Olfactory neuroblastoma (esthesioneuroblastoma, ЕNB) is a tumor arising from the olfactory neuroepithelium. Usually, the tumor mass originates from the superior nasal cavity meatus and it is presented as a nasal polyp that occupies superior turbinate, superior portion of nasal septum and cribriform plate. Its biological activity ranges from indolent growth to local recurrence and rapid widespread metastasis [1] . We report a rare case of olfactory neuroblastoma combined with thyroid gland carcinoma, treated successfully with surgical resections. One year after surgeries, the clinical examination of the patient showed gastrointestinal stromal carcinoma.

In the literature there are only few ENB casesarised from ectopic regions such as maxillary sinus, sphenoid sinus,

etc. In 2007, Lee and Kim reported a primary olfactory neuroblastoma originating from the inferior meatus of the nasal cavity [2] . So far, we have not found reported case of ENB combined with thyroid gland carcinoma and GIST.

Esthesioneuroblastoma has been described by Berger and Luc in 1924 [3] . This neoplasm is relatively rare and it is known by various names: esthesioneuroepithelioma, esthesioneurocytoma, esthesioneuroblastoma, olfactory esthesioneuroma, intranasal neuroblastoma, and neural olfactory tumor [4] . The tumor can affect both children and adults, with a bimodal peak incidence between 11 and 20 years and between 51 and 60 years [5] .

There are cases of 3-year-old [5] and 89-year-old man with ENB [2] . ENB is locally aggressive tumor that has an incidence of 3% to 6% of all intranasal tumors [6] and it metastasizes most commonly to cervical lymphnodes. Cervical lymph node metastasis (10% - 30%) and distant metastasis develop irrespective of tumour grade [7] . Distant metastases can be found in the lungs, the abdominal organs, thespinal cord or in the long bones.

The most common symptoms are nose bleeding, unilateral nasal obstruction, anosmia, facial pain and headache. Macroscopically ENB can be wrongly diagnosed as benign nasal polyp or malignant neoplasms such as: malignant lymphoma, sinonasal undifferentiated carcinoma, etc. Therefore any suspicious tissue should be subjected to histological analysis. One of the most important characteristics that can lead the surgeon to suspect a malignancy is the soft and easy to tear apart tumor mass tissue.

One of the most reliable histologic features is itslobular architecture. The circumscribed lobules or nests are made up of primitive neuroblastoma cells. They are usually located below an intact mucosa and in avascularized fibrous stroma. The tumor cells are small, round and blue [8] . The neoplastic cells form arosette- or pseudo- rosette-like pattern [9] [10] . The neoplastic ENB cells are characterized by uniform round nuclei, dispersed chromatin and scant cytoplasm. The final histopathological diagnosis can be established by light microscopy or by immunohistochemical staining and electron microscopy, depending on the tumor differentiation. The detailed analysis of ENB cytogenetic characterization is presented by Heidrun Holland et al. [11] .

Thus, olfactory neuroblastomas can be detected, delineated and its characteristics suspected by CT and MRI, but definite diagnosis however is still based on histopathology [12] . Depending on the propagation of the tumor mass Dulgerov and Calcaterra [13] proposed a four-stage classification.

The clinical behavior of olfactory epithelium tumors depends on patient age and the clinical stage of the neoplasm. In this particular case the esthesioneuroblastoma was classified as Kadish stage A, because the tumor was confined to the nasal cavity and according TNM system the tumor was ranged as stage T1N0M0.

The treatment of ENB depends on the stage and the presence of metastases. It seems that so far the best results are obtained with a combination of surgical resection and radiotherapy, with or without chemotherapy [14] .

Unfortunately, despite aggressive therapy, ENB has been noted to have a high local recurrence rate of 50% - 60% with 10% - 62% presenting as metastatic cases and 20% - 30% of those cases involving the CNS [15] . The patients with tumors of Kadish stage A have a 5-year survival rate ranging from 72% to 81% [5] [16] [17] .

Survival according to treatment modalities was 65% for surgery plus radiotherapy, 51% for radiotherapy and chemotherapy, 48% for surgery, 47% for surgery plus radiotherapy and chemotherapy, and 37% for radiotherapy alone [16] . The histopathological grading according to Hyams and the presence of cervical lymph-node metastases emerged as prognostic factors [16] [18] . The disease-free actuarial survival and overall survival rates were 77% and 61% at 5 years and 53% and 42% at 10 years, respectively [19] . In 2015, Petruzzelli et al. published a retrospective analysis of 32 patients, where the estimated overall rate of survival at 10 years was 78% based on Kadish and T stage [20] . Esthesioneuroblastoma is an uncommon malignancy of the head and neck for which there is no defined treatment protocol [20] .

In this case study we demonstrate that in some cases the diagnosis ENB might be unexpected because the tumor mass arises from the anterior end of the inferior nasal concha. The combination of ENB with thyroid gland carcinoma and GIST isextraordinary and we defined it as extremely rare.

In this particular case we did not recommended course of radiotherapy/chemotherapy because of the early stage of the ENB, its radical removal and the lack of regional or distant metastases. The thyroid gland carcinoma was removed radically as well. The GIST was considered as inoperable. Regardless of the course of chemotherapy the outcome was lethal 6 months after the diagnosis of gastrointestinal stromal tumor.

We presented a rare case of ENB with thyroid gland carcinoma as a second finding of cancer activity. The early stage of the tumors allowed applying surgical treatments. The thyroid gland carcinoma was found by PET/CT examination, which was applied in order to detect the presence of ENB possible metastases.

We cannot determine with certainty whether the thyroid gland carcinoma and gastrointestinal stromal tumor (diagnosed one year later) are metastatic from the ENB or whether they are primary cancer activities.

When identified as aggressive tumors such as ENB, it is necessary to provide regular examinations in order to detect distant ENB metastases or other neoplastic localisations.