A 12-year-old boy is brought to the emergency department after he vomited and said he was having double vision in school. He also says that he has been experiencing morning headaches, nausea, and dizziness over the last month. He has no past medical history and is not taking any medications. Physical exam reveals a broad-based gait, dysmetria on finger-to-nose testing, and nystagmus. Both serum and urine toxicology are negative, and radiography reveals a solid mass in the midline cerebellum that enhances after contrast administration. Biopsy of this lesion reveals cells of primitive neuroectodermal origin. Which of the following would most likely be seen on histology of this lesion?
Q162
A 34-year-old man presents to the office for evaluation of a lesion on his upper arm that appeared a few months ago and has not healed. The patient appears healthful but has a history of cardiovascular disease. He states that his friend at the industrial ammunition factory where he works told him he should "get it looked at." The patient admits to some nausea, vomiting, and diarrhea over the past year, but he states that he "feels fine now." On physical examination, the lesion is an erythematous, scaly, ulcerated plaque on the flexor surface of his upper arm. The rest of the exam is within normal limits. What is the most likely diagnosis?
Q163
A 28-year-old man presents with a 3-day history of cough and fever. He says that he recently became a factory worker in a huge plant that is involved in the polyvinyl chloride (PVC) polymerization process. Because he has heard about occupational diseases specifically related to this particular industry, he asks the physician whether his new job is associated with any serious conditions. His physician mentions that polyvinyl chloride is a known chemical carcinogen and that workers who have been exposed to it are known to be at increased risk of developing a particular type of cancer. Which of the following cancers is the physician most likely talking about?
Q164
A 47-year-old woman comes to the physician because of a 2-month history of a lump on her neck and a 1-week history of hoarseness. Examination shows a 3-cm, firm, non-tender nodule on the anterior neck. Further evaluation confirms a thyroid malignancy, and she undergoes thyroidectomy. Histopathologic examination of the surgical specimen shows lymphatic invasion. Genetic analysis shows an activating mutation in the RET/PTC genes. Microscopic examination of the surgical specimen is most likely to also show which of the following?
Q165
A 51-year-old woman presents to the dermatologist with concern for a new skin lesion (Image A). You note two similar lesions on her back. Which of the following is a true statement about these lesions?
Q166
A 70-year-old man comes to the physician because of a painless skin lesion on his neck for the past 5 months. The lesion has gradually become darker in color and is often pruritic. He has a similar lesion on the back. He is a retired landscaper. He has smoked half a pack of cigarettes daily for 45 years. Physical examination shows a 0.9-cm hyperpigmented papule on the neck with a greasy, wax-like, and stuck-on appearance. Histopathologic examination is most likely to show which of the following?
Q167
A 2-year-old boy is brought to the physician with complaints of gingival growth in the lower jaw with associated pain for the past few weeks. He has no history of trauma or any other significant medical conditions. His temperature is 37.0°C (98.6°F), pulse is 92/min, and respiratory rate is 24/min. On extraoral examination, a swelling of 4 cm x 2 cm is present on the left lower jaw. On intraoral examination, a diffuse erythematous swelling covered with necrotic slough is present on the gingiva. Computed tomography (CT) scan of the head shows multiple soft tissue density lesions involving mandibular, maxillary, left occipital, and temporal regions. Which of the following findings, if present, would be the most specific indicator of the disease in this patient?
Q168
A 59-year-old man comes to the physician for evaluation of a progressively enlarging, 8-mm skin lesion on the right shoulder that developed 1 month ago. The patient has a light-skinned complexion and has had several dysplastic nevi removed in the past. A photograph of the lesion is shown. The lesion is most likely derived from cells that are also the embryological origin of which of the following tumors?
Q169
A 45-year-old man comes to the physician for the evaluation of difficulty swallowing that has worsened over the past year. He also reports some hoarseness and generalized bone, muscle, and joint pain. During the past six months, he has had progressive constipation and two episodes of kidney stones. He also reports recurrent episodes of throbbing headaches, diaphoresis, and palpitations. He does not smoke or drink alcohol. He takes no medications. His vital signs are within normal limits. Physical examination and an ECG show no abnormalities. Laboratory studies show calcium concentration of 12 mg/dL, phosphorus concentration of 2 mg/dL, alkaline phosphatase concentration of 100 U/L, and calcitonin concentration of 11 pg/mL (N < 8.8). Ultrasonography of the neck shows hypoechoic thyroid lesions with irregular margins and microcalcifications. Which of the following is the most likely underlying cause of this patient's condition?
Q170
A previously healthy 68-year-old woman is brought to the emergency department because of a 3-day history of nausea, anorexia, polyuria, and confusion. Her only medication is acetaminophen, which she takes daily for back pain that started 6 weeks ago. Physical examination shows conjunctival pallor. She is oriented to person but not to time or place. Laboratory studies show a hemoglobin concentration of 9.3 g/dL, a serum calcium concentration of 13.8 mg/dL, and a serum creatinine concentration of 2.1 mg/dL. Her erythrocyte sedimentation rate is 65 mm/h. Which of the following is the most likely underlying cause of this patient's condition?
Neoplasia US Medical PG Practice Questions and MCQs
Question 161: A 12-year-old boy is brought to the emergency department after he vomited and said he was having double vision in school. He also says that he has been experiencing morning headaches, nausea, and dizziness over the last month. He has no past medical history and is not taking any medications. Physical exam reveals a broad-based gait, dysmetria on finger-to-nose testing, and nystagmus. Both serum and urine toxicology are negative, and radiography reveals a solid mass in the midline cerebellum that enhances after contrast administration. Biopsy of this lesion reveals cells of primitive neuroectodermal origin. Which of the following would most likely be seen on histology of this lesion?
A. Rosettes with small blue cells (Correct Answer)
B. Rosenthal fibers
C. Tooth enamel-like calcification
D. Foamy cells and high vascularity
E. Perivascular pseudorosettes
Explanation: ***Rosettes with small blue cells***
- The description of a **midline cerebellar mass** in a child, presenting with signs of **increased intracranial pressure (headaches, vomiting, double vision)** and **cerebellar dysfunction (broad-based gait, dysmetria, nystagmus)**, is classic for **medulloblastoma**.
- **Medulloblastomas** are primitive neuroectodermal tumors (PNETs) known for their distinctive histology of **small, round, blue cells** forming **Homer-Wright rosettes**.
*Rosenthal fibers*
- **Rosenthal fibers** are eosinophilic, corkscrew-shaped structures that are characteristic histological features of **pilocytic astrocytomas**.
- While pilocytic astrocytomas can be cerebellar and common in children, the question describes a "solid mass of primitive neuroectodermal origin" rather than the typical cystic lesion with mural nodule associated with pilocytic astrocytomas, and the aggressive presentation points away from pilocytic astrocytoma.
*Tooth enamel-like calcification*
- **Tooth enamel-like calcification** is a pathognomonic feature of **craniopharyngiomas**, which are typically supratentorial (in the sellar region) and cause symptoms related to pituitary dysfunction and optic chiasm compression, not cerebellar dysfunction.
- The location and symptoms provided in the vignette do not match the typical presentation of a craniopharyngioma.
*Foamy cells and high vascularity*
- **Foamy cells and high vascularity** are characteristic features of **hemangioblastomas**, which are typically seen in adults, often associated with **von Hippel-Lindau disease**, and are more commonly located in the cerebellum.
- However, the patient's age (12-year-old) and the description of cells of "primitive neuroectodermal origin" do not align with the typical presentation or origin of hemangioblastomas.
*Perivascular pseudorosettes*
- **Perivascular pseudorosettes** are the classic histological finding in **ependymomas**, another common pediatric brain tumor.
- While ependymomas can occur in the posterior fossa, they typically arise from the floor of the fourth ventricle and are not described as having primitive neuroectodermal origin in the same way medulloblastomas are, and the specific rosettes formed by medulloblastomas are Homer-Wright rosettes.
Question 162: A 34-year-old man presents to the office for evaluation of a lesion on his upper arm that appeared a few months ago and has not healed. The patient appears healthful but has a history of cardiovascular disease. He states that his friend at the industrial ammunition factory where he works told him he should "get it looked at." The patient admits to some nausea, vomiting, and diarrhea over the past year, but he states that he "feels fine now." On physical examination, the lesion is an erythematous, scaly, ulcerated plaque on the flexor surface of his upper arm. The rest of the exam is within normal limits. What is the most likely diagnosis?
A. Squamous cell carcinoma (SCC) (Correct Answer)
B. Erythema multiforme
C. Actinic keratosis
D. Erysipelas
E. Contact dermatitis
Explanation: ***Squamous cell carcinoma (SCC)***
- The patient's occupational exposure to chemicals at an **ammunition factory**, along with chronic non-healing, **ulcerated, scaly plaque**, raises suspicion for SCC, particularly **arsenic-induced SCC**.
- His history of vague **gastrointestinal symptoms** (nausea, vomiting, diarrhea) over the past year is also consistent with **chronic arsenic exposure**, which is a known carcinogen.
*Erythema multiforme*
- This is an **acute, self-limiting hypersensitivity reaction** to medications or infections, characterized by target lesions, not a chronic, non-healing ulcerated plaque.
- It would not typically present with a history of chronic GI symptoms related to occupational exposure.
*Actinic keratosis*
- This is a **precancerous lesion** caused by chronic sun exposure, typically presenting as a rough, scaly patch on sun-exposed areas.
- While it has malignant potential to transform into SCC, the description of an **ulcerated, non-healing lesion** with a history of probable chemical exposure makes SCC a more likely *current* diagnosis.
*Erysipelas*
- Erysipelas is a **superficial bacterial infection** of the skin characterized by a rapidly spreading, bright red, well-demarcated, and painful rash, often accompanied by fever and systemic symptoms.
- It would not manifest as a chronic, non-healing ulcerated plaque over several months.
*Contact dermatitis*
- This is an **inflammatory skin reaction** due to direct contact with an allergen or irritant, typically presenting as an itchy, erythematous rash with vesicles or papules.
- It would not typically result in a chronic, ulcerated, non-healing plaque and is not associated with the systemic symptoms or occupational exposure history presented.
Question 163: A 28-year-old man presents with a 3-day history of cough and fever. He says that he recently became a factory worker in a huge plant that is involved in the polyvinyl chloride (PVC) polymerization process. Because he has heard about occupational diseases specifically related to this particular industry, he asks the physician whether his new job is associated with any serious conditions. His physician mentions that polyvinyl chloride is a known chemical carcinogen and that workers who have been exposed to it are known to be at increased risk of developing a particular type of cancer. Which of the following cancers is the physician most likely talking about?
A. Bronchogenic carcinoma
B. Adenocarcinoma of the small intestine
C. Hepatic angiosarcoma (Correct Answer)
D. Malignant lymphoma
E. Urothelial carcinoma
Explanation: ***Hepatic angiosarcoma***
- Exposure to **polyvinyl chloride (PVC)**, especially in the polymerization process, is a well-established occupational risk factor for **hepatic angiosarcoma**.
- This knowledge is crucial for understanding the **carcinogenic potential** of specific industrial chemicals and conducting appropriate occupational health screenings.
*Bronchogenic carcinoma*
- While various occupational exposures (e.g., asbestos, radon) can cause **bronchogenic carcinoma**, PVC polymerization is not primarily linked to this malignancy.
- This diagnosis is more commonly associated with chronic inhalation of **pulmonary irritants** and smoking.
*Adenocarcinoma of the small intestine*
- This is a very rare primary malignancy of the gastrointestinal tract and it is not typically associated with **polyvinyl chloride exposure**.
- Its risk factors are generally related to chronic inflammatory conditions of the bowel, such as **Crohn's disease**, or certain genetic syndromes.
*Malignant lymphoma*
- Various chemical exposures can increase the risk of lymphoma, but **polyvinyl chloride exposure** is not a primary or well-established risk factor for its development.
- Lymphomas are a diverse group of cancers often linked to immune system dysfunction, viral infections (e.g., EBV), or certain genetic predispositions.
*Urothelial carcinoma*
- This cancer is primarily associated with exposure to **aromatic amines** and **cigarette smoking**, which are known bladder carcinogens.
- There is no strong evidence linking **polyvinyl chloride exposure** to an increased risk of urothelial carcinoma.
Question 164: A 47-year-old woman comes to the physician because of a 2-month history of a lump on her neck and a 1-week history of hoarseness. Examination shows a 3-cm, firm, non-tender nodule on the anterior neck. Further evaluation confirms a thyroid malignancy, and she undergoes thyroidectomy. Histopathologic examination of the surgical specimen shows lymphatic invasion. Genetic analysis shows an activating mutation in the RET/PTC genes. Microscopic examination of the surgical specimen is most likely to also show which of the following?
A. Pleomorphic giant cells with numerous atypical mitotic figures
B. Cuboidal cells arranged spherically around colloid lakes
C. Hyperplastic epithelium with colloid scalloping
D. Calcified spherules and large oval cells with empty-appearing nuclei (Correct Answer)
E. Sheets of polygonal cells surrounding amyloid deposition
Explanation: ***Calcified spherules and large oval cells with empty-appearing nuclei***
- The presence of an **activating mutation in RET/PTC genes**, **lymphatic invasion**, and a new neck lump with hoarseness (suggesting nerve involvement) are highly characteristic of **papillary thyroid carcinoma**.
- Microscopic features of papillary thyroid carcinoma include **Psammoma bodies (calcified spherules)**, **Orphan Annie eye nuclei (large oval cells with empty-appearing nuclei)**, and nuclear grooves.
*Pleomorphic giant cells with numerous atypical mitotic figures*
- This description typically refers to **anaplastic thyroid carcinoma**, a highly aggressive and undifferentiated tumor.
- While anaplastic carcinoma can present with rapid growth and hoarseness, it is less commonly associated with a **RET/PTC mutation** (BRAF mutations are more common) and typically has a much poorer prognosis, often presenting with a rapidly enlarging mass rather than a 2-month history suggestive of a more indolent tumor.
*Cuboidal cells arranged spherically around colloid lakes*
- This morphology is characteristic of **follicular thyroid carcinoma** or **follicular adenoma**.
- While follicular tumors can have RET/PTC mutations in some variants, the classic features described (empty-appearing nuclei and psammoma bodies) are absent here.
*Hyperplastic epithelium with colloid scalloping*
- This describes the histologic features seen in **Graves' disease** or **diffuse toxic goiter**, a benign condition.
- It is not indicative of malignancy, and the patient's presentation with a solitary nodule and hoarseness points to a malignant process.
*Sheets of polygonal cells surrounding amyloid deposition*
- This is the classic microscopic appearance of **medullary thyroid carcinoma**.
- Medullary thyroid carcinoma is also associated with **RET mutations**, but these are typically **germline or somatic RET point mutations** (e.g., RET M918T), not RET/PTC rearrangements, and it arises from parafollicular C cells, producing calcitonin, not thyroid hormones.
Question 165: A 51-year-old woman presents to the dermatologist with concern for a new skin lesion (Image A). You note two similar lesions on her back. Which of the following is a true statement about these lesions?
A. They must be followed closely for concern of malignancy.
B. They will likely regress spontaneously.
C. They may be associated with von Hippel-Lindau disease.
D. They will likely grow rapidly.
E. They will likely increase in number over time. (Correct Answer)
Explanation: ***They will likely increase in number over time.***
- The image likely displays **cherry angiomas**, which are common benign vascular lesions that typically increase in number with age.
- While individual lesions may remain stable, their overall prevalence on the skin tends to rise as a person ages, especially after the age of 30.
*They must be followed closely for concern of malignancy.*
- **Cherry angiomas** are **benign vascular proliferations** and do not carry a risk of malignant transformation.
- They are typically diagnosed clinically and do not require ongoing surveillance for malignancy.
*They will likely regress spontaneously.*
- **Cherry angiomas** are **permanent lesions** and do not typically regress spontaneously.
- Once they appear, they usually persist and often grow slightly in size over time.
*They may be associated with von Hippel-Lindau disease.*
- **Von Hippel-Lindau (VHL) disease** is associated with **hemangioblastomas** (in the CNS and retina), **pheochromocytomas**, and **renal cell carcinoma**, but not typically cherry angiomas.
- The characteristic skin lesions in VHL are often **cutaneous cavernous hemangiomas** or **capillary malformations**, not the common cherry angioma.
*They will likely grow rapidly.*
- While cherry angiomas can slowly increase in size over many years, they do **not typically grow rapidly**.
- Rapid growth of a cutaneous lesion would be a more concerning feature for other conditions, such as **malignant melanoma** or a **rapidly growing cyst**, not cherry angiomas.
Question 166: A 70-year-old man comes to the physician because of a painless skin lesion on his neck for the past 5 months. The lesion has gradually become darker in color and is often pruritic. He has a similar lesion on the back. He is a retired landscaper. He has smoked half a pack of cigarettes daily for 45 years. Physical examination shows a 0.9-cm hyperpigmented papule on the neck with a greasy, wax-like, and stuck-on appearance. Histopathologic examination is most likely to show which of the following?
A. Nests of melanocytes at the base of rete ridges and the dermis
B. Fibroblast proliferation with small, benign dermal growth
C. S100-positive epithelioid cells with fine granules in the cytoplasm
D. Koilocytes in the granular cell layer of the epidermis
E. Immature keratinocytes with small keratin-filled cysts (Correct Answer)
Explanation: ***Immature keratinocytes with small keratin-filled cysts***
- The clinical presentation of a **hyperpigmented papule** with a **greasy, wax-like, and stuck-on appearance** is highly characteristic of a **seborrheic keratosis**.
- Histopathologically, seborrheic keratoses are characterized by a proliferation of **immature keratinocytes** and often contain **horn cysts** (small keratin-filled cysts) and pseudo-horn cysts.
*Nests of melanocytes at the base of rete ridges and the dermis*
- This description is characteristic of a **melanocytic nevus** (mole) or potentially a melanoma, especially if there are nests of atypical melanocytes in the dermis.
- While seborrheic keratoses can be hyperpigmented, their clinical appearance is distinct from melanocytic lesions, lacking features like irregular borders or rapid changes.
*Fibroblast proliferation with small, benign dermal growth*
- This histological finding is more consistent with a **dermatofibroma** (fibrous histiocytoma), which presents as a firm, often pigmented nodule that may dimple inward when compressed.
- Dermatofibromas do not typically have the **greasy, stuck-on appearance** seen in seborrheic keratoses.
*S100-positive epithelioid cells with fine granules in the cytoplasm*
- **S100 positivity** is a marker for neural crest-derived cells, including melanocytes and Schwann cells. Epithelioid cells with fine granules could be seen in conditions like **granular cell tumor**, which stains positive for S100 protein.
- A granular cell tumor usually presents as a solitary, firm nodule and does not typically have the classic "greasy, stuck-on" appearance of a seborrheic keratosis.
*Koilocytes in the granular cell layer of the epidermis*
- **Koilocytes** are characteristic of **human papillomavirus (HPV) infection**, leading to conditions like common warts (verruca vulgaris) or genital warts (condyloma acuminatum).
- Warts typically have a rough, verrucous surface and do not present with the greasy, wax-like texture of a seborrheic keratosis.
Question 167: A 2-year-old boy is brought to the physician with complaints of gingival growth in the lower jaw with associated pain for the past few weeks. He has no history of trauma or any other significant medical conditions. His temperature is 37.0°C (98.6°F), pulse is 92/min, and respiratory rate is 24/min. On extraoral examination, a swelling of 4 cm x 2 cm is present on the left lower jaw. On intraoral examination, a diffuse erythematous swelling covered with necrotic slough is present on the gingiva. Computed tomography (CT) scan of the head shows multiple soft tissue density lesions involving mandibular, maxillary, left occipital, and temporal regions. Which of the following findings, if present, would be the most specific indicator of the disease in this patient?
A. Birbeck granules (Correct Answer)
B. Starry sky appearance
C. Auer rods
D. Owl's eye inclusions
E. Reed-Sternberg cells
Explanation: ***Birbeck granules***
- The clinical presentation, including multifocal bone lesions (mandibular, maxillary, occipital, temporal) and gingival swelling in a 2-year-old boy, is highly suggestive of **Langerhans cell histiocytosis (LCH)**.
- **Birbeck granules** are characteristic rod- or tennis racket-shaped cytoplasmic organelles found specifically in Langerhans cells and are considered the **pathognomonic microscopic finding** for LCH.
*Starry sky appearance*
- This refers to the microscopic appearance of a high-grade lymphoma, most famously **Burkitt lymphoma**, where dark tumor cells are interspersed with pale macrophages.
- While Burkitt lymphoma can cause jaw lesions, the multifocal bone involvement described in this case, particularly in multiple distant sites, makes LCH a more fitting diagnosis.
*Auer rods*
- These are **azurophilic, needle-like cytoplasmic inclusions** found in the cytoplasm of myeloid blasts in patients with **acute myeloid leukemia (AML)**.
- AML can present with gingival infiltration and bone lesions, but Auer rods are specific for myeloid leukemias, not the histiocytic proliferation suggested by the widespread bone involvement.
*Owl's eye inclusions*
- These refer to the characteristic appearance of **cytomegalovirus (CMV)**-infected cells, exhibiting an enlarged nucleus with a central basophilic inclusion body surrounded by a clear halo.
- CMV infection does not typically cause multifocal bone lesions or gingival growth in this manner.
*Reed-Sternberg cells*
- These are large, multinucleated cells with prominent nucleoli that are characteristic of **Hodgkin lymphoma**.
- Hodgkin lymphoma predominantly affects lymph nodes and rarely presents with widespread lytic bone lesions and gingival involvement as the primary manifestation in this age group.
Question 168: A 59-year-old man comes to the physician for evaluation of a progressively enlarging, 8-mm skin lesion on the right shoulder that developed 1 month ago. The patient has a light-skinned complexion and has had several dysplastic nevi removed in the past. A photograph of the lesion is shown. The lesion is most likely derived from cells that are also the embryological origin of which of the following tumors?
A. Adrenal adenoma
B. Liposarcoma
C. Basal cell carcinoma
D. Neuroblastoma (Correct Answer)
E. Medullary thyroid cancer
Explanation: ***Neuroblastoma***
- The skin lesion described, with history of dysplastic nevi and progressive growth, is highly suggestive of **melanoma**. Melanoma arises from **melanocytes**, which are derived from the **neural crest**.
- **Neuroblastoma** is a tumor of the **sympathetic nervous system** that also originates from **neural crest cells**, making it the correct embryological match.
- Neuroblastoma is the **classic example** of a neural crest-derived tumor taught alongside melanoma in medical education.
*Adrenal adenoma*
- **Adrenal adenomas** are benign tumors of the adrenal cortex, which is derived from the **mesoderm**.
- This embryological origin is distinct from the neural crest origin of melanocytes.
*Liposarcoma*
- **Liposarcomas** are malignant tumors of adipose tissue, which arises from the **mesoderm**.
- This origin does not match the neural crest origin of melanocytes.
*Basal cell carcinoma*
- **Basal cell carcinoma** originates from the **basal layer of the epidermis**, which is derived from **surface ectoderm** (not neural crest).
- While it's an ectodermal derivative, it does not share the neural crest origin of melanocytes.
*Medullary thyroid cancer*
- **Medullary thyroid cancer** originates from the **parafollicular C cells** of the thyroid gland, which are also derived from the **neural crest**.
- While this shares the same embryological origin as melanoma, **neuroblastoma** is the more commonly tested and classic pairing with melanoma in standard medical examinations when discussing neural crest-derived tumors.
Question 169: A 45-year-old man comes to the physician for the evaluation of difficulty swallowing that has worsened over the past year. He also reports some hoarseness and generalized bone, muscle, and joint pain. During the past six months, he has had progressive constipation and two episodes of kidney stones. He also reports recurrent episodes of throbbing headaches, diaphoresis, and palpitations. He does not smoke or drink alcohol. He takes no medications. His vital signs are within normal limits. Physical examination and an ECG show no abnormalities. Laboratory studies show calcium concentration of 12 mg/dL, phosphorus concentration of 2 mg/dL, alkaline phosphatase concentration of 100 U/L, and calcitonin concentration of 11 pg/mL (N < 8.8). Ultrasonography of the neck shows hypoechoic thyroid lesions with irregular margins and microcalcifications. Which of the following is the most likely underlying cause of this patient's condition?
A. Altered RET proto-oncogene expression (Correct Answer)
B. Deleted VHL gene
C. Disrupted menin protein function
D. Exposure to ionizing radiation
E. Mutated NF1 gene
Explanation: ***Altered RET proto-oncogene expression***
- This patient's symptoms are highly suggestive of **multiple endocrine neoplasia type 2A (MEN2A)**, which is caused by gain-of-function mutations in the **RET proto-oncogene**.
- **MEN2A** typically presents with **medullary thyroid carcinoma** (hypoechoic thyroid lesions, elevated calcitonin), **pheochromocytoma** (throbbing headaches, diaphoresis, palpitations), and **primary hyperparathyroidism** (hypercalcemia, hypophosphatemia, bone/muscle/joint pain, kidney stones).
*Deleted VHL gene*
- A deleted **VHL gene** is associated with **Von Hippel-Lindau disease**, characterized by **retinal and cerebellar hemangioblastomas**, **renal cell carcinoma**, and **pheochromocytoma**.
- While pheochromocytoma is present, the thyroid and parathyroid findings are not consistent with VHL disease.
*Disrupted menin protein function*
- Disrupted **menin protein function** is characteristic of **multiple endocrine neoplasia type 1 (MEN1)**, which includes **pituitary tumors**, **parathyroid adenomas** (leading to hyperparathyroidism), and **pancreatic endocrine tumors**.
- Although primary hyperparathyroidism is present, the thyroid carcinoma is medullary (not follicular/papillary) and the specific symptoms point more toward MEN2A.
*Exposure to ionizing radiation*
- Exposure to **ionizing radiation** is a risk factor for **papillary and follicular thyroid carcinomas**, but not typically **medullary thyroid carcinoma**.
- It also does not explain the concurrent **pheochromocytoma** and **hyperparathyroidism**.
*Mutated NF1 gene*
- A mutated **NF1 gene** is responsible for **neurofibromatosis type 1**, which manifests with **café-au-lait spots**, **neurofibromas**, **optic gliomas**, and sometimes **pheochromocytoma**.
- There are no cutaneous or neurological findings of neurofibromatosis in this patient, and the prominent medullary thyroid carcinoma and hyperparathyroidism are not features of NF1.
Question 170: A previously healthy 68-year-old woman is brought to the emergency department because of a 3-day history of nausea, anorexia, polyuria, and confusion. Her only medication is acetaminophen, which she takes daily for back pain that started 6 weeks ago. Physical examination shows conjunctival pallor. She is oriented to person but not to time or place. Laboratory studies show a hemoglobin concentration of 9.3 g/dL, a serum calcium concentration of 13.8 mg/dL, and a serum creatinine concentration of 2.1 mg/dL. Her erythrocyte sedimentation rate is 65 mm/h. Which of the following is the most likely underlying cause of this patient's condition?
A. Overproliferation of plasma cells (Correct Answer)
B. Decreased renal excretion of calcium
C. Excessive intake of calcium
D. Ectopic release of PTHrP
E. Excess PTH secretion from parathyroid glands
Explanation: ***Overproliferation of plasma cells***
- The patient's symptoms (nausea, anorexia, polyuria, confusion, back pain, anemia, hypercalcemia, acute kidney injury, and elevated ESR) are classic features of **multiple myeloma** (CRAB — Calcium elevation, Renal insufficiency, Anemia, Bone lesions).
- Multiple myeloma is characterized by the **malignant proliferation of plasma cells** in the bone marrow, leading to skeletal destruction (causing back pain and hypercalcemia), renal damage, and anemia.
*Decreased renal excretion of calcium*
- While **renal insufficiency** (creatinine 2.1 mg/dL) contributes to hypercalcemia by impairing calcium excretion, it is typically a **consequence** of the underlying disease rather than the primary cause of hypercalcemia, especially with such a high calcium level.
- The elevated calcium itself can worsen kidney function, creating a **vicious cycle**, but an underlying cause for hypercalcemia is still needed.
*Excessive intake of calcium*
- This typically occurs with **calcium and vitamin D supplementation** (milk-alkali syndrome) and is not suggested by the patient's history, as her only medication is acetaminophen.
- Her current symptoms are too severe and multi-systemic to be explained solely by dietary calcium excess without other contributing factors.
*Ectopic release of PTHrP*
- **Parathyroid hormone-related peptide (PTHrP)** is secreted by various solid tumors (e.g., squamous cell carcinoma of the lung, renal cell carcinoma) and causes humoral hypercalcemia of malignancy.
- While it causes hypercalcemia, the prominent **bone pain and anemia** in this patient are more characteristic of multiple myeloma than a solid tumor secreting PTHrP.
*Excess PTH secretion from parathyroid glands*
- This describes **primary hyperparathyroidism**, which causes hypercalcemia and can lead to bone pain and renal stones.
- However, primary hyperparathyroidism is typically associated with **normal or elevated PTH levels**, and it does not usually cause the degree of anemia or elevated ESR seen in this case.
