Background

Sinonasal Undifferentiated Carcinoma (SNUC) is a rare and highly aggressive neoplasm arising from the nasal cavity. Fewer than 100 patients have ever been diagnosed, and there appear to be only a handful alive in the US at any one time. Andy Martin was one of these, diagnosed as a medical student during his first year at Tulane University in New Orleans. Andrei Makovic was another, disgnosed at the age of 37 not long after the birth of his son. The treatments both patients received have worked well in other types of cancer, but have failed to cure SNUC. Both Andy and Andrei died within a few years of diagnosis, as these treatments also failed them.

Andy Martin understood the crucial problem facing his physicians: Without a stable population of SNUC cells living in a petri dish or as an engrafted tumor on an experimental mouse, it was impossible to study the cancer, treat it with different cancer drugs, and determine what killed it most effectively. Lacking this, both Andy and Andrei became their own ginuea pigs. Each drug given to them had never been shown to be effective in treating SNUC. Actually, each drug had already been proven to be largely ineffective, as the dozens of patients previously treated using these common drugs had died.

Using his own biopsy specimens, Andy was able to culture some neoplastic cells from his SNUC tumor before he became to weak to work in the lab. These cultures were placed in cryopreservation at Tulane when he died. When Andrei was diagnosed with SNUC a few months later, these cells could have provided a critical headstart in our own efforts to find an effective drug. Unfortunately, before the cells could be located and transferred, hurricane Katrina devastated Andy's former lab in New Orleans. At present, it is unknown whether these cultures are still in existence.

After this critical 12-month setback, Andrei agreed to a second major cranial surgery in order to obtain a fresh tumor biopsy. Using this biopsy, the team at Cayman again isolated a set of neoplastic-looking cells from the SNUC tumor. The cells were frustratingly fragile, difficult to culture, and phenotypically unstable, growing so slowly that we sometimes remarked, "All you need to do to cure SNUC is put it into one of our culture dishes." When Andrei died, these cultured cells were also cryogenically preserved. We were just barely able to keep them alive, but could never make them flourish. All of the immune compromised mice that we injected with the SNUC cells lived a happy, tumor free, if still immunocompromised life. Without duplicate and triplicate cultures for study controls, we could undertake only the most rudimentary anticancer drug screening.

We have learned a number of things about the antigens, tumor markers, and metabolic products that SNUC cells express. We know how to keep them alive. As of 2006, we are waiting to use what knowledge we have gained to bring a better outcome to the next SNUC patient who seeks our help.

"Sinonasal Undifferentiated Carcinoma (SNUC)is a rare and highly aggressive neoplasm arising from the nasal cavity and paranasal sinuses that was first described in 1986. The tumor is composed of small to medium-sized undifferentiated cells arranged in nests, frequently accompanied by extensive necrosis. Generally, the tumor is extensive at presentation and involves multiple sinonasal structures. Extension into the orbit and cranial cavity is frequent. Most patients die within one year of diagnosis." (From Jeng, et. al. in The American Journal of Surgical Pathology, 26, 371-376 (2002)

Sinonasal Undifferentiated Carcinoma With Orbital Invasion: Report of Three Cases. Ophthalmic Plastic & Reconstructive Surgery. 17(4):288-292, July 2001. Sharara, Nariman M.D. *; Muller, Susan M.D. +; Olson, Jeffrey M.D. ++; Grist, William J. M.D. [S]; Grossniklaus, Hans E. M.D. *

PMID:11476180

Purpose: To report three patients with sinonasal undifferentiated carcinoma (SNUC) that invaded the orbit. Methods: Retrospective small case series. The clinical, radiographic, and pathologic features of three patients with SNUC were reviewed. Results: Three patients with SNUC that invaded the orbit were evaluated. A biopsy was performed on the tumors, which were composed of small, hyperchromatic cells with numerous mitoses and areas of necrosis. Immunohistochemical staining was positive for cytokeratins AE1,3, epithelial membrane antigen, and neuron-specific enolase in all three tumors. Electron microscopic examination showed absence of neurosecretory granules and presence of basement membrane production. Two patients were treated with surgical resection and postoperative chemotherapy and/or radiation. One patient was treated with preoperative radiation and chemotherapy. Conclusions: Sinonasal undifferentiated carcinoma is a high-grade tumor that arises in the nasal and paranasal sinuses and may invade the orbit. SNUC should be distinguished from other small, round, blue cell tumors, in particular, esthesioneuroblastoma.


http://www.thedoctorsdoctor.com/diseases/sinonasal_undiff_ca.htm#ipox