```markdown THE UNIVERSITY OF WESTERN AUSTRALIA Special Topic: Potentially premalignant oral epithelial lesions (PPOEL) Vol. 125 No. 6 June 2018 # Oral potentially malignant disorders: risk of progression to malignancy Paul M. Speight, BDS, PhD, FDSRCPs, FDSRCS (Eng), FRCPath, ᵃ Syed Ali Khurram, BDS, MSc, PhD, MFDSRCS, FDSRCS, FRCPath, ᵃ and Omar Kujan, DDS, DipOPath, MSc, PhD ᵇ Oral potentially malignant disorders (OPMDs) have a statistically increased risk of progressing to cancer, but the risk varies according to a range of patient- or lesion-related factors. It is difficult to predict the risk of progression in any individual patient, and the clinician must make a judgment based on assessment of each case. The most commonly encountered OPMD is leukoplakia, but others, including lichen planus, oral submucous fibrosis, and erythroplakia, may also be seen. Factors associated with an increased risk of malignant transformation include sex; site and type of lesion; habits, such as smoking and alcohol consumption; and the presence of epithelial dysplasia on histologic examination. In this review, we attempt to identify important risk factors and present a simple algorithm that can be used as a guide for risk assessment at each stage of the clinical evaluation of a patient. (Oral Surg Oral Med Oral Pathol Oral Radiol 2018;125:612–627) ``` Oral potentially malignant disorders (OPMDs) represent a group of conditions characterized by a statistically increased risk of progressing to cancer. However, this risk is not uniform and varies significantly based on a range of patient-specific and lesion-related factors. Predicting the exact risk of progression for an individual patient remains a clinical challenge, requiring a comprehensive judgment based on the assessment of each unique case. #### Common Clinical Presentations The most frequently encountered OPMD is leukoplakia. Other conditions that may be observed in clinical practice include: - Lichen planus - Oral submucous fibrosis - Erythroplakia #### Factors Influencing Malignant Transformation Several key factors are associated with an increased likelihood of a lesion progressing to malignancy: - **Patient Demographics:** Factors such as sex. - **Lesion Characteristics:** The specific site and clinical type of the lesion. - **Lifestyle Habits:** Behaviors including smoking and alcohol consumption. - **Histologic Findings:** The presence and severity of epithelial dysplasia upon microscopic examination. #### Risk Assessment and Clinical Evaluation Identifying important risk factors is essential for effective patient management. A structured approach, such as a clinical algorithm, can serve as a guide for risk assessment at every stage of a patient's evaluation to better determine the prognosis and necessary interventions. ```mermaid graph TD %% Node Definitions Start([Suspicious oral lesion]) %% History Section subgraph History Male[Male] Female[Female] Age[Age >50] NonSmoker[Non-smoker] PersistentSmoker[Persistent smoker] Location[Tongue or floor of mouth] end %% Examination Section subgraph Examination Leukoplakia[Leukoplakia] Erythroplakia[Erythroplakia] Homogenous[Homogenous] NonHomogenous[Non-homogenous] White[White] Verrucous[Verrucous] Speckled[Speckled] PVL[Multiple, Persistent or recurrent - PVL] end %% Biopsy Section subgraph Biopsy Histology[Histology] Mild[Mild epithelia dysplasia] Moderate[Moderate epithelia dysplasia] Severe[Severe epithelia dysplasia] LowRisk[Low risk] HighRisk[High risk] end %% Connections Start --> History Start --> Leukoplakia Start --> Erythroplakia Leukoplakia --> Homogenous Leukoplakia --> NonHomogenous Homogenous --> White NonHomogenous --> Verrucous NonHomogenous --> Speckled Verrucous --> PVL %% Connections to Histology PVL --> Histology Erythroplakia --> Histology Speckled --> Histology Histology --> Mild Histology --> Moderate Histology --> Severe Mild --> LowRisk Moderate --> LowRisk Moderate --> HighRisk Severe --> HighRisk %% Styles style Start fill:#fff,stroke:#000,stroke-width:2px style Male fill:#8fbc8f style Leukoplakia fill:#8fbc8f style Homogenous fill:#8fbc8f style White fill:#8fbc8f style Mild fill:#8fbc8f style Age fill:#f4a460 style PersistentSmoker fill:#f4a460 style Verrucous fill:#f4a460 style Moderate fill:#f4a460 style LowRisk fill:#f4a460 style Female fill:#f08080,stroke:#f00 style NonSmoker fill:#f08080,stroke:#f00 style Location fill:#f08080,stroke:#f00 style Erythroplakia fill:#f08080,stroke:#f00 style NonHomogenous fill:#f08080,stroke:#f00 style Speckled fill:#f08080,stroke:#f00 style PVL fill:#f08080,stroke:#f00 style Severe fill:#f08080,stroke:#f00 style HighRisk fill:#f08080,stroke:#f00 ```  The clinical assessment of a suspicious oral lesion involves a multi-factorial approach considering patient history, clinical examination, and histological findings to determine the risk of malignancy. #### Patient History and Risk Factors Certain demographic and behavioral factors influence the risk profile of an oral lesion: - **Demographics:** Age >50, Male, or Female (noting specific risk variations). - **Habits:** Persistent smokers vs. non-smokers. - **Anatomical Site:** High-risk locations include the tongue or floor of the mouth. #### Clinical Examination and Morphology Lesions are categorized based on their appearance and clinical behavior: - **Erythroplakia:** Red patches (high risk). - **Leukoplakia:** White patches, further divided into: - **Homogenous:** Uniformly white appearance. - **Non-homogenous:** Higher risk presentations including: - Verrucous (wart-like) - Speckled (mixed red and white) - **Proliferative Verrucous Leukoplakia (PVL):** Characterized by multiple, persistent, or recurrent lesions; associated with high risk. #### Biopsy and Histological Grading Histology is used to grade epithelial dysplasia and determine the overall risk level: - **Mild Epithelial Dysplasia:** Generally categorized as low risk. - **Moderate Epithelial Dysplasia:** May be categorized as low or high risk depending on clinical context. - **Severe Epithelial Dysplasia:** Categorized as high risk. A flowchart diagram illustrating a clinical algorithm for assessing the risk of oral potentially malignant disorders (OPMDs). The diagram begins with a 'Suspicious oral lesion' and branches into three main sections: History, Examination, and Biopsy. Each section contains specific features and risk levels, color-coded as green (low risk), amber (medium risk), and red (high risk). The final outcomes are categorized as low risk or high risk based on histological findings. ```markdown # Idiopathic white patches clinically these are “leukoplakia” - keratosis with or without dysplasia - Presentation: homogeneous, nodular, verrucous, speckled - Site: sublingual keratosis - Presumed aetiology: Smokers’, actinic keratoses - Proliferative verrucous leukoplakia - squamous cell carcinoma ```  Idiopathic white patches are clinically referred to as "leukoplakia." These lesions may represent a range of histological changes from simple keratosis to malignancy. #### Keratosis and Dysplasia - **Clinical Presentations:** - Homogeneous - Nodular - Verrucous - Speckled - **Specific Variants and Sites:** - Sublingual keratosis - Proliferative verrucous leukoplakia - **Presumed Aetiology:** - Smokers' keratosis - Actinic keratoses #### Malignancy - **Squamous cell carcinoma:** Idiopathic white patches may also present as or progress to invasive squamous cell carcinoma. The University of Western Australia logo, featuring a blue shield with a white swan and the text "THE UNIVERSITY OF WESTERN AUSTRALIA" in blue and black.  A close-up photograph of the oral cavity showing sublingual keratosis, characterized by a white, thickened lesion on the floor of the mouth near the tongue. The image also displays teeth and surrounding oral tissues, with a red dot highlighting the specific area of interest.  A close-up medical photograph showing a tissue sample with a speckled and nodular appearance, identified as leukoplakia. The image displays a reddish-pink mucosal surface with white patches and a small red dot, likely indicating a point of interest or measurement.  The image displays two side-by-side photographs of a patient's oral cavity, showing the upper and lower teeth with visible dental restorations. The left photo includes a red dot indicating a specific area of interest, possibly a lesion or treatment site, while the right photo shows a broader view of the oral structures, including the tongue and palate. The images appear to be clinical photographs taken for diagnostic or educational purposes. ```markdown THE UNIVERSITY OF WESTERN AUSTRALIA Differential diagnosis of white lesions in the mouth ``` Establishing a differential diagnosis for white lesions in the mouth is essential for identifying potentially malignant disorders. - Number of possibilities - High frequency of insignificant lesions <img src="..."/> The diagnostic process is complicated by several factors: - There are a high number of clinical possibilities for white lesions. - There is a high frequency of insignificant or benign lesions that may mimic more serious conditions. ```markdown Useful categories of lesion - Not really a white lesion - Normal - Developmental - Traumatic - Infectious - Lichen planus and similar conditions - Idiopathic ```  To aid in diagnosis, lesions can be organized into the following useful categories: - Not really a white lesion (pseudo-membranes or debris) - Normal anatomical variations - Developmental conditions - Traumatic lesions - Infectious processes - Lichen planus and similar lichenoid conditions - Idiopathic lesions A slide from a presentation by The University of Western Australia, titled 'Useful categories of lesion,' which lists various categories including 'Not really a white lesion,' 'Normal,' 'Developmental,' 'Traumatic,' 'Infectious,' 'Lichen planus and similar conditions,' and 'Idiopathic.' The slide uses a bulleted list format to organize the information. # How to differentiate lesions - Carcinoma? - Is it normal? - Evidence for a developmental condition? - Habits and causes of friction? - Does site help - CHC, OHL, SN - Any striae? - Risk features for dysplasia or malignancy? - Smear it - Biopsy it Effective differentiation of oral lesions requires a systematic evaluation of clinical features and diagnostic testing. #### Diagnostic Questions and Observations - **Malignancy:** Is there clinical evidence of carcinoma? - **Normalcy:** Is the appearance within the range of normal anatomical variation? - **Developmental:** Is there evidence for a long-standing developmental condition? - **Etiology:** Are there specific habits or causes of friction (trauma) present? - **Site Specificity:** Does the location help narrow the diagnosis (e.g., Chronic Hyperplastic Candidiasis [CHC], Oral Hairy Leukoplakia [OHL], or Stomatitis Nicotina [SN])? - **Morphology:** Are there characteristic features like striae (Wickham striae)? #### Risk Assessment and Investigation - Evaluate specific risk features for dysplasia or malignancy. - Utilize diagnostic aids such as a smear (cytology). - Perform a biopsy for definitive histological diagnosis. ```markdown Clinical PRACTICE Evaluation of a Suspicious Oral Mucosal Lesion P. Michele Williams, BSN, DMD, FRCD(C); Catherine F. Poh, DDS, PhD, FRCD(C); Allan J. Hovan, DMD, MSD, FRCD(C); Samson Ng, DDS, MSc, FRCD(C); Miriam P. Rosin, BSc, PhD Contact Author Dr. Williams Email: mwill@bccancer.bc.ca ABSTRACT Dentists who encounter a change in the oral mucosa of a patient must decide whether the abnormality requires further investigation. In this paper, we describe a systematic approach to the assessment of oral mucosal conditions that are thought likely to be premalignant or an early cancer. These steps, which include a comprehensive history, step-by-step clinical examination (including use of adjunctive visual tools), diagnostic testing and formulation of diagnosis, are routinely used in clinics affiliated with the British Columbia Oral Cancer Prevention Program (BC OCPP) and are recommended for consideration by dentists for use in daily practice. For citation purposes, the electronic version is the definitive version of this article: www.cda-adc.ca/jcda/vol-74/issue-3/275.html ```  #### Clinical Evaluation of Suspicious Oral Mucosal Lesions Dentists encountering changes in the oral mucosa must determine if the abnormality requires further investigation. A systematic approach is recommended for assessing oral mucosal conditions likely to be premalignant or early-stage cancer. #### Diagnostic Protocol The British Columbia Oral Cancer Prevention Program (BC OCPP) utilizes a standardized process for daily practice, which includes: - Comprehensive patient history - Step-by-step clinical examination - Use of adjunctive visual tools - Diagnostic testing - Formulation of a definitive diagnosis A headshot of Dr. Williams, a woman with short brown hair and glasses, smiling, located in the contact author section of the document. # Introduction - More than 350,000 patients have oral cavity and lip cancer annually in the world #### Global Incidence - More than 350,000 patients are diagnosed with oral cavity and lip cancer annually worldwide. # Oral Malignant neoplasms - Common: OSCC - Less common: - Salivary gland tumours - Malignant melanoma - Lymphoma - Neoplasms of bone and connective tissue - Some odontogenic tumours - Maxillary antral carcinoma - Metastatic neoplasms - Kaposi sarcoma #### Common Malignancies - Oral Squamous Cell Carcinoma (OSCC) #### Less Common Malignancies - Salivary gland tumours - Malignant melanoma - Lymphoma - Neoplasms of bone and connective tissue - Specific odontogenic tumours - Maxillary antral carcinoma - Metastatic neoplasms - Kaposi sarcoma # Molecular alterations in OSCC - Oral Cancer is a genetic disease. - The genetic defects could be induced by **gene amplification** or **translocations** or point mutations or **rearrangements** and **deletions** - Oral cancer needs~ 6-7 specific mutations #### Genetic Basis of Oral Cancer Oral cancer is a genetic disease. Development typically requires approximately 6 to 7 specific mutations. #### Mechanisms of Genetic Defect Genetic defects in Oral Squamous Cell Carcinoma (OSCC) can be induced by several mechanisms: - Gene amplification - Translocations - Point mutations - Rearrangements - Deletions ```markdown Squamous cell carcinoma The most common malignant epithelial neoplasm of the oral region ``` #### Squamous Cell Carcinoma Overview Squamous cell carcinoma is the most common malignant epithelial neoplasm of the oral region. **Squamous cell carcinoma: common sites** <img src="https://i.imgur.com/8XZJzQl.jpg" alt="Two images showing oral lesions. Left: A white patch on the tongue. Right: A red, ulcerated lesion on the inner cheek near the teeth." />  #### Common Clinical Sites Clinical presentations often include: - White patches on the tongue - Red, ulcerated lesions on the buccal mucosa (inner cheek) near the dentition Two clinical photographs showing oral lesions associated with squamous cell carcinoma. The left image displays a white patch on the tongue, while the right image shows a red, ulcerated lesion on the inner cheek near the teeth. These images illustrate common sites for this type of cancer. # Features of malignant neoplasms **History**: slow- or fast-growing, pain or other neurological signs +/-, impaired function, risk factors (where known) **Consistency**: indurated, non-encapsulated **Size**: progressive increase, large or small **Ulceration**: +/- **Spread**: metastatic to lymph nodes **Imaging**: irreg. pattern of destruction in bone or invasion in soft tissues #### Clinical and Diagnostic Indicators - **History**: Growth may be slow or fast; may present with or without pain or neurological signs; impaired function; presence of known risk factors. - **Consistency**: Indurated (hardened) and non-encapsulated. - **Size**: Progressive increase in size; can present as large or small lesions. - **Ulceration**: May or may not be present. - **Spread**: Potential for metastasis to regional lymph nodes. - **Imaging**: Radiographic evidence of irregular patterns of bone destruction or soft tissue invasion. ```html <table border="1" cellpadding="5" cellspacing="0" style="border-collapse: collapse; width: 100%;"><tr><td style="text-align: center; vertical-align: middle;"><img src="https://i.imgur.com/8Q0Z8Qz.png" alt="Microscopic image of poorly differentiated squamous cell carcinoma" /></td><td style="text-align: center; vertical-align: middle;"><b>Poorly differentiated<br>squamous cell<br>carcinoma</b></td></tr></table> ```   #### Histological Classification - **Poorly differentiated squamous cell carcinoma**: Characterized by highly atypical cellular features and a lack of normal maturation patterns. Microscopic image of poorly differentiated squamous cell carcinoma, showing dense clusters of abnormal cells with irregular nuclei and minimal differentiation, characteristic of aggressive malignancy. High-magnification view of poorly differentiated squamous cell carcinoma, revealing disorganized tissue architecture, hyperchromatic nuclei, and increased mitotic activity, indicating advanced tumor progression. ```html <table border="1" cellpadding="5" cellspacing="0" style="border-collapse: collapse; width: 100%;"><tr><td style="text-align: center; font-weight: bold; color: #FFD700; background-color: #4B0026;">Poorly differentiated SCC</td></tr><tr><td style="text-align: center; background-color: #F0F0F0;"><img src="https://i.imgur.com/placeholder.jpg" alt="Microscopic image of poorly differentiated SCC showing irregular cell morphology and disorganized tissue architecture." /></td></tr></table> ```  #### Microscopic Architecture - **Poorly differentiated SCC**: Displays irregular cell morphology and disorganized tissue architecture. Microscopic image of poorly differentiated squamous cell carcinoma (SCC), showing irregular cell morphology with high nuclear-to-cytoplasmic ratios, prominent nucleoli, and disorganized tissue architecture. The image highlights areas of necrosis and inflammatory infiltration, characteristic of aggressive tumor behavior.  A close-up medical photograph showing a section of tissue with a reddish, inflamed area and a white, irregular lesion. A small red dot is visible on the lesion, possibly indicating a point of interest or measurement. The surrounding tissue appears moist and vascular. ```html <table border="1" cellpadding="5" cellspacing="0" style="border-collapse: collapse; width: 100%;"><tr><td style="text-align: center; font-weight: bold; color: #00FFFF;">Severe epithelial dysplasia</td></tr><tr><td style="text-align: center; background-color: #C0C0C0;"><img src="https://i.imgur.com/1234567.png" alt="Microscopic image showing severe epithelial dysplasia with abnormal cell growth and architecture." /></td></tr></table> ```  #### Severe Epithelial Dysplasia Severe dysplasia is characterized by significant abnormal cell growth and architectural changes within the epithelium. Microscopic image showing severe epithelial dysplasia with abnormal cell growth and architecture, characterized by increased nuclear size, irregular nuclear shapes, and loss of normal tissue organization. The image highlights areas of dysplastic cells with hyperchromatic nuclei and increased mitotic activity. # Dysplasia **Disturbed differentiation and proliferation** - Disordered architecture - Deep cell keratinisation - Cell and nuclear pleomorphism - Nuclear hyperchromatism - Increased nuclear/cytoplasmic ratio - Abnormal mitoses #### Characteristics of Dysplasia Dysplasia involves disturbed differentiation and proliferation, marked by the following features: - Disordered tissue architecture - Deep cell keratinisation - Cell and nuclear pleomorphism (variation in size and shape) - Nuclear hyperchromatism - Increased nuclear/cytoplasmic ratio - Abnormal mitotic figures # ORAL CANCER - LIP - Most commonly affected site. - Geographical variation; U-V light exposure. - Susceptibility; race and immunosuppression. #### Epidemiology and Risk Factors - Most commonly affected site. - Geographical variation often related to UV light exposure. - Susceptibility factors include race and immunosuppression. # ORAL CANCER - LIP - Non-healing ulcer. - Painless. - Easily overlooked. #### Clinical Presentation - Typically presents as a non-healing ulcer. - Characteristically painless. - Easily overlooked during clinical examination.  Close-up medical photograph of the lips showing a lesion on the lower lip, with visible textural changes and discoloration. The image appears to be part of a clinical case study or dermatological examination.  A close-up medical photograph showing a lesion on the lower lip of a person, with visible tissue damage and discoloration. The image appears to be used for diagnostic or educational purposes, highlighting a pathological condition. # ORAL CANCER-INTRAORAL - Typical presentation is a painless indurated ulcer. - Floor of mouth and ventral tongue are the most common intraoral sites. #### Common Presentations and Sites - The typical presentation is a painless indurated ulcer. - The floor of the mouth and the ventral tongue are the most common intraoral sites for carcinoma.  A close-up intraoral photo showing a patient's mouth with exposed bone and soft tissue, likely post-surgical, with visible teeth, gum tissue, and a dental instrument. The image captures a surgical site with some bleeding and a pinkish-white granular tissue, possibly indicating healing or graft material.  close-up view of oral cavity showing inflamed and ulcerated tissue, with visible teeth and a red dot indicating a specific area of interest, likely for medical or dental examination.  A close-up photograph of an oral cavity showing a large, pinkish lesion on the tongue with a white, ulcerated area. The lesion appears to be a medical condition, possibly a tumor or lesion, with surrounding teeth visible at the bottom of the image. # ORAL CANCER-INTRAORAL - Less common presentation - Red, soft, raised lesion #### Erythematous Presentation - A less common clinical presentation. - Appears as a red, soft, and raised lesion. # ORAL CANCER-INTRAORAL - Less common presentation - Indurated white patch #### Leukoplakic Presentation - A less common clinical presentation. - Appears as an indurated white patch.  Close-up intraoral photo showing a patient's mouth with multiple dental restorations, including amalgam fillings and a dental implant with a crown. The image highlights the condition of the teeth and surrounding gingival tissue, with a red dot indicating a specific area of interest on the lower anterior teeth.  Close-up photo of a surgical site in the mouth, showing a pinkish tissue area with a small incision or lesion highlighted by a red dot. A wooden tongue depressor is visible on the right side, holding the area open for examination. The surrounding tissue appears moist and slightly inflamed.  close-up photo showing a medical procedure on a patient's mouth, with a gloved hand holding a tool near a lesion or growth on the lip, which appears to be inflamed and possibly treated with a laser or similar device indicated by a red dot. # ORAL CANCER- ORO-PHARYNGEAL - Pain in the face and the ear. - Tongue deviation. #### Clinical Symptoms and Signs - Pain localized to the face and the ear. - Physical signs may include tongue deviation.  A close-up medical photograph showing a surgical site with exposed tissue, likely during a procedure. The image displays a reddish, textured area with visible blood vessels and surrounding pale tissue, possibly indicating a biopsy or excision. A small red dot is present in the lower right, potentially marking a specific point of interest.  A close-up medical photograph showing the interior of a patient's mouth, focusing on the tongue and surrounding tissue. The image displays a red laser dot targeting a specific area on the tongue, likely for diagnostic or therapeutic purposes. A metallic instrument is visible on the right side, suggesting a clinical examination or procedure.  close-up medical photograph showing a surgical procedure on a tissue sample, with metallic instruments holding the tissue and a red dot highlighting a specific area of interest.   Close-up photo of a person's open mouth showing the tongue with a white, patchy lesion on its surface, possibly indicating a medical condition. Another close-up photo of the oral cavity, focusing on the tongue and surrounding tissue, with a red dot highlighting a specific area of interest.  Close-up photograph of a dental procedure showing an open mouth with teeth and gums. A dental instrument is visible, interacting with the gum tissue near a tooth, highlighting a clinical examination or treatment in progress. # Standard clinical evaluation - Complete history of the disease - Alcohol and tobacco consumption - Weight and weight loss A thorough clinical assessment is essential for the evaluation of oral potentially malignant disorders and the risk of progression. This evaluation includes: - Complete history of the disease - Assessment of alcohol and tobacco consumption - Monitoring of weight and documentation of any weight loss ```markdown # TNM staging - TNM classification - International Classification of Diseases for Oncology, 3rd Edition (ICD-O-3) ``` The staging process utilizes standardized international systems to ensure accurate classification and communication of findings: - TNM classification system - International Classification of Diseases for Oncology, 3rd Edition (ICD-O-3) ```html <table> <tr> <td> <img src="https://i.imgur.com/1234567.jpg" alt="Specimen with label '1023/07' and ruler for scale"/> </td> <td> <img src="https://i.imgur.com/7654321.jpg" alt="Close-up of specimen with label '1023/07' and marked anatomical features"/> </td> </tr> </table> ```   #### Pathological Specimen Documentation Clinical evaluation involves the detailed examination of specimens (e.g., specimen 1023/07). Documentation includes: - Visual inspection of the specimen with a scale for measurement. - Identification and marking of specific anatomical features and margins. A specimen labeled '1023/07' with a ruler for scale, showing a biological sample with a label 'Fol001' and an orange marker. A close-up photo of a specimen labeled '1023/07', showing anatomical features with marked points and a blue ring, likely indicating specific regions of interest. ```markdown **TNM/AJCC** - Tis: Carcinoma in situ - T1: Tumor 2 cm or less in greatest dimension - T2: Tumor > 2 cm but ≤ 4 cm in greatest 4 cm in greatest dimension - T3: Tumor > 4 cm in greatest dimension - T4 (lip) Tumor invades adjacent structures (through cortical bone, inferior alveolar nerve, floor of mouth, skin of face) - T4 (oral cavity) Tumor invades adjacent structures (through cortical bone, into deep muscle of tongue, maxillary sinus, skin.) ```  #### Primary Tumor (T) Classification According to the TNM/AJCC guidelines, the primary tumor is categorized as follows: - **Tis**: Carcinoma in situ - **T1**: Tumor 2 cm or less in greatest dimension - **T2**: Tumor > 2 cm but ≤ 4 cm in greatest dimension - **T3**: Tumor > 4 cm in greatest dimension - **T4 (Lip)**: Tumor invades adjacent structures (through cortical bone, inferior alveolar nerve, floor of mouth, skin of face) - **T4 (Oral Cavity)**: Tumor invades adjacent structures (through cortical bone, into deep muscle of tongue, maxillary sinus, skin) The image displays a textual figure outlining the TNM/AJCC staging criteria for tumors, specifically detailing T-stage classifications. It includes definitions for Tis (carcinoma in situ), T1 (tumor 2 cm or less), T2 (tumor greater than 2 cm but less than or equal to 4 cm), T3 (tumor greater than 4 cm), and T4 (tumor invading adjacent structures) for both lip and oral cavity tumors. The information is presented in a bullet-point format with yellow text on a dark purple background. ```markdown TNM/AJCC - N0: no regional node metastasis - Nx: regional nodes cannot be assessed - N1: single ipsilateral node, ≤ 3 cm - N2a: single ipsilateral node, > 3 cm and ≤ 6 cm - N2b: multiple ipsilateral nodes, ≤ 6 cm - N2c: contralateral or bilateral nodes, ≤ 6 cm - N3: node > 6 cm ```  #### Regional Lymph Nodes (N) Classification - **N0**: No regional node metastasis - **Nx**: Regional nodes cannot be assessed - **N1**: Single ipsilateral node, ≤ 3 cm - **N2a**: Single ipsilateral node, > 3 cm and ≤ 6 cm - **N2b**: Multiple ipsilateral nodes, ≤ 6 cm - **N2c**: Contralateral or bilateral nodes, ≤ 6 cm - **N3**: Node > 6 cm A bulleted list detailing the TNM/AJCC staging criteria for regional lymph node involvement, with definitions for N0, Nx, N1, N2a, N2b, N2c, and N3 based on the number, size, and location of metastatic nodes.  A close-up photograph of a patient's neck and upper chest, showing a large, raised, reddish lesion on the anterior neck with blue surgical markings outlining the area. The skin appears inflamed and irritated, with a small red dot indicating a specific point of interest, likely for medical documentation or surgical planning. ```markdown TNM/AJCC - Mx: Distant metastasis cannot be assessed - M0: No distant metastasis - M1: Distant metastasis ```  #### Distant Metastasis (M) Classification - **Mx**: Distant metastasis cannot be assessed - **M0**: No distant metastasis - **M1**: Distant metastasis A bulleted list presenting the M category classifications for TNM/AJCC staging, including Mx (distant metastasis cannot be assessed), M0 (no distant metastasis), and M1 (distant metastasis). # Treatment of oral carcinoma - **T1-T2 N0**: Surgery T (only) Brachytherapy (T<3cm, no ulceration, no infiltration, dry vermilion) - **T3-T4 N0**: Surgery T + SOH ND ± post-operative RxTh1 - **T1-T4 N1**: Surgery T + SOH or radical modified ND ± post-operative RxTh1 - **T1-T4 N2a-N3**: Surgery T + radical modified ND2 ± postoperative  Treatment strategies for oral carcinoma are determined by the TNM stage: - **T1-T2 N0**: - Surgery of the primary tumor (T) only - Brachytherapy (indicated if T < 3cm, no ulceration, no infiltration, and located on dry vermilion) - **T3-T4 N0**: - Surgery of the primary tumor (T) + Supraomohyoid Neck Dissection (SOH ND) ± post-operative Radiotherapy - **T1-T4 N1**: - Surgery of the primary tumor (T) + SOH or radical modified Neck Dissection ± post-operative Radiotherapy - **T1-T4 N2a-N3**: - Surgery of the primary tumor (T) + radical modified Neck Dissection ± post-operative treatment The image displays a table outlining treatment protocols for oral carcinoma based on tumor stage (T) and lymph node status (N). It categorizes treatments into four groups: T1-T2 N0, T3-T4 N0, T1-T4 N1, and T1-T4 N2a-N3, detailing surgical and radiation therapy options for each stage. ```markdown # Follow-up - Clinical examination of head and neck mucosa (including fiberoptic) and neck palpation / performance status / nutritional assessment every 2 months (first 2 years), every 6 months (years 3-5), once a year (> 5 year) - Dental examination and orthopantomogram every 6 months - Chest X-ray every year - Chest spiral CT every year - Laboratory tests: TSH every year (if Radiotherapy delivered) ``` #### Clinical and Mucosal Surveillance - Clinical examination of head and neck mucosa (including fiberoptic) and neck palpation, performance status, and nutritional assessment: - Every 2 months for the first 2 years - Every 6 months for years 3 to 5 - Once a year after 5 years #### Diagnostic and Laboratory Monitoring - **Dental and Imaging**: - Dental examination and orthopantomogram every 6 months - Chest X-ray every year - Chest spiral CT every year - **Laboratory Tests**: - TSH levels every year (required if Radiotherapy was delivered) # ORAL CANCER - FIVE YEAR SURVIVAL - Stage I > 80% - Stage II ~60% - Stage III ~35% - Stage IV < 15%  #### Five-Year Survival Rates Survival outcomes for oral cancer are highly dependent on the stage at diagnosis: - **Stage I**: > 80% - **Stage II**: ~60% - **Stage III**: ~35% - **Stage IV**: < 15% A chart titled 'ORAL CANCER - FIVE YEAR SURVIVAL' displaying survival rates by cancer stage. It lists Stage I with >80% survival, Stage II with ~60%, Stage III with ~35%, and Stage IV with <15%. The data is presented in yellow text on a dark purple background with pink diamond bullet points. # Second Primary Head and Neck Cancer - Second Primary cancers of the aerodigestive pathway occur synchronously or metachronously in 20% of patients with an index of cancer of the head and neck. - “Field cancerization” #### Second Primary Head and Neck Cancer - Second primary cancers of the aerodigestive pathway occur synchronously or metachronously in 20% of patients with an index cancer of the head and neck. - This phenomenon is associated with the concept of "field cancerization." # What happens after Treatment? - Speech and Swallowing Therapy - Follow-up tests - Chemoprevention - Watch for new symptoms - General health considerations Post-treatment care focuses on rehabilitation and early detection of recurrence: - Speech and Swallowing Therapy - Routine follow-up tests - Chemoprevention strategies - Vigilance for new symptoms - Management of general health considerations # Prevention of Head and Neck Cancer in Primary Care Practice 1. Identify patients who use tobacco and alcohol products. 2. Counsel patients to stop using tobacco and alcohol products. 3. Maintain high index of suspicion. 4. Conduct comprehensive exams. 5. Attend to common symptoms. 6. Evaluate symptomatic patients. 7. Maintain close medical surveillance of patients in high-risk occupations. 8. Refer high-risk patients with persistent symptoms and no findings to a head and neck surgeon. Primary care providers play a critical role in the early detection and prevention of head and neck cancer through the following actions: 1. Identify patients who use tobacco and alcohol products. 2. Counsel patients to stop using tobacco and alcohol products. 3. Maintain a high index of suspicion. 4. Conduct comprehensive examinations. 5. Attend to common symptoms. 6. Evaluate symptomatic patients. 7. Maintain close medical surveillance of patients in high-risk occupations. 8. Refer high-risk patients with persistent symptoms and no findings to a head and neck surgeon. # Factors Delaying the Diagnosis of Head and Neck Cancers - Patient procrastination in seeking medical attention - Physician delay in diagnosis - Patient remains asymptomatic for a prolonged period Several factors can lead to a delay in the diagnosis of head and neck cancers: - Patient procrastination in seeking medical attention - Physician delay in diagnosis - The patient remaining asymptomatic for a prolonged period End of slide show, click to exit. #### Diagnosis and Management of Oral Lichen Planus - The American Academy of Oral and Maxillofacial Pathology recommends obtaining a biopsy for all suspected cases to confirm diagnosis. - Management is generally focused on symptom control: - Symptomatic treatment approach. - Primary use of topical anti-inflammatory therapy. - Occasional use of systemic anti-inflammatory therapy for severe cases. ```markdown Slide 56 Diagnosis and management - Position paper from the American Academy of Oral and Maxillofacial Pathology recommends obtaining a biopsy from everyone. - Most agree that oral lichen planus is treated - Symptomatically - With usually topical and occasionally systemic anti-inflammatory therapy Slide 57 Lupus erythematosus - LUPUS - Systemic (SLE) - Cutaneous - Acute cutaneous LE (ACLE) - Subacute cutaneous LE (SCLE) - Chronic cutaneous LE (CCLE) - Discoid LE (DLE) - The most common form of chronic cutaneous LE - Approximately 15-30% of SLE patients have DLE Slide 58 Lupus erythematosus Aetiology and pathogenesis - Autoimmune disease - Contribution of genetics and epigenetics - B and T cell signaling abnormalities - Ongoing, lethal apoptosis and defective clearance of cellular debris - Antibody formation and purpura/cutaneous damage Slide 59 Lupus erythematosus Clinical features - Begins: - Red purplish macules, or small plaques - Rapidly develop into hyperkeratotic surface - Evolve into: - Sharply demarcated discoid plaques covered by an adherent scale that extends into the orifice of dilated hair follicles Slide 60 Lupus erythematosus Clinical features - Oral - Sharp margins - Irregular, scalloped white borders with radiating violaceous and telangiectasia - Honeycomb appearance on the palatal mucosa - Painful ulceration is common Slide 61 Histopathological features - Both acanthosis and atrophy of the epithelium - Vacuolar degeneration of basal cells - Band-like lymphocytic infiltrate at the interface - DIF - Positive lupus band test - Immune complex deposition of IgG, IgM, or IgA at the basement membrane (lupus band test) Slide 62 Diagnosis and management - Diagnosis based on clinical presentation and obtaining a biopsy - Management - Long-term, stable, relapsing remitting course - Treatment with immunosuppression Slide 63 Oral potentially malignant disorders: risk of progression to malignancy Page 18, J. Oral Pathol. Med. 2009, 38, 463–469 Slide 64 ```html <table border="1" cellpadding="5" cellspacing="0"> <tr> <td>History</td> <td>Examination</td> <td>Biopsy</td> <td>Diagnosis</td> </tr> <tr> <td rowspan="2">History</td> <td>Signs and symptoms</td> <td>Biopsy</td> <td>Diagnosis</td> </tr> <tr> <td>Signs and symptoms</td> <td>Biopsy</td> <td>Diagnosis</td> </tr> <tr> <td>Examination</td> <td>Signs and symptoms</td> <td>Biopsy</td> <td>Diagnosis</td> </tr> <tr> <td>Biopsy</td> <td>Signs and symptoms</td> <td>Biopsy</td> <td>Diagnosis</td> </tr> <tr> <td>Diagnosis</td> <td>Signs and symptoms</td> <td>Biopsy</td> <td>Diagnosis</td> </tr> </table> ``` Slide 65 Idiopathic white patches clinically these are "leukoplakia" - keratosis with or without dysplasia - Presentation: homogeneous, nodular, verrucous, speckled - Site: sublingual keratosis, actinic keratosis - Presumed aetiology: Smokers', actinic keratosis - Proliferative verrucous leukoplakia - squamous cell carcinoma Slide 66 In principle every white patch in the mouth should have a biopsy sample removed Slide 67 Differential diagnosis of white lesions in the mouth ```        #### Classification of Lupus Erythematosus (LE) - **Systemic Lupus Erythematosus (SLE)** - **Cutaneous Lupus Erythematosus**: - Acute cutaneous LE (ACLE) - Subacute cutaneous LE (SCLE) - Chronic cutaneous LE (CCLE) - Discoid LE (DLE) - DLE is the most common form of chronic cutaneous LE. - Approximately 15-30% of patients with SLE also present with DLE. #### Aetiology and Pathogenesis Lupus erythematosus is an autoimmune disease driven by: - Genetic and epigenetic contributions. - Abnormalities in B and T cell signaling. - Ongoing, lethal apoptosis combined with defective clearance of cellular debris. - Antibody formation leading to purpura and cutaneous damage. #### Clinical Features - **Initial Presentation**: - Red-purplish macules or small plaques. - Rapid development of a hyperkeratotic surface. - **Evolution**: - Sharply demarcated discoid plaques. - Covered by an adherent scale extending into dilated hair follicle orifices. - **Oral Manifestations**: - Sharp margins with irregular, scalloped white borders. - Radiating violaceous striae and telangiectasia. - "Honeycomb" appearance, particularly on the palatal mucosa. - Painful ulceration is a common finding. #### Histopathological Features - Epithelial changes including both acanthosis and atrophy. - Vacuolar degeneration of the basal cell layer. - Band-like lymphocytic infiltrate at the interface. - **Direct Immunofluorescence (DIF)**: - Positive "lupus band test." - Characterized by immune complex deposition (IgG, IgM, or IgA) at the basement membrane. #### Diagnosis and Management of Lupus - **Diagnosis**: Based on clinical presentation and confirmed via biopsy. - **Management**: - Recognition of a long-term, stable, but relapsing-remitting disease course. - Treatment primarily involves immunosuppression. #### Clinical Guidelines for White Lesions - **Idiopathic White Patches (Leukoplakia)**: - May present as keratosis with or without dysplasia. - Clinical presentations: Homogeneous, nodular, verrucous, or speckled. - Specific types/sites: Sublingual keratosis, actinic keratosis, and proliferative verrucous leukoplakia. - Presumed aetiology often includes smoking or actinic damage. - Differential diagnosis must include squamous cell carcinoma. - **Biopsy Protocol**: In principle, every white patch in the mouth should have a biopsy sample removed for definitive diagnosis. A flowchart diagram illustrating the progression of oral potentially malignant disorders to malignancy, showing pathways from initial lesions to various stages of cancer development, with text referencing a study from the Journal of Oral Pathology & Medicine, 2009. A clinical photograph showing oral lesions of lupus erythematosus, with visible red, sharply demarcated plaques on the oral mucosa, including the palate, consistent with the described clinical features of discoid lupus. A clinical photograph depicting severe oral lesions, likely leukoplakia or squamous cell carcinoma, with white patches and ulcerations on the oral mucosa, illustrating the need for biopsy as emphasized in the presentation. A clinical photograph showing a large, irregularly shaped ulcerated lesion on the oral mucosa, consistent with a potentially malignant disorder, supporting the slide's message about the necessity of biopsy for all white patches. A clinical photograph displaying multiple white patches on the oral mucosa, including the tongue and gingiva, illustrating the appearance of idiopathic white patches or leukoplakia, which require biopsy for diagnosis. A histopathological image showing a section of oral tissue with features of oral lichen planus, including band-like lymphocytic infiltrate and vacuolar degeneration of basal cells, as described in the accompanying slide. A table with four columns labeled 'History', 'Examination', 'Biopsy', and 'Diagnosis', and five rows, creating a grid that appears to represent a diagnostic or decision-making process, though the content is repetitive and unclear. 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