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Abstract
Extramedullary plasmacytoma of the head and neck region is a rare malignant tumor comprising approximately 3% of all plasma tumors. Aproximately 80-90% involve the mucosa of the upper airway. These tumors are known to be very radiosensitive and therefore radiotherapy is considered the treatment of choice, surgery being limited to biopsy and to excision residual disease. A case of extramedullary plasmacytoma of the nasal cavity is reported  wich did not respond to radiotherapy.
Keywords: Extramedullary plasmacytoma, plasma cell tumor, nasal tumor, tumor persistent after radiation.

Introducci�n
Extramedullary plasmacytoma (EMP) is a plasmatic tumor characterized by monoclonal expansion of plasma cells that produce a single immunoglobulin molecule.1
The EMP was first describe in 1905 by Schridde, but it was in 1952 when Ewing described a large series of cases.2 The estimated global incidence of the disease is 1 case per 500.000 people.
It is important for the otolaryngologist to acquire knowledge oh this disease since 80 to 90% of the EMP cases are found in the head and neck and they represent only 1% of all cancers in this area.1 These tumors mainly occur in the upper respiratory tract due to its rich lymphatic tissue, especially the submucosa of the nasal cavity, paranasal sinuses and nasopharynx.3
To exclude multiple myeloma or plasmacytoma of the bone, a systemic work-up and follow-up of the patient are mandatory, including serum protein electrophoresis, urinalysis for the Bence-Jones protein, skeletal survey and bone marrow biopsy.4,5
Diagnosis can only be made after histopathological studies and immunohistochemical methods. Regarding the treatment of extramedullary plasmacytoma in the head and neck, the choice of radiotherapy or surgery alone is controversial. The primary method of treatment, if lymph node are not affected, is radiation therapy. The role of surgery is generally limited to open biopsy for diagnosis or for debulking a large tumor.1,6
We present a patient diagnosed with an Extramedullary Plamacytoma in the nasal cavity without clinically and imaging detectable reduction of the tumor size after radiation that underwent complete resection of the tumor by endonasal endoscopic surgery control.

Case report
A seventy-one year old male patient presented a 2-year history of intermittent epistaxis with right side nasal obstruction. Nasopharyngeal examination revealed a smooth surface tumor obstructing the nasopharynx and introduced into right nasal cavity. The blood vessels were visible owing to their transparency and bleeding.  The tumor seemed to be fixed to posterior wall of the nasopharynx and was very painful (Fig1).
Non contrast computed tomography (CT) of the nose and paranasal sinuses revealed a soft tissue tumor projecting from right nasal cavity into  nasopharynx (Fig2).  MRI showed a well-defined lesion, relatively homogeneous without areas of necrosis, cysts, calcifications or bleeding, within the right nasal cavity extending posteriorly into the nasopharynx that reduced significantly  the airway.
The histological finding, following nasal endoscopy biopsy, was plasmacytoma CD138+, CD79+ with light Kappa chain. A systemic work-up to exclude multiple myeloma (MM) was performed. Results of serum electrophoresis and urine test were negative for myeloma component or Bence-Jones protein. Bone marrow needle biopsy and skeletal survey were negative. 
The patient received irradiation of 40Gy during 27 sessions without clinically and imaging detectable reduction of tumor size. Exhaustive control is performed for 2 years with analysis every 3 months and MRI every 6 months (Fig3). Finally a surgical approach was decided by endonasal endoscopic control with complete resection and safety limits. The tumor was adhered to inferior turbinate, the floor nasal cavity, soft palate and posterior septum. It is suppose the adhesion was secondary to radiation. At 1 year follow-up, the patient was doing well with no signs of recurrences.

Discussion
Plasma cells are mature immunocompetent cells derived from B lymphocytes, and they provide specific noncellular immunity within the immune system. They produce specific antibodies against antigens in different tissues. Large populations are seen in the mucosa of the nasal and paranasal sinuses. Plasmacytomas arises from a neoplastic proliferation of theses antibody producing plasma cells.7
The most common location is the nasal cavity, sinuses and nasopharynx (75%). Other locations are oropharynx (12%), larynx (8%) and tongue, thyroid and minor salivary glands (5%).4,9 Men are predominantly affected, and these tumors are most commonly seen in the sixth to eighth decades, as in this case. Due to its presentation in the submucosa of the aereodigestive tracts, some authors have suggested that the aetiology of EMP may be related to chronic stimulation caused by inhaled irritants or viral infection.8 In our case, the patient worked in a bank and have no past related infections. Other publications propose risk factors that cause chronic antigenic stimulation such as osteomielitis, cholecystitis, rheumatoid arthritis and bacterial flora.9
EMP arising in the head and neck characteristically presents with localized disease and without clinical lymph node involvement. Theses observations are in agreement with most of the large reported series.10 
On gross examination, the masses are usually polypoid but can be sessile. They tend to appear granulomatous and red although some are yellow-gray, gray or dark brown. They are vascular and bleed easily and profusely. The most frequent clinical symptons are obstruction of the respiratory tract due to the tumor growth, epistaxis, rhinorrea, pain and swelling of the soft tissue of the neck.1,2
Fine needle aspiration is non-diagnostic because of the limited tissue available for special staining and for complete histologic examination. Therefore, incisional or excisional biopsy, depending on the size and location of the mass is necessary.3,10 Deep biopsies must be taken as the tumor is submucosal and the mucosa may be thickened as the result of an inflammatory reaction. Microscopically it appears as mononuclear proliferation of plasmatic cells in a dispersed array. It can have atipia nuclear and cellular minimal or prominent. Plasma cells have a core of dense chromatin along the nuclear membrane with form of wheel of wagon. The cytoplasm is abundant, basophilic and appears a perinuclear halo corresponding to the Golgi apparatus. 
Given this result pathology should do more tests to rule out systemic disease and confirm the diagnosis of extramedullary plasmacytoma. The study was performed with hemogram, myelogram, bone marrow biopsy, complete biochemical profile, calcium, serum proteins and plasma protein electrophoresis and urine, and x-ray to exclude lytic lesions.6,11
The differential diagnostic evaluation often is very difficult because of the similarity of the histologic appearance of EMP to that of others tumors like lymphoma, undefferentiated carcinoma, esthesioneuroblasts.1
The optimal management of EMP is controversial with therapeutic choices resting between radiotherapy or surgery. There have been no randomized controlled trials to define the best treatment, but there are several small retrospective case series that helped us to decide the best option to our patient.
Radiotherapy is accepted as the standard treatment for EMP of head and neck because of its high radiosensitivity. Published data supports high responses rates of 90-95% after radiotherapy and long-term local control rates of 90-100%.11 The optimal dosage regimen for radiotherapy is a matter of debate. Various protocols have been described, with a total dose ranging from 3.000 to 8.000 rads over treatment periods of 3 and 6 weeks.1,12 Other authors administer dose of radiotherapy depending on the tumour size  (for EMP up to 5cm a dose of 40Gy in 20 fractions and for EMP bigger than 5cm a higher dose of up 50Gy in 25 fractions). Cervical nodes respond to the same sensivity to radiotherapy. Since now surgery was recommended in cases of localized lesions that could be removed with minimal morbidity.
Publications described to date accepted a 50% of tumor reduction, only another publication and our actual case shows no response to radiotherapy.13
In general, EMP of the head and neck has a better prognosis than solitary bone plasmacytoma or MM. This may be due to early presentation, when the lesions are small and well localized and also probably due to easy accessibility of the tumor to examination.11
The evolution of EMP to MM is the determinant factor for survival. Only 10% to 30% of cases progress to MM within 2 years, but the prognosis for these patients is poor. Several factors predictive of progression to MM have been reported, such as the size of the tumor at diagnosis, total serum protein level, and a monoclonal spike observed on serum protein electrophoresis. Because recurrence is usually within 24 months but may be as late as 15 years after treatment, long-term follow-up, including not only local control but also systemic observation via blood counts and immunoglobulin measurement, is necessary .1,14 
Although the follow-up is not sufficiently long to consider the complete remission of disease as definitive, the therapeutic strategy adopted to date, in this case, might be considered valid.

Conclussions
Extramedullary plasmacytoma is a rare tumor wich predominantly occurs in the submucosa of the upper aerodigestive tract. The majority of patients are eldery and present with low-grade tumours. These low-grade tumours should be treated with radiotherapy to the primary site with a dose equivalent to 35-45 Gy in 3 weeks. The dose will depend on volume of treatment and inclusion of critical structures but is well tolerated. Since now surgery was recommended in cases of localized lesions that could be removed with minimal morbidity, we also indicate surgery when radioresistant cases. Conversion to MM is significantly lower with EMP compared with solitary plasmacytoma of bone, this being its main prognosis factor.

Figure Legends
Figure 1
Endoscopic vision of the lesion from right and left (A,B) nasal cavity.
Figure 2
Pre-radiation imaging. Coronal and axial non contrast CT (A,B) show a soft tissue polypoidal mass projecting from right nasal cavity into  nasopharynx that significantly reduces tha airway.
Figure 3
Postradiation imaging showing same tumor size. Axial MR T1 weighted image and T2 weighted image (A, B). Axial and sagittal post-contrast T1WI (C, D) show an homogenous enhancement of the mass.

Referentes
Anjos M, Granato L, Ikeda F, Pr�spero JD. Extramedullary plasmacytoma: Literatura review and a rare case report. Int. Arch. Otorhinolaryngol 2013;17(2):213-217.
Fernandes AM, Podovani JA, Maniglia JP. Plasmocitoma extramedular de nasofaringe: relato de um caso e revis�o da literatura. Rev Bras Otorrinolaringol. 1998;64:296-298.
Hazarika P, Balakrishnan R, Singh R, Pujary K, Aziz B. Solitary Extramedullary Plasmacytoma of the Sinonasal Region. Indian J Otolaryngol Head Neck Surg 2011;63(1):S33-S35.
Zabaleta M, Garc�a FJ, Preciado JA, Lacosta JL. Extramedullary plasmocytoma. Report of 5 cases. An Otorrinolaringol Ibero AM 2001;28:87-99.
Sulzner SE, Amdur RJ, Weider DJ. Extramedullary plasmacytoma of the Head and Neck. Am J Otolaryngol 1998;19:203-8.
Naser A, Braco G, Panussis F, Carrasco M. Plasmocitoma xtramedular nasal. Presentaci�n de un caso y revisi�n de la literatura. Rev Hosp. Clin Univ Chile 2010;2:12-17.
Rawar DS, Grover M, Verma PC. Extramedullary Plasmacytoma of nasal cavity: a rare entity. Clinical Rhinology: An internacional journal, 2010;3(1):39-41.
Attanasio G, Viccaro M, Barbaro M, De Seta E, Filipo R. Extramedullary Plasmacytoma of the paranasal sinuses. A combined therapeutic strategy. Acta Otorhinolaryngol Ital 2006; 26:118-120.
Ronald B, Kuppersmith. Extramedullary plasmacytoma of the head and neck. Rounds Archive al Baylor 1996.
Susnerwala SS, Shanks JH, Banerjee SS, Scarffe JH, Farrington WT, Slevin NJ. Extramedullary Plasmacytoma of the head and neck region: clinicopathological correlation in 25 cases. Cancer 1999; 85(11):2305-2314.
Hotz MA, Schwaab G, Bosq J, Munck JN. Extramedullary solitary plasmacytoma of the head and neck. A clinicopatological sudy. Anm Otol, Rhinol, Laryngol 1999:108(5):495-500.
Jyothirmayi R, Gangadharan VP, Nair MK, Rajan B. Radiotherapy in the treatment of solitary plasmacytoma. The Britsh Journal of Radiology 1997;70:511-516.
Bachar G, Goldstein D, Brown D, Tsang R et al. Solitary extramedullary plasmacytoma of the head and neck: long-term outcome analysis of 68 cases. Head Neck 2008;30(8):1012-9.
Kupfer TJ, Pfeiffer J, Offergeld C. Persistent extramedullary plasmacytoma of the nose to radiotherapy. HNO 2011; 59:119-121.











                                                                                                                                     

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