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Carcinoid tumor of the thymus with multiple endocrine adenomatosis
Path. Res. Pract. 175, 404-409 (1982) I
,
!
.
,'!
Air Force and Veterans AdmlmstratlOn General Hospital, Athens, Greece
Carcinoid Tumor of the Thymus with Multiple Endocrine Adenomatosis D. FLOROS*, TH. DOSIOS**, A. TSOURDIS**\ and N. YIATROMANOLAKIS****
Summary A rare case of carcmOld tumor of the thymus m a male patient aged 32 With multiple endocrme adenomatosIs type I IS reported. The histologic features, the diagnostic cntena and the pathogenesIs of the tumor are bnefly discussed,
Introduction Carcinoid tumors m patIents with multiple endocnne adenomatosis (MEA) or Wermers syndrome (Wermer, 1954) have been described by several authors (Fisher and Hicks, 1960; Williams and Celestin, 1962; Snyder et al., 1972). Almost all of these carcmoid tumors have been primary in foregut denvatives. CarcinOld tumor of the thymus associated WIth MEA is a very rare condItion described fust by Rosal et al., (1972) in three patIents. Since then another seven cases have been reported (Hill, 1967; Case 5, 1969; Manes and Taylor, 1973; Rosal and Levme, 1976). Our case, the eleventh one m the literature, IS another example of a carcmOld tumor of the thymus associated WIth MEA syndrome (Type I).
Case Report A 32 year old white male was admitted to Air Force and Veterans AdmmlstratlOn General Hospital m Athens for an enlargement of the antenor superior medlastmum which was found • Director of Pathology Laboratory •• Department of Surgery, DIVISion of ThoraCIC Surgery Director of Department of Endocrmology * * Head of Chest Diseases umt
*..*.
CarcinOid Tumor Thymus . 405
Fig. 1. PA chest roentgenogram showmg a huge well defmed medlastmal mass, extendmg outside the left cardiac border.
incidentally after a routme chest X-ray exammatlOn (Fig. 1). Two years prevIOusly the patient had hypoglycaemlc crises. Repeated fastmg blood sugar exammatlOns at that time revealed values of 31,29,26, 17 and 23 mg/lOO ml with Simultaneous blood msulm levels 18,23,22,50, and 37 j,tu/ ml respectively. At laparatomy two nodules with a diameter of 1,5 cm each were removed from the pancreas. The histological examinatIOn of these nodules showed the typical fmdmgs of the Islet-cell adenoma with no signs of mahgnancy The postoperative course of the patient was uneventful and he was completely asymptomatic after the operatIOn. HIS blood sugar level and blood msulm level returned to normal values. It should be noted that the patient had a hypercalcemia (13 mg/100 mil preoperatively which subsided after the operatIOn. ExammatlOn of the patient at thiS second admiSSIOn was unremarkable. Fluoroscopy showed that the mediastinal mass transmitted the cardiac pulses. C. T. scannmg of mediastinum showed a sohd tumor, which appeared to be adherent to the anterior surface of the left ventricle of the heart. At thoracotomy the tumor was found occupymg the entire anterior-superior medlastmum, where the thymus should be found normally and was attached to the pericardIUm. Wide radical eXCISIOn of the tumor mcludmg the anterior superior portIOn of the pericardIUm was performed. The tumor was dissected eastlv from the surroundmg tissues. Lymph nodes were not palpable. The postoperative course was uneventful and the patient was discharged on the tenth postoperative day. He has been followed up postoperatively and now, twelve months after the operation, he IS dOing absolutely well havmg no complamts after severe exertIOn.
406 .
D.
Floros, Th.
DOSIOS,
A. Tsourdls, and N. Glatromanolakis
il(KVX'
Fig. 2. The external appearance and the gross sectIon of the excised tumor.
PathologIc Fmdmgs
A Gross Exammatlon The tumor a was spheroidal to OVOid mass with 13 cm In greater diameter and weighed 504 gr. It was reddish brown and well circumscribed and encapsulated by a thIn capsule which was loosely attached to a piece of pericardIUm. The cut surface was relatively soft, fleshy, gray-white with scattered focI of necrosIs. At the periphery of the tumor close (In and outside) to the capsule were several focI of thymIC parenchyma (Fig. 2). B. MIcroscoPIc Fmdmgs. Microscopically, the tumor IS diVided In lobules by fibrous strands and consists of umform cells With central OVOId or round nuclei and eosmophllIc cytoplasm, With III defmed cytoplasmic borders. Several mitoses were seen The predomInant cellular pattern of the tumor was a radial arrangement around a central lumen In the manner of a rosette. RIbbons and festoons were also common espeCIally at the perIphery of the tumor where the stroma was very vascular and rich In collagen. Capsular and lymphatic InvaSIOn were often seen. Normal thymiC parenchyma With cysts and Invaded by tumor masses were present. FoCI of necrosIs were also seen. The SeVier-Munger staIn (Sevier and Munger, 1965) revealed several cells With argyrophilIc granules. Lymphocytes were absent In the tumor mass (Fig. 3, 4).
Fig. 3. The tumor IS dIVIded In lobules by thIn fibrous strands and forms numerous rossettes (H and E, X 125) Inset: Higher magnIficatIOn of a rossette (H and E, X 500).
Fig. 4. Ribbon and festoon formatIOn In the penphery of the tumor (H and E, X 31.2) Inset· In the center a neoplastIC cell With argyrophilic granules (SeVier-Munger, X 312.5).
408 .
D.
Floros, Th.
DOSIOS,
A. Tsourdls, and N. Glatromanolakls
Discussion The fmdings of our patIent mdicate that the tumor of the antenor superior mediastinum was denved from the thymus gland. Rosai et al. (1972), who first reported the entIty, suggested that the cell of ongin of this neoplasm is a neuroendocrine cell of Kultschitzky's type and that the thymus IS the most likely SIte of ongm for thIS endocrine neoplasm in view of Its characteristic anatomic locatIOn, the presence of thymIC parenchyma m the capsule and the known occurence of Kultschltzky-type cells m the normal thymus of some animals (Snyder et al., 1972). The histological differentIal diagnosis of carcinOid tumor of the thymus m patIents with MEA is diffICult. This is due to the presence of mIcroscopically similar tumors m other endocrine organs. The pOSSibility that the neoplasm represents a metastasis from other endocnne tumors must be excluded. In our patient the most dIfficult problem was to rule out a mediastmal metastasIs from Islet-cell carcmoma because of the history of the patient. This POSSlblhty however seems unlikely because the neoplasm showed all the features of the carcinoid tumor of the thymys which was described eloquently by Rosal et al. (1972), Rosai and Hlga (1972) and Rosai and Levme (1976). FIrst, the tumor was so huge that It was unlikely to be a metastasis of isletcell carcmoma without becoming ObVIOUS m the peritoneal cavity. Second, the lungs and the lymph nodes of the medlastmum were mtact. ThIrd, the patient showed no eVidence of msulm production. Fourth, the mICroscopIC appearance of the tumor was similar but not Identical to the islet cell adenoma of the patient. On the contrary, the tumor showed the histologIcal features of the carcmOid of the thymus such as the formation of rosettes, ribbons and festoons and the presence of argyprophIhc granules 10 the neoplastic cells. FIfth, at the periphery of the tumor multiple fOCI of normal thymic parenchyma were identified. In our opimon thiS fmding is the most Important. Only one other case of carcmOid tumor of the thymus associated with MEA surrounded by normal thymiC parenchyma has been descnbed (Manes and Taylor, 1973). In addltlon to these features m our patient there were found thymiC cysts closely related to the tumor. This feature was found only in other two cases (Rosal and Levine, 1976). As far as the high serum calcium level whICh was found initIally and subSided after resectIOn of the tumor, It can be explained by accepting the hypothesis of production of parathormone like sudstance by the msulinoma (Tashgian, Ir., 1974; Talmage, et al. 1975). In conclUSIOn, thIS case represents a typical example of carcinOid of the thymus assoCiated with MEA. The presence of the typical charactenstics of thIS rare pathologiC entity, mcludmg the presence of normal thymic tissue in
CarcinOid Tumor Thymus· 409
close relation to the neoplasm, remforces the VIew (Rosai et al., 1972; Rosai and Higa, 1972; Lowenthal et al., 1974; Rosal and Levine, 1976; Salyer et al., 1976) that thIS tumor derives from the thymus gland. Acknowledgment. The authors wish to thank Professor J. Rosal M. D. and Professor L. Dehner, M. D. Minneapolis, Minnesota, for their review of the slides.
References Case, 5.: Carcmoma of ectopic parathyrOid. Penrose Cancer, Semln. 4, 50-53 (1969) Fisher, E. R., and Hicks, J.: Further pathologic observatIOns on the syndrome of peptic ulcer on multiple endocnne tumors. Gastroenterology 38, 458-466 (1960) Hill, D. M.· Plunglandular syndrome. Multiple endocnne neoplasia Proc. R. Soc. Med 60, 650--651 (1967) Lowenthal, R. M., Gumpel, J M., Kreel, L., Me. Laughhn, J E., and Skeggs, D. B L CarCIllOid tumor of the thymus With systemic mamfestatlOns: a radIOlogICal and Pathological study. Thorax 29, 553-558 (1974) Mane&, J. L., and Taylor, H. B. ThymiC carCinOid In familial multiple endocnne adenomatosIs. Arch. Path. 95,252-255 (1973) Rosal, J., and Hlga E.. Medlastmal endocrine neoplasm of probable thymiC ongln, related to carCinOid tumor. Chmcopathologlc study of 8 cases Cancer 29, 1061-1074 (1972) Rosal, J., Hlga, E., and Davie, J .. Mediastinal endocnne neoplasm In patients With multiple endocnne adenomatosIs. A preVIOusly unrecogmzed assoCIatIOn. Cancer 29, 1075-1083 (1972) Rosal, J., and Levine, D. E . Atlas of tumor Pathology. Tumors of the thymus. Washington D. C. Fasclle 13, 167-181 (1976) Salyer, R. W., Salyer, C. D., and Egleston, J C .. CarCinOid tumors of the thymus. Cancer 37, 958-973 (1976) SeVier, C. A, and Munger, L B. A Silver method for paraffin sectIOns of neural tissue. J. Neuropath. Exp. Neurol. 24; 130-135 (1965) Snyder, N., Scurry, M T, and Deiss, W. P Five families With multiple endocnne adenomatosIs Amer. Int. Med. 76,53-58 (1972) Talmage, R. V , Owen, M., and Parsons, J. A . CalcIUm regulatlllg hormones. Exerpta Medica Amsterdam, Amencan ElseVier Publishmg Co, Inc., N. York, P 140, 1975 TashJian, A. H .. Tumor, humors and the hypercalcemia of cancer. New. Eng\. J. Med. 290, 905 (1974) Wermer, R.· Genetic aspects of adenomatosIs of endocnne glands. Amer. J. Med 16,363-371 (1954) Williams, E. D., and Celestm, L. R The aSSOCiation of bronchial carcmOid and plunglandular adenomatosIs. Thorax 17, 120-127 (1962 Received July 25, 1981 Accepted May 24, 1982
Key words: CarCinOId - Thymus - Multiple Endocrine AdenomatosIs Dr. Demosthenes Floros, Air Force and Veterans AdmllllstratlOn, General Hospital, MesoglOn and Katechakl, Goudl, Athens, Greece
,
!
.
,'!
Air Force and Veterans AdmlmstratlOn General Hospital, Athens, Greece
Carcinoid Tumor of the Thymus with Multiple Endocrine Adenomatosis D. FLOROS*, TH. DOSIOS**, A. TSOURDIS**\ and N. YIATROMANOLAKIS****
Summary A rare case of carcmOld tumor of the thymus m a male patient aged 32 With multiple endocrme adenomatosIs type I IS reported. The histologic features, the diagnostic cntena and the pathogenesIs of the tumor are bnefly discussed,
Introduction Carcinoid tumors m patIents with multiple endocnne adenomatosis (MEA) or Wermers syndrome (Wermer, 1954) have been described by several authors (Fisher and Hicks, 1960; Williams and Celestin, 1962; Snyder et al., 1972). Almost all of these carcmoid tumors have been primary in foregut denvatives. CarcinOld tumor of the thymus associated WIth MEA is a very rare condItion described fust by Rosal et al., (1972) in three patIents. Since then another seven cases have been reported (Hill, 1967; Case 5, 1969; Manes and Taylor, 1973; Rosal and Levme, 1976). Our case, the eleventh one m the literature, IS another example of a carcmOld tumor of the thymus associated WIth MEA syndrome (Type I).
Case Report A 32 year old white male was admitted to Air Force and Veterans AdmmlstratlOn General Hospital m Athens for an enlargement of the antenor superior medlastmum which was found • Director of Pathology Laboratory •• Department of Surgery, DIVISion of ThoraCIC Surgery Director of Department of Endocrmology * * Head of Chest Diseases umt
*..*.
CarcinOid Tumor Thymus . 405
Fig. 1. PA chest roentgenogram showmg a huge well defmed medlastmal mass, extendmg outside the left cardiac border.
incidentally after a routme chest X-ray exammatlOn (Fig. 1). Two years prevIOusly the patient had hypoglycaemlc crises. Repeated fastmg blood sugar exammatlOns at that time revealed values of 31,29,26, 17 and 23 mg/lOO ml with Simultaneous blood msulm levels 18,23,22,50, and 37 j,tu/ ml respectively. At laparatomy two nodules with a diameter of 1,5 cm each were removed from the pancreas. The histological examinatIOn of these nodules showed the typical fmdmgs of the Islet-cell adenoma with no signs of mahgnancy The postoperative course of the patient was uneventful and he was completely asymptomatic after the operatIOn. HIS blood sugar level and blood msulm level returned to normal values. It should be noted that the patient had a hypercalcemia (13 mg/100 mil preoperatively which subsided after the operatIOn. ExammatlOn of the patient at thiS second admiSSIOn was unremarkable. Fluoroscopy showed that the mediastinal mass transmitted the cardiac pulses. C. T. scannmg of mediastinum showed a sohd tumor, which appeared to be adherent to the anterior surface of the left ventricle of the heart. At thoracotomy the tumor was found occupymg the entire anterior-superior medlastmum, where the thymus should be found normally and was attached to the pericardIUm. Wide radical eXCISIOn of the tumor mcludmg the anterior superior portIOn of the pericardIUm was performed. The tumor was dissected eastlv from the surroundmg tissues. Lymph nodes were not palpable. The postoperative course was uneventful and the patient was discharged on the tenth postoperative day. He has been followed up postoperatively and now, twelve months after the operation, he IS dOing absolutely well havmg no complamts after severe exertIOn.
406 .
D.
Floros, Th.
DOSIOS,
A. Tsourdls, and N. Glatromanolakis
il(KVX'
Fig. 2. The external appearance and the gross sectIon of the excised tumor.
PathologIc Fmdmgs
A Gross Exammatlon The tumor a was spheroidal to OVOid mass with 13 cm In greater diameter and weighed 504 gr. It was reddish brown and well circumscribed and encapsulated by a thIn capsule which was loosely attached to a piece of pericardIUm. The cut surface was relatively soft, fleshy, gray-white with scattered focI of necrosIs. At the periphery of the tumor close (In and outside) to the capsule were several focI of thymIC parenchyma (Fig. 2). B. MIcroscoPIc Fmdmgs. Microscopically, the tumor IS diVided In lobules by fibrous strands and consists of umform cells With central OVOId or round nuclei and eosmophllIc cytoplasm, With III defmed cytoplasmic borders. Several mitoses were seen The predomInant cellular pattern of the tumor was a radial arrangement around a central lumen In the manner of a rosette. RIbbons and festoons were also common espeCIally at the perIphery of the tumor where the stroma was very vascular and rich In collagen. Capsular and lymphatic InvaSIOn were often seen. Normal thymiC parenchyma With cysts and Invaded by tumor masses were present. FoCI of necrosIs were also seen. The SeVier-Munger staIn (Sevier and Munger, 1965) revealed several cells With argyrophilIc granules. Lymphocytes were absent In the tumor mass (Fig. 3, 4).
Fig. 3. The tumor IS dIVIded In lobules by thIn fibrous strands and forms numerous rossettes (H and E, X 125) Inset: Higher magnIficatIOn of a rossette (H and E, X 500).
Fig. 4. Ribbon and festoon formatIOn In the penphery of the tumor (H and E, X 31.2) Inset· In the center a neoplastIC cell With argyrophilic granules (SeVier-Munger, X 312.5).
408 .
D.
Floros, Th.
DOSIOS,
A. Tsourdls, and N. Glatromanolakls
Discussion The fmdings of our patIent mdicate that the tumor of the antenor superior mediastinum was denved from the thymus gland. Rosai et al. (1972), who first reported the entIty, suggested that the cell of ongin of this neoplasm is a neuroendocrine cell of Kultschitzky's type and that the thymus IS the most likely SIte of ongm for thIS endocrine neoplasm in view of Its characteristic anatomic locatIOn, the presence of thymIC parenchyma m the capsule and the known occurence of Kultschltzky-type cells m the normal thymus of some animals (Snyder et al., 1972). The histological differentIal diagnosis of carcinOid tumor of the thymus m patIents with MEA is diffICult. This is due to the presence of mIcroscopically similar tumors m other endocrine organs. The pOSSibility that the neoplasm represents a metastasis from other endocnne tumors must be excluded. In our patient the most dIfficult problem was to rule out a mediastmal metastasIs from Islet-cell carcmoma because of the history of the patient. This POSSlblhty however seems unlikely because the neoplasm showed all the features of the carcinoid tumor of the thymys which was described eloquently by Rosal et al. (1972), Rosai and Hlga (1972) and Rosai and Levme (1976). FIrst, the tumor was so huge that It was unlikely to be a metastasis of isletcell carcmoma without becoming ObVIOUS m the peritoneal cavity. Second, the lungs and the lymph nodes of the medlastmum were mtact. ThIrd, the patient showed no eVidence of msulm production. Fourth, the mICroscopIC appearance of the tumor was similar but not Identical to the islet cell adenoma of the patient. On the contrary, the tumor showed the histologIcal features of the carcmOid of the thymus such as the formation of rosettes, ribbons and festoons and the presence of argyprophIhc granules 10 the neoplastic cells. FIfth, at the periphery of the tumor multiple fOCI of normal thymic parenchyma were identified. In our opimon thiS fmding is the most Important. Only one other case of carcmOid tumor of the thymus associated with MEA surrounded by normal thymiC parenchyma has been descnbed (Manes and Taylor, 1973). In addltlon to these features m our patient there were found thymiC cysts closely related to the tumor. This feature was found only in other two cases (Rosal and Levine, 1976). As far as the high serum calcium level whICh was found initIally and subSided after resectIOn of the tumor, It can be explained by accepting the hypothesis of production of parathormone like sudstance by the msulinoma (Tashgian, Ir., 1974; Talmage, et al. 1975). In conclUSIOn, thIS case represents a typical example of carcinOid of the thymus assoCiated with MEA. The presence of the typical charactenstics of thIS rare pathologiC entity, mcludmg the presence of normal thymic tissue in
CarcinOid Tumor Thymus· 409
close relation to the neoplasm, remforces the VIew (Rosai et al., 1972; Rosai and Higa, 1972; Lowenthal et al., 1974; Rosal and Levine, 1976; Salyer et al., 1976) that thIS tumor derives from the thymus gland. Acknowledgment. The authors wish to thank Professor J. Rosal M. D. and Professor L. Dehner, M. D. Minneapolis, Minnesota, for their review of the slides.
References Case, 5.: Carcmoma of ectopic parathyrOid. Penrose Cancer, Semln. 4, 50-53 (1969) Fisher, E. R., and Hicks, J.: Further pathologic observatIOns on the syndrome of peptic ulcer on multiple endocnne tumors. Gastroenterology 38, 458-466 (1960) Hill, D. M.· Plunglandular syndrome. Multiple endocnne neoplasia Proc. R. Soc. Med 60, 650--651 (1967) Lowenthal, R. M., Gumpel, J M., Kreel, L., Me. Laughhn, J E., and Skeggs, D. B L CarCIllOid tumor of the thymus With systemic mamfestatlOns: a radIOlogICal and Pathological study. Thorax 29, 553-558 (1974) Mane&, J. L., and Taylor, H. B. ThymiC carCinOid In familial multiple endocnne adenomatosIs. Arch. Path. 95,252-255 (1973) Rosal, J., and Hlga E.. Medlastmal endocrine neoplasm of probable thymiC ongln, related to carCinOid tumor. Chmcopathologlc study of 8 cases Cancer 29, 1061-1074 (1972) Rosal, J., Hlga, E., and Davie, J .. Mediastinal endocnne neoplasm In patients With multiple endocnne adenomatosIs. A preVIOusly unrecogmzed assoCIatIOn. Cancer 29, 1075-1083 (1972) Rosal, J., and Levine, D. E . Atlas of tumor Pathology. Tumors of the thymus. Washington D. C. Fasclle 13, 167-181 (1976) Salyer, R. W., Salyer, C. D., and Egleston, J C .. CarCinOid tumors of the thymus. Cancer 37, 958-973 (1976) SeVier, C. A, and Munger, L B. A Silver method for paraffin sectIOns of neural tissue. J. Neuropath. Exp. Neurol. 24; 130-135 (1965) Snyder, N., Scurry, M T, and Deiss, W. P Five families With multiple endocnne adenomatosIs Amer. Int. Med. 76,53-58 (1972) Talmage, R. V , Owen, M., and Parsons, J. A . CalcIUm regulatlllg hormones. Exerpta Medica Amsterdam, Amencan ElseVier Publishmg Co, Inc., N. York, P 140, 1975 TashJian, A. H .. Tumor, humors and the hypercalcemia of cancer. New. Eng\. J. Med. 290, 905 (1974) Wermer, R.· Genetic aspects of adenomatosIs of endocnne glands. Amer. J. Med 16,363-371 (1954) Williams, E. D., and Celestm, L. R The aSSOCiation of bronchial carcmOid and plunglandular adenomatosIs. Thorax 17, 120-127 (1962 Received July 25, 1981 Accepted May 24, 1982
Key words: CarCinOId - Thymus - Multiple Endocrine AdenomatosIs Dr. Demosthenes Floros, Air Force and Veterans AdmllllstratlOn, General Hospital, MesoglOn and Katechakl, Goudl, Athens, Greece