Carcinomas Of The Oral Cavity Histopathology Reporting Guide
Sponsored byCarcinomas of the Oral CavityAmerican Academy of Oral& Maxillofacial PathologyHistopathology Reporting GuideFamily/Last nameDate of birthDD – MM – YYYYGiven name(s)Patient identifiersDate of requestAccession/Laboratory numberDD – MM – YYYYElements in black text are CORE. Elements in grey text are NON-CORE.NEOADJUVANT THERAPY (Note 1)SCOPE OF THIS DATASETSPECIMENS SUBMITTED (select all that apply) (Note 3)Information not providedNot specifiedBuccal mucosaNot administeredLipBuccal vestibuleAdministered, specify typeChemotherapyTongueRetromolar trigoneGingivaAlveolar processRadiotherapyFloor of mouthMandibleTargeted therapy, specify if availableHard palateMaxillaOther, specifyImmunotherapy, specify if availableTUMOUR SITE (select all that apply) (Note 3)Not specifiedLipVermilion border upper lipOPERATIVE PROCEDURE (select all that apply) (Note 2)Not specifiedBiopsy (excisional, incisional), specifyLeftLeftMidlineMucosa of upper lipResection, specifyGlossectomy, specifyLeftMidlineMucosa of lower lipBuccal mucosa, specifyRightLaterality not specifiedRightLaterality not specifiedLeftRightMidlineLaterality not specifiedCommissure of lipLeftLip, specifyRightMidlineLaterality not specifiedVermilion border lower lipRightLaterality not specifiedOral cavityLateral border of tongueMandibulectomy, specifyLeftRightLaterality not specifiedVentral surface of tongue, not otherwise specified (NOS)Maxillectomy, specifyLeftRightMidlineLaterality not specifiedDorsal surface of tongue, NOSLeftRightPalatectomy, specifyMidlineNeck (lymph node) dissection*, specifyAnterior two-thirds of tongue, NOSLeftRightMidlineMidlineIf a neck dissection is submitted, then a separatedataset is used to record the information.Version 1.0 Published September 2018Laterality not specifiedUpper gingiva (gum)LeftRightOther, specify*Laterality not specifiedLaterality not specifiedLower gingiva (gum)LeftRightMidlineISBN: 978-1-925687-19-4International Collaboration on Cancer Reporting (ICCR)Laterality not specifiedPage 1 of 4
TUMOUR DIMENSIONS (select all that apply) (Note 5)Anterior floor of mouthLeftRightMidlineLaterality not specifiedFloor of mouth, NOSLeftLaterality not specifiedRightMidlineLaterality not specifiedBuccal mucosa (inner cheek)RightLaterality not specifiedRightLaterality not specifiedRetromolar trigoneLeftVestibule of mouthMaxillaryLeftRightMidlineLaterality not specifiedMandibularLeftMidlineAlveolar processMaxillaryxmmMaximum depth of invasion(to reconstructed basement membrane)mmHISTOLOGICAL TUMOUR TYPE (select all that apply) (Note 6)(Value list from the World Health Organization Classificationof Head and Neck Tumours (2017))Squamous cell carcinomaSquamous cell carcinoma, conventional typeRightBasaloid squamous cell carcinomaLaterality not specifiedPapillary squamous cell carcinomaVerrucous carcinomaLeftRightMidlineLaterality not specifiedMandibularMandibleAdditional dimensions (largest tumour)mmLeftLeftMaximum tumour dimension (largest tumour)mmRightMidlineHard palateCannot be determined/surgical resection margins involvedLeftRightMidlineLaterality not specifiedLeftRightMidlineLaterality not specifiedMaxillaLeftRightMidlineLaterality not specifiedSpindle (sarcomatoid) squamous cell carcinomaAdenosquamous cell carcinomaAcantholytic squamous cell carcinomaCarcinoma cuniculatumLymphoepithelial squamous cell carcinomaOther, specifyMinor salivary gland tumour, specify typeNeuroendocrine carcinoma, specify typeOther, specify including lateralityOther, specify typeCannot be assessed, specifyTUMOUR FOCALITY (Note 4)UnifocalBilateralMultifocal, specify number of tumours in specimenHISTOLOGICAL TUMOUR GRADE (Note 7)(Required for conventional squamous cell carcinoma only)Not applicableCannot be assessed, specifyGX: Cannot be assessedG1: Well differentiatedG2: Moderately differentiatedG3: Poorly differentiatedCannot be assessed, specifyDEPTH OF INVASION (Note 8)(Resection specimens and excisional biopsies only, notapplicable to incisional biopsies) 5 mm depth of invasion 5 mm and 10 mm depth of invasion 10 mm depth of invasionCannot be assessed, specifyVersion 1.0 Published September 2018ISBN: 978-1-925687-19-4International Collaboration on Cancer Reporting (ICCR)Page 2 of 4
Carcinoma in situ/moderate to severe dysplasiaPATTERN OF INVASIVE FRONT (Note 9)(Resection specimens and excisional biopsies only, notapplicable to incisional biopsies)InvolvedSpecify margin(s), if possibleCohesiveNon-cohesiveWidely dispersedNot involvedRESPONSE TO NEOADJUVANT THERAPY (Note 10)Distance of tumour from closest marginNo prior treatmentmmDistance not assessableIncomplete responseComplete responseSpecify closest margin, if possibleResponse cannot be assessed, explain reasonsCannot be assessed, specifyBONE INVASION (Note 11)Not identifiedCOEXISTENT PATHOLOGY (select all that apply) (Note 15)PresentNone identifiedErosive (cortical)Proliferative verrucous leukoplakiaInfiltrative (medullary involvement)Fungal infectionDysplasia, specify gradeCannot be assessed, specifyHPV positive dysplasiaSubmucous fibrosisInflammationPERINEURAL INVASION (Note 12)Not identifiedOther, specifyPresentNerve size, if knownmmCannot be assessed, specifyANCILLARY STUDIES (Note 16)Not performedPerformed, specifyLYMPHOVASCULAR INVASION (Note 13)Not identifiedPresentCannot be assessed, specifyMARGIN STATUS (Note 14)Invasive carcinomaInvolvedSpecify margin(s), if possibleNot involvedDistance of tumour from closest marginmmDistance not assessableSpecify closest margin, if possibleVersion 1.0 Published September 2018ISBN: 978-1-925687-19-4International Collaboration on Cancer Reporting (ICCR)Page 3 of 4
PATHOLOGICAL STAGING (UICC TNM 8th edition)## (Note 17)TNM Descriptors (only if applicable) (select all that apply)m - multiple primary tumoursr - recurrenty - post-therapyPrimary tumour (pT)**TXPrimary tumour cannot be assessedTisCarcinoma in situT1Tumour 2 cm or less in greatest dimension and 5 mmor less depth of invasion***T2Tumour 2 cm or less in greatest dimension and morethan 5 mm depth of invasion or, tumour more than2 cm but not more than 4 cm in greatest dimensionand depth of invasion no more than 10 mmT3Tumour more than 2 cm but not more than 4 cmin greatest dimension and depth of invasion morethan 10 mm or tumour more than 4 cm in greatestdimension and not more than 10 mm depth ofinvasionT4a (Lip) Tumour invades through cortical bone, inferioralveolar nerve, floor or mouth, or skin (of the chin orthe nose)T4a (Oral cavity) Tumour more than 4 cm in greatestdimension and more than 10 mm depth of invasionor tumour invades through the cortical bone of themandible or maxilla or involves the maxillary sinus,or invades the skin of the faceT4b (Lip and oral cavity) Tumour invades masticatorspace, pterygoid plates, or skull base, or encasesinternal carotid artery**Note that the results of lymph node/neck dissectionare derived from a separate dataset.***Superficial erosion alone of bone/tooth socket bygingival primary is not sufficient to classify a tumouras T4a.##Reproduced with permission. Source: UICC TNM Classification ofMalignant Tumours, 8th Edition, eds James D. Brierley, Mary K.Gospodarowicz, Christian Wittekind. 2017, Publisher Wiley-Blackwell.Version 1.0 Published September 2018ISBN: 978-1-925687-19-4International Collaboration on Cancer Reporting (ICCR)Page 4 of 4
ScopeThe dataset has been developed for the reporting of resection and biopsy specimens of invasivecarcinomas of the oral cavity, including lip and tongue. Mucosal melanoma, lymphomas andsarcomas are not included. In addition, neck dissections and nodal excisions are dealt with in aseparate dataset, and this dataset should be used in conjunction, where applicable.Note 1 – Neoadjuvant therapy (Non-core)Reason/Evidentiary SupportThere is no agreed upon system for grading tumour regression in oral squamous cell carcinoma thathas been treated with neoadjuvant therapy. However, a history of previous radiotherapy and/orchemotherapy should be included as histologic changes related to the therapy such as necrosis mayaffect interpretation of the tumour.BackNote 2 – Operative procedure (Core)Reason/Evidentiary SupportImportant to correlate the type of procedure (excisional biopsy or resection) with the materialreceived for patient safety. Site-specific designations are required for accurate staging and forcancer registration. Modification of the resection, e.g. partial, total should be described. Forexample: hemi-glossectomy, partial glossectomy; hemi-mandibulectomy, segmental (partial)mandibulectomy; partial maxillectomy, total maxillectomy; selective neck dissection, modified neckdissection.1,2BackNote 3 – Specimens submitted (Core) and Tumour site (Core)Reason/Evidentiary SupportThe anatomy and surgical interventions of the oral cavity are complex and it is important to ensureaccurate and precise communication between the pathologists and the treating and diagnostic teamwith respect to exact anatomic site of involvement, tumour laterality and specific operativeprocedures.3-5The protocol applies to all carcinomas arising at these sites (see Figure 1). For large cancers thatinvolve more than one site, the primary site of involvement should be recorded.1
Mucosal Lip. The lip begins at the junction of the vermilion border with the skin and includes onlythe vermilion surface or that portion of the lip that meets the opposing lip.Buccal Mucosa (Inner Cheek). Refers to the mucous membrane lining of the inner surface of thecheeks and lips of contact of the opposing lips to the line of attachment of mucosa of the upper andlower alveolar ridge and pterygomandibular raphe.Lower Alveolar Ridge. This refers to the mucosa overlying the alveolar process of the mandible,which extends from the line of attachment of mucosa in the buccal vestibule to the line of freemucosa of the floor of the mouth. Posteriorly it extends to the ascending ramus of the mandible.Upper Alveolar Ridge. This refers to the mucosa overlying the alveolar process of the maxilla, whichextends from the line of attachment of mucosa in the upper gingival buccal vestibule to the junctionof the hard palate. The posterior margin is the upper end of the pterygopalatine arch.Floor of the Mouth. This is a semilunar space over the mylohyoid and hypoglossus muscles,extending from the inner surface of the lower alveolar ridge to the undersurface of the tongue. Theposterior boundary is the base of the anterior pillar of the tonsil. It is divided into two sides of thesubmaxillary and sublingual salivary glands.Hard Palate. This is the semilunar area between the upper alveolar ridge and the mucous membranecovering the palatine process of the maxillary palatine bones. It extends from the inner surface ofthe superior alveolar ridge to the posterior edge of the palatine bone.Anterior Two-Thirds of the Tongue (Oral Tongue). This is the freely mobile portion of the tongue thatextends anteriorly from the line of circumvallate papillae to the undersurface (ventral) of the tongueat the junction of the floor of the mouth. It includes the tip of tongue, lateral borders, dorsal surfaceand ventral tongue.Retromolar trigone. A triangular shaped region extending distal from the mandibular third molar asthe base and attaches to the hamulus of the medial pterygoid process of the sphenoid bone as theapex.‘Not specified’ should be used rarely and only after good effort has been employed to obtain therequisite information.2
Figure 1. Anatomic sites and subsites for lip and oral cavityBackNote 4 – Tumour focality (Non-core)Reason/Evidentiary SupportTrue multifocal or synchronous oral cavity carcinomas are rare. Patients with oral squamous cellcarcinomas have a high incidence (2-3%) of developing a second primary lesion however these areusually metachronous lesions. The theory of field cancerization whereby contiguous geneticallyaltered areas of mucosa lead to the development of neoplasms have been supported by studiesevaluating clonality and other molecular markers. Proliferative verrucous leukoplakia has thepropensity of developing multifocal tumours. It is rare to have multiple tumours disconnected butnot uncommon to have more than one squamous cell carcinoma connected via dysplasia. Thelocation, proximity to dysplastic epithelium, depth and nodal status remain important. Tumourfocality seems to be a standard not just for staging and pathology but for clinical trials and treatmentconsiderations 6-9Back3
Note 5 – Tumour dimensions (Core)Reason/Evidentiary SupportTumour dimension is an important component in pathologic staging.10 The macroscopic diameter (inmillimetres) should be used unless the histological extent is greater than macroscopically apparent,in which case the microscopic dimension is used. At times only microscopic evaluation actuallydifferentiates what clinically (phenotypically) appears to be tumour from what is actual invasion (notdysplasia or inflammation). The maximum depth of invasion should be recorded as core and thediscussion should include how/why depth of invasion is different than tumour thickness. 11-19 As forother tissues, measurements are made pragmatically, acknowledging distortion of tissues by fixationand processing.20BackNote 6 – Histological tumour type (Core)Reason/Evidentiary SupportThe major histologic tumour types of squamous cell carcinoma as recognized by the World HealthOrganization (WHO) classification are squamous cell carcinoma, conventional type, basaloid,papillary, spindle, adenosquamous, acantholytic, lymphoepithelial, verrucous carcinoma andcarcinoma cuniculatum. Hybrid lesions such as verrucous carcinoma and squamous cell carcinomaexist and should be recognized as it may affect prognosis.21 Subtypes should be assigned for bothprognosis and cancer registry.22-24Salivary carcinoma histologic type essentially defines its biologic behaviour and thus influencesprognosis, patterns of recurrence and thus clinical management. 25,26 Some carcinoma types (i.e.basal cell adenocarcinoma, conventional acinic cell carcinoma) are more indolent with locoregionalrecurrence but low nodal and distant metastatic rates.27The major histologic salivary gland carcinomas of minor salivary glands as recognized by the WHOclassification are acinic cell carcinoma, adenoid cystic carcinoma, adenocarcinoma not otherwisespecified (NOS), (mammary analogue) secretory carcinoma, cystadenocarcinoma, epithelialmyoepithelial carcinoma, mucoepidermoid carcinoma (low, intermediate and high grade),polymorphous adenocarcinoma (low, intermediate and high grade), (hyalinizing) clear cellcarcinoma, intraductal carcinoma, carcinosarcoma, myoepithelial carcinoma, oncocytic carcinoma.Carcinoma ex pleomorphic adenoma is subclassifed by type and extent of invasion, the latterincluding minimally invasive, invasive and intracapsular (non-invasive) cancers. The definition forminimally invasive carcinomas varies, ranging from 1.5 mm to 6 mm. Invasive carcinomas extendbeyond 6 mm; non-invasive cancers are completely confined to within the capsule without evidenceof penetration into extracapsular tissue. Prior to diagnosing a non-invasive carcinoma expleomorphic adenoma, sectioning of the entire lesion for histologic evaluation is recommended toexclude the presence of invasive growth. Prognosis has been linked to degree of invasion with non-4
invasive and minimally invasive cancers apparently having a better prognosis than invasivecancers.28,29WHO classification of tumours of the oral cavity and mobile tonguea30DescriptorICD-OcodesEpithelial tumours and lesionsSquamous cell carcinomaOral epithelial dysplasiaLow gradeHigh grade8070/38077/08077/2a The morphology codes are from the International Classification of Diseases for Oncology (ICD-O). Behaviouris coded /0 for benign tumours; /1 for unspecified, borderline, or uncertain behaviour; /2 for carcinoma in situand grade III intraepithelial neoplasia; and /3 for malignant tumours WHO/International Agency for Research on Cancer (IARC). Reproduced with permissionBackNote 7 – Histological tumour grade (Core)Reason/Evidentiary SupportBased on the WHO classifications, three histologic grades of squamous cell carcinoma, conventionaltype are used: well, moderately or poorly differentiated.30 The most aggressive or highest gradeshould be recorded if the tumour has a varied histology. Grading requires the assessment ofkeratinization, mitotic activity, cellular and nuclear pleomorphism, pattern of invasion and hostresponse.1,31-34 Squamous cell carcinoma subtypes such as verrucous carcinoma, basaloid squamouscell carcinoma, papillary squamous cell carcinoma are not graded.Grading of minor salivary gland tumours follows the criteria for major salivary gland tumours. 27,28BackNote 8 – Depth of invasion (Core)Reason/Evidentiary SupportDepth of invasion (DOI) in oral cavity squamous cell carcinoma, particularly of the tongue, has beenidentified as an important prognostic indicator. DOI is not synonymous with tumour thickness. In therecent American Joint Committee on Cancer (AJCC) the tumour stage (T) has been changed to reflectthe importance of DOI.10 DOI increases T by 1 step for every 5 mm, whereby T1 is tumour 2 cm andDOI 5 mm, T2 is tumour 2 cm and DOI 5 mm and 10 mm or tumour 2 cm but 4 cm and 105
mm DOI and T3 is tumour 4 cm or any tumour 10 mm DOI. The Union for International CancerControl (UICC) staging system is similar to the AJCC with one exception: if the tumour is 4 cm AND 10 mm DOI then the stage is T4a.35 DOI measures the invasiveness of the carcinoma. To measureDOI, the basement membrane is identified and an imaginary line is drawn across the tumour. Avertical or “plumb line” extends to the deepest part of the tumour which represents the DOI. It isimportant to note that DOI is not synonymous with tumour thickness. An exophytic tumour (Figure2A) may be thicker than an ulcerative tumour (Figure 2B), but the DOI of the ulcerative lesion maybe greater.36-39Figure 2A. Measuring depth of InvasionFigure 2B. Measuring depth of Invasion6
Note 9 – Pattern of Invasive front (Core)Reason/Evidentiary SupportThe pattern of invasion in oral squamous cell carcinoma has proven prognostic value and should bereported as cohesive or non-cohesive (Figure 3). It is important to evaluate the most complex areaof tumour-stroma interface (“worst” area) and ideally assessment should only be made on resectionspecimens or excisional biopsies. Acknowledgement is made that at times non-surgical treatmentdecisions are made on incisional biopsy only specimens and consequently the best assessment ofpattern of invasion should be noted. Cohesive invasion is defined as broad sheets of cancer cellsand/or tumour nests 15 cells across. Non-cohesive invasion shows a spectrum of appearances thatincludes narrow strands, small groups of 15 tumour cells and single infiltrating tumour cells.36-39 Forstage T1/T2 oral squamous cell carcinoma, particularly those arising in the tongue there is evidencethat tumour satellites localized 1 mm away from the main tumour or nearest satellite (worstpattern of invasion WPOI-5) is a valid adverse prognostic factor.38,40Figure 3. Pattern of Invasive frontBackNote 10 – Response to neoadjuvant therapy (Non-core)Reason/Evidentiary SupportThere is no agreed system for grading tumour regression in oral squamous cell carcinoma that hasbeen treated with neoadjuvant therapy. Specific pathologic changes in response to neoadjuvantchemotherapy, although well described in other organ systems is lacking in oral cavity cancer. Thesechanges include necrosis, fibrosis, cytologic atypia and inflammation. As the field of neoadjuvant7
therapy for oral cavity cancer evolves histologic changes important for treating clinicians may bebetter elucidated.BackNote 11 – Bone invasion (Core)Reason/Evidentiary SupportInfiltrative bone involvement by squamous cell carcinoma correlates with a worse prognosis. Boneinvasion may be a
T4a (Oral cavity) Tumour more than 4 cm in greatest dimension and more than 10 mm depth of invasion or tumour invades through the cortical bone of the mandible or maxilla or involves the maxillary sinus, or invades the skin of the face T4b (Lip and oral cavity) Tumour invades mast
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