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Title: Imaging findings of necrotizing sialometaplasia of the parotid gland: case report and literature review Shortened title: Images of necrotizing sialometaplasia of the parotid gland

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Type of Manuscript: Case reports

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Authors: Tadataka Tsuji1, 2 *, DDS, PhD, Clinical chief, Yoshiya Nishide3, MD, Clinical chief, Hiroshi

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Nakano4, MD, Clinical chief, Kumiko Kida1, DDS, PhD, Clinical fellow, and Koichi Satoh2, DDS, PhD, Clinical chief

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Affiliations: 1 First Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Osaka

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University, 1-8 Yamadaoka, Suita City, Osaka, 565-0871, Japan. 2 Department of Oral and Maxillofacial Surgery, Saiseikai Matsusaka General Hospital, 15-6 Asahimachi 1-ku, Matsusaka City, Mie, 515-8557, Japan. 3 Department of Radiology, Saiseikai Matsusaka General Hospital, 15-6 Asahimachi 1-ku,

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Matsusaka City, Mie, 515-8557, Japan. 4 Department of Pathology, Saiseikai Matsusaka General Hospital, 15-6 Asahimachi 1-ku, Matsusaka City, Mie, 515-8557, Japan.

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Correspondence: Tadataka Tsuji, DDS, Ph. D. First Department of Oral and Maxillofacial Surgery, Graduate school of Dentistry, Osaka University, 1-8 Yamadaoka, Suita City, Osaka, 565-0871, Japan. Tel: +81-6-6879-2936, Fax: +81-6-6876-5298, E-mail: [email protected]

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Financial interest: none

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The importance and main points of our reports are as follows: Although necrotizing sialometaplasia (NS) of the parotid gland is a rare and occasionally presents as a lesion that mimics a malignant tumor, imaging findings in cases of NS have been rarely reported. We describe here a case of NS in which there was an acute, increasing lesion manifesting overnight on the parotid gland in an 83-year-old Japanese male. Furthermore, we investigated the use of preoperative imaging based on previous reports and discuss the importance of these images in helping to guard against overzealous treatment. It is critically important to closely examine whether there are aspects of NS in the preoperative MRI findings or not.

Manuscript - do not include author details!

Title: Imaging findings of necrotizing sialometaplasia of the parotid gland: case report and

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literature review

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Abstract

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Although necrotizing sialometaplasia of the parotid gland is a rare and occasionally

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presents as a lesion that mimics a malignant tumor, imaging findings in cases of necrotizing

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sialometaplasia have been rarely reported. We describe here a case of necrotizing

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sialometaplasia in which there was an increasing lesion manifesting overnight on the parotid

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gland in an 83-year-old male. We also investigated the use of preoperative imaging based on

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previous reports and discuss the importance of these images in helping to guard against

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overzealous treatment. It is critically important to closely examine whether there are aspects

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of necrotizing sialometaplasia such as the present case in the preoperative MRI findings for

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proper diagnosis and treatment.

Keywords: Necrotizing sialometaplasia; Parotid gland; Preoperative imaging; MRI

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Introduction Necrotizing sialometaplasia (NS) is a benign inflammatory disease often found in the

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minor salivary gland and seldom observed in major salivary glands.1 To the best of our

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knowledge, the number of imaging reports associated with NS arising from the parotid gland

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is very small. In some of the cases, unnecessary surgical excision and inappropriate therapy

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Although the pathogenesis of lesions is thought to be due to

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pathological findings.2,

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were performed due to misdiagnosis, using an ostensible definitive diagnosis based on

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ischemic changes in the salivary glands arising from causes such as traumatic injury and

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medical procedures, the precise etiology has not been fully elucidated.2, 4 We here report a

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case of NS in the parotid gland, with the definitive diagnosis confirmed after superficial

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parotidectomy. Furthermore we discuss the importance of preoperative imaging to guard

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against unnecessary treatment.

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Case report

An 83-year-old man was referred complaining of an acute enlarging mass in the right

parotid gland that had developed overnight. The patient had been taking oral medications for

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hypertension and hyperlipemia for several years. There was no history of trauma or surgical procedure of the parotid gland. On physical examination, a palpably hard and firm mass, measuring 40×50 mm, was found on the right parotid gland tail (Figure 1). Additionally, the 2

patient had the hemorrhagic macule on the forearm. There was no discharge of pus from the parotid duct.

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Ultrasonographic image (US, Linear probe PLT-1204BT, 13-18 mhz, XarioXG,

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TOSHIBA, Japan) of the mass had the inhomogeneous hypoechoic appearance in comparison

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with the normal parenchyma of the parotid gland. The size of the mass was 26.5 × 21.8 ×

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19.9 mm and the border was unclear (Figure 2). CT images (Acquilion ONETM, TOSHIBA,

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Japan) revealed a slightly high density mass in parotid gland. The border between the mass

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and normal parotid gland tissue was unclear, suggesting the inflammatory mass in the parotid

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gland tail (Figure 3). On MRI (Signa HDxt 1.5T, GE Healthcare, Japan), T2-WI

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(T2-weighted image) revealed an apparently well-circumscribed mass of 26 mm that was

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surrounded with high signal intensity. The outliner wall of the mass was observed as low

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signal on both T1-WI and T2-WI, suggesting that the lesion was covered with a capsule. The content of the mass exhibited a low intensity area as well as an asteroid high intensity area on

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T2-WI (Figure 4a and 4b). The slightly high intensity on the inner wall of the mass on T1-WI was observed (Figure 4c). This area was also observed as a high intensity area on T2-WI. These findings suggested degeneration and necrosis had occurred within the mass.

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To rule out a malignant tumor, we performed gallium scintigraphy (67Ga, SymbiaTM E,

TOSHIBA, Japan) as an auxiliary diagnosis. A faint accumulation of gallium was observed over the whole area of the right parotid gland comparison with the left parotid gland, 3

indicating that the lesion might not be due to a malignant tumor but to inflammation (Figure 5).

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We suspected a tumor-like lesion displaying NS with surrounding inflammation. To reach

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definitive diagnosis, superficial parotidectomy with certain peripheral tissues around the mass

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was performed after extinction. Microscopic findings after Hematoxylin and eosin staining of

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the section exhibited a mixture of normal salivary gland tissue (Figure 6a), squamous

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metaplastic tissue conforming to the outline of salivary ducts without any atypia (Figure 6b)

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and necrotic tissue (Figure 6c), consistent with NS. After 6 months followed-up, no

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Discussion

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recurrence has developed.

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NS, an inflammatory reaction of salivary tissues with a self-limiting disease course, was described in 1973 by Abrams et al.2 It mainly occurs in the minor salivary glands of the hard

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palate. The incidence of this lesion in the parotid gland is rare and has been estimated to be at most approximately 10%.3 To our knowledge, Donath5 reported six cases of NS occurring in the parotid gland in 1979, following which Batsakis et al.1 documented an additional seven

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cases with clinical and pathologic findings in 1987. Furthermore, Brannon et al.3 reviewed sixty-nine cases of NS including six cases in parotid gland in 1991. As far as we have been able to determine from the English literature, excluding NS accompanied by salivary tumor 4

such as the metaplastic warthin’s tumor,6 five reports4, 7-9 of NS of the parotid gland have appeared, including the current case.

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An examination of the five reports on NS in the parotid gland showed that the age ranged

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from 17 to 83 years, with an average age of 53.4 years. Clinical symptoms most commonly

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comprised swelling of the neck, followed by pain (case 20), discharge of pus from the

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salivary duct (case 21), and swelling of the pharynx and neck, vocal cord paralysis and neck

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lymphadenopathy (case 22). Most of the masses was less than 20 mm, consistent with

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previous investigation.1 In the present case, the size of the lesions was larger than the average

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size in previous reports.1

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The etiology of NS remains unknown, but it may be associated with salivary gland tissue

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ischemia,3 leading to infarction and subsequent necrosis of the tissue, followed by repair and

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metaplasia. In 1987, Batsakis et al.1 reported that seven of eight parotid gland cases had followed an operative procedure for another primary tumor of the parotid gland. It is

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noteworthy that the clinical manifestations presented within a period of three and one half weeks after the initial surgery. Since 2002, the number of reasons for operation of the parotid glands has decreased due to the following histological criteria. The other causes were thought

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to be pressure-induced ischaemia,7 vascular injury4, 9 and tumor.8 In the present case, it was speculated that the cause was due to vascular fragility as indicated by the hemorrhagic macule on the forearm, similar to the mechanical pressure as the aetiological factor leading to 5

ischemia reported by Prabhakaran et al.7 As shown in Table 1, our investigation demonstrated that US, CT and fine needle

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aspiration biopsy (FNAB) were performed in most of cases for preoperative diagnosis.

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Although MRI findings of NS of the parotid gland have never been reported, Farina et al.10

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reported a case of MRI findings of NS manifesting ulceration of the palatal mucosa. They

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speculated that the high intensity on T2-WI might be the feature of salivary gland necrosis,

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and the peripheral rim enhancement might reflect the inflammatory reaction, leading to be the

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MRI findings suggestive of NS. In the present case, the high intensity on the inner wall of the

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mass on T1-WI and an asteroid high intensity area within the mass on T2-WI was observed,

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suggesting that tissue degeneration and necrosis had occurred within the mass. The

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well-circumscribed mass was surrounded with high intensity signal on T2-WI, indicating that

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the inflammation may have spread peripherally. Furthermore gallium scintigraphy supported the determination that this was not a malignant tumor. These preoperative findings indicated

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that the lesion in the parotid gland tail was most likely the result of a tumor-like lesion displaying NS accompanied by inflammation. Palma et al.6 reported that trauma such as an FNAB caused infarction and squamous

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metaplasia in a case of warthin’s tumor, followed that a lesion analogous to NS was observed in non-neoplastic salivary glands. Scrupulous attention is required to perform FNAB in the course of an investigation of patients with a mass of neck. Thus, we have stressed that MRI 6

findings might be necessary and helpful for proper diagnosis and treatment of NS. However, this can present a diagnostic dilemma due to the histological findings as well as

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In order to avoid

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such as squamous cell carcinoma or mucoepidermoid carcinoma.2,

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the clinical examination and imaging, all having the potential to mimic a malignant neoplasm,

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needless surgery, certain reports have suggested the following specific criteria pathological

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diagnosis: necrosis of salivary tissue; a time variable prominence of granulation and acute

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and chronic inflammation; squamous metaplasia conforming to duct and/or acinar outlines;

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maintenance of the salivary morphology.1-3

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Anneroth et al.11 classified the pathological condition into 5 stages, following infarction

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(necrotic), sequestration, ulceration, reparative and healed. Suomalainen et al. 12 suggested

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that the degree of the inflammatory reaction can be reflected on the above stage of NS. In the

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present case, the specimen histologically displayed variable features consistent with different stages, including the necrotic, reparative and healed stages, apparently because the period

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from onset to operation was relatively-long 1 month. In conclusion, NS is a spontaneously resolving inflammatory process of salivary gland

that can mimic a malignant tumor. It is critically important to closely examine whether there

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are aspects of NS in the preoperative MR findings or not to avoid overzealous treatment. If the lesion in the parotid gland is not suspected of being a malignant tumor but rather NS, it might be preferable to adopt a “wait and see” approach due to the possibility of spontaneous 7

healing within 3 to 12 weeks3 may occur in cases of NS. When surgical excision of the lesion was performed, we should carefully examine whether there are aspects of NS in the

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histopathological findings, by following the pathological guidelines described above.

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Acknowledgments

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We thank Uemura Y and Hukumoto Y at Saiseikai Matsusaka General Hospital for technical

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advice.

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Conflict of interest

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The authors declare they have no conflict of interest.

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References 1.

Batsakis JG, Manning JT. Necrotizing sialometaplasia of major salivary glands. J

Abrams AM, Melrose RJ, Howell FV. Necrotizing sialometaplasia. A disease

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2.

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Laryngol Otol 1987; 101:962-966.

Brannon

RB,

Fowler

CB,

Hartman

KS.

Necrotizing

sialometaplasia.

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3.

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simulating malignancy. Cancer 1973; 32:130-135.

Aydin O, Yilmaz T, Ozer F, Sarac S, Sokmensuer C. Necrotizing sialometaplasia of

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4.

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Oral Med Oral Pathol 1991; 72:317-325.

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clinicopathologic study of sixty-nine cases and review of the literature. Oral Surg

Donath K. Pathohistology of necrotizing sialometaplasia in parotid glands. Laryngol

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5.

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64:171-174.

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parotid gland: a possible vasculitic cause. Int J Pediatr Otorhinolaryngol 2002;

Rhinol Otol 1979; 58:70-76. Di Palma S, Simpson RH, Skalova A, Michal M. Metaplastic (infarcted) Warthin's

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6.

tumour of the parotid gland: a possible consequence of fine needle aspiration biopsy.

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7.

Histopathology 1999; 35:432-438. Prabhakaran VC, Flora RS, Kendall C. Pressure-induced necrotizing sialometaplasia of the parotid gland. Histopathology 2006; 48:464-465.

8.

Yoshioka T, Harada M, Umekita Y, et al. Necrotizing sialometaplasia of the parotid 9

gland associated with angiocentric T-cell lymphoma: a case report and review of the literature. Pathol Int 2010; 60:326-329. Kim YH, Joo YH, Oh JH. A case of necrotizing sialometaplasia involving bilateral

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9.

Farina D, Gavazzi E, Avigo C, Borghesi A, Maroldi R. Case report. MRI findings of

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10.

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parotid glands. Am J Otolaryngol 2013; 34:163-165.

Anneroth G, Hansen LS. Necrotizing sialometaplasia. The relationship of its

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11.

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necrotizing sialometaplasia. Br J Radiol 2008; 81:e173-175.

Suomalainen A, Tornwall J, Hagstrom J. CT findings of necrotizing sialometaplasia.

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12.

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pathogenesis to its clinical characteristics. Int J Oral Surg 1982; 11:283-291.

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Dentomaxillofac Radiol 2012; 41:529-532.

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Figure legends Figure 1: A palpable hard and firm mass was found on the right parotid gland tail at the first

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visit.

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Figure 2: Ultrasonography showing the inhomogeneous hypoechoic appearance on the right

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parotid gland.

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Figure 3: CT images showing the poorly-marginated mass with normal parotid gland tissue.

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Figure 4: (a) an axial and (b) a coronal section with T2-weighted MRI showing an apparently

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well-circumscribed mass with surrounding high signal intensity in the right parotid gland tail.

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(c) a coronal section with T1-weighted MRI showing the high intensity on the inner wall of

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the mass.

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Figure 5: A faint accumulation of gallium (67Ga) was observed over the whole area of the

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right parotid gland comparison with the left parotid gland. Figure 6: (a) Normal salivary gland tissues can be seen in the right portion and the

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inflammatory tissues are present in the left portion. (b) The fibrous connective tissue with inflammatory cell infiltrate and squamous metaplasic tissues conforming to the outline of salivary ducts can be observed. (c) On a high-power view, squamous metaplasia without

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cytological atypia around the salivary gland duct can be observed. (d) Necrotic tissues and inflammatory infiltration with histiocytes can be observed. Original magnifications: (a, b) ×40; (c) ×200; (d) ×100, H&E-stained. 11

Table 1 Characteristics of the reported cases of necrotizing sialometaplasia arising in the parotid gland. Preoperative Case

Year

Author

Age/sex

Cause

Size (cm)

Clinical Presentation

1979

Donath5

7-13

1987

Batsakis et al.1

Mean age of M; 54

post-operative

0.6-1.0

Post-operative salivary

Mean age of F; 49

vascular injuries

(Mean of

mass: 86%

Sex ratio; M:F=1:2

(11/13cases)

6 cases)

Sialadenitis: 14%

1991

Brannon et al.3

NS

vascular injuries

NM

20

2002

NM

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(5/6cases)

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post-operative 14-19

NM

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1- 6

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examination

NM

Pain

Aydin et al.4

17/F

vascular injury

2

US/CT/FNAB

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Swelling of neck Swelling of neck

21

2005

Prabhakaran et al.

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pressure-induced 32/M

NM

Pus discharge from the

CT

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2010

Yoshioka et al.8

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ischemia

malignant

66/M

Swelling of neck Swelling of pharynx

NM

FNAB Vocal cord paralysis

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lymphoma

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parotid duct

Neck lymphadenopathy

vascular injury

2013

Kim et al.9

69/F

Current report

3×2, due to heavy

Swelling of neck

CT/FNAB

1.5×1.5 smoking

pressure-induced

83/M

US/CT/MRI/ 4×5

Swelling of neck

ischemia

Ga Sci

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2013

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M, male; F, female; CT, computed tomography; FNAB, fine needle aspiration biopsy; MRI, magnetic resonance imaging; Sci, Scintigraphy; US, ultrasonography; NM, not mentioned

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Itemised List of Revisions

Author Responses to Referees Letter (DMFR-D-14-00127)

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Imaging findings of necrotizing sialometaplasia of the parotid gland: case report and literature review Thank you very much for the valuable comments. Following these comments, we have

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revised the text, and the results have been included in the revised text with the highlight. Followings are our replies. Reviewer #1 (Comments to the Author):

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1. Please have the paper read by an English native speaker, as the words 'the', 'a' and 'an' are not always used appropriately. This will increase the readability of your paper. Many thanks for the valuable suggestions. According to these comments, we have revised the text. Pacific Edit reviewed the manuscript prior to submission.

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2. Hypoechoic genicity; I suggest to replace the word genicity by 'character' or 'appearance' - this in the text and in the figure 2 capture

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I replaced the word “genicity” to “appearance”. Please check the modified text and the figure 2 caption.

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3. Can you be a bit more specific on the ultrasound transducer that was used and the settings?

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I added the text about the ultrasound transducer. Please check the modified text. 4. Page 5, line 3; I think it should be masses instead of mass

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I corrected the word “mass”. Please check the modified text.

5. Page 7, paragraph that starts with 'Although FNAB...' ; this sentence is not correct and need re-editing. I omitted the sentence “Although FNAB … gland”. Please check the modified text.

6. Page 7, last paragraph; I would add another section to this as a conclusion from this

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case report, to warn clinicians about the risks of overzealous treatment in these cases. I corrected this section as described below. In conclusion, NS is a spontaneously resolving inflammatory process of salivary gland that can mimic a malignant tumor. It is critically important to closely examine whether

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there are aspects of NS in the preoperative MR findings or not to avoid overzealous treatment. If the lesion in the parotid gland is not suspected of being a malignant tumor but rather NS, it might be preferable to adopt a “wait and see” approach due to the possibility of spontaneous healing within 3 to 12 weeks may occur in cases of NS.

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When surgical excision of the lesion was performed, we should carefully examine whether there are aspects of NS in the histopathological findings, by following the pathological guidelines described above.

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7. Fig. 1 capture; I think it should be palpable, instead of palpably

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I corrected the word “palpably”. Please check the modified text. 8. Fig. 2 capture; genicity - I would replace that with appearance or character

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I replaced the word “genicity” to “appearance”

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9. Fig. 6 capture; H&E stained needs some explanation

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I replaced the Fig. 6 to the high-quality figures and corrected the explanation as described below. (a) Normal salivary gland tissues can be seen in the right portion and the inflammatory tissues are present in the left portion. (b) The fibrous connective tissue with inflammatory cell infiltrate and squamous metaplasic tissues conforming to the outline

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of salivary ducts can be observed. (c) On a high-power view, squamous metaplasia without cytological atypia around the salivary gland duct can be observed. (d) Necrotic tissues and inflammatory infiltration with histiocytes can be observed. Original magnifications: (a, b) ×40; (c) ×200; (d) ×100, H&E-stained. 10. Table 1; NS is here used as 'not stated', while in the text, one reads NS all the time and then it means necrotizing sialometaplasia. This is confusing to me. I would suggest

to replace NS in table 1 and use MI (missing information) or NM (not mentioned)

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instead. Following the advice, I changed the word “NS (not stated)” to “NM (not mentioned)”. Reviewer #2 (Comments to the Author):

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This paper reports an interesting and rare case of necrotizing sialometaplasia arising in the parotid gland. The image findings described are effective for clinics in diagnosing parotid masses. Although it could be accepted in the present form, the key of MR findings should be described more in detail to include the diagnosis of necrotizing

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sialometaplasia. Many thanks for the valuable suggestions. Following the comments, I added the text about the specific MRI findings in the section of “case report” as described below. On MRI (Signa HDxt 1.5T, GE Healthcare, Japan), T2-WI (T2-weighted image)

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revealed an apparently well-circumscribed mass of 26 mm that was surrounded with high signal intensity. The outliner wall of the mass was observed as low signal on both T1-WI and T2-WI, suggesting that the lesion was covered with a capsule. The content of the mass exhibited a low intensity area as well as an asteroid high intensity area on

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T2-WI (Figure 4a and 4b). The slightly high intensity on the inner wall of the mass on T1-WI was observed (Figure 4c). This area was also observed as a high intensity area on T2-WI. These findings suggested degeneration and necrosis had occurred within the mass.

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We hope that above responses will fulfill the reviewers’ comments. We look forward to hearing good news. Best wishes, Tadataka Tsuji, DDS, Ph.D.

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Osaka University, Japan.

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Author Contribution Statement

Author Contribution Statement

DMFR requires that for all submitted papers: •

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all the authors have made substantive contributions to the article and assume full responsibility for its content; and all those who have made substantive contributions to the article have been named as authors.

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The International Committee of Medical Journal Editors recommends the following definition for an author of a work, which we ask our authors to adhere to: Authorship be based on the following 4 criteria [1]:

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• • •

Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work; AND Drafting the work or revising it critically for important intellectual content; AND Final approval of the version to be published; AND Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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Please list below all authors of this work and a brief description of how they each contributed towards your submission:

Yoshiya Nishide

Analysis and interpretation of radiological data collected, Final approval of the version, Agreement to be accountable for all aspects of the work

Analysis and interpretation of pathological data collected, Final approval of the version, Agreement to be accountable for all aspects of the work

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HIroshi Nakano

Conception and design of the work, Acquisition of all data, Drafting of article, Final approval of the version, Agreement to be accountable for all aspects of the work

E C

Tadataka Tsuji

Contribution

T

Author name

C O

Kumiko Kida

Final approval of the version, Agreement to be accountable for all aspects of the work

U

N

Koichi Satoh

Acquisition of data: laboratory or clinical/literature search, Final approval of the version, Agreement to be accountable for all aspects of the work

Please continue on further pages if needed. 1 The International Committee of Medical Journal Editors, Roles and Responsibilities of Authors, Contributors, Reviewers, Editors, Publishers, and Owners: Defining the Role of Authors and Contributors, http://www.icmje.org/roles_a.html

Imaging findings of necrotizing sialometaplasia of the parotid gland: case report and literature review.

Although necrotizing sialometaplasia (NS) of the parotid gland is rare and occasionally presents as a lesion that mimics a malignant tumour, imaging f...
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