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True Malignant Mixed Tumor (Carcinosarcoma)
Updated: Aug 21, 2009
Definition
Different patterns of malignant change occur in pleomorphic adenoma, of which true malignant mixed tumor (carcinosarcoma) is one form; the other 2 forms are carcinoma ex pleomorphic adenoma and metastasizing benign pleomorphic adenoma.
By definition, carcinosarcoma is a biphasic malignant tumor with both a carcinomatous component and a sarcomatous component. Most arise in the background of pleomorphic adenoma. However, some arise de novo .
Carcinosarcoma of the salivary glands was first described by Kirklin et al in 1951.1 The term true malignant mixed tumor in the salivary glands was first used by King in 1967 in a study that helped to renew interest in this tumor group.2
Epidemiology
Almost 70 cases of malignant mixed tumor have been reported in the literature. Most of them (43 cases) were summarized by Gnepp in 1993.3 Carcinosarcoma remains an extremely rare and aggressive entity. It accounts for only 0.04-0.16% of all salivary gland tumors. In the reported cases, patients ranged in age from 15-85 years. There was no predilection with regard to gender. Many of the patients had a history of pleomorphic adenoma, recurrent pleomorphic adenoma, or recurrent carcinoma ex pleomorphic adenoma.4,5,6,3,7,8,9,10,11 Some cases, however, seem to arise de novo, in the absence of a previous pleomorphic adenoma.12,3,13,14 Approximately 30 de novo cases have been reported.15
Etiology
No clear etiology is known. However, accumulation of genetic mutations could be a factor. A history of exposure to irradiation to pleomorphic adenoma has been reported.11,16 The reported interval between the irradiation and the onset of carcinosarcoma varied from 1 to 36 years.
Two schools of thought exist as to the origin of these of tumors. The convergence hypothesis maintains that multiclonal stem cells of the epithelial and mesenchymal components play a causative role. The divergence hypothesis postulates a monoclonal origin from a single totipotent stem cell with divergent differentiation.17,18 The latter hypothesis is more favored. Gotte et al hypothesized that the tumor originates from a myoepithelial cell precursor.19 Other investigators have postulated that the tumor originates from inner ductal cells5 or a pluripotent primitive cell.13
Location
In the major salivary glands, most reported cases (65%) occurred in the parotid gland.1,3,4 Some cases (19%) have been reported in the submandibular gland.13,3,20 In the minor salivary glands, the palate is the most common site.6
Clinical Features and Imaging
The tumor presents as a mass that may be rapidly enlarging. In some cases, the mass is painful; the pain may be localized, referred, or both. If the parotid gland is involved, signs of facial nerve weakness/paralysis are commonly encountered.
Gross Findings
True malignant mixed tumors are poorly circumscribed, with infiltrative borders. They are gray, and focal areas of hemorrhage and necrosis may be present. Some tumors are well circumscribed. Most reported tumors range from 2-13 cm in greatest dimension.
Microscopic Findings
Carcinosarcoma is a biphasic tumor in which the carcinomatous component is usually a poorly differentiated adenocarcinoma, an undifferentiated carcinoma, or a squamous cell. It may also include adenoid cystic carcinoma, epithelial myoepithelial carcinoma, and salivary duct carcinoma. The sarcomatous component is usually a chondrosarcoma. Other reported sarcomatous elements include spindle cell sarcoma NOS, fibrosarcoma, osteosarcoma, leiomyosarcoma, liposarcoma, follicular dendritic cell sarcoma, undifferentiated sarcoma, myxoid sarcomas, and rhabdomyosarcoma,21,15 among others. The relative proportion of the 2 components is variable, and either component may dominate the histologic picture.
In the accompanying figures, the sarcomatous (spindle cell sarcoma) component is dominant, with a smaller portion of poorly differentiated adenocarcinoma (see Media files 1-2).
The carcinomatous component of a carcinosarcoma of the parotid gland. In this case, the tumor is a poorly differentiated adenocarcinoma.
The sarcomatous component of a carcinosarcoma of the parotid gland. In this case, the tumor is a spindle cell sarcoma NOS.
The histologic picture depends on the types of the constituent cells of sarcoma and carcinoma. Extensive infiltration and tissue destruction are common, as is perineural invasion and angioinvasion. Lymphatic spread is less common.22
Metastases to other sites or lymph nodes may show the carcinomatous or the sarcomatous components alone, or they may be mixed.
Immunohistochemistry
The immunohistochemical panel varies, depending on the observed biphasic components of the tumor. Generally speaking, however, the carcinomatous component is usually cytokeratin and EMA positive. However, it should be noted that in very poorly differentiated tumors, the carcinomatous component may show only focal or weak positive staining for cytokeratins or EMA, a feature that is sometimes encountered in very poorly differentiated cancers of the head and neck. In such cases, electron microscopy may be helpful. The sarcomatous component is vimentin positive.
Molecular/Genetics
Few genetic studies have been performed on these tumors, owing to their rarity. However, abnormalities in chromosomes 7, 8, 9, 10, 12, 13, 17, and 18 have been described.18,19 A recent study18 showed specific amplifications of MUC 20 in mesenchymal elements (gene products known to be overexpressed in various cancers that correlate with poor outcome). BMI-1 (a proto-oncogene found to be deregulated in several neoplasms, including salivary gland tumors) was observed in both element loci.18
Tumor Spread and Staging
The American Joint Committee on Cancer23 (AJCC) lists the staging of major salivary gland (ie, parotid, submandibular, sublingual) malignant tumors as follows:
TNM classification
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Table
| T- | Primary tumor |
| Tx | Primary tumor cannot be assessed |
| T0 | No evidence of primary tumor |
| T1 | Tumor 2 cm or less in greatest dimension without extraparenchymal extension |
| T2 | Tumor more than 2 cm but not more than 4 cm in greatest dimension without extraparenchymal extension |
| T3 | Tumor more than 4 cm and/or tumor having extraparenchymal extension |
| T4a | Tumor invades skin, mandible, ear canal, and/or facial nerve |
| T4b | Tumor invades skull base and/or pterygoid plates and/or carotid artery |
| N- | Regional lymph nodes |
| NX | Regional lymph nodes cannot be assessed |
| N0 | No regional lymph node metastasis |
| N1 | Metastasis into a single ipsilateral lymph node, 3 cm or less in greatest dimension |
| N2 | Metastasis into a single ipsilateral lymph node, greater than 3 cm in greatest dimension but not greater than 6 cm in greatest dimension, or in multiple ipsilateral lymph nodes, none greater than 6 cm in greatest dimension, or in bilateral or contralateral lymph nodes, none greater than 6 cm in greatest dimension |
| N3 | Metastasis in a lymph node greater than 6 cm in greatest dimension |
| M- | Distant metastasis |
| MX | Distant metastasis cannot be assessed |
| M0 | No distant metastasis |
| M1 | Distant metastasis |
| T- | Primary tumor |
| Tx | Primary tumor cannot be assessed |
| T0 | No evidence of primary tumor |
| T1 | Tumor 2 cm or less in greatest dimension without extraparenchymal extension |
| T2 | Tumor more than 2 cm but not more than 4 cm in greatest dimension without extraparenchymal extension |
| T3 | Tumor more than 4 cm and/or tumor having extraparenchymal extension |
| T4a | Tumor invades skin, mandible, ear canal, and/or facial nerve |
| T4b | Tumor invades skull base and/or pterygoid plates and/or carotid artery |
| N- | Regional lymph nodes |
| NX | Regional lymph nodes cannot be assessed |
| N0 | No regional lymph node metastasis |
| N1 | Metastasis into a single ipsilateral lymph node, 3 cm or less in greatest dimension |
| N2 | Metastasis into a single ipsilateral lymph node, greater than 3 cm in greatest dimension but not greater than 6 cm in greatest dimension, or in multiple ipsilateral lymph nodes, none greater than 6 cm in greatest dimension, or in bilateral or contralateral lymph nodes, none greater than 6 cm in greatest dimension |
| N3 | Metastasis in a lymph node greater than 6 cm in greatest dimension |
| M- | Distant metastasis |
| MX | Distant metastasis cannot be assessed |
| M0 | No distant metastasis |
| M1 | Distant metastasis |
Stage grouping
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Table
| Stage | Grouping |
| Stage I | T1 N0 M0 |
| Stage II | T2 N0 M0 |
| Stage III | T3 N0 M0 |
| T1 N1 M0 | |
| T2 N1 M0 | |
| T3 N1 M0 | |
| Stage IVA | T4a N0 M0 |
| T4a N1 M0 | |
| T1 N2 M0 | |
| T2 N2 M0 | |
| T3 N2 M0 | |
| T4a N2 M0 | |
| Stage IVB | T4b Any N M0 |
| Any T N3 M0 | |
| Stage IVC | Any T Any N M1 |
| Stage | Grouping |
| Stage I | T1 N0 M0 |
| Stage II | T2 N0 M0 |
| Stage III | T3 N0 M0 |
| T1 N1 M0 | |
| T2 N1 M0 | |
| T3 N1 M0 | |
| Stage IVA | T4a N0 M0 |
| T4a N1 M0 | |
| T1 N2 M0 | |
| T2 N2 M0 | |
| T3 N2 M0 | |
| T4a N2 M0 | |
| Stage IVB | T4b Any N M0 |
| Any T N3 M0 | |
| Stage IVC | Any T Any N M1 |
Tumor spread may occur by direct extension, hematogenous, lymphatic, or perineural invasion.
The staging of tumor in the salivary gland depends on whether the tumor is located in the head or neck area.
Prognosis and Predictive Factors
Carcinosarcoma is an aggressive, high-grade tumor. Recurrence, distant metastasis (54%), and angiolymphatic invasion are frequently encountered. The lungs are the most common site of metastasis. Metastasis may also occur to liver, bone, and brain. Involvement of cervical lymph nodes with metastasis is uncommon.
In a review by Gnepp,3 58% of patients died as a result of the tumor. In a review of 19 cases of de novo carcinosarcomas by Staffeieri et al,15 31.6% of patients died of the disease. The median period of survival after diagnosis was 10 months; in 63% of cases, there was no evidence of recurrence after a median period of 22.4 months.
Because of the rarity of the tumor, whether arising de novo or in a pleomorphic adenoma, consensus on therapeutic approaches has been lacking. A combination of surgery followed by radiotherapy seems to be statistically superior to resection alone.15 The role of chemotherapy remains unclear.
Differentials
| Biphasic synovial sarcoma | Other sarcomas |
| Carcinoma Ex Pleomorphic Adenoma | Salivary duct carcinoma with a infiltrating
desmoplastic component |
| Collision tumors | Sarcomatoid variant of salivary duct
carcinoma |
| Giant cell carcinoma | Spindle cell carcinoma |
Multimedia
 | Media file 1: The carcinomatous component of a carcinosarcoma of the parotid gland. In this case, the tumor is a poorly differentiated adenocarcinoma. |
 | Media file 2: The sarcomatous component of a carcinosarcoma of the parotid gland. In this case, the tumor is a spindle cell sarcoma NOS. |
Keywords
true malignant mixed tumor, carcinosarcoma, pleomorphic adenoma, carcinoma ex pleomorphic adenoma, metastasizing mixed tumor, metastasizing pleomorphic adenoma
More on True Malignant Mixed Tumor (Carcinosarcoma) |
| References |
| Further Reading |
References
Kirklin JW, Mcdonald JR, Harrrington SW, New GB. Parotid tumors; histopathology, clinical behavior, and end results. Surg Gynecol Obstet. Jun 1951;92(6):721-33. [Medline].
King OH Jr. Carcinosarcoma of accessory salivary gland. First report of a case. Oral Surg Oral Med Oral Pathol. May 1967;23(5):651-9. [Medline].
Gnepp DR. Malignant mixed tumors of the salivary glands: a review. Pathol Annu. 1993;28 Pt 1:279-328. [Medline].
Stephen J, Batsakis JG, Luna MA, von der Heyden U, Byers RM. True malignant mixed tumors (carcinosarcoma) of salivary glands. Oral Surg Oral Med Oral Pathol. Jun 1986;61(6):597-602. [Medline].
Alvarez-Cañas C, Rodilla IG. True malignant mixed tumor (carcinosarcoma) of the parotid gland. Report of a case with immunohistochemical study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. Apr 1996;81(4):454-8. [Medline].
Carson HJ, Tojo DP, Chow JM, Hammadeh R, Raslan WF. Carcinosarcoma of salivary glands with unusual stromal components. Report of two cases and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. Jun 1995;79(6):738-46. [Medline].
Gandour-Edwards RF, Donald PJ, Vogt PJ, Munn R, Min KW. Carcinosarcoma (malignant mixed tumor) of the parotid: report of a case with a pure rhabdomyosarcoma component. Head Neck. Jul-Aug 1994;16(4):379-82. [Medline].
Granger JK, Houn HY. Malignant mixed tumor (carcinosarcoma) of parotid gland diagnosed by fine-needle aspiration biopsy. Diagn Cytopathol. 1991;7(4):427-32. [Medline].
Hellquist H, Michaels L. Malignant mixed tumour. A salivary gland tumour showing both carcinomatous and sarcomatous features. Virchows Arch A Pathol Anat Histopathol. 1986;409(1):93-103. [Medline].
López JI, Ballestin C, Garcia-Prats MD, De Agustin P. Carcinosarcoma of the parotid gland: immunohistochemical study of a case. Histopathology. Oct 1994;25(4):388-90. [Medline].
Spraggs PD, Rose DS, Grant HR, Gallimore AP. Post-irradiation carcinosarcoma of the parotid gland. J Laryngol Otol. May 1994;108(5):443-5. [Medline].
Latkovich P, Johnson RL. Carcinosarcoma of the parotid gland: report of a case with cytohistologic and immunohistochemical findings. Arch Pathol Lab Med. Aug 1998;122(8):743-6. [Medline].
Bleiweiss IJ, Huvos AG, Lara J, Strong EW. Carcinosarcoma of the submandibular salivary gland. Immunohistochemical findings. Cancer. Apr 15 1992;69(8):2031-5. [Medline].
Grenko RT, Tytor M, Boeryd B. Giant-cell tumour of the salivary gland with associated carcinosarcoma. Histopathology. Dec 1993;23(6):594-5. [Medline].
Staffieri C, Marioni G, Ferraro SM, Marino F, Staffieri A. Carcinosarcoma de novo of the parotid gland. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. Aug 2007;104(2):e35-40. [Medline].
Hellquist H, Michaels L. Malignant mixed tumour. A salivary gland tumour showing both carcinomatous and sarcomatous features. Virchows Arch A Pathol Anat Histopathol. 1986;409(1):93-103. [Medline].
Thompson L, Chang B, Barsky SH. Monoclonal origins of malignant mixed tumors (carcinosarcomas). Evidence for a divergent histogenesis. Am J Surg Pathol. Mar 1996;20(3):277-85. [Medline].
Vékony H, Leemans CR, Ylstra B, Meijer GA, van der Waal I, Bloemena E. Salivary gland carcinosarcoma: oligonucleotide array CGH reveals similar genomic profiles in epithelial and mesenchymal components. Oral Oncol. Mar 2009;45(3):259-65. [Medline].
Götte K, Riedel F, Coy JF, Spahn V, Hörmann K. Salivary gland carcinosarcoma: immunohistochemical, molecular genetic and electron microscopic findings. Oral Oncol. Jul 2000;36(4):360-4. [Medline].
Bhalla RK, Jones TM, Taylor W, Roland NJ. Carcinosarcoma (malignant mixed tumor) of the submandibular gland: A case report and review of the literature. J Oral Maxillofac Surg. Sep 2002;60(9):1067-9. [Medline].
Kwon MY, Gu M. True malignant mixed tumor (carcinosarcoma) of parotid gland with unusual mesenchymal component: a case report and review of the literature. Arch Pathol Lab Med. Jun 2001;125(6):812-5. [Medline].
Qureshi A, Barakzai A, Sahar NU, Gulzar R, Ahmad Z, Hassan SH. Spectrum of malignancy in mixed tumors of salivary gland: a morphological and immunohistochemical review of 23 cases. Indian J Pathol Microbiol. Apr-Jun 2009;52(2):150-4. [Medline].
American Joint Committee on Cancer. Major salivary glands. In: Greene FL, Page DL, Fleming ID, Fritz AG, Balch CM, Haller DG, et al, eds. AJCC Cancer Staging Manual. 6th ed. New York: Springer-Verlag; 2002:69-75.
Further Reading
Related eMedicine topics
Pleomorphic Adenoma
Carcinoma Ex Pleomorphic Adenoma
Metastasizing Pleomorphic Adenoma
Keywords
true malignant mixed tumor, carcinosarcoma, pleomorphic adenoma, carcinoma ex pleomorphic adenoma, metastasizing mixed tumor, metastasizing pleomorphic adenoma
