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Subspecialties Histology, Oncology, Biochemistry and molecular biology, Profession

More than a Mouthful

The oral and maxillofacial (OMF) region may be small compared with other body parts, but these complex anatomical structures are home to some of the most fascinating and unique pathological findings (although we may be slightly biased). It may surprise you to know that the majority of pathologists specializing in OMF pathology in the UK chose this career after completing a degree in dentistry, but there is far more to this specialty than just teeth. Currently, only 36 OMF pathologists are on the General Dental Council specialist register in the UK. These numbers are higher in places like the US, but are way below the amount of general pathologists. Though the specialty is quite small, the profession covers disease in some of the most complex anatomy within the human body. Dentally qualified OMF pathologists are highly respected within the remit of oral, maxillofacial, and head and neck pathology, and make significant contributions to WHO medical resources (1). You may be surprised to know that the most recent virtual meeting of the International Association of Oral Pathologists (IAOP) attracted more than 5000 attendees from across the world highlighting the interest in the specialty.

In this article, we share some insights about our field – including what you might expect in a typical workday.

How to become an oral and maxillofacial pathologist
 

Most dental undergraduates in the UK receive pathology teaching to acquire an understanding of oral and dental diseases. For some, this exposure sparks an interest and a passion to pursue it after their dental degree. Such graduates are required to complete foundation training for a year which supports newly qualified dentists transitioning from dental school to dental practice. Graduates can then take up a hospital-based Dental Core Training (DCT) post for up to three years in an array of specialties, including oral and maxillofacial surgery, oral surgery, pediatric dentistry, oral medicine, and most importantly, OMF pathology. After this, graduates can apply for specialty training – which is highly competitive with only a limited number of posts. Many of these positions involve an academic and research training component (at pre- and postdoctoral levels).

What does OMF pathology specialist training involve?
 

The training takes place over five years and is the only dedicated programme recognised by the Royal College of Pathologists to study oral, maxillofacial, and head and neck pathology. This makes the programme truly unique. Our medical peers take five years of general histopathology training in the UK and only decide their “specialty of interest” just before, or even after completion of their training. So, one may wonder: why does OMF pathology training take five years? Well, there are a few reasons. Despite the perceived “relatively small” area of the body that OMFP accounts for, the anatomy, surgical resection specimens, and sheer volume of entities that can be found in the region is vast and complex. Maneuvering this network requires significant training to fully prepare trainees for consultant roles and independent working. This includes a full year in general histopathology, with rotations in all specialties – including autopsies – before the first part of the Fellowship of Royal College of Pathologists (FRC Path) exam. This is followed by a further period of intensive diagnostic training before the exam’s second portion (a two day clinical/diagnostic exam). The trainees undergo formal appraisals and work-place based assessments throughout their training to monitor and guide their professional development. When all these steps are completed, the trainees can be listed as a specialist in OMF pathology on the General Dental Council (GDC) UK register as well as with the RCPath. Many will either work within dental hospitals with involvement in NHS diagnostic reporting duties and the delivery of university teaching, or within a general histopathology department reporting oral and head and neck specimens with some consultants also reporting endocrine pathology. Understandably, these exams and regulatory authorities would be different in other countries.

The wide scope of OMF pathology
 

There is far more to oral and maxillofacial pathology than just teeth! The head and neck, oral cavity, dental hard tissues, and craniofacial bones are all part of the specialty.

Figure 1. Left hemimaxillectomy. A) inferior view, B) palatal view.

The surgeries and procedures for oral and maxillofacial malignancies can be life changing for patients – leading to altered appearance, speech, and a new found inability to eat. The anatomy of these sites and of the resections carried out can be extremely complex. Clearly, OMF pathologists require thorough anatomical knowledge to adequately assess and sample specimens, before communicating their findings clearly with other teams. The specimens that OMF pathologists receive from these kinds of procedures often include partial or full maxillectomy (see Figure 1), mandibulectomy (see Figures 2, 3), parotidectomy in continuity with neck dissection (see Figure 4), and nasal resections or orbital exenteration containing both soft tissue and bone margins, which only adds another level of complexity to the dissection process. It is important to note that specimens submitted with bone can take several weeks to report as the bone must be decalcified for processing and subsequent histological examination. Several different solutions are available and although some, such as hydrochloric or nitric acid, may decalcify bone margins in the shortest time, they macerate the tissue and can make microscopic analysis challenging.

Figure 2. Left hemimandibulectomy; A) lingual view, B) superior view

There is an agreed protocol which allows for better tissue preservation and more accurate assessments of bone invasion and clear margin status – such as formic acid – but it does take longer. However, it can be used in combination with specialist diamond saws that can cut hard tissue into thin slices to speed up the decalcification process.

Figure 3. Cross sectional views of a hemimandibulectomy for an ameloblastoma. The cystic nature of the tumor is seen alongside extensive expansion of the mandible bucco-lingually.

Figure 4. Parotidectomy with attached neck dissection for an adenocarcinoma of the parotid gland involving the overlying skin. Sutures are used for orientation purposes and the lymph node levels of the neck have been labeled with numbered tags.

Bone lesions
 

The craniofacial bones are also home to some interesting and site-specific entities. There are times when OMF pathologists need to use some of their wider skills and interpret accompanying radiological imaging for clinicopathological correlation. This skill is vital to an OMF pathologist, as oftentimes they may find several lesions – such as giant cell, odontogenic and fibro-osseous lesions – in the craniofacial region with histologically overlapping features; definitive diagnosis can then only be achieved after correlation with radiology.

Fibro-osseous lesions
 

Several fibro-osseous lesions can be found in the jaws – fibrous dysplasia, cemento-ossifying fibroma, and cemento-osseous dysplasia, to name just a few. The lesions can be diagnostically challenging based upon incisional biopsy alone; however, these have very different appearances from a radiographical point of view. Radiology can also help highlight the extent of disease involvement for certain fibro-osseous lesions, which can be focal (associated with one tooth), periapical (associated with the apical regions of the anterior mandibular incisors), or florid (involving multiple quadrants) (see Figure 5). Perhaps confusingly, there are also some ossifying fibromas that are not odontogenic in origin. According to the WHO classification in 2017, cemento-ossifying fibromas and cemento-ossifying dysplasias must occur within the tooth bearing areas of the jaws. There are examples within the literature of ossifying fibromas that have occurred in the frontal and nasal bones with an indolent clinical course. This argument has suggested that all ossifying fibromas should be re-classified as conventional ossifying fibromas to take into account the varying sites in which ossifying fibromas can originate (2).

Figure 5. Histological and radiographic appearances of different fibro-osseous lesions; A) H&E section showing an example of fibrous dysplasia. Note the thin, irregular trabeculae of bone in a fibrous background without osteoblastic rimming; B) H&E section with an example of a cemento-ossifying fibroma. The lesional tissue comprises small spherical deposits of calcified material in a hypercellular background stroma. The lesion is partially encapsulated with a shell of bone at the periphery; C) Cropped OPT with arrow highlighting fibrous dysplasia of the mandible; D) Cropped OPT demonstrating florid COD. Areas affected in the right and left mandible are highlighted by the arrows.

Odontogenic lesions
 

The maxillofacial complex is also home to an array of odontogenic lesions, including odontogenic and non-odontogenic cysts; benign epithelial, mesenchymal, and mixed odontogenic tumors; and, more rarely, odontogenic carcinomas, sarcomas, and carcinosarcomas. The histological features and findings of these are unique and correlation with imaging is essential for diagnosis. For example, small biopsies can show overlapping features between lesions and without radiological correlation there is significant potential for odontogenic tumors to be misdiagnosed as cysts (cystic ameloblastoma being a prime example) and an incorrect odontogenic cyst subtype being reported.

Salivary gland neoplasms
 

Salivary gland neoplasms exhibit significant diversity in morphology, immunohistochemistry, and molecular makeup, making them one of the most challenging areas of pathology. Advances in molecular techniques have allowed for the subtyping of many tumors previously assigned to the category of adenocarcinoma NOS. For example, the discovery of the MEF2C-SS18 gene fusion in microsecretory adenocarcinoma has recently allowed this tumor to be identified as an entity in its own right (3). Indeed, molecular techniques, such as fluorescent in situ hybridisation (FISH), are often used as an adjunct to immunohistochemistry to identify the presence of gene fusions, translocations and rearrangements including ETV6-NTRK3 in secretory carcinoma, CRTC1-MAML2 in mucoepidermoid carcinoma, and EWSR1-ATF in clear cell carcinoma (see Figure 6).

Figure 6. H&E presentation of a selection of salivary gland tumors with recognized gene fusions and rearrangements; A) mucoepidermoid carcinoma identified at the base of tongue with MAML2 gene fusion; B) secretory carcinoma with ETV6 gene translocation; C) clear cell carcinoma of salivary gland origin with EWSR1 gene rearrangement; D) Microsecretory adenocarcinoma of salivary glands with MEF2C-SS18 gene fusion.

Metastases
 

The oral cavity and jaw bones can also be a rare site for the presentation of metastatic disease from other organ systems, including the lungs, breasts, kidneys, and gastrointestinal tract (see Figure 7). It is necessary, then, that clinicians provide a thorough history on the request form to inform pathologists of such information. On rare occasions, incidental synchronous primary tumors can also be identified in cervical lymph node dissection specimens. Often, OMF pathologists receive cervical lymph node dissection specimens as part of the main resection for head and neck cancer patients. However, sometimes metastatic deposits from a different primary tumor, whose presence is not currently known about by the surgical team, can present.

Figure 7. Examples of metastatic disease to the head and neck; A) metastatic lung adenocarcinoma presenting as a lesion in the zygoma. Extensive immunohistochemistry was completed showing the tumor to be diffusely positive for CK7, AE1/AE3 and TTF1. Further imaging revealed a 54mm intrapulmonary primary tumor; B) metastatic clear cell renal carcinoma to the upper alveolus; C) metastatic colorectal adenocarcinoma presenting in the buccal mucosa. The patient had widespread disseminated disease at the time of the presentation of the buccal metastasis; D) an incidental finding of metastatic papillary thyroid carcinoma (follicular variant) in a neck dissection completed for the treatment of a primary squamous cell carcinoma of the head and neck.

For example, incidental variants of papillary thyroid carcinoma have previously been identified within cervical lymph node resections for head and neck squamous cell carcinoma (Figure 7D). Therefore, knowledge and understanding of the pathology of the rest of the body is crucial in ensuring correct interpretation and diagnosis. That is why a year of training dedicated to general pathology as part of the training program is so valuable in the creation of well-rounded OMF pathologists. 

Tooth pathology
 

As former general dental practitioners who are now OMF pathologists, it is not possible to discuss OMF pathology without mentioning teeth. Teeth are one of the more uncommon specimens for OMF pathologists to receive and report, however numerous conditions can be diagnosed microscopically, including amelogenesis imperfecta, dentinogenesis imperfecta, and dentine dysplasia. Some systemic conditions also have characteristic tooth histology, such as X-linked hypophosphatemia (see Figure 8). Processing of teeth is unique; approximately half of the tooth is ground to adequately assess enamel quality, as very little enamel remains after decalcification processes. The other half of the tooth is decalcified to assess dental caries, as well as the architecture and structure of the dentine, cementum, and pulp. This process is only conducted in limited centers and is a niche area of practice specific to OMF pathology that requires extensive skills and diagnostic ability.

Figure 8. Histological examination of primary incisor tooth; A) ground section showing a normal thickness of regular, prismatic enamel overlying dentine; B, C) H&E stained sections showing prominent interglobular dentine, overall in keeping with a diagnosis of X-linked hypophosphatemia.

Consulting and dealing with expert/second opinion cases
 

The unusual and niche nature of the specimens OMF pathologists receive is mirrored in the number of cases we receive as referrals for second opinions and expert consults. Because of the specificity, complexity, and site-specific nature of many of the lesions found within the head and neck, many general pathologists may never come across such entities and hence send diagnostically challenging cases to OMF pathologists for an expert opinion. This further highlights the need for specialist OMF pathologists in diagnoses of more complex and rarer entities within the head and neck (4). These expert opinions are invaluable and not only facilitate correct patient management, but promote good clinical practice and allow general pathologists with an interest in head and neck to further their knowledge within the subject field. 

A day in the life of an OMF consultant pathologist 
 

Working days are somewhat varied, though many find this an attractive aspect of the job; no two days are quite the same. One day may include presentation of new cancer diagnoses and completed cancer resection cases at the weekly head and neck MDT (multidisciplinary team meeting or tumor board meeting). The next day may involve specimen dissection and reporting duties. Most OMF pathologists are also involved in undergraduate dental student training, postgraduate teaching, and diagnostic training of OMF pathology clinical trainees. Many OMF consultant pathologists also have clinical academic backgrounds with active research outputs and publications, as well as involvement in local, national, and international reporting standards and guidelines (5). 

If you are interested in finding out more about our field or have a keen interest in head and neck pathology, there societies; for example, the British Society for Oral and Maxillofacial Pathology, the American Academy of Oral and Maxillofacial Pathology (AAOMP), and the International Association for Oral and Maxillofacial Pathologists (IAOP). In the end, although cases can be challenging, the vast array of entities that arise at these sites coupled with constant advancements in the treatment of head and neck neoplasms make OMF pathology an extremely interesting and stimulating career.

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  1. WHO Classification of Tumors Editorial Board, “Head and neck tumors" (2022). Available at: https://tumourclassification.iarc.who.int/chapters/52.
  2. D Baumhoer et al., “Ossifying Fibroma of Non-odontogenic Origin: A Fibro-osseous Lesion in the Craniofacial Skeleton to be (Re-)considered,” Head Neck Pathol, 16, 257 (2022). PMID: 34173971.
  3. JA Bishop et al., “Microsecretory Adenocarcinoma: A Novel Salivary Gland Tumor Characterized by a Recurrent MEF2C-SS18 Fusion,” Am J Surg Pathol, 43, 1023, (2019). PMID: 31094920.
  4. MH Mullin, et al., “Second opinion reporting in head and neck pathology: the pattern of referrals and impact on final diagnosis,” Oral Surg Oral Med, 119, 656 (2015). PMID: 25956218.
  5. The Royal College of Pathologists, “Datasets for histopathology reporting of head and neck cancers” (2013, 2014). Available at: https://www.rcpath.org/profession/guidelines/cancer-datasets-and-tissue-pathways.html
About the Authors
Hannah Walsh

Unit of Oral and Maxillofacial Pathology School of Clinical Dentistry, University of Sheffield, UK.


Syed Ali Khurram

Unit of Oral and Maxillofacial Pathology School of Clinical Dentistry, University of Sheffield, UK.

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