Malignant mixed tumor of the salivary glands is a rare neoplasm, andthe majority of these tumors arise from the parotid gland.1 Histopathologically,3 distinct variants of malignant mixed tumors are recognized, the most commonbeing carcinoma arising from a preexisting pleomorphic adenoma.1- 2 Thesecond type is the metastasizing mixed tumor, which has benign-appearing epithelialand stromal components.1- 2 Thetrue malignant mixed tumor or carcinosarcoma, an exceptionally rare tumor,is the third subtype and is composed of malignant epithelial and malignantmesenchymal elements.2- 3
Less than 5% of all salivary gland neoplasms are seen in patients youngerthan 16 years and 13% of these tumors are solid, of which only 23% are malignant.4 The most common malignant salivary gland tumorin children is mucoepidermoid carcinoma, followed by rhabdomyosarcoma andacinic cell carcinoma.4 We herein describea highly unusual patient with a carcinosarcoma of the parotid gland that metastasizedto ipsilateral orbit and intraocular structures.
A 10-year-old boy was seen at another institution because of right orbitaland preauricular masses that evolved gradually during a period of 6 months(Figure 1). His medical historyincluded trabeculectomy for right congenital glaucoma at the age of 3 years.His records indicate that there was no evidence of an intraocular mass oriris neovascularization.
Patient at initial examination,the day after the incisional biopsy was performed.
Visual acuity in the right eye had remained no light perception sincethen. Magnetic resonance images showed a right anterior orbital and preseptalmass, as well as a large noncystic tumor occupying the right anterior superficialpart of the parotid gland (Figure 2).After an unsuccessful trial of systemic antibiotics for 10 days, an incisionalbiopsy specimen obtained through the superior lid crease was reported as showingalveolar rhabdomyosarcoma. A fine-needle aspiration biopsy specimen from theparotid mass showed round-cell malignant tumor, which was interpreted as metastaticrhabdomyosarcoma.
T1-weighted axial magnetic resonanceimages. A, The anterior orbital mass is homogeneously hypointense relativeto the orbital fat. B, A large, homogeneous solid mass arises from the rightanterior superficial part of the parotid gland.
The patient received 14 cycles of vincristine sulfate, 1.5 mg/m2; etoposide, 150 mg/m2; ifosfamide, 2 mg/m2;and doxorubicin hydrochloride, 20 mg/m2. The right orbit and theparotid gland region were irradiated with a total dose of 5400 rad (54 Gy)by 200-rad (2-Gy) fractions. Because there was only partial response to thistreatment, the patient was referred to our center.
On our examination, the right eye had no light perception and the visualacuity in the left eye was 20/20. On the right side, there was a single largeepiscleral mass that was fleshy, red, immobile, painless, and hard on palpation(Figure 3). The cornea was opaque,and no fundus details could be seen. Ultrasonography failed to detect a definableintraocular solid lesion. The left eye was normal. A systemic workup failedto show any distant metastases.
Lack of total regression of theepibulbar and preauricular tumors 15 months later, despite radiotherapy andintensive chemotherapy.
A total right parotidectomy and enucleation of the right eye includingthe episcleral nodule were performed. Histopathologic examinations showedcarcinosarcoma of the parotid gland with episcleral and in traocular metastases.The patient then received 6 cycles of cisplatin, 120 mg/m2, andfluorouracil, 1000 mg/m2. He did not have any recurrence or metastasisduring 50 months of follow-up.
The excised parotid gland was firm and had nodular contours, and thecut surfaces were partly tan or creamy white (Figure 4). The globe was small and soft with a firmly adherent superiorepiscleral nodule (Figure 5). Therewere scleral thickening and posterior staphyloma formation. The site of trabeculectomythrough which neoplastic tissues extended into the globe was easily identified.On light microscopy, the tumor was composed of columns of epithelial cellsforming adenoid structures and islands of hypercellular cartilage (Figure 6). There were atypical chondroidcells showing pleomorphism, and the lacunae contained more than 1 nucleus,suggesting malignancy (Figure 7).Residual islands of normal parotid gland tissues were also observed. The intraoculartumor was also composed of mixed malignant chondroid and epithelial elements(Figure 8). There was no evidenceof uveal tract involvement. The results of immunohistochemical and histochemicalstudies are shown in Table 1 and Table 2, respectively. The chondroid andepithelial cells contained abundant glycogen, and the luminal surface of epithelialcells had neutral mucin. Almost identical features were observed on reevaluationof the slides of the initial incisional biopsy, erroneously reported as rhabdomyosarcoma.
Gross view of the parotid glandshowing the cut surface. The tumor measured 7 × 5.5 × 3.5 cm.There was no intratumoral hemorrhage or necrosis despite previous treatment.
Gross view of the enucleated eyeshowing the large episcleral metastatic tumor and the trabeculectomy site(arrow) through which the tumor presumably invaded the intraocular compartment.
Photomicrograph showing the epithelial-dominantpart of the episcleral tumor. The epithelial cells have hyperchromic and vesicularnuclei with prominent nucleoli and eosinophilic cytoplasms. A single islandof cartilage is present at the lower right of the figure (hematoxylin-eosin,original magnification ×100).
Photomicrograph showing the mesenchymal-dominantpart of the episcleral tumor. Many hypercellular islands of cartilage canbe identified with interspersed malignant epithelial elements (hematoxylin-eosin,original magnification ×40).
Photomicrograph demonstratingthe intraocular tumor with both malignant chondroid and epithelial components.At the left side of the figure, disorganized retinal pigment epithelia arerecognized (hematoxylin-eosin, original magnification ×40).
This patient underwent a series of extremely unusual events, includingparotid gland malignancy with the exceptionally rare form of de novo carcinosarcomaat the age of 10 years and metastases to the orbit and epibulbar tissues,with intraocular invasion through a trabeculectomy site. Patients with malignantmixed tumor of the parotid gland usually have onset in the fifth decade oflife (range, 7-86 years), with a history of a mass of 10 to 50 years' duration.5 Carcinosarcoma composes only 0.4% of all salivarygland tumors, and, by definition, both epithelial and mesenchymal componentsshould fulfill the criteria for malignancy and typically metastasize together.3,6 Criteria for malignancy includedestruction of normal tissues, invasiveness, cellular anaplasia, pleomorphism,and atypical mitoses.2 A high-grade ductalcarcinoma is the usual epithelial component, whereas chondrosarcoma is themost common mesenchymal component.2 However,fibrosarcoma, leiomyosarcoma, osteosarcoma, and rhabdomyosarcoma may alsobe encountered.3,7 Our patientclearly showed definable carcinomatous and sarcomatous areas in the primaryand metastatic tumors. Carcinosarcoma may also develop years after irradiationof a pleomorphic adenoma.2- 3 Ourcase probably represents carcinosarcoma arising de novo, which is anotherrarity in itself.
Controversy surrounds the cell of origin of malignant mixed tumor ingeneral and carcinosarcoma in particular. There is recent evidence that myoepithelialcells may serve as a common stem cell for both carcinomatous and sarcomatouscomponents.8 Myoepithelial cells expresskeratins, vimentin, and S100.9 Tests forsmooth-muscle actin and muscle-specific actin may be positive in 50% of cases,whereas tests for carcinoembryonic antigen, which indicates luminal differentiationand epithelial membrane antigen, are typically negative.9 Neoplasticchondrocytes express vimentin and are thought to develop by metaplastic myoepithelialcells.10 Our immunohistochemical stainingresults support these findings.
Malignant teratoid medulloepithelioma must be considered in the differentialdiagnosis of our case. This tumor may cause neovascular or angle-closure glaucoma,and histopathologically it may contain undifferentiated neuroblastic cellsresembling retinoblastoma and heteroplastic tissues including brain, skeletalmuscles, and cartilage.11 Furthermore, criteriafor malignancy include uveal invasion and the presence of sarcomatous elementslike chondrosarcoma, rhabdomyosarcoma, or embryonal sarcoma, among others.12 However, a carcinomatous component and the presenceof both mesenchymal and carcinomatous elements at metastatic sites are notfeatures of malignant teratoid medulloepithelioma, which shows intracranialextension rather than distant metastases in most cases.
More than 50% of patients with carcinosarcoma develop metastases, andthe most common sites include lungs, liver, bones, local and hilar lymph nodes,and central nervous system.2,7 Tothe best of our knowledge, orbit and intraocular structures have not beenpreviously reported as metastatic sites. This unique case, therefore, representsa collection of exceptionally rare events and demonstrates that carcinosarcomamay occur in children and metastasize regionally as well.
The authors have no relevant financial interest in this article.
Corresponding author: Hayyam Kiratli, MD, Ophthalmology, HacettepeHastanesi Goz ABD, Sýhhiye 06100, Ankara, Turkey (e-mail: email@example.com).
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