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CC56 year old male comes to your office saying that last week he noticed a lump in the right side of his neck, and wants to know what that meant. He has no symptoms.

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HPINone. No pain, no other complaints, no earlier findings.

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PMHLIH repair 5 years ago.Had a normal colonoscopy at 52

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ROSNC

4.OK, what SHOULD you write?

ROSConstitutional: No complaintsEyes: No complaintsENT: No complaintsCardiovascular: No complaintsRespiratory: No complaintsGastrointestinal: No complaintsGenitourinary: No complaintsMusculoskeletal: No complaintsIntegumentary: Has this lump in his right neckNeurological: No complaintsPsychiatric: No complaintsHematologic: No complaintsAllergic/Immunologic: No complaints5.Next?

MED/ALLA baby ASA a day

No allergies

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SH/FHSmokes 25 pk/yrs since the age of 18 years, drinks socially, meaning at gatherings, parties, weekends, nights.

FH: wife healthy, two healthy grown children, parents: Father died at 86 of pneumonia, mother alive at 78, healthy

7Any comments?8Next?

PENormal except neck exam: a 2x2 cm soft, movable mass is located above the clavicle, medial to the SCM muscle. Vital Signs: T 97.4 HR 56 bpm BP 132/78 O2 sat 96%RA RR 16GENERAL APPEARANCE: Well developed, well nourished, alert and cooperative, and appears to be in no acute distress.HEAD: Normocephalic.EYES: PERRL, EOMI. Fundi normal, vision is grossly intact.NOSE: No nasal discharge.EARS: External auditory canals and tympanic membranes clear, hearing grossly intact.THROAT: Oral cavity and pharynx normal. No inflammation, swelling, exudate, or lesions. Teeth and gingiva in good general condition.NECK: Neck supple, non-tender. 2x2 cm mass medial to the R SCM, movable. No thyromegaly.CARDIAC: Normal S1 and S2. No S3, S4 or murmurs. Rhythm is regular. There is no peripheral edema, cyanosis or pallor. Extremities are warm and well perfused. Capillary refill is less than 2 seconds. No carotid bruits.LUNGS: Clear to auscultation and percussion without rales, rhonchi, wheezing or diminished breath sounds.ABDOMEN: Positive bowel sounds. Soft, nondistended, nontender. No guarding or rebound. No masses.MUSKULOSKELETAL: ROM intact spine and extremities. No joint erythema or tenderness. Normal muscular development. Normal gait.EXTREMITIES: No significant deformity or joint abnormality. No edema. Peripheral pulses intact. No varicosities, normal range of motion, normal sensation with distal capillary filling of less than 2 seconds without tenderness, swelling, discoloration, nodules, weakness or deformity; examination of both ankles, knees, legs, and hips reveals normal range of motion, normal sensation without tenderness, swelling, discoloration, crepitus, weakness or deformity.NEUROLOGICAL: CN II-XII intact. Strength and sensation symmetric and intact throughout. Reflexes 2+ throughout. Cerebellar testing normal.PSYCHIATRIC: The mental examination revealed the patient was oriented to person, place, and time. The patient was able to demonstrate good judgement and reason, without hallucinations, abnormal affect or abnormal behaviors during the examination. Patient is not suicidal. 9Now what?

Now what?How about an FNA? Now what?FNA of neck mass showed moderately differentiated invasive SCC

10.What is SCC? 11.Any markers?What is SCC?Head and neck SCC is a cancer that starts in the lip, oral cavity, nasal cavity, paranasal sinuses, pharynx, and larynxSCC originates from the squamous mucosa or from ciliated respiratory epithelium that has undergone squamous metaplasia HNSCCs express epithelial markers such as cytokeratins. In well-differentiated tumors, no additional stains are usually needed. In poorly-differentiated lesions, immunohistochemistry may be useful. HNSCCs are immunopositive for cytokeratin cocktails, AE1/AE3 and pancytokeratin. CK5/CK6 and p63 are also excellent markers to detect squamous differentiation. 11Any histological features typical of SCC?

This is a well-differentiated, keratinizing squamous cell carcinoma of the oral cavity at medium magnification. The pinker or more eosinophilic areas are keratin whorls or pearls. 12How do we work this up?

PET-CT

2.9 cm right level 2 LN w/ intense uptake and SUV max of 12.9Second 8mm node adjacentSubtle asymmetric uptake in R posterior BOT (base of the tongue, a normal variation) potential uptake in right tonsil

No mass on CT/enhanced CT

13Whats an SUV?

Whats an SUV? (no, its not some sort of car)Cancerous cells multiply more rapidly than normal cells, so they are more active. A positron emission tomography (PET) scan creates images of cell activity, using standardized uptake value (SUV) as a measurement. SUV describes the level of activity in a particular spot compared to activity elsewhere in the body. An SUV reading of 1 is baseline or normal cellular activity. An SUV of 2.5 or greater can indicate metastatic cancer activity, but other factors can provoke above-normal readings.

Right inferior internal jugular node metastases with extranodal invasion.PET scan 64 minutes after fludeoxyglucose (18F) was administered, shows some fluff around the tumor.

STAGING SCC of the Head and NeckPatient Staging:T0:No tumor LN: N2b multiple ipsilateral LN, none more than 6 cmMetastases: M0 none

14What does this mean?

Primary tumor (T) TX Primary tumor cannot be assessed T0 No evidence of primary tumor Tis Carcinoma in situ T1 Tumor 2 cm or less in greatest dimension T2 Tumor > 2 cm but not more than 4 cm in greatest dimension T3 Tumor > 4 cm in greatest dimension T4a Moderately advanced local disease Lip - Tumor invades through cortical bone, inferior alveolar nerve, floor of mouth, or skin of face

Oral cavity - Tumor invades adjacent structures (eg, through cortical bone into deep extrinsic muscle of the tongue, maxillary sinus, or skin of face)

T4b Very advanced local disease Tumor invades masticator space, pterygoid plates, or skull base and/or encases internal carotid artery

Regional lymph nodes (N) NX Regional nodes cannot be assessed N0 No regional lymph node metastasis N1 Metastasis in a single ipsilateral lymph node 3 cm or less in greatest dimension N2 Metastasis in a single ipsilateral lymph node > 3 cm but not more than 6 cm in greatest dimension; or in multiple ipsilateral lymph nodes, none > 6 cm in greatest dimension; or in bilateral or contralateral lymph nodes, none > 6 cm in greatest dimension N2a Metastasis in a single ipsilateral lymph node > 3 cm but not more than 6 cm in greatest dimension N2b Metastasis in multiple ipsilateral lymph nodes, none > 6 cm in greatest dimension N2c Metastasis in bilateral or contralateral lymph nodes, none > 6 cm in greatest dimension N3 Metastasis in a lymph node > 6 cm in greatest dimension Distant metastasis (M) M0 No distant metastasis M1 Distant metastasis 15.Prognosis?Prognosis of HNSCCThere are two prognostic factors for HNSCC: HPV (Human Papilloma Virus) positivity and exposure to tobacco and alcoholHPV is one of the most important independent favorable prognostic factors in HNSCC. However, only the rate of locoregional recurrence, but not that of distant disease, is diminished in patients with HPV-positive SCC. Increased sensitivity to chemotherapy and radiotherapy in HPV-positive oropharyngeal cancer may be related to absence of exposure to tobacco and presence of functional p53 protein. Increased survival of patients with HPV-positive SCC may be in part attributable to absence of dysplastic fields related to tobacco and alcohol exposure.

Prognosis of HNSCCIt has been demonstrated that the presence and type of TP53 mutation is also of prognostic relevance. Several studies have shown a correlation between p53 mutation and lower response rates to chemotherapy and shorter overall survival times. Prognosis of HNSCCAbout one third of patients presents with early-stage disease, whereas two thirds present with advanced cancer with lymph node metastases. Early-stage tumors are treated with surgery or radiotherapy and have a favorable prognosis. The standard of care for advanced tumors is surgery combined with adjuvant radiation therapy and/or chemotherapy. Survival outcomes are poor (40-50% five-year survival rates) and the treatment is uniformly morbid. Organ-preservation protocols, with combined chemotherapy/radiation therapy and surgery for salvage, are increasingly performed. 16What should our patient have first? Surgery? What surgery? Radiation? Chemo?Our patients Surgical TreatmentDirect Laryngoscopy with biopsy 17.Whats this?Percutaneous Gastrostomy 18.Whats this?Extraction of 4 wisdom teeth 19. Why?Trans-oral Robotic Radical Tonsillectomy 20.Whats this?L and R Node Dissection, R 1-4, L 1 21.Whats this?R Submandibular gland transfer (to keep gland out of future radiation field) 22. Whats this?

23Anything else?

Lymph nodes of the Head and NeckLevel IA submental nodesLevel IB submandibular nodesLevels IIA and IIB upper jugular nodes along SCM to the inferior border of the hyoid bone above and below spinal accessory nerve. IIA: drains oral cavity and larynx. IIB: drains oropharynxLevel III middle jugular nodes to the inferior border of the cricoid cartilage. Drain oral cavity, oropharynx, nasopharynx, hypopharynx, and larynx. Level IV lower jugular nodes to the clavicle. Drain hypopharynx, thyroid, cervical esophagus, and larynx. Levels V A and B posterior triangle nodes. Drain nasopharynx, oropharynx, and the skin of the posterior scalp and neckLevel VI anterior compartment. Drain thyroid gland, glottic and subglottic larynx, apex of the pyriform sinus, and the cervical esophagus

Future Treatment

Awaiting radiation therapy (5 weeks after surgery)

Surgical Therapy

Panendoscopy is the primary surgical therapy used to discover an occult primary lesion. The procedure begins with nasal endoscopy using a 0 rigid endoscope to examine the nasopharynx. Generous biopsy samples of the nasopharynx are obtained for both frozen sectioning and permanent sectioning. Frozen sectioning of the nasopharynx is the first portion of the endoscopy.If the results are positive for carcinoma, the procedure is halted because definitive treatment of nasopharyngeal carcinoma is radiation and chemotherapy. By performing this aspect of the procedure first and by obtaining results that are positive, the patient is spared both the additional morbidity of alternate biopsies of the site and the probable surgical treatment of the cervical lymphadenopathy.

Surgical TherapyIf the results from the frozen sections of the nasopharynx are negative, the oral cavity, oropharynx, hypopharynx, and larynx are inspected and palpated. These areas can be evaluated with a laryngoscope. After thoroughly palpating the base of the tongue, the examiner obtains biopsy samples. The tonsillar fossa is then inspected. Considerable controversy surrounds the proper sampling technique of a tonsil. Some clinicians obtain biopsy samples of any suspicious sites found on the tonsil. Others perform elective tonsillectomy to eliminate sampling errors. The unilateral tonsillectomy adds little morbidity and allows thorough sampling of this site. Others argue that bilateral tonsillectomy also adds little morbidity and decreases confusion of asymmetric tonsils in follow-up examination. The only clinical situation that apparently justifies a bilateral tonsillectomy is the presence of bilateral metastatic cervical lymphadenopathy.Surgical TherapyNext, a cervical esophagoscopy is performed to examine the esophagus. If any suspicious lesions are present, biopsy samples are obtained and sent for permanent sectioning.Depending on the results of the panendoscopy, either the newly found primary lesion (other than the nasopharynx) is addressed surgically along with the cervical lymphadenopathy or the lymphadenopathy is addressed separately with the appropriate neck dissection.

Radiation TherapyThe entire pharyngeal axis is generally accepted as the mucosal sites to be included in the radiation field in patients with occult primary lesions. Theoretically, this should prevent the occurrence of the primary lesion. In order to decrease the morbidity of radiation induced xerostomia, some practitioners would not include the nasopharynx within the radiation field if the results of the endoscopy and the findings on imaging studies are negativeRadiation TherapyAlthough the value of radiation therapy has been confirmed, the field to be covered by the radiation therapy is controversial. Bilateral neck irradiation?Unilateral neck irradiation?Bilateral cervical irradiation with surgical therapy improves locoregional control of cancer and is accepted as the standard of care for patients with advanced cervical disease (>N2).Chemotherapy for Squamous cell carcinoma

Chemotherapy is generally reserved for patients with clinical or pathologic indicators of aggressive disease or primary nasopharyngeal carcinoma. Patients with extensive lymphadenopathy (>N2C), pathologic evidence of extracapsular spread of the carcinoma outside of individual lymph nodes, unresectable local disease, or distant metastatic spread of the carcinoma often undergo chemotherapy for curative intent or palliative treatment.

Chemotherapy for Squamous cell carcinoma

Treatments that include platinum-based chemotherapy are used in patients with squamous cell carcinoma. The most commonly used chemotherapeutic agents are 5-FU and cisplatin. Alternatively, docetaxel has also been used in combination with cisplatin.Paclitaxel 175 mg/m2IV infusion over 3h on day 1pluscisplatin 100 mg/m2IV on day 2plus5-FU(5-fluorouracil) 500 mg/m2/day IV continuous infusion over 120h every 21dorDocetaxel 75 mg/m2IV on day 1pluscisplatin 75 mg/m2IV on day 1plus5-FU 750 mg/m2/day IV continuous infusion on days 1-5; every 21dConcomitant Radiation and ChemotherapyAggressive medical management consisting of both chemotherapy and radiation is reserved for advanced disease in patients who are deemed poor candidates for surgery, inoperable, or palliation. Concurrent chemoradiotherapy of N2 and N3 nodal disease from an unknown primary was able to give patients a 5-year survival rate and control rate of 75% and 87%, respectively.Also, patients with nasopharyngeal carcinoma are treated with combined chemoradiation therapy without surgery.

Monoclonal Antibody ChemotherapyRecently, the use of targeted drugs has entered the field. Cetuximab is one of the most well studied monoclonal antibodies directed against EGFR. Binding of the antibody to EGFR prevents activation of the receptor by endogenous ligands. An overall survival benefit and an increased duration of locoregional control have been observed in advanced HNSCCs treated with a combination of radiation therapy and cetuximab, compared to radiation therapy alone.