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2 Global Scenario, Aetiology and Risk Factors Associated with Oral and Maxillofacial Diseases: An Overview
22
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3
The Role of Laboratory Diagnosis in Oral and Maxillofacial
Pathology: An Overview
Hannah Walsh and Daniel J. Brierley
Unit of Oral and Maxillofacial Pathology, School of Dentistry, University of Sheffield, Sheffield, UK
3.1 Introduction
Laboratory diagnosis is a cornerstone in investigating diseases identified within the oral and
maxillofacial complex. Ultimately, as the diagnosis often impacts subsequent management, there
is an excellent level of responsibility as a pathologist to carefully assess the submitted tissue
sample. This may require additional ancillary tests, clinicopathological correlation with imaging
or discussion of the pathological findings in a multidisciplinary team (MDT) meeting setting
before establishing an appropriate treatment plan. This chapter reviews the importance of
histopathological assessment as an investigative procedure while appreciating how context and
adjunctive tests can alter or inform a diagnosis.
27
3.2 The Need fora Diagnosis
Pathology, by definition, is the study of disease and, in the oral and maxillofacial setting,
encompasses the diagnosis of conditions identified within the head and neck and craniofacial
bones, including the maxilla and mandible. The pathological assessment of patient tissue is often
a fundamental process in the patient treatment pathway. It goes without saying that if the clinical
team treating a patient does not know what a lesion is, it is very difficult to adopt the correct treatment regimen for the patient. Therefore, histopathological assessment, clinical assessment and
appropriate imaging are fundamental to enabling the proper treatment for patients.
Within the anatomical boundaries of the oral and maxillofacial complex, several disease
processes occur, varying from benign to malignant. Many conditions are benign, with inflammatory and reactive processes being the most frequently encountered pathologies in the oral and
maxillofacial setting. In most cases, removing the lesion (i.e. excision of a benign fibroepithelial
polyp caused by recurrent trauma or enucleation of a radicular cyst from a non- vital tooth) is
curative. In other cases, the histopathological findings influence a short course of treatment
(e.g.prescription of antifungal therapy in response to chronic hyperplastic candidosis) or lead to a
long- term treatment plan (e.g. management of lichen planus). A wide range of malignant disease
Pathological Basis of Oral and Maxillofacial Diseases, First Edition. Edited by S. R. Prabhu, Syed Ali Khurram,
Omar Kujan and Merva Soluk Tekkesin.
© 2025 John Wiley & Sons Ltd. Published 2025 by John Wiley & Sons Ltd.
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3 The Role of Laboratory Diagnosis in Oral and Maxillofacial Pathology: An Overview
28
processes also occur within this setting, and treatments often significantly impact a patient’s physical appearance, speech and mastication. Thus, pathologists have considerable responsibility to
ensure the diagnosis is correct, as the outcomes can be detrimental if misdiagnoses are made.
Although pathologists mostly work ‘behind the scenes’ and are not in direct patient- facing roles,
they still have a duty of care to the patients they serve. They are a core member of head and neck
oncology MDT meetings (or tumour boards) alongside surgeons, radiologists, oncologists and
other healthcare professionals(1). Based upon the histological examination of patient material,
pathologists can provide prognostic information from the tissue examined, such as the type or differentiation of the tumour, depth of tumour invasion into the underlying connective tissue, presence of tumour within nerves (perineural invasion) or blood vessels (lymphovascular invasion)
and metastatic spread of disease to lymph nodes. The clinical care team uses the prognostic information gleaned from the patient sample and findings from imaging studies to plan a suitable
course of treatment for the patient based on the diagnostic findings. This highlights the importance of achieving a diagnosis to facilitate effective patient treatment planning.
3.3 Summary ofPathology Common toOral
andMaxillofacial Region
The oral and maxillofacial region is anatomically complex, with numerous and varied pathologies
arising in this location. In short, pathology may arise from odontogenic apparatus, salivary glands,
mucosa of the oral and sinonasal mucosa, skin, bone and soft tissue. It is also not an uncommon
site for local and distant metastases. The following text is not exhaustive and is intended to offer a
‘flavour’ of what may be encountered.
Tooth pathology, odontogenic cysts and tumours are specific to the jaws and require specialist
knowledge and experience to report. Knowledge of tooth development and dentistry is useful with
clinical and radiological information often needed to reach definitive diagnoses.
Salivary gland tumours can be challenging to diagnose, with significant morphological overlap
and heterogeneity between cases. Many are now being characterised by their genetic mutations
and translocations, and new entities are being reported relatively frequently.
Most of the pathologies affecting the oral mucosa are reactive entities such as fibrous polyps,
pyogenic granulomas and mucoceles. However, several mucocutaneous conditions, such as lichen
planus and vesiculobullous conditions, may require immunofluorescent testing on fresh tissue and
are commonly encountered. Pre- malignant and malignant epithelial pathology of the oral mucosa
is a challenging area, often requiring double- reporting and discussion with colleagues.
The sinonasal mucosa is a common site for sinonasal polyps, most reactive and benign. Other
characteristic tumours are specific to this site, such as sinonasal papillomas and nasopharyngeal
angiofibroma. A range of small round blue cell tumours can occur in this location, where a pathologist will often need to use panels of immunohistochemistry (IHC) and cytogenetic testing to
reach a definitive diagnosis(2).
Being a relatively sun- exposed part of the body, head and neck skin is a common site for malignancies such as squamous cell carcinoma, basal cell carcinoma and malignant melanoma. There
are also several skin adnexal tumours which are common on the facial skin, such as trichilemmoma.
The bones of the oral maxillofacial region may be affected by tumours that also arise in the long
bones of the body, such as osteosarcoma. However, their clinical presentation and pathology are
somewhat different. There are also pathologies which have a propensity to this region, such as
cemento- ossifying fibroma, ossifying fibroma, giant cell granulomas, cemento- osseous dysplasia
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3.4 Clinicopathological Correlation
and fibrous dysplasia, which show a high degree of morphological overlap and require significant
experience to report.
Sarcomas and lymphomas are also encountered in the oral and maxillofacial area and require
work- up and collaboration with pathologists specialising in these tumours.
Given the range of pathologies encountered in the oral and maxillofacial regions, one must have
a broad and up- to- date knowledge base to accurately and safely diagnose this pathology field. The
use of additional testing, such as cytogenetics, clinical and radiological information and sound
clinic- pathological correlation, is paramount in our diagnostic algorithms.
3.4 Clinicopathological Correlation
Clinicopathological correlation is crucial in pathology as it ensures that the pathological findings
are consistent with the clinical presentation, leading to accurate diagnoses and optimal treatment
strategies. While some pathologies, such as fibro- epithelial polyps, need a little extra information,
many diagnoses require acquiring and evaluating other information that can influence or frame the
diagnosis, such as the clinical presentation, radiological features and patient demographics. This
clinicopathological correlation is required by the pathologist when reporting the specimen. Ideally,
the clinician should complete the pathology request form while submitting the sample. The clinician may also require it when the pathological diagnosis needs further insight or exploration.
If we consider a poorly differentiated tumour in the sinonasal region, a pathologist’s initial
thoughts about the likelihood of specific tumours occurring at this site will be influenced by the
patient’s age (histology aside). Tumours such as rhabdomyosarcomas are more common in childhood, whereas carcinomas are more common in adulthood. This is an oversimplification, but having a grounded, logical and sensible approach to diagnosis is essential. Another example would be
differentiating lichen planus from lichenoid tissue reactions where the histology is very similar
and distinguishing the two conditions from each other requires, in short, information on the site,
onset and distribution of the lesions alongside the patient’s medical and drug history.
Many benign fibro- osseous lesions of the jaws and surrounding bones have very similar histology, and correlation with radiology is paramount in reaching a definitive diagnosis. For example,
cemento- osseous dysplasia and cemento- ossifying fibromas show a cellular fibroblastic stroma
containing varying amounts of calcified material. However, their radiological appearances can be
quite different. Similarly, a biopsy of the dental follicle surrounding an unerupted tooth is likely to
contain myxoid connective tissue, which could be mistaken for an odontogenic myxoma if the
pathologist does not appreciate the context and radiology.
In other cases, the pathologist may suggest to the clinician that further investigations are required
if the histology is not entirely specific. This is well exemplified by granulomatous inflammation,
which can be seen in several conditions, such as Crohn’s disease, sarcoidosis and tuberculosis.
However, each has differing clinical presentations and specific investigations, which would allow
the clinicians to eliminate the other possibilities.
Clinicopathological correlation is essential for the proper diagnosis. It should be required when
insufficient information is sent with a pathology request form. Sometimes, it is best practice to be
cautious and suggest a discussion with the clinician or another biopsy when required. It is not
unusual for a biopsy to arrive with a history of a large, fungating mass. Yet, the biopsy is only a few
millimetres in diameter, containing no apparent tumour!
While only a few examples of clinicopathological correlation have been described, they are
hoped to demonstrate to the reader the need to seek information and report pathology in context.
29
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3 The Role of Laboratory Diagnosis in Oral and Maxillofacial Pathology: An Overview
(b)(a)
30
3.5 Macroscopic Assessment
3.5.1 Key Steps
Oral and maxillofacial pathologists receive a wide range of specimens for macro- and microscopic
assessment. The macroscopic description of the specimen is documented in the final report alongside the microscopic assessment. Here, we will briefly discuss the main types of specimens received
and the general approach to the macroscopic assessment of such specimens.
Biopsies: Biopsy specimens are usually small and include incisional and excisional specimens.
Biopsy specimens are not usually orientated, and larger excisional biopsy specimens are usually
taken for benign reactive lesions, such as fibroepithelial polyps or mucous extravasation cysts.
Thus, orientation is not required. The specimen should be measured in three dimensions with a
description regarding the qualities of the mucosa, such as the colour, shape, texture and any
other discernible features (i.e. ulceration, pigmentation, etc.) documented. Small specimens are
usually left untrimmed and are embedded whole. However, more generous elliptical biopsy
specimens (i.e. with a width greater than 5 mm) or excisional biopsy specimens can be bisected
before being embedded.
Resection Specimens: Resection specimens for malignant tumours require additional information to be
recorded at dissection to ensure all clinically relevant information is recorded and, thus, accurate
tumour staging can be achieved. Often, excision specimens arrive with orientation sutures or tags
placed by the surgeon (Figures3.1 and3.2). This is important to document and allows the specimen
to be measured accurately in three dimensions. Orientation of resection specimens is paramount as
clinicians need to know whether the tumour has been completely excised if residual tumour
remains, and if so, where it is located. After the entire specimen has been measured, a macroscopic
description including the location (e.g. lateral border of the tongue, left alveolar ridge in the premolar region), appearance (e.g. exophytic mass, irregular area of ulceration), and the maximum diameter of the malignant tumour should be documented. The distance of the tumour to the closest
surgical margin should also be recorded. The peripheral margins of the specimen are then painted
Figure3.1 Left hemiglossectomy; (a) Superficial view, (b) Deep view. The suture placed by the surgeon
indicates the anterior aspect of the specimen. An exophytic mass is identified on the lateral border of the
tongue. In this example, the superior margin (dorsal surface) could be inked one colour, and the inferior
margin (ventral surface) could be inked another colour to allow the margins to be easily differentiated if
sectioning the specimen from anterior to posterior. The ink should cover the mucosal margins and extend
to the deep soft tissue margin.
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(a) (b)
Figure3.2 Right partial maxillectomy; (a) inferior view, (b) superior view. When a specimen contains
identifiable anatomical structures (i.e. teeth), orientation sutures are not always required. An area of
ulceration is identified on the palatal mucosa adjacent to the upper right first molar tooth (UR6). When a
specimen includes teeth, the macroscopic description should also document the teeth present with a
summary of their restorative status and the presence of mobility.
31
with coloured inks to allow pathologists to differentiate specific surgical margins (e.g. buccal margin inked blue, lingual margin inked orange) and to easily identify the accurate surgical margins
under the microscope. The specimen is then sectioned to allow visualisation of the whole tumour.
Sections of the specimen should then be selected for microscopic assessment. The chosen sections
should allow for adequate assessment of the tumour so that the main characteristics and findings
relevant to patient prognosis, such as proximity of the tumour to the surgical margins, maximum
depth of invasion of the tumour, tumour differentiation and pattern of invasion, can be recorded
and discussed in the microscopic report.
This is a brief overview of some of the fundamentals of macroscopic assessment. A more detailed
discussion is beyond the scope of this book. However, further clear guidance is available from The
Royal College of Pathologists under their published guidelines for Cancer Datasets and Tissue
Pathways(3) and the International Collaboration on Cancer Reporting Datasets(4). The sampling
approach may also vary according to tumour type (i.e. sarcoma, bone tumours) or site of origin (i.e.
skin, nasal cavity, etc.), and thus, the relevant datasets and TNM staging should be adopted where
appropriate(5).
3.6 Photographs andRadiographs
Photographs and radiographs can help assess some specimens, particularly those that may be unusual, more complex or difficult to visualise from a macroscopic description alone (Figure 3.3).
Resections for head and neck cancers can be extensive, involving various structures and therefore have multiple surgical margins requiring sampling. In these situations, one can take colour
photographs of the specimen from several different angles, which provides a record of the intact
specimen to aid the orientation of the specimen in subsequent reporting. In challenging cases,
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