Proposed sub-compartmentalization of high infratemporal fossa involvement in gingivobuccal cancers and its impact on clinical outcome and staging: A narrative review : Cancer Research, Statistics, and Treatment

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Proposed sub-compartmentalization of high infratemporal fossa involvement in gingivobuccal cancers and its impact on clinical outcome and staging

A narrative review

Mahajan, Abhishek; Agarwal, Ujjwal; Patil, Vijay M.1; Patil, Vasundhara; Vaish, Richa2; Noronha, Vanita1; D' Cruz, Anil K.2; Pankaj Chaturvedi, Shreya Shukla2; Laskar, Sarbani Ghosh4; Sable, Nilesh; Janu, Amit; Patil, Asawari3; Menon, Munita3; Rane, Swapnil3; Mittal, Neha3; Joshi, Amit1; Menon, Nandini1; Prabhash, Kumar1

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Cancer Research, Statistics, and Treatment: Apr–Jun 2022 - Volume 5 - Issue 2 - p 269-275
doi: 10.4103/crst.crst_293_21
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Despite significant recent advances, head and neck cancers continue to remain a serious and growing problem, primarily due to the disfigurement consequential to the disease and the high cost of treatment, causing significant morbidity and mortality. Buccal mucosa and gingivobuccal sulcus (GBS) squamous cell carcinomas are some of the most common oral cancers in India.[12] Many patients present at an advanced stage, and have adverse outcomes, owing to the high local recurrence rate after therapy.[3] According to the eighth edition of the American Joint Committee on Cancer (AJCC), involvement of the masticator space signifies advanced disease. It is assigned a T4b category, conveying an impression of unresectable disease.[4] Even though the involvement of the masticator space indicates a poor prognosis, this may not be true in every case. Based on our experience in one of the busiest cancer centers in the world, we strongly recommend that T4b disease in oral cancer can be subclassified according to distinct outcomes. This imaging-based sub-compartmentalization of T4b disease could impact patient management and foster efficient utilization of scarce hospital resources.

In our experience, stage T4b with infra-notch disease (below the mandibular notch) is associated with a more favorable prognosis than supra-notch disease (above the mandibular notch). This was first observed by Liao et al.[5] in a cohort of 58 patients with advanced buccal carcinomas. They reported that a specific subset of T4b buccal cancers could be operated with acceptable outcomes. They showed that tumors above the mandibular notch, that is, supra-notch disease, had poorer outcomes than those limited to the infra-notch compartment[6] [Table 1]. Mohiyuddin et al.[7] similarly showed that disease inferior to the lateral pterygoid muscle or involving the anterior half of the masticator compartment had reasonably good outcomes. This observation further substantiates the need to clarify the exact extent of disease involvement in T4b buccal cancers to aid optimal surgical management. Trivedi et al.[8] showed that compartment surgery provides an opportunity to achieve negative margins for cancers actually contained within the masticator space. Kumar et al.[9] showed that the survival of patients with T4b oral cancers with involvement of three or fewer masticatory space structures was similar to that of those with T4a tumors. Thus, selecting cases based on imaging criteria becomes the most important clinical outcome predictor. Since infratemporal fossa (ITF) space involvement has a different prognosis and survival outcome depending on the exact structures involved, we propose that T4b disease should be further compartmentalized.

Table 1:
Comparison of different studies evaluating the infratemporal fossa involvement in oral cavity cancers


We conducted a comprehensive search of abstracts of ITF subdivision and their impact on staging as per the eighth edition of AJCC. We included studies published in English that reported data on ITF subdivision and its impact on clinical outcomes. The key words for Medical Subject Headings were “cross-sectional imaging,” “oral carcinoma,” “AJCC 8th edition,” “infratemporal fossa,” “masticator space,” “survival,” and “neoadjuvant chemotherapy.” Filters applied included full text, humans, English, cancer; article types included “guideline,” “meta-analysis,” “systematic review,” and “randomized control trial;” and publication date was from 2000 to 2021. We also searched in Embase, MEDLINE, Cochrane Central, and Google Scholar. We excluded articles for which the full text was not available, non-human studies, and those that were not in English. The search strategy is outlined in Figure 1.

Figure 1:
The search strategy for identifying articles relevant to the infratemporal fossa subdivision and its impact on clinical outcomes


Relevant anatomy

The ITF is not mentioned in the eighth edition of AJCC,[10] resulting in the vague and interchangeable use of the terms “masticator space” and “infratemporal fossa” in patient records. This point needs to be urgently addressed, as there is a clear difference between the anatomic boundaries of the masticator space and the ITF, and these terminologies cannot be used interchangeably. Moreover, this differentiation is of utmost importance from the clinician's perspective, as management and clinical outcomes differ for tumors that involve the masticator space and the ITF.

The T4b category comprises the radiologist's masticator space and the surgeon's ITF. The masticator space constitutes the suprahyoid deep fascial space formed by the splitting of the layers of the investing layer of cervical fascia. It contains the posterior body and ramus of the mandible with the masseter and temporalis muscles. The medial and lateral pterygoid muscles and the mandibular division of the trigeminal nerve, which continues as the inferior alveolar nerve exiting at the mental foramen, are also part of the masticator space.[11]

On the other hand, the ITF is bordered by a non-fascial plane between the skull base, lateral pharyngeal wall, and the ramus of the mandible. The ITF communicates with the temporal fossa via the space deep to the zygomatic arch, with the pterygopalatine fossa via the pterygomaxillary fissure, and with the middle cranial fossa via the foramen ovale and spinosum. The contents of the ITF are the medial and lateral pterygoid muscles, internal maxillary artery, mandibular division of the trigeminal nerve, and pterygoid venous plexus. The masseter is not a part of the ITF. The ITF thus includes the medial part of the masticator space, part of the parapharyngeal space, and the retroantral buccal space.[12] The ITF is further classified into high and low ITF using the sigmoid notch as a landmark. The sigmoid/mandibular notch between the coronoid and condyloid processes of the mandible is used as an anatomical landmark to demarcate disease extent and distinguish supra-notch from infra-notch disease[11] [Figures 2 and 3].

Figure 2:
Axial (a) and coronal (b) images show masticator space on the right bounded by fascia (yellow) and infratemporal fossa bordered by an imaginary line (green). Color codes: light green: masseter; pink: temporalis; light brown: lateral pterygoid; purple: medial pterygoid; orange: prestyloid parapharyngeal space; light blue: retroantral space
Figure 3:
Surgical anatomy of the infratemporal fossa. (a) The arrow denotes the masseter muscle originating from the zygomatic arch and inserted at an angle and lateral surface ramus. The asterisk denotes the buccal pad of fat. (b) The arrow denotes the temporalis muscle insertion on the coronoid process exposed after cutting the masseter muscle fibers. (c) The asterisks denote the two heads of origin of the medial pterygoid muscle. (d) The arrow denotes the inferior alveolar nerve

Role of imaging

Patients usually present with ulcer, pain, swelling, bleeding, poorly fitting dentures, speech alteration, and enlarged lymph nodes in the neck. A local examination is performed, which includes inspection, palpation of the ulcer and neck nodes, and indirect mirror exam ± fiberoptic endoscopy. Biopsy of the tumor and/or lymph nodes is done, and further workup is planned. After histological confirmation, routine laboratory tests are done. Computed tomography (CT) head and neck, and thorax is done for cancers of the buccal mucosa, retromolar trigone, and alveolus, and magnetic resonance imaging (MRI) head and neck, and thorax is done for tongue carcinoma. After detailed staging, treatment is planned in a multidisciplinary meet according to the T and N classification and the extent of disease.[13]

CT with puffed-cheek technique is the investigation of choice for evaluating disease of the buccal mucosa, retromolar trigone, alveolus, mandible, and lip. Images are acquired in soft tissue windows and further reconstructed in bone algorithms with multiplanar reconstruction, which provides us insight into the spread of disease, relationship with important structures, and the presence of bone erosion and perineural spread. Involvement of the GBS and perineural spread going above the mandibular notch are best evaluated on coronal reformation. In contrast, the oblique sagittal view is best used for assessment of the retromolar trigone. Paramandibular soft tissue extent, mandibular foramen widening, and extension into the high ITF are best evaluated on axial images. Coronal images are used for measuring the depth of invasion.[141516]

Preoperative imaging is very important to determine the presence or absence of mandibular erosion and whether the erosion is superficial or deep, cortical, or medullary. For planning the type of mandibulectomy, radiologists must report the anteroposterior extent of erosion on axial images and the height of the uninvolved segment of the mandible on coronal imaging, as this has a significant impact on surgical planning (mandible sparing vs. marginal vs. segmental mandibulectomy), particularly in tumors arising from the GBS and retromolar trigone, since they present with early bone involvement.[1718] Multidetector Computed Tomography has a high specificity (87%–90%), while MRI has a high sensitivity (96%–97%) and a high negative predictive value for assessment of bone involvement; however, MRI has a low specificity (54%) for cortical invasion, making it a less valuable imaging tool for assessment of these malignancies.[19] The oblique reformations are helpful for determining inferior alveolar canal involvement. Multiplanar and oblique reformations done on workstations with spatial cursor localization further enhance the assessment of mandibular canal involvement. It is necessary to provide information regarding sparing of the condyloid process and posterior segment of the mandible, which helps plan the reconstruction necessary after segmental mandibular resection.[20]

Highlighting the significant points in synoptic reporting leads to more detailed reports and ensures that nothing is missed. This is important for better surgical planning and communication with clinicians for optimal decision-making. Templates should be regularly updated according to the recent guidelines and clinicians' requirements. If reminders and alerts are included as a part of the synoptic reporting, patient care tasks can be kept on schedule, thus avoiding unnecessary delays. Synoptic reporting facilitates data analysis, as all data elements can be analyzed. Hence, it helps in understanding patient outcomes with different therapies. The following parameters have to be included in the report [Figure 4]:

Figure 4:
Reporting format used in our department for staging of oral cancers
  • Epicenter of the tumor
  • Size
  • Depth of invasion
  • Soft tissue extent: Retromolar trigone, gingivolingual sulcus, tongue, floor of mouth, masseter muscle, masticator space, medial pterygoid, low anterior retroantral fat, ITF, high ITF, high anterior retroantral fat, temporalis muscle, lateral pterygoid, pterygomaxillary fissure and pterygopalatine fossa, condylar fossa, intracranial extension
  • Radiological assessment of bone and perineural spread: Tumor mass with adjacent cortical break is regarded as positive for malignant erosion.[14] Marrow invasion is defined as contiguous trabecular destruction.[14] Tumor reaching into the canal with a breach of the bony canal wall is regarded as canal invasion with suspicious inferior alveolar nerve involvement.[14] Obliteration of fat or excessive enhancement within the mandibular foramen or foramen ovale, with or without widening or erosion of the foramen, is regarded as perineural spread.[14]
  • Detailed N-stage categorization: Criteria for labeling nodes as metastatic nodes include round nodes, loss of fatty hilum, necrosis, heterogeneous enhancement, and capsular irregularity. Criteria for extranodal extension are capsular irregularity with fat stranding, capsular irregularity with fat invasion, and gross muscle/vessel invasion.[14]

Implications on management

The implications on management are presented in Table 2.

Table 2:
Sub-compartments with imaging findings and implications on management and staging as per the AJCC eighth edition

Patients presenting with early-stage disease, that is, stage T1–2N0 can be treated with upfront surgical resection of the primary tumor with ipsilateral or bilateral selective neck dissection (consider bilateral neck dissection for tumors approaching the midline, oral tongue, or floor of mouth) with postoperative radiotherapy for close margins, perineural invasion, and lymphovascular space invasion and postoperative chemoradiotherapy (CRT) for positive margin.[13] Patients with T3–T4a or N1–N3 disease require surgical resection of the primary with ipsilateral or bilateral selective neck dissection (consider bilateral neck dissection for tumors approaching the midline, oral tongue, floor of mouth, and N2c category) with reconstruction as indicated with postoperative radiotherapy to all and postoperative CRT, if indicated for cases with close or positive margins or pathological extracapsular extension.[13]

Disease extension closer to the skull base (high ITF or supra-notch disease) has unfavorable outcomes and high morbidity if treated surgically. In contrast, low ITF disease (compartment 1) has favorable outcomes if treated surgically and can be regarded as “surgeon friendly.”[21] This concept is well known and widely accepted in practice. However, we have observed that a specific subset of high anterior retroantral ITF involvement (compartment 2) can also be operated on with good clinical outcomes.[222324]

The extent of disease and masticator space/ITF involvement can be easily evaluated on imaging by an experienced radiologist, which can then be communicated to the treating oncologist. Cases with advanced disease involving high ITF (posterior high ITF involvement) can now be treated with neoadjuvant chemotherapy. They may become resectable after tumor regression post-therapy, thus improving the overall prognosis. This newly emerging disease management concept was first reported by two landmark trials, TAX323 and TAX324.[2526] Patil et al.[25] showed that the use of induction chemotherapy is safe and can achieve resectability in 30.9% of patients with T4b primaries; patients with supra-notch T4b disease who underwent surgical resection post-induction chemotherapy had a better overall survival compared to those undergoing non-surgical local treatment.[262728] However, tumor extension to the base of skull, prevertebral muscles, and/or encasement (>270°) of the carotid artery are absolute contraindications to surgery; these patients are treated with palliative intent.[29]

Moreover, it has been observed that patients with supra-notch T4b disease who undergo surgical resection post-induction chemotherapy have a much better overall survival compared to those undergoing non-surgical local treatment.[25] Induction chemotherapy effectively downstages technically unresectable oral cavity cancers to resectable disease in approximately 40% of patients, resulting in significantly improved overall survival compared to non-surgical treatment.[252627]

The Response Evaluation Criteria in Solid Tumors (RECIST) guidelines do not have a significant role in the post-induction chemotherapy response assessment. This is because tumors in these regions tend to be amoeboid or geographic/irregular in shape rather than well-circumscribed masses; thus, the volume of disease and proximity to critical structures may serve as more robust markers of disease load rather than the maximal axial dimensions and could be more suitable for response assessment.[29]

Hypothesized sub-compartments of the ITF and their management

Since involvement of the ITF space has a different prognosis and survival outcome depending on the exact structures involved, we propose that T4b disease should be further classified into the following compartments [Figure 5]:

Figure 5:
Hypothesized sub-compartments of the ITF. (a) Compartment 1: low ITF: medial pterygoid (purple) and masseter (green). (b) Compartment 2: anterior high ITF (retroantral fat) (blue). (c) Compartment 3: posterior high ITF. Compartment 3a: paramandibular compartment (paramandibular fat/temporalis) (pink). Compartment 3b: muscle compartment (lateral pterygoid) (light brown). Compartment 3c: perineural compartment (pterygopalatine fossa and pterygomaxillary fissure) (red). ITF = infratemporal fossa
  • Compartment 1: Low ITF (medial pterygoid and masseter)
  • Compartment 2: Anterior high ITF (retroantral fat)
  • Compartment 3: Posterior high ITF
  • Compartment 3a: Paramandibular compartment (paramandibular fat/temporalis)
  • Compartment 3b: Muscle compartment (lateral pterygoid)
  • Compartment 3c: Perineural compartment (pterygopalatine fossa and pterygomaxillary fissure).


Cases with posterior high ITF involvement need an MRI of the skull base apart from the baseline CT paranasal sinuses and thorax to rule out perineural spread and pterygopalatine fossa involvement.[14] In cases with extensive perineural spread and pterygopalatine fossa involvement, further evaluation with positron emission tomography-CT (PET-CT) is suggested to rule out distant metastasis before planning induction chemotherapy.[30] The imaging modality used for the pre-chemotherapy baseline evaluation should be used for the follow-up imaging for adequate response assessment, which is usually done after two cycles of 21 days each.


We believe that demarcation of the ITF compartments, and inclusion of this information in the radiology report, will enhance the communication between the surgical oncologist and the radiologist. This could lead to better decision-making and patient selection and provide clarity to the clinician for the formulation of an optimal treatment plan, ultimately paving the way for the practice of personalized cancer medicine.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.


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infratemporal fossa; CT; imaging; survival; gingivobuccal cancer; sub compartments

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