Accepted Manuscript Palatal Basal Cell Adenocarcinoma from misdiagnosis to cure: a unique case report and review Ramzey Tursun, DDS, FACS, Dhafer Alsuwied, DDS, Lieutenant Commander J Marshall Green, III, DDS, FACS, James Melville, DDS, FACS PII: S0278-2391(18)30878-4 DOI: 10.1016/j.joms.2018.08.003 Reference: YJOMS 58413 To appear in: Journal of Oral and Maxillofacial Surgery Received Date: 4 May 2018 Revised Date: 7 August 2018 Accepted Date: 7 August 2018 Please cite this article as: Tursun R, Alsuwied D, Green III JM, Melville J, Palatal Basal Cell Adenocarcinoma from misdiagnosis to cure: a unique case report and review, Journal of Oral and Maxillofacial Surgery (2018), doi: 10.1016/j.joms.2018.08.003. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. ACCEPTED MANUSCRIPT ABSTRACT TITLE: Palatal Basal Cell Adenocarcinoma from misdiagnosis to cure: a unique case report and review. AUTHORS: Ramzey Tursun, DDS, FACS, Dhafer Alsuwied DDS, LCDR J Marshall Green III DDS, James Melville DDS, FACS EP TE D M AN U SC RI PT INSTITUTIONAL AFFILIATION: 1) Ramzey Tursun, DDS, FACS University of Miami- Miller School of Medicine, Miami Fl Associate Professor of Clinical Surgery Director, Head & Neck Oncologic and Microvascular Reconstructive Surgery 2) Dhafer Alsuwied DDS University of Texas Health Science Center at Houston Fellow- Oral, Head & Neck Oncology and Microvascular Reconstructive Surgery 3) Lieutenant Commander J Marshall Green III DDS, FACS Associate Program Director- Naval Medical Center Portsmouth Assistant Professor of Surgery-Uniformed Services University of Health Sciences Adjunct Assistant Professor of Surgery- University of Miami-Miller School of Medicine 4) James Melville DDS, FACS University of Texas Health Science Center at Houston Assistant Professor of Surgery Oral, Head & Neck Oncology and Microvascular Reconstructive Surgery AC C CORRESPONDING AUTHOR AND CONTACT INFORMATION: Ramzey Tursun DDS Associate Professor of Surgery Director of Head and Neck Oncology and Microvascular Reconstructive Surgery Division of Oral and Maxillofacial Surgery University of Miami- Miller School of Medicine Deering Medical Plaza 9380 S.W. 152nd St., Miami, FL 33157 Office#: 305.256.5277 Email address: firstname.lastname@example.org ACCEPTED MANUSCRIPT Disclaimer The views expressed in this article are those of the author(s) and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, or the United States Government. AC C EP TE D M AN U SC RI PT I am a military service member. This work was prepared as part of my official duties. Title 17 U.S.C. 105 provides that “Copyright protection under this title is not available for any work of the United States Government.” Title 17 U.S.C. 101 defines a United States Government work as a work prepared by a military service member or employee of the United States Government as part of that person’s official duties. ACCEPTED MANUSCRIPT RI PT Palatal Basal Cell Adenocarcinoma from misdiagnosis to cure: a unique case report and review. M AN U SC INTRODUCTION: Basal cell adenocarcinoma (BCAC) is a rare malignant lesion of the salivary gland, accounting for less than 2% of all salivary neoplasms.1 In 2005, World Health Organization defined basal cell adenocarcinoma (BCAC) as "an epithelial neoplasm that has cytological characteristics of basal cell adenoma (BCA), but a morphologic growth pattern indicative of malignancy."2 Here we describe a 66-year-old woman treated by University of Miami Oral/Head and Neck Oncology Service that was misdiagnosed twice as benign neoplasms prior appropriate diagnosis of the BCAC. At the time of her recurrence, her care was assumed by the senior author and was appropriately diagnosed and treated to cure including transoral microvascular reconstruction, as well as adjuvant radiation. A review of the current literature of this disease entity is also included. AC C EP TE D CASE REPORT: A 66-year-old woman originally presented for evaluation of a swelling in her right posterior palate to the Oral/Head and Neck Oncology service at the University of Miami. In August 2011, she the patient had undergone a biopsy and definitive resection of the area. Upon histopathologic evaluation, the lesion was definitively described as a canalicular adenoma. The patient then failed to follow up as scheduled. Following this period of time, the patient returned for evaluation after a biopsy by an oral and maxillofacial surgeon at an outside facility with concerns of swelling in the area of the right hard and soft palate. The senior author then took over her care and upon evaluation noted a mass in the right posterior palate with mild facial swelling on the patient's right side (Image 1). In the right posterior palate, a boggy lesion, approximately 2.5 X 2.5 cm was palpated. No ulceration noted over the lesion. Mucosa over lesion was noted to be pink but thinned, with mild erythema and no pulsation (Image 2). The biopsy that had been performed before arrival had the histopathologic diagnosis of ameloblastoma and was then reviewed by two general pathologist as well as an oralmaxillofacial pathologist (OMP) on consultation who agreed with the diagnosis. A computed tomography (CT) scan showed a radiolucent lesion in the right posterior maxilla extending on to the palate with elevation of the right nasal floor and a small perforation through bone. Osseous erosion of the alveolus is also noted seen in this region (Images 3,4). A magnetic resonance image (MRI) was obtained to mitigate the CT scan artifact and to better visualize the lesion boundaries. The axial view revealed a hyperdense lesion of the right maxilla and palate and further elucidated the location and extension (Image 5). ACCEPTED MANUSCRIPT RI PT Based upon clinical impression, her past surgical history, and a detailed radiographic examination, the patient was offered the treatment of surgical resection and immediate reconstruction with vascularized free tissue transfer. Subsequently, the patient was taken to the operating room, the lesion outlined and the resection was performed. Due to the history of recurrence and differing previous diagnoses, frozen sections were utilized in surgery to ensure disease control. While nonspecific, intraoperative frozen sections returned the finding of a malignant neoplasm of minor salivary gland origin. Wide local excision was completed bearing the new malignant pathologic diagnosis in mind and immediate reconstruction was performed with an anteromedial thigh fasciocutaneous flap utilizing an intraoral anastomosis technique (Image 6-8). M AN U SC The patient's post-operative course was uneventful and she was discharged home with the appropriate care. Final pathology was reviewed and found to be basal cell adenocarcinoma. Furthermore, despite the frozen margins being clear upon completion, final pathology was read as a close margin in one focal area. The case was reviewed by our multidisciplinary tumor board where adjuvant radiation was recommended. Due to the finding of carcinoma, a workup for metastasis was performed and no distant disease was identified. The patient then successfully underwent a course of postoperative radiation without complication and to the date of submission is 38 months out with no evidence of disease. TE D DISCUSSION: AC C EP Basal cell adenocarcinoma (BCAC) is a rare malignant lesion of the salivary glands, accounting for less than 2% of all salivary neoplasms.1 In 2005, the World Health Organization defined basal cell adenocarcinoma (BCAC) as "an epithelial neoplasm that has cytological characteristics of basal cell adenoma (BCA), but a morphologic growth pattern indicative of malignancy."3 It is considered to be the malignant counterpart of the BCA. Histological differentiation between the two is difficult, and frequently they can only be separated by identification of the invasion of local structures or by perineural or vascular invasion.2 This case is a perfect example of the difficulties in the pathologic differentiation where the patient was twice diagnosed with a benign lesion prior to the malignant BCAC diagnosis being rendered. Most BCACs arise de novo, but approximately 20% arise from a preexisting basal cell adenoma. Approximately 90% of BCACs are found in the parotid gland, and the remainder occur in the submandibular gland. 4 Lo et al were the first to report a basal cell adenocarcinoma of the palate, but the clinicopathologic behavior of this tumor, which originates from the minor salivary gland, is still unclear. 5 It is necessary to differentiate BCAC from other basaloid cell tumors of the minor salivary glands such as canalicular adenoma, BCA, adenoid cystic carcinoma, polymorphous low-grade adenocarcinoma, myoepithelial tumors, epithelial-myoepithelial carcinoma, and basaloid squamous cell carcinoma because of ACCEPTED MANUSCRIPT RI PT the prognosis and potential differences in treatment.6 BCAs with capsular invasion shared several pathological features with BCACs, including large size and frequent cribriform patterns but the malignant potential of these tumors seems highly limited and should be reexamined (Image 9a,b). Additionally, β-catenin immunostaining may aid when differentiating between a basal cell neoplasm and adenoid cystic carcinoma.7 TE D M AN U SC Overall, BCAC has a more favorable outcome than other common malignant salivary gland tumors and is considered to be a low-grade malignancy.8 The most common location for minor salivary gland tumor is the palate (42-54%) followed by the lips, but any other oral site harboring minor salivary glands may be affected.9 The diagnosis of BCAC depends on the presence of features similar to adenoma but with an infiltrative growth pattern. Furthermore, adenoid cystic carcinoma, sialoblastoma, and basaloid carcinoma must be excluded.10 The widely-accepted treatment for BCAC is complete surgical excision.11 Ellis and Wiscovitch have reported that among 29 patients with basal cell adenocarcinoma of the major salivary gland, 7 patients (28%) experienced at least 1 incidence of local tumor recurrence, and 3 patients (12%) had metastasis to the lung or cervical lymph nodes.12 An extensive literature review performed by Cuthbertson et al. included international and non-English literature in addition to their reported case identified a total of 72 total cases of minor salivary gland BCAC.13 Regional lymph node dissection is recommended only if there is evidence of metastatic disease to the cervical chain, and adjuvant radiation therapy has been used for invasive tumors and local recurrences.14 It is unclear whether radiotherapy plays a major role in the management of this tumor, but it can be effective if the margin of the surgical specimen is close or the lesion demonstrates local recurrence.15 AC C EP A discussion could also be considered with regards to the plan for the immediate reconstruction of the maxillectomy defect. In review of the literature, this topic remains controversial. It has been the experience of the authors as well as the findings of others, as discussed by Moreno et al, that in maxillectomy defects consisting of >50% resection of the hard palate, immediate free flap reconstruction results in superior functional outcomes when compared to obturation. Furthermore, it is often posited, that immediate reconstruction leads to a delay in the diagnosis of recurrence when compared to obturation, but this assertion has not been the experience of the authors nor the finding of Moreno et al. 16 In this case, an aggressive resection and clear frozen margins led the surgical team toward an immediate reconstruction. In retrospect, the permanent specimen finding of a close surgical margin could be used in making a case for delayed reconstruction. CONCLUSION: Diagnosis of BCAC can be difficult to make with a simple biopsy and the lesion may be easily mistaken for a benign basaloid tumor. Retrospectively, in review of this case, the new finding of ameloblastoma by an outside pathologist with a previous diagnosis of canalicular adenoma necessitated an oral-maxillofacial pathology consultation which ACCEPTED MANUSCRIPT AC C EP TE D M AN U Disclosures: Dr Tursun serves as a consultant to AxoGen, Inc. SC RI PT confirmed the diagnosis. In this case, it would have also been beneficial for an original slide request to be performed and a comparison completed of both sets of specimens despite the recurrence diagnosis having been confirmed by two general pathologists as well as an OMP. Due to the many similar features, despite this review, inadequate sampling of the lesion may have left the pathologist without the ability to determine the infiltrative growth pattern that differentiates BCAC from other similar lesions. In many such cases, the authors prefer to rebiopsy or personally review all outside pathologic diagnoses, and in this case that may have proven beneficial. Basal cell adenocarcinoma should be considered rare but none the less included in the differential diagnosis of lesions in this anatomical location when the lesions demonstrate similar clinical behavior. Furthermore, in this case, the patient not only underwent surgical ablation but also adjuvant radiation due to the history of recurrence as well as a close margin and is currently disease-free 3 years following surgery. (Image 10a,b, 11) ACCEPTED MANUSCRIPT References AC C EP TE D M AN U SC RI PT 1. Klima M, Wolfe K, Johnson PE. Basal cell tumors of the parotid gland. ArchOtolaryngol.1978;104(2):111-116. 2. Barnes L, Eveson JW, Reichart P, Sidransky D. Pathology and genetics of tumors of the head and neck. World Health Organization Classification of Tumors. Vol. 9. Lyon: IARC Press; 2005. 3. Ellis GL, Wiscovitch JG. Basal cell adenocarcinomas of the major salivary glands. Oral Surg Oral Med Oral Pathol. 1990; 69 (4):461 469. Franzen A, Koege lK, Knieriem HJ, Pfaltz M. Basal cell adenocarcinoma of the parotid gland: a rare tumor entity: case report and review of the literature[ inGerman]. HNO.1998;46(9):821-825. 4. Jäkel KT, Löning T. Differential diagnosis of basaloid salivary gland tumors. Pathology 2004;25:46-55. 5. DavidW. Cuthbertson, MD; Nikhila Raol, MD; John Hicks, MD, DDS, Ph.D.; Linda Green, MD; Robert Parke, MD, Minor Salivary Gland Basal Cell Adenocarcinoma A Systematic Review and Report of a New Case, JAMA Otolaryngol Head Neck Surg. 2015;141(3):276-283. doi:10.1001/jamaoto.2014.3344 Published online January 2, 2015 6. Barnes, L: World health organization, international agency for research on cancer: Pathology and genetics of head and neck tumors. Lyon: IARC press; 2005 7. Min Jung Jung et al, basal cell adenocarcinoma of the salivary gland: a morphological and immunohistochemical comparison with basal cell adenoma with and without capsular invasion; 2013 8. Ellis GL, Auclair PL. Atlas of tumor pathology. Tumors of the salivary glands. Washington (DC): Armed Forces Institute of pathology; 1996. Yamagata K, Oka K, Yoshida H, Yanagawa T, Onizawa K, Yusa H, et al. Basel Cell adenocarcinoma arising from the minor salivary gland in the soft palate: a case report. Pathol Res Orac 2006;202:475-80. 9. Neville BW, Damm DD ,Allen CM ,Bouquot JE. Salivary gland pathology. In: Neville BW, Damm DD ,Allen CM, Bouquot JE, editors. Oral and maxillofacial pathology. 2nd ed. Philadelphia: Saunders;2002.p.406-10. 10. Ellis GL, Auclair PL. Malignant epithelial tumours. In: Rosai LH, Sobin LH, editors. Atlas of tumour pathology, 3rd series, Fascicle 17. Tumors of salivary glands. Washington DC: Armed Forces Institute of Pathology; 1996.p.257–67. 11. Quddus MR, Henley JD, Afﬁfy AM, Dardick I,Gnepp DR. Basal cell adenocarcinoma of the salivary gland. Anultra structural and immunohistochemical study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;87:485–92. 12. Ellis GL, Wiscovitch JG: Basal cell adenocarcinomas of the major salivary glands. Oral Surg Oral Med Oral Patho l69:461,1990 13. Akiyama K, Karaki M, Hosikawa H, Mori N. A massive basal cell adenocarcinoma of the palatal minor salivary gland that progressed into the pterygopalatine fossa. Int J Oral Maxillofac Surg. 2012;41(4):444-447 ACCEPTED MANUSCRIPT AC C EP TE D M AN U SC RI PT 14. Gross M, Maly B, Goldfarb A, Eliashar R. Basal cell adenocarcinoma in a buccal minor salivary gland. Acta Otolaryngol. 2004;124(2):213-216. 15. Wada T, Morita N, Sakamoto T, Nakamine H, Basal cell Adenocarcinoma of the minor salivary gland: A case report. J Oral Maxillofac Surg 2000; 58:811-4 16. Moreno MA, Skoracki RJ, Hanna EY, Hanasono MM. Microvascular free flap reconstruction versus palatal obturation for maxillectomy defects. Head Neck. 2010 Jul;32(7):860-8. ACCEPTED MANUSCRIPT Images Image 1. Patient at representation with noted mild fullness on the patient's right side. RI PT Image 2 Preoperative clinical photograph of the lesion and right posterior palate Image 3 Axial view of soft tissue window of facial CT scan showing Right posterior maxilla and palate soft tissue mass SC Image 4 A Coronal views of soft tissue and bone windows of facial CT B. Multiple windows of the CT scan are limited secondary to dental prosthesis artifact M AN U Image 5 A. T1 axial view shows hyperdense lesion of the right maxilla and palate; B. T2 axial view shows hyperdense lesion of the right maxilla and palate; C. Sagittal views elucidating lesion location and extension D. Coronal views elucidating lesion location and extension Image 6 Ablative defect of wide excision following intraoperative finding of BCAC on frozen section. TE D Image 7 Intra-oral anastomosis of the antero-medial thigh flap prior to inset. No extraoral incision was used in preparing the facial vessels for microvascular anastomosis EP Image 8 Inset of the antero-medial thigh flap into the ablative defect. Image 9 A. Low power view of histological examination with signs of invasion, the absence of a capsule, and evidence of mitotic figures B. Higher power view showing evidence of mitotic figures AC C Image 10 A. Frontal view of the patient at 3 years without significant deformity well healed. B. Lateral view with no scarring to neck or face due to intraoral approach for vascular anastomosis to facial vessels. Image 11 Intraoral view of the well-healed flap and no signs of clinical recurrence.