Timing and Extent of Surgery for a Pediatric Patient with Hereditary MTC and Positive Screening for the S891A RET Mutation

Patient no., gender, age (years)

Preoperative calcitonin (pg/mL)

Extent of surgery

Histopathology; pTNM

Postoperative calcitonin (pg/mL)

Basal

Peak

Basal

Peak

1.1; f; 78

312

2634

TT, LND central and lateral

Bilateral MTC (10 mm, 11 mm); 1/45 LNM; pT1bpN1aM0

2.3; m; 46

TT, LND central and lateral

Bilateral MTC (3 mm, 5 mm), unilateral PTC (1 mm); 0/31 LNM; pT1apN0M0

3.1.2; m; 17

510

TT, LND central

Bilateral MTC (3 mm, 3 mm), 0/7 LNM; pT1apN0M0

3.2.4; f; 10

Bilateral CCH, no MTC, 0/1 LNM

3.1.3; m; 8

No CCH, no MTC; 0/1 LNM

3.2.3; m; 8

Bilateral CCH, no MTC

3.2.2; m; 6

Bilateral CCH, no MTC, 0/1 LNM

3.2.1; f; 5

Bilateral CCH, no MTC, 0/1 LNM

Patient numbers are the same as in Fig. 45.1. The calcitonin assay’s upper normal limit was <5.0 pg/mL for women and <8.4 for men (Immulite 2000 assay, Diagnostic Products Corp., Los Angeles, CA)

pTNM according to Sobin LH, Gospodarowicz MK, Wittekind Ch (eds.): TNM Classification of Malignant Tumors, 7th Edition, 2009

TT total thyroidectomy, LND lymph node dissection, CCH C-cell-hyperplasia, f female, m male, MTC medullary thyroid cancer, LNM lymph node metastasis, nd not determined

Fig. 45.1

Pedigree of the 3-generational family carrying the heterozygous S891A RET mutation. Filled circle, filled square Gene carrier (female, male). Open circle, open square Kindred (female, male) without S891A mutation. Open circle with filled square Male index patient of the family. Asterisk Patients with MTC

Evaluation for Surgery

On stimulation with pentagastrin, the adolescent carrier’s calcitonin serum levels rose from 24 pg/mL basally (upper normal limit <8.4 pg/mL; Immulite 2000 assay, Diagnostic Products Corp., Los Angeles, CA) to a peak level of 510 pg/mL after 5 min (patient 3.1.2; Table 45.1, Fig. 45.1). Physical examination of the thyroid gland and high-resolution neck ultrasonography were negative. Thyroid examination of the other eight non-index patients, including ultrasonography, identified multinodular goiter disease without evidence of lymph node metastases in the 78-year-old grandmother (patient 1.1) and a suspicious small hypoechoic lesion in her 46-year-old son (patient 2.3) (Fig. 45.2). With the exception of two 5- and 8-year-old children (patients 3.2.1 and 3.1.3), all non-index patients exhibited elevated basal calcitonin levels. All family members who had a pentagastrin stimulation test performed showed peak calcitonin levels markedly increased over baseline (Table 45.1). None of the eight non-index patients had biochemical or imaging evidence for adrenal medullary or parathyroid disease.