basic Medullary thyroid CA Surgical MANAGEMENNT.pptx

medullary thyroid CA

1. MEDULLARY THYROID CARCINOMA Insight on basic surgical guidelines WHAT TO DO AND WHEN.. 6/7/2024 12:16 AM 1

2. Why All These Discussion ? Rare disease, hence experience of even high volume centers may be a little Inexperience may lead to over treating or under treating / over evaluating or under evaluating ultimately impacting patient in one or other way INITIAL WORKUP FOR SPORIADIC cases remains same... USG  FNAC when indicated Further workup changes as MTC has a debatable role of Genetic / CEA / calcitonin / Imaging / during pre-surgical work-up / surgical modality / post-surgical surveillance. 6/7/2024 12:16 AM 2

3. Working up undiagnosed Thyroid nodule Obviously, history  USG  FNAC as indicated USG Features MAY MIMIC BENIGH NODULES Most benign / MTC nodules  regular borders (63.4%, MTC and 75%, benigh ) PTC nodule 64 % irregular borders Microcalcifications less common in MTC (16%) Also uncommon in benigh (<1%) PTC appx 70% Trimboli et al 2014, N - 254 hypoechogenicity appx 70% for PTC , 50% for MTC and 20.1% for benign nodules higher prevalence of round or oval shapes in MTC. Choe et al 2011  30 patients with MTC (36 nodules )  hypoechoic 72.2% solid 91.7% smooth borders 52.8% round or oval shape 63.9% micro- or macro calcifications 58.3% Increased vascularity 90.9% compared with PTC 9.5%. (N= 87) Liu MJ et al. 2017 USG, the 1 st step of work up for thyroid nodule 6/7/2024 12:16 AM 3

4. Working up undiagnosed Thyroid nodule Role of FNAC  most important to raise suspicion Misdianosed as follicular neoplasm , plasmacytoma or even sarcoma Individual studies reported accuracy ranging from 80 to 90% Chang TC , 2005, Papaparaskeva K , 2007 Recent metaanalysis of 15 studies reported lower accuracy < 60% …! Trimboli et al 2015 FNA Aspirate for calcitonin : More sensitive than FNA, reports suggests sensitivity >97% Cut-off value  debatable,, 39.6 pg /mL provided 100% senstitivity ( Trimboli et al 2015) range used  7.4–67 pg /mL (>95% sensitivity) IHC for FNA specimen for calcitonin or CEA  enhances sensitivity by up to 90% false-positive results of bCtn : Neuroendocrine tumors . PPI, renal failure, pregnancy and hypothyroidism, in Children (<6 months, especially 3 yrs ) Calcitonin. & CEA When, why and How ? 6/7/2024 12:16 AM 4

5. Verbeek HHG, et al. Calcitonin testing for detection of medullary thyroid cancer in people with thyroid nodules. Cochrane Database of Systematic Reviews 2020 , Issue 3. Art. No.: CD010159. 6/7/2024 12:16 AM 5

6. So, in practice, when should we order Ctn / CEA in UNDIAGNOSED Case..? Although surgeons usually don’t understand much cyto / pathology..! MTC cells are usually discohesive or weakly cohesive Can be spindle-shaped (mimic sarcomas ) Plasmacytoid (mimic plasmacytomas ) or epithelioid (mimic thyroid follicular lesions ) bizarre giant cells, oncocytic cells, clear cells, and cells with a small cell carcinoma–like appearance. tumor cells may contain azurophilic perinuclear cytoplasmic granules. The eccentric nuclei exhibit chromatin granularity as a ‘‘salt and pepper’’ appearance that is typical of NETs Amyloid can be mistaken for colloid and on its own is not diagnostic REMEMBER Few word of FNA picture, if they raises a suspicion (B III / IV category especially) 6/7/2024 12:16 AM 6

7. IMAGING, WHEN AND WHAT.? Ctn level 20  ipsilateral central neck Ctn 50  ipsilateral lateral neck Ctn 200  Contralateral central Ctn 500  the contralateral lateral neck, and the upper mediastinum Recommendation : ( Ctn > 500) CECT Neck and chest 3 phase protocol CE liver protocol CT or CE magnetic resonance imaging (MRI) of the liver, Bone scan and skeletal MRI NCCN and ATA ( DOTATATE) PET/CT can be optionally considered in such patients because of the improved localization of MTC F-DOPA-PET/CT were available in MTC patients with high serum calcitonin levels (≥500 pg /mL ) ESMO recommendation, but ATA does not recommend BUT HAVE ROLE IN DISEASE PROGRESSION / SURVEILLENCE BASED ON Ctn level, generally >150 Post Tx . patients with extensive neck disease, serum calcitonin levels greater than 500 pg /mL, or elecated CEA levels signs of distant metastasis 6/7/2024 12:16 AM 7

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9. How to proceed sporadic MTC… SPORADIC MTC Dx on FNA Basal serum calcitonin level CEA Pheochromocytoma screening Serum calcium Screen for germline RET proto‐oncogene mutations USG Neck Consider evaluation of vocal cord mobility SPORADIC MTC Dx after thyroidectomy Basal serum calcitonin level CEA Screen for germline RET proto‐oncogene mutations USG Neck for LNs if not previously done Additional cross‐sectional imaging ( based on high burden of disease, calcitonin g >400 pg /mL, or elevated CEA levels ) CECT neck/chest and liver MRI or 3 phase CT of liver Ga‐68 DOTATATE PET CT/ Bone scan/ Skeletal MRI 6/7/2024 12:16 AM 9

10. Surgery : Mainstay of Tx , TT + CCND Therapeutic lateral SND for clinically or radiologically identifiable disease Elective lateral SND based on clinical judgement  high‐volume or gross disease in the adjacent central neck or based on Ctn Values therapeutic EBRT/IMRT for grossly incomplete tumor resection when additional attempts at surgical resection have been ruled out Adjuvant EBRT/IMRT is rarely recommended Postoperative administration of levothyroxine to normalize TSH < 1 cm, Unilateral  TT + CCND (based on risk factors) > 4cm Total thyroidectomy + bilateral central neck dissection + ipsilateral modified neck dissection (levels II–V ) 6/7/2024 12:16 AM 10 ≥1.0 cm < 4 cm in diameter or bilateral thyroid disease

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12. 6/7/2024 12:16 AM 12 US-negative patients: elective neck dissection based on Ctn levels; US-positive patients: bilateral CND plus therapeutic neck dissection of involved levels plus contralateral LND if serum Ctn > 200 pg /ml.

13. Hemithyroidectomy Don’t fear, if your diagnosis is clear…!!! 6/7/2024 12:16 AM 13 Machens , A.; Lorenz, K .; Brandenburg , T.; Fuhrer, D.;Weber, F .; Dralle , H. Latest Progress in Risk-Adapted Surgery for Medullary Thyroid Cancer. Cancers 2024 , 16 , 917. https :// doi.org/10.3390/ cancers16050917

14. sporadic medullary thyroid cancer 1/3 rd tumor are desmoplasia negative, low risk 6/7/2024 12:16 AM 14

15. Hereditary Medullary Thyroid Cancer Total thyroidectomy , without node dissection, in the absence of an identifiable primary thyroid tumor, Total thyroidectomy, with or without a diagnostic ipsilateral central node dissection, for one ( or more ) desmoplasia -negative primary thyroid tumor(s), Total thyroidectomy with concomitant ipsilateral central and lateral node dissections, with or without a diagnostic contralateral central node dissection , for one (or more ipsilateral) less advanced desmoplasia -positive primary thyroid tumor(s), Total thyroidectomy with concomitant bilateral central and lateral node dissections for one or more desmoplasia -positive primary thyroid tumor(s), one of which is advanced ) 6/7/2024 12:16 AM 15

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17. Germline RET mutation identified : Syndromic workup  Tx MEN2B TT during 1 st year or Immediate after Dx B/L CCND to be considered. SND as indicated Consider more extensive node dissection (levels II–V) if tumor (s) >0.5 cm in diameter Postoperative administration of levothyroxine to normalize TSH MEN2A/Familial MTC : Pth workup NO PHPT TT before 5 yr , or immediate after Dx CCND based on imaging / calcitonin level SND in high volume disease Postoperative administration of levothyroxine to normalize TSH PHPT If single adenoma – excise If multiglandular disease -- autotransplant or leave the equivalent mass of one normal parathyroid gland Consider cryopreservation of parathyroid tissue 6/7/2024 12:16 AM 17

18. Follow-up : CEA and Calcitonin Detectable basal calcitonin or Elevated CEA Neck ultrasound If Ctn ≥150 pg /mL, CECT liver, chest, neck Bone scan, Skeletal MRI in >>>> Ctn (500) Basal calcitonin undetectable and CEA within reference range Annual serum Ctn , CEA, USG Neck for LNs Additional studies or more frequent testing if significantly rising calcitonin or CEA Imaging Positive : Mx of recurrent / Mets. Accordingly (Palliative / Therapeutic based on assessment) Imaging Negative : Frequent studies / CEA calcitonin doubling time  tests aat 6 / 12 months FDG PET/CT or Ga‐68 DOTATATE or MRI with contrast of the neck, chest, abdomen with liver protocol No additional imaging required if calcitonin and CEA stable 6/7/2024 12:16 AM 18

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20. RECURRENT OR PERSISTENT DISEASE – LOCOREGIONAL DISEASE Surgical resection is the preferred treatment modality EBRT/IMRT can be considered for unresectable disease or, less commonly, after surgical resection Consider systemic therapy for unresectable disease that is symptomatic or progressing by RECIST criteria preferred Regimens Vandetanib (category 1) Cabozantinib (category 1) Selpercatinib ( RET mutation‐positive) Pralsetinib ( RET mutation‐positive ) Useful in Certain Circumstances -- Pembrolizumab (TMB‐H [≥10 mut /Mb] Disease monitoring 6/7/2024 12:16 AM 20