RetractionRetracted: Primary Small Cell Undifferentiated(Neuroendocrine) Carcinoma of the Maxillary Sinus

Case Reports in Dentistry

Received 31 August 2014; Accepted 31 August 2014; Published 21 October 2014

Copyright © 2014 Case Reports in Dentistry. This is an open access article distributed under the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properlycited.

The paper titled “Primary Small Cell Undifferentiated(Neuroendocrine) Carcinoma of the Maxillary Sinus” [1],published in Case Reports in Dentistry, has been retractedas it was submitted without the knowledge or consent ofcoauthor Dr. Premalatha Shetty who was responsible for thepatient whose case was presented in the manuscript.

References

[1] S. K. Yadav and P. Shetty, “Primary small cell undifferentiated(neuroendocrine) carcinoma of the maxillary sinus,” CaseReports in Dentistry, vol. 2014, Article ID 463109, 5 pages, 2014.

Hindawi Publishing CorporationCase Reports in DentistryVolume 2014, Article ID 609802, 1 pagehttp://dx.doi.org/10.1155/2014/609802

Case ReportPrimary Small Cell Undifferentiated (Neuroendocrine)Carcinoma of the Maxillary Sinus

Santosh Kumar Yadav1 and Premalatha Shetty2

1 Department of Oral and Maxillofacial Surgery, Chitwan Medical College (P) Ltd, P.O. Box 42, Bharatpur-10, Chitwan, Nepal2 Department of Oral and Maxillofacial Surgery, Manipal College of Dental Sciences, Manipal University,Lighthouse Hill Road, Mangalore 575001, India

Correspondence should be addressed to Santosh Kumar Yadav; nepalsantoshyadav@gmail.com

Received 29 November 2013; Accepted 24 December 2013; Published 3 February 2014

Academic Editors: R. V. Lo Vasco, S. Pezelj-Ribaric, and S. R. Watt-Smith

Copyright © 2014 S. K. Yadav and P. Shetty. This is an open access article distributed under the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properlycited.

Primary small cell neuroendocrine carcinoma (SNEC) of the paranasal sinuses is an extremely rare and distinctive tumor withaggressive clinical behavior. Moreover, SNECs originating in the head and neck region have been reported to be highly aggressiveand to have a poor prognosis. This report describes a patient with a maxillary sinus SNEC who was successfully treated withneoadjuvant chemotherapy and concurrent chemoradiotherapy.

1. Introduction

Carcinoma developing in the paranasal sinuses accounts forapproximately 0.3% of all cancers [1]. Squamous cell carci-noma is by far the most common malignancy, followed byadenocarcinoma. Extrapulmonary small cell neuroendocrinecarcinoma (EPSNEC) of sinonasal tract is rare. The firstcase of SNEC of the paranasal sinuses was reported byRaychowdhuri [2] in 1965. SNECs originating in the head andneck region have been reported to be highly aggressive and tohave a poor prognosis. This report describes a patient witha maxillary sinus SNEC who was successfully treated withneoadjuvant chemotherapy and concurrent chemoradiother-apy.The clinical and pathologic features of the tumor and theoptimal treatment of this patient are discussed.

2. Case Report

A 70-year-old female presented to the oral and maxillofacialdepartmentwith gradual onset of right cheek swelling aroundthe right gingival and a painful mass for about 1 month.Physical examination showed hard cheek swelling (Figure 1)and epiphora of the right eye, but the patient’s eye movementwas normal and she did not have any double vision. The skinaround the right eyelids was regular and not reddish, whereas

the right posterior alveolar gingival was ulceration (2 × 2)cm, irregular, and reddish in areas (Figure 2). No history ofnasal bleed, nasal congestion, and pus from ears. Clinicallythe patient had an enlarged right submandibular lymph nodemeasuring approximately 3 cm in diameter. The patient wasadmitted, and imaging studies were performed.

Computed tomography (CT) scan of head showed alarge mass measuring approximately 6 cm in diameter in theright maxillary sinus invading the right orbit, ethmoid sinus,and the skin of the cheek (Figures 3(a) and 3(b)). Histo-logic examination of biopsy sample stained sections showedmucosal tissue bits with features suggestive of poorly dif-ferentiated squamous cell carcinoma/neuro-endocrine car-cinoma and immunohistochemistry was advised for furtherevaluation. Immunohistochemical staining was performedon the formalin-fixed, paraffin-embedded tissue sections.Thetumor cells were positive for synaptophysin and cytokeratinand negative for neuron specific enolase. These histologic(Figure 4) and immunophenotypic features were character-istic of SNEC, and clinical findings supported the diagnosisof small cell undifferentiated neuroendocrine carcinoma ofrightmaxillary sinus. An extensive search for a primary lesionelsewhere was performed; however, findings from wholebody CT imaging, urinary amine secretions, and sputumcytology were unremarkable.

Hindawi Publishing CorporationCase Reports in DentistryVolume 2014, Article ID 463109, 5 pageshttp://dx.doi.org/10.1155/2014/463109

2 Case Reports in Dentistry

Figure 1: Preoperative right cheek swelling.

Figure 2: Preoperative intraoral swelling and ulceration.

This case was discussedwith consultingmedical and radi-ation oncologists and planned for combination of chemother-apy followed by radiotherapy. The patient was treated with3 cycles of induction chemotherapy, consisting of cisplastin(40mg/m2) and etoposide (100mg/m2) on days 1 to 3 every4 weeks. After induction chemotherapy, it was extremelyeffective, with remarkable reduction in facial swelling andcomplete loss of intraoral swelling (Figures 5 and 6). Thepatient was subsequently started on concurrent chemora-diation, consisting of 1 course of cisplastin and etoposidesimilar to the induction chemotherapy, and a total doseof 60Gy of intensity modulated radiation therapy in 30fractions, 5 days a week for a total of 6 weeks. The patient’sposttherapeutic course was uneventful. Follow-up 2-yearpostradiotherapy showed no evidence of local recurrence ormetastasis (Figures 7, 8, and 9).

(a)

(b)

Figure 3: Imaging analysis. (a) Initial coronal section computedtomography of head showing mass in the right maxillary sinusinvading the right orbit, ethmoid sinus. (b) Initial enhanced axialcomputed tomography of head showing complete destruction of theanterior wall of the maxillary sinus.

Figure 4: Histologic findings of biopsy tissue. The tumor wascomposed of small round to oval hyperchromatic nuclei with densechromatin and scanty cytoplasm.

3. Discussion

SNEC occursmainly in lungs and accounts for approximately20% of primary lung carcinomas [3]. EPSNEC represents 4%of all cases of SNEC [4], and a limited number of SNECcases of the nasal and paranasal cavities have been previouslyreported. Among these tumors, primary SNEC arising inthe maxillary sinus is extremely rare. The classification ofneuroendocrine tumor is particularly difficult, as indicatedby several investigators [5]. Carcinoid tumor is considereda well-differentiated neuroendocrine carcinoma, althoughatypical carcinoid tumor is regarded as moderately differ-entiated neuroendocrine carcinoma. SNEC is classified as

Case Reports in Dentistry 3

Figure 5: Chemotherapy after 4th cycle, remarkable reduction infacial swelling.

Figure 6: Chemotherapy after 4th cycle, complete loss of intraoralswelling.

poorly differentiated neuroendocrine carcinoma. Similar toSNEC of the lung, SNEC of the nasal and paranasal cavitieshas demonstrated aggressive clinical behavior and a poorprognosis, with fast tumor expansion, early local recurrence,and widespread dissemination.

As originally described by Koss et al. [6] and Geor-giou et al. [7], SNEC of all anatomic sites shares similarhistopathologic features. The tumor forms sheets or nestsand is composed of medium-sized tumors cells with a highnuclear/cytoplasmic ratio and hyperchromatic nuclei withindistinct or occasional small basophilic nucleoli.

According to criteria of the World Health Organization[8], small cell carcinomas are defined as malignant epithelialtumors consisting of small cells with scant cytoplasm, ill-defined cell borders, finely granular nuclear chromatin, andabsent or inconspicuous nucleoli. Specific cells are round,oval, and spindle shaped, and nuclear molding is prominent.Necrosis is usually extensive, and the mitotic count is high.

Figure 7: Follow-up 2-year postradiotherapy.

Figure 8: Follow-up 2-year postradiotherapy.

More than 90%of small cell carcinomas have neuroendocrinefeatures [8].

The immunohistochemical tumor profile has been previ-ously investigated [1, 9] and has demonstrated that the tumoris usually strongly positive for synaptophysin and CD56 andweakly positive for chromogranins and CAM5.2/AE1. Thepresent patient showed positive staining for synaptophysin,indicating that the tumor was of neuroendocrine origin.Tumor cells also were positive for cytokeratin, indicating thatthe tumor originated from the epithelium.

Because of the rarity of SNEC of the nasal and paranasalcavity, no agreement for adequate management has beenreached among oncologists; therefore, much informationhas been extrapolated from data on SNECs at other sites,especially pulmonary SNECs (PSNECs). Because SNEC is anaggressivemalignancy with high rates of local recurrence andmetastatic spread, multimodal therapy is increasingly used,including chemotherapy, radiotherapy, and possibly surgery,

4 Case Reports in Dentistry

Figure 9: Follow-up 2-year CT image.

depending on the extent of disease or the primary site. Sincethe late 1990s, the combination of chemotherapy and radio-therapy, with or without surgery, has been recommended[10, 11]. The largest study to date tested platinum-basedchemotherapy followed by radiotherapy [11].The chemother-apeutic regimens used for patients with EPSNEC are similarto those used for patients with PSNEC, with the combinationof etoposide and cisplastin being the first-line treatment andyielding a response rate of 69% [12]. Radiotherapy also hasbeen shown to be curative at many sites, although the histo-logic similarity of SNEC of the nasal and paranasal sinusesto PSNEC has suggested that chemotherapy should be thefirst option. The best method for integrating chemotherapyand head and neck radiotherapy remains unknown. Thechemoradiotherapy regimen for the present patient consistedof 4 cycles of cisplastin plus etoposide chemotherapy con-current with 60Gy of locoregional radiation administeredonce or twice daily. Although introduced for the treatmentof lung cancer in the late 1970s [13], the combination ofcisplastin and etoposide emerged as primary therapy onlyin the early 1980s [14]. A clear advantage of cisplastin plusetoposide is that this combination can be given concurrentlywith relatively full doses of thoracic radiotherapy, with lowermorbidity rates than observed with doxorubicin-based [15]or cyclophosphamide-based [16] regimens.

The higher rate of intracranial metastases in patientswith SNEC of the nasal and paranasal sinuses than in thosewith PSNEC suggests that patients with the former shouldbe treated with systemic chemotherapy and radiotherapyand prophylactic cranial irradiation [17]. Recurrence andmetastasis of SNEC of the nasal and paranasal sinuses during3 years of follow-up have been reported in up to 70% ofpatients [18], with an overall local recurrence rate of 33% anda metastasis rate of 31% [19]. The 1- and 5-year survival rateshave been reported to be approximately 57% and 10%, respec-tively, and comparable to rates in patients with EPSNEC,with a 5-year survival rate of 13% and a median survival

of 13 months [20]. With the present management strategy,local failure remains an important problem. However, untilwhat governed failure has been appreciated, the surgeon andthe oncologist should try to optimize the treatment for eachpatient with improved local therapy. This may contributeto local control and survival so that cure will be achievedwith minimal morbidity. More extensive studies are neededto assess the optimal management and develop standardizedtreatment protocols.

Conflict of Interests

The authors declare that there is no conflict of interestsregarding the publication of this paper.

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Case Reports in Dentistry 5

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