Keywords

FormalPara Thyroid Gland
  1. 1.

    Summary of applications and limitations of useful markers (Table 17.1)

  2. 2.

    Markers for normal thyroid follicles (Table 17.2)

  3. 3.

    Summary of useful markers in common tumors of the thyroid gland (Table 17.3)

  4. 4.

    Other encapsulated follicular-patterned thyroid tumors (Table 17.4)

  5. 5.

    Markers for solid cell nests (Table 17.5)

  6. 6.

    Markers for hyalinizing trabecular tumor (Table 17.6)

  7. 7.

    Markers for paraganglioma (Table 17.7)

  8. 8.

    Markers for Hurthle (oncocytic) cell tumor (Table 17.8)

  9. 9.

    Markers for follicular thyroid carcinoma, NOS (Table 17.9)

  10. 10.

    Markers for papillary thyroid carcinoma (Table 17.10)

  11. 11.

    Markers for medullary thyroid carcinoma (Table 17.11)

  12. 12.

    Markers for poorly differentiated thyroid carcinoma (Table 17.12)

  13. 13.

    Markers for anaplastic thyroid carcinoma (Table 17.13)

  14. 14.

    Markers for mucoepidermoid carcinoma of the thyroid (Table 17.14)

  15. 15.

    Markers for sclerosing mucoepidermoid carcinoma with eosinophilia of thyroid (Table 17.15)

  16. 16.

    Markers for spindle epithelial tumor with thymus-like differentiation (Table 17.16)

  17. 17.

    What is the utility of BRAF mutation-specific antibody in diagnosing papillary thyroid carcinoma?

FormalPara Differential Diagnosis
  1. 18.

    Solid cell nests versus nodular C-cell hyperplasia (Table 17.17)

  2. 19.

    Solid cell nests versus papillary microcarcinoma (Table 17.18)

  3. 20.

    Hyalinizing trabecular tumor versus paraganglioma (Table 17.19)

  4. 21.

    Hyalinizing trabecular tumor versus papillary carcinoma (Table 17.20)

  5. 22.

    Hyalinizing trabecular tumor versus medullary carcinoma (Table 17.21)

  6. 23.

    Follicular adenoma versus follicular carcinoma (Table 17.22)

  7. 24.

    Differentiation of follicular adenoma with clear cell changes (Table 17.23)

  8. 25.

    Follicular variant of papillary thyroid carcinoma versus follicular neoplasm (Table 17.24)

  9. 26.

    Differential diagnosis of anaplastic carcinoma (Table 17.25)

  10. 27.

    Metastatic cystic papillary carcinoma versus metastatic cystic squamous cell carcinoma (Table 17.26)

  11. 28.

    Proliferative, prognostic, and cell cycling markers in normal follicular epithelium and thyroid carcinomas (Table 17.27)

FormalPara Parathyroid Gland
  1. 29.

    Summary of useful markers in the evaluation of the parathyroid gland (Table 17.28)

  2. 30.

    Markers for normal parathyroid gland (Table 17.29)

  3. 31.

    Markers for parathyroid neoplasms (Table 17.30)

FormalPara Adrenal Gland
  1. 32.

    Summary of useful markers used in evaluation of the adrenal glands (Table 17.31)

  2. 33.

    Expression of markers in normal adrenal gland (Table 17.32)

  3. 34.

    Markers for sustentacular cells versus chief cells in the medulla (Table 17.33)

  4. 35.

    Cortical neoplasms versus pheochromocytoma (Table 17.34)

  5. 36.

    Differential of tumors with abundant clear to granular cytoplasm, round nuclei, and nucleoli (Table 17.35)

  6. 37.

    Differential of normal and neoplastic oncocytic cells (Table 17.36)

  7. 38.

    Markers useful in the differential of tumors most frequently metastatic to adrenal gland (Table 17.37)

Table 17.1 Summary of applications and limitations of useful markers
Fig. 17.1
figure 1

TTF1 expression pattern in normal and various neoplasm of thyroid; (a) TTF1 expression in normal thyroid tissue; (b) TTF1 expression in papillary thyroid carcinoma, strong and diffuse; (c) TTF1 expression in follicular thyroid carcinoma, weaker in intensity; (d) TTF1 expression in medullary carcinoma, weaker in intensity

Fig. 17.2
figure 2figure 2

PAX8 expression in various neoplasms of thyroid; (a) PAX8 expression in follicular adenoma; (b) PAX8 expression in papillary thyroid carcinoma; (c) PAX8 expression in follicular thyroid carcinoma, weak; (d) Lack of expression of PAX8 in medullary carcinoma

Table 17.2 Markers for normal thyroid follicles
Table 17.3 Summary of useful markers in common tumors of the thyroid gland
Table 17.4 Recommended nomenclature for encapsulated follicular-patterned tumors on the bases of the presence or absence of nuclear features of papillary thyroid carcinoma (PTC) and capsular or vascular invasion, 2017 WHO Classification
Table 17.5 Markers for solid cell nests
Table 17.6 Markers for hyalinizing trabecular tumor
Fig. 17.3
figure 3

(a) Hyalinizing trabecular adenoma, hematoxylin and eosin (H&E); (b) hyalinizing trabecular adenoma shows membranous and cytoplasmic staining pattern for MIB-1

Table 17.7 Markers for paraganglioma
Table 17.8 Markers for Hurthle (oncocytic) cell tumor
Table 17.9 Markers for follicular thyroid carcinoma
Fig. 17.4
figure 4

(a) Follicular thyroid carcinoma, negative for AE1/3; (b) follicular thyroid carcinoma, positive for RCCMa

Table 17.10 Markers for papillary thyroid carcinoma
Fig. 17.5
figure 5

TROP-2 staining pattern in thyroid neoplasm and lesions; (a) Papillary thyroid carcinoma (PTC), follicular variant, hematoxylin and eosin (H&E); (b) PTC, follicular variant, diffuse (4+) TROP-2 staining, membranous pattern. 90% of PTCs on TMA sections showed TROP-2 expression in a membranous staining pattern; (c) follicular carcinoma (FC), H&E; (d) FC, focal (1+) strong cytoplasmic staining for TROP-2. Follicular neoplasms (FC and follicular adenoma [FA]) showed no TROP-2 expression; only 2/51 FAs and 4/37 FCs showed focal (1+) cytoplasmic staining without membranous pattern; (e) H&E, focal cystic degeneration in a case of lymphocytic thyroiditis; (f) Focal membranous staining for TROP-2 in the lining cells of the cyst. All 20 cases of benign thyroid lesions (10 lymphocytic thyroiditis, 10 nodular goiter) were negative for TROP-2

Fig. 17.6
figure 6

Typical staining pattern of papillary thyroid carcinoma (PTC); (a) PTC, membranous staining pattern for TROP2; (b) PTC, cytoplasmic, and membranous staining for HBME-1; (c) PTC, cytoplasmic, and membranous staining for CK19; (d) PTC, cytoplasmic staining for galectin-3; (e) PTC, cytoplasmic staining for thyroglobulin; (f) PTC, nuclear staining for cyclin D1; (g) PTC, cytoplasmic staining for S100A1; (h) PTC, cytoplasmic staining for vimentin

Fig. 17.7
figure 7

A rare case of papillary thyroid carcinoma (PTC) showing CDX-2 reactivity; (a) PTC, hematoxylin and eosin (H&E); (b) PTC, CDX-2 positive; (c) PTC, TTF1 positive; (d) PTC, thyroglobulin positive

Table 17.11 Markers for medullary thyroid carcinoma
Fig. 17.8
figure 8

Typical phenotype of medullary carcinoma (MC); (a) MC, hematoxylin and eosin (H&E); (b) MC, positive for calcitonin; (c) MC, positive for CEA; (d) MC, positive for chromogranin; (e) MC, positive for S100A6; (f) MC, negative for S100A1

Table 17.12 Markers for poorly differentiated thyroid carcinoma
Table 17.13 Markers for anaplastic thyroid carcinoma
Table 17.14 Markers for mucoepidermoid carcinoma of the thyroid
Table 17.15 Markers for sclerosing mucoepidermoid carcinoma with eosinophilia of thyroid
Table 17.16 Markers for spindle epithelial tumor with thymus-like differentiation

What Is the Utility of BRAF Mutation-Specific Antibody in Diagnosing Papillary Thyroid Carcinoma?

The BRAF oncogene has been demonstrated to be mutated in several types of tumors, such as colorectal adenocarcinoma, PTC, glioma, gastrointestinal adenocarcinoma, melanoma, and pulmonary adenocarcinoma. The most common mutation in BRAF is due to a T to A switch at position 1796, which results in an alteration from valine to glutamate at V600E. The BRAF V600E point mutation has been reported in 30–90% of PTCs of all histotypes, with a higher frequency in tall cell variant (60–95%) and oncocytic variant and a much lower frequency (5–25%) in follicular variant. The BRAF V600E mutation is generally negative in benign follicular lesions, normal thyroid tissue, MC, and FC. A meta-analysis of 5655 patients suggested PTC with the BRAF mutation is associated with a higher risk of recurrent persistent disease, lymph node metastasis, and extrathyroidal extension. Many molecular techniques have been employed to detect the BRAF V600E point mutation, including single-strand conformation polymorphism, mutation-specific polymerase chain reaction (PCR), direct gene sequencing, and colorimetric mutation analysis. These methods tend to be expensive, time-consuming, labor-intensive, and difficult to validate and implement in some clinical settings.

There are two commercially available, mutation-specific antibodies against BRAF V600E; one is VE1 clone (Spring Bioscience, Pleasanton, CA) and the other is anti-B-Raf mouse monoclonal antibody (New East Bioscience, Malvern, PA). Most studies used the VE1 clone, and only rare studies used anti-B-Raf mouse monoclonal antibody. In general, BRAF mutation-specific antibody has been shown to be useful in detection of the BRAF V600 mutation, with a sensitivity and specificity of over 95% when compared to other molecular methods. In fact, some studies suggested that anti-BRAF mutation-specific antibody may be more sensitive than molecular testing in detecting the BRAF mutation. An example of the BRAF mutation in a papillary thyroid microcarcinoma detected by IHC using the VE1 clone is shown in Fig. 17.9a, b.

References: [191,192,193,194,195,196,197].

Fig. 17.9
figure 9

(a) Papillary thyroid carcinoma (PTC), hematoxylin and eosin (H&E); (b) PTC, positive for BRAF

Differential Diagnosis

Table 17.17 Solid cell nests versus nodular C-cell hyperplasia
Table 17.18 Solid cell nests versus papillary microcarcinoma
Table 17.19 Hyalinizing trabecular tumor versus paraganglioma
Table 17.20 Hyalinizing trabecular tumor versus papillary carcinoma
Table 17.21 Hyalinizing trabecular tumor versus medullary carcinoma
Table 17.22 Follicular adenoma versus follicular carcinoma
Table 17.23 Differentiation of follicular adenoma with clear cell changes
Table 17.24 Follicular variant of papillary thyroid carcinoma versus follicular neoplasm
Table 17.25 Differential diagnosis of anaplastic carcinoma
Table 17.26 Metastatic cystic papillary carcinoma versus metastatic cystic squamous cell carcinoma
Table 17.27 Proliferative, prognostic, and cell cycling markers in normal follicular epithelium and thyroid carcinomas
Table 17.28 Summary of useful markers in the evaluation of the parathyroid gland

Parathyroid Gland

Table 17.29 Markers for normal parathyroid gland
Table 17.30 Markers for parathyroid neoplasms
Fig. 17.10
figure 10

(a) Expression of parafibromin is more frequent in parathyroid adenoma; (b) loss expression of parafibromin in parathyroid carcinoma

Adrenal Glands

Table 17.31 Summary of useful markers for evaluation of adrenal glands
Table 17.32 Expression of markers in normal adrenal gland
Table 17.33 Markers for sustentacular cells versus chief cells in the medulla
Table 17.34 Cortical neoplasms versus pheochromocytoma
Fig. 17.11
figure 11

SF-1 is a newer antibody for marking steroid producing cells. Here steroid producing cells in the adrenal cortex demonstrate nuclear staining for SF-1 protein

Fig. 17.12
figure 12

Calretinin is a useful marker to identify adrenocortical cells; here it nicely demonstrates the bubbly appearance of the steroid product in the cytoplasm

Fig. 17.13
figure 13

Synaptophysin stains the chief cells in a pheochromocytoma (right half of photo), but does not stain the adrenal cortical cells (left half of photo)

Fig. 17.14
figure 14

S100 stains the sustentacular cells in this pheochromocytoma, but not the chief cells

Table 17.35 Differential of tumors with abundant clear to granular cytoplasm, round nuclei, and nucleoli
Table 17.36 Differential of normal and neoplastic oncocytic cells
Table 17.37 Markers useful in the differential of tumors most frequently metastatic to adrenal gland