Endocrine Pathology Practice Questions

Q: Regarding anaplastic thyroid carcinoma, which of the following statements is true?

Associated with p53 mutation. ***Associated with p53 mutation*** - **Anaplastic thyroid carcinoma** is a highly aggressive cancer frequently characterized by **p53 tumor suppressor gene mutations**. - These mutations contribute to its rapid growth, dedifferentiation, and resistance to therapy. *Common in young* - **Anaplastic thyroid carcinoma (ATC)** is a rare and highly aggressive malignancy that primarily affects **older adults**, typically those over 60 years of age. - It is one of the least differentiated forms of thyroid cancer and has a poor prognosis. [1] *Surrounding neck tissue is usually free* - ATC is characterized by **rapid growth** and **aggressive local invasion**, often involving surrounding neck tissues such as the trachea, esophagus, and great vessels. [1] - This extensive local involvement contributes to symptoms like dysphagia, dyspnea, and hoarseness, and makes surgical resection difficult or impossible. *Radiotherapy cures* - **ATC is largely refractory to conventional therapies**, including surgery, radiotherapy, and chemotherapy, due to its aggressive biology and common presence of dedifferentiated cells. - While radiation therapy may be used for **palliative management** of local symptoms, it very rarely achieves a cure; the prognosis remains extremely poor, with median survival measured in months. [1] **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Endocrine System, pp. 1101-1102.

Q: Radiation exposure can lead to which type of thyroid carcinoma?

Papillary carcinoma. ***Papillary carcinoma*** - Papillary thyroid carcinoma is strongly associated with **radiation exposure**, particularly during childhood [1]. - It is the most prevalent type of thyroid cancer and typically has a **good prognosis** [1]. *Lymphoma* - Thyroid lymphoma is rare and generally not linked to **radiation exposure**; it often presents as a **rapidly enlarging goiter**. - It is more commonly associated with **autoimmune thyroiditis**, not primary radiation effects. *Follicular carcinoma* - Follicular carcinoma shows a correlation with **iodine deficiency** rather than radiation exposure [1]. - Its presentation is more subtle, compared to the classical association of **radiation with papillary carcinoma**. *Medullary carcinoma* - Medullary thyroid carcinoma is primarily linked to **familial syndromes** like MEN 2 and not radiation exposure. - It arises from **parafollicular C cells**, making it clinically distinct from radiation-related types. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Endocrine System, pp. 1098-1099.

Q: A 65-year-old female patient presented with complaints of a swelling in the neck which moved with deglutition along with multiple episodes of diarrhea, hoarseness, mild dysphagia and mild shortness of breath. Lab findings revealed raised serum calcitonin levels and hypercalcemia. Which of the following histology corresponds with the above disease?

. *** *** - The clinical presentation of **neck swelling moving with deglutition**, combined with **raised serum calcitonin levels**, is highly suggestive of **medullary thyroid carcinoma (MTC)** [1][2], which is associated with these findings. - **Hypercalcemia** indicates possible bone involvement or parathyroid hormone-related mechanisms typically seen in MTC patients. *None of the above* - This option is invalid as it implies that no histological features correlate with the disease, which is incorrect given the identified tumor type. - The presence of **calcitonin** suggests a specific subtype of thyroid cancer [2], making this option unviable. * * - While the histology may appear related, it does not match the classic features of **medullary thyroid carcinoma**, which shows a distinct pattern of **calcitonin-producing C-cells** [2]. - Medullary thyroid carcinoma typically demonstrates **solid nests and trabecular patterns**, not represented by this option. * * - This option lacks the characteristic histological features associated with **medullary thyroid carcinoma**, such as **dense nests of neoplastic cells**. - The histology of MTC is unique, with **amyloid deposits** and positivity for **calcitonin**, which this image does not portray. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Endocrine System, pp. 1102-1103. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Liver And Biliary System Disease, pp. 428-429.

Q: A well-differentiated follicular carcinoma of the thyroid can be best differentiated from a follicular adenoma by:

Vascular invasion. ***Vascular invasion*** - The definitive distinction between a **follicular adenoma** (benign) and a **follicular carcinoma** (malignant) is the presence of **capsular or vascular invasion** [1]. - **Vascular invasion**, specifically, indicates that tumor cells have entered blood vessels, signifying metastatic potential and malignancy [1]. *Hürthle cell change* - **Hürthle cells** (oncocytes) are characterized by abundant granular eosinophilic cytoplasm due to numerous mitochondria. - While they can be seen in both benign conditions (e.g., adenomas, Hashimoto's thyroiditis) and malignant conditions (**Hürthle cell carcinoma**, a variant of follicular carcinoma), their presence alone does not differentiate between adenoma and carcinoma. *Lining of tall columnar and cuboidal cells* - The appearance of **tall columnar and cuboidal cells** is a general histological feature seen in various thyroid conditions and is not specific for differentiating follicular adenoma from carcinoma. - While these cell types can form follicular structures, their morphology alone does not indicate malignancy or benignity without evidence of invasion [1]. *Nuclear features* - Nuclear features like **grooves**, **inclusions**, and **"orphan Annie eye" nuclei** are characteristic of **papillary thyroid carcinoma**, not typically follicular carcinoma. - Follicular carcinomas generally have bland nuclear features similar to normal follicular cells, making nuclear changes unreliable for differentiating them from follicular adenomas [1]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Endocrine System, pp. 1100-1101.

Q: What is the key histological feature that differentiates follicular carcinoma from follicular adenoma of the thyroid?

Capsular invasion. ***Capsular invasion*** - **Capsular invasion** is the **classic and most commonly cited** histological criterion used to differentiate follicular carcinoma from follicular adenoma. - **Follicular adenomas** have an intact, well-defined capsule, while **follicular carcinomas** demonstrate tumor cells invading through or destroying the capsular boundary. - This is the **primary feature** taught in medical education and is easier to identify than vascular invasion. *Nuclear atypia* - **Nuclear atypia** is characteristic of **papillary thyroid carcinoma** (nuclear grooves, pseudoinclusions, ground-glass nuclei) rather than follicular lesions. - Nuclear features are **not reliable** for distinguishing follicular adenoma from carcinoma, as both can show similar nuclear morphology. - Atypia alone is insufficient to diagnose malignancy in follicular neoplasms. *Vascular invasion* - **Vascular invasion** (tumor cells within blood vessel lumens) is also a **valid diagnostic criterion** for follicular carcinoma and, when present, is sufficient for diagnosis. - Both capsular invasion and vascular invasion are **equally definitive** for diagnosing malignancy in follicular neoplasms. - However, **capsular invasion** is more commonly emphasized in teaching as the "key" differentiating feature and is more frequently encountered. *Presence of colloid* - The presence or absence of **colloid** reflects the functional activity of thyroid follicles, not malignant potential. - Both **follicular adenomas** and **follicular carcinomas** can contain abundant colloid, making this feature unreliable for differentiation.

Q: Malignancy in pheochromocytoma is indicated by:

Metastasis. ***Metastasis*** - The definitive criterion for diagnosing **malignancy in pheochromocytoma** is the presence of **metastatic disease**, meaning tumor cells have spread to sites where chromaffin tissue is not normally found. - The distinction between benign and malignant pheochromocytomas often cannot be made based on histological features alone. *Mitotic figures* - While increased **mitotic activity** can be a feature indicating aggressive tumor behavior, it is not a standalone definitive criterion for malignancy in pheochromocytoma. - Benign pheochromocytomas can occasionally show mitotic figures, and their presence alone does not confirm malignancy. *Capsular invasion* - **Capsular invasion** suggests an aggressive tumor but is not a definitive indicator of malignancy in pheochromocytoma. - Tumors that exhibit capsular invasion without distant spread are still considered to have uncertain malignant potential rather than overt malignancy. *Vascular invasion* - Similar to capsular invasion, **vascular invasion** indicates an increased risk of metastasis but is not a conclusive sign of malignancy. - The presence of tumor cells within blood vessels raises suspicion, but true malignancy is only confirmed by the presence of distant metastases.

Q: Mark the false statement regarding Hürthle cell carcinoma:

It can be diagnosed by FNAC.. ***It can be diagnosed by FNAC.*** - **Fine-needle aspiration cytology (FNAC)** alone cannot definitively diagnose Hürthle cell carcinoma because distinguishing between **benign Hürthle cell adenoma** and **malignant Hürthle cell carcinoma** requires evidence of **capsular or vascular invasion**, which cannot be assessed cytologically [1]. - FNAC results typically return as "**follicular neoplasm, Hürthle cell type**" or "**suspicious for Hürthle cell neoplasm**," necessitating surgical excision for definitive diagnosis [1]. *Arises from Hürthle cells of the thyroid.* - This statement is **true** because Hürthle cell carcinoma originates from **Hürthle cells** (also known as oxyphil cells or oncocytes), which are found in the thyroid gland. - These cells are characterized by abundant **eosinophilic, granular cytoplasm** due to a high concentration of mitochondria. *Central neck dissection is performed in certain cases.* - This statement is **true** because **central neck dissection** is considered in Hürthle cell carcinoma when there is evidence of **lymph node metastasis** or **high-risk disease features**. - While Hürthle cell carcinoma is less likely to metastasize to lymph nodes than papillary thyroid carcinoma, such an intervention may be necessary for staging and disease control. *It is not a variant of papillary thyroid cancer.* - This statement is **true** because Hürthle cell carcinoma is a distinct entity, classified as a variant of **follicular thyroid carcinoma**, not papillary thyroid carcinoma [1]. - It has a separate biological behavior and treatment strategy compared to papillary thyroid cancer. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Endocrine System, pp. 1100-1101.

Q: The expression of which gene is most strongly associated with a high incidence of medullary carcinomas of the thyroid?

Ret proto-oncogene. ***Ret proto-oncogene (Correct Answer)*** - **Mutations** in the **RET proto-oncogene** are central to the development of **medullary thyroid carcinoma (MTC)**, especially in hereditary forms like **Multiple Endocrine Neoplasia type 2 (MEN 2)** [1], [2]. - Activating mutations in *RET* lead to constitutive activation of its tyrosine kinase domain, promoting uncontrolled cell growth and survival in **parafollicular C cells** [1], [3]. - Found in ~98% of hereditary MTC and ~40-50% of sporadic cases. *p53 (Incorrect)* - The **p53 tumor suppressor gene** is frequently mutated in a wide variety of human cancers, but it is not the primary driver in **medullary thyroid carcinoma**. - Its role is often seen in later-stage or more aggressive cancers, typically losing normal cell cycle control. *Her2/neu (Incorrect)* - The **HER2/neu (ERBB2) gene** encodes a receptor tyrosine kinase primarily associated with **breast cancer** and some **gastric cancers**, where its overexpression is a therapeutic target [1]. - Its overexpression is not a characteristic feature or driver mutation for **medullary thyroid carcinoma**. *Rb gene (Incorrect)* - The **retinoblastoma (Rb) gene** is a **tumor suppressor gene** crucial for regulating the cell cycle, and mutations are associated with retinoblastoma and other cancers like **osteosarcoma** and **small cell lung cancer**. - While it's a significant tumor suppressor, mutations in the *Rb gene* are not directly linked to the pathogenesis of **medullary thyroid carcinoma**. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, p. 292. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Endocrine System, pp. 1139-1140. [3] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Liver And Biliary System Disease, pp. 428-429.

Question 1

Regarding anaplastic thyroid carcinoma, which of the following statements is true?

Accepted Answer

Associated with p53 mutation

Answer

Common in young

Answer

Radiotherapy cures

Answer

Surrounding neck tissue is usually free

Question 2

Radiation exposure can lead to which type of thyroid carcinoma?

Accepted Answer

Papillary carcinoma

Answer

Lymphoma

Answer

Medullary carcinoma

Answer

Follicular carcinoma

Question 3

A 65-year-old female patient presented with complaints of a swelling in the neck which moved with deglutition along with multiple episodes of diarrhea, hoarseness, mild dysphagia and mild shortness of breath. Lab findings revealed raised serum calcitonin levels and hypercalcemia. Which of the following histology corresponds with the above disease?

Accepted Answer

Answer

None of the options

Question 4

A well-differentiated follicular carcinoma of the thyroid can be best differentiated from a follicular adenoma by:

Accepted Answer

Vascular invasion

Answer

Lining of tall columnar and cuboidal cells

Answer

Nuclear features

Answer

Hürthle cell change

Question 5

What is the key histological feature that differentiates follicular carcinoma from follicular adenoma of the thyroid?

Accepted Answer

Capsular invasion

Answer

Nuclear atypia

Answer

Vascular invasion

Answer

Presence of colloid

Question 6

Malignancy in pheochromocytoma is indicated by:

Accepted Answer

Metastasis

Answer

Mitotic figures

Answer

Capsular invasion

Answer

Vascular invasion

Question 7

Mark the false statement regarding Hürthle cell carcinoma:

Accepted Answer

It can be diagnosed by FNAC.

Answer

Arises from Hürthle cells of the thyroid.

Answer

Central neck dissection is performed in certain cases.

Answer

It is not a variant of papillary thyroid cancer.

Question 8

The expression of which gene is most strongly associated with a high incidence of medullary carcinomas of the thyroid?

Accepted Answer

Ret proto-oncogene

Answer

p53

Answer

Rb gene

Answer

Her2/neu

Question 9

All the following statements about thyroid carcinoma are true, except which one?

Accepted Answer

Papillary carcinoma primarily spreads via hematogenous routes.

Answer

Medullary ca is associated with MEN2a

Answer

Follicular carcinoma primarily spreads via hematogenous routes.

Answer

Thyroid lymphoma is often associated with Hashimoto's thyroiditis

Endocrine Pathology — MCQs

Endocrine Pathology — MCQs

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