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. 2022 Apr 27;13:866572. doi: 10.3389/fendo.2022.866572

Table 4.

Review of previously published reports and series of E-MTCs.

Author, year [reference] Description of reported E-MTCs (with definition of encapsulation when available) E-MTC (%) Capsule integrity (%) Tumor size (mm) Metastatic MTC (%), site Biochemical Cure (%)
Williams et al., 1966 (24) MTC sharply demarcated from the surrounding thyroid tissue by a complete or partial fibrous capsule 9/67 (13.4) 2/9 (22.2) NR NR NR
Beskid, 1979 (25) “C cell adenoma” surrounded by a thick hyaline capsule with no infiltration of the capsule by the nodule cells 1/1 (100) 1/1 (100) 40 0 1/1 (100)
Kodama et al., 1988 (26) “C cell adenomas” (one with incomplete very thin capsule without infiltrative growth) with positive Ctn and no CEA staining; low serum CEA 1/2 (50) 0/1 (0) 40 (both) 0 2/2 (100)
Driman et al., 1991 (27) MTC surrounded by a distinct fibrous capsule with weak Ctn, CEA and CgA staining; normal-high serum Ctn and low serum CEA 1/1 (100) NR 20 0 1/1 (100)
Ozkara et al., 2002 (28) Encapsulated (intact capsule) papillary variant MTC with extensive cystic degeneration and positive Ctn, CEA, CgA staining 1/1 (100) 1/1 (100) 40 0 1/1 (100)
Miccoli et al., 2007 (17) MTCs divided in completely encapsulated and non-encapsulated 18/70 (34.6) 18/18 (100) NR 0 18/18 (100)
Santosh et al., 2011 (29) Well-encapsulated HTA-like variant MTC with positive Ctn staining 1/1 (100) 1/1 (100) 30 0 1/1 (100)
Bhat and Jena, 2012 (30) Well-encapsulated HTA-like variant MTC with positive Ctn staining 1/1 (100) 1/1 (100) 30 0 NR
Aubert et al., 2018 (14) MTCs with or without tumor capsule (not otherwise specified) 21/54 (38.9) NR NR 3 (14.3), N 18/18 (100)
Cipri et al., 2019 (31) Encapsulated microMTC with positive Ctn and CgA staining; undetectable serum Ctn 1/1 (100) NR ≤ 10 0 1/1 (100)
Censi et al., 2019 (32) Well-encapsulated “borderline tumor” (between adenoma and carcinoma) with weak CEA and no CgA staining; low serum CEA 1/1 (100) 1/1 (100) 70 0 1/1 (100)
Alzumaili et al., 2020 (13) MTCs divided in completely encapsulated/well circumscribed, partially encapsulated or totally lacking a capsule; capsular invasion defined as complete tumoral penetration of the capsule 26/143 (18.2) 8/26 (30.8) NR NR NR*
Singh et al., 2020 (33) Encapsulated papillary variant MTC with extensive cystic degeneration and positive Ctn and CgA staining 1/1 (100) NR 80 1 (100), N NR §§
Moura et al., 2021 (15) Collateral reporting of encapsulated MTC (not otherwise specified) 8/65 (12.3) NR NR 1 (12.5), N NR
Machens et al., 2021 (18) Tumor capsule integrity was classed into 5 subgroups: tumor capsule evenly demarcated; tumor capsule irregular but intact, with or without invasion; breach of the tumor capsule with ≤3 tumor extensions measuring ≤3 mm in width; breach of the tumor capsule with >3 tumor extensions or one tumor extension measuring >3 mm in width; diffuse tumor growth without tumor capsule. 81/139 (58.3) 47§/81 (58) Between 7 and 12§§ (median) 0 45/46§§§ (97.8)
Sum of published cases 172/548 (31.4) 80/140 (57.1) 5 (2.9), N 89/90 (98.9)
Present series 7/44 (15.9) 4**/7 (57.1) 0 7/7 (100)
Total cases 179/592 (30.2) 84/147 (57.1) 5 (2.8), N 96/97 (98.9)

E-MTC, encapsulated medullary thyroid carcinoma; CEA, carcinoembrion antigen; CgA, cromogranin A; Ctn, calcitonin; HTA, hyalinizing trabecular adenoma; N, nodal metastases; NR, not reported.

*Tumor encapsulation improved loco-regional free survival but had no effect on disease specific survival and distant metastasis free survival.

§ Included cases with tumor capsule evenly demarcated, irregular but intact, or with less than 3 tumor extensions < 3 mm in width.

§§Only tumors with size ≤ 25 mm on histopathologic evaluation were included in the entire study.

**Only encapsulated tumors without full-thickness capsular invasion (albeit focal).

§§§One patient lost at follow-up.