Answer: Sinonasal teratocarcinosarcoma

Histology: The hallmark histologic feature of this tumor is the intimate admixture of epithelial and mesenchymal elements.

Glandular/ductal elements: The presence of irregular spaces lined by a columnar ductal epithelium is a striking feature. The degree of atypia is highly variable, and often occurs along a cytologic spectrum that ranges from bland (sometimes ciliated) columnar epithelium to adenomatous to overtly malignant adenocarcinoma.

Squamous elements: The columnar epithelium often shows very abrupt transition with a squamous epithelium. These squamous nests are given their distinctive appearance by their prominent cytoplasmic clearing. Intercellular bridges are not evident. Instead, the clear cells are separated by defined cell partitions. The cells have bland cytologic features without significant cellular atypia. Some have noted that these cells bear a striking histologic resemblance to squamous mucosa of the fetus.

Mesenchymal stromal component: The ductal and squamous elements are surrounded by zones of a fibrous stroma that shows remarkable variability in the degree of cellularity and atypia, ranging from a loosely cellular reactive fibroblastic/myofibroblastic proliferation to a highly cellular sarcomatous proliferation. It is not uncommon to encounter specific types of mesenchymal differentiation including rhabdomyoblastic and cartilaginous differentiation.

Neuroectodermal element: The neuroepithelial component takes on a highly primitive and high grade appearance. It is seen as a sheet-like proliferation of small blue cells with necrosis and abundant mitotic figures. Scattered rosettes are sometimes apparent. The primitive cells are often positive for synaptophysin and chromogranin.

Discussion: Sinonasal teratocarcinoma sarcoma (SNTCS) is a peculiar malignant sinonasal neoplasm that is characterized by a complex admixture of epithelial, mesenchymal and primitive cellular elements along a histologic spectrum ranging from benign to atypical to overtly malignant. The confusing histologic makeup is reflected in the various terminologies that have historically been applied to this tumor including malignant teratoma, carcinosarcoma and blastoma. Its most detailed and comprehensive description was provided by Drs. Hefner and Hyams in 1984 in their report of 20 cases (Heffner, Hyams, Teratocarcinosarcoma (malignant teratoma?) of the nasal cavity and paranasal sinuses: A clinicopathologic study of 20 cases. Cancer 53:2140-2154, 1984). In this sentinel paper, the authors favored the term “teratocarcinosarcoma” over malignant teratoma largely based on the supposition that the tumor is histogenically derived from a multipotential somatic stem cell of the neuroepithelium rather than an embryologically displaced germ cell.< More often than not, SNTCS is misdiagnosed on pre-resection biopsies. The problem in establishing a correct diagnosis largely reflects the inability to fully appreciate the heterologous nature of this unusual neoplasm in a limited tumor sampling. The pre-resection diagnosis is, of course, strongly influenced by the tumor component that is represented in the biopsy. A biopsy that captures the ductal component may be mistaken for a sinonasal adenocarcinoma. One where the squamous component is present may be misdiagnosed as a squamous cell carcinoma. When the histologic picture is dominated by the stromal component, the tumor may be misclassified as a fibrosarcoma, chondrosarcoma or a rhabdomyosarcoma depending on the nature of mesenchymal differentiation. As the primitive neuroectodermal component represents the overriding histologic component of many SNTCSs, most tumors are misdiagnosed as esthesioneuroblastoma. SNTCS is a highly aggressive neoplasm that requires an aggressive therapeutic approach. Most studies advocate multimodality treatment that includes aggressive surgical resection and radiation therapy. The role for chemotherapy is less clear, particularly in the absence of large and prospective clinical trials to gauge the effectiveness of various chemotherapeutic regimens. Even following aggressive therapy, about half of all patients die of disease, usually within 3 years of initial diagnosis. Treatment failure may take the form of local, regional or distant relapse.