- Email: [email protected]
MRI evaluation of involvement of parotid and submandibular glands by tongue squamous cell carcinoma
Oral Oncology 102 (2020) 104557
Contents lists available at ScienceDirect
Oral Oncology journal homepage: www.elsevier.com/locate/oraloncology
MRI evaluation of involvement of parotid and submandibular glands by tongue squamous cell carcinoma
T
⁎
Aarati Panchbhai , Rahul Bhowate Department of Oral Medicine and Radiology, S P Dental College & Hospital, DMIMSDU, Sawangi-M, Wardha, Maharastra, India Department of Oral Medicine and Radiology, S P Dental College & Hospital, DMIMSDU, Sawangi-M, Wardha 442001, Maharastra, India
A R T I C LE I N FO
A B S T R A C T
Keywords: Tongue OSCC Salivary gland Spread MRI
Objectives: The majority of cases of salivary gland involvement are diagnosed in its late stages as may be missed in the evaluation, the low detection rate of involvement of salivary gland by OSCC may have significant impact on spread and recurrence of the OSCC. The study aimed to evaluate involvement of parotid and submandibular salivary glands by tongue oral squamous cell carcinoma. Material and method: The 144 histo-pathologically proven cases of tongue squamous cell carcinoma were evaluated for clinical staging, margins and extent of tumor and involvement of salivary gland on T1-T2 Weighted, STIR, diffusion-weighted and contrast-enhanced MRI sequences and data was subjected to analysis. Results: In tongue OSCC, total 9 (6.25%) patients showed salivary gland involvement, 2 of them involved parotid glands and 7 of them involved submandibular gland. The OSCC involving the salivary glands were in Stage 4 except for 2 cases with predilection for antero-lateral border and tendency towards midline crossing. Out of 9 cases that showed salivary gland involvement, the 5 cases showed direct involvement from the spreading lesion, the 3 cases showed the infiltration from adjacent lymph nodes and 2 cases showed infiltration from sublingual gland and medial pterygoid muscle. Conclusion: The present study revealed the greater percentage of OSCC with salivary gland involvement as compared to previous studies; in contradiction present study demonstrated higher involvement of submandibular gland compared to parotid gland with additional imaging features in salivary glands (15.97%) suggesting the likely possibility of their involvement by OSCC in near future.
Introduction Oral cavity squamous cell carcinomas (OSCC) form a significant percentage of cancers seen in India [1–4]. Oral squamous cell carcinoma has an aggressive nature as it grows rapidly and penetrates well with a high recurrence rate, the buccal mucosa and tongue OSCC being the soft tissue malignancies are the most aggressive form of oral cancers with the greater prevalence in India. The prevalence of squamous cell carcinoma of Tongue (tongue OSCC) was found to be in the range 13.5–58.4% in various studies conducted in India [1–7]. There is a rising incidence of tongue OSCC both in India as well as in the western countries; hence the tongue OSCC needs comprehensive evaluation of prognostic factors in addition to comorbidity, tumor differentiation, extracapsular spread, and perineural invasion. In aggressive cancers, local spread and nodal metastases are adverse prognostic factors and require accurate detection for optimized treatment.
⁎
Metastases of OSCC to the salivary glands are of special importance for therapy and prognosis. Earlier studies demonstrated the involvement of parenchyma or the lymph nodes of the parotid gland and submandibular gland. The relative frequency of metastases in the lymph nodes of the salivary glands may be due to the intense drainage with lymph vessels and the presence of many lymph nodes which are localized especially in the gland parenchyma or around the gland. While evaluating the metastasis to salivary gland from OSCC, the other distant metastatic sources to salivary gland needed to be ruled out as the metastatic tumors may originate from lung cancers, renal cancers, mammary cancers, colonic cancer, thyroid cancers and uterus cancer [8]. The tongue OSCC may arise from body or base of tongue; the majority of them arises from the lateral border followed by few from ventral surface. The tongue OSCC arising from base of the tongue are similar to oropharyngeal cancers. Notably, the tongue OSCC may be
Corresponding author. E-mail address: [email protected] (A. Panchbhai).
https://doi.org/10.1016/j.oraloncology.2019.104557 Received 13 September 2019; Received in revised form 23 November 2019; Accepted 25 December 2019 1368-8375/ © 2019 Elsevier Ltd. All rights reserved.
Oral Oncology 102 (2020) 104557
A. Panchbhai and R. Bhowate
The data pertaining to demographic details, clinical findings with TNM staging [16] and histopathological evaluation of the patient was obtained. The selected patients had undergone MRI evaluation (GE Brivo355, 1.5 Tesla) before surgery using following protocol for tongue OSCC. Images were obtained with T1 weighted; T2 weighted, STIR, diffusion-weighted and contrast-enhanced MRI sequences and evaluated using following criteria:
manifested as very shallow ulcers to apparently negate the need of imaging, however due to a high incidence of occult cervical lymph node metastasis it is always prudent to go for imaging. While clinical examination allows direct visualization, it cannot evaluate deep extension of disease. Cross-sectional imaging has become the cornerstone in the pre-treatment evaluation of these cancers and provides accurate information about the extent, depth and spread of disease that can help decide the appropriate management strategy and indicate prognosis [9,10]. Imaging for tongue SCC requires a modality with superior soft tissue characterization and hence magnetic resonance imaging (MRI) is the optimal modality displaying exquisite anatomical detail, and involvement of base of tongue, floor of mouth and oro-pharynx which is extremely difficult to be seen on CT. In addition, MRI is used to assess the extent of loco-regional tumor spread, depth of invasion, extent of lymphadenopathy and occult metastasis. Excellent soft-tissue discrimination of MRI readily reveals tumor invasion and spread to surrounding structures. The efficiency of MRI has been enhanced by exploiting suppression and tumor-induced metabolic, vascular, or micro structural changes. Diffusion-weighted imaging can precisely detect structures involved by cancer and it can also differentiate between reactive and metastatic lymph nodes. Contrast-enhanced T1W images help assess marrow invasion, soft tissue extent, tumor thickness and best demonstrate necrosis in nodes. It is also used to assess the presence of occult metastatic lymph nodes [11–15]. Considering the propensity for locoregional spread and recurrence of Tongue OSCC, the involvement of salivary gland by OSCC also needs to be estimated. The majority of cases of salivary gland involvement are diagnosed in its late stages as may be missed in the evaluation, the low detection rate of involvement of salivary gland by oral SCC is a considerable clinical issue. This may have significant impact on spread and recurrence of the OSCC. In addition, it is difficult to diagnose metastases in lymph nodes in and around salivary glands, which is important for planning the scope of resection and further treatment. The preservation of the glandular function due to damage to the salivary duct during surgery may also be one of the considerations dealing with these cancers. Earlier studies evaluated the salivary gland involvement by OSCC based on histopathological evaluation which has a limitation that it relies on resected specimen as only the biopsied or resected tissue would be examined wherein imaging especially MRI evaluation may allow to perform the comprehensive evaluation of the tumor, and adjacent or distant soft tissue that needs evaluation. Imaging studies are performed as part of the routine work-up in OSCC; however, they are not intended to assess the involvement of salivary glands especially for the apparently early stages of disease on clinical examination or the occult cases that are missed in clinical evaluation of OSCC patients. There are very few imaging studies in literature that have explored the involvement of the parotid and submandibular salivary gland by OSCC. In view of this, the present study was aimed to evaluate the involvement of parotid and submandibular salivary glands by tongue oral squamous cell carcinoma using magnetic resonance imaging.
Protocol for MRI
• frFSE: l/160 • FOV: 24 × 30 • WW: 1529, WL: l 764 • TR: 5476, TE: 118 Criteria for MRI evaluation MR images were assessed for the following: ▪ ▪ ▪ ▪
signal intensity of lesions extent of lesion margins of lesion involvement of salivary glands by tongue OSCC
The tongue OSCCs were evaluated using all the MRI sequences in axial, coronal and sagital views of the images. The findings were tabulated for tongue OSCC and subjected to analysis. Results The selected patients had undergone MRI evaluation (GE Brivo 1.5 Tesla) before surgery, the images obtained with T1-T2 Weighted, STIR, diffusion-weighted and contrast-enhanced MRI sequences were evaluated for signal intensity, margin and extent of tumour and involvement of parotid and submandibular salivary glands (Figs.1–3). The gender wise distribution of total 144 Tongue OSCC patients showed male (106) predilection over female (38) with male to female ratio of almost 3:1 (Table 1). For age wise distribution of Tongue OSCC patients, the total of 144 patients were divided in the 2 age ranges as shown, the sample showed almost equal distribution in the given age ranges (Table 1). In tongue OSCC, total 9 (6.25%) patients showed salivary gland involvement, 2 of them involved parotid glands and 7 of them involved submandibular gland (Table 1). The Table 2 summarized the imaging characteristics of the 9 Tongue OSCCs involving salivary glands; it showed male predominance with only 2 female patients. In age wise distribution, out of 9, 7 cases belonged to 21–50 age range suggesting involvement of salivary gland in lower age group in tongue OSCC. The OSCC involving the salivary glands were in Stage 4 except for 2 cases that belonged to Stage 3, the right and left side of tongue were equally involved with predilection for antero-lateral border and tendency towards midline crossing. The adjacent structures involved were base of tongue, floor of mouth, mandible, sublingual space, salivary glands, mylohoid, retromolar trigone, and medial pterygoid. Out of the 9 patients, the 7 OSCCs had ill-defined margins while 2 had well-defined margins. The MRI images were hypointense to isointense on T1weighted, hyperintense on T2 weighted and STIR, and heterogeneously enhancing on contrast-enhanced sequences. In 4 patients, the restricted diffusion was seen in diffusion-weighted sequence (Table 2). Table 3 showed the mode of involvement and imaging characteristics of involved salivary glands in Tongue OSCC. Out of 9 cases that showed salivary gland involvement, the 5 cases showed direct involvement from the spreading lesion, the 3 cases showed the infiltration from the adjacent lymph node and 2 cases showed infiltration from sublingual gland and medial pterygoid muscle. Most of the involved salivary glands showed heterogenous enhancement of the ipsilateral
Materials and method The present ethics committee approved study was conducted at Sharad Pawar Dental College, DMIMS (DU), Sawangi-Meghe, Wardha, India in collaboration with department of Radio-diagnosis, AVBRH. At the outset, the study design was explained to each study participant and the voluntary consent was obtained. The 144 histo-pathologically proven cases of tongue squamous cell carcinoma were included in the study following the exclusion criteria. Exclusion criteria
• Oral malignancies other than squamous cell carcinoma • Metastatic OSCC 2
Oral Oncology 102 (2020) 104557
A. Panchbhai and R. Bhowate
Fig. 1. Tongue OSCC involving right half of the tongue in T1-weighted image and Contrast-enhanced Image (Coronal section). Table 1 Tongue OSCC cases showing salivary gland involvement.
Gender Age range (years) Salivary gland involvement
Variable
No. of subjects (%)
Total
Male Female 21–50 Years 51–72 Years Parotid G. Submandibular G.
106 (73.61%) 38 (26.38%) 71 (48.97%) 73 (51.02%) 2 (1.38%) 7 (4.86%)
144 (100%) 144 (100%) 9 (6.25%)
salivary glands, with few showing the necrotic areas. Table 4 summarizes the additional imaging features suggesting the likely possibility of involvement of salivary gland by tongue OSCC in near future, the percentage of involvement was 15.97%.
Discussion The study was carried out with the purpose to evaluate the involvement of salivary gland by tongue OSCC. The sample showed predominance of male over female in tongue OSCCs, most of the patients with salivary gland involvement were in 21–50 years age range. The total 9 (6.25%) patients showed salivary gland involvement, 2 (2.04%) of them involved parotid glands and 7 (7.14%) of them involved submandibular gland. The involvement of submandibular gland was greater than parotid gland. The literature revealed the involvement of the involvement of parotid gland in the range 0.79–3% [8,17,23] with varied prevalence in various studies. Melhoranse BG et al. (2016), reported parotid metastases of around 3% and indicate aggressive local disease as well as more severe prognosis [19]. Stanley MW et al. (1995), reviewed 20 patients (39–89 years) of poorly differentiated carcinomas involving salivary glands, out of which 11 were primary tumors and nine were metastatic malignancies [24]. Seifert G et al. (1986), scrutinized the salivary Gland Register and found 108 cases of metastatic tumors to the parotid and submandibular gland [8]. The 47 cases (43%) of metastatic tumors were localized in the parenchyma of the parotid gland (37 cases) or of the submandibular gland (10 cases). The 65 metastatic tumors originated from adjacent primary tumors in head and neck, mainly from skin, followed by nasopharyngeal cancers and thyroid cancers while 21 metastatic tumors were originated from primary tumors from distant sites. Chen TC et al. (2009), retrospectively reviewed the pathologic records of 383 submandibular glands in OSCC patients in which 7 (1.8%) exhibited tumor involvement which was uncommon [19]. Kruse and
Fig. 2. Tongue OSCC involving the left submandibular gland (Coronal section).
Fig. 3. Histopathological section of submandibular gland showing acini (white arrow) and epitheial cells (black arrow), (H/E stain, 40x).
3
Oral Oncology 102 (2020) 104557
A. Panchbhai and R. Bhowate
Table 2 Imaging characteristics of Tongue OSCC involving salivary glands. TONGUE
Imaging characteristics of Primary tumors showing salivary gland involvement
Sn
Age sex
Tumour stage
Region
Tumor Margin
T1
T2
STIR
Contrast
Diffusion Weighted
Case 1 Case2 Case3
46F 42M 62M
Stage 4 T2N2M0 Stage 3 T3N1M0 Stage 4 T4N2CM0
ill defined Well defined ill defined
Hypo-iso Hypo Hypo
Hyper Hyper Hyper
Hyper Hyper Hyper
Heterogeneously enhancing Altered intensity Heterogeneously enhancing
– – Restricted diffusion
Case 4
49M
Stage 3 T3N1M0
Left Lateral, floor Right Lateral Right Postero Lateral Left post 1/3rd
ill defined
Hypo
Hyper
Hyper
–
Case Case Case Case Case
40M 38M 37M 47M 56M
Stage Stage Stage Stage Stage
Base, floor Right Lateral Base, floor Left Lateral Right Lateral
ill defined ill defined ill defined Well defined ill defined
Hypo Hypo-iso Hypo hypo hypo
Hyper Hyper hetero Hyper Hyper
Hyper Hyper Hyper Hyper Hyper
Heterogeneously enhancing with areas of necrosis Altered intensity enhancing Heterogeneously enhancing intensely enhancing Heterogeneously enhancing
5 6 7 8 9
4 4 4 4 4
T4N2BM0 T4N2BM0 T4N2CM0 T3N2CM0 T4N2CM0
Gratz (2009), evaluated 171 submandibular glands in head and neck malignancy patients (average age, 61.1 years), the 6 patients showed involvement of salivary glands through tumor infiltration (5), and intraglandular lymph node (1) along with chronic sialadenitis and atrophy [25]. Malik A et al. (2016), assessed the pattern of nodal metastasis in OSCC in relation to the submandibular gland [26]. The fibrofatty tissue surrounding the submandibular gland was divided into 6 parts depending upon its location with the submandibular gland. In cases with cervical lymphadenopathy, deep metastasis was seen in 4 cases only (14.8%) and none of them had a primary tumor in the tongue. Naidu TK et al. (2012), revealed 2.9% of submandibular gland metastases in 69 cases of OSCC in mean age 58 years [20]. Panda NK et al. (2015), analyzed 163 submandibular glands for involvement in cases of oral cavity cancers, 3.68% (6) glands showed involvement by the tumor [22]. In retrospective review, Fives C et al. (2017), investigated the incidence and mechanism of submandibular gland involvement in of 177 patient of floor of mouth cancer, submandibular gland involvement was present in 2 patients, representing 1% of all oral cancers, and 4% floor of mouth cancer cases [23]. In the present study, all the cases of tongue OSCC showed ipsilateral salivary gland involvement. his was in accordance with Naidu TK et al. (2012), Byeon HK et al. (2009)and Spiegel JH et al. (2004) [20,27,28] and in contradiction to finding in a case reviewed by Shivkumar et al. (2013) [18] where the delayed nodal metastasis was reported to the contralateral intra-parotid node. Byeon HK et al. (2009) examined the pathologic record of 201 OSCC patients in which only 2 cases (1%) had involvement of submandibular gland but 21.9% showed ipsilateral level I metastasis [27]. Accordingly, the incidence of submandibular gland metastasis in OSCC is extremely rare. Spiegel JH et al. (2004), determined that all the primary lesions were ipsilateral to the involved
Restricted diffusion Restricted diffusion Restricted diffusion –
Table 4 No. of cases with Imaging features suggesting possibility of involvement of salivary gland by OSCC. Sn
OSCC
N (%)
Tongue OSCC
23 (15.46%)
Imaging features gland • Bulky enhancing gland • Unilaterally signal intensity of gland • Altered defined margins of the gland • IllInvolvement • tumour of the glandular space by of fat planes of gland • Loss of mylohyoid • Involvement of masticator space, ie • Involvement masseter/medial pterygoid lymph nodes • Enlarged of sublingual space • Involvement infiltrating base of tongue, or crossing • OSCC midline
gland and originated from cancers of floor of mouth, alveolar ridge and tongue. Naidu TK et al. (2012) observed that only 2 (2.9%) submandibular glands demonstrated ipsilateral contiguous tumour involvement [20]. The metastatic tumors originated from primary tumors distant than the head and neck region may include the sites as lung, renal, mammary, colon, thyroid and uterus [8]. In the present study, the mode of involvement of salivary glands was either through direct spread from primary tumor or from infiltration from adjacent lymph nodes. Chen TC et al. (2012), observed that 5 glands were involved by direct extension from the primary tumor, 1 gland showed local invasion from an adjacent involved lymph node in level I and 1 was from intraglandular lymph node metastasis [21]. Spiegel JH et al. (2004), revealed that submandibular gland has no
Table 3 Mode of involvement and Imaging characteristics of involved salivary glands in Tongue OSCC. TONGUE
Imaging characteristics of Salivary gland involvement
Sn
Age sex
Tumour stage
Mode of involvement
Imaging characteristics
Case 1
46 F
Stage 4 T2N2M0
Left parotid showing heterogeneous enhancement
Case2 Case3 Case 4 Case 5 Case 6 Case 7
42 62 49 40 38 37
Stage Stage Stage Stage Stage Stage
Infiltration from adjacent large jugulodiagrastric lymph node Direct spread from base Direct spread Infiltration from sublingual gland Infiltration from adjacent lymph node Direct spread Direct spread
Case 8 Case 9
47 M 56M
M M M M M M
3 4 3 4 4 4
T3N1M0 T4N2CM0 T3N1M0 T4N2BM0 T4N2BM0 T4N2CM0
Stage 4 T3N2CM0 Stage 4 T4N2CM0
Infiltration from adjacent lymph node Infiltration from adjacent medial pterygoid Direct spread
4
Right submandibular gland showing isointense heterogeneous enhancement Right submandibular gland showing heterogeneous enhancement left submandibular gland showing heterogeneous enhancement Right submandibular gland showing heterogeneous enhancement Right submandibular gland showing Altered intensity Bilateral involvement of submandibular gland showing heterogeneous enhancement Very bulky enhancing gland left submandibular gland Involving both right parotid and right submandibular glands –Deep lobe of right parotid with heterogeneous enhancement and necroses –Right submandibular enhancing gland
Oral Oncology 102 (2020) 104557
A. Panchbhai and R. Bhowate
more than N2b [21]. Naidu TK et al. (2012) revealed that 62.3% had advanced tumor stage three or four lesions of OSCC amongst which only few showed salivary gland involvement [20]. Melhoranse BG et al. (2016), reported the importance of parotid involvement as an isolated prognostic factor and a therapy guide. The parotid nodes have long been recognized as potential sites for lymphatic spread of tumors with guarded prognosis of SCC in the head and neck region [19]. Harada H et al. (2009), reported that likelihood of metastasis to parotid nodes increased with the number of cancer-positive cervical nodes. Resection of the tail of parotid gland is warranted during the neck dissection [17]. Kenji Y et al. (2014), mentioned that metastasis of the parotid lymph node is associated with a poor prognosis in SCC of the head and neck. There is no consensus on the appropriate treatment for the parotid lymph node metastasis in OSCC because of the small number of reported cases [30]. Diaz EM et al. (2003), observed that muscle invasion, Stensen's duct involvement and extracapsular spread of involved lymph nodes were all associated with decreased survival [31]. Additionally, Melhoranse BG et al. (2016) reported that the current AJCC TNM staging system does not comprise the parotid gland involvement. In TNM staging, all patients with parotid and/or neck nodal metastasis are classified as N1. O’Brien proposed a new classification to distinguish between parotid node involvement (“P”) and neck nodal disease (“N”) (Melhoranse, Barbosa, Carneiro, El Hadj, Fernandes, 2016) [19]. This classification considers that the higher the parotid involvement, the lower the survival index.
intraparenchymal lymph nodes, its involvement in upper aerodigestive tract carcinomas must be through extension from a locally involved lymph node or the primary tumor [28]. Byeon HK et al. (2009), demonstrated that the incidence of submandibular gland involvement is through direct extension from a primary lesion; both the cases had direct extension from a primary lesion (retromolar trigone and floor of mouth) and no submandibular glands showed pathologic evidence of isolated metastasis or local extension of metastatic lymph nodes in their study [27]. Ashfaq K et al. (2014) observed that the submandibular gland was involved in 2 cases (1.8%) via direct spread; the submandibular gland metastasis from early oral cavity tumors is rare [29]. In the study by Panda NK et al, 4 of the 6 involved glands showed direct contiguous spread from primary lesion, 1 showed extra-capsular spread from level IB lymph nodes and evidence of both modes of spread was seen in one of their cases [22]. Fives C et al. (2017), al demonstrated a newer mechanism of carcinoma growing along Wharton's ducts in addition to direct extension [23]. It was further mentioned that in spite of the high incidence of level I metastasis in floor of mouth, the lymphatic metastases to submandibular gland are unlikely. This is similar to finding by Malik A et al. (2016), who revealed that direct metastases to the submandibular glands are rare in presence of level I involvement [26]. In the study by Seifert A et al. (1986), the 61 cases (57%) displayed metastases in the lymph nodes of the parotid gland (38 cases) or of the submandibular gland (23 cases) [8]. Shivakumar T et al. (2013), revealed that the metastasis to intra-parotid nodes is commonly seen from cutaneous malignancies of head and neck region, and rarely from primaries of upper aero-digestive tract squamous cell carcinoma. Intraparotid nodal metastasis from upper aero-digestive tract squamous cell carcinoma is common when neck nodal levels other than Level 1 are involved [18]. Yamagata K et al presented a rare case of metastasis to the parotid lymph node in a patient with tongue SCC and mentioned that the inferior parotid nodes were most commonly involved in cases with substantial cervical metastases [30]. The relative frequency of metastases in the lymph nodes of parotid glands is due to the intense drainage with lymph vessels and the presence of many lymph nodes localized in the gland parenchyma (intraglandular) or around the gland (extraglandular). These lymph nodes in turn drain into the deep cervical nodes. The parotid nodes are about 15–20 in number, the intraglandular nodes lies in both the superficial and deep lobe while the extraglandular nodes present on superficial aspect to gland in pre-auricular and infra-auricular locations adjacent to the retromandibular vein. The intra parotid lymph nodes place the parotid gland at risk for nodal metastasis from various sites both by direct extension and by haematogenous or lymphatic spread. Melhoranse BG et al reported that parotid nodes receive lymphatic drainage from a large area because this gland is the first to form and the last to encapsulate during the embrionary process [19]. Thus, parotid nodes have long been recognized as potential sites for lymphatic spread of tumors but their importance in the prognosis of SCC in the head and neck region has emerged relatively recently. Metastatic disease to the parotid nodes is primarily caused by squamous cell carcinoma followed by adenocarcinoma. The first nodal station for drainage from oral cavity is to levels I-III, second drainage station being the parotid nodes and levels IV-V. The upper aero-digestive tract squamous cell carcinoma with parotid metastasis most often arises from the oral cavity [8,18,20] (Seifert, Hennings, Caselitz (1986), Shivakumar and Nair, 2013). The metastatic disease to the parotid gland is uncommon and usually arises from a primary in the head and neck and less commonly from infraclavicular primary tumors as kidney, prostrate, lung, breast, or gastrointestinal cancers [8] (Seifert, Hennings, Caselitz, 1986). In the present study, the tongue OSCC cases involving salivary glands were primarily in tumor stage 4 and 3. This finding was in accordance with Chen TC et al. (2009) and Naidu TK et al. (2012). Chen TC et al. (2009) mentioned that the 6 tumors with submandibular gland involvement were T4 disease and the neck nodal status on each was
• For early P stages, (P0 – no parotid involvement – or P1 – metastatic parotid node of up to 3 cm), the survival index is about 82%. • At later stages (P2 – metastatic parotid node of 3–6 cm or multiple nodules; or P3 – metastatic parotid node > 6 cm or involvement of facial nerve or skull base), the survival index is 69%.
There are many risk factors that increase significantly the risk of parotid nodal metastasis:
• tumor sizes of over 2 cm in diameter • invasion depths above 5 mm in thickness • proximity to the parotid gland • advanced age Panda NK et al. (2015). Byeon HK et al. (2009), Naidu TK et al. (2012) and Chen TC et al. (2009) mentioned that the patients with early-stage oral squamous cell carcinoma with preoperative N0 neck may be candidates for preservation of the submandibular gland [22,27,20]. Similarly, Spiegel JH et al. (2004) concluded that it is oncologically sound to consider transplantation and replantation of the contralateral submandibular gland for patients with head and neck squamous cell carcinoma when level I lymph nodes are unlikely to be involved [28]. Malik A et al. (2016) also assessed possibility of preserving the submandibular gland in cases of carcinoma of the tongue and expressed that submandibular gland mobilization for dissection at level Ib is not required as no metastases deep to the submandibular glands are seen in early tongue OSCCs [26]. In contradiction, Kruse and Gratz (2009), revealed the possibility of occult metastases in level I in oral cavity carcinomas; hence the excision of the submandibular gland should be performed in cases with positive lymph nodes at level I and in high risk tumor sites [5]. According to Hyung K et al. (2017), the oral mucosa SCC is aggressive, grows rapidly and has a high recurrence rate; therefore, careful treatment is required even if the cancer is at an early stage. In cases of tumor stage 2 or higher, the prophylactic neck dissection is recommended and postoperative radiotherapy may be helpful for local control. It is also necessary to consider preservation of parotid glandular function due to damage to the Stensen's duct during surgery especially in buccal 5
Oral Oncology 102 (2020) 104557
A. Panchbhai and R. Bhowate
mucosal [32]. The low T-stage and negative margins may not be adequate predictors of local control [33] (Sieczka, Datta, Singh, Loree, Rigual, Orner, 2001). The present study revealed the greater percentage of OSCC with salivary gland involvement as compared to previous studies. The literature revealed the involvement of submandibular gland to be uncommon; in contradiction present study demonstrated higher involvement of submandibular gland compared to parotid gland. Notably, the MRI evaluation of uninvolved salivary glands in tongue OSCC revealed additional imaging features in salivary glands (15.97%) suggesting the likely possibility of their involvement by OSCC in near future. The previous study findings were based mainly on histopathological evaluation of the OSCC cases while the present study based on MRI evaluation of the OSCC cases which demonstrated the higher involvement of salivary glands along with additional imaging features that indicated the suspicion or likely possibility of salivary gland involvement by OSCC in cases of delayed interventions or delayed reporting to hospitals. The magnitude of salivary gland involvement by OSCC revealed in the present study certainly directs towards the systematic evaluation in terms of ruling out the salivary gland involvement by OSCC that may also be occult at times. The future extended study may be carried out with broader representation.
[12]
[13]
[14]
[15]
[16]
[17]
[18]
[19]
[20]
Declaration of Competing Interest The authors declared that there is no conflict of interest.
[21]
References
[22]
[1] Arya S, Chaukar D, Pai P. Imaging in oral cancers. Indian J Radiol Imag 2012;22(3):195–208. https://doi.org/10.4103/0971-3026.107182. [2] Ashfaq K, Ashfaq M, Ahmed A, Khan M, Azhar M. Submandibular gland involvement in early stage oral cavity carcinomas: can the gland be left behind? J Coll Phys Surg Pak 2014;24(8):565–8. [3] Alam S, Siddiqui S, Perween R. Epidemiological profile of head and neck cancer patients in Western uttar Pradesh and analysis of distributions of risk factors in relation to site of tumour. J Can Res Ther 2017;13:430–5. [4] Ajay, Ashwiniraj S, Surgimth A, Nayak G. Oral cancer prevalence in Western population of Maharastra, India for period of 5 years. J Oral Res Rev 2018;10:11–4. [5] Burket’s oral medicine, diagnosis & treatment. Oral cancer, 10th ed. BC Decker Inc; 2003. p. 19. [6] Byeon HK, Lim YC, Koo BS, Choi EC. Metastasis to the submandibular gland in oral cavity squamous cell carcinomas: pathologic analysis. Acta Otolaryngol 2009;129(1):96–100. https://doi.org/10.1080/00016480802032801. [7] Bobdey S, Sathwara J, Jain A, Saoba S, Balasubramaniam G. Squamous cell carcinoma of buccal mucosa: an analysis of prognostic factors. South Asian J Cancer 2018;7(1):49–54. https://doi.org/10.4103/sajc.sajc_317_16. [8] Chen TC, Lo WC, Ko JY, Lou PJ, Yang TL, Wang CP. Rare involvement of submandibular gland by oral squamous cell carcinoma. Head Neck 2009;31(7):877–81. https://doi.org/10.1002/hed.21039. [9] Diaz Jr EM, Holsinger FC, Zuniga ER, Roberts DB, Sorensen DM. Squamous cell carcinoma of the buccal mucosa: one institution's experience with 119 previously untreated patients. Head Neck 2003;25(4):267–73. [10] Fives C, Feeley L, Sadadcharam M, O’Leary G, Sheahan P. Incidence of intraglandular lymph nodes within submandibular gland, and involvement by floor of mouth cancer. Eur Arch Otorhinolaryngol 2017;274(1):461–6. https://doi.org/10. 1007/s00405-016-4205-0. [11] Goel V, Parihar P, Parihar A, Goel A, Waghwani K, Gupta R, Bhutekar U. Accuracy of MRI in prediction of tumour thickness and nodal stage in oral tongue and
[23]
[24]
[25] [26] [27]
[28] [29] [30] [31]
[32] [33]
6
gingivobuccal cancer with clinical correlation and staging. J Clin Diagn Res 2016;10(6):TC01–5. https://doi.org/10.7860/JCDR/2016/17411.7905. Published online 2016 Jun 1. Harada H, Omura K. Metastasis of oral cancer to the parotid node. Eur J Surg Oncol 2009;35(8):890–4. https://doi.org/10.1016/j.ejso.2008.09.013. Epub 2008 Nov 11. Hyung KI, Hoon MC. Squamous cell carcinoma of the buccal mucosa involving the masticator space: a case report. J Korean Assoc Oral Maxillofac Surg 2017;43(3):191–6. https://doi.org/10.5125/jkaoms.2017.43.3.191. Kruse A, Grätz KW. Evaluation of metastases in the submandibular gland in head and neck malignancy. J Craniofacial Surg 2009;20(6):2024–7. https://doi.org/10. 1097/SCS.0b013e3181be87a3. Kenji Y, Naomi IK, Hiroyuki I, Shogo H, Toru Y, Kojiro O, et al. Parotid lymph node metastasis in a patient with tongue cancer. Case Rep Clin Med 2014;3(1):23–7. https://doi.org/10.4236/crcm.2014.31006. Kurabayashi T, Ida M, Tetsumura A, Ohbayashi N, Yasumoto M, Sasaki T. MR imaging of benign and malignant lesions in the buccal space. Head Neck 2014;31:6. https://doi.org/10.1038/sj.dmfr.4600723. Malik A, Joshi P, Mishra A, Garg A, Mair M, Chakrabarti S, et al. Prospective study of the pattern of lymphatic metastasis in relation to the submandibular glands in carcinoma of oral cavity. Head Neck 2016;38(11):1703–7. https://doi.org/10. 1002/hed.24508. Epub 2016 May 27. Melhoranse BG, Barbosa MHM, Carneiro LH, El Hadj LA, Fernandes NC. The prognostic importance of parotid envolvement by head and neck squamous cell carcinoma – case report. An Bras Dermatol 2016;91(3):351–3. https://doi.org/10. 1590/abd1806-4841.20163995. Naidu TK, Naidoo SK, Ramdial PK. Oral cavity squamous cell carcinoma metastasis to the submandibular gland. J Laryngol Otol 2012;126(3):279–84. https://doi.org/ 10.1017/S0022215111002660. Panda NK, Patro SK, Bakshi J, Verma RK, Das A, Chatterjee D. Metastasis to submandibular glands in oral cavity cancers: can we preserve the gland safely? Auris Nasus Larynx 2015;42(4):322–5. https://doi.org/10.1016/j.anl.2015.02.006. Epub 2015 Feb 25. Pałasz P, Adamski L, Górska-Chrząstek M. Contemporary diagnostic imaging of oral squamous cell carcinoma – a review of literature. Pol J Radiol 2017;82:193–202. https://doi.org/10.12659/PJR.900892. Seifert G, Hennings K, Caselitz J. Metastatic tumors to the parotid and submandibular glands–analysis and differential diagnosis of 108 cases. Pathol Res Pract 1986;181(6):684–92. https://doi.org/10.1016/S0344-0338(86)80044-9. Sieczka E, Datta R, Singh A, Loree T, Rigual N, Orner J, et al. Cancer of the buccal mucosa: are margins and T-stage accurate predictors of local control? Am J Otolaryngol 2001;22:395–9. Stanley MW, Bardales RH, Farmer CE, Frierson Jr. HF, Suhrland M, Powers CN. Primary and metastatic high-grade carcinomas of the salivary glands: a cytologichistologic correlation study of twenty cases. Diagn Cytopathol 1995;13(1):37–43. Shah GV, Fischbein NJ, Patel R, Mukherji SK. Newer MR techniques for head and neck. Magn Reson Imaging Clin N Am 2003;11:449–69. Spiegel JH, Brys AK, Bhakti A, Singer MI. Metastasis to the submandibular gland in head and neck carcinomas. Head Neck 2004;26:1064–8. Shivakumar T, Nair SV. Delayed contralateral intra-parotid nodal metastasis from an oral squamous cell carcinoma. J Case Rep 2013;3(2):317–21. https://doi.org/10. 17659/01.2013.0074. Sawlani K, Kumari N, Mishra A, Agrawal U. Oral cancer prevalence in tertiary care hospital in India. J Family Med Com Health 2014;1(4, 1022):1–5. Sharma D, Singh G. Squamous cell carcinoma of the oral cavity and oropharynx in young adults. Indian J Cancer 2016;53:399–401. Singh A, Thukral C, Gupta K, Sood A, Singla H, Singh K. Role of MRI in evaluation of malignant lesions of tongue and oral cavity. Pol J Radiol 2017;82:92–9. Sharma S, Satyanarayana L, Smitha A, Shivalingesh K, Goutham B, Ramachandra S. Oral cancer statistics in India on the basis of first report of 29 population-based cancer registries. J Oral Maxillofac Pathol 2018;22(1):PMC5917535. Tart R. CT and MRI imaging of the buccal space and buccal space masses. RSNA 1995;15(3):531–50. Tandon P, Dadhich A, Saluja H, Bawane S, Sachdeva S. The prevalence of squamous cell carcinoma in different sites of oral cavity at our Rural Health Care Centre in Loni, Maharashtra – a retrospective 10-year study. Contemp Oncol (Pozn) 2017;21(2):178–83. https://doi.org/10.5114/wo.2017.68628.
Contents lists available at ScienceDirect
Oral Oncology journal homepage: www.elsevier.com/locate/oraloncology
MRI evaluation of involvement of parotid and submandibular glands by tongue squamous cell carcinoma
T
⁎
Aarati Panchbhai , Rahul Bhowate Department of Oral Medicine and Radiology, S P Dental College & Hospital, DMIMSDU, Sawangi-M, Wardha, Maharastra, India Department of Oral Medicine and Radiology, S P Dental College & Hospital, DMIMSDU, Sawangi-M, Wardha 442001, Maharastra, India
A R T I C LE I N FO
A B S T R A C T
Keywords: Tongue OSCC Salivary gland Spread MRI
Objectives: The majority of cases of salivary gland involvement are diagnosed in its late stages as may be missed in the evaluation, the low detection rate of involvement of salivary gland by OSCC may have significant impact on spread and recurrence of the OSCC. The study aimed to evaluate involvement of parotid and submandibular salivary glands by tongue oral squamous cell carcinoma. Material and method: The 144 histo-pathologically proven cases of tongue squamous cell carcinoma were evaluated for clinical staging, margins and extent of tumor and involvement of salivary gland on T1-T2 Weighted, STIR, diffusion-weighted and contrast-enhanced MRI sequences and data was subjected to analysis. Results: In tongue OSCC, total 9 (6.25%) patients showed salivary gland involvement, 2 of them involved parotid glands and 7 of them involved submandibular gland. The OSCC involving the salivary glands were in Stage 4 except for 2 cases with predilection for antero-lateral border and tendency towards midline crossing. Out of 9 cases that showed salivary gland involvement, the 5 cases showed direct involvement from the spreading lesion, the 3 cases showed the infiltration from adjacent lymph nodes and 2 cases showed infiltration from sublingual gland and medial pterygoid muscle. Conclusion: The present study revealed the greater percentage of OSCC with salivary gland involvement as compared to previous studies; in contradiction present study demonstrated higher involvement of submandibular gland compared to parotid gland with additional imaging features in salivary glands (15.97%) suggesting the likely possibility of their involvement by OSCC in near future.
Introduction Oral cavity squamous cell carcinomas (OSCC) form a significant percentage of cancers seen in India [1–4]. Oral squamous cell carcinoma has an aggressive nature as it grows rapidly and penetrates well with a high recurrence rate, the buccal mucosa and tongue OSCC being the soft tissue malignancies are the most aggressive form of oral cancers with the greater prevalence in India. The prevalence of squamous cell carcinoma of Tongue (tongue OSCC) was found to be in the range 13.5–58.4% in various studies conducted in India [1–7]. There is a rising incidence of tongue OSCC both in India as well as in the western countries; hence the tongue OSCC needs comprehensive evaluation of prognostic factors in addition to comorbidity, tumor differentiation, extracapsular spread, and perineural invasion. In aggressive cancers, local spread and nodal metastases are adverse prognostic factors and require accurate detection for optimized treatment.
⁎
Metastases of OSCC to the salivary glands are of special importance for therapy and prognosis. Earlier studies demonstrated the involvement of parenchyma or the lymph nodes of the parotid gland and submandibular gland. The relative frequency of metastases in the lymph nodes of the salivary glands may be due to the intense drainage with lymph vessels and the presence of many lymph nodes which are localized especially in the gland parenchyma or around the gland. While evaluating the metastasis to salivary gland from OSCC, the other distant metastatic sources to salivary gland needed to be ruled out as the metastatic tumors may originate from lung cancers, renal cancers, mammary cancers, colonic cancer, thyroid cancers and uterus cancer [8]. The tongue OSCC may arise from body or base of tongue; the majority of them arises from the lateral border followed by few from ventral surface. The tongue OSCC arising from base of the tongue are similar to oropharyngeal cancers. Notably, the tongue OSCC may be
Corresponding author. E-mail address: [email protected] (A. Panchbhai).
https://doi.org/10.1016/j.oraloncology.2019.104557 Received 13 September 2019; Received in revised form 23 November 2019; Accepted 25 December 2019 1368-8375/ © 2019 Elsevier Ltd. All rights reserved.
Oral Oncology 102 (2020) 104557
A. Panchbhai and R. Bhowate
The data pertaining to demographic details, clinical findings with TNM staging [16] and histopathological evaluation of the patient was obtained. The selected patients had undergone MRI evaluation (GE Brivo355, 1.5 Tesla) before surgery using following protocol for tongue OSCC. Images were obtained with T1 weighted; T2 weighted, STIR, diffusion-weighted and contrast-enhanced MRI sequences and evaluated using following criteria:
manifested as very shallow ulcers to apparently negate the need of imaging, however due to a high incidence of occult cervical lymph node metastasis it is always prudent to go for imaging. While clinical examination allows direct visualization, it cannot evaluate deep extension of disease. Cross-sectional imaging has become the cornerstone in the pre-treatment evaluation of these cancers and provides accurate information about the extent, depth and spread of disease that can help decide the appropriate management strategy and indicate prognosis [9,10]. Imaging for tongue SCC requires a modality with superior soft tissue characterization and hence magnetic resonance imaging (MRI) is the optimal modality displaying exquisite anatomical detail, and involvement of base of tongue, floor of mouth and oro-pharynx which is extremely difficult to be seen on CT. In addition, MRI is used to assess the extent of loco-regional tumor spread, depth of invasion, extent of lymphadenopathy and occult metastasis. Excellent soft-tissue discrimination of MRI readily reveals tumor invasion and spread to surrounding structures. The efficiency of MRI has been enhanced by exploiting suppression and tumor-induced metabolic, vascular, or micro structural changes. Diffusion-weighted imaging can precisely detect structures involved by cancer and it can also differentiate between reactive and metastatic lymph nodes. Contrast-enhanced T1W images help assess marrow invasion, soft tissue extent, tumor thickness and best demonstrate necrosis in nodes. It is also used to assess the presence of occult metastatic lymph nodes [11–15]. Considering the propensity for locoregional spread and recurrence of Tongue OSCC, the involvement of salivary gland by OSCC also needs to be estimated. The majority of cases of salivary gland involvement are diagnosed in its late stages as may be missed in the evaluation, the low detection rate of involvement of salivary gland by oral SCC is a considerable clinical issue. This may have significant impact on spread and recurrence of the OSCC. In addition, it is difficult to diagnose metastases in lymph nodes in and around salivary glands, which is important for planning the scope of resection and further treatment. The preservation of the glandular function due to damage to the salivary duct during surgery may also be one of the considerations dealing with these cancers. Earlier studies evaluated the salivary gland involvement by OSCC based on histopathological evaluation which has a limitation that it relies on resected specimen as only the biopsied or resected tissue would be examined wherein imaging especially MRI evaluation may allow to perform the comprehensive evaluation of the tumor, and adjacent or distant soft tissue that needs evaluation. Imaging studies are performed as part of the routine work-up in OSCC; however, they are not intended to assess the involvement of salivary glands especially for the apparently early stages of disease on clinical examination or the occult cases that are missed in clinical evaluation of OSCC patients. There are very few imaging studies in literature that have explored the involvement of the parotid and submandibular salivary gland by OSCC. In view of this, the present study was aimed to evaluate the involvement of parotid and submandibular salivary glands by tongue oral squamous cell carcinoma using magnetic resonance imaging.
Protocol for MRI
• frFSE: l/160 • FOV: 24 × 30 • WW: 1529, WL: l 764 • TR: 5476, TE: 118 Criteria for MRI evaluation MR images were assessed for the following: ▪ ▪ ▪ ▪
signal intensity of lesions extent of lesion margins of lesion involvement of salivary glands by tongue OSCC
The tongue OSCCs were evaluated using all the MRI sequences in axial, coronal and sagital views of the images. The findings were tabulated for tongue OSCC and subjected to analysis. Results The selected patients had undergone MRI evaluation (GE Brivo 1.5 Tesla) before surgery, the images obtained with T1-T2 Weighted, STIR, diffusion-weighted and contrast-enhanced MRI sequences were evaluated for signal intensity, margin and extent of tumour and involvement of parotid and submandibular salivary glands (Figs.1–3). The gender wise distribution of total 144 Tongue OSCC patients showed male (106) predilection over female (38) with male to female ratio of almost 3:1 (Table 1). For age wise distribution of Tongue OSCC patients, the total of 144 patients were divided in the 2 age ranges as shown, the sample showed almost equal distribution in the given age ranges (Table 1). In tongue OSCC, total 9 (6.25%) patients showed salivary gland involvement, 2 of them involved parotid glands and 7 of them involved submandibular gland (Table 1). The Table 2 summarized the imaging characteristics of the 9 Tongue OSCCs involving salivary glands; it showed male predominance with only 2 female patients. In age wise distribution, out of 9, 7 cases belonged to 21–50 age range suggesting involvement of salivary gland in lower age group in tongue OSCC. The OSCC involving the salivary glands were in Stage 4 except for 2 cases that belonged to Stage 3, the right and left side of tongue were equally involved with predilection for antero-lateral border and tendency towards midline crossing. The adjacent structures involved were base of tongue, floor of mouth, mandible, sublingual space, salivary glands, mylohoid, retromolar trigone, and medial pterygoid. Out of the 9 patients, the 7 OSCCs had ill-defined margins while 2 had well-defined margins. The MRI images were hypointense to isointense on T1weighted, hyperintense on T2 weighted and STIR, and heterogeneously enhancing on contrast-enhanced sequences. In 4 patients, the restricted diffusion was seen in diffusion-weighted sequence (Table 2). Table 3 showed the mode of involvement and imaging characteristics of involved salivary glands in Tongue OSCC. Out of 9 cases that showed salivary gland involvement, the 5 cases showed direct involvement from the spreading lesion, the 3 cases showed the infiltration from the adjacent lymph node and 2 cases showed infiltration from sublingual gland and medial pterygoid muscle. Most of the involved salivary glands showed heterogenous enhancement of the ipsilateral
Materials and method The present ethics committee approved study was conducted at Sharad Pawar Dental College, DMIMS (DU), Sawangi-Meghe, Wardha, India in collaboration with department of Radio-diagnosis, AVBRH. At the outset, the study design was explained to each study participant and the voluntary consent was obtained. The 144 histo-pathologically proven cases of tongue squamous cell carcinoma were included in the study following the exclusion criteria. Exclusion criteria
• Oral malignancies other than squamous cell carcinoma • Metastatic OSCC 2
Oral Oncology 102 (2020) 104557
A. Panchbhai and R. Bhowate
Fig. 1. Tongue OSCC involving right half of the tongue in T1-weighted image and Contrast-enhanced Image (Coronal section). Table 1 Tongue OSCC cases showing salivary gland involvement.
Gender Age range (years) Salivary gland involvement
Variable
No. of subjects (%)
Total
Male Female 21–50 Years 51–72 Years Parotid G. Submandibular G.
106 (73.61%) 38 (26.38%) 71 (48.97%) 73 (51.02%) 2 (1.38%) 7 (4.86%)
144 (100%) 144 (100%) 9 (6.25%)
salivary glands, with few showing the necrotic areas. Table 4 summarizes the additional imaging features suggesting the likely possibility of involvement of salivary gland by tongue OSCC in near future, the percentage of involvement was 15.97%.
Discussion The study was carried out with the purpose to evaluate the involvement of salivary gland by tongue OSCC. The sample showed predominance of male over female in tongue OSCCs, most of the patients with salivary gland involvement were in 21–50 years age range. The total 9 (6.25%) patients showed salivary gland involvement, 2 (2.04%) of them involved parotid glands and 7 (7.14%) of them involved submandibular gland. The involvement of submandibular gland was greater than parotid gland. The literature revealed the involvement of the involvement of parotid gland in the range 0.79–3% [8,17,23] with varied prevalence in various studies. Melhoranse BG et al. (2016), reported parotid metastases of around 3% and indicate aggressive local disease as well as more severe prognosis [19]. Stanley MW et al. (1995), reviewed 20 patients (39–89 years) of poorly differentiated carcinomas involving salivary glands, out of which 11 were primary tumors and nine were metastatic malignancies [24]. Seifert G et al. (1986), scrutinized the salivary Gland Register and found 108 cases of metastatic tumors to the parotid and submandibular gland [8]. The 47 cases (43%) of metastatic tumors were localized in the parenchyma of the parotid gland (37 cases) or of the submandibular gland (10 cases). The 65 metastatic tumors originated from adjacent primary tumors in head and neck, mainly from skin, followed by nasopharyngeal cancers and thyroid cancers while 21 metastatic tumors were originated from primary tumors from distant sites. Chen TC et al. (2009), retrospectively reviewed the pathologic records of 383 submandibular glands in OSCC patients in which 7 (1.8%) exhibited tumor involvement which was uncommon [19]. Kruse and
Fig. 2. Tongue OSCC involving the left submandibular gland (Coronal section).
Fig. 3. Histopathological section of submandibular gland showing acini (white arrow) and epitheial cells (black arrow), (H/E stain, 40x).
3
Oral Oncology 102 (2020) 104557
A. Panchbhai and R. Bhowate
Table 2 Imaging characteristics of Tongue OSCC involving salivary glands. TONGUE
Imaging characteristics of Primary tumors showing salivary gland involvement
Sn
Age sex
Tumour stage
Region
Tumor Margin
T1
T2
STIR
Contrast
Diffusion Weighted
Case 1 Case2 Case3
46F 42M 62M
Stage 4 T2N2M0 Stage 3 T3N1M0 Stage 4 T4N2CM0
ill defined Well defined ill defined
Hypo-iso Hypo Hypo
Hyper Hyper Hyper
Hyper Hyper Hyper
Heterogeneously enhancing Altered intensity Heterogeneously enhancing
– – Restricted diffusion
Case 4
49M
Stage 3 T3N1M0
Left Lateral, floor Right Lateral Right Postero Lateral Left post 1/3rd
ill defined
Hypo
Hyper
Hyper
–
Case Case Case Case Case
40M 38M 37M 47M 56M
Stage Stage Stage Stage Stage
Base, floor Right Lateral Base, floor Left Lateral Right Lateral
ill defined ill defined ill defined Well defined ill defined
Hypo Hypo-iso Hypo hypo hypo
Hyper Hyper hetero Hyper Hyper
Hyper Hyper Hyper Hyper Hyper
Heterogeneously enhancing with areas of necrosis Altered intensity enhancing Heterogeneously enhancing intensely enhancing Heterogeneously enhancing
5 6 7 8 9
4 4 4 4 4
T4N2BM0 T4N2BM0 T4N2CM0 T3N2CM0 T4N2CM0
Gratz (2009), evaluated 171 submandibular glands in head and neck malignancy patients (average age, 61.1 years), the 6 patients showed involvement of salivary glands through tumor infiltration (5), and intraglandular lymph node (1) along with chronic sialadenitis and atrophy [25]. Malik A et al. (2016), assessed the pattern of nodal metastasis in OSCC in relation to the submandibular gland [26]. The fibrofatty tissue surrounding the submandibular gland was divided into 6 parts depending upon its location with the submandibular gland. In cases with cervical lymphadenopathy, deep metastasis was seen in 4 cases only (14.8%) and none of them had a primary tumor in the tongue. Naidu TK et al. (2012), revealed 2.9% of submandibular gland metastases in 69 cases of OSCC in mean age 58 years [20]. Panda NK et al. (2015), analyzed 163 submandibular glands for involvement in cases of oral cavity cancers, 3.68% (6) glands showed involvement by the tumor [22]. In retrospective review, Fives C et al. (2017), investigated the incidence and mechanism of submandibular gland involvement in of 177 patient of floor of mouth cancer, submandibular gland involvement was present in 2 patients, representing 1% of all oral cancers, and 4% floor of mouth cancer cases [23]. In the present study, all the cases of tongue OSCC showed ipsilateral salivary gland involvement. his was in accordance with Naidu TK et al. (2012), Byeon HK et al. (2009)and Spiegel JH et al. (2004) [20,27,28] and in contradiction to finding in a case reviewed by Shivkumar et al. (2013) [18] where the delayed nodal metastasis was reported to the contralateral intra-parotid node. Byeon HK et al. (2009) examined the pathologic record of 201 OSCC patients in which only 2 cases (1%) had involvement of submandibular gland but 21.9% showed ipsilateral level I metastasis [27]. Accordingly, the incidence of submandibular gland metastasis in OSCC is extremely rare. Spiegel JH et al. (2004), determined that all the primary lesions were ipsilateral to the involved
Restricted diffusion Restricted diffusion Restricted diffusion –
Table 4 No. of cases with Imaging features suggesting possibility of involvement of salivary gland by OSCC. Sn
OSCC
N (%)
Tongue OSCC
23 (15.46%)
Imaging features gland • Bulky enhancing gland • Unilaterally signal intensity of gland • Altered defined margins of the gland • IllInvolvement • tumour of the glandular space by of fat planes of gland • Loss of mylohyoid • Involvement of masticator space, ie • Involvement masseter/medial pterygoid lymph nodes • Enlarged of sublingual space • Involvement infiltrating base of tongue, or crossing • OSCC midline
gland and originated from cancers of floor of mouth, alveolar ridge and tongue. Naidu TK et al. (2012) observed that only 2 (2.9%) submandibular glands demonstrated ipsilateral contiguous tumour involvement [20]. The metastatic tumors originated from primary tumors distant than the head and neck region may include the sites as lung, renal, mammary, colon, thyroid and uterus [8]. In the present study, the mode of involvement of salivary glands was either through direct spread from primary tumor or from infiltration from adjacent lymph nodes. Chen TC et al. (2012), observed that 5 glands were involved by direct extension from the primary tumor, 1 gland showed local invasion from an adjacent involved lymph node in level I and 1 was from intraglandular lymph node metastasis [21]. Spiegel JH et al. (2004), revealed that submandibular gland has no
Table 3 Mode of involvement and Imaging characteristics of involved salivary glands in Tongue OSCC. TONGUE
Imaging characteristics of Salivary gland involvement
Sn
Age sex
Tumour stage
Mode of involvement
Imaging characteristics
Case 1
46 F
Stage 4 T2N2M0
Left parotid showing heterogeneous enhancement
Case2 Case3 Case 4 Case 5 Case 6 Case 7
42 62 49 40 38 37
Stage Stage Stage Stage Stage Stage
Infiltration from adjacent large jugulodiagrastric lymph node Direct spread from base Direct spread Infiltration from sublingual gland Infiltration from adjacent lymph node Direct spread Direct spread
Case 8 Case 9
47 M 56M
M M M M M M
3 4 3 4 4 4
T3N1M0 T4N2CM0 T3N1M0 T4N2BM0 T4N2BM0 T4N2CM0
Stage 4 T3N2CM0 Stage 4 T4N2CM0
Infiltration from adjacent lymph node Infiltration from adjacent medial pterygoid Direct spread
4
Right submandibular gland showing isointense heterogeneous enhancement Right submandibular gland showing heterogeneous enhancement left submandibular gland showing heterogeneous enhancement Right submandibular gland showing heterogeneous enhancement Right submandibular gland showing Altered intensity Bilateral involvement of submandibular gland showing heterogeneous enhancement Very bulky enhancing gland left submandibular gland Involving both right parotid and right submandibular glands –Deep lobe of right parotid with heterogeneous enhancement and necroses –Right submandibular enhancing gland
Oral Oncology 102 (2020) 104557
A. Panchbhai and R. Bhowate
more than N2b [21]. Naidu TK et al. (2012) revealed that 62.3% had advanced tumor stage three or four lesions of OSCC amongst which only few showed salivary gland involvement [20]. Melhoranse BG et al. (2016), reported the importance of parotid involvement as an isolated prognostic factor and a therapy guide. The parotid nodes have long been recognized as potential sites for lymphatic spread of tumors with guarded prognosis of SCC in the head and neck region [19]. Harada H et al. (2009), reported that likelihood of metastasis to parotid nodes increased with the number of cancer-positive cervical nodes. Resection of the tail of parotid gland is warranted during the neck dissection [17]. Kenji Y et al. (2014), mentioned that metastasis of the parotid lymph node is associated with a poor prognosis in SCC of the head and neck. There is no consensus on the appropriate treatment for the parotid lymph node metastasis in OSCC because of the small number of reported cases [30]. Diaz EM et al. (2003), observed that muscle invasion, Stensen's duct involvement and extracapsular spread of involved lymph nodes were all associated with decreased survival [31]. Additionally, Melhoranse BG et al. (2016) reported that the current AJCC TNM staging system does not comprise the parotid gland involvement. In TNM staging, all patients with parotid and/or neck nodal metastasis are classified as N1. O’Brien proposed a new classification to distinguish between parotid node involvement (“P”) and neck nodal disease (“N”) (Melhoranse, Barbosa, Carneiro, El Hadj, Fernandes, 2016) [19]. This classification considers that the higher the parotid involvement, the lower the survival index.
intraparenchymal lymph nodes, its involvement in upper aerodigestive tract carcinomas must be through extension from a locally involved lymph node or the primary tumor [28]. Byeon HK et al. (2009), demonstrated that the incidence of submandibular gland involvement is through direct extension from a primary lesion; both the cases had direct extension from a primary lesion (retromolar trigone and floor of mouth) and no submandibular glands showed pathologic evidence of isolated metastasis or local extension of metastatic lymph nodes in their study [27]. Ashfaq K et al. (2014) observed that the submandibular gland was involved in 2 cases (1.8%) via direct spread; the submandibular gland metastasis from early oral cavity tumors is rare [29]. In the study by Panda NK et al, 4 of the 6 involved glands showed direct contiguous spread from primary lesion, 1 showed extra-capsular spread from level IB lymph nodes and evidence of both modes of spread was seen in one of their cases [22]. Fives C et al. (2017), al demonstrated a newer mechanism of carcinoma growing along Wharton's ducts in addition to direct extension [23]. It was further mentioned that in spite of the high incidence of level I metastasis in floor of mouth, the lymphatic metastases to submandibular gland are unlikely. This is similar to finding by Malik A et al. (2016), who revealed that direct metastases to the submandibular glands are rare in presence of level I involvement [26]. In the study by Seifert A et al. (1986), the 61 cases (57%) displayed metastases in the lymph nodes of the parotid gland (38 cases) or of the submandibular gland (23 cases) [8]. Shivakumar T et al. (2013), revealed that the metastasis to intra-parotid nodes is commonly seen from cutaneous malignancies of head and neck region, and rarely from primaries of upper aero-digestive tract squamous cell carcinoma. Intraparotid nodal metastasis from upper aero-digestive tract squamous cell carcinoma is common when neck nodal levels other than Level 1 are involved [18]. Yamagata K et al presented a rare case of metastasis to the parotid lymph node in a patient with tongue SCC and mentioned that the inferior parotid nodes were most commonly involved in cases with substantial cervical metastases [30]. The relative frequency of metastases in the lymph nodes of parotid glands is due to the intense drainage with lymph vessels and the presence of many lymph nodes localized in the gland parenchyma (intraglandular) or around the gland (extraglandular). These lymph nodes in turn drain into the deep cervical nodes. The parotid nodes are about 15–20 in number, the intraglandular nodes lies in both the superficial and deep lobe while the extraglandular nodes present on superficial aspect to gland in pre-auricular and infra-auricular locations adjacent to the retromandibular vein. The intra parotid lymph nodes place the parotid gland at risk for nodal metastasis from various sites both by direct extension and by haematogenous or lymphatic spread. Melhoranse BG et al reported that parotid nodes receive lymphatic drainage from a large area because this gland is the first to form and the last to encapsulate during the embrionary process [19]. Thus, parotid nodes have long been recognized as potential sites for lymphatic spread of tumors but their importance in the prognosis of SCC in the head and neck region has emerged relatively recently. Metastatic disease to the parotid nodes is primarily caused by squamous cell carcinoma followed by adenocarcinoma. The first nodal station for drainage from oral cavity is to levels I-III, second drainage station being the parotid nodes and levels IV-V. The upper aero-digestive tract squamous cell carcinoma with parotid metastasis most often arises from the oral cavity [8,18,20] (Seifert, Hennings, Caselitz (1986), Shivakumar and Nair, 2013). The metastatic disease to the parotid gland is uncommon and usually arises from a primary in the head and neck and less commonly from infraclavicular primary tumors as kidney, prostrate, lung, breast, or gastrointestinal cancers [8] (Seifert, Hennings, Caselitz, 1986). In the present study, the tongue OSCC cases involving salivary glands were primarily in tumor stage 4 and 3. This finding was in accordance with Chen TC et al. (2009) and Naidu TK et al. (2012). Chen TC et al. (2009) mentioned that the 6 tumors with submandibular gland involvement were T4 disease and the neck nodal status on each was
• For early P stages, (P0 – no parotid involvement – or P1 – metastatic parotid node of up to 3 cm), the survival index is about 82%. • At later stages (P2 – metastatic parotid node of 3–6 cm or multiple nodules; or P3 – metastatic parotid node > 6 cm or involvement of facial nerve or skull base), the survival index is 69%.
There are many risk factors that increase significantly the risk of parotid nodal metastasis:
• tumor sizes of over 2 cm in diameter • invasion depths above 5 mm in thickness • proximity to the parotid gland • advanced age Panda NK et al. (2015). Byeon HK et al. (2009), Naidu TK et al. (2012) and Chen TC et al. (2009) mentioned that the patients with early-stage oral squamous cell carcinoma with preoperative N0 neck may be candidates for preservation of the submandibular gland [22,27,20]. Similarly, Spiegel JH et al. (2004) concluded that it is oncologically sound to consider transplantation and replantation of the contralateral submandibular gland for patients with head and neck squamous cell carcinoma when level I lymph nodes are unlikely to be involved [28]. Malik A et al. (2016) also assessed possibility of preserving the submandibular gland in cases of carcinoma of the tongue and expressed that submandibular gland mobilization for dissection at level Ib is not required as no metastases deep to the submandibular glands are seen in early tongue OSCCs [26]. In contradiction, Kruse and Gratz (2009), revealed the possibility of occult metastases in level I in oral cavity carcinomas; hence the excision of the submandibular gland should be performed in cases with positive lymph nodes at level I and in high risk tumor sites [5]. According to Hyung K et al. (2017), the oral mucosa SCC is aggressive, grows rapidly and has a high recurrence rate; therefore, careful treatment is required even if the cancer is at an early stage. In cases of tumor stage 2 or higher, the prophylactic neck dissection is recommended and postoperative radiotherapy may be helpful for local control. It is also necessary to consider preservation of parotid glandular function due to damage to the Stensen's duct during surgery especially in buccal 5
Oral Oncology 102 (2020) 104557
A. Panchbhai and R. Bhowate
mucosal [32]. The low T-stage and negative margins may not be adequate predictors of local control [33] (Sieczka, Datta, Singh, Loree, Rigual, Orner, 2001). The present study revealed the greater percentage of OSCC with salivary gland involvement as compared to previous studies. The literature revealed the involvement of submandibular gland to be uncommon; in contradiction present study demonstrated higher involvement of submandibular gland compared to parotid gland. Notably, the MRI evaluation of uninvolved salivary glands in tongue OSCC revealed additional imaging features in salivary glands (15.97%) suggesting the likely possibility of their involvement by OSCC in near future. The previous study findings were based mainly on histopathological evaluation of the OSCC cases while the present study based on MRI evaluation of the OSCC cases which demonstrated the higher involvement of salivary glands along with additional imaging features that indicated the suspicion or likely possibility of salivary gland involvement by OSCC in cases of delayed interventions or delayed reporting to hospitals. The magnitude of salivary gland involvement by OSCC revealed in the present study certainly directs towards the systematic evaluation in terms of ruling out the salivary gland involvement by OSCC that may also be occult at times. The future extended study may be carried out with broader representation.
[12]
[13]
[14]
[15]
[16]
[17]
[18]
[19]
[20]
Declaration of Competing Interest The authors declared that there is no conflict of interest.
[21]
References
[22]
[1] Arya S, Chaukar D, Pai P. Imaging in oral cancers. Indian J Radiol Imag 2012;22(3):195–208. https://doi.org/10.4103/0971-3026.107182. [2] Ashfaq K, Ashfaq M, Ahmed A, Khan M, Azhar M. Submandibular gland involvement in early stage oral cavity carcinomas: can the gland be left behind? J Coll Phys Surg Pak 2014;24(8):565–8. [3] Alam S, Siddiqui S, Perween R. Epidemiological profile of head and neck cancer patients in Western uttar Pradesh and analysis of distributions of risk factors in relation to site of tumour. J Can Res Ther 2017;13:430–5. [4] Ajay, Ashwiniraj S, Surgimth A, Nayak G. Oral cancer prevalence in Western population of Maharastra, India for period of 5 years. J Oral Res Rev 2018;10:11–4. [5] Burket’s oral medicine, diagnosis & treatment. Oral cancer, 10th ed. BC Decker Inc; 2003. p. 19. [6] Byeon HK, Lim YC, Koo BS, Choi EC. Metastasis to the submandibular gland in oral cavity squamous cell carcinomas: pathologic analysis. Acta Otolaryngol 2009;129(1):96–100. https://doi.org/10.1080/00016480802032801. [7] Bobdey S, Sathwara J, Jain A, Saoba S, Balasubramaniam G. Squamous cell carcinoma of buccal mucosa: an analysis of prognostic factors. South Asian J Cancer 2018;7(1):49–54. https://doi.org/10.4103/sajc.sajc_317_16. [8] Chen TC, Lo WC, Ko JY, Lou PJ, Yang TL, Wang CP. Rare involvement of submandibular gland by oral squamous cell carcinoma. Head Neck 2009;31(7):877–81. https://doi.org/10.1002/hed.21039. [9] Diaz Jr EM, Holsinger FC, Zuniga ER, Roberts DB, Sorensen DM. Squamous cell carcinoma of the buccal mucosa: one institution's experience with 119 previously untreated patients. Head Neck 2003;25(4):267–73. [10] Fives C, Feeley L, Sadadcharam M, O’Leary G, Sheahan P. Incidence of intraglandular lymph nodes within submandibular gland, and involvement by floor of mouth cancer. Eur Arch Otorhinolaryngol 2017;274(1):461–6. https://doi.org/10. 1007/s00405-016-4205-0. [11] Goel V, Parihar P, Parihar A, Goel A, Waghwani K, Gupta R, Bhutekar U. Accuracy of MRI in prediction of tumour thickness and nodal stage in oral tongue and
[23]
[24]
[25] [26] [27]
[28] [29] [30] [31]
[32] [33]
6
gingivobuccal cancer with clinical correlation and staging. J Clin Diagn Res 2016;10(6):TC01–5. https://doi.org/10.7860/JCDR/2016/17411.7905. Published online 2016 Jun 1. Harada H, Omura K. Metastasis of oral cancer to the parotid node. Eur J Surg Oncol 2009;35(8):890–4. https://doi.org/10.1016/j.ejso.2008.09.013. Epub 2008 Nov 11. Hyung KI, Hoon MC. Squamous cell carcinoma of the buccal mucosa involving the masticator space: a case report. J Korean Assoc Oral Maxillofac Surg 2017;43(3):191–6. https://doi.org/10.5125/jkaoms.2017.43.3.191. Kruse A, Grätz KW. Evaluation of metastases in the submandibular gland in head and neck malignancy. J Craniofacial Surg 2009;20(6):2024–7. https://doi.org/10. 1097/SCS.0b013e3181be87a3. Kenji Y, Naomi IK, Hiroyuki I, Shogo H, Toru Y, Kojiro O, et al. Parotid lymph node metastasis in a patient with tongue cancer. Case Rep Clin Med 2014;3(1):23–7. https://doi.org/10.4236/crcm.2014.31006. Kurabayashi T, Ida M, Tetsumura A, Ohbayashi N, Yasumoto M, Sasaki T. MR imaging of benign and malignant lesions in the buccal space. Head Neck 2014;31:6. https://doi.org/10.1038/sj.dmfr.4600723. Malik A, Joshi P, Mishra A, Garg A, Mair M, Chakrabarti S, et al. Prospective study of the pattern of lymphatic metastasis in relation to the submandibular glands in carcinoma of oral cavity. Head Neck 2016;38(11):1703–7. https://doi.org/10. 1002/hed.24508. Epub 2016 May 27. Melhoranse BG, Barbosa MHM, Carneiro LH, El Hadj LA, Fernandes NC. The prognostic importance of parotid envolvement by head and neck squamous cell carcinoma – case report. An Bras Dermatol 2016;91(3):351–3. https://doi.org/10. 1590/abd1806-4841.20163995. Naidu TK, Naidoo SK, Ramdial PK. Oral cavity squamous cell carcinoma metastasis to the submandibular gland. J Laryngol Otol 2012;126(3):279–84. https://doi.org/ 10.1017/S0022215111002660. Panda NK, Patro SK, Bakshi J, Verma RK, Das A, Chatterjee D. Metastasis to submandibular glands in oral cavity cancers: can we preserve the gland safely? Auris Nasus Larynx 2015;42(4):322–5. https://doi.org/10.1016/j.anl.2015.02.006. Epub 2015 Feb 25. Pałasz P, Adamski L, Górska-Chrząstek M. Contemporary diagnostic imaging of oral squamous cell carcinoma – a review of literature. Pol J Radiol 2017;82:193–202. https://doi.org/10.12659/PJR.900892. Seifert G, Hennings K, Caselitz J. Metastatic tumors to the parotid and submandibular glands–analysis and differential diagnosis of 108 cases. Pathol Res Pract 1986;181(6):684–92. https://doi.org/10.1016/S0344-0338(86)80044-9. Sieczka E, Datta R, Singh A, Loree T, Rigual N, Orner J, et al. Cancer of the buccal mucosa: are margins and T-stage accurate predictors of local control? Am J Otolaryngol 2001;22:395–9. Stanley MW, Bardales RH, Farmer CE, Frierson Jr. HF, Suhrland M, Powers CN. Primary and metastatic high-grade carcinomas of the salivary glands: a cytologichistologic correlation study of twenty cases. Diagn Cytopathol 1995;13(1):37–43. Shah GV, Fischbein NJ, Patel R, Mukherji SK. Newer MR techniques for head and neck. Magn Reson Imaging Clin N Am 2003;11:449–69. Spiegel JH, Brys AK, Bhakti A, Singer MI. Metastasis to the submandibular gland in head and neck carcinomas. Head Neck 2004;26:1064–8. Shivakumar T, Nair SV. Delayed contralateral intra-parotid nodal metastasis from an oral squamous cell carcinoma. J Case Rep 2013;3(2):317–21. https://doi.org/10. 17659/01.2013.0074. Sawlani K, Kumari N, Mishra A, Agrawal U. Oral cancer prevalence in tertiary care hospital in India. J Family Med Com Health 2014;1(4, 1022):1–5. Sharma D, Singh G. Squamous cell carcinoma of the oral cavity and oropharynx in young adults. Indian J Cancer 2016;53:399–401. Singh A, Thukral C, Gupta K, Sood A, Singla H, Singh K. Role of MRI in evaluation of malignant lesions of tongue and oral cavity. Pol J Radiol 2017;82:92–9. Sharma S, Satyanarayana L, Smitha A, Shivalingesh K, Goutham B, Ramachandra S. Oral cancer statistics in India on the basis of first report of 29 population-based cancer registries. J Oral Maxillofac Pathol 2018;22(1):PMC5917535. Tart R. CT and MRI imaging of the buccal space and buccal space masses. RSNA 1995;15(3):531–50. Tandon P, Dadhich A, Saluja H, Bawane S, Sachdeva S. The prevalence of squamous cell carcinoma in different sites of oral cavity at our Rural Health Care Centre in Loni, Maharashtra – a retrospective 10-year study. Contemp Oncol (Pozn) 2017;21(2):178–83. https://doi.org/10.5114/wo.2017.68628.