☠️🤕Anaplastic Thyroid carcinoma Flashcards
(11 cards)
WHO definition of Anaplastic Thyroid carcinoma
WHO definition - a highly aggressive thyroid malignancy composed of undifferentiated follicular thyroid cells.
Epidemiology of Anaplastic Thyroid carcinoma
- Very poor prognosis. Survival measured in months. Median survival is 5–6 months and the 1-year survival is 20%.
- 1% of well-differentiated thyroid cancer can transform into ATC.
- Mean age 70 years, F : M = 2:1
- May be associated with radiation and iodine deficiency.
- Differential include - primary thyroid lymphoma, SCC of the head and neck, and
metastatic cancer (especially from lung).
Presenntation of Anaplastic Thyroid carcinoma
- Rapid expanding thyroid mass, firm, hard and fixed, compressing the trachea and skin causing skin necrosis.
- Local tumor extension → fixation of larynx, esophagus and carotid vessels, Dysphagia, Dysphonia, Dyspnea, Hoarseness.
- LN’s enlargement (84%), Systemic metastasis (75%) → lungs, bones, brain, adrenals.
Investigation
1) FNAC + IHC
- To exclude lymphoma and medullary, tall cell papillary and metastatic cancer.
- TG & TTF-1 expected to be absent.
2) CNB
- Cases in which cellular yield is insufficient, core biopsy may be diagnostic.
- BRAF assessment by IHC and NGS testing of tumor.
Next-generation sequencing (NGS) is a new technology used for DNA and RNA sequencing and variant/mutation detection
3) 18F FDG PET/CT
4) CE-CT - neck, chest, abdomen, and pelvis
5) MRI - if PET unavailable - and as needed for surgical decision-making
6) Laryngoscopy - evaluation of vocal cords at initial presentation, and thereafter based upon changing symptoms.
7) Esophagoscopy as indicated to assess invasion.
staging for anaplastic thyroid carcinoma
All anaplastic thyroid cancers are considered stage IV, reflecting the poor prognosis for people with this type of cancer.
Surgical Options for anaplastic thyroid carcinoma
Definitive Surgery
- Total or near-total thyroidectomy with therapeutic CLND and PLND the most optimal surgical treatment in patients with resectable disease.
- Rationale for a total or near-total thyroidectomy 20% of patients with ATC have coexisting DTC, and a complete resection (R0/R1) may be associated with improved disease-free survival and overall survival with or without combination chemotherapy and radiotherapy.
Debulking surgery
- May improve patient survival, most ATCs progress rapidly but need to weigh the possibility of delayed EBRT or systemic chemotherapy because of wound complications.
Surgical resection rarely can achieve complete excision (R0) with extensive surgery causing more morbidity.
- Tumor debulking surgery is not recommended as tumor has rapid rate of regrowth.
- Palliative chemoradiation in unresectable tumor can reduce rate of tumor growth and relieving pressure on
surrounding structure. - In stage 4 disease, treatment need to balance between local control and therapy for the metastasis
If locoregional disease is threatening: primary chemoradiation
If airway not at risk or already on tracheostomy: systemic chemotherapy
Palliative options for Anaplastic Thyroid carcinoma
As a preventive procedure
- Securing the airway because of impending airway compromise,
- Resection of locoregional disease in a patient with distant metastases, especially in patients with low-volume distant metastases if it can be done with minimal morbidity so that it would not affect initiation of systemic therapy.
- Palliative for symptoms associated with disease (pain from bulky locally invasive disease, airway obstruction, esophageal obstruction).
Role of Tracheostomy in Anaplastic Thyroid carcinoma
- Patients without impending airway compromise, advised against prophylactic tracheostomy placement, it may overcome acute airway distress with some prolongation of life, meaningful or not remains controversial.
- Best avoided in unresectable ATC.
- Patients in severe airway distress, tracheostomy in operating room under anesthesia with preoperative intubation, if possible. Patients often require isthmusectomy or debulking of the pretracheal tumor to obtain adequate access for a tracheostomy.
Adjuvant Therapy for Anaplastic Thyroid carcinoma
RADIOTHERAPY
- R0 or R1 resection, with good performance status and M0 disease who wish an aggressive approach → standard fractionation Intensity-modulated radiation therapy (IMRT) with concurrent systemic therapy.
- Radiation therapy should begin no later than 6 weeks after surgery.
- R2 resection or unresectable but nonmetastatic disease with good performance status and who wish an aggressive approach → standard fractionation IMRT with systemic therapy.
- Alternative to RT, in BRAFV600E-mutated ATC, combined BRAF/MEK inhibitors can be considered in this context.
- Unresectable disease during initial evaluation in whom radiotherapy and/or systemic (chemotherapy or combined BRAF/MEK inhibitors) therapy render the tumor potentially resectable → reconsideration of surgical resection.
- Poor performance status, palliative or preventative (no residual disease present) → locoregional radiotherapy over high-dose radiotherapy is suggested.
CHEMOTHERAPY
- Cytotoxic chemotherapy involving a taxane (paclitaxel or docetaxel), administered with or without anthracyclines (doxorubicin) or platin (cisplatin or carboplatin), is recommended in patients treated with definitive intention radiation.
Targeted therapy as 1st line therapy only approved in ATC with known BRAFV600E mutation.
* Combination BRAF inhibitor (Dabrafenib) and MAPK/ERK (MEK) inhibitor (Trametinib)- high ORR 70%.
HPE of Anaplastic Thyroid carcinoma
- Infiltrative (so that externally, there is no discernible thyroid shape) large solid tumor with necrosis, cystic change and hemorrhage.
- Pauci-cellular variant: hard fibrotic mass
There are three main histological growth patterns to ATC: spindle cell, pleomorphic giant cell, and squamoid
Prognosis of anaplastic thyroid carcinoma
- Median survival 2.5 - 9 months with 2-year survival < 20%
- Higher survival includes young age (<45 y), female, tumor < 6cm, disease confined to neck, complete resection.
