Thyroid Malignancy Flashcards
Biosynthetic defect and dec iodine
Dec efficiency of thyroid hormone synthesis
Inc TSH
Inc thyroid stimulating Ig
Upregulation of TSH receptor
Hyperthyroidism
Grave’s
Lymphocytic infiltration
Release of immune system growth factor
Hypothyroidism
Hashimoto’s thyroiditis
Grayscale sonographic features of thyroid cancer
Hypoechoic compared with surrounding thyroid 81% M sensitivity
Hypoechogenicity (94% high specificity)
Microcalcification
Irregular microlobulated margin
Solid consistency (highest median sensitivity 78-91)
Taller than wide shape on transverse view
Most common malignancy of endocrine system
2x common in women than men
Male worse prognosis
Thyroid cancer
Rf for thyroid ca
Head and neck irrad before 18 Ionizing radiation from fallout in childhood <20 >65 years Rapid enlarging mass Male gender Family hx of papillary
Thyroid CA pathogenesis
Radiation
High TSH
Oncogenes
Papillary thyroid ca alteration
Most common
Rearrangement
BRAF V600E
RET rearrangement/PTC/RAS/MAPK
Follicular CA genetic alteration
PAX8-PPARy1 rearrangement
Anaplastic Thyroid Ca genetic alteration
TERT
BRAF
CTNNB1
And
P53
Loss of iodine uptake by tumor cell
BRAF mutation
BRAF + thyroid ca signals
inc recurrence rate
Medullary thyroid Ca is related to point mutation in
With hyperplasia of C cell
RET gene MEN 2
C cell produces calcitonin
PTH increases
serum calcium
Calcitonin dec
serum calcium
80-85% of well differentiated thyroid malignancies are
Pathognomonic histologic finding
Papillary
Orphan annie eye Clear cell nuclei
Multifocal
Invade locally within thyroid gland ane capsule and neck
Spreads via
Papillary thyroid ca
Lymlhatic but mets hematogenously bone and lung
Excellent prognosis
Follicular TC histology
Hurthle cell
Marked vascular invasion
Well differentiated thyroid ca tx
Small micropap thyroid T1a
Active surveillance
Tumor >1cm T1b or larger tx
Surgical excision
Tumor >4cm in presence of metastases
Neart total thyroidectomy
Mainstay tx of well diff thyroid cancer
Levothyroxine supression of TSH
TARGET
low risk: 0.5-2.0
Intermediate 0.1-0.5
After near total thyroidectomy, g of thyroid tissue remains in thyroid bed
Follow up with
<1 g
Postsurgical RAI eliminate residual gland
Contraindicated in pregnancy
Thyroid ablation and tx
Iodine dep for 2 weeks Inc serum TSH >25? Pretx scan Ablation Whole body scan post ablation
Indications of RAI
Large tumors More aggressive variants of papillary Extrathyroidal invasion Tumor vascular invasion Presence of large volume LN mets
Surveillance thyroid test
Sensitive marker of residual recurrent thyroid cancer after ablation
Neck UTZ
External beam RT
Serum thyroglobulin tg
RAS BRAF RET EGFR VEGR Angiogenesis
Kinase inhibitors
Doubling of PFS To 10.8 months among progressive metastatic thyroid cancer
sorafenib multikinase inhibitor
Poorly differentiated
Aggressive
Poor prognosis die within 6 mos
Anaplastic thyroid cancer
Anaplastic thyroid tx
Chemo: paclitaxel and anthracycline (daunorubicin, doxo)
EBRT
Use of checkpoint inhibition therapy
Background of Hashimoto’s thyroiditis
Rapidly expanding thyroid mass
Sensitive to RT
Thyroid lymphoma
Most common thyroid lymphoma
Diffuse large b cell lymphoma
5% of thyroid cancer
3 familial forms
Medullary thyroid
Men2A
Men2B - more aggressive
Non tender palpable solitary neck mass
First dx
TSH
High
UTZ
Detectes on UTZ -> FNAB w cytology
TSH LOW
radionucleotide scanning
Hyperfuxn nodule
Thyroid cytology done by
Bethesda classification
Hyperthyroidism from single hyperfunctioning nodule
RAI scanning shows hot nodule with suppression of rest of thyroid gland
Rarely malignant
Smaller nodule - antithyroid med and RAI
lobectomy and isthmusectomy - larger nodule
Plummer’s disease
Toxic adenoma
Notorious for causinf hypo or hyper
Amiodarone
Most common location of cancer in esophagus
Middle third
Most common malignancy in iodine deficient region
Follicular TC
Calcitonin producing TC
Medullary thyroid
Carcinoma assoc with Hashimoto’s
Thyroid lymphoma
Thyroid lymphoma is thought to arise from
Chronic antigenic stimulation leading to proliferation of lymphoid tissue, somatic mutation, clonal proliferation, lymphoma
Thyroid lymphoma is thought to arise from
Hashimoto’s thyroiditis
as rapidly expanding thyroid mass
Most cases of thyroid carcinoma present with
a thyroid nodule
CLADs in thyroid carcinoma signify
local progression
Most common metastases of thyroid cancer
Lung
Bone
Rapidly enlarging thyroid mass
Regional or distant metasteses
Anaplastic TC
MTC may present with paraneoplastic secretion of ectopic
adrenocorticotropic hormone ACTH
Most common symptoms of Medullary TC
Diarrhea
Flushing
due to calcitonin
Diagnosis made on basis of cytologic features from FNA or surgical pathology
Multifocal
Invade locally within thyroid gland and through thyroid capsule into adjacent structures in the neck
Grows slowly
Papillary TC
PTC has propensity to spread via
Lymphatics
but may spread hematogenously particularly to bone and lung
significant burden of pulmonary metastases may accumulate sometimes with few symptoms
Diagnosis is made on the bases of characteristic cytologic features on specimens from SURGICAL PATHOLOY
Difficult to diagnose by FNA nor cytopathology nor frozen section
Follicular TC
Distinction between benign and malignant Follicular TC rests on evidence of
invasion into vessels, nerves, capsules and adjacent structures
Follicular TC tends to spread
Hematogenously to bone, lung and CNS
Diagnosis is made on the basis of cytologic features on specimen from FNA or surgical pathology
Poorly differentiated and aggressive arising from differentiated thyroid carcinoma due to V600E alteration in BRAF as with papillary
Uptake of radioiodine negligible
Anaplastic TC
Definitive diagnosis made on the basis of cytologic features on specimens from FNA or surgical pathology
High serum calctonin and CEA can be indicative
Radioiodine scans not helpful since they do not accumulate radioiodine
Medullary TC
Routine measurement of calcitonin is not recommended to detect MTC or in a patient with thyroid nodule
and should be tested instead only in persons presenting with
Diarrhea
Flushing
Diagnosis of primary thyroid lymphoma rests on demonstration of
sheets of lymphoid cells in FNA
core biopsy specimen
Can aid distinction of lymphoma from small cell lung cancer or Anaplastic TC
Immunophenotyping
Most common Primary Thyroid Lymphoma
Diffuse Large Cell Non-Hodgkin Lymphoma
Reed Sternberg Cells
Hodgkins B Lymphoma
Starry sky appearance
Burkitt lymphoma
TSH level in 95% of TC patients
Normal
Marker for residual, recurrent or metastatic disease in WELL-DIFFERENTIATED TC
in patients with complete excision/ablation
Thyroglobulin Tg
Sensitivity of Tg increases when TSH is elevated
Interference of 20% can invalidate serum Tg assay
Tg measurement suggests persistent ir recurrent thyroid carcinoma
> 2 ng/mL
Tg level is increased in most metastatic
Papillary
Follicular
Serum calcitonin level associated with cancer
500-2000 pg/mL
CEA
Should be performed in sporadic cases of MTC to evaluate possibility of MEN2
RET mutational analysis
Useful to aid in accurate needle placement in FNA
Used preoperatively in pathologically confirmed thyroid cancer to identify potential metastatic nodes and assist in planning the appropriate nodal dissection during surgical resection
Also useful to monitor for/identify sites of recurrent disease
Ultrasonography of neck
Radioactive iodine uptake is significant in these types of TC in areas of residual or recurrent disease including bone and soft-tissue metastases
Papillary
Follicular TC
Used to identify sites of distant metastases
18-Fluoro-deoxyglucose FDG positron emission tomography PET
Good sensitivity and specificity
Accurate for detecting Papillary TC
FNA
Nondiagnostic biopsies occur because
Fibrotic reaction with few cells available for aspiration
Cyst in which cellular components reside along cyst margin
Nodule too small for aspiration
Additional preop diagnositc imaging after positive FNA
Chest radiography
Preoperative neck ultrasonography
CT or MRI of the neck, for fixed or substernal lesions
Evaluation of vocal cord mobility
Papillary TC variant
Pure papillary
Follicular
Diffuse sclerosing
Tall-cell, columnar-cell
Folicullar TC variant
Minimally invasive
Widely invasive
Hurthle Cell Carcinoma (oncocytic)
Insular carcinoma
T1 staging
= 2 cm
limited to thyroid
T2 staging
2-4cm
limited to thyroid
T3 staging
> 4cm limited to thyroid or minimal extrathyroidal extension
T4a
any size extending beyong capsule to soft tissue, larynx, trachea, esophagus or recurrent laryngeal nerve
T4b
Tumor invades prevertebral fascia
Encases carotid artery
Mediastinal vessels
N1
Regional lymph node metastasis
N1a
Metastasis to level VI (pre, paratracheal, Delphian)
N1b
Metastasis to unilateral, bilateral or contralateral cervical or superior mediastinal lymph nodes
Stage grouping for PTC or FTC in <45
Stage I
Stage II
Any T, N, M0
Any T, N, M1
Stage grouping for PTC or FTC >/= 45 or MTC any age
Stage IVc
Any T, Any N, M1
only M1
Stage grouping for anaplastic carcinoma
All stages are considered stage IV
Primary mode of therapy for well-differentiated thyroid carcinoma and MTC
Total thyroidectomy
Total thyroidectomy is indicated as primary mode of treatment for well differentiated TC because
Removes primary lesion
Allows accurate histologic diagnosis and staging
Allows assessment of lymph node involvement and spread
Allows post-therapeutic surveillance using Tg as tumor marker
Thyroidectomy + Postsurgical radioablation is performed in
Age <15 >45 History of radiation Known distant metastases Bilateral disease Extrathyroidal invasion Tumor >4cm Cervical lymph node metastases Family history of thyroid cancer
Used for postsurgical ablation of residual thyroid tissue
Treatment of residual or recurrent TC
Reduction in recurrence rates
Improved monitoring with whole-body scanning and serial Tg
Radioiodine treatment
Most stage 1 PTC primary tumor <1.5 can be managed safely with thyroxine supression
Patients who generally require thyroid ablation and radioiodine treatment
Larger papillary carcinomas adjacent lymph node involvement or extrathyroidal invasion
FTC
Evidence of metastases
Strategy for postop radioiodine remnant ablation
2 weeks of liothyronine T3 25ug and then
Complete thyroid withdrawal for 2 weeks
Avoid pretreatment of scanning dise 131I to avoid stunning thyroid cells
Proceed directly to ablation unless suspicion that anount of residual tissue will alter therapy
To increase radioiodine uptake patient must be placed on this diet
Low iodine <50 ug/d urinary iodine
Alternate strategy: Recombinant human TSH (rhTSH) to enhance 131 uptake for post surgical ablation
Used to treat specific metastatic lesions when they cause bone pain or threaten neurologic injury (vertebral metastases)
External-beam radiotherapy
Anaplastic TC therapy
Multimodal
Chemotherapy: cisplatin, bleomycin, 5-fu, cyclophosphamide
EBRT if responsive
Thyroid lymhpoma is highly sensitive to
External-beam radiation
Avoid surgical resection
Primary mode of therapy in MTC
Radioiodine treatment not indicated
Total thyroidectomy
EBRT for extensive local metastasis
Chemotherapy: doxorubicin, vincristine, cyclophosphamide, dacarbazine
Monitoring of Well-differentiated TC
TSH supression (0.1-0.5 mU/L)
If high risk of recurrence or metastatic, complete supression <0.1
FT4 monitored to avoid excessive treatment
Monitoring for recurrence 2
Primary technique
Imaging 131I whole body scanning and/or thyroid ultrasonography
Serum Tg
Initial whole body scan following post therapy scan should be performed after how long post surgery/thyroid ablation
6-12 months
For patients at low risk of recurrence Tg <2 ng/ml this may be used as an alternative to thyroid hormone withdrawal to stimulate Tg 131I uptake after ablation
Avoids symptoms of hypothyroidism and risk of prolonged TSH stimulated growth tumor
Recombinant human TSH
Residual disease or metastases is treated with
Therapeutic 131I
Continue surveillance measures if there is no apparent disease
PE should be done in differentiated TC
every 3-6 months for 2 years
annually if disease-free
TSH and Tg antibodies in differentiated TC should be done
at 6 and 12 months
Anually if disease free
Radioiodine scan in differentiated thyroid carcinoma every
12 months until 1 negative scan if undergone total thyroidectomy and ablation
Surveillance protocol for differentiated TC
Periodic neck UTS and chest radiograph
Additional FDG PET or CT if Tg >10 ng/mL if 131I are negative and stimulated Tg level is >2-5 ng/mL
Consider rhTSh stimulated Tg in low risk patients with negative neck ultrasonography
MTC surveillance
Annual measurement of basal calcitonin and CEA
Periodic neck ultrasonography
Ocreotide scanning to localize
Complications specific to MTC
Secretion of serotonin and prostaglandin causing Flushing, diarrhea
Secretion of ACTH or CRH
Cushing’s
Complications of 131I ablation
Sialodenitis
Radiation thyroiditis
Nausea
Dysgeusia and metallic taste sensation
Infertility and chromosomal abnormalities in offspring occur very rarely after exposure to high doses
Radiation fibrosis or lung (very high cumulative doses)
<20 years >45 years
Prognosis
Worse
Male sex
Prognosis
Worse
Mortality is markedly increased in stage IV disease (1%)
Papillary
Poor prognostic factors in Follicular TC
Distant metastases Age >50 years Primary tumor size >4 cm Hurthle cell histology Presence of marked vascular invasion
Medullary TC may be prevented in patients known to harbor a germline mutation of
RET protooncogene MEN2
By early prophylactic thyroidectomy
Men2A 10 years
Men2B 4 years
