“Tl MALIGNANT TUMORS OF THE EPITHELIAL TISSUE ORIGIN SQUAMOUS CELL CARCINOMA (Epidermoid carcinoma)Introduction Definition Squamous cell carcinoma is defined as “a malignant epithelial neoplasm exhibiting squamous differentiation as characterized by the formation of keratin and/or the presence of intercellular bridges” (Pindborg JJ et al, 1997) e most common malignant neoplasm of the oral cavity (more than 90%)Epidemiology ° The incidence - ranges from approximately 2-10 per 100,000 population per year e differs widely in various parts of the world - basis of environmental differences or lifestyle and habits among certain populations, such as betel quid chewing, snuff dipping or the habit of reverse smoking ¢ The incidence of oral carcinoma in blacks is somewhat lower than in whites « after the fourth decade e male-female ratio is approximately 2 : 1 « Carcinoma of the vermilion border of the lower lip - strong male predominanceEpidemiology South-East Asian scenario e In India, oral cancer, constituting 9.8% of an estimated 644,600 incident cancer cases in 1992, ranks first among all cancer cases in males e Third most common among females in many regions, with age standardized incidence rates e 7-17/100,000 persons/ year; the incidence rate being higher than the western rate of 3— 4/100,000/ year e the Too G08) rate is lowest for lip cancer (0.04 per 100,00 e the ese § rate is highest for the tongue (0.7 per 100,000)Epidemiology « 80% of oral cancers were preceded by oral precancerous lesions or conditions « Sometimes oral cancer arises from otherwise clinically normal mucosaEtiology e Multifactorial e No single causative agent or factor (carcinogen) has been clearly defined or accepted e more than a single factor is needed to produce such a malignancy (cocarcinogenesis)dj EtiologyEtiology Tobacco Smoking * Tobacco smoke contains more than 70 carcinogens 1. nitrosamines, 2. arsenic, 3. benzo[a]pyrene, and 4. benzene ¢ In addition, smoking produces free radicals and oxidants that promote the destruction and counteract the protective effects of endogenous antioxidants (such as, glutathione-S-transferase, glutathione reductase, and superoxide dismutase)Etiology Tobacco Smoking « Much indirect clinical evidence implicates tobacco smoking in the development of oral squamous cell carcinoma * The proportion of smokers (80%) among patients with oral carcinoma is about four times greater than that among the general population e For patients who quit smoking, the risk for developing oral cancer declines over timeEtiology Tobacco Smoking e the pooled risk for oral cancer is approximately three times greater among smokers than non smokers Moreover, the relative risk (smoker's risk for oral cancer compared with that of a nonsmoker) is dose-dependent The risk also increases the longer a person smokes cigar or pipe smoking is associated with a similar or greater risk for oral cancer compared to cigarette smokingEtiology Tobacco Smoking e In India, bidi smoking is associated with an approximately threefold greater risk of oral cancer compared to cigarette smoking e The highest - practice of reverse smoking is popular, especially among women e In reverse smoking 50% of all oral malignancies are found on the hard a aEtiology Smokeless Tobacco e Smokeless tobacco use - risk for oral carcinoma by a factor ranging from less than two to as high as 26 e lower risk associated with moist snuff and chewing tobacco and a higher risk associated with dry snuff abnormal male-to-female ratio for oral carcinoma (>1.0 : 1.5) in geographic areas where the habit is more popular among women than among men. approximately 50% of all oral cancers in smokeless tobacco users occur at the site where the tobacco is habitually placedEtiology Betel Quid (Paan) e combination of natural substances (i.e., areca palm nuts, betel leaf, slaked lime, and perhaps tobacco leaf ) chewed for their psychostimulating effects « The carcinogenicity of betel quid traditionally has been attributed to tobacco, although areca nut alone also appears to be carcinogenic e the lifetime risk of developing oral cancer is a remarkable 8% e also is associated with development of precancers, such as leukoplakiaEtiology Alcohol e alcohol in combination with tobacco is a significant risk factor for oral cancer development e generally appears to be dose dependent and time-dependent e approximately one-third of male patients with oral cancer are heavy alcohol users e cirrhosis of the liver is found in at least 20% of male patients with oral cancerEtiology Alcohol * The exact role of alcohol in oral carcinogenesis is not well understood « Ethanol in alcoholic beverages is metabolized into acetaldehyde, which is a known carcinogen « In addition, carcinogenic impurities—such as, polycyclic aromatic hydrocarbons and nitrosamines—may be present in some alcoholic beverages « Moreover, alcohol may help solubilize other carcinogenic compounds and may increase the permeability of oral epithelium to these compounds e Nutritional deficiencies associated with heavy alcohol consumption also may be a contributory factorEtiology Occupational Exposures and Environmental Pollutants e increased oral cancer risk for workers in the wood products industry chronically exposed to certain chemicals, such as phenoxyacetic acids e In regions of Taiwan with a particularly high incidence of oral cancer, investigators have reported elevated levels of heavy metal pollutants (e.g., nickel, chromium, and arsenic) in farm soil and increased blood concentrations of some of these metals in affected patientsEtiology Radiation e radiotherapy to the head and neck area increases the risk for later development of a new primary oral malignancy, either a carcinoma or sarcoma « dosedependentEtiology Vitamin/Mineral Deficiencies and Dietary Factors. lron deficiency, especially the severe, chronic form known as the Plummer-Vinson or Patersan-Kelly syndrome is associated with an elevated risk for squamous cell carcinoma of the esophagus, oropharynx, and posterior mouth. develop at an earlier age Iron deficiency may cause impaired cell-mediated immunity In addition, because the epithelium of the upper digestive tract has a relatively high turnover rate, rapid loss of iron-dependent enzymes may lead to degenerative changes, including mucosal atrophy and esophageal webs (intertwining fibrous bands of scar tissue), with heightened susceptibility to malignant transformationEtiology Vitamin/Mineral Deficiencies and Dietary Factors e Vitamin-A deficiency produces excessive keratinization of the skin and mucous membranes e this vitamin may help to prevent oral precancer and cancerEtiology Vitamin/Mineral Deficiencies and Dietary Factors « high intake of fruits and vegetables decreases the risk for numerous cancer types, including oral cancer e may be related to the protective effects of not only vitamin A but also various other ee vitamins C and E, folate, flavonoids, fiber, lycopene, and phytosterols) present within plant foods e animal fats and processed or salted meat may increase the risk for oral cancerEtiology Bacteria * oral bacteria may interact with tobacco and alcohol e Ethanol is metabolized into thecarcinogen acetaldehyde by not only hepatocytes and oral epithelial cells but also bacteria « high levels of acetaldehyde production have been associated with certain Streptococcus species, Neisseria species, and other bacteria e Candida may contribute to acetaldehyde productionEtiology Bacteria « Periodontal disease-causing bacteria may induce production of pro- inflammatory cytokines * may enhance cell proliferation and inhibit apoptosis, thereby producing a microenvironment favorable for carcinogenesis e tertiary syphilis has been associated with a fourfold increased risk for development of dorsal tongue carcinomaEtiology Candida e Hyperplastic candidiasis frequently is cited as an oral precancerous condition(also has been called candidal leukoplakia e However, the evidence for the promotion of oral carcinogenesis by Candida is largely circumstantialEtiology Oncogenic Viruses e Oncogenic (tumor producing) viruses may play a major role in a wide variety of cancers e Viral integration into the host’s genetic material may result in abnormal cell growth and proliferation e The oncogenic viruses may immortalize the host cell, thereby facilitating malignant transformation e play a role in the development of oral carcinoma - HPV and HIVEtiology Oncogenic Viruses « HPV actually is best known for its role in the development of cancers of the anogenital region (especially the uterine cervix but also the anus, vulva, vagina, and penis) only a small subset of oral carcinomas has been attributed to HPV infection The high-risk HPV types are most closely associated with dysplasia and squamous cell carcinoma detection of HPV 16 in exfoliated oral epithelial cells is associated with a nearly fourfold increased risk for oral cancer and a more than fourteen fold increased risk for oropharyngeal cancer the proportion of oral carcinomas caused by HPV infection appears to be small .Etiology Oncogenic Viruses * The characteristic risk profile for patients with HPV positive head and neck squamous cell carcinoma 1. male predilection 2. 10 years younger among the HPV-positive group 3. affect individuals of higher socioeconomic status 4. more strongly associated with certain parameters of sexual behavior (e.g., increased number of lifetime sexual or oral sexual partners, early age at sexual debut) 5. Less likely to occur in patients with an extensive history of tobacco and alcohol historyEtiology Immunosuppression * some malignancies of the upper aerodigestive tract e Persons with HIV infection and those who are undergoing immunosuppressive therapy for malignancy or organ transplantation are at increased risk for oral squamous Cell carcinoma and other head and neck malignancies, especially when tobacco smoking and alcohol abuse are presentEtiology Oncogenes and Tumor Suppressor Genes « The molecular basis of carcinogenesis involves an accumulation of mutations or epigenetic changes in two broad classes of genes: proto-oncogenes and tumor suppressor genes Proto-oncogenes may be transformed into activated oncogenes by environmental agents (e.g, viruses, irradiation, and chemical carcinogens) or inherited changes Activated oneagenes promote uncontrolled cell division and are involved in the initiation and progression of a wide variety of malignancies Tumor suppressor genes, on the other hand, inhibit cell division and indirectly allow tumor production when they become inactivated or mutated * an accumulation of several genetic aberrations is necessary before the affected cell expresses a malignant phenotypeEtiology Oncogenes and Tumor Suppressor Genes « Genetic aberrations commonly identified in oral squamous cell carcinomas include abnormalities of the ras, myc, and epidermal growth factor receptor (EGFR; also known as c-erbB1) oncogenes, and the TP53, pRb, p16, and E- cadherin tumor suppressor genes e Head and neck squamous cell carcinomas associated with tobacco and alcohol use often exhibit mutated TP53, pRb overexpression, and decreased p16 expression « In contrast, HPV-associated cases typically express wild-type TP53, low levels of pRb, and increased levels of p16Clinical Features e Mostly older men e minimal pain during the early growth phase e Oral squamous cell carcinoma has a varied clinical presentation, including the following: « Exophytic (mass-forming; fungating, papillary, and verruciform) « Endophytic (invasive, burrowing, and ulcerated) * Leukoplakic (white patch) * Erythroplakic (red patch) * Erythroleukoplakic (combined red-and-white patch)Clinical Features * The leukoplakic and erythroplakic examples are probably early cases that have not yet produced a mass or ulceration Clinical features are identical to those described for premalignant leukoplakia and erythroplakiaClinical Features e An exophytic lesion - surface that is irregular, fungating, papillary, or verruciform ¢ color - normal to white or red (depending on the amount of keratin and vascularity) e surface is often ulcerated e feels hard (indurated) on palpation‘+ Fig. 10-100 Squamous Coll Garcinoma, An eco: DUCA leson shoe areughened and megub sta wih ania of enter acrrand wi eral areas of whe heraiods. Serce ulcer ‘+ Fig. 10-101 Squamous. Got Carcinoma. Civonc uctaind feaion on fe sgn vont sutooe cf fhe tong, Te reled aniaaar smug ft incuraled cr palpation.Clinical Features endophytic growth pattern - central, depressed, irregularly shaped ulcer with a surrounding “rolled” border of pink, red, or white mucosa * The rolled border results from invasion of the tumor downward and laterally under adjacent epithelium « Perineural invasion may - cause paresthesia as © Destruction of underlying — ‘20% wo bes, Tis cance vas panes attough hist party bone, when present, a may be painful or completely painless.Clinical Features D/D of endophytic growth pattern : e Traumatic granulomas, e deep fungal infections, e tuberculosis, e tertiary syphilis, and e oral lesions of Wegener granulomatosis or Crohn's diseaseRadiological Features « Destruction of underlying bone appears on radiographs as a “moth-eaten” radiolucency with ill-defined or 3 tagged margins (an s appearance SIMIlAP «Fg to.103 squamous Cat Carcinoma 5 haractened by an irequtar, ‘moth-csten" sack to osteomyelitis) syns wesw one wom #Lip Vermillion Carcinoma ¢ found in light skinned persons with chronic exposure to UV radiation from sunlight « Seventy percent of affected individuals have outdoor occupations e elderly men « usually is associated with actinic cheilosis ° may arise at the site where the patient holds a cigarette, cigar, or pipe e Almost 90% of lesions are located on the lower lipLip Vermillion Carcinoma Clinical Features e crusted, oozing, non tender, indurated ulceration e usually less than1 cm in greatest diameter ° grows slowly e Metastasis is a late event; at diagnosis, fewer than 10% of patients have lymph node metastasis, usually in the submental region e Perineural invasion may result in extension of the tumor into the mandible through the mental foramen e patient neglect can result in considerable destruction of normal tissueFig. 10-704 Squamous Cal Carcinoma, Crista, conc Ef A Tak chine stearamerrionmenie ona erate Tecan eonest S's we neanonegentwan oem (F-10105 Squamous cat fe eae ‘etl in torso Feokvement. oven recy vie ote Such ws ‘ep vermin Tis iceratng ein ofthe rp had baer resent fox more than | year befow agnosisIntraoral Carcinoma e the most common sites for intraoral carcinoma are the 1. tongue (usually the posterior lateral and ventral surfaces) 2. floor of mouth 3. gingiva, 4. Alveolar bone, 5. buccal mucosa, 6. labial mucosa, and 7. hard palateCarcinoma of Tongue e 25 to 50% of all intraoral cancer « less common in women than in men * essentially a disease of the elderly, but it may occur in relatively young persons Biglegy 1. Syphilis . Leukoplakia . poor oral hygiene . chronic trauma . alcohol and tobacco akwWns=Carcinoma of Tongue Clinical Features « Painless masses or ulcers lesion ultimately becomes painful, especially when it becomes secondarily infected ° may begin as a superficially indurated ulcer with slightly raised borders proceed either to develop a fungating, exophytic mass or to infiltrate the deep layers of the tongue, producing fixation and induration without much surface change e Mostly posterior lateral border e 20% occur on anterior lateral or ventral surfaces, and * only 4% occur on the dorsum (syphilitic glossitis)Carcinoma of Tongue Clinical Features e Lesions near the base of the tongue are particularly insidious e asymptomatic until far advanced ° presenting manifestations may be a sore throat and dysphagia e the lesions on the posterior portion of the tongue are usually of a higher grade of malignancy, metastasize earlier and offer a poorer prognosis, especially because of their inaccessibility for treatment e Metastases occur with great frequency in cases of tongue cancer© Fig, 10-107 Squarnous Cal Carcinoma, Cifven, rc onc wale lesion cf the postr neal onder oe creaCarcinoma of Floor of the Mouth 15% of all intraoral carcinomas « Average age — 57 years e Mostly men e most often associated with the development of a second primary malignancy * Floor of mouth carcinomas most often arise in the midline region near the frenum Etiology ° preexisting leukoplakia or erythroplakia « Alcohol * Tobacco e Poor oral HygieneCarcinoma of Floor of the Mouth Clinical Features « indurated ulcer of varying size * one side of the midline * may or may not be painful * more frequently in the anterior portion of the floor than in the posterior area Early extension into adjacent tissues * may invade the deeper tissues and may even extend into the submaxillary and sublingual glands limitation of motion of tongue, often induces a peculiar ‘thickening or slurring of the speech * Metastases from the floor of the mouth are found most commonly in the submaxillary group of lymph nodes, and Since the primary lesion frequently occurs near the midline where a lymphatic cross drainage exists, contralateral metastases are often present Fortunately, distant metastases are rare‘Fig. 10-108 Squamous Cali Caremoma, Grom rect an whe lesen nh antaniyRoor of mouCarcinoma of Gingiva Etiology « least associated with tobacco smoking * no more specific or defined e may speculate the possible role of chronic irritation Clinical Features: ° usually painless e most frequently arise from keratinized, posterior mandibular mucosa « have the greatest predilection for femalesCarcinoma of Gingiva Clinical Features: ° 61 years — average age e mandibular gingiva > maxillary gingiva e initially as an area of ulceration which may be a purely erosive lesion or may exhibit an exophytic, granular or verrucous type of growth ° have a special propensity to mimic common, benign inflammatory and reactive lesions, such as the pyogenic granuloma, gingivitis and periodontal disease ¢ arises more commonly in edentulous areas e fixed gingiva is more frequently involved primarily than the free gingivaCarcinoma of Gingiva Clinical Features: « Often destroy the underlying bone and cause tooth mobility Pathologic fracture sometimes occur The lesion may go unrecognized until after tooth extraction, when it proliferates out of the socket to mimic the hyperplastic granulation tissue of an epulis granulomatosa Cancers that develop in an edentulous area may “wrap around” a denture flange and superficially resemble inflammatory fibrous hyperplasia (epulis fissuratum) e Metastasis is a common sequela of gingival carcinoma Cancer of the mandibular gingiva metastasizes more frequently than cancer of the maxillary gingiva °1 Fig. 10-110 Squarsoum Cot Careinema. fn eocusus, pond sutiee charge of Bw gegen Ws Poel as renter Unt mecca nite erat SneopS igre 228. Carcinoma ots payin. Teel cepa te gro ateerwny oan he 2 yd il gt jeameled amr grew eerie Meccnecs: camer A ‘be groMCNy seca EAL EARN Ca. T a UE deed prance ae ad at fr fin tecpa be many ry ce sae co vaya (ey Malt Sct arc Chars 4 Mean, Remains 3196.Carcinoma of Alveolar Bone e alveolar carcinomas - usually painless e most frequently arise from posterior mandibular region e Sometimes as extension of gingival carcinoma e mimic common, benign inflammatory and reactive lesions e Tumors of the maxillary alveolar ridge may extend onto the hard palate* Fig. 10-111 Squamous Cell Carcinoma. An sxophrytic lesion weit an requir and pebtied surtace. Thee fsa inaar ideation ‘ong the anal aspect reauing Won pracsura tom fe patent's ue denture. he inden ater bone was ested ‘ipre 220, Pathologie rctre of mance eaesnd by Me evasion permet carcinoma ing on the swore,Carcinoma of Buccal Mucosa e approximately 10 times more common in men than in women e occurs chiefly in elderly persons * average age at occurrence was 58 years Etiology * not better understood e use of chewing tobacco e habit of chewing betel nut e Leukoplakia - precursorCarcinoma of Buccal Mucosa Clinical Features: * more aggressive * recurrence — high * common site where betel quid use is prevalent « develop most frequently along or inferior to a line opposite the plane of occlusion painful ulceration induration and infiltration of deeper tissues are common Sametimes - superficial and appear to be growing outward from the surface rather than invading the tissues - called exophytic or verrucous growths * Metastases - relatively high ° The most common sites of metastases are the submaxillary lymph nodes ° °Carcinoma of right buccal mucosaCarcinoma of the Palate e not a particularly common lesion e Less percentage of occurrence — approx 0.5% Clinical Features: e poorly defined, ulcerated, painful lesion on one side of the midline (tumors of accessory salivary gland origin, even the malignant lesions, are often not ulcerated, but are covered with an intact mucosa. This fact may be of some aid in helping to distinguish clinically between these two types of neoplasms)Carcinoma of the Palate Clinical Features: « frequently crosses the midline * may extend laterally to include the lingual gingiva or posteriorly to involve the tonsillar pillar or even the uvula * may invade into the bone or occasionally into the nasal cavity, while infiltrating lesions of the soft palate may extend into the nasopharynx « Metastases to regional lymph nodes — considerable percentage of casesa. : Epidenmoid carcisoma of palate.Carcinoma of Retromolar Trigone ° may spread to numerous adjacent structures, including the oropharynx, buccal mucosa, alveolar ridge, and pterygomandibular raphe Invasion of the pterygomandibular raphe may lead to involvement of the skull base, masticator space, and floor of mouthOropharyngeal Carcinoma © . ° base of tongue, tonsillar region (i.e., tonsil, tonsillar fossa, and pillars), and posterior pharyngeal wall the tonsillar region accounts for the majority (approximately 70% to 80%) of cases Favored site for HPV-associated carcinomas Oropharyngeal carcinomas - same basic clinical appearance as more anterior carcinomas posterior location lesions often go unrecognized for long periods persistent sore throat, difficulty in swallowing (dysphagia), pain on swallowing (adynophagia) pain may be dull or sharp frequently is referred to the ear“+ Fig. 10-113 Squamous Gott Carcinoma, Oropharyngeal, A. large, entracak teton icing the ot so pala and tonsa regon-B, krmunctistochemical sa showed the timer to bo ove 0016. Wich sa surge mark er rane Bony act. fick human pankcma vrs (PV fection among oropharyngeal squemaus ex caronomas.C, in Stu hytretaton (SH) demensraiod thn presence of iran cia HEV 16:Carcinoma of Maxillary Sinus ° an exceedingly dangerous disease e Uncommon malignancy e unknown cause ° squamous cell carcinomas of the paranasal sinuses have been associated only weakly with tobacco use e HPV may be an etiologic factor in some casesCarcinoma of Maxillary Sinus Clinical Features: * only 3% of all head and neck carcinomas * asymptomatic or mimic sinusitis for long periods ¢ chronic unilateral nasal stuffiness or an ulceration or mass of the hard palate or alveolar bone e The tumor grows to fill the sinus e Perforate through the surrounding bone e more common in men e chiefly a disease of elderly personsCarcinoma of Maxillary Sinus Clinical and Radiographic Features « lf the tumor perforates the lateral wall of the sinus, unilateral facial swelling and pain are usually present e With medial extension, nasal obstruction and hemorrhage are common * Superior extension results in displacement or protrusion of the eyeball e Approximately 9% to 14% of patients have cervical or submandibular lymph node metastasis at the time of diagnosis « Distant metastasis is uncommon until late in the progression of diseaseCarcinoma of Maxillary Sinus Clinical Features: « When the second division of the trigeminal nerve is involved, intense pain or paresthesia of the midface or maxilla may occur, perhaps simulating a toothache. e Adjacent teeth may become loose Radiographic Features: e Dental radiographs often reveal a “moth-eaten” destruction of the lamina dura and surrounding bone e Apanoramic radiograph shows a cloudy sinus with destruction of its bony wall; however, the rie of the tumor is best visualized by CT orFigure 2-32, Epidermoid carcinoma of the maxillary sinus. (A) The atvootar ridge shows thickoning, reddoring and deformity, though there is 0 wceration of the mucosa (B) The radiograph reveals raggedness of the manila sinus and obvious bony athocaion. ‘Fig. 10-126 Carcinoma of tho Maxtiary Sinus. Tho baron has ‘roouced a buge of he posteror malin sack age ad i DOO fang te wowrate Dwcugg the surtace mucosaMetastasis e Largely via the lymphatics to the ipsilateral cervical lymph nodes * Acervical lymph node that contains metastatic carcinoma is usually firm to stony hard, nontender, and enlarged e if the malignant cells have perforated the capsule of the node and invaded into surrounding tissues, then the node will feel “fixed,” or not easily movable e Extracapsular spread (extension of metastatic deposits outside of the lymph node capsule) is a microscopic feature associated with poor prognosis e Occasionally, contralateral or bilateral metastatic deposits, distant (“below the clavicles”) metastasis at diagnosisMetastasis e most common sites of distant metastasis are the lungs, liver, and bones, but any part of the body may be affected e Carcinoma of the lower lip and oral floor - submental nodes e posterior portions of the mouth - the superior jugular and digastric nodes e oropharyngeal carcinoma - jugulodigastric or retropharyngeal a a115 Squamous Cell Carcinoma. Metastatic depots + Fig. 10174 Squamous Gen Carcinoma, Metastatic Spreaa, WHA cencal hmph nodes precent as frm, painless entargements 2s Dara Gerrensiaing potent ses tor matastaoc normed cf cra seen inthis patient with metastasis to a superior jugar node from a arerenna to mena har cece ostaror lateral tongue carcinoma,Multiple Carcinomas e Patients with one carcinoma of the mouth or throat are at increased risk for additional concurrent (synchronous) or, more commonly, later (metachronous) primary surface epithelial malignancies of the upper aerodigestive tract, stomach, lungs, and other sites ° 6% - 44% e male patientsMultiple Carcinomas This tendency - field cancerization - a process whereby exposure to carcinogens, such as tobacco and alcohol, creates a diffuse field of altered epithelial cells with increased potential for malignant ‘transformation Molecular analyses of various markers, including loss of heterozygosity (LOH), microsatellite alterations, TP53 tumor suppressor gene mutations, and X-chromosome inactivation, have identified genelic alterations shared between tumor tissue and cl adjacent clinically normal appearing tissue in one-third to one-half of cases examined significant proportion of second primary tumors develop from the same preneoplastic precursor lesion or “field,” with the remaining cases representing tumors that develop independently patches of clonal cells can progress to develop additional mutations and give rise to subclones in a process known as clonal divergence, which would account for the genetic heterogeneity typically seen among these tumors Interestingly, field cancerization does not appear to be associated with malignancies attributed to HPV infectionTNM Staging Tumor size and the extent of metastatic spread are the best prognostic indicators for oral squamous cell carcinoma Quantifying these clinical parameters is called staging three basic clinical features: . T—Size of the primary tumor, in centimeters . N—Regional lymph node involvement . M—Distant metastasis These three parameters are tallied together to determine the stage the higher the stage, the worse the prognosis But survival rates are similar for patients with stage |, Il, and Ill disease « HPV status appears to be the most important prognostic factor for patients with oropharyngeal carcinoma wh e‘Tumor node matastass CHA Staging Systane Ol and Oropharyngeal Catena R= by ees baat To _ Nokes afer Aaror Ta Nees Fae Ree Coe ree NR nA pe OE AES _ Motes rae ern one em Pa ES te ren “Res _ Won Dae or cont ne oe fom Rl 7S as ara Ron Ran on gateTumor-node-metastasis (THM) Clinical Staging Categories for Oral and Oropharyngeal Squamous Call pm Carcinoma with Corresponding Survival Rates ‘aero cara ooa 2 Pm ipa ning ne ona Hv te ete cattnir nrasethve Een 8 wean rome mre et ‘neering te SEEM ans Por tne ST Sane Cou hve panes es Yar avs ae ase 29 TH) OL ‘Siena eos year usar We Jeane ngm nam BSHistopathology e Squamous cell carcinoma arises from dysplastic surface epithelium e invasive islands and cords of malignant squamous epithelial cells « At the earliest moment of invasion, the adjectives superficially invasive or microinvasive often are used « Invasion is represented by irregular extension of lesional epithelium through the basement membrane and into subepithelial connective tissueHistopathology . Individual squamous cells and sheets or islands of cells proliferate within the connective tissue, without attachment to the surface epithelium The invading tumor destroys normal tissue and may extend deeply into underlying adipose tissue, muscle, or bone Lesional cells may breach the perineurium that encases nerve bundles (perineural invasion) or may invade the lumina of veins or lymphatics (vascular invasion) strong inflammatory or immune cell response to invading epithelium necrosis may be present may induce dense fibrosis (desmoplasia or scirrhous change) and the formation of new blood vessels (angiogenesis)* Fig. 10-116 Squamous Cell Carcinoma. A, Perineural invasion. Tumor has breached the perineurium encasing this nerve fiber B, Angioinvasion. Tumor is present within the lumen of this vessel.Histopathology e The lesional cells - abundant eosinophilic cytoplasm with large, often darkly staining (hyperchromatic) nuclei « an increased nuclear-to-cytoplasmic ratio e Varying degrees of cellular and nuclear pleomorphism « keratin pearls (a round focus of concentrically layered, keratinized cells) e Individual cells also may undergo keratinizationHistopathology e Histopathologic grading of squamous cell carcinoma is based upon the degree of resemblance to normal squamous epithelium and the amount of keratin production e Lesions are graded on a three-point (grades | to Ill) or a four-point (grades | to IV) scale e The less differentiated tumors receive the higher numerals e The histopathologic grade of a tumor is related somewhat to its biologic behavior| /| Histopathology Ya] a « Low-grade, grade | |, or well- differentiated -a tumor that is mature enough to closely resemble its tissue of origin often grows ata | slightly slower pace and metastasizes later in its courseHistopathology e High-grade, grade III/IV, poorly differentiated, or anaplastic - a tumor with marked pleomorphism and little or no keratin production may be so immature that it becomes difficult to identify the tissue of origin. In such cases, immunohistochemical studies (e.g., for NR ie } i cytokeratins or p63) may ee Wy eM di Nae Le, be needed to support an Fig. 10-118 Poorly Diferentiated Squamous Cell Carcinoma. epithelial origin. Such The numerous pleomorhic cals win the mina proora reeresent tumors often enlarge Sooo rapidly, metastasize early4 Histopathology Cc « Grade Il, } 1 Moderately differentiated -A tumor with a microscopic appearance somewhere es between these two extremesHistopathology Oropharyngeal Carcinoma * For oropharyngeal squamaus cell carcinoma, detection of ‘transcriptionally active HPV infection is especially important in determining prognosis + HPV-positive oropharyngeal squamous cell carcinomas often are peony differentiated and nonkeratinizing with basaloid cytologic features « The gold standard for determining whether a carcinoma likely was caused by HPV is high-risk HPV E6 and IE7 oncogene expression analysis by Guanine reverse transcriptase polymerase chain reaction (qRT-PCR) best suited for fresh frozen tissue technically demanding detection of p16 by immunohistochemistry is more widely available, is readily performed on formalin-fixed paraffin-embedded tissue, and is considered a highly sensitive (albeit not highly specific) surrogate for transcriptionally active, high-risk HPV infection in oropharyngeal carcinomas