumour was partly removed; she died on the third day after the operation. A four-year-old little girl presented with a petrosal lesion. She had been suffering for the last three months from pains in the left ear, left suppurative otitis and a painless, soft tumour, about the size of half a walnut, which appeared in the left occipital region two months before her admission on August 2, 1954. The X-ray showed occipital lysis, with a maplike aspect extending further than soft tumour, and in the outer third and basal region of the left petrous bone, an area of destruction measuring 1-6 cm. The occipital tumour, an eosinophilic granuloma, was extirpated and the petrosal granuloma healed spontaneously, without cortisone or X-ray therapy. The patient subsequently became an employee of our Hospital and was followed up for a further 22 years. She still feels quite well. According to Kormann (1964) location in the petrous bone may produce the GradenigoLannois syndrome, with paralysis of the abducens and trigeminal nerves, headache and cerebellar signs, when the lesion is in the internal half of the petrosal bone; in the external half it may produce suppurative otitis and mastoiditis. Ancillary examinations. The most important is the X-ray examination, which may re-
Fig. 1: (a) Round, parietal osteolysis, (b) Long, angular parieto-temporal osteolysis, (c) Round, frontal osteolysis with central sequestrum.
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194
Cranial Eosinophilic Granuloma
acteristic of eosinophilic granuloma. The differential diagnosis has to be established from osteomyelitis, sarcoma, metastases, plasmacytoma, meningioma, tuberculous osteoma,
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veal a round (fig. la), oval or long angulate (fig. lb) osteolytic area, as a rule empty and only exceptionally with a central sequestrum ( % lc). Initially, the lesion is intradiploic (fig. 2a) and asymptomatic and may only be discovered casually. In the second phase the tumour destroys the outer table and extends outwards (fig. 2b), as revealed by tangential Xray views. In the third phase the tumour also invades the inner table (fig. 2c) and reaches the dura. Most patients are admitted to hospital at this stage. The lesion may be single as in fig. 1, double (fig. 3) or multiple, taking on a map-like aspect, with irregular contour due to the agglomeration of many cavities (fig. 4a, b, c, d). It contrasts with the neighbouring normal bone, is not decalcified and shows no endosteal or periosteal perifocal reaction. A postoperative recurrence may occur, either on the opposite side or in other bones of the head or body, as in the child with a fronto-orbital location. These lytic areas are fairly sharply demarcated, with absent or hazy reactive changes, not resembling dermoid or epidermoid tumours, as demonstrated by Arseni, Dänäilä and Constantinescu (1975).
195
In general, the X-ray is characterized by circumscribed lysis of the bone without surrounding sclerosis; this is actually of diagnostic value in youthful subjects. When the base of the skull or the orbit is involved, the radiological diagnosis is more difficult, and tangential views or tomographs alone may reveal the existence of an osteolytic process. Jelstna describes an irregular, punched-out area of decreased density, without any sunburst appearance on tangential views as in haemangioma. For Févre (1957) the radiographic image of a depressible swelling is characteristic. Leger (1947) proposed the term of "mottled porosity". During the process of recovery the lesion is surrounded by a fine area of sclerosis of the bone, suggesting reaction of the neighbouring tissue. The X-ray image is not, however, char13*
Fig. 2: (a) Tangential X-ray in phase I: the lesion is intradiploic. (b) Tangential X-ray in phase II: the tumour has destroyed the outer table and extrudes, (c) Tangential X-ray in phase III: the tumour has now also destroyed the inner table of the skull.
C. Arseni, L. Dänäilä, Al. Constantinescu graphy, scintigraphy, pneumoencephalography, electroencephalography and examination of the cerebrospinal fluid are as rule normal. Blood tests performed in 22 cases only revealed eosinophilia in eight cases. In three of these cases lymphocytosis was also present, in four anaemia (two anisocytosis and anisochromia) and in four cases elevated ESR values. These tests were normal in the other 14 patients. Sternal puncture performed in four cases, only revealed anomalies in the case of fronto-orbital tumour, described above.
Fig. 3: Bilateral frontal osteolysis.
and parieto-temporal
osteomyeloma, solitary myeloma, syphilis, etc. The other ancillary examinations - arterio-
Electrophoresis performed in one case showed 0-7680/o proteins (Kingsley method), 1/4 albumin/globulin ratio, 5-91 °/o albumins, 6-75 alpha-globulins, 9-50 alpha 2 -globulins, 10-80 beta-globulins, 13-85 gamma-globulins.
Fig. 4: Map-like appearance: (a) Recurrent eosino philic granuloma, initially parietal then extending frontally (b) and subsequently parietally on the o pposite side (c), with recurrence towards the occipital area.
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Walthard and Zuppinger (1949) explain the essential eosinophilic nature of the granuloma by the migration of the eosinophils to the affected area. François et al. (1963) found increased ESR, gamma-globulins, alpha 2 -glycoproteins and lipoproteins. Mertens and Ullerich (1954) reported on an abnormal Thorn test in one case. Treatment. Surgical removal of the tumour was performed in 19 cases. Three of these patients died (granuloma of the base of the skull, recurrent orbito-frontal granuloma and orbital tumour that subsequently extended intracranially in the temporal region) after recurrence and renewed surgical intervention. In a 39-year-old patient (fig. 4) who had been suffering for three years from a small left parietal tumour the size of a hazelnut, the tumour had disappeared leaving a punchedout area in the bone. Six months before admission diabetes insipidus set in and the tumour again developed rapidly, measuring 2-0 cm in November 1968 when he was operated on. Four months later there was a recurrence of the left parietal tumour, which was extirpated. Two months after the second operation a left frontal tumour, the size of a plum, and a right parietal tumour, the size of an egg, developed, and were removed on August 30, 1969. In 1970, a right parieto-occipital tumour reached the size of an egg and was extirpated on February 6, 1971. X-ray therapy and cortisone were administered and the patient has remained quite well up to the present. The diabetes insipidus treated with pitressin showed marked improvement. Such cases should be treated, we believe, from the very beginning by a combined attack operation, X-rays, steroid therapy). In four cases of small eosinophilic granulomas, that were not visible or palpable and only caused local pains, X-ray and steroid therapy were employed, arresting the evolution of the tumour. In general, when the tumour bulges under the scalp and is clearly visible, operation followed by cranioplasty is
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recommended. The bone is resected by sharp dissection down to the healthy tissue and the dura curetted but not removed. De Sa (1959) doubts the effectiveness of irradiation and steroid therapy after operation. The lesion rarely regresses spontaneously. Cortisone alone or combined with X-ray therapy may only be applied in phase I and II, and necessitates constant surveillance of the patients. Waltbard and Zuppinger (1949) obtained good results with X-ray therapy in an inoperable case. Contradictory reports have been published concerning the value of corticosteroids and cytostatic agents. In general the evolution of eosinophilic granuloma is favourable and benign, although alarming symptoms, recurrences and death may occur. As a rule the duration is of months, seldom lasting years. Recurrences developed in four cases (15 °/o). There were three deaths (ll°/o).The prognosis depends on the initial location of the pathological process and the patient's age. The cases of solitary, isolated lesions of the bone have a good prognosis and recovery may occur spontaneously.
Conclusions - Eosinophilic granuloma more frequently affects the frontal and parietal bone and more rarely the occipital bone and orbit. - A single esosinophilic granuloma was found in 85 % of the cases, and multiple lesions in 15 %. - An eosinophilic granuloma of the calvarium develops in three phases: phase I intradiploic, phase II when the tumour develops outwards destroying the outer table of the skull and phase III when the morbid process extends inwards, destroying the inner table and invading the dura, but rarely extending beyond it. - The precise diagnosis can only be established by microscopic examination of the specimen removed surgically or by biopsy puncture. Notwithstanding, owing to the pro-
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Cranial Eosinophilie Granuloma
C. Arseni, L. Danäilä, AI. Constantinescu
gress of radiology and clinical experience and observation, a clinical diagnosis may also be established. - There is no characteristic X-ray image of eosinophilic granuloma. - Eosinophilic granuloma may be considered a precancerous state that may run a malignant course in a small number of cases. - Eosinophilic granuloma may be solitary, with recovery after operation, X-ray or steroidtherapy, or it may relapse, taking on a malignant character as in four of our cases (base of the skull, orbital, fronto-orbital and cranial) with a fatal outcome in 3 cases.
- The best results were obtained by radical surgery, excising up to the healthy bone tissue, with cranioplasty at the same session. - Treatment with cortisone or combined with X-ray therapy may give good results in phases I and II, but necessitates constant surveillance of the patients. Recurrences occurred in four cases (15 °/o). There were three deaths (11 °/o). - The prognosis depended upon the initial site of the morbid process, the patient's age and number of lesions. The solitary, isolated lesions had a good prognosis, with spontaneous recovery.
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