Carcinosarcoma is a true malignant mixed tumor and differs from other forms of malignant mixed tumor. The histogenesis of malignant mixed tumor remains unknown. Two antithetic hypotheses have been suggested to explain the histogenesis of biphasic malignant tumors. Although the multiclonal hypothesis proposes an origin from 2 or more undifferentiated progenitor cells (convergence hypothesis), the monoclonal hypothesis proposes an origin from a single totipotential stem cell that differentiates into separate epithelial and mesenchymal cells (divergence hypothesis). One study showed a monoclonal origin of systemic carcinosarcoma, thus supporting the monoclonal hypothesis.13
There are 3 forms of malignant mixed tumor.14
The most common form is carcinoma ex pleomorphic adenoma, which results from malignant change in a long-standing pleomorphic adenoma or a recurrent mixed tumor that has been incompletely removed. The second form is a metastasizing mixed tumor, which contains benign-appearing epithelial and stromal components. This is thought to arise from 2 progenitor cells, including epithelial (ductal) and mesenchymal (myoepithelial) precursor cells. The third form is a true malignant mixed tumor, also referred to as carcinosarcoma, which is composed of both a malignant epithelial and a malignant mesenchymal component. This form is thought to arise from a monoclonal stem cell that is totipotential (monoclonal hypothesis) and represented by both of our cases. The tumors in our patients may have arisen in accessory lacrimal glands and submucosal glands in the area of the lacrimal sac or paranasal sinus.
The first reported case of carcinosarcoma was in 1899 in a description of a uterine tumor.1
The first reported case of carcinosarcoma of the orbit was in 1992 by Ni et al,9
who described a lacrimal gland tumor. There have only been 3 reported cases of primary carcinosarcoma of the orbit.9–11
Of those 3 cases, only 1 was described in sufficient detail to verify the presence of a bona fide carcinosarcoma.11
One patient had no evidence of local recurrence or metastasis 10 months after surgical resection,11
and another patient developed lung metastases.10
There was no follow-up information provided for the third patient.9
These 3 cases along with our current 2 cases are summarized in .
Because orbital carcinosarcoma may arise from or extend into the paranasal sinuses, we also reviewed previously reported cases of carcinosarcoma of the paranasal sinuses.15–26
We identified 5 cases of carcinosarcoma that originated in the maxillary sinus or ethmoid sinus with extension into the orbit.15,16,19,23,26
These cases are summarized in . These patients were 45 to 86 years old, most were women (12/19), and most were Japanese (12/14). The most common symptoms were nasal obstruction and epistaxis. There were 2 patients with ophthalmic symptoms, and both had diplopia. Histologic examination of the tumors showed that the carcinomatous component was squamous cell carcinoma in all tumors and that the sarcomatous component included fibrosarcoma (6/14), osteosarcoma (4/14), sarcoma not otherwise specified (3/14), and leiomyosarcoma (1/14). The majority of the cases were treated with a combination of surgical resection, radiation, and chemotherapy, including vincristine, etoposide, ifosfamide, doxorubicin, 5-FU, and cisplatin. Because of the rarity of cases of carcinosarcoma, prospective trials evaluating chemotherapeutic regimens have not been performed. According to a review on ovarian carcinosarcomas, they seem to be sensitive to platinum-based chemotherapy and encouraging results have been shown with platinum-ifosfamide and platinum-taxane schedules, which are usually considered the treatment of choice.2
Six patients had tumor recurrence, and 4 patients had evidence of metastasis. Four of the 6 patients with tumor recurrence had a recurrence of the sarcomatous portion of the tumor.15,20,22,23
Sites of metastasis included submandibular, submaxillary, and cervical lymph nodes; lung; pleurae; brain; diaphragm; bone; and liver. Although 1 patient was reported to be alive 28 months after diagnosis, most patients died within a few months to approximately 1.5 years after diagnosis.
Carcinosarcoma of the Paranasal Sinuses
The tumors in both of our patients arose in the medial canthal region. Both tumors were composed of poorly differentiated carcinoma and sarcoma, not otherwise specified. Although the tumor in our first patient appeared to originate in the lacrimal sac area, it is possible that the tumors in both patients arose in the nasal cavity or paranasal sinuses. Both patients were women and presented with nonspecific symptoms. Our first patient died 14 months after diagnosis, and our second patient was lost to follow-up.
The pathologic differential diagnosis of carcinosarcoma includes spindle cell carcinoma, pleomorphic carcinoma, desmoplastic melanoma, teratocarcinosarcoma, and malignant teratoma. Histologic features and immunohistochemical findings differentiate these entities from carcinosarcoma. Carcinosarcoma is an aggressive neoplasm that exhibits local tissue invasion and often metastasizes. Carcinosarcoma of the orbit may locally invade the intracranial cavity, as seen in our first patient, and thus be related to a high rate of mortality. For these reasons, we recommend aggressive surgical excision of orbital carcinosarcoma along with adjuvant chemotherapy and radiation therapy. It appears that the carcinomatous component of the tumor is more sensitive than the sarcomatous component to radiation and chemotherapy.20,22