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Carcinoma of the maxillary sinus following Thorotrast instillation
Carcinoma
of the Maxillary Sinus Following Thorotrast Instillation A FURTHER
JOSEPH A. BUDA, M.D., JOHN J. CONLEY,
AND ROBIN RANKOW, M.D., New Yorlz, New York
M.D.
From tbe Departments of Surgery and Otolaryngology, College of Physicians and Surgeons, Columbia University, and tbe Head and Neck Service of the Presbyterian Hospital, New York, New York.
INCE the report
from this Institution in 1960 by Kligerman, Lattes and Rankow [I], of three cases of carcinoma of the maxillary sinus three addifolIowing Thorotrast@ instillation, tionaI cases of maxiIIary sinus carcinoma foIIowing Thorotrast instiIIation have come under our care. One of these cases was mentioned by these authors in an addendum to their report. This paper wiI1 present that case as we11 as two additiona cases which have had Thorotrast instiIIation into the maxiIIary sinus some years prior to the deveIopment of carcinoma of the maxiIIary sinus. Thorotrast is a radiopaque coIIoida1 soIution containing thorium dioxide in a dextrin medium. First introduced by BIiihbaum, Frik and KaIkbrenner [z] in 1928, it was used for a variety of roentgenographic studies. When used intravenously, the coIIoida1 particles are readily taken up by the ceIIs of the reticuIoendotheIia1 system. The organs which show the greatest concentration are the Iiver, spIeen, bone marrow and lymph nodes. PracticaIIy a11 of the thorium injected remains in the body throughout the Iifetime of the patient. During the disintegration of thorium, radiothorium is produced. This element, whose haIf-life is I .90 years, is chiefly responsibIe for the radioactivity. However, with the continuous decay of thorium, whose bioIogic haIf-Iife is 200 years, to mesothorium and the Iatter to radiothorium, there is a constant supply of radiothorium for an extended period of time. The carcinogenic properties of Thorotrast have been demon-
S
American
Journal of Surgery,
Volume 106, November 1063
REPORT
868
strated in experimental animals [3] and there are numerous cIinica1 reports of its apparent carcinogenic capacity [4,7]. Budin and CershonCohen [6] have discussed the latent period between the use of thorium and the discovery of tumor. Looney [7,8] has reviewed the problem of tumor production in man foIIowing Thorotrast administration. Baserga, Yokoo and Henegar [9] have tabulated a11 reported malignant tumors in man attributed to injection of Thorotrast. Hofer [IO] described a carcinoma of the maxillary antrum in a sixty-four year oId woman demonstrated ten years foIIowing Thorotrast instiIIation. Radioactivity was demonstrated in the specimen by means of exposure to photographic fiIm for five days. Gros et a1. [rr,rz] reported a case of carcinoma of the maxiIIary sinus in a thirty-six year old man fifteen years after instiIIation of Thorotrast into the antrum for contrast study. Radioactivity of the specimen was demonstrated by radioautograph. FruhIing, Gros and BatzenschIager [13] reviewed the probIem of Thorotrast induced tumors and mentioned the same case. Looney and CoIodzin [x4] reported one case of the occurrence of carcinoma of the maxiIIary sinus foIIowing Thorotrast instiIIation. Kligerman, Lattes and Rankow [I] reported three cases of carcinoma of the maxiIIary antrum foIIowing Thorotrast instiIIation. In a11 three cases radiopaque materia1 was evident in the antrum. In one case, significant radioactivity was demonstrated in the specimen. The folIowing case reports include a detaiIed presentation of the case included in the addendum of the report by Kligerman et al. [I], as we11 as two additiona cases. In a11 three
Carcinoma of Sinus FolIowing Thorotrast InstiIIation
FIG. I. (A-87229.) Photomicrograph (Originai magnification X 112.)
FIG. 2. (A-68613.) pattern. (Original
showing
Photomicrograph showing magnification X 112.)
squamous
mdtiple
celI carcinoma
nests
869
with areas of good and of poor
of squamous
cell carcinoma
with
differentiation,
a highly
invasive
Buda, ConIey and Rankow CASE
CASE
REPORTS
The patient was a seventy year oId woman who was admitted on May 8, 1960, with a complaint of a discharge from the roof of her mouth. Past history incIuded asthma, chronic sinusitis and severa food alIergies. She gave a history of roentgenographic studies of her sinuses with Thorotrast about twenty years prior to this admission. Examination reveaIed a draining fistuIa in the right upper gingivo-buccal suIcus. Roentgenograms showed destruction of the IateraI and media1 waIIs of the right maxiIIary antrum as we11 as three large, irregular radiopaque objects in the antrum. A biopsy specimen was taken of the tumor in the antrum and three foreign bodies of wax-Iike consistency were removed from the antrum. Biopsy diagnosis was squamous ceII epithelioma of the right maxiIIary sinus. (Fig. I.) On May 17, 1960, a right radical maxiIIectomy was done. AnaIysis by means of a scintiIIation detector and a 256 channel anaIyzer of the materia1 removed from the antrum showed radioactivity consistent with thorium and its decay products. I.
CASE II. The patient was a forty-nine year oId man who was admitted in May, 1958, with a chief compIaint of nasa1 discharge of one year’s duration. The patient’s past history incIuded chronic sinusitis and asthma. He gave a history of having had an injection into the right maxillary sinus about
FIG. 4. (B-1567.) Photomicrograph (Original magnification X 112.)
showing masses of tumor ceIIs in squamous sheets as we11as in gIand-Iike spaces. 870
Carcinoma
of Sinus FoIIowing
Thorotrast
InstiIIation
years following instillation of Thorotrast into the maxiIIary sinus are presented. 2. The carcinogenic effect of the radioactivity of thorium and its decay products is discussed. 3. The need for investigation of radiopaque material in the maxiIIary sinuses is re-emphasized.
twenty years before admission for aIIergy studies. Examination of the head and neck revealed a tumor of the right maxillary antrum invading the orbit and the right nasa1 cavity. Roentgenograms showed the destruction of the waIIs and floor of the antrum. On May 12, 1958, a right radical maxillectomy, including the orbit and its contents was performed. PathoIogic diagnosis was squamous cell epithelioma of the right maxillary sinus. (Fig. 2.) Gamma ray analysis of the tissue showed radioactivity consistent with that of thorium.
REFERENCES I. KLIGEKMAN,M., LATTES, R.
and RANI
CASE 111.
The patient was a forty-six year old white man first seen in September 1961 with a complaint of a draining oro-antral fistula of four months’ duration, foIlowing the extraction of several maxillary teeth. The patient gave a history of aIIergy and stated that he had had radiopaque materia1 injected into his sinus cavity for roentgenographic studies about fifteen years prior to this admission. At time of this admission roentgenograms of the right maxiIIa showed a foreign body in the antrum as well as destruction of the medial wall of the antrum with a mass projecting into the right nasal cavity. (Fig. 3.) Biopsy done on October 2, 1961, revealed squamous cell epithelioma of the right maxiIIary sinus. Since mucicarmin stains of the sections showed mucin secretions in the tumor celIs, the tumor was reclassified as carcinoma, muco-epidermoid type. (Fig. 4.) On October IO, 1961, a right radical maxillectomy was done. AnaIysis of the specimen by means of a scintilIation detector and a 256 channe1 anaIyzer showed radioactivity consistent with that of thorium and its decay products.
2. BL~~HBAUM,T., FRIK, K. and KALKBRENNER, M. Eine neue Anwendungsart der KolIoide in der Rontgendiagnostik. Forts&r. Geb. Rihtgenstrablen., 37: 18, 1928. 3. JOHANSEN, C. Carcinogenesis of thorium. Acta Unio. internat. contra &crum, 16: 425, 1960. 4. CATTELL. R. B. and KAHN. F. Thorotrast and carcindgenesis. Report of a case. J. A. M. A., 174: 413, 1960. 5. GARDXER, D. L. and OGILVIE, R. F. Late results of injection of thorotrast. J. I’d. P Butt., 78: 133, ‘959. 6. BUXN, E. and GERSHON-COHEN, J. The danger of cancer from thorotrast as a diagnostic medium. Am. J. Roentgenol., 75: I 188, 1956. 7. LOONEY, W. B. An investigation of the Iate clinical findings folIowing thorotrast (thorium dioxide) administration. Am. J. Roentgenol., 83: 163, 1960. 8. LOONEY. W. B.. HIRSCH., J. B.., COLADZIN. M. and STEDMAN, L. T. Tumor induction in man foIIowing thorotrast administration. Acta Unio. Internat. contra cancrum, 16: 435, 1960. 9. BASERGA, R., YOKOO, H. and HENEGAR, G. C. Thorotrast-induced cancer in man. Cancer, 13: 1021, 1960. IO. HOFEK. 0. Kieferhohlenkarzinom durch radiumhaItiges KontrastmitteI hervorgerufen. Deutscbe zabniirztl. Ztg., 7: 736, 1952. I I. GROS, C. M., FRUHLING, L., BATZENSCHLAGER,A. and KEILING, R. L’autoradiographie dans Ie cancer du au thorotrast. Acta C’nio. internat. contra cencrum, 16: 429, 1960. 12. GROS, C. M., FRUHLING, L. and KEILING, R. Injection de thorotrast dans Ie sinus maxillaire; r5 ans apres, apparition dun epithelioma malpighien. Bull. Assoc. frang. &de cancer, 42: 556,
COMMENTS
The cases reported here add to the mounting number which impIicate the persistent radioactivity of thorium as a carcinogenic hazard. The specimen, in a11 three cases, showed radioactivity consistent with that of thorium and its decay products. The latent period between injection and discovery of tumor in these three cases varied from fifteen to twenty years.
1955. 13. FRUHLLNC;, L., GROS, C. M., BATZENSCHLAGER, A. and DORNER, M. La maladie du thorotrast. Ann. m&d., 57: 297 and 409, 1956. 14. LOONEY, W. B. and COLODZIN, M. Late foIIow-up studies after internal deposition of radioactive materials. J. A. M. A., 160: I, 1956.
SUMMARY I. Three new cases of carcinoma of the maxiIIary sinus developing fifteen to twenty
871
of the Maxillary Sinus Following Thorotrast Instillation A FURTHER
JOSEPH A. BUDA, M.D., JOHN J. CONLEY,
AND ROBIN RANKOW, M.D., New Yorlz, New York
M.D.
From tbe Departments of Surgery and Otolaryngology, College of Physicians and Surgeons, Columbia University, and tbe Head and Neck Service of the Presbyterian Hospital, New York, New York.
INCE the report
from this Institution in 1960 by Kligerman, Lattes and Rankow [I], of three cases of carcinoma of the maxillary sinus three addifolIowing Thorotrast@ instillation, tionaI cases of maxiIIary sinus carcinoma foIIowing Thorotrast instiIIation have come under our care. One of these cases was mentioned by these authors in an addendum to their report. This paper wiI1 present that case as we11 as two additiona cases which have had Thorotrast instiIIation into the maxiIIary sinus some years prior to the deveIopment of carcinoma of the maxiIIary sinus. Thorotrast is a radiopaque coIIoida1 soIution containing thorium dioxide in a dextrin medium. First introduced by BIiihbaum, Frik and KaIkbrenner [z] in 1928, it was used for a variety of roentgenographic studies. When used intravenously, the coIIoida1 particles are readily taken up by the ceIIs of the reticuIoendotheIia1 system. The organs which show the greatest concentration are the Iiver, spIeen, bone marrow and lymph nodes. PracticaIIy a11 of the thorium injected remains in the body throughout the Iifetime of the patient. During the disintegration of thorium, radiothorium is produced. This element, whose haIf-life is I .90 years, is chiefly responsibIe for the radioactivity. However, with the continuous decay of thorium, whose bioIogic haIf-Iife is 200 years, to mesothorium and the Iatter to radiothorium, there is a constant supply of radiothorium for an extended period of time. The carcinogenic properties of Thorotrast have been demon-
S
American
Journal of Surgery,
Volume 106, November 1063
REPORT
868
strated in experimental animals [3] and there are numerous cIinica1 reports of its apparent carcinogenic capacity [4,7]. Budin and CershonCohen [6] have discussed the latent period between the use of thorium and the discovery of tumor. Looney [7,8] has reviewed the problem of tumor production in man foIIowing Thorotrast administration. Baserga, Yokoo and Henegar [9] have tabulated a11 reported malignant tumors in man attributed to injection of Thorotrast. Hofer [IO] described a carcinoma of the maxillary antrum in a sixty-four year oId woman demonstrated ten years foIIowing Thorotrast instiIIation. Radioactivity was demonstrated in the specimen by means of exposure to photographic fiIm for five days. Gros et a1. [rr,rz] reported a case of carcinoma of the maxiIIary sinus in a thirty-six year old man fifteen years after instiIIation of Thorotrast into the antrum for contrast study. Radioactivity of the specimen was demonstrated by radioautograph. FruhIing, Gros and BatzenschIager [13] reviewed the probIem of Thorotrast induced tumors and mentioned the same case. Looney and CoIodzin [x4] reported one case of the occurrence of carcinoma of the maxiIIary sinus foIIowing Thorotrast instiIIation. Kligerman, Lattes and Rankow [I] reported three cases of carcinoma of the maxiIIary antrum foIIowing Thorotrast instiIIation. In a11 three cases radiopaque materia1 was evident in the antrum. In one case, significant radioactivity was demonstrated in the specimen. The folIowing case reports include a detaiIed presentation of the case included in the addendum of the report by Kligerman et al. [I], as we11 as two additiona cases. In a11 three
Carcinoma of Sinus FolIowing Thorotrast InstiIIation
FIG. I. (A-87229.) Photomicrograph (Originai magnification X 112.)
FIG. 2. (A-68613.) pattern. (Original
showing
Photomicrograph showing magnification X 112.)
squamous
mdtiple
celI carcinoma
nests
869
with areas of good and of poor
of squamous
cell carcinoma
with
differentiation,
a highly
invasive
Buda, ConIey and Rankow CASE
CASE
REPORTS
The patient was a seventy year oId woman who was admitted on May 8, 1960, with a complaint of a discharge from the roof of her mouth. Past history incIuded asthma, chronic sinusitis and severa food alIergies. She gave a history of roentgenographic studies of her sinuses with Thorotrast about twenty years prior to this admission. Examination reveaIed a draining fistuIa in the right upper gingivo-buccal suIcus. Roentgenograms showed destruction of the IateraI and media1 waIIs of the right maxiIIary antrum as we11 as three large, irregular radiopaque objects in the antrum. A biopsy specimen was taken of the tumor in the antrum and three foreign bodies of wax-Iike consistency were removed from the antrum. Biopsy diagnosis was squamous ceII epithelioma of the right maxiIIary sinus. (Fig. I.) On May 17, 1960, a right radical maxiIIectomy was done. AnaIysis by means of a scintiIIation detector and a 256 channel anaIyzer of the materia1 removed from the antrum showed radioactivity consistent with thorium and its decay products. I.
CASE II. The patient was a forty-nine year oId man who was admitted in May, 1958, with a chief compIaint of nasa1 discharge of one year’s duration. The patient’s past history incIuded chronic sinusitis and asthma. He gave a history of having had an injection into the right maxillary sinus about
FIG. 4. (B-1567.) Photomicrograph (Original magnification X 112.)
showing masses of tumor ceIIs in squamous sheets as we11as in gIand-Iike spaces. 870
Carcinoma
of Sinus FoIIowing
Thorotrast
InstiIIation
years following instillation of Thorotrast into the maxiIIary sinus are presented. 2. The carcinogenic effect of the radioactivity of thorium and its decay products is discussed. 3. The need for investigation of radiopaque material in the maxiIIary sinuses is re-emphasized.
twenty years before admission for aIIergy studies. Examination of the head and neck revealed a tumor of the right maxillary antrum invading the orbit and the right nasa1 cavity. Roentgenograms showed the destruction of the waIIs and floor of the antrum. On May 12, 1958, a right radical maxillectomy, including the orbit and its contents was performed. PathoIogic diagnosis was squamous cell epithelioma of the right maxillary sinus. (Fig. 2.) Gamma ray analysis of the tissue showed radioactivity consistent with that of thorium.
REFERENCES I. KLIGEKMAN,M., LATTES, R.
and RANI
CASE 111.
The patient was a forty-six year old white man first seen in September 1961 with a complaint of a draining oro-antral fistula of four months’ duration, foIlowing the extraction of several maxillary teeth. The patient gave a history of aIIergy and stated that he had had radiopaque materia1 injected into his sinus cavity for roentgenographic studies about fifteen years prior to this admission. At time of this admission roentgenograms of the right maxiIIa showed a foreign body in the antrum as well as destruction of the medial wall of the antrum with a mass projecting into the right nasal cavity. (Fig. 3.) Biopsy done on October 2, 1961, revealed squamous cell epithelioma of the right maxiIIary sinus. Since mucicarmin stains of the sections showed mucin secretions in the tumor celIs, the tumor was reclassified as carcinoma, muco-epidermoid type. (Fig. 4.) On October IO, 1961, a right radical maxillectomy was done. AnaIysis of the specimen by means of a scintilIation detector and a 256 channe1 anaIyzer showed radioactivity consistent with that of thorium and its decay products.
2. BL~~HBAUM,T., FRIK, K. and KALKBRENNER, M. Eine neue Anwendungsart der KolIoide in der Rontgendiagnostik. Forts&r. Geb. Rihtgenstrablen., 37: 18, 1928. 3. JOHANSEN, C. Carcinogenesis of thorium. Acta Unio. internat. contra &crum, 16: 425, 1960. 4. CATTELL. R. B. and KAHN. F. Thorotrast and carcindgenesis. Report of a case. J. A. M. A., 174: 413, 1960. 5. GARDXER, D. L. and OGILVIE, R. F. Late results of injection of thorotrast. J. I’d. P Butt., 78: 133, ‘959. 6. BUXN, E. and GERSHON-COHEN, J. The danger of cancer from thorotrast as a diagnostic medium. Am. J. Roentgenol., 75: I 188, 1956. 7. LOONEY, W. B. An investigation of the Iate clinical findings folIowing thorotrast (thorium dioxide) administration. Am. J. Roentgenol., 83: 163, 1960. 8. LOONEY. W. B.. HIRSCH., J. B.., COLADZIN. M. and STEDMAN, L. T. Tumor induction in man foIIowing thorotrast administration. Acta Unio. Internat. contra cancrum, 16: 435, 1960. 9. BASERGA, R., YOKOO, H. and HENEGAR, G. C. Thorotrast-induced cancer in man. Cancer, 13: 1021, 1960. IO. HOFEK. 0. Kieferhohlenkarzinom durch radiumhaItiges KontrastmitteI hervorgerufen. Deutscbe zabniirztl. Ztg., 7: 736, 1952. I I. GROS, C. M., FRUHLING, L., BATZENSCHLAGER,A. and KEILING, R. L’autoradiographie dans Ie cancer du au thorotrast. Acta C’nio. internat. contra cencrum, 16: 429, 1960. 12. GROS, C. M., FRUHLING, L. and KEILING, R. Injection de thorotrast dans Ie sinus maxillaire; r5 ans apres, apparition dun epithelioma malpighien. Bull. Assoc. frang. &de cancer, 42: 556,
COMMENTS
The cases reported here add to the mounting number which impIicate the persistent radioactivity of thorium as a carcinogenic hazard. The specimen, in a11 three cases, showed radioactivity consistent with that of thorium and its decay products. The latent period between injection and discovery of tumor in these three cases varied from fifteen to twenty years.
1955. 13. FRUHLLNC;, L., GROS, C. M., BATZENSCHLAGER, A. and DORNER, M. La maladie du thorotrast. Ann. m&d., 57: 297 and 409, 1956. 14. LOONEY, W. B. and COLODZIN, M. Late foIIow-up studies after internal deposition of radioactive materials. J. A. M. A., 160: I, 1956.
SUMMARY I. Three new cases of carcinoma of the maxiIIary sinus developing fifteen to twenty
871