- Email: [email protected]
Carney's Triad
Case reports
147
Carney's Triad E. de Jong, W. Mulder*, E. Nooitgedachtt, C.W. Taat, J. Bras:l: Department of Surgery of Academic Medical Centel; Amsterdam, *The Onze Lieve Vrouwe Gasthuis, Amsterdam, ~ The Department of Radiology of the Rivierenlandhospital, Tiel and ~The Department of Pathology of Academic Medical Center; Amsterdam
The purpose of this study is to provide an overview of cases of Carney's triad and to discuss the clinical implications of this diagnosis. A search was made of the English-language literature for original articles, reviews and abstracts addressing Carney's triad. A new patient was described and added to the number of known patients. In literature 40 patients were found with a complete or incomplete triad. There exists no agreement on the pathology and possible common origin of these tumours. Directions are given for diagnostics and therapy. The diagnosis of Carney's triad has specific clinical implications that make a good knowledge of this syndrome mandatory.
Key words: Carney, triad.
Introduction
Case report
In 1977, Carney described a triad of gastric epitheloid leiomyosarcoma, functioning extraadrenal paraganglioma and pulmonary chondromaJ In this publication he reported on four patients. Carney concluded after studying other cases in the literature that this combination of tumours obviously concerned an etiological syndrome, since three different, rather uncommon tumours appeared in a patient of an age in which neoplasms are rare.-" A few years later he presented another 24 cases) There was a female preponderance (22 out of 24 patients), which was also observed in the majority of later reports?-" As the appearance of the different tumours lacks a particular chronological order, the presence of at least two of these three lesions should be accepted as evidence of the presence of Carney's triad. The triad can have serious consequences, especially the paragangliomas. "'~-" The gastric tumour has metastasized in several cases)'" The interval between the appearance of the component of the triad can be very long, even decades, and therefore a longterm follow-up is indicated) '~° The symptomatology of the disease is determined by the first presenting tumour. Severe upper gastrointenstinal bleeding is a frequent sign in epitheloid leiomyosarcoma of the stomach. Other symptoms are pain and a palpable mass in the abdomen, t3 In cases of functioning paraganglioma, symptoms are caused by elevated plasma levels of catecholamines, e.g. headaches, perspiration, hypertension and facial flushingY 4
In 1989 a 28-year-old man was admitted to hospital because of intensified complaints of the upper abdomen, related to chronic relapsing pancreatitis with formation of pseudocysts. A cystogastrostomy was performed. During this procedure an abnormal thickening of the posterior gastric wall was noticed and open biopsies were taken for histological examination. The biopsies revealed a tumour highly suggestive of a leiomyosarcoma. At relaparotomy a total gastrectomy with an en bloc splenectomy, left adrenalectomy and resection of the pancreatic tail was performed. The post-operative course was uneventful. The patient was seen at regular intervals at the outpatient clinic. In February 1991 a routine chest X-ray showed a mass situated dorsocaudally of the right pulmonary hilus. A pulmonary chondroma, as described in Carney's triad, was suggested by the radiologist and a right lower lobectomy was performed. Again the post-operative course was uneventful. As the third component of Carney's triad is a paraganglioma, another CT scan of the thorax and abdomen was performed several months later. There were no signs of a paraganglioma, although one enlarged para-aortic lymph node was seen. An MRI scan of the cervical carotid region showed multiple small lymph nodes, which could suggest paraganglioma, but the scan was inconclusive. Analysis of 24-hour urine samples showed no elevation of catecholamine metabolites. With the exception of a pneumonia in 1994 the patient is still symptom-free at the time of writing. Pathology
*Correspondence to: E de Jong, Department of Surgery, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. Fax: 31-20-6914858.
Histology showed closely packed, epitheloid to spindleshaped cells. Mitotic activity varied from zero to four
148
Case reports
Fig. 1. Malignant stroma cell tumour with smooth muscle differentiation, characterized by spindle to epitheloid cells with intracytoplasmicvacuolization. H&E, original magnification x 100. Reproduced here at 47%.
•
~" ~:~"~" • -~ .~\._M~L,~a:~,~I- ~
~.,2k.',,.~mK.~
I.
Fig. 2. Intravascular extension of the tumour shown in Fig. 1. Antifactor VIII-hematoxylin stain, original magnification x25. Reproduced here at 47%.
mitoses per HPF (objective 40 x ) with a total of 10 mitoses per 50 HPF (Fig. 1). The lesions infiltrated the adjacent smooth muscle. In the minor omentum, tumour spread was found in two lymph nodes, in capillaries (Fig. 2) and a vein. Based on immunohistochemistry, a diagnosis of malignant stroma-cell tumour with smooth muscle differentiation was made. The resection specimen of the lower lobe of the right lung showed a chrondroma (Fig. 3).
Discussion The stroma-cell tumours in Carney's triad show a varying expression for muscle antigens with, in a few cases, eoexpression for neurogenic markers, t~-~9One can question the exact nature of these epitheloid tumours, especially those found in Carney's triad. It may be that the epitheloid stroma-cell and paraganglionic tumours found in Carney's triad have a common progenitor cell possibly, as suggested by Tortella and others, of autonomic nerve origin.4,~2,2°,z~
Fig. 3. Pulmonary chondroma. Less cellular hyalin cartilage with secondary ossification at the edges. H&E, original magnification x 50. Reproduced here at 47%.
This could explain the multifocal character of the epitheloid stroma-cell and paraganglionic tumours in Carney's triad, but not the presence of pulmonary chondromas. The epitheloid leiomyosarcoma is a highly aggressive neoplasm with metastases in 63% of patients, ~2'-'-but ' appears to have a much milder clinical course within Carney's triad. Even resection of metastatic foci has been followed by longterm survival.7J2 The gastric leiomyosarcoma is treated by a radical excision, i.e. partial or total gastrectomy, while pulmonary chondroma is resected for diagnostic reasons. Only if cytology can confirm the diagnosis of a benign chondroma can a policy of roentgenographical monitoring of the tumour be proposed. 3 The extraadrenal paragangliomas, the third component of the triad, are considered as potentially malignant and must, if possible, be resected. 23 Carney's triad is rare and its clinical expression varies. Awareness of the combination of these three different, rather uncommon tumours is mandatory in correct diagnosis.
References I. Carney JA, Sheps SG, Go VLW, et al. The triad of gastric leiomyosarcoma, functioning extra-adrenal paraganglioma and pulmonary chondroma. New Engl J Med 1977; 296: 1517-18. 2. Carney JA. The triad of gastric epitheloid leiomyosarcoma, functioning extra-adrenal paraganglioma, and pulmonary chondroma. Cancer 1979; 43: 374-82. 3. Carney JA. The triad of gastric epitheloid leiomyosarcoma, pulmonary chondroma, and functioning extra-adrenal paragangliom: a five-year review. Medicine 1983; 62: 159-69. 4. Tortella BJ, Antonioni DA, Dvorak AM, et al. Gastric autonomic nerve (GAN) tumour and extra-adrenal paragangli'oma in Carney's triad. Ann Surg 1987; 205: 221-5. 5. Margulies KB, Sheps SG. Carney's triad: guidelines for management. Mayo Clin Proc 1988; 63: 496-502. 6. Evans RA, Salisbury JR, Gimson A, et aL Case report: indolent gastric epitheloid leiomyosarcomain Carney's triad. Clin Radiol 1990; 42: 437-9. 7. Cardwell JR, Solaiman AR, Kim K, et al. Carney's triad with recurrent gastric leiomyoblastoma. Am Surg 1990; 56: 355-9. 8. Blei A, Gonzalez-Crussi F. The intriguing nature of gastric tumours in Carney's triad. Cancer 1992; 69: 292-300. 9. Perez-Atayde AR, Shamberger RC, Kozakewich HW.
Case reports
10. 11.
12. 13. 14. 15. 16. 17.
Neuroectodermal differentiation of the gastrointestinal tumours in the Carney triad. An ultrastructural and immunohistochemical study. Am J Surg Pathol 1993; 17: 706-14. Lancha C, Diez L, Mitjavila M, et al. A case of complete Carney's syndrome. Clin Nucl Med 1994; 19: 1008-10. Tisell LE, Angervall L, Dahl I, et al. Recurrent and metastasizing gastric leiomyoblastoma (epitheloid leiomyosarcoma) associated with multiple pulmonary chondrohamartomas. Cancer 1978; 41: 259-65. Appelman HD, Helwig EB. Gastric epitheloid leiomyoma and leiomyosarcoma (leiomyoblastoma). Cancer 1976; 38: 708-28. Lecomte P, Bruneton JN, Sicart M. Leiomyoblastoma of the stomach. Fortschr Roentgenstr 1981; 135: 57-60. Knake JE, Gross MD. Extraadrenal paraganglioma, pulmonary chondroma and gastric leiomyoblastoma: triad in young females. A JR 1979; 132: 448-451. Pike AM, Loyd RV, Appelman HD. Cell markers in gastrointestinal stromal tumours. Human Pathol 1988; 19: 830-4. Thompson EM, Evans DJ. The significance of PGP 9.5 in tumours: an immunohistochemical study of gastrointestinal stromal tumours. Histopathology 1990; 17: 175-7. Newman PL, Wadden C, Fletcher CDM. Gastrointestinal stromal tumours: correlation of immunophenotype with clinicopathologic features. J Pathol 1991; 164: 107-17.
149
18. Ma CK, Amin MB, Kintenar E, et aL Immunologic characterization of gastrointestinal stromal tumours: a study of 82 cases compared with I 1 cases of leiomyomas. Mod Pathol 1993; 6: 139-44. 19. Enzinger FM, Weis SW. Epitheloid smooth muscle tumours. In: Enzinger FM, Weiss SW (eds) Soft Tissue Turnouts. Third edition. St. Louis; Mosby, 1995; 511-22. 20. Appelman HD, Helwig EB. Sarcomas of the stomach. Am J Clin Pathol 1977; 67: 2-10. 21. Appelman HD, Helwig EB. Cellular leiomyomas ofthe stomach in 49 patients. Arch Pathol Lab Med 1977; !01: 373-7. 22. Evans HL. Smooth muscle tumours of the gastrointestinal tract, a study of 56 cases followed for a minimum of 10 years. Cancer 1985; 56: 2242-50. 23. Lacquet LK, Moulijn AC, Jongerius CM, et aL Intrathoracic chemodectoma with multiple Iocalisations. Thorax 1977; 32: 203-9. 24. Blandino A, Salvi L, Faranda C, et al. Unusual malignant paraganglioma of the anterior mediastinum: CT and MR findings. Eur J Radiol 1992; 15: 1-3. 25. Persson S, Kindblom LG, Angervall K, et al. Metastasizing gastric epitheloid leiomyosarcomas (leiomyoblastomas) in young individuals with long-term survival. Cancer 1992; 70: 721-32.
Accepted for publication 10 December 1996
Localization of monoclonal antibody CC49 in colonic metastasis from renal cell carcinoma Shmuel Avital, Charles L. Hitchcockt, Mimi Baratz*, Riad Haddad, Yehuda Skornick and Schlomo Schneebaum Departments o f Surgery " A " and *Pathology, Tel-Aviv S o u r a s k y Medical Center and Sackler Faculty o f Medicine, Tel-Aviv University, lsrael, and "~Department o f Pathology, J a m e s Cancel" Center and Research Institute, The Ohio S t a t e UniversiO; Columbus, Ohio, USA
We report a rare case of solitary metastasis from renal cell carcinoma which manifested as a primary colonic tumour 5 years after nephrectumy. A monoclonal antibody CC49 (anti-TAG-72 antibody), used in Radioimmunoguided Surgery TM, was found to localize in the tumour. Pathological examination revealed metastasis of renal cell carcinoma in the colon, lmmunohistochemistry with CC49 showed moderate staining of the colonic mucosa around the metastasis with no reaction in the turnout itself. Based on this case and other published studies, we conclude that TAG-72, the antigen manifested in many adenocarcinomas, can be up-regulated and expressed in normal colonic mucosa adjacent to another tumour as a result of stimulations, such as cytokine release, in response to this tumour.
Key words: colorectal carcinoma; monoclonal antibody; renal cell carcinoma.
Introduction
Renal cell carcinoma metastasizes predominantly to the lungs, bones, lymph nodes, liver and brain, t-3 Metachronous metastatic disease is common and may develop in about 50% of patients who undergo curative nephrectomy? '4 Metastasis to the colon is rare but when it occurs usually takes the form of disseminated
Correspondence to: Dr. Shmuel Avital, Department of Surgery "A", TeI-Aviv Sourasky Medical Center, 6 Weizmann Street, TelAviv 64239, Israel. Fax: 972-3-6974621.
disease.~'s Recurrence manifested as a solitary colonic metastasis is extremely unusualY Radioimmunoguided SurgeryTM (RIGS R) is a surgical method used for colorectal carcinoma whereby the patient is injected 3 weeks prior to surgery with a ~-'SI-labelled monoclonal antibody (MoAb). During this time, the radioactive MoAb attaches to the tumour and clears from normal tissue. The surgeon can locate the cancer using a gamma-detecting probe, detect occult metastases (not found by traditional surgical methods) and assess better the extent of the disease as well as the completeness of the resection. 8 The currently used MoAb, CC49, a second-generation antitumour associated antigen-72 (TAG-72), usually localizes in
147
Carney's Triad E. de Jong, W. Mulder*, E. Nooitgedachtt, C.W. Taat, J. Bras:l: Department of Surgery of Academic Medical Centel; Amsterdam, *The Onze Lieve Vrouwe Gasthuis, Amsterdam, ~ The Department of Radiology of the Rivierenlandhospital, Tiel and ~The Department of Pathology of Academic Medical Center; Amsterdam
The purpose of this study is to provide an overview of cases of Carney's triad and to discuss the clinical implications of this diagnosis. A search was made of the English-language literature for original articles, reviews and abstracts addressing Carney's triad. A new patient was described and added to the number of known patients. In literature 40 patients were found with a complete or incomplete triad. There exists no agreement on the pathology and possible common origin of these tumours. Directions are given for diagnostics and therapy. The diagnosis of Carney's triad has specific clinical implications that make a good knowledge of this syndrome mandatory.
Key words: Carney, triad.
Introduction
Case report
In 1977, Carney described a triad of gastric epitheloid leiomyosarcoma, functioning extraadrenal paraganglioma and pulmonary chondromaJ In this publication he reported on four patients. Carney concluded after studying other cases in the literature that this combination of tumours obviously concerned an etiological syndrome, since three different, rather uncommon tumours appeared in a patient of an age in which neoplasms are rare.-" A few years later he presented another 24 cases) There was a female preponderance (22 out of 24 patients), which was also observed in the majority of later reports?-" As the appearance of the different tumours lacks a particular chronological order, the presence of at least two of these three lesions should be accepted as evidence of the presence of Carney's triad. The triad can have serious consequences, especially the paragangliomas. "'~-" The gastric tumour has metastasized in several cases)'" The interval between the appearance of the component of the triad can be very long, even decades, and therefore a longterm follow-up is indicated) '~° The symptomatology of the disease is determined by the first presenting tumour. Severe upper gastrointenstinal bleeding is a frequent sign in epitheloid leiomyosarcoma of the stomach. Other symptoms are pain and a palpable mass in the abdomen, t3 In cases of functioning paraganglioma, symptoms are caused by elevated plasma levels of catecholamines, e.g. headaches, perspiration, hypertension and facial flushingY 4
In 1989 a 28-year-old man was admitted to hospital because of intensified complaints of the upper abdomen, related to chronic relapsing pancreatitis with formation of pseudocysts. A cystogastrostomy was performed. During this procedure an abnormal thickening of the posterior gastric wall was noticed and open biopsies were taken for histological examination. The biopsies revealed a tumour highly suggestive of a leiomyosarcoma. At relaparotomy a total gastrectomy with an en bloc splenectomy, left adrenalectomy and resection of the pancreatic tail was performed. The post-operative course was uneventful. The patient was seen at regular intervals at the outpatient clinic. In February 1991 a routine chest X-ray showed a mass situated dorsocaudally of the right pulmonary hilus. A pulmonary chondroma, as described in Carney's triad, was suggested by the radiologist and a right lower lobectomy was performed. Again the post-operative course was uneventful. As the third component of Carney's triad is a paraganglioma, another CT scan of the thorax and abdomen was performed several months later. There were no signs of a paraganglioma, although one enlarged para-aortic lymph node was seen. An MRI scan of the cervical carotid region showed multiple small lymph nodes, which could suggest paraganglioma, but the scan was inconclusive. Analysis of 24-hour urine samples showed no elevation of catecholamine metabolites. With the exception of a pneumonia in 1994 the patient is still symptom-free at the time of writing. Pathology
*Correspondence to: E de Jong, Department of Surgery, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. Fax: 31-20-6914858.
Histology showed closely packed, epitheloid to spindleshaped cells. Mitotic activity varied from zero to four
148
Case reports
Fig. 1. Malignant stroma cell tumour with smooth muscle differentiation, characterized by spindle to epitheloid cells with intracytoplasmicvacuolization. H&E, original magnification x 100. Reproduced here at 47%.
•
~" ~:~"~" • -~ .~\._M~L,~a:~,~I- ~
~.,2k.',,.~mK.~
I.
Fig. 2. Intravascular extension of the tumour shown in Fig. 1. Antifactor VIII-hematoxylin stain, original magnification x25. Reproduced here at 47%.
mitoses per HPF (objective 40 x ) with a total of 10 mitoses per 50 HPF (Fig. 1). The lesions infiltrated the adjacent smooth muscle. In the minor omentum, tumour spread was found in two lymph nodes, in capillaries (Fig. 2) and a vein. Based on immunohistochemistry, a diagnosis of malignant stroma-cell tumour with smooth muscle differentiation was made. The resection specimen of the lower lobe of the right lung showed a chrondroma (Fig. 3).
Discussion The stroma-cell tumours in Carney's triad show a varying expression for muscle antigens with, in a few cases, eoexpression for neurogenic markers, t~-~9One can question the exact nature of these epitheloid tumours, especially those found in Carney's triad. It may be that the epitheloid stroma-cell and paraganglionic tumours found in Carney's triad have a common progenitor cell possibly, as suggested by Tortella and others, of autonomic nerve origin.4,~2,2°,z~
Fig. 3. Pulmonary chondroma. Less cellular hyalin cartilage with secondary ossification at the edges. H&E, original magnification x 50. Reproduced here at 47%.
This could explain the multifocal character of the epitheloid stroma-cell and paraganglionic tumours in Carney's triad, but not the presence of pulmonary chondromas. The epitheloid leiomyosarcoma is a highly aggressive neoplasm with metastases in 63% of patients, ~2'-'-but ' appears to have a much milder clinical course within Carney's triad. Even resection of metastatic foci has been followed by longterm survival.7J2 The gastric leiomyosarcoma is treated by a radical excision, i.e. partial or total gastrectomy, while pulmonary chondroma is resected for diagnostic reasons. Only if cytology can confirm the diagnosis of a benign chondroma can a policy of roentgenographical monitoring of the tumour be proposed. 3 The extraadrenal paragangliomas, the third component of the triad, are considered as potentially malignant and must, if possible, be resected. 23 Carney's triad is rare and its clinical expression varies. Awareness of the combination of these three different, rather uncommon tumours is mandatory in correct diagnosis.
References I. Carney JA, Sheps SG, Go VLW, et al. The triad of gastric leiomyosarcoma, functioning extra-adrenal paraganglioma and pulmonary chondroma. New Engl J Med 1977; 296: 1517-18. 2. Carney JA. The triad of gastric epitheloid leiomyosarcoma, functioning extra-adrenal paraganglioma, and pulmonary chondroma. Cancer 1979; 43: 374-82. 3. Carney JA. The triad of gastric epitheloid leiomyosarcoma, pulmonary chondroma, and functioning extra-adrenal paragangliom: a five-year review. Medicine 1983; 62: 159-69. 4. Tortella BJ, Antonioni DA, Dvorak AM, et al. Gastric autonomic nerve (GAN) tumour and extra-adrenal paragangli'oma in Carney's triad. Ann Surg 1987; 205: 221-5. 5. Margulies KB, Sheps SG. Carney's triad: guidelines for management. Mayo Clin Proc 1988; 63: 496-502. 6. Evans RA, Salisbury JR, Gimson A, et aL Case report: indolent gastric epitheloid leiomyosarcomain Carney's triad. Clin Radiol 1990; 42: 437-9. 7. Cardwell JR, Solaiman AR, Kim K, et al. Carney's triad with recurrent gastric leiomyoblastoma. Am Surg 1990; 56: 355-9. 8. Blei A, Gonzalez-Crussi F. The intriguing nature of gastric tumours in Carney's triad. Cancer 1992; 69: 292-300. 9. Perez-Atayde AR, Shamberger RC, Kozakewich HW.
Case reports
10. 11.
12. 13. 14. 15. 16. 17.
Neuroectodermal differentiation of the gastrointestinal tumours in the Carney triad. An ultrastructural and immunohistochemical study. Am J Surg Pathol 1993; 17: 706-14. Lancha C, Diez L, Mitjavila M, et al. A case of complete Carney's syndrome. Clin Nucl Med 1994; 19: 1008-10. Tisell LE, Angervall L, Dahl I, et al. Recurrent and metastasizing gastric leiomyoblastoma (epitheloid leiomyosarcoma) associated with multiple pulmonary chondrohamartomas. Cancer 1978; 41: 259-65. Appelman HD, Helwig EB. Gastric epitheloid leiomyoma and leiomyosarcoma (leiomyoblastoma). Cancer 1976; 38: 708-28. Lecomte P, Bruneton JN, Sicart M. Leiomyoblastoma of the stomach. Fortschr Roentgenstr 1981; 135: 57-60. Knake JE, Gross MD. Extraadrenal paraganglioma, pulmonary chondroma and gastric leiomyoblastoma: triad in young females. A JR 1979; 132: 448-451. Pike AM, Loyd RV, Appelman HD. Cell markers in gastrointestinal stromal tumours. Human Pathol 1988; 19: 830-4. Thompson EM, Evans DJ. The significance of PGP 9.5 in tumours: an immunohistochemical study of gastrointestinal stromal tumours. Histopathology 1990; 17: 175-7. Newman PL, Wadden C, Fletcher CDM. Gastrointestinal stromal tumours: correlation of immunophenotype with clinicopathologic features. J Pathol 1991; 164: 107-17.
149
18. Ma CK, Amin MB, Kintenar E, et aL Immunologic characterization of gastrointestinal stromal tumours: a study of 82 cases compared with I 1 cases of leiomyomas. Mod Pathol 1993; 6: 139-44. 19. Enzinger FM, Weis SW. Epitheloid smooth muscle tumours. In: Enzinger FM, Weiss SW (eds) Soft Tissue Turnouts. Third edition. St. Louis; Mosby, 1995; 511-22. 20. Appelman HD, Helwig EB. Sarcomas of the stomach. Am J Clin Pathol 1977; 67: 2-10. 21. Appelman HD, Helwig EB. Cellular leiomyomas ofthe stomach in 49 patients. Arch Pathol Lab Med 1977; !01: 373-7. 22. Evans HL. Smooth muscle tumours of the gastrointestinal tract, a study of 56 cases followed for a minimum of 10 years. Cancer 1985; 56: 2242-50. 23. Lacquet LK, Moulijn AC, Jongerius CM, et aL Intrathoracic chemodectoma with multiple Iocalisations. Thorax 1977; 32: 203-9. 24. Blandino A, Salvi L, Faranda C, et al. Unusual malignant paraganglioma of the anterior mediastinum: CT and MR findings. Eur J Radiol 1992; 15: 1-3. 25. Persson S, Kindblom LG, Angervall K, et al. Metastasizing gastric epitheloid leiomyosarcomas (leiomyoblastomas) in young individuals with long-term survival. Cancer 1992; 70: 721-32.
Accepted for publication 10 December 1996
Localization of monoclonal antibody CC49 in colonic metastasis from renal cell carcinoma Shmuel Avital, Charles L. Hitchcockt, Mimi Baratz*, Riad Haddad, Yehuda Skornick and Schlomo Schneebaum Departments o f Surgery " A " and *Pathology, Tel-Aviv S o u r a s k y Medical Center and Sackler Faculty o f Medicine, Tel-Aviv University, lsrael, and "~Department o f Pathology, J a m e s Cancel" Center and Research Institute, The Ohio S t a t e UniversiO; Columbus, Ohio, USA
We report a rare case of solitary metastasis from renal cell carcinoma which manifested as a primary colonic tumour 5 years after nephrectumy. A monoclonal antibody CC49 (anti-TAG-72 antibody), used in Radioimmunoguided Surgery TM, was found to localize in the tumour. Pathological examination revealed metastasis of renal cell carcinoma in the colon, lmmunohistochemistry with CC49 showed moderate staining of the colonic mucosa around the metastasis with no reaction in the turnout itself. Based on this case and other published studies, we conclude that TAG-72, the antigen manifested in many adenocarcinomas, can be up-regulated and expressed in normal colonic mucosa adjacent to another tumour as a result of stimulations, such as cytokine release, in response to this tumour.
Key words: colorectal carcinoma; monoclonal antibody; renal cell carcinoma.
Introduction
Renal cell carcinoma metastasizes predominantly to the lungs, bones, lymph nodes, liver and brain, t-3 Metachronous metastatic disease is common and may develop in about 50% of patients who undergo curative nephrectomy? '4 Metastasis to the colon is rare but when it occurs usually takes the form of disseminated
Correspondence to: Dr. Shmuel Avital, Department of Surgery "A", TeI-Aviv Sourasky Medical Center, 6 Weizmann Street, TelAviv 64239, Israel. Fax: 972-3-6974621.
disease.~'s Recurrence manifested as a solitary colonic metastasis is extremely unusualY Radioimmunoguided SurgeryTM (RIGS R) is a surgical method used for colorectal carcinoma whereby the patient is injected 3 weeks prior to surgery with a ~-'SI-labelled monoclonal antibody (MoAb). During this time, the radioactive MoAb attaches to the tumour and clears from normal tissue. The surgeon can locate the cancer using a gamma-detecting probe, detect occult metastases (not found by traditional surgical methods) and assess better the extent of the disease as well as the completeness of the resection. 8 The currently used MoAb, CC49, a second-generation antitumour associated antigen-72 (TAG-72), usually localizes in