olfactory neuroblastoma or esthesioneuroblastoma is a rare malignant neoplasm of neuroectodermal origin arising from olfactory membrane of the sinonasal tract . it was originally described in french literature by berger et al . in 1924 who coined the term the various synonyms used for this entity are olfactory esthesio - neuroepithelioma , esthesio - neurocytoma , esthesio - neuroepithelioma , esthesio - neuroblastoma , olfactory neuroblastoma and olfactory placode tumor . the first case in american literature this tumor has broad histologic spectrum and is often histologically confused with peripheral neural ectodermal tumors and is notorious for its wide clinical behaviors . the common clinical symptoms include nasal obstruction , recurrent epistaxis , hyposomia , rhinorrhea , headache and visual disturbances . here we report a rare case of esthesioneuroblastoma in a female with presenting symptom as tooth pain . a 50-year - old female reported to the department of oral medicine with the complaint of pain in the left side of the upper jaw since seven months , which was spontaneous , dull and reduced on taking analgesics . she visited a general dentist five months ago and maxillary left second molar was extracted as it was considered as the causative tooth for pain , however , the patient did not get relief and the pain continued . she noticed swelling of left side of the face , which gradually increased in size and there was a concomitant decrease in size of her left eye opening and the eyeball was pushing superiorly since two months . her medical and family history was noncontributory and upon general physical examination , all her vital signs were within normal limits . on extraoral examination , a diffuse swelling was seen on the left maxillary area extending from infraorbital margin to mid of the cheek supero - inferiorly and ala of nose to outer canthus of eye antero - posteriorly , which was soft in consistency and tender on palpation [ figure 1a ] . intraorally , swelling was evident on palpation extending from maxillary tuberosity to the vestibule causing vestibular obliteration till the posterior aspect , which was tender and soft in consistency on palpation [ figure 1b ] . clinical photograph showing swelling on maxillary region and decrease in the size of the left eye ( a ) . intraorally , vestibular obliteration was evident ( b ) on the basis of history and clinical examination , a provisional diagnosis of malignant neoplasm of maxillary sinus was considered . the coronal ct revealed a large mass originating in left maxillary sinus with destruction of its medial , superior and postero - lateral wall . medially , this mass was extending into left nasal fossa leading to marked luminal compromise on the left side and superiorly extension into left orbit was noticed . posteriorly it was extending into infra - temporal fossa , left masseteric space and left pterygomaxillary fissure . partial erosion of anterior maxillary wall , hard palate and lateral pterygoid plate on left side and extension of this mass from lateral maxillary wall into left cheek was also noticed [ figure 2a and b ] . coronal computed tomographic scan showing extension of lesion into sinus and nasal fossa incisional biopsy was performed and on histopathological examination , hematoxylin and eosin stain showed basophilic cells arranged in large lobar sheets with intertwining connective tissue septa . cells had large round nucleus with minimal pleomorphism and a thin rim of cytoplasm . pronounced vascularity and formation of pseudorosettes ( homer - wright type ) were seen in some areas , suggestive of esthesioneuroblastoma [ figure 3a and b ] . immunohistochemistry revealed strongly positive neuron - specific enolase among the tumor cells and s-100 showed weak association [ figure 4a and b ] . so based on clinical examination and the investigations performed , a final diagnosis of esthesioneuroblastoma was given . the case was referred to the oncology institute for the management and the patient was started with chemotherapy , cisplatin 50 mg ( per day ) and 5 fluorouracil 1 mg ( per day ) , and recalled after 15 days ; there was improvement in the symptoms after which the patient was lost to follow up . photomicrograph showing cells arranged in sheets and intervening connective tissue stroma ( a ) ( h&e stain , 40 ) . photomicrograph showing cells with large round nucleus , thin rim of cytoplasm arranged in large sheets with intertwining connective tissue septa and formation of pseudorosettes ( homer - wright type ) ( b ) ( h&e stain , 100 ) immunohistochemistry showing strongly positive neuronspecific enolase among the tumor cells ( a ) ( ihc stain , 200 ) and weak association with s-100 protein ( b ) ( ihc stain , 200 ) esthesioneuroblastoma is a rare malignant tumor arising from olfactory epithelium and its neural origin was established by trojanowaski et al . in 1982 who demonstrated the presence of neurofilament proteins ( nfp ) in the tumor cells . though , it has been reported in patients as young as two years to 90 years , a bimodal age distribution has been noted in the second and sixth decades of life . there are no known etiologic agents for human olfactory neuroblastoma , however , injection of diethylnitrosamine in syrian hamsters and n - nitrosopiperidine in rats has produced tumors histologically identical to human olfactory neuroblastoma . the common symptoms associated are unilateral nasal obstruction ( 70% ) and epistaxis ( 46% ) , and less common manifestations are anosmia , headache , pain , excessive lacrimation and ocular disturbances . in the present case , the patient complained of pain in left maxillary molar teeth , which is a rare symptom and also , there was decrease in size of left eye , which may be due to superior extension of tumor in the left orbit . the most common site of origin is in the upper nasal cavity in the region of the cribriform plate ; other primary sites such as maxillary sinus and nasopharynx have also been reported . esthesioneuroblastoma is generally believed to be derived from the neurosensory receptor cells of olfactory mucosa . other sources of origin suggested include sphenopalatine ganglion by escat , organ of jacobson , ganglion of luci by martin et al . and olfactory placode . the tumor in the present case was seen to arise from left maxillary sinus and extended to involve nasal fossa , infra - temporal fossa , masseteric space , cheek and the left orbit . according to this classification , stage a tumors are confined to the nasal cavity , stage b tumors have paranasal sinus extension and stage c tumors have extra - paranasal extension including the involvement of the cribriform plate , base of skull , orbit or intracranial cavity . this classification was modified by morita et al . in 1993 who established stage d in the classification for tumors with metastasis to cervical lymph nodes or distant site . kadish 's classification has been used by various authors and appears to correlate well with the clinical outcome . the present case can be categorized as belonging to stage c of kadish 's classification . in evaluation of esthesioneuroblastoma , the extent of disease is best determined by pre- and post - contrast mr imaging in which there is intense signal in t2-weighted images with marked enhancement of t1-weighted images after gadolinium injection . details of bone erosion ( lamina papyracea , cribriform plate and fovea ethmoidalis ) are better demonstrated by ct scan . tumor is presented as homogenous density mass , equal or greater to the surrounding soft tissue and no tumor cysts or calcifications . coronal images were of value in evaluating extension to the orbit and through the cribriform plate and the anterior cranial fossa . ( 2001 ) demonstrated the usefulness of technetinium-99m - ethyl cysteinate dimer ( tc - ecd ) spect in detection of olfactory neuroblastoma . ( 1960 ) stated that the characteristic histologic features of olfactory neuroblastoma are plexiform intercellular fibrils , round - to - oval - shaped nuclei with scanty cytoplasm , distinct and sharply defined chromatin , which may be coarse or fine , compartmentation of sheets of neoplastic cells into lobules by slender vascular fibrous septa , true neural rosettes ( flexner - wintersteiner type ) and pseudorosettes ( homer - wright type ) . they concluded that if fibrils were absent , then the tumor can not be classified as neuroblastoma with certainity . histologically neuroblastoma has been classified as olfactory neurocytoma ( pattern i of mendeloff ) , a tumor with a sheet of round small cells separated by connective tissue septa and occasionally pseudorosettes ; olfactory neuroepithelioma ( pattern ii of mendeloff ) , a tumor containing round to oval nuclei clear nuclear membrane , scant cytoplasm and rosettes ; and a tumor similar to neuroblastomas found elsewhere in the body . immunologically , it is most reactive with neuron - specific enolase ( nse ) as seen in the reported case . it has shown reactivity with s-100 , synaptophysin , nfp , class iii beta - tubulin and microtubule - associated protein . light microscopy can usually establish the diagnosis , but highly undifferentiated tumors make this difficult . in case when light microscopy fails to establish diagnosis , electron microscopy is helpful . esthesioneuroblastoma must be distinguished from lymphosarcoma , transitional cell carcinoma , plasmacytoma , reticulum cell carcinoma , small cell undifferentiated carcinoma and ewing 's sarcoma . small cell carcinoma typically is a submucosal hypercellular proliferation growing in sheets , cords and ribbons ; the distinct lobular pattern of olfactory neuroblastoma is absent . the cells are small and hyperchromatic with oval- to spindle - shaped nuclei , absent nucleoli and minimal cytoplasm . although uncommon , neural - type rosettes similar to those seen in olfactory neuroblastoma can be seen in association with small cell carcinoma . in contrast to olfactory neuroblastoma , nse reactivity in small cell carcinoma is more likely to be focal than diffusely positive and the s-100 protein staining , if present , is dispersed throughout the cellular proliferation and not limited to sustentacular cells . ewing 's sarcoma is composed of solid sheets or masses of solid round cells with very little stroma , scanty cytoplasm and ovoid large nuclei ; necrosis is common . the characteristic cells of plasmacytoma and so - called cylinders in cylindromas readily help in identifying these tumors . small cell undifferentiated carcinomas does not contain fibrils and the distinct cytoplasmic borders can be seen . the current accepted standard of treatment is craniofacial resection followed by adjuvant radiotherapy to a dose of 55 - 65 gy for kadish stages b and c. small kadish stage a disease is treated by surgery alone in some situations by some groups , but most suggest adjuvant radiotherapy for these lesions also . neoadjuvant chemotherapy has been used in advanced disease and where complete resection is not possible , with cyclophosphamide , vincristine ifosphamide , etoposide and cisplatin combined with preoperative radiotherapy . the overall five , 10 and 15-year survival rates have been reported to be 78% , 71% and 68% , respectively . initial multimodality therapy is associated with five - year survival of 80% for low - grade tumors and 40% for high - grade tumors . the most hazardous and often fatal complication is intracranial extension of tumor through destruction of cribriform plate and orbital plates and secondly due to distant metastasis . prognosis has been correlated to clinical staging with five - year survival of 75 - 91% , 68 - 71% and 41 - 47% for stages other factors that have been implicated in prognosis include histologic grading , proliferation rate and ploidy . histologically lower grade tumors ( grades i and ii ) have been reported to have a better five - year survival than higher grade tumors ( grades iii and iv ) . the tumor metastasizes widely by both hematogenous and lymphatic routes , approximately 10 - 60% will experience distant metastasis . the most common site for metastasis spread are cervical lymph nodes , and less frequent are lungs , brain , bone , spinal column , breast and abdominal viscera . metastasis to the central nervous system is infrequent and in spinal cord 80% of metastasis is in cauda equine . , this tumor has been difficult to recognize and diagnose pathologically and the wide spectrum of presentation of this tumor has resulted in its frequent misdiagnosis . thus , the diagnosis of esthesioneuroblastoma demands a specialized and experienced head and neck pathologist , especially as incidence rate is low . also , esthesioneuroblastoma may present , only as tooth pain as in the present case . so , it may be considered as a possible differential diagnosis , though rare in cases of dento - facial pain of idiopathic cause .
esthesioneuroblastoma , also called olfactory neuroblastoma , is a rare malignant tumor originating in the olfactory epithelium in the upper nasal cavity with intracranial extension and may also be associated with secondary sinus diseases . 
 esthesioneuroblastoma has been observed to cause death by distant metastasis or by invasion through the cribriform plate and secondary meningitis . 
 it usually produces nasal obstruction , epistaxis and less commonly anosmia , headache and pain . 
 we report a case of esthesioneuroblastoma in a 50-year - old female who reported with tooth pain as a presenting symptom .