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Chapter 50: Non-MEN Thyroid Cancer Syndromes

Kepal Patel

INTRODUCTION

Thyroid malignancies are classified on the basis of the origin of cells into medullary thyroid cancer (MTC), which originates from the parafollicular cells, and nonmedullary thyroid cancer (NMTC), which originates from the follicular cells. NMTC mainly includes papillary and follicular thyroid cancer (PTC and FTC). Both PTC and FTC are differentiated thyroid cancers that constitute the vast majority of thyroid cancers (>90%) and carry an excellent prognosis with an overall 5-year survival exceeding 95%. 1-4

Both MTC and NMTC can occur sporadically or as part of an inherited syndrome or familial predisposition. This chapter will focus on the diagnosis and management of nonsyndromic familial NMTC (FNMTC) and NMTC associated with inherited syndromes (Table 50-1). Inherited syndromes involving MTC such as multiple endocrine neoplasia type 2 (MEN2a, familial MTC and MEN2b) are not covered in this chapter.

TABLE 50-1:

The Clinical Features Associated with Familial Thyroid Cancer Syndromes

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TABLE 50-1:

The Clinical Features Associated with Familial Thyroid Cancer Syndromes
Familial Thyroid Cancer Syndrome Clinical Features
Cowden syndrome

  • Multiple hamartomas

  • Acral keratosis

  • Oral papillomatous papules

  • Trichilemmoma

  • Benign and malignant breast disease

  • Benign and malignant uterine disease

  • Benign and malignant thyroid disease
Familial adenomatous polyposis

  • Intestinal:

    • Gastric and duodenal polyps (periampullary cancer)

    • >100 colon and rectal adenomas (colorectal cancer)

  • Extraintestinal (Gardner's syndrome):

    • Osteomas

    • Dental abnormalities

    • Epidermal cysts

    • Desmoids tumors

    • CHRPE (Congenital Hypertrophy of the Retinal Pigment Epithelium)

    • Hepatoblastoma

    • Medulloblastoma (Turcot syndrome)

    • Thyroid cancer
Carney complex

  • Myxomas:

    • Heart

    • Skin and soft tissue

    • External auditory canal

    • Breast

  • Pituitary adenomas

  • Primary pigmented micronodular adrenal hyperplasia

  • Cushing's syndrome

  • Schwannomas

  • Testicular tumors

  • Thyroid disease
Werner syndrome

  • Premature aging

  • Short stature

  • Age-related disorders (osteoporosis, cataracts, diabetes, peripheral vascular disease, malignancy)

  • Epithelially derived malignancy (melanoma, soft tissue sarcoma, osteosarcoma)

Abbreviation: CHRPE, congenital hypertrophy of the retinal pigment epithelium.

NONSYNDROMIC FAMILIAL NONMEDULLARY THYROID CANCER

Familial NMTC is commonly defined by the presence of well-differentiated thyroid cancer (WDTC) in two or more first-degree relatives in the absence of predisposing hereditary syndromes (i.e., Cowden syndrome, Gardner's syndrome) or environmental factors (ionizing radiation to the neck, iodine deficiency). 5,6 It is estimated that FNMTC accounts for 3% to 10% of all the thyroid cancer cases with an autosomal dominant pattern of inheritance with incomplete penetrance. 6-9 However, the true incidence of FNMTC is not known, and it is estimated that PTC is in fact sporadic in 45% to 69% of the cases with only two affected family members. 10

The most common histologic subtype of FNMTC is PTC. Women seem to be affected approximately two to three times more than men and the age at diagnosis for patients with FNMTC seems to be less than that of sporadic cases (41 vs. 47). 6,8,10-12 This, however, may be an artifact of early screening for patients with ...

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