A 55 year old lady presents with a 1.5 cm palpable thyroid nodule. You order a TSH which shows low TSH. What do you order at this point and how do you further work this patient up according to the ATA guidelines?
Tc Scan or 123I scan (patients with a low TSH)
Hyperfunctioning - "HotNodule" present in 5%, is almost always benign disease and suggests evaluation and treatment for Hyperthyroidism
Non-functioning - "ColdNodule" present in 95%, warrants a diagnostic U/S guided FNA biopsy of lesion to assess for benign vs. malignant disease
What is the percentage chance of a thyroid nodule that was biopsied, showing "Indeterminate cytology" reported as "follicular neoplasm" or "Hurtle cell neoplasm" have of being malignant (according to the ATA guidelines)?
NOTE: 15-30% according to Bethesda Classification
What percentage chance does a biopsy of a thyroid nodule have of being malignant, if it is reported as "atypia" or "follicular lesion" of undertermined significance (according to the ATA guidelines)?
NOTE: 5-15% according to Bethesda Classification
What are the 4 types of results obtained from a FNA of a thyroid nodule (according to the Bethesda Classification)?
What are considered "Low-risk features" on U/S of an enlarged thyroid nodule?
Hyperechoic - Cystic or microcystic (>50% nodule volume)
Spongioform (not solid)
It is recommended that all benign thyroid nodules be followed with serial U/S examinations in 6-18 months after the initial FNA. What is considered significant growth on repeat U/S?
More than 50% change in volume
More than 20% increase in at least two dimensions in solid nodules of 2mm in solid nodules or in the solid portion of mixed cystic-solid nodules
Both warrant a repeat U/S guidance and biopsy
What are the goals of initial therapy of Differentiated Thyroid Cancer (DTC), according to the ATA guidelines?
1. To remove the primary tumor
2. To minimize the treatment-related morbidity
3. To permit accurate staging of the disease
4. To facilitate postoperative treatment with radioactive iodine, where appropriate
5. To permit accurate long-term surveillance for disease recurrence
6. To minimize the risk of disease recurrence and metastatic spread
What is percentage frequency of micrometastases to cervical lymph nodes in well differentiated (particularly papillary) thyroid carcinoma?
What percentage of the time does U/S detect suspicious metastatic cervical adenopathy in patients with well differentiated thyroid carcinoma?
20-30% of the time
What are the sonographic features suggestive of abnormal metastatic lymph nodes, in patients with metastatic well-differentiated thyroid carcinoma?
Loss of fatty hilum
Peripheral vacularity (*86% sensitive)
What are the lymph node compartments, their levels, and sub-levels in the neck?
Level Ia - Submental (above hyoid)
Level Ib - Submandibular region (above hyoid & anterior to posterior border of submandibular gland)
Level IIa - Above hyoid to base of skull posterior to the posterior border of the submandibular gland to the spinal accessory nerve posteriorly)
Level IIb - Above the hyoid to the base of skull (region behind the CN XI)
Level III - cricoid to hyoid
Level IV- cricoid to thoracic inlet
Level V - posterior triangle
What are the contents & boundaries of the level VI lymph node compartment in the neck?
Superiorly the hyoid,
Inferiorly the innominate (brachiocephalic) artery
Laterally the carotid sheaths
What is the ATA recommendations for management of thyroid nodules >1cm and <1cm?
Lobectomy alone - for small, <1cm, intrathyroidal, unifocal, well-differentiated thyroid cancer, in the absence of prior head and neck irradiation or radiologically or clinically involved cervical nodal metastases
TotalThyroidectomy - for larger, >1cm, non-intrathyroidal, or hx of prior irradiation and/or cervical nodal metastases
What are the indications according to the ATA guidelines to perform a central (level VI) neck dissection?
1. Involved level VI or lateral nodes
2. Prophylactic level VI may be performed for T3 or T4 primary lesions
* Note: No level VI necessary for small T1 or T2 primary lesions
What is the significance of the MACIS score in thyroid cancer? How is it calculated and used?
MACIS score developed for the assessment of risk of recurrence & treatment options are based on a three-level stratification (low, intermediate, high-risk)
Metastasis [0 or 3]
Age [<40 = 3.1, >40 = age x 0.08]
Completeness of resection [0 or 1]
Invasion [0 or 1]
Size [cm x 0.3]
***RESULTS: <4=suppression therapy, 5-6=tumor board, >6 RAI ablation therapy (20 year survival <6 is 99%)
What is the TNM classification system for differentiated thyroid carcinoma for patients age 45 years or older?
Stage I - T1N0M0
Stage II - T2N0M0
Stage III- T3N0M0 & T1-3N1aM0
Stage IVA- T4a or any N1b
Stage IVB- T4b, any N, M0
Stage IVC- Any T, Any N, M1
Compare the lymphatic drainage of the upper and the lower lip?
Due to embryologic origin (fusion plates) the upper lip has ipsilateral lymphatic drainage where as the lower lip has ipsilateral AND contralateral drainage
Which lip is most commonly affected by what tumor? What is the prognosis?
1. Lower lip - SCC > 90% of time with >90% 5 year survival if treated early
2. Upper lip - BCC
What percentage of patients with SCC of the lip have nodal mets?
<10% for T1
~65% for T4
Describe the T staging for lip and oral cancer cancer?
Keratotic Odontogenic Tumor (previously known as OKC) *like epidermoid cyst of mandible. Develop from dental lamina remnants (rests of Serres) & most commonly found in ramus and posterior body of mandible. Well-circumscribed uni- or multilocular lucency, bone expansion/erosion
Rare & locally aggressive tumors that occur at the anterior mandible with mucus secreting cells within the epithelial lining. Multilocular radiolucencies that frequently cross midline.
Treatment: Enucleation & Currettage +/- marginal resection to avoid recurrence
Calcifying Odontogenic (Gorlin's) Cyst
Arise from remnants of dental lamina (Rests of Serres) in anterior portion of either jaw that often is painless. 25% occur extra-osseous & appear radiographically as well-circumscribed mixed radiolucent-radiopaque lesion w/ central calcifications & presence of GHOST CELLS (on histo)
Treatment: Enucleation & Curettage
Incisive Canal Cyst - (a true cyst) from epithelium & remnant of 2 nasopalatine ducts (consider if >1cm)
Stafne Bone Cyst - (not a true cyst) from a depression on lingual aspect of the posterior body of mandible & is filled with an accessory lobe of the SMG gland
Traumatic Bone Cyst - (not a true cyst) found in the posterior mandible & has straw colored fluid due to trauma & bleeding
AmeloblastomaBenign tumor arising from rest of Mallassez/Serres, Dental Follicle, or Dentigerous Cyst. Can be very large & usually located in the posterior mandible showing multilocular radiolucency (soap bubble) & cortical expansion. Classified as: Peripheral vs. Central (Unicystic, Multicystic/Solid, Plexiform)
Treatment: E & C if superficial, 1 or 1.5cm bony surgical margins (recommended), 3 cm if aggressive type (PLEXIFORM UNICYSTIC)
What is the blood supply to skin flaps in neck dissection cases?
Transverse Cervical arteries
As it enters into the neck (from the chest) it is posteromedial to the carotid artery
As it enters up into the neck it arches superolaterally & anterior behind the Internal Jugular vein & in front of the scalene muscle and phrenic nerve
It opens into the IJV, the subclavian artery and occasionally at the junction between
What are the fascial compartments of the neck?
Superficial Cervical Fascia (Investing) - platysma
Superfical layer of the deep cervical fascia - SCM, Trapezius, Parotid & SMGs, Straps, & Muscles of mast
Middle layer of the deep cervical fascia - MUSCULAR DIVISION: Straps, Buccinator, Constrictors. VISCERAL DIVISION: Larynx, Thyroid, Esophagus, Trachea
Deep layer of the deep cervical fascia - ALAR DIVISION: lies btw the prevertebral and middle DCF. PREVERTEBRAL LAYER: Phrenic Nerve, Prevertebral & Paraspinal muscles
Central Necrosis (most accurate CT criterion)
Loss of Fatty hilum
Round (vs. ovoid appearance)
Size (>1cm or 1.5cm for jugulodigastric nodes)
Extracapsular Spread or Attachment to Surrounding Structures
Describe TOPO-ISOMERASE INHIBITORS and its use in the treatment of head and neck cancers, the MOA, and side-effects?
Topo-Isomerase Inhibitors: Etoposide, Topotecan
MOA: Interfere with the action of Topoisomerase enzymes (topo-isomerase I & II) which are enzymes that control the changes in DNA structure by catalyzing the breaking and rejoining of the phosphodiester backbone of DNA strands durng the normal cell cycle
SE: Myelosuppression, Mucositis, Alopecia
Describe BIOLOGIC RESPONSE MODIFIERS and its use in the treatment of head and neck cancers, their MOAs, and side-effects?
How does ChemoRT compare to RT alone in the treatment of nasopharyngeal carcinoma?
ChemoRT with Cisplatin (at 100mg/m2 dose q3weeks during treatment) offers 30% greater 5 year survival advantage over RT alone
IMRT - Intensity Modulated Radiation Therapy is a technique that utilizes complex computer modeling software to deliver numerous differently shaped treatment fields and radiation intensities during each fraction. This allows a high volume of radiation to be delivered to the tumor volume sparing the surrounding tissues.
The leaves of the multileaf linear accelerator are continuously moving during each treatment painting the tumor with XRT
Describe Stereotactic Radiotherapy?
Stereotactic Radiotherapy - radiation is delivered as >200 pencil thin beams all focused on a specific site allowing a tightly conformed dose of XRT to be delivered in each fraction. All beams have the same intensity.
What percentage of actinic keratosis become SCC?
Keratoacanthoma can clinically resemble what?
SCC (histologically similar)
Skin Type I - (White) Always burns, never tans
Skin Type II - (White) Usually burns, tans with difficulty
Skin Type III- (White) Sometimes burns, sometimes tans
Skin Type IV - (White) Rarely burns, tans with ease
Skin Type V - (Brown) Very rarely burn, tans very easily
Skin Type VI - (Brown) Never burns, always tans
Name the benign skin appendage tumors?
TrichoepitheliomaTrichilemmomas - precedes breast cancer in Cowden's disease (AD, hamartomas & trichilemmomas in breast, gastrointestinal, thyroid increase risk of cancer) Syringoma - eccrine duct adenoma Pilomatrixoma Nevus sebaceous - BCC develops in 5-7%
What are the indicators of metastatic potential in cutaneous SCC lesions?
Depth: >2mm (or into reticular dermis or subcutaneous tissue *Clarks level III at least)
Invasion: into bone, muscle, cartilage, nerve
Site: Ear and Lip
Differentiation: Poorly (Broder's 3 & 4)
What are the treatment options for non-melanoma cutaneous malignancies?
Curettage with Electrodessication
Cryotherapy: liquid nitrogen
Photodynamic Therapy (porphyrin and argon laser)
1. Photosensitizing drug (porphyrin, 5-ALA - Aminolevulinic Acid) applied topically, orally or parenterally and localizes into: tumor cells, acne, psoriasis
2. Drug is activated by exposure to light (laser)
3. Efficacy is low (45%)
4. Side-effects include: local edema, erythema, blistering, ulceration
5. Typically used in Skin Cancers (BCC), Acne and Psoriasis
Describe the T staging for basal cell carcinoma and squamous cell carcinoma?
T1 - ≤ 2 cm with <2 high-risk features
T2 - >2 cm with ≥ 2 high-risk features
T3 - Invades mandible, maxilla, orbit, temporal bone
T4 - Invasion of skeleton (axial or appendicular) or perineural invasion of skull base
*High-Risk Features: >2mm thick, Clark ≥ IV, Perineural spread;Primary site ear; Primary site non-hair bearing lip; Poorly differentiated or Undifferentiated
What percentage of melanomas lack melanin?
10% are amelanotic
Typically desmoplastic melanomas
What are the risk factors for melanoma?
1. Family history of cutaneous malignancies2. Presence of atypical moles 3. Prior Melanoma 4. Days plastic Nevus 5. Hutchinson Freckle (lentigo maligna) 6. History of childhood sun exposure/burns 7. Giant hairy nevus (5% develop melanoma within 5 years)
What are the subtypes of melanoma?
Lentigo Maligna Melanoma (5%) [best prognosis]
Acral Lentiginous (10-15%) - soles of feet, hands, orogenital
Nodular (10-15%) [worst prognosis]
Desmoplastic - (<1%) rare, amelanotic, neuroptropic, tendency to recur locally
Also known as Hutchinson's Melanotic Freckle (associated with solar damage & atypical melanocytes, radial spread along dermal/epidermal junction, focal nests of cells)
5% transform into malignant melanoma (invasive)
Nasal cavity - 50%
Oral cavity - worst prognosis
A rare histological variant characterized by a deeply infiltrating type of melanoma with an abundance of fibrous matrix. It usually occurs in the head and neck region of older people with sun-damaged skin.
Amelanotic (diagnosis is often delayed)
Neurotropic, but low incidence of regional metastasis
Tendency to recur locally
Define Clark's Levels?
Clark Level I: Epidermis Clark Level II: Papillary Dermis Clark Level III: Papillary-Reticular Dermis Clark Level IV: Reticular Dermis Clark Level V: Subcutaneous Tissue
Define T-staging for melanoma?
I: 0-1 mm II: 1-2 mmIII: 2-4 mm IV: > 4 mm
a - without ulceration b - with ulceration
Note: stage Ia: <1mm2 mitosis; Ib: >1mm2 mitosis
What is the T-stages for melanoma (AJCC)?
Tis - melanoma in situ (Clark's Stage I)
T1 - <1.0mm (A- Clark's II or III; no ulceration; B- Clark's IV or V; OR ulcerated)
T2 - 1.01-2mm (A- no ulceration; B- with ulceration)
T3 - 2.01-4mm (A- no ulceration; B-with ulceration)
T4 - >4mm (A- no ulceration; B- with ulceration)
What is the nodal staging of melanoma (AJCC 2010)?
N0 - no regional metastases
N1 - one node (1A micrometastasis; 1B macrometastasis)
N2 - 2 or 3 nodes (2A micrometastasis, 2B macrometastasis, 2C sattelite/in-transit mets without metastatic nodes)
N3 - 4 or more metastatic nodes, or matted nodes, or in-transit mets/sattelite(s) with metastatic nodes
What are the clinical stages of melanomas (AJCC 2010)?
Stage Ia: T1aN0M0
Stage Ib: T1bN0M0, T2aN0M0
Stage IIa: T2bN0M0, T3aN0M0
Stage IIb: T3bN0M0, T4aN0M0,
Stage IIc: T4bN0M0
Stage III: any T, N1-3, M0
Stage IV: any T, any N, M1
What is the embryologic origin of melanocytes?
What are the features of melanoma on immunohistochemistry?
HMB-45S-100 Melan-AVimentin Tyrosinase
What are the appropriate resection margins for melanoma?
Tis = 0.5cm T1-T2 = 1cm T2-T4 = 2cm (or more)
When is sentinel lymph node biopsy indicated in melanoma?
1. Stage IB, Stage IIA, B, C2. Tumor Regression 3. Lymphovascular Invasion 4. Tumor extension to deep margin of biopsy
When is neck dissection indicated?
Positive Sentinel Node
Stage III (patient <60 years, primary 1-2 mm in depth)
When is adjuvant therapy for melanoma indicated?
RT given is Dacarbazine, Cisplatin, Lamustine, Hydroxyurea, Alpha-Interferon, IL-2, BCG, Ganglioside GM (combined with BCG) and is indicated for:
1. Stage IIB-III (N-positive)
What is the rate of recurrence in treated melanoma?
2 years - 70%
3 years - 80%
What is the appropriate follow-up for treated melanoma?
Follow up is based on STAGE:
STAGE 0: periodic skin exam STAGE 1A: History & Physical and annual skin exam STAGE 1B-III: History & Physical skin exam and f/u: 3-6months x 3 years 4-12 months x 2 years CXR, LDH, CBC 3-12 months +/- CT (as indicated)
Poorly differentiated neuroendocrine tumor from tactile mechanoreceptor that originates in dermis & subcutis
High incidence of nodal and distant mets (~50%) and high Recurrence rate
Requires post op XRT after wide resection
Cutaneous malignancy arises from dermis
High recurrence rate (rec. 3cm margin)
Firm irregular nodules
Can mimic melanoma or morpheaform BCC
What is plasmacytoma?
90% present in the head and neck
Must rule out: Multiple Myeloma
A virtual line from angle of mandible to medial canthus
Divides maxillary antrum into anterior and posterior (better prognosis for tumors below Ohngren's line)
What are the VASCULAR orbital tumors?
Cavernous Hemangioma - adult, slowly progressive, unilateral proptosis, 88% intraconal, enhance with IV contrast. RX: surgical excision
Capillary Hemangioma: children, strawberry mark on eyelid, 90% regression by 9 years. RX: surgical excision if amylopia, corneal exposure, or optic nerve compression
Lymphangioma: children, superficial and deep types, spontaneous hemorrhage "chocolate cysts". RX: complete resection usually impossible - surgical debulking as required
What are the HEMATOPEITIC orbital tumors and how are they treated?
Lymphoma - Most are NHL, "Salmon Patch" under conjunctiva, Proptosis. RX: RT +/- Chemo
Leukemia - Granulocytic sarcoma (Chloroma - immature myeloid cell collection seen in AML & CML) causing painless proptosis, violaceous lid swelling. RX: ChemoRT but has poor prognosis with death usually seen within 18 months.
Histocytosis X - Circumscribed lytic bone lesion without sclerosis
Optic Nerve Glioma - 2nd most common pediatric orbital tumor from fibrillary astrocyte & associated wth NF2 (18-50% of cases). CT showing isodence homogenous enlargement of the optic nerve. RX: Follow (if vision good), Surgical excision if symptomatic
Orbital Meningioma - From optic nerve dura, cannot excise without severe vision loss, monitor for intracranial extension
What are the MESENCHYMAL orbital tumors and how are they treated?
Rhabdomyosarcoma - most common primary malignancy tumor of orbit in children (3 types: alveolar - worst, pleomorphic - most common in adults)
Fibrous Dysplasia - Lucent lytic bone, "ground-glass" appearance on CT, observe unless significant cosmetic issues or compressive neuropathy
Osteosarcoma - poor prognosis, RT + Surgery
Osteoma - benign, most from the frontoethmoidal region, RX: Follow (small), Excise (large)
Yellow spots on the buccal mucosa lateral to the edges of the lips, usually bilateral, representing remnants of atrophied sebaceous cysts
General: Bening Tumor involving 80% parotid and enhances with Technitium-99 scan
Gross: Well circumscribed, usually unencapsulated (noncystic, firm, rubbery), slow-growing
Histologically: oncocytes contain granular eosinophilic cells with lots of mitochondria, & a rare clear cell variant exists and may be confused with metastatic renal cell carcinoma
Rx: Surgical excision (as it can undergo malignant transformation)
What is an oncocyte?
It is an epithelial cell characterized by an excessive amount of mitochondria, resulting in an abundant acidophilic, granular cytoplasm. Oncocytes can be benign or can undergo malignant transformation.
Histologically: Three patterns: SOLID, TUBULO-TRABECULAR, MEMBRANOUS & has characteristic cells with peripheral pallisading sharply demarcated from surroundng stroma. It lacks myxochondroid (vs. pleomorphic adenomas)
Rx: Total Parotidectomy +/- postop XRT if residual dx
They are dendritic cells (antigen presenting cells) found within the skin and contain Birbeck granules. Typicaly found in the stratum spinosum and in the papillary dermis but can also be found in the lymph nodes in conditions such as Langerhans Histocytosis X.
General: Most common minor salivary gland tumor, considered aggressive and likely to metastasize, and may have the presence of perineural invasion & recur more commonly(MSG>parotid)
Gross & Histologically: Firm/hard and attached to surrounding tissues. Cylindric cells with variable height, papillae, acini, solid masses; mucin producing. Key feature to differentiate from mucoep carcinoma is NEGATIVE KERATIN STAINING!
Rx: Surgery, XRT, +/- Elective Neck Dissection
Define Polymorphous Low-Grade Adenocarcinoma?
General: 2nd most common malignancy of the salivary glands & exclusively seen in minor salivary glands (typically at the hard-soft palate junction, buccal mucosa and upper lip)
Gross & Histologically:Well-circumscribed but non-encapsulated, firm/painless,+/- perineural invasion
Rx: Wide local excision (indolent invasive with mets uncommon)
Define Carcinoma Ex-Pleomorphic?
General: Arise in pre-existing pleomorphic adenoma and typically present with sudden increase in size
Gross & Histologically: Mixed tumor adjacent to typical benign pleomorphic adenoma (+/- capsular invasion), and display malignant transformation in epithelial component (whereas in malignant mixed tumors there display malignant transformation in BOTH epithelial and stromal components)
Rx: Surgery and RT (prognosis poor)
Define SCC of the salivary gland?
General: Uncommon (rare) as primary salivary tumor. Need to rule out high grade mucoepidermoid (with mucin stain - Mucicarmine and PAS Diastase) & mets. The submandibular gland is more common than the parotid and contiguous spread or intraparotid nodal involvement from SCC skin or distant mets need to be rule out as well.
Identical to giant Cell granuloma but secondary to hyperparathroidism
Rule out elevated serum calcium and phosphate
Panoramic radiograph showing unilocular cystic lesion distal to the left mandibular second premolar with histopathologic studies showing numerous multinucleated giant cells (NOTE: this lesion healed following removal of the parathyroid tumor)
Histology: Chinese characters (seen in image), ground-glass appearance, lack of osteoblastic rimming! Treatment - defer until full grown if quiescent, contour excision or en bloc resection if increasing growth
Focal areas of sclerotic bone from apex of root causing reactive sclerosis to pulp inflammation
No treatment required
The presence of multiple keratocysts is suggestive of what entity?
What are four things should be considered in selecting where to place a neck incision?
No trifurcations over the carotid Possible need to extend the incision Flap blood supply Cosmesis (relaxed skin tension lines)
What is the management of a carotid blowout?
Manual pressure to stop bleedingBlood products/IV fluids OR ligation or carotid +/- Fogarty catheterization to help control bleed
NOTE: For carotid blowout/impending blowout (eg.sentinel bleed) there is no role for interventional radiology or vascular surgeon. Emergently bring patients to the OR & tie off the carotid high & low (the risk of stroke is secondary)!
NOTE (updated): more recent papers state that if patient stable, then interventional radiology may be an option (if available)
What are the risk factors for postoperative major vessel rupture ?
Fistula/infection Exposure of vessel Adventitia removed Recurrent tumor Radiation
What are the complications of neck dissection?
Bleeding (Hematoma/Carotid blowout)
What is the course of the spinal accessory nerve with respect to the IJV at the skull base?
80% anterior to the IJV 17% posterior to IJV 3% through IJV
What are the spinal root contributions to the phrenic nerve?
C3, C4, C5
"Keeps the diaphragm alive!"
What is Horner's Syndrome?
Horner's Syndrome refers to a constellation of signs produced when sympathetic innervation to the eye is interrupted. Characterized by:
Ptosis - drooping of upper eyelid from loss of sympathetic innervation of Muller's Muscle
Anhidrosis - decrease sweating on the affected side of face
Meiosis - small pupils
Enophthalmos - sunk in eye
Loss of the Ciliospinal Reflex - dilation of the pupil ipsilateral to a pain stimulus to neck
What is the sensitivity & specificity for physical exam, CT and combine for detecting neck disease in HNSCC?
What are the major clinical didfferences between Hodgkin's Disease and Non-Hodgkin's Lymphoma?
HD - often single axial group of nodes, orderly/contigous spread, mesenteric and Waldeyer's involvement rare, Extranodal tumor uncommon, bimodal peak (teens & 60s)
NHL - Frequently involves multiple peripheral nodes, non-contiguous spread, mesenteric and Waldeyers involvement common, increased risk with age
What is the Ann Arbor staging of Hodgkin's and Non-Hodgkin's Lymphoma?
Stage I - one LN or extralymphatic site Stage II - 2 or more LNs or single EL site on the same side of the diaphragm Stage III - Nodal regions and single EL site +/- Spleen on involvement on both sides of the diaphragm Stage IV - Diffuse & Multifocal involvement of EL organ +/- regional lymph nodes (bone marrow, liver, not spleen) A (absence) or B (presence of unexplained weigth loss >10% of TBW, fever temp >38, night sweats
What is the Working Classification of Non-Hodgkin's Lymphoma?
Low Grade - Small Lymphocytic, Follicular Small Cleaved, Follicular mixedIntermediate Grade - Follicular Large Cell, Diffuse Small Cleaved Cell, Diffuse Mixed, Diffuse Large Cell (most common) High Grade - Immunoblastic, Lymphoblastic, Small Noncleaved Cell "San Francisco Fortyniners Does Do DalLIS"
What Chemotherapy is used to treat Lymphoma?
CHOP - Cycolphosphamide, Doxorubicin, Vincristine, Prednisone
+/- Retuximab - monoclonal antibody binds to CD-20+cells (all B-cells)
Describe High stage Non-Hodkin's Lymphoma?
1) Burkitt lymphoma (small noncleaved) – Diffuse B-cell malignancy, classic starry sky pattern of phagocytic histiocytes and tumor cells
2) Lymphoblastic – Immature T-cell origin, small lymphoblasts with round/convoluted nuclei, distinct nuclear membranes, basophilic cytoplasm
3) Immunoblastic/Large cell – Heterogeneous group of lymphocytic & histiocytic tumors; 80% of adults are B-cell; in children equal B & T cells.
How would you clinically assess a patient with Non-Hodgkin's Lymphoma?
1. H&P with direct laryngoscopy
2. CBC/Diff, LFTs, LDH
3. CT neck, chest, abdomen & pelvis
4. Barium Swallow (10% patients with Waldeyer's ring involvement have GI involvement)
5. Bone Marrow biopsy (20% have extranodal involvement)
6. Lumbar Puncture (CNS)
What is Burkitt's Lymphoma?
It is a type of high grade Non-Hodgkin's Lymphoma that is EBV-related (high incidence in Africa)
Due to a translocation in 8-14 or c-myc oncogene.
It typically involves the facial bones (esp. the maxilla)
What is Richter's Transformation?
Low grade lymphoma that transforms to aggressive high grade
Has a poor prognosis with an average survival of <1year
What are the treatment outcomes for Hodgkin's ?
Early stage - 80-90% cure rates at 10 years
Advanced stage - 50-60% cure rates at 10 years
How do you treat Hodgkin's Lymphoma (according to the NCCN guidelines)?
Stage 1 & 2 – radiotherapy (chemotherapy may be used in combination) – 95% remission has classically been used. More recently chemotherapy has been incorporated (ABVD & Stanford V) to avoid SE of radiation treatments by reducing there dosing requirements (20Gy of IFRT)
What is the pathological staging for melanoma (AJCC 2010)?
Stage Ia: T1aN0M0
Stage Ib: T1bN0M0, T2aN0M0
Stage IIa: T2bN0M0, T3aN0M0
Stage IIb: T3bN0M0, T4aN0M0,
Stage IIc: T4bN0M0
Stage IIIa: T1-4aN1aM0, T1-4aN2aM0
Stage IIIb: T1-4aN1b/2b/2c, T1-4bN1a/2a
Stage IIIc: T1-4bN1b/N2b/2c, any TN3M0
Stage IV: any T, any N, M1
How is thyroid hormone produced?
Thyroid incorporates iodine into amino acid tyrosine to form T4 (stored in thyroglobulin)
T4 mostly bound in circulation (thyroid binding protein) ~98%
Name 3 factors affecting thyroglobulin levels?
high estrogen = high TBG
high steroids = low TBG
liver failure = low TBG (since TBG synthesized in the liver as 54kDa protein)
What is the risk of malignancy in goiter?
What are the incidences of cancer in "hot" and "cold" nodules identified on radionucleotide imaging (I123, Tcm99)
4% incidence of ca
16% incidence of ca
What are the categories of FNA results and how should you manage the patient with these results?
Unsatisfactory- repeat with ultrasound guidance
Indeterminate - some atypia; consider lobectomy
Benign - repeat ultrasound in 1 year to check for growth; if it grows repeat FNA, if high risk AMES consider lobectomy
Suspicion of Malignancy - Lobectomy + intraop frozen sections, possible total since ~20% risk of having to go back in if "suspicious" FNA
Diagnosis of Malignancy - definitive surgery
How is benign thyroid disease classified?
diffuse multinodular goiter
multinodular goiter + solitary hot nodule
thyroiditis (acute, subacute & chronic)
What is the most common thyroid neoplasm?
What percentage of patients have a pyramidal lobe?
What is the Wolff-Chaikoff effect?
A transient antithyroid effect of iodides
What is Jod-Besdow effect?
Hyperthyroid effect after giving iodine
What percent of subacute granulomatous thyroiditis become permanently hypothyroid? What percent become temporarily hypothyroid?
What should you do insetting thyroid cancer on the recurrent laryngeal nerve and the nerve is still working? What should you do if the nerve is not working?
Peel the tumor off the nerve as best as possible
Resect the nerve
What are the two syndrome associated with papillary thyroid cancer
Gardner's Syndrome - AD assoc w fibromas, osteomas, leiomyomas, lipomas, Epidermal cyts, well-differentiated thyroid ca, polyposis of colon and rectum "FOLLE Thyroid & Colon"
Cowden's Syndrome - AD assoc with thyroid ca, breast ca, hamartomas of skin/breast/thyroid/GIT, Trichilemmomas, Gingival Fibromatosis "The Beast Has Three Fingers"
What is Gardner's Syndrome?
Gardner's Syndrome - AD associated with fibromas, osteomas, leiomyomas, lipomas, Epidermal cyts, well-differentiated thyroid ca, polyposis of colon and rectum (Adenocarcinoma occurs in 100% of cases by the age of 50 years
"FOLLE Thyroid & Colon"
What is Cowden's Syndrome?
Cowden's Syndrome - AD associated with multiple hamartomas associated with well-differentiated thyroid ca, breast cancer, Hamartomas of skin/breast/thyroid/GI tract, Trichilemmomas on face, Gingival Fibromatosis "The Beast Has Three Fingers"
What is the AMES method of risk stratifying thyroid cancer patients?
A - age, F>50 or M>40M = distant mets E = extent of local disease S - Size
Give five reasons for doing total thyroidectomy in well-differentiated thyroid carcinoma?
1. Potential for Multicentricity
2. Recurrence rate in remaining tissue 5-25%
3. 40-50% die b/c of disease in remaining tissue
4. Better for I131 treatment
5. Morbidity of completion thyroid only (3%)
What are the 6 most common types of malignant thyroid cancer?
1) Papillary (80%) - Originating from follicular thyroid cell, well differentiated 2) Follicular (10%) - Originating from follicular thyroid cell, well differentiated 3) Anaplastic (1-5%) - Undifferentiated thyroid cancer 4) Medullary(5%)- Originating from parafollicular cells
Discuss Papillary Thyroid Carcinoma?
General: Represents 80% of thyroid cancers, multicentric in 80%, 3rd & 4th decades, F:M = 3:1
Histopathology: Poorly encapsulated, High locoregional mets to nodes (37-65%), low rate of distant metastasis (2-17%), can display mucinous, ciliary or squamous metaplasia
Treatment: Thyroidectomy, RAI, ND, +/- XRT (Age and size most important prognostic factors)
What are the histological subtypes of Papillary Thyroid Cancer associated with worse prognosis?
Poorly differentiated/Insular Cell
Hyrthle Cell (Oxyphillic)
Note: LN mets increase the incidence of local recurrence but NOT mortality (5y survival 70-90%)
What are histological subtypes of Papillary Thyroid Cancer associated with better prognosis?
Papillary Microcarcinoma (<1cm)
Diffuse Follicular & Macrofollicular
What are the characteristic features of papillary thyroid cancer on microscopy?
What pathologic finding is necessary to make a diagnosis of follicular thyroid cancer?
Angioinvasion or capsule penetration
What is the incidence of distant mets in Follicular Thyroid Cancer?
NOTE: has a lower rate of nodal metastasis (20%), but a higher rate of distant mets due to hematogenous spread
What is the prognosis for treated Follicular Thyroid Cancer?
5 year survival:
70% without distant mets,
20% with distant mets
10 year survival:
What is the follow-up schedule for well differentiated thyroid cancer patients?
Q3months for 2 years; Q6months for 3years; Qyearly for life
1/3 of recurrence is >10 years from diagnosis
At each visit: Exam, TSH, Thyroglobulin (<10 on T4, <40ng.ml off T4), ionized calcium, CXR yearly, U/S neck yearly
What are the subtypes of follicular thyroid cancer?
Hurtle Cell (Oxyphillic)
What is the cell of origin in MTC?
Parafollicular cells = secrete calcitonin
Amyloid - "apple-green" birefringence with Congo red stain
Nests of eosinophilic oval to spindle shaped tumor cells
What is the incidence of sporadic (vs. familial) MTC?
solitary tumors are usually sporadic
multicentric tumors are usually familial
Which has a better prognosis, MTC in MEN IIA or MEN IIB? Sporadic or familial?
MEN IIA - carries the better prognosis
Familial MTC - carries a better prognosis than sporadic
What gene is associated with Medullary Thyroid Cancer in MEN IIA & IIB?
90% of people with RET point mutation get MTC within 20 years
MEN IIA - total thyroidectomy w/n 5 years
MEN IIB - total thyroidectomy w/n 6-12 months
NOTE: MEN IIB much more aggressive!
What is the prognosis for treated MTC?
5-year survival of 70-80%
What are the indications for neck dissection in Medullary Thyroid Cancer (according to AMA 2009 guidelines) ?
1. MEN 2A/FMTC(<5years) or MEN 2B (<1year)- Evidence of central nodes (radiologically/clinical), Thyroid nodules >5mm, Calcitonin >40pg/ml
2. MEN 2A/FMTC (>5years) or MEN 2B (>1year)
3. MTC patients with high suspicion, node positive, palpable thyroid disease, or lateral neck nodes
4. Palliative MTC patients for symptomatic relief
What is the prognosis for anaplastic thyroid carcinoma?
1 year survival = 10%
What is the pathogenesis of Anaplastic Thyroid Cancer?
Transformation from a well-differentiated tumour (usually papillary) to anaplastic
What is the treatment for Anaplastic Thyroid Cancer?
Often presents with unresectable disease
Rx: Doxorubicin + RT
Possible salvage surgery for responders
What percentage of school age children have a thyroid nodule?
2% of school-age children have a thyroid nodule
What is the incidence of malignancy in a solitary thyroid nodule in a child?
50% (85% of these have cervical lymph node mets)
What is the traditional protocol for I-131 administration (without Thyrogen)?
Stop thyroid hormone x 2-3 weeks (low iodine diet x 3-4 weeks)
TSH and TGB measured (ideal if TSH >30mU/L)
Total body scan followed by ablative dose of I-131
Continue thyroid replacement
What is Thyrogen?
Thyrogen - Recombinant TSH (Thyrotropin α) that binds to TSH receptors & stimulates iodine uptake and secretion of thyroglobulin, T3 and T4. Used to avoid patients being taken off Synthroid to generated elevated TSH levels.
Dose: 0.9mg IM qOD x 2 (~$1600 for 2 doses) 24h apart
NOTE: TBG serum levels should be obtained 72 hours after final injection (note TGB levels generally lower than true hormonal withdrawal)
Discuss post-op TSH suppression for well-differentiated thyroid cancers?
1. Thyroxine (T4) given at 2.1mg/kgdaily
2. Titrate to keep TSH below 0.1mU/L 3. Eliminates TSH dependent growth of well-differentiated thyroid cancer that have TSH receptors that allow them to grow 4. Risk of subclinical hyperthyroidism: tachyarrthmias, diastolic heart failure, osteoporosis in postmenopausal women
What is the typical dose of I-131 for adjuvant cancer treatment (according to the ATA guidelines)?
Recommendation 36: The minimum activity (30-100mCi) necessary to achieve successful remnant ablation should be utilized, particularly for low-risk patients
Recommendation 37: If residual microscopic disease or documented, or if there is a more aggressive tumor histology (Insular, Tall Cell) then 100-200mCi may be appropriate
What are the acute & long-term complications of I-131 in the treatment of well-differentiated thyroid cancer?
CHRONIC: Bone marrow induction tumor, Bladder ca, Gonadal dysfunction, Pulmonary fibrosis, Hypoparathyroidism
When is a neck dissection indicated for Papillary Thyroid Carcinoma?
T1 & T2 - may be treated with total thyroidectomy without level VI neck dissection (unless there is presence of central neck disease)
NOTE: *Hemithyroidectomy ok only for: unifocal, <1cm, intrathyroidal, node negative, low-risk tumors
T3 & T4 - treated with total thyroidectomy and bilateral central neck dissection (with or without palpable level VI disease)
What is the general treatment protocol for well-differentiated Thyroid Cancer?
Hemithyroidectomy only for: unifocal, <1cm, intrathyroidal, node negative, low-risk tumors.
Total thyroidectomy (80% chance of multicentricity/ cancer on the other side), Bilateral level VI neck dissection for clinically apparent level VI nodes (macroscopic disease), Postop suppression, Postop TSH suppression
What is the role of Chemo in well-differentiated thyroid cancer? What agents are typically used?
For diffuse disease that:Is not amenable to treatment with surgery Does not concentrate I131 Not amenable to radiotherapy
Agents: Doxorubicin, Cisplatinum
What is the role of external beam RT in well differentiated thyroid cancer?
1. High grade tumors that do not concentrate radioactive iodine
2. Gross evidence of local invasion at surgery and significant macro-or microscopic residual disease that does not concentrate I131
3. Recurrent disease in neck which is not amenable to I131 or further surgery
4. For palliation of recurrent or metastatic disease (especially good in CNS and pulmonary mets
What is the AJCC T staging for thyroid malignancies?
What are the different types of Hyperparathyroidism?
Primary - Adenoma or Hyperplasia
Secondary - Hyperplasia caused by malfunction of other organ system; Renal Failure/Dysfunction, Osteogenesis Imperfecta, Paget's Disease, Multiple Myeloma, Bone mets, Pituitary Basophilism OR Vitamin D deficiency
Tertiary- Autonomous secondary response with corrected organ system, normal calcium & ↑ PTH
What cancers tend to metastasize to bone?
Prostate, breast, thyroid, lung, kidney
Describe Parathyroid embryology?
5th week GA
3rd Pharyngeal Pouch - inferior parathyroid descends with thymus. Longer migration therefore more variable final position
4th Pharyngeal Pouch - superior parathyroid + C-cell complex. Shorter migration therefore less variable final position
Inferior Thyroid Artery (mostly)
Superior Thyroid Artery (limited)
Four gland hyperplasia represents what percent of all the cases of hyperparathyroidism?
5-10% (the majority are adenomas)
Both thyroid tissue and abnormal parathyroid tissue take up 99m Tc sestamibi within a few minutes. The examination is based on the differential washout of 99m Tc sestamibi from thyroid tissue (10-15min) compared with abnormal parathyroid tissue (1.5-3hours). The rate of washout from abnormal parathyroid tissue, such as parathyroid adenoma, is much slower than that of normal thyroid tissue.
What are the four indications for parathyroidecomy in chronic renal failure?
Intractable bone pain/pruritus
Calciphylaxis (tissue calcification) unresponsive to hemodialysis or medications
Name two causes of congenital hypothyrodism?
What are four things that can affect a Sestamibi scan?
What are two groups of genes involved in cell growth and cancer?
Normal cell genes that influence cell growth in a positive way
Tumor Suppresor Gene
Encode proteins that normally exert negative regulatory control in a cell
What are 5 oncogenes classified according to Protein's Function?
Growth factor - interleukin-2
Growth factor Receptors - erbB/neu
Signal Transducers - ras
Protein Kinases - b-raf, c-raf
Transcription Regulator - myc
Describe four antagonistic relationships in cancer genes?
bcl-2 and p53
p53 and Cyclin
p16/p21 and Cyclin
RB and TF E2F
Describe the p53 gene?
Controls the cell cycle by binding to cyclin-dependent KININS and arrests cell replication in G1; can induce apoptosis if DNA cell repair mechanisms fail, and decreases angiogenesis
CT and MRI criteria for diagnosis of Carotid invasion in HNSCC?
1. Effacement of the fascial plane surrounding greater than 25% of the vessel circumference
2. Tumor involvement of 75% or more of the circumference of the carotid
What is the incidence of cerebral complications following common carotid occlusion?
Abrupt ligation = 42%
Occluded gradually over <7 days = 30.6%
Occluded gradually over >8 days = 5.3% (significantly decreased)
Unselected ICA interruption = 26% rate of cerevral infarction (depends on age)
Define Simultaneous, Synchronous, and Metachronous tumors?
Simultaneous = diagnosed at the same time
Synchronous = found <6 months later
Metachronous = found >6 months later
What is the criteria for the second primary?
Has distinct metastases
NOTE: Overal incedence of second primaries is 10%,80% of which is METASYNCHRONOUS (>6 months apart) and discovered within first 2 years
What is the risks of post-treatment locoregional recurrence & 2nd primary development with continued smoking and ETOH consumption?
Locoregional Recurrence = 30-50% risk
Second Primary = 10-40% risk
What is the Response Evaluation Criteria in Solid Tumors (RECIST)?
COMPLETE - Disappearance of alldetectable dx ≥28d
PARTIAL - >50% reduction in tumor size ≥ 28 days
MINOR RESPONSE - <50% regression in size
STABLE Dx = No appreciable change in dimensions
PROGRESSIVE Dx = New lesions or >25% ⇑ in size
Describe the Phases of Clincal Trials?
PHASE I = Measures the Maximal Tolerated Dose of a drug and its pharmacological properties; determines the spectrum of toxicity
PHASE II = Efficacy of a drug in a specific Disease and Stage at a defined Dose; define Activity within tolerable levels of toxicity, endpoint: Response Rate
PHASE III = Comparison of 2 therapies in a randomized manner; endpoints are response rates, response duration, Disease Free Survival, Overall Survival
What are six roles for chemotherapy in Head & Neck Oncology?
1. Primary treatment of NPC
2. Organ preservation in Laryngeal Cancer
3. Unresectable Disease
4. Post-operative adjuvant therapy
5. Investigative Therapy
6. Recurrent of metastatic disease
What are three tumor factors affecting chemotherapy sucess?
1. Tumor Burden
2. Percentage of cells in chemo-responsive phase
3. Number of cells with resistance to chemotherapy
What are four points about combined chemotherapy?
Higher response rates with some combinations
Overall survival rates not improved
Toxicity is more severe
Cisplatin & 5-FU are the "gold standard" (act synergistically)
NOTE: more recently Carbo-Taxol being used
What are characteristics of Megavoltage x-rays/Gamma rays (photons)?
Low (4-6MeV) or high (15-25MeV) energy
Depth-dose properties (penetration)
Isodose distribution (Beam uniformity)
Describe 3 types of Brachytherapy source placement?
3. Surface mold
What are the Brachytherapy time frames used for treatment?
Long-lived isotopes used
Radium, Iridium, Cesium (RIC)
Short-lived isotopes used
Palladium, Iodine, Gold (PIG)
In Radiotherapy, what is the definition of "CELL DEATH"?
CELL DEATH = inability to proliferate (both DNA strands must be knocked out)
In Radiotherapy, what is the definition of "LOG CELL KILL"?
LOG CELL KILL = particular radiation Dose will kill the same proportion of cells
In Radiotherapy, what is the definition of "CELL DEATH"?
In Radiotherapy, what is the definition of "Therapeutic Window"?
Dose Response curves between Tumor cell & Tissue damage; relative positions of curves determine safety of tumor control
What time is required post-XRT to call a biopsy reliable?
Cell lysis occurs at mitosis, 4-5 divisions occur before lysis
What are the dose limiting factors for Intensity and Total Dose?
Intensity = acute toxicity leading to MUCOSITIS
Total Dose = late toxicity leading to SOFT TISSUE FIBROSIS
When is the best postoperative time interval for adjuvant XRT?
Within 6 weeks
What is the distance of tumor to resection margin that is considered a "Close Margins"?
Found to have the same prognostic significance for recurrence as positive margins
What are the 4 treatment modalities for Osteoradionecrosis (ORN)?
1. Medical: local topical care, biopsy, culture, IV Abx
2. Hyperbaric oxygen
3. Debridement and partial mandibular resection
4. Vascularized tissue transfer (local/regional/free)
What are the three typical osseous findings of mandibular ORN on CT scans?
Radiolucency, Demineralization, Sequestrum
What are four intraorbital complications of Radiotherapy, maximum doses where applicable?
Cataracts ~6 Gy
Lacrimal Gland injury ~35Gy
Radiation Retinopathy ~50Gy
Optic Nerve Injury ~50Gy
List Cahan's 4 criteria in the diagnosis of Post-Radiation Sarcoma (PRS)?
1. Histologic features of the original lesion and PRS are completely different2. PRS is located within the field of irradiation 3. Patients with cancer syndromes such as Li-Fraumeni and Tothmund-Thomson are excluded 4. Latent period (period between initiation of radiotherapy and histologic diagnosis of second neoplasm) is >4years
Dose of XRT for Microscopic disease and N0 neck?
Microscopic disease = 65GyN0 neck = 55Gy
When do you do an Elective Neck Dissection (or Irradiate) according to Nose and Paranasal Sinuses?
When do you do an Elective Neck Dissection (or Irradiate) according to Glottis?
Unilateral levels II-IV
When do you do an Elective Neck Dissection (or Irradiate) according to Oral Cavity?
Unilateral levels I-III, unless approaching midline, anterior tongue and FOM
When do you do an Elective Neck Dissection (or Irradiate) according to Supraglottis?
Bilateral levels II-IV
When do you do an Elective Neck Dissection (or Irradiate) according to Subglottis?
Bilateral levels II-VI +/- V, and total thyroidectomy
When do you do an Elective Neck Dissection (or Irradiate) according to Tonsil?
Unilateral levels I-III & Retropharyngeal nodes
When do you do an Elective Neck Dissection (or Irradiate) according to Base of Tongue?
Bilateral levels I-V
When do you do an Elective Neck Dissection (or Irradiate) according to Hypopharynx?
Bilateral levels II-V, & Retropharyngeal nodes
When do you do an Elective Neck Dissection (or Irradiate) according to Nasopharynx?
Bilateral levels II-V & Retropharyngeal nodes
Summarize the Veterans Affairs study?
Advanced Laryngeal Ca randomized into 2 arms:
Group 1:Standard Surgery + Postop RT
Group 2:Neoadjuvant Cisplatinum + 5-FU, then XRT..... but if no (even partial) response after 2 cycles OR recurrent/residual disease after XRT then Surgery
Overall Survival rate at 2 years identical = 68%
Laryngeal Preservation rate in group 2 = 64%
Summarize the RTOG 91-11?
Advanced larynx ca, randomized into 3 arms (larynx preservation, locoregional control & OS rates):
Group 1: Concomitant Cisplatinum + XRT= 88%, 78%
Group 2:NA Cisplatinum + 5-FU, then XRT=75%, 61%
Group 3: XRT alone = 70%, 56%
Locoregional control & Laryngeal Preservation better in Concomitant ChemoRT but Overall Survival rates not improved!
Name seven types of skin cancer, in descending frequency?
Basal Cell Cancer (75%)
Merkle Cell Carcinoma
Name three Basal Cell Carcinomas and 2 SCC lesions associated with worse prognosis?
De novo SCC
Describe the Nevoid Basal Cell Carcinoma Syndrome (Gorlin's Syndrome)?
NBCCS: AD mutation of chromosome 9q (PTCH gene)
DIAGNOSIS (2 major OR 1 major & 2 minor criteria): MAJOR: >2 BCCs or 1 BCC in a person <20 y, OKC of jaw, ≥3 plantar pits, 1st degree relative, falx cerebri calcifications, splayed/bifid ribs
• Most common form of melanoma (80% of oral lesions) on skin and mucous membranes
• Appears as a dark brown or black lesion
• Are usually poorly-delineated; irregular margins; satellite lesions
• May have dark pigmented areas mixed with non-pigmented areas
• Pagetoidused to describe clear cells in unique intraepithelial growth pattern
High-risk sites for cutaneous malignancy (for recurrence and aggressiveness)
Junction of the ala with the nasolabial fold, nasal ala, the septum, inner canthi and lower eyelidss, preauricular region extending to the temple, certain scalp regions
A shower of Seborrheic keratoses as a sign of internal malignancy, most commonly colonic adenocarcinoma
Outline the management options for cutaneous malignancies?
Medical - Topical 5-FU, Retinoic acid, Interferon α Surgical - E & C, Excision, Cryosurgery, Photodynamic therapy, Moh's Radiotherapy - generally not indicated due to duration, complications, carcinogenesis, lack of margin control, increased aggressiveness of recurrences
What are the 13 indications for Moh's Surgery?
Histology - high risk lesions
Ear, Lip, Central face, Temporal, Nasal tip, Chin, etc