A 58-year-old woman presents to a physician with a painless swelling behind her right ear, which she noticed 1 month ago. She has no other complaint nor does she have any specific medical condition. On physical examination, her vital signs are stable. An examination of the right post-auricular area shows enlarged lymph nodes, which are non-tender and rubbery in consistency, with normal overlying skin. A detailed general examination reveals the presence of one enlarged axillary lymph node on the left side with similar features. Complete blood counts are within normal limits but atypical lymphocytes are present on the peripheral blood smear. The patient’s serum lactate dehydrogenase level is slightly elevated. Excisional biopsy of the lymph node is performed and histopathological examination of the tissue yields a diagnosis of follicular lymphoma. Further cytogenetic studies reveal that the condition is associated with overexpression of the BCL-2 gene. Which of the following cytogenetic abnormalities is most likely to be present?
Q172
A 33-year-old woman comes to the physician 1 week after noticing a lump in her right breast. Fifteen years ago, she was diagnosed with osteosarcoma of her left distal femur. Her father died of an adrenocortical carcinoma at the age of 41 years. Examination shows a 2-cm, firm, immobile mass in the lower outer quadrant of the right breast. A core needle biopsy of the mass shows adenocarcinoma. Genetic analysis in this patient is most likely to show a defect in which of the following genes?
Q173
A 30-year-old boxer seeks evaluation by his physician after he noticed swelling at the angle of his jaw a few days ago. He recalls a recent boxing match when he was punched in his face. He says that his jaw is very painful. On examination, a firm mass is palpated, measuring 4 x 4 cm. An ultrasound was performed, which shows a thin, encapsulated, well-circumscribed, predominantly solid mass with occasional cystic areas. The mass is surgically excised, after which he develops a hoarse voice for a few days, but recovers within 1 week. The histopathologic evaluation of the surgical specimen reports a pseudocapsule with a hypocellular stromal component consisting of a myxoid background and cartilage arranged in clusters and a hypercellular epithelial component with cells arranged in sheets and trabeculae. From which of the following structures did the mass most likely arise?
Q174
A 62-year-old woman presents to her primary care physician because of fever, fatigue, and shortness of breath. She has noticed that she has a number of bruises, but she attributes this to a hike she went on 1 week ago. She has diabetes and hypertension well controlled on medication and previously had an abdominal surgery but doesn’t remember why. On physical exam, she has some lumps in her neck and a palpable liver edge. Peripheral blood smear shows white blood cells with peroxidase positive eosinophilic cytoplasmic inclusions. The abnormal protein most likely seen in this disease normally has which of the following functions?
Q175
A 68-year-old man comes to his physician because of fatigue, night sweats, chills, and a 5-kg (11-lb) weight loss during the past 3 weeks. Eight years ago, he was treated for a hematological malignancy after biopsy of a neck swelling showed CD15+ and CD30+ cells. Physical examination shows conjunctival pallor and scattered petechiae. A peripheral blood smear is shown. Which of the following is the most likely explanation for this patient's current condition?
Q176
A 45-year-old woman is found to have multiple masses in her liver while performing abdominal ultrasonography for recurrent right upper quadrant abdominal pain. Biopsy of one of the masses discloses large plates of adenoma cells, which are larger than normal hepatocytes and contain glycogen and lipid. Regular septa, portal tracts, and bile ductules are absent. Which of the following is associated with this patient's condition?
Q177
A 21-year-old female presents to the family physician with 3 weeks of headaches, sweating, and palpitations. Her BP was 160/125 mmHg, and a 24-hour urine test revealed elevated vanillylmandelic acid (VMA) and normetanephrine. Past medical history is notable for bilateral retinal hemangioblastomas, and family history is significant for three generations (patient, mother, and maternal grandfather) with similar symptoms. Genetic analysis revealed a mutation of a gene on chromosome 3p. Which of the following is the patient at risk of developing?
Q178
A 50-year-old woman presents to the outpatient clinic because of a swollen and enlarged right breast. Clinical examination shows no evidence of mass or axillary lymphadenopathy. There is no history of trauma or inflammation. Her past medical and surgical history is positive for breast augmentation with a textured implant 15 years ago. Magnetic resonance imaging (MRI) shows an accumulation of fluid around the right breast implant with intact implant integrity. Which of the following is the most appropriate next step in the management?
Q179
A 55-year-old woman presents with symptoms of rectal bleeding and pruritus in the perianal region. She works as a real estate agent and has a history of gastroesophageal reflux disease (GERD). On physical examination, her spleen and liver are enlarged. A blood smear reveals teardrop red blood cells (RBCs), and a leucoerythroblastic picture with the presence of nucleated RBC precursors and immature myeloid cells. A complete blood count shows a normocytic anemia. The physician explains that her condition is due to a JAK2 mutation in one of her chromosomes. What is a characteristic bone marrow aspirate of this condition?
Q180
A 10-year-old boy who recently immigrated to the United States from Africa with his family is brought to the emergency department by his mother for a progressively worsening ulcerative lesion on his jaw. His mother reports that her son’s right jaw has rapidly enlarged over the past few months. He says that it is very tender though he doesn’t recall any trauma to the site. In addition, the mother says her son hasn’t been himself the past few months with intermittent fever, weakness, and fatigue. Physical exam reveals a large, ulcerating right jaw mass that is draining serous fluid and painless cervical and axillary lymphadenopathy. Laboratory results are notable for an elevated serum lactate dehydrogenase. A biopsy of the right jaw mass is shown in the photograph. Which of the following chromosomal translocations is most likely to be found in this patient’s lesion?
Neoplasia US Medical PG Practice Questions and MCQs
Question 171: A 58-year-old woman presents to a physician with a painless swelling behind her right ear, which she noticed 1 month ago. She has no other complaint nor does she have any specific medical condition. On physical examination, her vital signs are stable. An examination of the right post-auricular area shows enlarged lymph nodes, which are non-tender and rubbery in consistency, with normal overlying skin. A detailed general examination reveals the presence of one enlarged axillary lymph node on the left side with similar features. Complete blood counts are within normal limits but atypical lymphocytes are present on the peripheral blood smear. The patient’s serum lactate dehydrogenase level is slightly elevated. Excisional biopsy of the lymph node is performed and histopathological examination of the tissue yields a diagnosis of follicular lymphoma. Further cytogenetic studies reveal that the condition is associated with overexpression of the BCL-2 gene. Which of the following cytogenetic abnormalities is most likely to be present?
A. t(3;14)(q27;q32)
B. t(11;18)(q21;q21)
C. t(8;14)(q24;q32)
D. t(11;14)(q13;q32)
E. t(14;18)(q32;q21) (Correct Answer)
Explanation: ***t(14;18)(q32;q21)***
- This translocation is the **hallmark of follicular lymphoma**, present in approximately **85-90% of cases**.
- The **BCL-2 gene** on chromosome **18q21** is translocated to the **immunoglobulin heavy chain (IGH) locus** on chromosome **14q32**, leading to **BCL-2 overexpression**.
- BCL-2 is an **anti-apoptotic protein** that promotes **B-cell survival** by inhibiting programmed cell death, resulting in accumulation of malignant lymphocytes.
*t(3;14)(q27;q32)*
- This translocation involves the **BCL6 gene** on chromosome **3q27** and the immunoglobulin heavy chain locus on chromosome **14q32**.
- It is more commonly associated with **diffuse large B-cell lymphoma (DLBCL)** and occasionally seen in follicular lymphomas with transformation.
- BCL6 rearrangements promote lymphomagenesis through dysregulation of germinal center B-cell differentiation, but this is **not the mechanism** in primary follicular lymphoma with BCL-2 overexpression.
*t(11;18)(q21;q21)*
- This translocation is characteristic of **extranodal marginal zone lymphoma** of mucosa-associated lymphoid tissue (**MALT lymphoma**).
- It results in the **API2-MALT1 fusion gene**, which activates NF-κB signaling.
- This is distinct from the BCL-2 overexpression mechanism seen in follicular lymphoma.
*t(8;14)(q24;q32)*
- This translocation is the **hallmark of Burkitt lymphoma**, leading to **MYC gene overexpression**.
- The **MYC oncogene** on chromosome **8q24** is juxtaposed to the immunoglobulin heavy chain locus on chromosome **14q32**.
- MYC overexpression drives aggressive cell proliferation through dysregulation of cell cycle control, which is different from the anti-apoptotic mechanism of BCL-2 in follicular lymphoma.
*t(11;14)(q13;q32)*
- This translocation is the **hallmark of mantle cell lymphoma**, leading to **cyclin D1 (CCND1) overexpression**.
- The **CCND1 gene** on chromosome **11q13** is translocated to the immunoglobulin heavy chain locus on chromosome **14q32**.
- Cyclin D1 overexpression promotes cell cycle progression from G1 to S phase, which is a different pathogenic mechanism from BCL-2-mediated inhibition of apoptosis in follicular lymphoma.
Question 172: A 33-year-old woman comes to the physician 1 week after noticing a lump in her right breast. Fifteen years ago, she was diagnosed with osteosarcoma of her left distal femur. Her father died of an adrenocortical carcinoma at the age of 41 years. Examination shows a 2-cm, firm, immobile mass in the lower outer quadrant of the right breast. A core needle biopsy of the mass shows adenocarcinoma. Genetic analysis in this patient is most likely to show a defect in which of the following genes?
A. BRCA1
B. KRAS
C. TP53 (Correct Answer)
D. Rb
E. PTEN
Explanation: ***TP53***
- This patient's presentation with **early-onset breast cancer**, a history of **osteosarcoma** at a young age, and a father's death from **adrenocortical carcinoma** at 41 years strongly suggests **Li-Fraumeni syndrome**.
- Li-Fraumeni syndrome is an autosomal dominant disorder caused by a germline mutation in the **tumor suppressor gene TP53**, increasing the risk for multiple primary cancers at a young age.
*BRCA1*
- While **BRCA1 mutations** are associated with an increased risk of breast and ovarian cancer, they are not typically linked to osteosarcoma or adrenocortical carcinoma.
- The constellation of cancers in this patient is more indicative of Li-Fraumeni syndrome than solely a BRCA1-related cancer syndrome.
*KRAS*
- **KRAS** is an oncogene commonly mutated in several cancers, including pancreatic, colorectal, and lung cancer, but is not primarily associated with either Li-Fraumeni syndrome or the specific tumors seen in this family history.
- Mutations in KRAS are typically somatic mutations acquired during a person's lifetime, not germline mutations causing inherited cancer syndromes like the one suggested here.
*Rb*
- Mutations in the **retinoblastoma (Rb) gene** are associated with retinoblastoma and an increased risk of osteosarcoma, but not typically with adrenocortical carcinoma or breast cancer as part of a classic inherited syndrome.
- The combination of breast cancer, osteosarcoma, and adrenocortical carcinoma points more specifically to TP53.
*PTEN*
- **PTEN mutations** are associated with Cowden syndrome, which increases the risk for breast cancer, thyroid cancer, and endometrial cancer, along with benign growths.
- However, Cowden syndrome does not typically include osteosarcoma or adrenocortical carcinoma as prominent features, making PTEN less likely than TP53 for this specific family history.
Question 173: A 30-year-old boxer seeks evaluation by his physician after he noticed swelling at the angle of his jaw a few days ago. He recalls a recent boxing match when he was punched in his face. He says that his jaw is very painful. On examination, a firm mass is palpated, measuring 4 x 4 cm. An ultrasound was performed, which shows a thin, encapsulated, well-circumscribed, predominantly solid mass with occasional cystic areas. The mass is surgically excised, after which he develops a hoarse voice for a few days, but recovers within 1 week. The histopathologic evaluation of the surgical specimen reports a pseudocapsule with a hypocellular stromal component consisting of a myxoid background and cartilage arranged in clusters and a hypercellular epithelial component with cells arranged in sheets and trabeculae. From which of the following structures did the mass most likely arise?
A. Salivary duct
B. Thyroid
C. Parotid gland (Correct Answer)
D. Minor salivary gland
E. Seventh cranial nerve
Explanation: ***Parotid gland***
- The location of the mass at the **angle of the jaw** is highly suggestive of the parotid gland, as the superficial lobe often extends into this region.
- The histopathological findings of a **pseudocapsule**, hypocellular stromal component with **myxoid background and cartilage**, and a hypercellular epithelial component are classic features of a **pleomorphic adenoma**, which is the most common tumor of the parotid gland.
- The temporary **hoarseness** after surgery suggests inadvertent injury to the **recurrent laryngeal nerve**, which can occur if the surgical dissection extends deeper into the neck near the carotid sheath. Note that the **facial nerve (CN VII)** runs through the parotid gland and is at risk during parotidectomy, but facial nerve injury typically causes facial weakness rather than voice changes.
*Salivary duct*
- While salivary ducts are present within salivary glands, a tumor arising directly from a salivary duct rather than the gland parenchyma would likely present with very different histological features, such as those of a **ductal papilloma** or **adenocarcinoma, salivary duct type**.
- The complex **stromal and epithelial components** with cartilage described are characteristic of a pleomorphic adenoma, which originates from both epithelial and mesenchymal elements of the gland, not solely the duct.
*Thyroid*
- The thyroid gland is located in the **anterior neck**, inferior to the laryngeal prominence (Adam's apple), not at the **angle of the jaw**.
- Tumors of the thyroid gland, such as papillary or follicular carcinoma, would have distinct histological features and would not typically present with the described myxoid and cartilaginous stromal components.
*Minor salivary gland*
- Minor salivary glands are numerous and widely distributed in the oral cavity and upper aerodigestive tract, but a mass of this size (4 x 4 cm) at the **angle of the jaw** specifically points to one of the major salivary glands.
- While pleomorphic adenomas can arise in minor salivary glands (most commonly in the palate), their presentation as a large mass at the angle of the jaw is far less common than their occurrence in the parotid gland.
*Seventh cranial nerve*
- The seventh cranial nerve (facial nerve) passes through the parotid gland but does not itself give rise to tumors with the described histological features.
- Tumors involving the facial nerve are typically **schwannomas** or **neurofibromas**, which originate from Schwann cells and would show different microscopic characteristics such as Antoni A and B patterns, not the mixed epithelial-mesenchymal features of pleomorphic adenoma.
Question 174: A 62-year-old woman presents to her primary care physician because of fever, fatigue, and shortness of breath. She has noticed that she has a number of bruises, but she attributes this to a hike she went on 1 week ago. She has diabetes and hypertension well controlled on medication and previously had an abdominal surgery but doesn’t remember why. On physical exam, she has some lumps in her neck and a palpable liver edge. Peripheral blood smear shows white blood cells with peroxidase positive eosinophilic cytoplasmic inclusions. The abnormal protein most likely seen in this disease normally has which of the following functions?
A. Binding to anti-apoptotic factors
B. Binding as cofactor to kinases
C. Inhibiting pro-apoptotic factors
D. Recruiting histone acetylase proteins (Correct Answer)
E. Interacting with IL-3 receptor
Explanation: ***Recruiting histone acetylase proteins***
- The clinical presentation with **fever, fatigue, shortness of breath, bruising**, and **hepatomegaly** along with a **peripheral blood smear showing white blood cells with peroxidase-positive eosinophilic cytoplasmic inclusions** strongly suggests **Acute Promyelocytic Leukemia (APL)**.
- APL is characterized by a **chromosomal translocation t(15;17)**, which fuses the **PML (promyelocytic leukemia)** gene with the **RARα (retinoic acid receptor alpha)** gene. The **PML-RARα fusion protein** acts as an **abnormal transcriptional repressor**, recruiting histone deacetylase (HDAC) proteins and forming a complex that blocks gene expression essential for myeloid differentiation, while the **normal RARα protein** (which is being asked about in the question "abnormal protein most likely seen in this disease normally has which of the following functions") normally **recruits histone acetylase proteins** to promote gene transcription crucial for cellular differentiation.
*Binding to anti-apoptotic factors*
- While a protein's function might involve apoptosis regulation, the **PML-RARα fusion protein**'s primary mechanism in APL is related to **transcriptional repression** and **differentiation block**, not directly binding to anti-apoptotic factors in its normal state.
- The normal function of **RARα** is to promote differentiation, and its dysregulation in APL leads to apoptosis resistance due to the block in differentiation and subsequent proliferation, rather than directly binding anti-apoptotic factors.
*Binding as cofactor to kinases*
- **RARα** is a nuclear receptor and a **ligand-activated transcription factor**, not typically known for directly binding as a cofactor to kinases in its normal physiological role.
- Its main function involves **DNA binding** and interaction with co-activator/co-repressor complexes to regulate gene expression.
*Inhibiting pro-apoptotic factors*
- The normal **RARα protein** is involved in promoting cellular differentiation, and its dysregulation in APL leads to a block in differentiation, which can contribute to the accumulation of immature cells that resist apoptosis.
- However, its normal function is not described as directly **inhibiting pro-apoptotic factors**; rather, its absence or altered function in APL leads to an environment that less efficiently triggers apoptosis in undifferentiated cells.
*Interacting with IL-3 receptor*
- The **IL-3 receptor** is a cell surface receptor involved in cytokine signaling that promotes the growth and differentiation of hematopoietic cells.
- **RARα** is a nuclear receptor located within the cell and primarily interacts with **DNA** and **transcriptional co-regulators**, not with cell surface receptors like the IL-3 receptor.
Question 175: A 68-year-old man comes to his physician because of fatigue, night sweats, chills, and a 5-kg (11-lb) weight loss during the past 3 weeks. Eight years ago, he was treated for a hematological malignancy after biopsy of a neck swelling showed CD15+ and CD30+ cells. Physical examination shows conjunctival pallor and scattered petechiae. A peripheral blood smear is shown. Which of the following is the most likely explanation for this patient's current condition?
A. Accelerated phase of chronic myeloid leukemia
B. Leukemic transformation of myelodysplastic syndrome
C. Richter transformation of small lymphocytic lymphoma
D. Radiation-induced myeloid leukemia (Correct Answer)
E. Leukemic transformation of T-cell lymphoma
Explanation: ***Radiation-induced myeloid leukemia***
- The patient's prior diagnosis with **CD15+ and CD30+ cells** 8 years ago is pathognomonic for **Hodgkin lymphoma** (Reed-Sternberg cells). Treatment for Hodgkin lymphoma typically involves **chemotherapy and/or radiation therapy**, both of which are established risk factors for **therapy-related myeloid neoplasms** (t-MN).
- The current symptoms of fatigue, night sweats, chills, weight loss, **conjunctival pallor** (anemia), and **petechiae** (thrombocytopenia) are consistent with **acute myeloid leukemia (AML)**. The peripheral blood smear would show blast cells.
- **Therapy-related AML** typically develops 5-10 years after exposure to alkylating agents or radiation, which matches this patient's 8-year timeline. This is the **most direct and specific explanation** for his current condition.
*Accelerated phase of chronic myeloid leukemia*
- The initial presentation with **CD15+ and CD30+ cells** indicates **Hodgkin lymphoma**, not chronic myeloid leukemia (CML). CML is characterized by the **BCR-ABL1 fusion gene** and presents with elevated WBC count with left shift, not the CD markers described.
- The described acute presentation with cytopenias is more consistent with acute leukemia rather than accelerated phase CML.
*Leukemic transformation of myelodysplastic syndrome*
- While therapy-related myeloid neoplasms can progress through a **myelodysplastic phase** before developing into overt AML, this option is less specific than identifying the **underlying cause** (prior therapy for Hodgkin lymphoma).
- There is no mention of a prior MDS diagnosis. The question asks for the **most likely explanation**, and the direct causal link to prior cancer treatment is more precise than describing an intermediate stage of disease progression.
*Richter transformation of small lymphocytic lymphoma*
- **Richter transformation** refers to transformation of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) into aggressive diffuse large B-cell lymphoma.
- The patient's initial malignancy with **CD15+ and CD30+ cells** is characteristic of **Hodgkin lymphoma**, not SLL, making this diagnosis incompatible with the clinical history.
*Leukemic transformation of T-cell lymphoma*
- The initial diagnosis with **CD15+ and CD30+ cells** is highly specific for **Hodgkin lymphoma**, not T-cell lymphoma. While Hodgkin lymphoma has various subtypes, the CD15+/CD30+ phenotype of Reed-Sternberg cells is the hallmark finding.
- The clinical presentation represents a **new therapy-related myeloid malignancy** rather than transformation of the original lymphoid malignancy.
Question 176: A 45-year-old woman is found to have multiple masses in her liver while performing abdominal ultrasonography for recurrent right upper quadrant abdominal pain. Biopsy of one of the masses discloses large plates of adenoma cells, which are larger than normal hepatocytes and contain glycogen and lipid. Regular septa, portal tracts, and bile ductules are absent. Which of the following is associated with this patient's condition?
A. Polyvinyl chloride
B. Smoking
C. Carbon tetrachloride
D. Oral contraceptive pills (Correct Answer)
E. Aflatoxin
Explanation: ***Oral contraceptive pills***
- The description of **large plates of adenoma cells** containing **glycogen and lipid**, along with the absence of normal liver architecture (septa, portal tracts, bile ductules), points to a **hepatic adenoma**.
- **Hepatic adenomas** are strongly associated with **oral contraceptive pill (OCP)** use, especially in women aged 35-50.
*Polyvinyl chloride*
- Exposure to **polyvinyl chloride (PVC)** is mainly linked to **angiosarcoma of the liver**, a rare and aggressive vascular tumor, not hepatic adenomas.
- PVC exposure is typically found in occupational settings, which is not mentioned in this patient's history.
*Smoking*
- **Smoking** is a risk factor for various cancers, including hepatocellular carcinoma (HCC), but it is **not directly associated** with the development of **hepatic adenomas**.
- While smoking can contribute to overall disease burden, it does not fit the specific liver tumor characteristics described.
*Carbon tetrachloride*
- Exposure to **carbon tetrachloride** is known to cause severe **hepatotoxicity**, leading to centrolobular necrosis and potentially cirrhosis.
- It is an industrial solvent and is not primarily linked to the formation of **hepatic adenomas**.
*Aflatoxin*
- **Aflatoxin** exposure, primarily from contaminated food products (e.g., peanuts, corn), is a well-established risk factor for **hepatocellular carcinoma (HCC)**, especially in endemic areas.
- It is not associated with the development of benign **hepatic adenomas**, which have different histopathological features and risk factors.
Question 177: A 21-year-old female presents to the family physician with 3 weeks of headaches, sweating, and palpitations. Her BP was 160/125 mmHg, and a 24-hour urine test revealed elevated vanillylmandelic acid (VMA) and normetanephrine. Past medical history is notable for bilateral retinal hemangioblastomas, and family history is significant for three generations (patient, mother, and maternal grandfather) with similar symptoms. Genetic analysis revealed a mutation of a gene on chromosome 3p. Which of the following is the patient at risk of developing?
A. Osteosarcoma
B. Breast cancer
C. Retinoblastoma
D. Clear cell renal cell carcinoma (Correct Answer)
E. Ovarian cancer
Explanation: ***Clear cell renal cell carcinoma***
- The patient's symptoms (headaches, sweating, palpitations, hypertension) along with elevated **VMA** and **normetanephrine** suggest a **pheochromocytoma**.
- The combination of **bilateral retinal hemangioblastomas**, a family history of similar symptoms across generations, and a **mutation on chromosome 3p** points to **Von Hippel-Lindau (VHL) disease**. Individuals with VHL are at a high risk of developing **clear cell renal cell carcinoma**.
*Osteosarcoma*
- Osteosarcoma is a primary malignant bone tumor, not typically associated with VHL disease.
- Its risk factors include genetic conditions like **Li-Fraumeni syndrome** and **hereditary retinoblastoma**, which do not match the clinical presentation.
*Breast cancer*
- Breast cancer is a common malignancy but is not directly linked to VHL disease.
- Genetic predispositions for breast cancer include mutations in **BRCA1** and **BRCA2** genes, which are different from the VHL gene.
*Retinoblastoma*
- Retinoblastoma is a childhood eye cancer caused by mutations in the **RB1 gene** on **chromosome 13q14**.
- While this patient has retinal hemangioblastomas, these are distinct from retinoblastoma and are characteristic of VHL disease.
*Ovarian cancer*
- Ovarian cancer is a gynecological malignancy, and its common genetic associations include **BRCA1** and **BRCA2** mutations.
- It is not a known component tumor type of VHL syndrome.
Question 178: A 50-year-old woman presents to the outpatient clinic because of a swollen and enlarged right breast. Clinical examination shows no evidence of mass or axillary lymphadenopathy. There is no history of trauma or inflammation. Her past medical and surgical history is positive for breast augmentation with a textured implant 15 years ago. Magnetic resonance imaging (MRI) shows an accumulation of fluid around the right breast implant with intact implant integrity. Which of the following is the most appropriate next step in the management?
A. Chemotherapy
B. Mastectomy
C. Surgical replacement of textured implant with a smooth implant
D. Mammogram
E. Cytological analysis for CD30 and ALK (Correct Answer)
Explanation: ***Cytological analysis for CD30 and ALK***
- The presentation of a **swollen and enlarged breast** with an **accumulation of fluid around a textured breast implant**, particularly 15 years after implantation, is highly suggestive of **Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL)**.
- **Cytological analysis of the periprosthetic fluid** for **CD30** (a surface marker expressed by BIA-ALCL cells) and **ALK** (typically negative in BIA-ALCL) is crucial for diagnosis.
*Chemotherapy*
- This is a treatment, not a diagnostic step, and is not the initial appropriate action for a suspected periprosthetic fluid accumulation without a definitive diagnosis.
- The specific type of chemotherapy would also depend on the confirmed diagnosis and staging of the lymphoma, if present.
*Mastectomy*
- While mastectomy might be part of the treatment for advanced BIA-ALCL, it is an aggressive surgical intervention and not the initial diagnostic step in this scenario.
- A definitive diagnosis is required before considering such a radical procedure.
*Surgical replacement of textured implant with a smooth implant*
- This option addresses the implant itself but does not diagnose or treat the underlying cause of the fluid accumulation, especially if it is indeed BIA-ALCL.
- Surgical intervention might be part of the treatment, but only after a diagnosis is confirmed.
*Mammogram*
- A mammogram is primarily used to detect breast masses and calcifications indicative of breast cancer, not typically for evaluating periprosthetic fluid or lymphoma.
- While imaging is useful, an MRI has already been performed, and the key diagnostic step now is to analyze the fluid.
Question 179: A 55-year-old woman presents with symptoms of rectal bleeding and pruritus in the perianal region. She works as a real estate agent and has a history of gastroesophageal reflux disease (GERD). On physical examination, her spleen and liver are enlarged. A blood smear reveals teardrop red blood cells (RBCs), and a leucoerythroblastic picture with the presence of nucleated RBC precursors and immature myeloid cells. A complete blood count shows a normocytic anemia. The physician explains that her condition is due to a JAK2 mutation in one of her chromosomes. What is a characteristic bone marrow aspirate of this condition?
A. Hypocellular bone marrow
B. Hypercellular with numerous abnormal megakaryocytes (Correct Answer)
C. Hypercellular bone marrow with fibrosis in later stages
D. Ringed sideroblasts and < 20% of myeloblasts
E. Fibrous tissue with sclerotic spicules in later stages
Explanation: ***Hypercellular with numerous abnormal megakaryocytes***
- **Primary myelofibrosis (PMF)**, driven by a **JAK2 mutation**, presents with characteristic bone marrow findings that evolve over time.
- In the **early (prefibrotic) phase**, bone marrow aspirate shows **hypercellularity** with increased proliferation of all three myeloid lineages.
- The hallmark feature is the presence of **abnormal, dysplastic megakaryocytes** which are enlarged, hyperchromatic, with cloud-like or irregularly lobulated nuclei, often appearing in clusters.
- These megakaryocytes are key to the diagnosis and are visible on aspirate in early disease before significant fibrosis develops.
*Hypocellular bone marrow*
- This is characteristic of **aplastic anemia** or hypoplastic myelodysplastic syndromes, not PMF.
- PMF is a **myeloproliferative neoplasm** characterized by increased hematopoietic cell proliferation, resulting in hypercellularity.
*Hypercellular bone marrow with fibrosis in later stages*
- While PMF does progress to **reticulin and collagen fibrosis** in later stages, this option combines features from different disease phases.
- The question asks for characteristic aspirate findings, and **fibrosis makes aspiration difficult** (often resulting in a "dry tap").
- Early aspirate shows hypercellularity with megakaryocyte abnormalities before extensive fibrosis develops.
*Ringed sideroblasts and < 20% of myeloblasts*
- This description is characteristic of **myelodysplastic syndromes (MDS)**, specifically MDS with ring sideroblasts.
- Ringed sideroblasts are not a feature of PMF, and the clinical presentation with **teardrop RBCs, marked splenomegaly, and JAK2 mutation** points to PMF, not MDS.
*Fibrous tissue with sclerotic spicules in later stages*
- **Reticulin and collagen fibrosis** is indeed a hallmark of PMF, but this develops in **later stages** of the disease.
- In advanced PMF, the bone marrow shows extensive fibrosis with osteosclerosis, making aspiration nearly impossible ("dry tap").
- The characteristic aspirate findings refer to the **early phase** when aspiration is still possible and shows the hypercellular, megakaryocyte-rich picture.
Question 180: A 10-year-old boy who recently immigrated to the United States from Africa with his family is brought to the emergency department by his mother for a progressively worsening ulcerative lesion on his jaw. His mother reports that her son’s right jaw has rapidly enlarged over the past few months. He says that it is very tender though he doesn’t recall any trauma to the site. In addition, the mother says her son hasn’t been himself the past few months with intermittent fever, weakness, and fatigue. Physical exam reveals a large, ulcerating right jaw mass that is draining serous fluid and painless cervical and axillary lymphadenopathy. Laboratory results are notable for an elevated serum lactate dehydrogenase. A biopsy of the right jaw mass is shown in the photograph. Which of the following chromosomal translocations is most likely to be found in this patient’s lesion?
A. t(11;14)
B. t(15;17)
C. t(8;14) (Correct Answer)
D. t(9;22)
E. t(14;18)
Explanation: ***t(8;14)***
- The clinical presentation, including a rapidly enlarging jaw mass in an African child, systemic symptoms (fever, weakness, fatigue), and elevated LDH, is highly suggestive of **endemic Burkitt lymphoma**.
- **Burkitt lymphoma** is characterized by the **t(8;14) translocation**, which leads to the overexpression of the *MYC* oncogene.
- The biopsy typically shows a "**starry sky**" pattern due to tingible body macrophages scattered among sheets of rapidly proliferating lymphocytes with a very high mitotic index (Ki-67 approaching 100%).
*t(11;14)*
- This translocation is associated with **Mantle Cell Lymphoma**, which typically affects older adults and presents with generalized lymphadenopathy, splenomegaly, and bone marrow involvement, not primarily a jaw mass in a child.
- Mantle Cell Lymphoma is characterized by the overexpression of **cyclin D1**, driven by this translocation.
*t(15;17)*
- This translocation is characteristic of **Acute Promyelocytic Leukemia (APL)**, a subtype of acute myeloid leukemia, which presents with symptoms of bone marrow failure (bleeding, infection, anemia) and **DIC risk** rather than a solid jaw mass.
- APL shows abnormal promyelocytes with numerous Auer rods and responds to **all-trans retinoic acid (ATRA)** therapy.
*t(9;22)*
- This translocation, also known as the **Philadelphia chromosome**, is characteristic of **Chronic Myeloid Leukemia (CML)** and some cases of acute lymphoblastic leukemia (ALL). CML typically presents with splenomegaly, leukocytosis, and constitutional symptoms, while ALL presents with bone marrow failure, neither of which aligns with this patient's jaw mass.
- The t(9;22) translocation results in the **BCR-ABL fusion gene**, a constitutively active tyrosine kinase targeted by **imatinib** therapy.
*t(14;18)*
- This translocation is characteristic of **Follicular Lymphoma**, which commonly presents as painless generalized lymphadenopathy in older adults. It is rarely seen in children and does not typically present as a rapidly growing jaw mass.
- Follicular lymphoma involves overexpression of the **Bcl-2 anti-apoptotic protein**, promoting cell survival and resulting in an indolent clinical course.
