Endocrine Malignancies



Endocrine Malignancies





THYROID CANCER

Payal D. Shah

Eric J. Sherman


Epidemiology



  • Incidence: 240% ↑ in incidence over prior 3 decades, in part due to ↑ detection of small papillary CA; incidence of anaplastic thyroid CA declining


  • Mortality: Mortality rate stable; accounts for 95% of endocrine CA but 66% of endocrine CA death


  • Subtypes: 80-85% of malignant epithelial thyroid tumors in developed countries are papillary; 3-12% medullary; 1-3% anaplastic


  • Median age at dx early 40s for papillary thyroid CA, late 40s for follicular; 60-70 y for anaplastic




















Risk Factors


Papillary


  • Radiation exposure to thyroid gland (esp younger age w/latency period at least 3-5 y, linear relationship to exposure dose, nuclear fallout events including Chernobyl)



  • Age



  • Female sex



  • FHx (4-10× ↑ risk in 1st degree family members of papillary/follicular CA pts)



  • 5% differentiated thyroid CA are a/w FAP, Gardner syn, Cowden syn, Carney complex



  • No clear causal a/w iodine ingestion


Follicular


Anaplastic


Medullary


  • FMTC syn including FMTC, MEN-2 (20-25%)



  • 75-80% sporadic/nonfamilial involving RET gene Mt



Biology



  • MAPK signaling pathway: Mt involving one of three genes, RET/PTC

    (rearrangement in 20% of adult sporadic papillary carcinomas), BRAF, or RAS in 70% of papillary carcinomas; rarely overlap in same tumor


  • PAX8-PPAR in 35% follicular carcinomas, some Hurthle cell


Clinical Presentation and Diagnosis



  • Commonly p/w incidental solitary thyroid nodules: Median tumor size 2-3 cm; 5-10% malignant; higher percentage if radiation exposure; majority hypofunctional; presence of microcalcifications, irregular margins, spotty intranodular flow, hypervascularity are suggestive of malignancy


  • U/S: For FNA, to assess number & characteristics of nodules


  • FNA: Accuracy of dx 70-97%; varies w/sample quality, cytopathologist skill; ˜70% benign, 4% malignant, 10% suspicious/indeterminate; 17% insufficient sample


  • Medullary: Familial often detected by screening w/stimulation tests/molecular analysis; sporadic by asx thyroid mass; secretory diarrhea if bulky disease w/high calcitonin


  • Anaplastic: Prior or concurrent dx of well-differentiated thyroid CA or benign nodular thyroid disease; rapidly ↑ palpable neck mass (median tumor size 8-9 cm); invasion into airways & recurrent laryngeal nerve leads to obstructive sx, hemoptysis, dysphagia, hoarseness; 20-50% have distant mets at dx in lung > bone, liver


  • Familial tumors tend to be more aggressive than nonfamilial


Natural History and Prognosis



  • Natural hx: 2/3 pts w/papillary carcinomas have disease limited to thyroid at dx


  • Prognosis: Papillary: 90-95% long-term survival; follicular: 70-80% long-term survival; distant mets strong negative prognostic indicator; prognosis ⇔ stage; anaplastic: Median survival 4-5 mos from dx


  • Poor prognostic factors for well-differentiated thyroid CA: Age >45 y, male sex, poorly differentiated histology, tumor size, extrathyroid extension at dx; nodal involvement does not confer ↓ survival in younger pts


  • Mayo Clinic Model: AGES (age, tumor grade, tumor extent, tumor size)



  • BRAF Mt: May be a/w ↑ likelihood of extrathyroidal extension, node met, recurrence; point Mt in 45% of thyroid papillary carcinomas (Cancer 2012;118:1764)


Staging



  • Papillary/follicular, under age 45: Stage I: M0; Stage II: M1


  • Papillary/follicular, 45+: Stage I: T1 (<2 cm confined to thyroid); Stage II: T2 (>2 but <4 cm confined to thyroid); Stage III: T3 & early nodal involvement; Stage IV: All else including M1


  • Medullary: Stage I: T1, node negative; Stage II: T2-T3, node negative; Stage III: T1-T3, early nodal involvement (N1a); Stage IV: All T4, N1b, M1 disease


  • Anaplastic: Stage IV


Pathology



  • Cell Derivation: Papillary, follicular, Hurthle cell, anaplastic arise from follicular cells that produce thyroid hormones; Tumors usu PAX8 & TTF1 positive

























Pathology


Papillary

Papillae; follicular variant has no papillary areas; enlarged, ovoid nuclei that frequently overlap; propensity to invade lymphatic spaces so high incidence of regional node involvement; microcarcinoma <1 cm


Follicular

True follicular carcinoma rare (5-10% of nonendemic goiter area thyroid malignancies); unifocal, thickly encapsulated, invasion of capsule/vessels frequent


Intermediately differentiated tumors

10-15% tumors w/in category of papillary & follicular subtypes including tall cell, columnar cell & diffuse sclerosing variants, insular carcinoma types of papillary; Hurthle cell (oncocytic, oxyphilic) carcinomas as type of follicular; more aggressive biology


Medullary

Arises from calcitonin-producing parafollicular C cells, w/c are embryologically from neural crest


Anaplastic

“Giant cell” variant; possibly a/w dedifferentiation of previously well-differentiated tumor; rapidly growing, invasive




Treatment



  • Surgery: Mainstay of tx for all subtypes, but rarely possible w/anaplastic; complications of total thyroidectomy include recurrent laryngeal nerve injury & hypocalcemia 2/2 hypoparathyroidism


  • Differentiated thyroid CA: Levothyroxine suppression of TSH as it is a potential growth factor for microscopic CA deposits, RAI administration to ablate any nl thyroid remnant


  • Met disease: RAI, external-beam radiotherapy, & chemotherapy (doxorubicin + platinum) for met disease; TKIs (eg, sorafenib) have activity in iodinerefractory disease (J Clin Oncol 2008;26:4714) & are the preferred tx by guidelines


  • MTC: Total thyroidectomy w/b/l central compartment node dissection & at least unilateral neck dissection; radiation & chemotherapy not considered effective; targeted therapies vandetanib (J Clin Oncol 2012;30:134) & cabozantinib (J Clin Oncol 2011;29:2660) approved for tx of met disease; treat local recurrences surgically; screen for germline RET gene Mt as total thyroidectomy is preventive in young, at-risk family members


  • Anaplastic thyroid CA: May require urgent tracheostomy; if unresectable at dx, radiation-based Rx, often w/chemotherapy for sensitization; RAI not useful


  • Tumor markers for surveillance: Thyroglobulin (highly sensitive & specific in the absence of all nl thyroid tissue) for differentiated CA; surveillance w/CEA & calcitonin for MTC



SELLAR TUMORS

Jane L. Meisel

Monica Girotra

Kevin C. De Braganca

Thomas J. Kaley


Sellar Masses



  • Presentation



    • Neuro sx: HA (expansion of sella), diplopia (oculomotor nerve compression), pituitary apoplexy (sudden hemorrhage into the mass), CSF rhinorrhea (inferior extension of mass), visual field deficits


    • Hormonal abnormalities (hyper- or hyposecretion; see below)


    • Incidental finding on MRI done for other reason (“incidentaloma”)


  • Causes



    • Pituitary adenomas = most common cause; ˜85% of sellar masses


    • Also: Physiologic pituitary enlargement (pregnancy, 1° hypothyroidism, 1° hypogonadism); cyst, abscess or AV fistula of cavernous sinus; hypophysitis (lymphocytic = most common kind, seen in postpartum ♀ or in anti-CTLA-4 tx of malignancies); benign tumors (craniopharyngioma, meningioma); 1° malignant tumors (germ cell, chordoma, 1° CNS lymphoma, sarcoma, pituitary carcinoma-rare); met disease (breast/lung 1° most common)



      • In a large registry of pituitary tumors (N = 4122), 84.6% were adenomas, 3.2% were craniopharyngioma, 1.8% were Rathke cysts, 1.8% were Crooke cells (w/o adenoma), ˜1% were meningiomas, 0.6% were mets, & 0.5% were chordomas. Sellar tumors of all other types each occurred no more often <0.5% of the time (CNS lymphoma 0.02%, GCT 0.15% as described below) (Eur J Endocrinol 2007;156(2):203)


  • Evaluation



    • Sellar MRI to better characterize the lesion


    • Evaluation of hypothalamic-pituitary hormonal function


Pituitary Adenoma



  • Classification: By size & cell of origin



    • Size: <1 cm = microadenoma; >1 cm = macroadenoma


    • Cell type: Arise from any type of cell of the anterior pituitary; can lead to ↑ secretion of hormone(s) produced by that cell and/or ↓ secretion of other hormones due to compression of other cell types



      • Gonadotroph: Usu clinically nonfunctional


      • Corticotroph: Usu causes Cushing


      • Lactotroph: ↑ PRL → hypogonadism (♂/♀)


      • Thyrotroph: Can be clinically nonfunctional (secreting only α or TSH-β subunits, or can cause hyperthyroidism from ↑ secretion of intact TSH)


      • Somatotroph: ↑ GH → acromegaly


      • Lactotroph/somatotroph combinations also occur, leading to sx of both


  • Evaluation



    • MRI: Best imaging procedure to evaluate sellar masses


    • Evaluation of hypothalamic-pituitary hormonal function:



      • Hormonal hypersecretion is caused only by pituitary adenomas & defines the sellar mass as such


      • Hormonal hyposecretion can be caused by any hypothalamic or pituitary lesion; does not help narrow the ddx (unless DI is found, as this indicates a lesion/↓ ADH release from hypothalamus or stalk)


  • Tx

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Aug 17, 2016 | Posted by in ONCOLOGY | Comments Off on Endocrine Malignancies

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