Malignant Epithelial Pathology Case Presentations (Dr. Abdelsayad) (10am)

(Slide 55) What is the Staging System we use for many cancers (including oral SCC) ?

- Stage I, II, III: • The larger the stage, the larger the primary cancer and-or the greater the number of local metastases - Stage IV: • Cancer has metastasized to distant parts of the body

(Slide 102) What are Factoids and Risk factors for HPV related Oral Pharynx Squamous Cell Carcinoma?

-People tested positive for HPV16 oral infection have a 14 times increased risk of developing HPV+OPC - -Risk is associated w/ increase in No of sexual partners (25% ↑ ≥ 6 partners) - -Risk is associated w/ history of oral-anogenital sex (125% ↑ ≥ 4 partners) - -Risk is elevated for a ♂ who has a ♀ partner w/ a history of either abnormal Pap smear or cervical dysplasia - -Risk is elevated for a ♀ who has first intercourse w/ a ♂ who has venereal warts - Marijuana is an independent risk factor in HPV+OPC (immunomodulatory effect)

(Discussed) Common Questions, 1) Can someone "get" HPV related cancer? 2) Should we screen partners of HPV + oropharyngeal or cervical cancer patients? 3) If your partner is diagnosed with HPV cancer, should you avoid having oral and genital sex? 4) Are there tonsil screening tests?

1) Yes, reports in the literature of 2 partners couples, both non smokers, non drinkers getting tonsil cancer DNA sequences of the HPV were identical in each couple, but different the other couple (Andrews et al J Infectious Disease, 2009) 2) No, they have already been exposed and it is unreliable 3) No, because you have already been exposed 4) There are not reliable tests because the crypts

(Slide 25) Case 2 Presentation - A 61 yo non-smoker female presented w/ a tender gingival mass, between teeth #8 & #9 - At presentation, patient reported that she had "masses on both sides of her neck" - Her physician referred her to a dental clinician to r/o dental infection A Mucosal graft was taken from the cheek mucosa using the same blade that was used in the excision of gingival mass What is a likely diagnosis?

Dx: Squamous Cell Carcinoma of gingiva; w/ transplanted Carcinoma in the cheek, and Bilateral Metastatic Neck Lymphadenopathy Luckily the Patient began treatment and is doing okay. May she hopefully continue getting well!

(Slide 60) Which cancer has the best prognosis, which cancer has the worst prognosis and what is the main cause of death with cancer?

Lip cancer has best prognosis, where as posterior oral or oropharyngeal (HPV-ve) cancer has worst prognosis • 10-25% of patients develop additional mouth/throat malignancies - Especially if continue to use cigarettes/alcohol • Main cause of death is local invasion of vital structures

(Slide 22) Case 1 Presentation • A 65 year-old female patient presented to her dentist initially with a 5mm gingival nodule between #27 and #28. Bleeding and pain were reported. A clinical impression of "Pyogenic Granuloma" (PG) was considered. The lesion was excised and the patient was given antibiotic therapy and dismissed. Tissue was not submitted. • The patient returned to clinic 6 weeks later with a recurrence, now 1cm in diameter. The lesion was re-excised, and assumed to be recurrent PG. The area was thoroughly curetted and teeth were scaled and planned, lesion was not excised • The patient returned 3 months later for a second recurrence, now >2cm in diameter with marked mobility of #27. Lesion was excised and extraction of #27. Tissue was not submitted. • Patient returned for a third recurrence two months later, now 4cm in diameter, and the extraction socket did not heal • The patient was finally referred to a local oral surgeon for management. An incisional biopsy was performed (Hint: There were moth eaten radiolucencies in the radiographs) What is a likely Diagnosis?

Notice the Keratin Pearls in the Diagnostic Slides

(Slide 76) (Picture Slide) What is Verrucous carcinoma?

associated with smokeless tobacco

(Slide 35) What is the Relevant Histopathology of Squamous Cell Carcinoma in terms of what this carcinoma breaches, how we grade it, what we correlate with higher rates of recurrence and metastasis and depth of invasion?

• Breach of basement membrane • SCC assigned a grade of well, moderately, or poorly differentiated based on how it resembles (differentiates toward) normal epithelium - Some evidence shows the worse the grade, the worse the prognosis • Angiolymphatic (ALI) & perineural (PNI) invasion correlate w/ higher rates of recurrence and metastasis • Depth of invasion (DI) is proven predictive in some studies; - Lesions > 4mm in depth have tendencies of invasion into anatomic structures like fat, muscle, nerves & have higher rates of metastases - DI >4mm → neck dissection along w/ resection of the primary tumor

(Slide 47) What is the stepwise fashion in which we manage a Patient with a Suspicious Lesion?

• Establish a diagnosis: - Incisional biopsy or refer to OMFS for incisional biopsy • Referral to medical center for workup: - CT/MRI/PET to evaluate extent of disease • Size of disease at primary site • Presence/absence of metastatic disease - Regional metastasis to cervical lymph nodes - Distant metastasis to other organs: lung most common site for oral SCC - Evaluation of patient health, social history - Cancer staging (TNM system)

(Slide 63) What are considerations when treating cancer patients?

• Staging of disease determines treatment: - Treatment with curative or palliative intent - Surgery, radiation therapy, and/or chemotherapy - Surgery with or without cervical lymph node dissection Patient ability to withstand treatment must also be evaluated - Morbidity/ mortality of surgery -Side effects of chemotherapy, radioation Mucositis, trismus, xerostomia, infections...

(Slide 53) What is the system for TNM cancer staging (Prognosis Marker) ?

• System of measuring extent of cancer • Endorsed by American Joint Committee on Cancer (AJCC) - T: size of primary tumor • T1, T2, T3, T4 - N: presence/absence of locoregional lymph node metastasis • N0, N1, N2, N3 - M: presence/absence of distant (blood-borne) metastases • M0-M1 • For example, one's cancer may be staged as T1N0M0, T3N1M1, etc...

(Slide 75) What are Squamous cell carcinoma subtypes?

• There are many histologic subtypes of SCC, most of which have an unknown clinical relevance: - Papillary SCC - Verrucous carcinoma - Basaloid SCC - Adenosquamous SCC - Adenoid SCC -Sarcomatoid/ spindle cell SCC - HPV-associated oropharyngeal SCC -Keratoacanthoma -like SCC - Cuniculate SCC

(Slide 124) What are other Tonsillar (Oropharyngeal) Masses used for Differential Diagnosis against HPV?

• Tobacco-related squamous cell carcinoma • Papilloma • Lymphoepithelial cyst • Salivary gland tumor (deep lobe of parotid) • Cervical Chordoma