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Question 1

This thyroid tumor is named after which of the following salivary gland tumors?

  1. Lymphadenoma
  2. Oncocytic carcinoma
  3. Oncocytoma
  4. Sialadenoma papilliferum
  5. Warthin tumor
Answer 1
E. Warthin tumor. Warthin-like variant of papillary thyroid carcinoma is characterized on histomorphology by papillae lined by oncocytic cells and a dense lymphoplasmacytic infiltrate within the papillary cores, closely mimicking Warthin tumor of salivary gland. The latter shows oncocytic columnar cells with underlying basal cells, resting on a dense lymphoid stroma.

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Reference: Warthin-like variant
Question 2
Which of the following is typically associated with Warthin-like variant of papillary thyroid carcinoma?

  1. Favorable clinical outcome
  2. Frequent dedifferentiation
  3. Mitochondrial DNA mutations
  4. Multiple (soap bubble-like) intranuclear inclusions
  5. Tumor cells have height 2 to 3 times the width
Answer 2
A. Favorable clinical outcome. Warthin-like variant of papillary thyroid carcinoma (PTC) has a favorable clinical outcome and dedifferentiation is unusual. It harbours BRAFV600E mutation in 65 - 75% cases. Mitochondrial DNA mutations are characteristic of oncocytic variant of PTC. Tumor cells having height 2 to 3 times the width is a diagnostic feature of tall cell variant of PTC. Multiple soap bubble-like intranuclear inclusions are typically described in tall cell variant of PTC but can be seen in other variants like hobnail variant also.

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Reference: Warthin-like variant
Question 3

    What is the most likely histological diagnosis of this thyroid aspirate consistent with suspicious for malignancy diagnostic category?

  1. Classic papillary thyroid carcinoma
  2. Follicular adenoma
  3. Follicular variant of papillary thyroid carcinoma
  4. Medullary thyroid carcinoma
  5. Poorly differentiated carcinoma
Answer 3
C. Follicular variant of papillary thyroid carcinoma follicular cells appear as microfollicular pattern. A few follicular cells showing nuclear enlargement, pale and powdery chromatin and nuclear grooves are present.

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Reference: Suspicious for malignancy
Question 4
    What is the most common histological equivalent of suspicious for malignancy aspirate of thyroid?

  1. Anaplastic thyroid carcinoma
  2. Follicular carcinoma
  3. Medullary thyroid carcinoma
  4. Papillary thyroid carcinoma
  5. Poorly differentiated thyroid carcinoma
Answer 4
D. Papillary thyroid carcinoma. More than 85% of suspicious for malignancy cases are papillary thyroid carcinoma.

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Reference: Suspicious for malignancy
Question 5
Which statement is false regarding metastatic clear cell renal cell carcinoma to the thyroid?

  1. Metastasis from renal cell carcinoma is generally a solitary mass
  2. Metastatic clear cell renal cell carcinoma can have a very long latency after nephrectomy
  3. Metastatic clear cell renal cell carcinoma can have a spurious thyroglobulin stain
  4. TTF1 and PAX8 can be used to differentiate tumors of renal and thyroid origins
  5. Metastatic tumor to the thyroid gland is the initial manifestation of renal cell carcinoma in 33% of cases
Answer 5
D. TTF1 and PAX8 can be used to differentiate renal and thyroid origins. Tumors from both thyroid and kidney can be positive for PAX8.

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Reference: Secondary tumors / metastases
Question 6
Which of the following statements is true?

  1. Metastases to the thyroid are a common finding
  2. Most patients with thyroid metastases have no known primary
  3. Melanoma is a common primary that metastasizes to the thyroid
  4. PAX8 may be positive in both thyroid and renal tumors
Answer 6
D. PAX8 may be positive in both thyroid and kidney tumors.

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Reference: Secondary tumors / metastases
Question 7
Which item is correct regarding sclerosing mucoepidermoid carcinoma with eosinophilia?

  1. Sclerosing mucoepidermoid carcinoma with eosinophilia is not associated with Hashimoto thyroiditis
  2. Lymph nodes metastases, extracapsular spread, vascular invasion and perineural invasion are common
  3. Death due to sclerosing mucoepidermoid carcinoma with eosinophilia is common
  4. Eosinophil infiltration is common, and no keratin pearls and keratin debris are seen
  5. The squamous component is highly malignant
Answer 7
B. Lymph nodes metastases, extracapsular spread, vascular invasion and perineural invasion are common. Death due to disease is uncommon, although lymph nodes metastases, extracapsular spread, vascular invasion and perineural invasion are common.

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Reference: Sclerosing mucoepidermoid carcinoma with eosinophilia
Question 8

    What is the most common molecular alteration of this thyroid tumor?

  1. BRAFV600E mutation
  2. EGFR mutation
  3. HRAS mutation
  4. TERT promoter mutation
  5. TP53 mutation
Answer 8
A. BRAFV600E mutation

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Reference: Papillary thyroid carcinoma
Question 9
    Which of the following variants of papillary thyroid carcinoma is considered as an aggressive variant?

  1. Follicular variant
  2. Oncocytic variant
  3. Papillary microcarcinoma
  4. Tall cell variant
  5. Warthin-like variant
Answer 9
D. Tall cell variant. Tall cell variant is one of the aggressive variants that is considered as intermediate risk by the American Thyroid Association Management Guidelines.

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Reference: Papillary thyroid carcinoma
Question 10

A thyroid tumor is resected, as shown above. What is the most common molecular alteration of this tumor?

  1. BRAF V600E mutation
  2. HRAS Q61R mutation
  3. NRAS Q61R mutation
  4. RET-PTC rearrangement
Answer 10
A. BRAF V600E mutation. This is papillary thyroid carcinoma, classic type.

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Reference: Classic papillary thyroid carcinoma
Question 11
Which of the following histologic findings is a feature of classic type of papillary thyroid carcinoma?

  1. Composed entirely of follicles
  2. Nuclei of the lesional cells are small and round without nuclear membrane irregularity
  3. Contains well formed papillae with a fibrovascular core
  4. Lesional cells have a cell height at least 2 - 3 times of the cell width
Answer 11
C. Contains well formed papillae with a fibrovascular core

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Reference: Classic papillary thyroid carcinoma
Question 12

Which of the following statements concerning the tall cell variant of papillary thyroid carcinoma is correct?

  1. It usually has an indolent clinical course
  2. Most cases are associated with a RAS mutation
  3. Patients are usually older adults
  4. The tumor is positive for TTF1, synaptophysin and calcitonin
  5. Tumor cells are stratified and only focal areas show characteristic papillary thyroid carcinoma nuclear features
Answer 12
C. Patients are usually older adults

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Reference: Papillary carcinoma, tall cell variant
Question 13

Which of the following diagnostic features are associated with the tall cell variant of papillary thyroid carcinoma?

  1. A dense lymphocytic infiltration of tumor stroma
  2. Cells with granular eosinophilic cytoplasm and nuclei with a soap bubble appearance on cytology
  3. Focal positivity for GATA3
  4. Infrequent nuclear grooves and pseudoinclusions
  5. High nucleus to cytoplasm ratio
Answer 13
B. Cells with granular eosinophilic cytoplasm and nuclei with a soap bubble appearance on cytology

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Reference: Papillary carcinoma, tall cell variant
Question 14
What is the most common molecular alteration seen in follicular variant of papillary thyroid carcinoma?

  1. BRAF V600E mutation
  2. RAS mutation
  3. RET / PTC fusion
  4. TP53 mutation
Answer 14
B. RAS mutation

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Reference: Follicular variant
Question 15

A 45 year old woman underwent thyroid lobectomy for a 2.2 cm thyroid mass. The histology of the tumor is shown above. What is the diagnosis of this tumor?

  1. Adenomatoid nodule
  2. Follicular adenoma
  3. Follicular carcinoma
  4. Papillary thyroid carcinoma, follicular variant
Answer 15
D. Papillary thyroid carcinoma, follicular variant

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Reference: Follicular variant
Question 16

    Which of the following is a typical finding on ultrastructural examination of this thyroid tumor?

  1. Abnormal mitochondria
  2. Filament-ribosomal complexes
  3. Membrane bound crystals
  4. Neurosecretory granules
  5. Paranuclear whorls of intermediate filaments
Answer 16
A. Abnormal mitochondria. This is oncocytic variant of papillary thyroid carcinoma. The cells of have abundant abnormal mitochondria, displaying stacks of parallel cristae, filamentous bundles and woolly densities.

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Reference: Oncocytic
Question 17
    Oncocytic variant of papillary thyroid carcinoma is typically associated with which of the following molecular alterations?

  1. BRAFV600E mutation
  2. Mitochondrial DNA mutations
  3. PAX8/PPARγ translocation
  4. RAS mutations
  5. TERT promoter mutations
Answer 17
B. Mitochondrial DNA mutations. Oncocytic papillary thyroid carcinomas show accumulation of mitochondrial DNA mutations. BRAFV600E mutation can be found in oncocytic papillary thyroid carcinoma but is much more prevalent in tall cell variant of papillary thyroid carcinoma. PAX8/ PPARγ translocation and RAS mutations are usually associated with follicular variant of papillary thyroid carcinoma. TERT promoter mutations have been reported to occur with increasing frequency in cases with de-differentiation.

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Reference: Oncocytic
Question 18
Which thyroid FNA cytologic appearance is classified as nondiagnostic / unsatisfactory?

  1. ≥ 6 groups of well visualized follicular cells
  2. Abundant thick colloid
  3. A few cells with cytological atypia
  4. Foamy histiocytes only
  5. Numerous inflammatory cells
Answer 18
D. Foamy histiocytes only. When the aspirated material contains only foamy histiocytes and no follicular epithelium or colloid, it is qualified as nondiagnostic / unsatisfactory. However, in some local reporting systems (e.g. Japanese), these cases are reported as "adequate, cyst fluid only" because their malignancy risk is almost the same as the benign category and lower than the nondiagnostic / unsatisfactory category.

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Reference: Nondiagnostic / unsatisfactory
Question 19

Which of the histological features is seen in nodular goiter?

  1. Nodules with distinct thick capsule
  2. Papillary projections of the epithelium with nuclear features of papillary thyroid carcinoma
  3. Variably sized follicles with flattened hyperplastic epithelium, cysts, hemorrhage, granulomatous response, fibrosis, calcification or osseous metaplasia
  4. Vascular invasion
Answer 19
C. Variably sized follicles with flattened hyperplastic epithelium, cysts, hemorrhage, granulomatous response, fibrosis, calcification or osseous metaplasia. Nodules may or may not be present in nodular goiter but generally lack a thick capsule. Prominent features are variably sized dilated follicles with flattened hyperplastic epithelium. Secondary changes include foci of fresh or old hemorrhage, rupture of follicles with granulomatous response, fibrosis, calcification and even osseous metaplasia. Some of the cystically dilated follicles may show papillary projections (Sanderson polsters). Cytologic atypia in the form of highly atypical nuclei occurs in patients exposed to radioactive substances.

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Reference: Multinodular goiter
Question 20
Multinodular goiter Multinodular goiter


These images from a thyroid nodule belong in what category of The Bethesda System for Reporting Thyroid Cytopathology?

  1. Category I
  2. Category II
  3. Category III
  4. Category IV
  5. Category V
Answer 20
B. Category II (benign). These images represent a colloid nodule / benign thyroid nodule. They are typically managed by clinical and sonographic followup.

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Reference: Multinodular goiter
Question 21
Which statement is not true for mucoepidermoid carcinoma of thyroid?

  1. Comedo necrosis and psammoma bodies may be seen
  2. Foci of associated papillary thyroid carcinoma are often seen
  3. Lymph nodes metastases, extrathyroidal invasion are common
  4. Mucoepidermoid carcinoma of thyroid is associated with lymphocytic thyroiditis
  5. Similar to sclerosing mucoepidermoid carcinoma with eosinophilia, it cannot have t (11;19) - CRTC1 / MAML2 rearrangement
Answer 21
E. Similar to sclerosing mucoepidermoid carcinoma with eosinophilia, it cannot have t (11;19) - CRTC1 / MAML2 rearrangement. Mucoepidermoid carcinoma can have t (11;19) - CRTC1 / MAML2 rearrangement.

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Reference: Mucoepidermoid
Question 22

Which of the following statements about papillary thyroid microcarcinoma (shown in the image) is correct?

  1. Can always be diagnosed on cytology alone
  2. Can contain tall cell features
  3. More likely to show a pure papillary rather than follicular architecture
  4. Must be incidental and measure ≤ 1 cm
  5. Requires a total thyroidectomy
Answer 22
B. Can contain tall cell features. Papillary thyroid microcarcinoma may show features of other variants including tall cell. Tall cell features should be recognized and reported since they are associated with more aggressive behavior. The other answer choices are incorrect because the 2017 World Health Organization definition is based only on tumor size (irrespective of it being incidental or not), the final size is most often determined on a surgical resection specimen (though it may also be estimated by ultrasound), follicular architectural pattern is more common than pure papillary (classical) pattern and may be managed by a lobectomy or active surveillance.

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Reference: Papillary thyroid microcarcinoma (PTMC)
Question 23
Which of the following immunostains is usually not expressed in papillary thyroid microcarcinoma?

  1. BRAF V600E
  2. CK19
  3. Galectin3
  4. HBME
  5. p63
Answer 23
E. p63. Papillary thyroid microcarcinoma is usually negative for p63, in contrast to the mimicker solid cell nests which are usually positive for p63. HBME, galectin3 and CK19 are expressed in most and can be used to support the diagnosis. BRAF V600E immunostain is often expressed and can be used as a reliable surrogate marker for the corresponding BRAF V600E gene mutation, present in 30 - 67%.

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Reference: Papillary thyroid microcarcinoma (PTMC)
Question 24

    What is the most likely histological diagnosis of this thyroid aspirate?

  1. Anaplastic thyroid carcinoma
  2. Follicular carcinoma
  3. Medullary thyroid carcinoma
  4. Papillary thyroid carcinoma
  5. Poorly differentiated thyroid carcinoma
Answer 24
C. Medullary thyroid carcinoma. Numerous isolated spindle cells indicate medullary thyroid carcinoma.

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Reference: Malignant
Question 25
    Which thyroid malignancy is included in the malignant category of the Bethesda system for reporting thyroid cytopathology?

  1. Chronic thyroiditis
  2. Follicular carcinoma
  3. Hyalinizing trabecular tumor
  4. Nodular goiter
  5. Poorly differentiated thyroid carcinoma
Answer 25
E. Poorly differentiated thyroid carcinoma. Nodular goiter and chronic thyroiditis belong to the benign category, the follicular carcinoma belongs to follicular neoplasm / suspicious for a follicular neoplasm category and hyalinizing trabecular tumor belongs to the suspicious for malignancy category.

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Reference: Malignant
Question 26

What is a widely used IHC marker for Langerhans cell histiocytosis?

  1. CD1a
  2. CD20
  3. Cytokeratin
  4. Thyroglobulin
  5. TTF1
Answer 26
Question 27
What is the most common molecular alteration in Langerhans cell histiocytosis?

  1. BRAF V600E mutation
  2. EGFR mutation
  3. RAS family mutations
  4. TERT promoter mutation
  5. TP53 mutation
Answer 27
A. BRAF V600E mutation

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Reference: Langerhans cell histiocytosis
Question 28

    A 40 year old male presented with a mass in the left lower pole of the thyroid. The tumor is shown in the photomicrograph. The tumor is positive for p63, CD5 and CD117, and negative for thyroglobulin and TTF1. Which of the following is most likely the correct diagnosis?

  1. Squamous cell carcinoma
  2. Intrathyroid thymic carcinoma / carcinoma showing thymus-like differentiation (CASTLE)
  3. Medullary carcinoma
  4. Follicular carcinoma
  5. Papillary carcinoma
Answer 28
B. Intrathyroid thymic carcinoma / carcinoma showing thymus-like differentiation (CASTLE)

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Reference: ITC / CASTLE
Question 29
    Which of the following is true about intrathyroid thymic carcinoma / carcinoma showing thymus-like differentiation (CASTLE)?

  1. Most commonly located in upper pole of thyroid
  2. PAX8 can be used to distinguish from thyroid carcinoma
  3. Most patients have a poor prognosis and die from this tumor
  4. Nests of squamoid cells with lymphocytes infiltrate is the key microscopic feature
  5. CD5 in CASTLE only highlights the lymphocytes
Answer 29
D. Nests of squamoid cells with lymphocytes infiltrate is the key microscopic feature

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Reference: ITC / CASTLE
Question 30
Which statement is incorrect about hobnail PTC?

  1. Rare variant of papillary thyroid carcinoma
  2. Relatively aggressive clinical behavior
  3. Microscopically characterized by hobnail cells and micropapillary pattern
  4. Common BRAF V600E , TP53 and TERT promoter mutations
  5. High mortality
Answer 30
E. High mortality. Hobnail papillary thyroid carcinoma is an unusual and aggressive variant of PTC characterized by predominance of cells with a hobnail appearance often arranged in micropapillary pattern. Despite multiple mutations and frequent nodal (up 75%) and distant (up to 40%) metastases, mortality is relatively low - disease specific survival rates are 80+% and 70+% at 5 and 10 years after surgery.

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Reference: Hobnail
Question 31
What proportion of a hobnail micropapillary pattern in the tumor is required for a diagnosis of PTC hobnail variant?

  1. 5%
  2. 10%
  3. 25%
  4. 30%
  5. 50%
Answer 31
D. 30%. The presence of at least 30% of cells with hobnail micropapillary features is mandatory to diagnose a tumor as PTC hobnail variant. Nevertheless, a minor hobnail micropapillary pattern (5 - 30%) has prognostic significance and should be noted in the pathology report.

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Reference: Hobnail
Question 32
What category of the Bethesda System of Reporting Thyroid Cytopathology corresponds best to FNA smears of hobnail PTC with comet-like cells?

  1. I (non-diagnostic)
  2. III (AUS/FLUS)
  3. IV (FN/SFN)
  4. V (suspicious for malignancy)
  5. VI (malignant)
Answer 32
E. VI (malignant). Cases with diagnostic hobnail cells are easily placed into the Bethesda VI category.

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Reference: Hobnail
Question 33
Which finding is not helpful in distinguishing medullary carcinoma from a Hürthle cell neoplasm?

  1. Salt and pepper chromatin
  2. Metachromasia in Romanowsky stain
  3. Calcitonin measurement using needle washout fluid
  4. PTH value measurement using needle washout fluid
  5. Calcitonin immunostaining
Answer 33
D. PTH value measurement using needle washout fluid; PTH value measurement is useful for parathyroid lesions

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Reference: Hürthle cell neoplasm
Question 34

What is the most likely diagnosis of this thyroid aspirate?

  1. Chronic thyroiditis
  2. Adenomatous nodule
  3. Hürthle cell neoplasm
  4. Medullary carcinoma
  5. Parathyroid adenoma
Answer 34
D. Medullary carcinoma; salt and pepper chromatin indicates medullary carcinoma

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Reference: Hürthle cell neoplasm
Question 35
Which lesion is not included in follicular neoplasm / suspicious for a follicular neoplasm category?

  1. Conventional papillary carcinoma
  2. Follicular carcinoma
  3. Invasive follicular variant of papillary carcinoma
  4. Nodular goiter
  5. Noninvasive follicular thyroid neoplasm with papillary-like nuclear features
Answer 35
A. Conventional papillary carcinoma. Lesions included in this category are follicular patterned lesions. Conventional papillary carcinoma is a papillary lesion with remarkable nuclear morphology.

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Reference: Follicular neoplasm
Question 36

Which histological diagnosis is most likely to correspond with this cytologic aspirate?

  1. Conventional papillary carcinoma
  2. Follicular adenoma or follicular carcinoma
  3. Invasive follicular variant of papillary carcinoma or noninvasive follicular thyroid neoplasm with papillary-like nuclear features
  4. Nodular goiter
  5. Parathyroid adenoma
Answer 36
C. Invasive follicular variant of papillary carcinoma or noninvasive follicular thyroid neoplasm with papillary-like nuclear features. Although the architectural features suggest a follicular neoplasm, the nuclei show grooves and powdery chromatin indicating papillary carcinoma

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Reference: Follicular neoplasm
Question 37
    Which histopathologic feature is not mandatory to report according to the CAP thyroid protocol?

  1. Extranodal extension
  2. Histologic type
  3. Lymphatic invasion
  4. Perineural invasion
  5. Tumor focality
Answer 37
D. Perineural invasion is an optional feature to report, because its clinical significance is not well defined.

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Reference: Features to report
Question 38
Which statement regarding endemic goiter is false?

  1. Increases risk for follicular neoplasm
  2. Increases risk for papillary neoplasm
  3. May cause tracheal compression
  4. Most common cause is dietary deficiency of iodine
Answer 38
B. Endemic goiter increases the risk of follicular neoplasm and anaplastic carcinoma. On the contrary, papillary neoplasms occur more in iodine sufficient areas.

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Reference: Endemic goiter
Question 39
Which of the following are the main genes involved in regulation of thyroid development?

  1. BRAF, TP53, TERT
  2. HRas, NRAS, KRAS
  3. NKX2-1, FOXE1, PAX8, HHEX
  4. PAX6, ASPM, KATNB1, TUBB5
  5. RET, PPARg, NTRK
Answer 39
C. NKX2-1, FOXE1, PAX8, HHEX

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Reference: Embryology
Question 40
Thyroid gland is derived from which of the following embryonal structures?

  1. 1 lateral and 2 medial anlagen
  2. 1 medial, 1 lateral and 2 intermediate anlagen
  3. 1 medial and 1 lateral anlagen
  4. 1 medial and 2 lateral anlagen
  5. 2 lateral anlagen only
Answer 40
D. 1 medial and 2 lateral anlagen

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Reference: Embryology
Question 41
Dyshormonogenetic goiter is characterized by all of the following except:

  1. Decreased T3, T4 and increased TSH
  2. Family history of hypothyroidism or goiter in 20% cases
  3. Highly atypical pleomorphic and hyperchromatic nuclei in internodular areas
  4. Increased T3, T4 and decreased TSH
  5. Markedly cellular nodules showing a variety of architectural patterns with minimal to absent pale colloid
Answer 41
D. Increased T3, T4 and decreased TSH. Dyshormonogenetic goiter is characterized by thyroid enlargement due to various hereditary defects in thyroid hormone synthesis. It is the second most common cause of congenital hypothyroidism after thyroid agenesis / dysgenesis. Family history of hypothyroidism or goiter is present in 20% of cases. Lack of circulating thyroid hormone activates TSH secretion, which causes overstimulation and hyperplasia of defective thyroid gland. There is diffuse asymmetric enlargement of thyroid gland with multinodular cut surface with absent to minimal pale colloid. Nodular and internodular thyroid parenchyma is markedly hypercellular. Nodular follicular cells are without atypia whereas internodular areas show fibrosis with single highly pleomorphic and hyperchromatic nuclei.

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Reference: Dyshormonogenetic goiter
Question 42
Which microscopic feature of dyshormonogenetic goiter mimics thyroid malignancy?

  1. Capsular invasion of the nodules
  2. Highly atypical pleomorphic and hyperchromatic (bizarre) nuclei
  3. Large areas of necrosis
  4. Orphan Annie nuclei
  5. Scattered psammoma bodies
Answer 42
B. Highly atypical pleomorphic and hyperchromatic (bizarre) nuclei. Dyshormonogenetic goiter is a benign thyroid hyperplasia due to hereditary defects in thyroid hormone synthesis. It lacks malignant features common for papillary (Orphan Annie nuclei, psammoma bodies), follicular (capsular invasion) or high grade (necrosis) thyroid cancer. However, internodular tissue in dyshormonogenetic goiter often displays marked nuclear atypia with bizarre nuclei (enlarged, irregularly shaped, pleomorphic, hyperchromatic) similar to those found in radiation thyroiditis and anaplastic carcinoma.

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Reference: Dyshormonogenetic goiter
Question 43
How are calcium oxalate crystals useful in frozen sections from thyroid and parathyroid?

  1. Differentiate cancer from benign tissue
  2. Distinguishing thyroid from parathyroid tissue
  3. Helps to locate psammoma bodies
  4. Identify age of patient
  5. No practical utility
Answer 43
B. Distinguishing thyroid from parathyroid tissue. Calcium oxalate crystals are useful in differentiating thyroid tissue (scattered to abundant crystals) from parathyroid tissue (no crystals) at frozen section.

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Reference: Crystals
Question 44

Which of the following is the most likely immunohistochemical profile of this thyroid tumor?

  1. TTF1+, PAX8+, CDX2+
  2. TTF1+, PAX8+, CDX2-
  3. TTF1+, PAX8-, CDX2+
  4. TTF1-, PAX8+, CDX2-
  5. TTF1-, PAX8-, CDX2-
Answer 44
A. TTF1+, PAX8+, CDX2+. Cells of columnar cell variant of papillary thyroid carcinoma are positive for thyroid specific markers (TTF1 / PAX8), as well as the intestinal epithelial marker CDX2.

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Reference: Columnar cell variant
Question 45
Which of the following is true about columnar cell variant of papillary thyroid carcinoma?

  1. An indolent clinical course
  2. Abundant oncocytic cytoplasm
  3. Multiple intranuclear pseudoinclusions
  4. One of the most common variants of papillary thyroid carcinoma
  5. Morphology mimics metastatic adenocarcinoma
Answer 45
E. Morphology mimics metastatic adenocarcinoma. Columnar cell variant is rare and an aggressive papillary thyroid carcinoma type, characterized by scant clear or eosinophilic cytoplasm and lack of well developed nuclear features of papillary thyroid carcinoma. Due to absence of typical nuclear features of papillary thyroid carcinoma, metastatic adenocarcinoma needs to be ruled out.

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Reference: Columnar cell variant
Question 46
What risk of malignancy is associated with benign thyroid cytology?

  1. 0 - 3%
  2. 5 - 10%
  3. 12 - 15%
  4. 20 - 30%
  5. 40 - 50%
Answer 46
A. 0 - 3% Most published studies reported that a benign FNA diagnosis is associated with a very low false negative rate, estimated to be in the range of 0 - 3%. It should be noted that the precise risk of malignancy for cytologically benign nodules is difficult to assess because only a minority of these patients undergo surgery.

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Reference: Benign
Question 47
    Which case belongs to architectural atypia?

  1. A sparsely cellular aspirate comprised of Hürthle cells with minimal colloid
  2. Atypical lymphoid cells
  3. Focally prominent microfollicles with minimal nuclear atypia
  4. Most of the aspirate appears benign but rare cells have irregular nuclear contours
  5. Psammomatous calcifications in the absence of nuclear features of PTC
Answer 47
C. Focally prominent microfollicles with minimal nuclear atypia. Microfollicles are architectural atypia suggesting follicular neoplasm.

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Reference: Atypia of undetermined significance / follicular lesion of undetermined significance
Question 48

    A 70 year old man underwent FNA for the nodule of the thyroid right lobe. A cytological image of the lesion is shown. Which marker would most likely show positive staining?

  1. PAX8
  2. Calcitonin
  3. GATA3
  4. Thyroglobulin
  5. TTF1
Answer 48
C. GATA3. This is intrathyroidal parathyroid adenoma.

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Reference: Atypia of undetermined significance / follicular lesion of undetermined significance
Question 49
Which statement about amyloid goiter of the thyroid is false?

  1. Can be seen in renal transplant patients on dialysis
  2. Commonly seen in males
  3. Is associated with medullary thyroid carcinoma
  4. Microscopically shows diffuse deposition of amyloid
  5. Rarely presents with dysphagia, dysphonia or dyspnea
Answer 49
C. Is associated with medullary thyroid carcinoma. Amyloid goiter is not associated with medullary thyroid carcinoma. It is defined as amyloid deposits in thyroid associated with a goiter, but not with a malignant neoplasm.

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Reference: Amyloid goiter
Question 50
Which cytologic appearance of thyroid FNA specimen is classified as adequate?

  1. 3 groups with 10 follicular cells
  2. Abundant thick colloid only
  3. Air dried specimen without any atypical cells
  4. Foamy histiocytes only
  5. Respiratory epithelium only
Answer 50
B. Abundant thick colloid

When the aspirated material contains only abundant thick colloid and no follicular epithelium, it is qualified as adequate. Colloid may have variable appearance. It is important to recognize a substance as a colloid, not blood. 3 groups with 10 benign follicular cells are not sufficient to be qualified as diagnostic per the current criteria.

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Reference: Adequacy
Question 51
The following statements about adenolipoma of the thyroid gland are correct, except

  1. Clinical presentation of adenolipoma is usually a slow growing neck mass
  2. Imaging studies of cold thyroid nodule are usually nonspecific with extensive differential diagnosis
  3. Large adenolipoma can cause airway obstruction
  4. Recurrence of adenolipoma after surgical resection is common
Answer 51
D. "Recurrence of adenolipoma after surgical resection is common" is incorrect. Surgical resection of thyroid adenolipoma is curative with no recurrence or malignant potential.

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Reference: Adenolipoma
Question 52

Which of the following statements is true about the diffuse sclerosing variant of papillary thyroid carcinoma (PTC)?

  1. Extrathyroidal extension and lymph node metastasis are usually not detected
  2. Not considered an aggressive type of papillary thyroid carcinoma
  3. Patients are usually older than those with classical papillary thyroid carcinoma
  4. Presents as a solitary thyroid nodule in which calcifications are infrequent
  5. Shows a high 10 year disease specific survival
Answer 52
E. Shows a high 10 year disease specific survival. Despite being an aggressive variant of PTC with some adverse prognostic features, mortality rates are similar to those of classical PTC with 93% disease specific survival at 10 years.

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Reference: Papillary thyroid carcinoma, diffuse sclerosing variant
Question 53

What is the most common molecular alteration found in the diffuse sclerosing variant of papillary thyroid carcinoma?

  1. ALK translocation
  2. BRAF V600E mutation
  3. ETV6 / NTRK rearrangement
  4. RAS mutation
  5. RET / PTC rearrangement
Answer 53
E. RET / PTC rearrangement. RET / PTC rearrangements are common (~ 60%), including RET / PTC1 (28 - 46%) and RET / PTC3 (14 - 16%). Overall, BRAF V600E is uncommon (0 - 24%), except in Korea (50 - 61%). ALK translocation is also uncommon (13%). RAS mutation and ETV6 / NTRK rearrangement have not been reported in diffuse sclerosing variant of papillary thyroid carcinoma.

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Reference: Papillary thyroid carcinoma, diffuse sclerosing variant
Question 54

How is the variant of papillary thyroid carcinoma shown in the image distinct from other variants?

  1. BRAF V600E mutation in epithelial component
  2. EWSR1 fusions
  3. CTNNB1 (beta catenin) mutation in mesenchymal component
  4. HRAS mutation in epithelial component
  5. CTNNB1 (beta catenin) mutation in epithelial component
Answer 54
C. CTNNB1 (beta catenin) mutation in mesenchymal component

CTNNB1 (beta catenin) mutations have been documented in the mesenchymal component of papillary thyroid carcinoma (PTC) with fibromatosis / fasciitis-like stroma. The PTC (epithelial) component of this tumor lacks CTNNB1 mutation; it instead usually harbors BRAF V600E mutation and less commonly HRAS mutation. BRAF and HRAS mutations are, however, not specific for PTC with fibromatosis / fasciitis-like stroma. CTNNB1 mutations are seen in cancer cells of cribriform-morular variant of PTC. EWSR1 gene fusions are a hallmark of Ewing sarcoma.

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Reference: Fibromatosis / fasciitis-like
Question 55
Which of the following is true about papillary thyroid carcinoma with fibromatosis / fasciitis-like stroma?

  1. Aggressive clinical course
  2. Fibromatosis may recur postthyroidectomy
  3. Only the epithelial component can metastasize
  4. Membranous expression of beta catenin in both epithelial and mesenchymal elements
  5. Stroma always mimics desmoid type fibromatosis
Answer 55
B. Fibromatosis may recur postthyroidectomy

Clinical course of papillary thyroid carcinoma (PTC) with fibromatosis / fasciitis-like stroma is usually similar to classical PTC. The tumor is characterized by a prominent myofibroblastic proliferation reminiscent of fibromatosis or nodular fasciitis, hence the name. Stromal component of tumors with fibromatosis-like stroma commonly harbors CTNNB1 (beta catenin) mutation, which on immunohistochemistry is depicted by nuclear positivity and loss of membranous staining. The PTC component retains normal membranous beta catenin immunoreactivity. The tumor is also unique in that the patients can develop recurrence of fibromatosis postthyroidectomy. Metastases can show both mesenchymal and epithelial components similar to the primary tumor.

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Reference: Fibromatosis / fasciitis-like
Question 56
A patient presented with a parathyroid carcinoma directly invading thyroid and adjacent fibroadipose tissue. What is the pT category?

  1. pTis
  2. pT1
  3. pT2
  4. pT3
  5. pT4
Answer 56
Question 57
A 72 year old man presented with a 4 cm advanced parathyroid carcinoma invading trachea and thyroid and showing cervical lymph nodes metastasis along with dissemination in the lungs. What is the clinical stage as per the AJCC / TNM 8th edition?

  1. Stage I
  2. Stage II
  3. Stage III
  4. Stage IV
  5. Not applicable
Answer 57
E. Not applicable; no AJCC / TNM staging system for parathyroid carcinoma is available so far, only standalone TNM categories

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Reference: Staging-parathyroid
Question 58

    Which of the following is diagnostic for parathyroid carcinoma in a parathyroid lesion?

  1. Tumor cells within the capsule
  2. Perineural invasion
  3. Increased mitotic activity (> 5/50 HPF)
  4. Broad fibrous bands
  5. Parafibromin loss
Answer 58
B. Perineural invasion of tumor cells is diagnostic of malignancy for parathyroid lesion

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Reference: Parathyroid carcinoma
Question 59
    Which of the following markers has diagnostic and prognostic role for parathyroid carcinoma?

  1. Isocitrate dehydrogenase 1 (IDH1)
  2. Menin
  3. Parafibromin
  4. SMARCB1/INI1
  5. Succinate dehydrogenase B (SDHB)
Answer 59
C. Parafibromin

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Reference: Parathyroid carcinoma
Question 60

What is the best diagnosis for this neck mass?

  1. Parathyroid adenoma, oxyphil type
  2. Oncocytoma
  3. Hurthle cell adenoma
  4. Granular cell tumor
Answer 60
A. Parathyroid adenoma, oxyphil type

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Reference: Parathyroid adenoma
Question 61
Which of the following features is seen in parathyroid carcinoma but not adenoma?

  1. Adherence to adjacent thyroid
  2. Nuclear atypia
  3. Necrosis
  4. Perineural invasion
Answer 61
D. Perineural invasion

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Reference: Parathyroid adenoma
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