BDS10016 Oral Neoplasia (Malignancy) PDF

BDS10016 Oral neoplasia – histopathology of common oral malignancies Aims: The aim of this lecture is to detail the histopathological aspects if common oral mucosal malignancy Objectives: On completion of this lecture, the student should be able to: • Understand the histopathology of oral squamou...

BDS10016 Oral neoplasia – histopathology of common oral malignancies Aims: The aim of this lecture is to detail the histopathological aspects if common oral mucosal malignancy Objectives: On completion of this lecture, the student should be able to: • Understand the histopathology of oral squamous cell carcinoma • Understand the histopathology of nonHodgkin’s lymphoma and Kaposi’s sarcoma of the oral tissues According To Tissue of origin Epithelial Mesenchymal Oral squamous cell carcinoma Variants of squamous cell carcinoma Fibrosarcoma Osteosarcoma Chondrosarcoma Lymphomas Kaposi sarcoma Ewing sarcoma melanoma Malignant neoplasms are a large group of diseases characterized by growth of abnormal cells beyond their usual boundaries that can then invade adjoining parts of the body and/or spread to other organs. Cancer is another common term for such malignant neoplasms which represents the second leading cause of death globally More than 90% of cancers in the oral cavity are oral squamous cell carcinomas Squamous cell carcinoma • It is a malignant neoplasm of squamous epithelium origin. • It accounts about 90% of all head and neck cancers Etiology • multifactorial. • extrinsic [smoking, alcohol, UV radiation (lip carcinomas)] and intrinsic factors [such as oncogenic viruses: HPV and EBV] work together Extrinsic factors Genetic basis of cancer • Cancer is the end product of unregulated proliferation of cells, resulting from the accumulation of sequential genetic alterations (mutations) in a precursor cell [from the basal cell layer of the mucosa] • For a cancer to become "initiated," a cell must manage to accumulate at least six of these genetic mutations over a long period, then pass it along to a daughter cell • This forms a clone consisting of many daughter cells with an accumulation of altered genes called "oncogenes." Genetic basis of cancer Oncogenes versus tumor suppressor genes In normal conditions, proto-oncogenes regulate cell growth & cell proliferation. Mutations of protooncogenes convert them into oncogenes [carcinogenic form] Genetic basis of cancer Oncogenes versus tumor suppressor genes In normal conditions, tumor suppressor genes protect the body by:  repair damaged DNA initiate apoptosis, causing cell death restrict the proliferation of cells (sterility). Unlike oncogenes, tumor suppressor genes produce cancer by their genetic loss or inactivation Clinical features  It can affect any area of the oral mucosa, however, the most common sites are tongue, floor of mouth and gingiva  Cancer of lower lip typically appear as a crusting lesion often preceded by actinic cheilitis  Early lesions appear as painless red, speckled or white patches [indistinguishable clinically from potentially malignant diseases]  Later, lesions are either nodular (exophytic) or undergo ulcerative changes (endophytic) Clinical features Exophytic lesions  May have irregular papillary surface  Color varies from normal to red or white.  The surface is often ulcerated  Hard on palpation (indurated) [due to inflammation and fibrosis as well as infiltration of the surrounding tissues Endophytic lesions (Malignant ulcer)  A non- healing ulcer for 2 weeks  Irregular, with everted, raised “rolled” border [due to invasion of the tumor  Indurated base, may be fixed to underlying structures  Bleeding and necrotic floor may be seen Clinical features • Pain is generally considered of little value in the diagnosis of carcinoma early carcinoma is often painless, ulceration may be associated with soreness • Perineural invasion paraesthesia may cause • Destruction of underlying bone may be seen and appears as moth eaten radiolucency with ill defined or ragged margin Clinical staging (TNM system): • Cancer staging describes the malignancy when it was first diagnosed. This system is useful for: • treatment planning and • predicting the prognosis • Suspected lesions should be staged before they are biopsied, because: The biopsy, potential wound scarring or infection may distort the lesions in addition to induced inflammation within regional lymph nodes, all of these may confuse later staging. After staging, mandatory biopsy is Clinical staging (TNM system): T Primary tumor size the greatest diameter of visible lesion (in centimeters). TX primary tumor can’t be assessed T0 no evidence of primary tumor Tis Carcinoma in situ T1 Tumor size 0-2 cms T2 Tumor size 2-4 cms T3 Tumor size  4 cms T4 Massive tumor or tumor invading bone or muscles Clinical staging (TNM system): N Regional Lymph node palpable nodes (felt clinically) NX regional lymph nodes can’t be assessed N0 No clinically palpable nodes N1 Clinically palpable ipsilateral (same side) nodes  3 cms N2 Clinically palpable ipsilateral (same side) nodes 3- 6 cms N2a, b, c N3 Fixed; Bilateral or contralateral palpable; or ipsilateral 6 cms Clinical staging M Distant Metastasis evaluated by physical examination and radiographs. Mx Metastasis not assessed M0 No distant metastasis M1 Metastasis present Stage 0 Stage I Stage II Stage III Stage IVA Stage IVB Stage IVC Tis T1 T2 T3 T1 T2 T3 T4a T4a T1-4a Any T T4b Any T N0 N0 N0 N0 N1 N1 N1 N0 N1 N2 N3 Any N Any N M0 M0 M0 M0 M0 M0 M0 M0 M0 M0 M0 M0 M1 Histopathological Tumor Grading • Based on microscopic examination to determine the degree of their resemblance of tumor cells to tissue of origin (squamous epithelium) [this is referred to as differentiation] and keratin production Tumors are graded on three-point (I-III) or four-point (I-IV) depending on degree of differentiation. Well differentiated Or Low grade Or Grade I moderately differentiated Or intermediate grade Or Grade II or III Poorly differentiated Or high grade Or Grade IV Histopathology • Basement membrane is invaded by the neoplastic epithelium into the connective tissue. • The connective tissue stroma contains an inflammatory infiltrate of lymphocytes, plasma cells, and macrophages. • Signs of dysplasia are seen in varying degrees according to tumor differentiation. In well-differentiated carcinomas: • Malignant epithelial nests, keratin formation in the form of keratin pearls or individual cell keratinization • nests of malignant cells maintaining intercellular bridges • Generally, cellular & nuclear pleomorphism • Nuclear hyperchromasia • Mitotic figures increase with tumor grade poorly-differentiated carcinomas: Features of squamous differentiation are minimal or absent requiring immunohistochemical confirmation such as cytokeratins or p63 moderately-differentiated carcinomas show microscopic features between those of well and poorly differentiated carcinomas Squamous cell carcinoma However, Histological grade correlates poorly with patient outcome. Tumor size and nodal status are the most significant prognostic factors Major risk factors that adversely influence prognosis Non-cohesive pattern of invasion Presence of two or more positive regional nodes, extracapsular extension of nodal disease,  positive margins of resection. A tumor thickness >4mm Perineural & lymphovascular invasion Metastasis of SCC I – Lymph node metastasis: • Most common • Lymph nodes with metastasis are firm to hard, enlarged and fixed (not easily movable) II- Distant Metastasis: • metastasis via blood, often go to the lungs, liver and bone. Treatment • Wide surgical excision • Radiation therapy • A variety of chemotherapeutic agents may be used Causes of death in oral cancer 1. Tumor load The tumor secretes a greater amount of blocking factors (as cytokines) which prevent normal cells from utilizing nutrients 2. Infection (pneumonia) General weakness & narcotic analgesics (required for pain control) both reduce the cough reflex and depress respiration. 3. Complications of treatment a smaller percentage of patients die from side effects of treatment. •Chemotherapy produces severe marrow suppression reducing white blood cell count and resulting in fatal systemic infection • Radiotherapy rarely produce life threatening complications but may produce dysphagia from fibrosis in the pharyngeal musculature, limited jaw opening, xerostomia which will reduce the nutritional intake Causes of death in oral cancer 4. Progression of comorbidities Oral squamous cell carcinoma usually occur in old individuals with alcohol & smoking history. Many of them have hypertension, chronic bronchitis and ischemic cardiovascular disease. The physiologic impact of surgery, chemotherapy and radiotherapy often make them difficult to control and increase their rate of progression Key points   • • • Cancer is the end product of unregulated proliferation of cells, resulting from the accumulation of sequential genetic alterations (mutations) Proto-oncogenes and tumor suppressor genes regulate cell growth & proliferation. Mutations in these genes render them oncogenic [carcinogenic form] Malignant epithelial neoplasms include: squamous cell carcinoma [accounts for more than 90% of cancers in the oral cavity] Squamous cell carcinoma could be exophytic or endophytic TNM is used for clinical staging before biopsy taking Verrucous carcinoma Verrucous carcinoma is a low grade variant of SCC Etiology: chronic chewing of smokeless tobacco It may arise from proliferative verrucous leukoplakia Verrucous carcinoma Clinical features  Mandibular vestibule is the most common site [related to the site of habitual tobacco placement [snuff dipping habit]  Followed by buccal mucosa and gingiva  In cultural groups who keep tobacco in maxillary vestibule or under the tongue, these locations are involved  It appears as diffuse, well demarcated, painless, thick plaque with papillary or verruciform surface projections  Lesions are typically white but may appear erythematous Verrucous carcinoma Histopathology  The architecture of this tumor is diagnostic. It appears deceptively benign.  Rete ridges are blunt-ended, wide and elongated they push into the underlying connective tissue The surface of the lesion is verrucous, hyperkeratotic and clefted. Verrucous carcinoma Histopathology •Clefts are full of keratin (keratin plugs or parakeratin clefts). •epithelium generally shows no significant cellular atypia •The basement membrane is well defined.  Differential diagnosis It is mandatory to distinguish verrucous carcinoma from papillary squamous cell carcinoma [that has papillary surface and shows evident epithelial atypia]  Adequate incisional biopsy and serial sections of the lesion are highly recommended because dysplastic features are not significant & the pathologist must evaluate the overall histomorphologic configuration. Moreover, verrucous carcinoma may harbor foci of invasive squamous cell carcinoma. Fibrosarcoma Definition Malignant neoplasm of fibroblasts. It is a rare lesion in the head and neck region. Clinical features • It may arise anywhere in the head and neck region • Fibrous, fleshy masses (3-5 cm), early lesions are painless. • It appears as firm swelling with ulceration and hemorrhage Fibrosarcoma Histopathology • The cells are spindle shaped and lie in fascicles, often forming a herringbone pattern. Fibrosarcoma Histopathology • Well differentiated cases show cells with little variation in size and shape. Mitoses are present. Collagen production is noted. • Poorly differentiated cases (high grade): more cellular, with less organization. Cells produces less collagen and have greater mitotic activity Osteosarcoma • Osteosarcomas are malignant neoplasms arising from mesenchymal stem cells that have the ability to produce osteoid or immature bone [most common malignant bone tumor] Etiology As in case of most malignant tumors, osteosarcoma is of unknown etiology but: Bone irradiation and Paget’s disease of bone, increase the risk for developing osteosarcoma Osteosarcoma  Osteosarcomas of the jaws are uncommon [It is more common in long bones]  Hard painful bony swelling  Paraesthesia due to involvement of inferior alveolar nerve (in mandibular lesions) or infra-orbital nerve (in maxillary lesions)  Loosening and displacement of teeth  nasal obstruction (in the case of maxillary tumors) also may be noted Radiographic picture  Symmetric widening of periodontal ligament space around a tooth or several teeth (Garrington sign). This is the result of tumor infiltration along the periodonlal ligament space, it is not specific for osteosarcoma and may be seen with other malignancies    Lesions appear as radio-opaque, mixed radiopaque and radiolucent lesion or entirely radiolucent [This depends on the amount of bone formation in the lesion] The borders of the lesion are ill defined Resorption of roots Radiographic picture Osteosarcomas have a radiographic "Sunburst or sun-ray" appearance (in 25% of cases) [Due to sub-periosteal bone formation perpendicular to surface of bone (thin irregular spicules of new bone)] In few cases a triangular ridge of new bone is formed where periosteum is elevated by the tumor and termed Codman’s triangle. Histopathology:    The essential microscopic criterion is production of osteoid tissue by malignant mesenchymal cells. The tumor cells vary from uniform round or spindle shaped cells to highly pleomorphic cells with bizarre nuclear shapes and mitotic figures Depending on the relative amounts osteoid, cartilage or collagen produced by the tumor, they are subclassified into: osteoblastic, chondroblastic & fibroblastic Fibroblastic osteosarcoma Histopathology Chondroblastic osteosarcoma is prevalent in the jaws, it contains malignant cartilage and osteoid tissue Telangiectatic osteosarcoma is less common than other histologic variants of osteosarcoma. It is characterized by numerous wide vascular channels . Chondrosarcoma It is a malignant tumor that produces cartilaginous matrix Clinical features  these tumors are rare in jaws and facial bones  the maxilla is involved more often than the mandible (common anterior part of maxilla or posterior mandible)  Symptoms are non specific  Maxillary tumors may cause nasal obstruction  Loosening of teeth Chondrosarcoma Radiographic Picture: • Radiolucent lesion with poorly defined borders. [moth eaten] • The radiolucent area often contains variable amounts of radiopacities, which are caused by calcification of the cartilage matrix. Histopathology: It is composed of large pleomorphic chondroblasts with hyperchromatic nuclei Cells are often binucleated or multinucleated well differentiated tumors resemble chondroma Lymphoma is a heterogenous malignant disease of the lymphatic system, characterized by proliferation of lymphoid cells or their precursors Lymphoma is a heterogenous malignant disease of the lymphatic system, characterized by proliferation of lymphoid cells or their precursors Hodgkin’s lymphoma (HL) Rare in the oral cavity Non-Hodgkin’s lymphoma (NHL) Common in the head and neck region. most common histological types: --Diffuse large B cell lymphoma --Burkitt’s lymphoma Hodgkin’s lymphoma Clinical features It occurs mainly in the lymph nodes (>90%) with low incidence in extranodal sites (1–4%). The usual presenting sign is persistently enlarging non tender discrete mass or masses in one lymph node region As the condition progresses, the involved lymph nodes become matted and fixed Histopathology •It is characterized by presence of Reed-Sternberg cells in a background rich in inflammatory cells •These cells are binucleate cells with abundant cytoplasm and two large nucleoli (one in each core) that appear like ‘owl eyes OR pennies on a plate Non Hodgkin’s lymphoma Clinical features In the oral cavity, lymphoma usually appears extranodal. It may occur as: Soft tissue lesions usually appear as nontender, diffuse swellings with boggy consistency • The swellings may be erythematous or purplish, & may be ulcerated Lymphoma of bone may cause vague pain or discomfort which might be mistaken for a toothache • If untreated, it causes expansion of bone and eventually perforation of the cortical plate and production of a soft tissue swelling Non Hodgkin’s lymphoma Radiographic features Ill defined or ragged radiolucency Histopathology Normal lymphocyte Infiltrative sheets of relatively uniform neoplastic cells [lymphocytic appearing cells with varying degrees of differentiation] Low grade lesions consist of well differentiated small cells. High grade lesions consist of less differentiated cells Burkitt lymphoma • It is a peripheral B-cell lymphoma that has an extremely high proliferation rate & often presents in extranodal sites Etiology Translocation involving MYC is highly characteristic but not specific Epstien Barr virus is detected in many cases Malarial infection play a role in pathogenesis of Burkitt lymphoma Burkitt lymphoma Three variants are recognized: • Endemic [occur in malaria-endemic regions of the world] • Sporadic [occur where malaria is not endemic] • Immunodeficiency associated [occur in immunocompromised & HIV positive patients] Clinical features  Common in posterior segments of jaw bones [Maxilla affected more than mandible] Bulky tumor mass may produce facial swelling and proptosis Marked tooth mobility due to aggressive destruction of alveolar bone Pain, tenderness and paraesthesia are minimal Burkitt lymphoma Radiographic features Ill defined or ragged radiolucency Histopathology:  Sheets of cohesive neoplastic cells with round nuclei and minimal basophilic cytoplasm  Presence of macrophages [have abundant cytoplasm which appears less intensely stained than surrounding cells] which contribute to the characteristic “starry sky pattern”  Numerous mitotic figures Kaposi Sarcoma It is a locally aggressive vascular neoplasm associated with human herpes virus 8 (HHV8). Types include: ◊ Epidemic OR AIDS-related ◊ Immunocompromised or transplant associated ◊ Classic, or sporadic ◊ Endemic (African)  Oral manifestations are commonly seen in the AIDS related type Kaposi Sarcoma Clinical features • Common sites palate, followed by ginigiva and tongue. • Multiple red to violaceous macules or papules that may progress to plaques or nodules • Bleeding, ulceration and pain may be seen in advanced cases Kaposi Sarcoma Histopathology: The tumor is highly vascular, containing  abnormally dense and irregular blood vessels [Slit-like spaces] which contain red blood cells & hemosiderin  Extravasated blood cells are also seen and give the tumor its dark color.  infiltrating atypical spindle cells  increased mitotic activity may be seen Prognosis Kaposi sarcoma is often multifocal but rarely metastasizes Ewing sarcoma  Ewing sarcoma is an undifferentiated small round cell sarcoma that affects bone and soft tissue  Although it is rare, Ewing sarcoma is the second most common primary malignant bone tumor in pediatric patients Etiology • It is defined by chromosomal translocation involving EWSR1 and FLI1 which encodes the EWS-FLI1 fusion protein (in 85% of the cases) Ewing sarcoma Clinical features  pain and swelling  Fever, leukocytosis, and elevated erythrocyte sedimentation rate  Jaw involvement is more common in the mandible than the maxilla  may result in paresthesia and tooth mobility.  The nonspecific clinic-radiographic presentation may lead to a misdiagnosis of odontogenic infection or osteomyelitis Histopathological features  hypercellular sheets and nests of uniform (monotonous) small round cells with ill-defined cellular borders Mucosal Melanoma  Mucosal melanoma is a malignant neoplasm of mucosal melanocytes General knowledge A melanocyte is a cell that produces melanin, which is a responsible for the color of the skin, hair, and eyes. The melanocyte is located in the basal cell layer and has dendritic processes that allow the mobilization of produced melanin to the neighboring keratinocytes for protection of the underlying skin layers from sunlight damage Mucosal Melanoma  Mucosal melanoma is a malignant neoplasm of mucosal melanocytes  it may arise de novo or from a preexisting benign melanocytic lesion Clinical features  It is often asymptomatic, with dark brown to black macules, plaques or nodules Mucosal Melanoma Clinical features The “ABCDE” Clinical Features of Melanoma  Asymmetry [because of its uncontrolled growth pattern]  Border irregularity  Color variegation [which varies in colour depending on the amount and depth of melanin pigmentation]  Diameter greater than 6 mm  Evolving (lesions that have changed its size, shape, color, surface, or symptoms over time Key points  The histopathological architecture of verrucous carcinoma is diagnostic. No significant cellular atypia and the basement membrane is well defined.  Malignant mesenchymal neoplasms [in soft tissue] include: fibrosarcoma [may arise from periosteum] and lymphoma [may occur in bone]  Malignant Mesenchymal neoplasms [occur in jaw bone] include: osteosarcoma and chondrosarcoma  Oral manifestations are commonly seen in the AIDS related type of Kaposi sarcoma  Burkitt lymphoma has an extremely high proliferation rate and is characterized by translocation involving MYC gene  The nonspecific clinical presentation of Ewing sarcoma may lead to a misdiagnosis of odontogenic infection or osteomyelitis  The “ABCDE” clinical Features of mucosal melanoma identify it from benign melanocytic lesions Aims: The aim of this lecture is to detail the histopathological aspects if common oral mucosal malignancy Objectives: On completion of this lecture, the student should be able to: • Understand the histopathology of oral squamous cell carcinoma • Understand the histopathology of nonHodgkin’s lymphoma and Kaposi’s sarcoma of the oral tissues Reading material: Students are advised to review any relevant teaching provided in the first year. In addition they are advised to read relevant sections of the following texts: • Odell E.W. Cawson’s Essentials of Oral Pathology and Oral Medicine. 9th Edition. Elsevier, 2017 pp 317335, 394-396 • Robinson M et al. Soames’ and Southam’s Oral Pathology. 5th edition. Oxford University Press, 2018 pp 68-84 Thank you