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Test and teach number ninety nine: part 2
Pathology (2000) 32, pp. 63– 64
TEST AND TEACH Number Ninety Nine: Part 2 See page 41 for Fig. 1 and case details
EXPLANATION AND DIAGNOSIS: CARCINOSARCOMA OF THE GALLBLADDER On microscopic examination, the tumor contained both mesenchymal and epithelial elements (Fig. 2). The sarcomatous component was made up largely of interlacing bundles of spindle cells with occasional mitotic figures. There were also small foci of malignant cartilage (Fig. 3) and numerous rhabdomyoblastic cells, showing cross striations (Fig. 4). Malignant epithelial elements were in the form of ordinary adenocarcinoma, composed of glandular and cribriform structures which are formed by pleomorphic epithelial cells.
PAS and Alcian blue positivity was found in these glandular structures. Two components of the neoplasm were diffusely mixed but showed clear distinction. The liver biopsy specimen was occupied by the necrotic tumor tissue. Immunohistochemical examination was also performed to support morphological and histochemical findings. The sarcomatous component showed diffuse vimentin expression and the rhabdomyoblasts were desmin positive. Epithelial elements remained negative for these two antibodies. Conversely, epithelial membrane antigen and pancytokeratin were demonstrated in the glandular and the
Fig. 2 Malignant glandular and cribriform structures intermingle with spindle-cell sarcomatous stroma (H & E, ´ 125).
Fig. 4 Cross striations in a spindle-shaped rhabdomyoblastic cell (Masson’s trichrom, ´ 500).
Fig. 3 A malignant cartilage-including area of the gallbladder tumor (Masson’s trichrom, ´ 125).
Fig. 5 Positive immunostaining for pancytokeratin in glandular structures of the tumor (aminoethyl carbasole-peroxidase, ´ 310).
ISSN 0031–3025 printed/ISSN 1465– 3931 online/00/010063 – 02 © 2000 Royal College of Pathologists of Australasia
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cribriform elements (Fig. 5), while the sarcomatous elements remained negative. These findings were all features of the carcinosarcoma. Malignant tumors containing both epithelial and mesenchymal elements are usually called carcinosarcomas. There are few cases in the medical literature, reported as carcinosarcoma or malignant mixed tumor of the gallbladder.1– 7 The majority of the carcinosarcomas involving the gallbladder are exophytic and polypoid masses that project into the lumen and distend the gallbladder.8 Most patients present with right upper quadrant pain with or without jaundice, and either local invasion of the gallbladder bed or distant metastasis occur in the majority of cases. Our case shares the described clinical findings and growth pattern. The epithelial component was generally adenocarcinoma in the majority of previously reported cases, although squamous cell carcinoma was also seen. The sarcomatous component was usually spindle cell sarcoma in most cases,1– 4 but heterotopic elements, such as rhabdomyoblasts and cartilage, were reported by some authors2,9 and osteoclast-like giant cells by others.10,11 The epithelial component was ordinary adenocarcinoma in our case and PAS and Alcian blue positivity and positive immunoreaction for epithelial membrane antigen and pancytokeratin gave clear evidence for the epithelial nature of these structures. The sarcomatous component contained mainly ordinary spindle cell sarcoma; additionally, numerous rhabdomyoblasts and occasional malignant cartilage were present. There may be differently sited tumors with different histopathological features in the same organ. These are called collision tumors. They have a distinct border between each other and are not intermingled into each other. The presence of diffusely intermingled sarcomatous and epithelial elements and the peculiar polypoid shape of our case are sufficient findings to reject the probablity of a collision tumor. At present, the pathogenesis of these tumors remains unknown, but it has been speculated that they arise from totipotential stromal stem cells.12 In a ultrastructural study, it was postulated that cells of sarcoma-like stromal component had an epithelial nature.13 We believe that the stromal elements in our case have a malignant nature; also, heterotopic elements in the form of rhabdomyoblasts and malignant cartilage were present. Neither epithelial membrane antigens nor pancytokeratin expression were found in these sarcomatous cells. However, none of these findings give sufficient evidence to reject the probability of pure epithelial origin for our case. Furthermore, many similar neoplasms of other anatomic sites have been regarded as being of pure epithelial origin and called sarcomatoid carcinoma by many authors.14,15 The biological behavior of gallbladder carcinosarcoma is similar to the more common malignancies in this location, and a rather poor prognosis is described for such cases. In a
study including 18 cases, data showed that patients’ ages ranged from 45 to 90 years, the female to male ratio was 4.3 and the longest survival after the diagnosis of this tumor was 8 months with a mean survival of 1.9 months.4 However, in another case report it was stated that a patient was well for 31 months after a complete removal of the tumor which was confined to the gallbladder. These authors suggested that, like carcinoma, carcinosarcoma of the gallbladder may be curable when resected at an early stage.3 However, the biological behavior of this tumor is not exactly understood. Our patient died due to disseminated tumor 3 months after diagnosis. In our opinion, wherever they originate from, the peculiar histological features and aggressive biological behavior of gallbladder carcinosarcomas cause them to be of importance. Furthermore, more case reports are needed to understand the exact nature of these tumors. Address for correspondence: Dr E. Yavuz, Department of Pathology, Istanbul Medical Faculty, Çapa, Topkapõ, 34390 Istanbul, Turkey. Fax: + 90 212 6311367.
References 1. Higgs WR, Mocega EE, Jordan PH. Malignant mixed tumor of the gallbladder. Cancer 1973; 32: 471– 5. 2. Mansori KS, Cho SY. Malignant mixed tumor of the gallbladder. Am J Clin Pathol 1980; 73: 709–11. 3. Von Kuster LC, Cohen C. Malignant mixed tumor of the gallbladder: report of two cases and review of the literature. Cancer 1982; 50: 1116–70. 4. Born MW, Ramey WG, Ryan SF, Gordon PE. Carcinosarcoma and carcinoma of the gallbladder. Cancer 1984; 53: 2171–7. 5. Inoshita S, Iwashita A, Enjoji M. Carcinosarcoma of the gallbladder. Report of a case and review of the literature. Acta Pathol Jpn 1986; 36: 913– 20. 6. Lopez GA, Strimel W, Herrera-Ornelas L. Carcinosarcoma of the gallbladder. Report of a case. J Surg Oncol 1985; 29: 224– 6. 7. Lumsden AB, Mitchell WE, Wohman MD. Carcinosarcoma of the gallbladder: a case report and review of the literature. Am Surg 1988; 54: 492– 4. 8. Iezzoni JC, Mills SE. Sarcomatoid carcinomas (carcinosarcomas) of the gastrointestinal tract. A review. Semin Diagn Pathol 1993; 10: 176– 87. 9. Ishisara T, Kawano H, Takahashi M, et al. Carcinosarcoma of the gallbladder. A case report with immunohistochemical and ultrastructural studies. Cancer 1990; 66: 992–7. 10. Grosso LE, Gonzalez JG. Stromal osteoclast-like giant cells in an adenosquamous carcinoma of the gallbladder. Hum Pathol 1992; 32: 703– 6. 11. Ito M, Hsu CT, Naito S, et al. Osteoclast-like giant cell tumour of the gallbladder. Virchow’s Arch 1992; 420: 359– 66. 12. Albares-Saavedra J, Cruz-Ortiz H, Alcantara-Vazques A, Henson DE. Unusual types of gallbladder carcinoma. Arch Pathol Lab Med 1981; 105: 287–93 13. Alpers CE, Smuckler EA. Pleomorphic carcinoma of the gallbladder. Case report and ultrastructural study. Ultrastruct Pathol 1984; 6: 29– 38. 14. Weidner N. Sarcomatoid carcinoma of the upper aerodigestive tract. Semin Diagn Pathol 1987; 4: 157–68. 15. Zarbo RJ, Crissman JD, Venkat H, Weiss MA. Spindle cell carcinoma of the upper aerodigestive tract mucosa. An immunohistochemical and ultrastructural study of 18 biphasic tumors and comparison with seven monophasic spindle-cell tumors. Am J Surg Pathol 1986; 10: 741– 53.
TEST AND TEACH Number Ninety Nine: Part 2 See page 41 for Fig. 1 and case details
EXPLANATION AND DIAGNOSIS: CARCINOSARCOMA OF THE GALLBLADDER On microscopic examination, the tumor contained both mesenchymal and epithelial elements (Fig. 2). The sarcomatous component was made up largely of interlacing bundles of spindle cells with occasional mitotic figures. There were also small foci of malignant cartilage (Fig. 3) and numerous rhabdomyoblastic cells, showing cross striations (Fig. 4). Malignant epithelial elements were in the form of ordinary adenocarcinoma, composed of glandular and cribriform structures which are formed by pleomorphic epithelial cells.
PAS and Alcian blue positivity was found in these glandular structures. Two components of the neoplasm were diffusely mixed but showed clear distinction. The liver biopsy specimen was occupied by the necrotic tumor tissue. Immunohistochemical examination was also performed to support morphological and histochemical findings. The sarcomatous component showed diffuse vimentin expression and the rhabdomyoblasts were desmin positive. Epithelial elements remained negative for these two antibodies. Conversely, epithelial membrane antigen and pancytokeratin were demonstrated in the glandular and the
Fig. 2 Malignant glandular and cribriform structures intermingle with spindle-cell sarcomatous stroma (H & E, ´ 125).
Fig. 4 Cross striations in a spindle-shaped rhabdomyoblastic cell (Masson’s trichrom, ´ 500).
Fig. 3 A malignant cartilage-including area of the gallbladder tumor (Masson’s trichrom, ´ 125).
Fig. 5 Positive immunostaining for pancytokeratin in glandular structures of the tumor (aminoethyl carbasole-peroxidase, ´ 310).
ISSN 0031–3025 printed/ISSN 1465– 3931 online/00/010063 – 02 © 2000 Royal College of Pathologists of Australasia
64
Pathology (2000), 32, February
TEST AND TEACH
cribriform elements (Fig. 5), while the sarcomatous elements remained negative. These findings were all features of the carcinosarcoma. Malignant tumors containing both epithelial and mesenchymal elements are usually called carcinosarcomas. There are few cases in the medical literature, reported as carcinosarcoma or malignant mixed tumor of the gallbladder.1– 7 The majority of the carcinosarcomas involving the gallbladder are exophytic and polypoid masses that project into the lumen and distend the gallbladder.8 Most patients present with right upper quadrant pain with or without jaundice, and either local invasion of the gallbladder bed or distant metastasis occur in the majority of cases. Our case shares the described clinical findings and growth pattern. The epithelial component was generally adenocarcinoma in the majority of previously reported cases, although squamous cell carcinoma was also seen. The sarcomatous component was usually spindle cell sarcoma in most cases,1– 4 but heterotopic elements, such as rhabdomyoblasts and cartilage, were reported by some authors2,9 and osteoclast-like giant cells by others.10,11 The epithelial component was ordinary adenocarcinoma in our case and PAS and Alcian blue positivity and positive immunoreaction for epithelial membrane antigen and pancytokeratin gave clear evidence for the epithelial nature of these structures. The sarcomatous component contained mainly ordinary spindle cell sarcoma; additionally, numerous rhabdomyoblasts and occasional malignant cartilage were present. There may be differently sited tumors with different histopathological features in the same organ. These are called collision tumors. They have a distinct border between each other and are not intermingled into each other. The presence of diffusely intermingled sarcomatous and epithelial elements and the peculiar polypoid shape of our case are sufficient findings to reject the probablity of a collision tumor. At present, the pathogenesis of these tumors remains unknown, but it has been speculated that they arise from totipotential stromal stem cells.12 In a ultrastructural study, it was postulated that cells of sarcoma-like stromal component had an epithelial nature.13 We believe that the stromal elements in our case have a malignant nature; also, heterotopic elements in the form of rhabdomyoblasts and malignant cartilage were present. Neither epithelial membrane antigens nor pancytokeratin expression were found in these sarcomatous cells. However, none of these findings give sufficient evidence to reject the probability of pure epithelial origin for our case. Furthermore, many similar neoplasms of other anatomic sites have been regarded as being of pure epithelial origin and called sarcomatoid carcinoma by many authors.14,15 The biological behavior of gallbladder carcinosarcoma is similar to the more common malignancies in this location, and a rather poor prognosis is described for such cases. In a
study including 18 cases, data showed that patients’ ages ranged from 45 to 90 years, the female to male ratio was 4.3 and the longest survival after the diagnosis of this tumor was 8 months with a mean survival of 1.9 months.4 However, in another case report it was stated that a patient was well for 31 months after a complete removal of the tumor which was confined to the gallbladder. These authors suggested that, like carcinoma, carcinosarcoma of the gallbladder may be curable when resected at an early stage.3 However, the biological behavior of this tumor is not exactly understood. Our patient died due to disseminated tumor 3 months after diagnosis. In our opinion, wherever they originate from, the peculiar histological features and aggressive biological behavior of gallbladder carcinosarcomas cause them to be of importance. Furthermore, more case reports are needed to understand the exact nature of these tumors. Address for correspondence: Dr E. Yavuz, Department of Pathology, Istanbul Medical Faculty, Çapa, Topkapõ, 34390 Istanbul, Turkey. Fax: + 90 212 6311367.
References 1. Higgs WR, Mocega EE, Jordan PH. Malignant mixed tumor of the gallbladder. Cancer 1973; 32: 471– 5. 2. Mansori KS, Cho SY. Malignant mixed tumor of the gallbladder. Am J Clin Pathol 1980; 73: 709–11. 3. Von Kuster LC, Cohen C. Malignant mixed tumor of the gallbladder: report of two cases and review of the literature. Cancer 1982; 50: 1116–70. 4. Born MW, Ramey WG, Ryan SF, Gordon PE. Carcinosarcoma and carcinoma of the gallbladder. Cancer 1984; 53: 2171–7. 5. Inoshita S, Iwashita A, Enjoji M. Carcinosarcoma of the gallbladder. Report of a case and review of the literature. Acta Pathol Jpn 1986; 36: 913– 20. 6. Lopez GA, Strimel W, Herrera-Ornelas L. Carcinosarcoma of the gallbladder. Report of a case. J Surg Oncol 1985; 29: 224– 6. 7. Lumsden AB, Mitchell WE, Wohman MD. Carcinosarcoma of the gallbladder: a case report and review of the literature. Am Surg 1988; 54: 492– 4. 8. Iezzoni JC, Mills SE. Sarcomatoid carcinomas (carcinosarcomas) of the gastrointestinal tract. A review. Semin Diagn Pathol 1993; 10: 176– 87. 9. Ishisara T, Kawano H, Takahashi M, et al. Carcinosarcoma of the gallbladder. A case report with immunohistochemical and ultrastructural studies. Cancer 1990; 66: 992–7. 10. Grosso LE, Gonzalez JG. Stromal osteoclast-like giant cells in an adenosquamous carcinoma of the gallbladder. Hum Pathol 1992; 32: 703– 6. 11. Ito M, Hsu CT, Naito S, et al. Osteoclast-like giant cell tumour of the gallbladder. Virchow’s Arch 1992; 420: 359– 66. 12. Albares-Saavedra J, Cruz-Ortiz H, Alcantara-Vazques A, Henson DE. Unusual types of gallbladder carcinoma. Arch Pathol Lab Med 1981; 105: 287–93 13. Alpers CE, Smuckler EA. Pleomorphic carcinoma of the gallbladder. Case report and ultrastructural study. Ultrastruct Pathol 1984; 6: 29– 38. 14. Weidner N. Sarcomatoid carcinoma of the upper aerodigestive tract. Semin Diagn Pathol 1987; 4: 157–68. 15. Zarbo RJ, Crissman JD, Venkat H, Weiss MA. Spindle cell carcinoma of the upper aerodigestive tract mucosa. An immunohistochemical and ultrastructural study of 18 biphasic tumors and comparison with seven monophasic spindle-cell tumors. Am J Surg Pathol 1986; 10: 741– 53.