Clinical records Facial nerve paralysis caused by carcinoma developed in thorotrastoma in the parotid gland By N. J.
JOHNSEN,
S.
PRYTZ
and R.
ALBRECHTSEN
(Copenhagen)
Introduction nerve paralysis associated with parotid tumours is considered to be a criterion of malignancy (Eneroth, 1972). In the case presented here an unusual tumour, a so-called thorotrastoma in the parotid gland, was followed by persistent facial paralysis. A thorotrastoma is defined as a local granuloma caused by deposits of the X-ray contrast medium Thorotrast R (Dahlgren, 1967). It is well known that benign thorotrastomas in the neck sometimes cause paresis of anatomically related nerves (Backer et al., 1958; Blomquist and Freidenfeldt, 1959; Novik, i960). The tumour in our case was for that reason originally considered most probably benign, but was later proved to be malignant. FACIAL
Case report
V.H.M., a 59-year-old woman, was admitted in January 1974 for a tumour in the right parotid gland associated with an ipsilateral facial nerve paralysis. The tumour had been present for several years, without significant growth. During the month before admission she developed severe pain around the ear and a slowly progressive facial paralysis. Her past history included a sialography of the right parotid gland performed in 1946. Examination revealed a firm, indolent mass in the right parotid region the size of a hazelnut. It was not well defined and appeared to be deeply fixed. There was a partial right facial nerve paralysis of peripheral type, with normal nasolacrimal and stapedial reflex. Taste was reduced equally on both sides of the tongue. A fine-needle biopsy failed because the tumour was too haid. Only normal blood was aspirated. Malignant degeneration of a pleomorphic adenoma of the parotid gland was considered to be the most likely diagnosis and the first operation was performed under general anaesthesia on 10 January 1974. The gland was infiltrated by dense, tumour-like tissue, such that the main trunk of the facial nerve could not be isolated. Before the planned radical parodectomy two biopsies were sent for frozen section. To our great surprise the diagnosis was connective tissue with conspicuous pigment, without evidence of malignancy. The operation was therefore discontinued and the patient was from now on followed at regular intervals. The facial nerve paralysis slowly progressed and was complete after 6 months. However there was no growth of the remaining tumour until the check 10 months after the first operation. At that time a very rapidly growing tumour developed in the region. A new operation was performed on 19 December 1974. Biopsies now showed definite malignancy and a total parodectomy 571
N. J. Johnsen, S. Prytz and R. Albrechtsen together with a radical neck dissection on the right side was carried out. Because tumour infiltrated the skin, skin excision followed by transposition by Bacamjian's method was performed at the same session. The patient has been followed up since operation and a recurrence has been diagnosed by explorative biopsies in April 1975, so the prognosis in inevitable extremely poor. Pathology Microscopic investigation of paraffin sections from the parotid region in the first exploration (Fig. 1) showed nothing remaining of the normal structure of acini. The tissue was composed of dense connective tissue with thick collagen
FIG. 1 The first biopsy from the parotid region showed no remains of the normal structure of acini. Thorotrast granules were lying in the dense connective tissue between the collagen bundles, both extracellularly and in the cytoplasm of macrophages (H. and E. X250).
bundles, which in many places showed hyalin transformations. Inconspicuous vessels were found, without thrombosis or inflammation. In the connective tissue lying between the collagen bundles fine globules resembling yellowish-brown pigment were found, both extracellularly and in the cytoplasm of macrophages. Special staining of the pigment for iron and melanin was negative. There was no evidence of malignancy. The diagnosis was connective tissue with presumably thorotrast pigment. This was strongly supported by an X-ray of the region which revealed densely lobulated shadows (Fig. 2) and was definitively confirmed by autohistoradiography which showed emission from several thorium isotopes. Sections from the parotid gland removed 11 months later (Fig. 3) showed a poorly differentiated carcinoma in the connective tissue with Thorotrast granules lying between the collagen bundles. 572
Clinical records
FIG. 2 X-ray of the right parotid region showing densely lobulated shadows.
Discussion Thorotrast R , a colloid solution containing 25 per cent thorium dioxide, was introduced as an X-ray contrast medium in 1930 and was in regular use in many countries until about 1950. It was commonly used for cerebral angiography, but has also been used for other kinds of X-ray examinations (Dahlgren, 1961; Faber, 1967; da Silva Horta and de Motta, 1967). Thorotrast affords a good contrast. Unfortunately it has dangerous properties even when used appropriately. Thorium is radioactive with a half life of i-4Xio 1 0 years, and the radiation emitted consists of 90 per cent alpha, 9 per cent beta and I per cent gamma rays. After intravascular injection the colloidal solution accumulates in the reticulo-endothelial system, mainly in the liver, spleen and bone marrow, where it remains for life, and induces cirrhosis and in some cases malignant degeneration. The first case of a malignant tumour, an endothelial-cell sarcoma 573
N. J. Johnsen, S. Prytz and R. Albrechtsen
FIG. 3 Section from the removed parotid gland, showing a poorly differentiated carcinoma in the connective tissue with thorotrast granules (H. and E. x 250).
of the liver, was reported by MacMahon et al. (1947). After accidental extravascular or intracanalicular injection the Thorotrast remains at the site of injection and provokes the development of a local hard granuloma called a thorotrastoma. Since the use of thorotrast was forbidden follow-up investigations have revealed, in addition to an increasing incidence of cirrhosis, liver cancer, leukaemia and other serious blood diseases (Dahlgren, 1961; Johansen, 1967; Faber and Johansen, 1967; da Silva Horta and de Motta, 1967; Visfeldt and Poulsen, 1972), a large number of primary thorotrastomas in the neck following arteriography (Backer et al., 1958; Blomberg et al., 1963; Dahlgren, 1967; da Silva Horta and de Motta, 1967). In some cases these thorotrastomas have been associated with paresis of anatomically related cranial nerves, especially the recurrent laryngeal nerve, caused by excessive fibrosis (Backer et al., 1958; Blomquist and Freidenfeldt, 1959; Novik, i960), and in a few cases malignant tumours have developed in the vicinity of the thorotrastomas (Novik, i960; Blomberg et al., 1963). The complications are seen after a latent period of 10-35 years after the X-ray examination. New cases are continually reported. Thorotrast has probably not been used very often for sialography. Nevertheless, Verhaeghe et al. (1970) published a case which has many points of resemblance with our case. A thorotrastoma with palsy of the facial nerve was observed 34 years after parotid sialography. A total parodectomy was performed. The microscopic picture was identical with our first biopsy. There was no evidence of malignancy. 574
Clinical records Summary A carcinoma developed in a thorotrastoma of the right parotid gland and caused facial paralysis 28 years after a sialography with radioactive thorotrast. The literature is reviewed, and another case is reported in which facial nerve paralysis occurred without evidence of malignancy. REFERENCES BACKER, O. G., FABER, M., and RASMUSSEN, H. (1958) ActaChirurgica
Scandinavica,
115, 417. BLOMBERG, R., LARSSON, L. E., LINDELL, B., and LINDGREN,
E. (1963)
Ada
Radiologica, 1, 995. BLOMQUIST, C , and FREIDENFELDT, H. (1959) Opscula Medica, 4, 56. DAHLGREN, S. (1961) Ada Pathologica et Mikrobiologica Scandinavica, 53, 147. DAHLGREN, S. (1967) Annals of the New York Academy of Sciences, 145, 786. DA SILVA HORTA and DE MOTTA, L. C. (1967) Annals of the New York Academy
of Sciences, 145, 830. ENEROTH, C. M. (1972) Archives of Otolaryngology, 95, 300. FABER, M. (1967) Annals of the New York Academy of Sciences, 145, 843. FABER, M., and JOHANSEN, C. (1967) Annals of the New York Academy of Sciences, 145. 755JOHANSEN, C. (1967) Annals of the New York Academy of Sciences, 145, 724. MACMAHON, H. E., MURPHY, A. S., and BATES, M. I. (1947) American Journal of
Pathology, 23, 585. NOVIK, A. (1960) Acta Otolaryngologica, 52, 509. VERHAEGHE, M., ADENIS, L., DEMAILLE, A., and TOMEAU, M. (1970) Journal de
Chirurgie (Paris), 100, 271. VISFELDT, J., POULSEN, H. (1972) Ada Pathologica et Mikrobiologica Scandinavica, Section A, 80, 97. Niels Jon Johnsen, M.D., University E.N.T. Department, Rigshospitalet, Blegdamsvej 9, DK 2100 Copenhagen, Denmark.
575
JOHNSEN,
S.
PRYTZ
and R.
ALBRECHTSEN
(Copenhagen)
Introduction nerve paralysis associated with parotid tumours is considered to be a criterion of malignancy (Eneroth, 1972). In the case presented here an unusual tumour, a so-called thorotrastoma in the parotid gland, was followed by persistent facial paralysis. A thorotrastoma is defined as a local granuloma caused by deposits of the X-ray contrast medium Thorotrast R (Dahlgren, 1967). It is well known that benign thorotrastomas in the neck sometimes cause paresis of anatomically related nerves (Backer et al., 1958; Blomquist and Freidenfeldt, 1959; Novik, i960). The tumour in our case was for that reason originally considered most probably benign, but was later proved to be malignant. FACIAL
Case report
V.H.M., a 59-year-old woman, was admitted in January 1974 for a tumour in the right parotid gland associated with an ipsilateral facial nerve paralysis. The tumour had been present for several years, without significant growth. During the month before admission she developed severe pain around the ear and a slowly progressive facial paralysis. Her past history included a sialography of the right parotid gland performed in 1946. Examination revealed a firm, indolent mass in the right parotid region the size of a hazelnut. It was not well defined and appeared to be deeply fixed. There was a partial right facial nerve paralysis of peripheral type, with normal nasolacrimal and stapedial reflex. Taste was reduced equally on both sides of the tongue. A fine-needle biopsy failed because the tumour was too haid. Only normal blood was aspirated. Malignant degeneration of a pleomorphic adenoma of the parotid gland was considered to be the most likely diagnosis and the first operation was performed under general anaesthesia on 10 January 1974. The gland was infiltrated by dense, tumour-like tissue, such that the main trunk of the facial nerve could not be isolated. Before the planned radical parodectomy two biopsies were sent for frozen section. To our great surprise the diagnosis was connective tissue with conspicuous pigment, without evidence of malignancy. The operation was therefore discontinued and the patient was from now on followed at regular intervals. The facial nerve paralysis slowly progressed and was complete after 6 months. However there was no growth of the remaining tumour until the check 10 months after the first operation. At that time a very rapidly growing tumour developed in the region. A new operation was performed on 19 December 1974. Biopsies now showed definite malignancy and a total parodectomy 571
N. J. Johnsen, S. Prytz and R. Albrechtsen together with a radical neck dissection on the right side was carried out. Because tumour infiltrated the skin, skin excision followed by transposition by Bacamjian's method was performed at the same session. The patient has been followed up since operation and a recurrence has been diagnosed by explorative biopsies in April 1975, so the prognosis in inevitable extremely poor. Pathology Microscopic investigation of paraffin sections from the parotid region in the first exploration (Fig. 1) showed nothing remaining of the normal structure of acini. The tissue was composed of dense connective tissue with thick collagen
FIG. 1 The first biopsy from the parotid region showed no remains of the normal structure of acini. Thorotrast granules were lying in the dense connective tissue between the collagen bundles, both extracellularly and in the cytoplasm of macrophages (H. and E. X250).
bundles, which in many places showed hyalin transformations. Inconspicuous vessels were found, without thrombosis or inflammation. In the connective tissue lying between the collagen bundles fine globules resembling yellowish-brown pigment were found, both extracellularly and in the cytoplasm of macrophages. Special staining of the pigment for iron and melanin was negative. There was no evidence of malignancy. The diagnosis was connective tissue with presumably thorotrast pigment. This was strongly supported by an X-ray of the region which revealed densely lobulated shadows (Fig. 2) and was definitively confirmed by autohistoradiography which showed emission from several thorium isotopes. Sections from the parotid gland removed 11 months later (Fig. 3) showed a poorly differentiated carcinoma in the connective tissue with Thorotrast granules lying between the collagen bundles. 572
Clinical records
FIG. 2 X-ray of the right parotid region showing densely lobulated shadows.
Discussion Thorotrast R , a colloid solution containing 25 per cent thorium dioxide, was introduced as an X-ray contrast medium in 1930 and was in regular use in many countries until about 1950. It was commonly used for cerebral angiography, but has also been used for other kinds of X-ray examinations (Dahlgren, 1961; Faber, 1967; da Silva Horta and de Motta, 1967). Thorotrast affords a good contrast. Unfortunately it has dangerous properties even when used appropriately. Thorium is radioactive with a half life of i-4Xio 1 0 years, and the radiation emitted consists of 90 per cent alpha, 9 per cent beta and I per cent gamma rays. After intravascular injection the colloidal solution accumulates in the reticulo-endothelial system, mainly in the liver, spleen and bone marrow, where it remains for life, and induces cirrhosis and in some cases malignant degeneration. The first case of a malignant tumour, an endothelial-cell sarcoma 573
N. J. Johnsen, S. Prytz and R. Albrechtsen
FIG. 3 Section from the removed parotid gland, showing a poorly differentiated carcinoma in the connective tissue with thorotrast granules (H. and E. x 250).
of the liver, was reported by MacMahon et al. (1947). After accidental extravascular or intracanalicular injection the Thorotrast remains at the site of injection and provokes the development of a local hard granuloma called a thorotrastoma. Since the use of thorotrast was forbidden follow-up investigations have revealed, in addition to an increasing incidence of cirrhosis, liver cancer, leukaemia and other serious blood diseases (Dahlgren, 1961; Johansen, 1967; Faber and Johansen, 1967; da Silva Horta and de Motta, 1967; Visfeldt and Poulsen, 1972), a large number of primary thorotrastomas in the neck following arteriography (Backer et al., 1958; Blomberg et al., 1963; Dahlgren, 1967; da Silva Horta and de Motta, 1967). In some cases these thorotrastomas have been associated with paresis of anatomically related cranial nerves, especially the recurrent laryngeal nerve, caused by excessive fibrosis (Backer et al., 1958; Blomquist and Freidenfeldt, 1959; Novik, i960), and in a few cases malignant tumours have developed in the vicinity of the thorotrastomas (Novik, i960; Blomberg et al., 1963). The complications are seen after a latent period of 10-35 years after the X-ray examination. New cases are continually reported. Thorotrast has probably not been used very often for sialography. Nevertheless, Verhaeghe et al. (1970) published a case which has many points of resemblance with our case. A thorotrastoma with palsy of the facial nerve was observed 34 years after parotid sialography. A total parodectomy was performed. The microscopic picture was identical with our first biopsy. There was no evidence of malignancy. 574
Clinical records Summary A carcinoma developed in a thorotrastoma of the right parotid gland and caused facial paralysis 28 years after a sialography with radioactive thorotrast. The literature is reviewed, and another case is reported in which facial nerve paralysis occurred without evidence of malignancy. REFERENCES BACKER, O. G., FABER, M., and RASMUSSEN, H. (1958) ActaChirurgica
Scandinavica,
115, 417. BLOMBERG, R., LARSSON, L. E., LINDELL, B., and LINDGREN,
E. (1963)
Ada
Radiologica, 1, 995. BLOMQUIST, C , and FREIDENFELDT, H. (1959) Opscula Medica, 4, 56. DAHLGREN, S. (1961) Ada Pathologica et Mikrobiologica Scandinavica, 53, 147. DAHLGREN, S. (1967) Annals of the New York Academy of Sciences, 145, 786. DA SILVA HORTA and DE MOTTA, L. C. (1967) Annals of the New York Academy
of Sciences, 145, 830. ENEROTH, C. M. (1972) Archives of Otolaryngology, 95, 300. FABER, M. (1967) Annals of the New York Academy of Sciences, 145, 843. FABER, M., and JOHANSEN, C. (1967) Annals of the New York Academy of Sciences, 145. 755JOHANSEN, C. (1967) Annals of the New York Academy of Sciences, 145, 724. MACMAHON, H. E., MURPHY, A. S., and BATES, M. I. (1947) American Journal of
Pathology, 23, 585. NOVIK, A. (1960) Acta Otolaryngologica, 52, 509. VERHAEGHE, M., ADENIS, L., DEMAILLE, A., and TOMEAU, M. (1970) Journal de
Chirurgie (Paris), 100, 271. VISFELDT, J., POULSEN, H. (1972) Ada Pathologica et Mikrobiologica Scandinavica, Section A, 80, 97. Niels Jon Johnsen, M.D., University E.N.T. Department, Rigshospitalet, Blegdamsvej 9, DK 2100 Copenhagen, Denmark.
575
