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Data Set for the Reporting of Malignant Odontogenic Tumors: Explanations and Recommendations of the Guidelines From the International Collaboration on Cancer Reporting.

As a starting point, an international panel of pathologists with particular experience in the diagnosis and management of malignant odontogenic tumors discussed all issues considered significant in formulating a data set for reporting these neoplasms. The panel was organized under the auspices of the International Collaboration on Cancer Reporting (ICCR), established in 2011 through a collaboration between the College of American Pathologists, the Canadian Association of Pathologists-Association Canadienne des Pathologistes in association with the Canadian Partnership Against Cancer, the Royal Colleges of Pathologists of Australasia and the United Kingdom, joined in 2013 by the European Society of Pathologists, and followed by the American Society of Clinical Pathology and the Royal College of Physicians of Ireland, Faculty of Pathology as sustaining members. The members of the data set authoring committee were nominated from the additional sponsoring organizations: North American Society of Head and Neck Pathology; American Academy of Oral and Maxillofacial Pathology; the British Society for Oral and Maxillofacial Pathology; and the International Association of Oral and Maxillofacial Pathologists. Working via multiple teleconferences and reviewing a series of drafts that included many comments and clarifications, the final data set contained core and noncore elements. (30) A core element (as defined by the ICCR) represents an essential piece of information for the management of the tumor, whereas a noncore element constitutes an element that provides additional useful, but not critical, information about the neoplasm. In some cases, an element was designated noncore because the value was not yet established but may be elevated to the status of a core element in the future. Sometimes, elements can be both. Because this group of tumors is rare, with only limited prognostic data, selection of core and noncore elements was principally based on basic oncologic principles applicable to most malignant tumors and not necessarily on data specifically derived from studies of large prospective cohorts of malignant odontogenic tumors. In this way, the policy of the ICCR was implemented, namely, that generic descriptors that apply to all cancer types should be included in data sets irrespective of the level of evidence in the literature to support their inclusion. Hopefully, in due time, higher levels of evidence may be achieved. Currently, the level of evidence is mainly based on small case series and "expert opinion."


Core (Required) Elements

Specimens Submitted.--As for all pathology specimens, the kind of specimen should be listed, including debulking or curettage, excisional or incisional biopsy, and surgical resection. Not specified is used only in rare instances and is to be discouraged. Instead, there should be active personal communication with the treating physicians to obtain the required information. In case of a resection, appropriate and concise terms to be used would be mandibulectomy or maxillectomy with a prefix indicating the extent (hemi-, partial, or total). In case of a neck dissection submitted together with a tumor specimen, a separate, linked data set for Nodal Excisions and Neck Dissection Specimens for Head & Neck Tumours (31) would be used to describe the neck lymph node findings.

Tumor Site.--The tumor site belongs to standard items listed in agreement with general rules regarding pathology reports, irrespective of the kind of lesion. Giving the exact anatomic site of involvement is most helpful, a finding that may require correlation with clinical and imaging findings.

Tumor Dimensions (Core and Noncore).--Owing to the intraosseous nature of odontogenic lesions, reference to any imaging studies or consultation with a radiologist is recommended in order to achieve the best interpretation of maximum tumor dimension, combining macroscopy, specimen or clinical radiology, and microscopy. Size criteria for possible staging have been suggested. (1) Using data from the National Cancer Institute's SEER (Surveillance, Epidemiology, and End Results) database for the period 1973-2011, Agarwal et al (2) and Lee et al (3) showed that size was an independent prognostic indicator with smaller tumor size significantly associated with a better overall survival. Patients with tumors greater than 41 mm were twice as likely to die of disease as patients with smaller lesions. (2) The rationale for using both core and noncore is the need to use both pathologic and imaging data to determine the lesion's dimensions, with the latter potentially not easily available to the prosecting pathologist.

Histologic Tumor Type.--The gnathic bones give rise to a variety of neoplasms, including odontogenic and bone/ cartilage forming tumors; however, this data set is designed to report only the malignant odontogenic tumors (carcinomas as well as sarcoma) as classified according to the most recent edition of the World Health Organization's (WHO) Classification of Head and Neck Tumours (4) (Table). Bone and cartilage forming tumors are classified using a different data set.

Histologic Tumor Grade.--For primary intraosseous squamous carcinoma, the conventional squamous cell carcinoma grade is used. (5,6) Although other malignant odontogenic tumors are generally not graded, the pathologist can still comment on the extent of tissue changes (for these non-squamous cell carcinoma tumors, histologic tumor grade is a noncore item). This especially applies to ameloblastic carcinoma, where there may be varying degrees of cytologic atypia (Figure 1).

Necrosis.--Tumor necrosis is not only a tool to aid in tumor grading, but also the presence of necrosis often helps to confirm a diagnosis of malignancy in odontogenic tumors in general (Figure 2). Thus, while large clinical series of these rare tumors are not available, there is strong support that reporting tumor necrosis aids in diagnosis, grade, and tumor classification. (7,8)

Perineural Invasion.--Perineural invasion is included as a generic descriptor that is considered to be relevant for all types of malignant tumors (Figure 3). Note, however, that the extensive perineural spread seen in sclerosing odontogenic carcinoma does not appear to be a poor prognostic feature (Figures 4 and 5, A and B). (9-11)

Lymphovascular Invasion.--Lymphovascular invasion is generally a feature seen in malignancy, and thus, it is included here, although data specific to malignant odontogenic tumors are not yet reported (Figure 6).

Margin Status.--Margin status is considered a key prognostic factor. Clear margins are commonly achieved only with a thin layer of normal tissue between the tumor and the resection margin. It is therefore of crucial importance to assess whether the excision has an adequate margin around the entire lesion, since if there is focal margin positivity, reoperation may be necessary.

The prognosis is worse when an incomplete excision is located at the infratemporal fossa and/or base of skull and thus, reporting the specific anatomic site of involved margins must be clearly specified (Figure 7).

Noncore (Recommended) Elements

Extent of Invasion.--Extent of invasion is best assessed by a combination of radiographic, macroscopic, and microscopic features (Figure 8). Use of a diagram (Figure 9) is strongly recommended, as the pertinent anatomic landmarks can be easily identified and assessed in the embedding and sectioning protocol.

Ancillary Studies.--There are several immunohistochemical and molecular studies that may be clinically relevant, (12) with some to have potential but unproven therapeutic benefit. Examples include EWSR1 rearrangements in clear cell odontogenic carcinoma and BRAF V600E point mutation in ameloblastic carcinoma. (13,14) Such tests may also increase diagnostic certainty. Thus, if any of these tests are performed, they should be recorded.


This data set is based almost exclusively on professional judgement owing to the lack of high-quality evidence to support individual data items. Malignant odontogenic tumors are rare and published series are often not homogeneous by tumor type, classification, stage, or treatment, making conclusions about the value of individual items difficult. In general, the tumors that show aggressive histologic features are more likely to be associated with poor survival, but this tumor group is characterized by unpredictable behavior; low-grade tumors may recur or metastasize many years after excision. For all types, large size, local recurrence, and metastasis are poor prognostic features (2,3,15,16) and outcomes are relatively poor after local recurrence. (17-19) Published mortality rates are generally limited by short follow-up. Ameloblastic carcinomas appear to carry a better prognosis than other tumor types for reasons that are still unclear, (2) although maxillary tumors behave worse than mandibular neoplasms, (20) with up to one-third of maxillary tumors yielding lung metastases. Odontogenic sarcomas are overall of low grade and tend to locally recur rather than to metastasize, but are still associated with significant mortality rates (21-23) owing to local involvement of vital structures.

There are no validated grading systems for odontogenic tumors, although primary intraosseous squamous cell carcinomas are graded by conventional squamous cell carcinoma grading schemes, ostensibly showing some value. (5,6) Tumor necrosis is included as a histologic core feature but is also considered useful in confirming a diagnosis of malignancy in general. Perineural invasion is an included element, although it must be emphasized that in sclerosing odontogenic carcinoma, despite extensive perineural spread, this carcinoma nevertheless carries a relatively good prognosis. (9,10,11)

Margin status after surgical excision is thought to be the key prognostic feature (15,24-27) and the best evidence relates to ameloblastic carcinoma, (2,28) primary intraosseous carcinoma, (5,17) and clear cell carcinoma. (24) Surgical margin clearances may be very small or inadequate and extension into soft tissues beyond the periosteum is usually associated with a significant risk of local recurrence. The prognosis is worse when incomplete excision is seen at the infratemporal fossa and/or base of skull and therefore the anatomic site of involved margins must be clearly specified and marked on a diagram (Figure 9) during macroscopic and microscopic examination.

Tumor dimensions (size) and site are also important prognostic features. Further, carcinomas arising in or limited to cysts carry a better prognosis than those with widespread infiltration. (29)

The role for adjuvant or salvage radiotherapy remains to be defined. The literature does not provide useful information on specific radiotherapy indications or the intent when it has been used. Despite its use to locally control incompletely excised malignant odontogenic tumors, its value appears limited, (24,25) although it has been supported in some large series (2) and is usually considered most effective as part of a multimodality treatment approach. This is true particularly for maxillary lesions in which vital structures may prevent surgical management.

Ancillary studies still play a relatively limited role (12-14); they are sometimes helpful in diagnosis, while molecular findings may help to guide targeted therapeutic options. However, availability and cost constraints limit widespread adoption, especially in developing nations.

Finally, while ameloblastomas are benign, they often require an oncologic (surgical) approach to management, and thus, the panel recommends discussion of ameloblastomas at a multidisciplinary team meeting (tumor board) to ensure optimal management. Furthermore, this tumor would also benefit from a standardized reporting data set. While this data set was prepared for malignancies, the panel also strongly advocates its use for ameloblastoma.

Accepted for publication October 1, 2018.

Published online November 30, 2018.

The authors would like to express their appreciation to the sponsoring societies and organizations and give special thanks to Fleur Webster and Hannah B. Canlas for their exceptional organizational and editing contributions. The views expressed are those of the authors solely.


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Pieter J. Slootweg, MD, DMD, PhD; Edward W. Odell, DDS, FRCPath; Daniel Baumhoer, MD; Roman Carlos, DDS; Keith D. Hunter, BSc (Hons), BDS, FDS RCSEd, PhD, FRCPath, FHEA; Adalberto Mosqueda Taylor, DDS, MSc; Mary S. Richardson, MD, DDS; Lee Slater, DDS, MS; Paul M. Speight, BDS, FDSRCPS, FDSRCS, PhD, FRCPath; John Wright, DDS, MS; Lester D. R. Thompson, MD

From the Department of Pathology, Radboud University Medical Center, Nijmegen, the Netherlands (Dr Slootweg); Head and Neck Pathology, King's College London, United Kingdom (Dr Odell); Institute of Pathology, University Hospital Basel, Basel, Switzerland (Dr Baumhoer); Centro Clinico de Cabeza y Cuello, Pathology Division, Guatemala City, Guatemala (Dr Carlos); Oral and Maxillofacial Medicine, Surgery and Pathology (Dr Hunter) and the Department of Oral Pathology (Dr Speight), University of Sheffield, Sheffield, United Kingdom; Health Care Department, Universidad Autonoma Metropolitana Xochimilco, Mexico City, Mexico (Dr Mosqueda Taylor); the Department of Pathology & Laboratory Medicine, Medical University of South Carolina, Charleston (Dr Richardson); Scripps Oral Pathology Service, San Diego, California (Dr Slater); the Department of Diagnostic Sciences, Texas A&M College of Dentistry, Dallas (Dr Wright); and the Department of Pathology, Southern California Permanente Medical Group, Woodland Hills (Dr Thompson).

The authors have no relevant financial interest in the products or companies described in this article.

Corresponding author: Lester D. R. Thompson, MD, Department of Pathology, Southern California Permanente Medical Group, Woodland Hills Medical Center, 5601 De Soto Avenue, Woodland Hills, CA 91365 (email:

Caption: Figure 1. Ameloblastic carcinoma showing the pattern of ameloblastoma but also cytonuclear atypia, which allows for the distinction between the entities (hematoxylin-eosin, original magnification X400).

Caption: Figure 2. Area of necrosis in spindle cell-type ameloblastic carcinoma (hematoxylin-eosin, original magnification X150).

Caption: Figure 3. Histology of sclerosing odontogenic carcinoma: inconspicuous epithelial strands in a fibrocellular background (hematoxylin-eosin, original magnification X400).

Caption: Figure 4. Ameloblastic carcinoma showing perineural invasion of the inferior alveolar nerve (a named nerve) (hematoxylin-eosin, original magnification X40).

Caption: Figure 5. Perineural growth is a typical feature of sclerosing odontogenic carcinoma (A), highlighted by an S100 protein study (B) (hematoxylineosin, original magnification X600 [A]; original magnification X600 [B]).

Caption: Figure 6. Vascular invasion in ameloblastic carcinoma can be highlighted by a CD31 immunohistochemistry study, with tumor filling the endothelial lined space (original magnification X400).

Caption: Figure 7. A positive margin in ghost cell odontogenic carcinoma (hematoxylin-eosin, original magnification X100).

Caption: Figure 8. Cross appearance of clear cell odontogenic carcinoma. Note tumor spread beyond the cortical border of the mandible into the adjacent soft tissues.

Caption: Figure 9. A diagram depicting anatomic sites, useful in determining the extent of tumor involvement. Reproduced with permission from International Collaboration on Cancer Reporting (ICCR).
World Health Organization Classification
of Malignant Odontogenic Tumors

Descriptor                             ICD-O Codes (a)

Ameloblastic carcinoma                      9270/3
Primary intraosseous carcinoma, NOS         9270/3
Sclerosing odontogenic carcinoma            9270/3
Clear cell odontogenic carcinoma            9341/3
Ghost cell odontogenic carcinoma            9302/3
Odontogenic carcinosarcoma                  8980/3
Odontogenic sarcomas                        9330/3

Abbreviation: NOS, not otherwise specified.

(a) The morphology codes are from the International Classification of
Diseases for Oncology (ICD-O). Behavior is coded /0 for benign
tumors; /1 for unspecified, borderline, or uncertain behavior; /2 for
carcinoma in situ and grade III intraepithelial neoplasia;and /3 for
malignant tumors.

Reproduced with permission from World Health Organization (WHO)/
International Agency for Research on Cancer (IARC). (4)
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No portion of this article can be reproduced without the express written permission from the copyright holder.
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Author:Slootweg, Pieter J.; Odell, Edward W.; Baumhoer, Daniel; Carlos, Roman; Hunter, Keith D.; Taylor, Ad
Publication:Archives of Pathology & Laboratory Medicine
Article Type:Report
Date:May 1, 2019
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