A 57-year-old post-menopausal woman comes to the physician because of intermittent, bloody post-coital vaginal discharge for the past month. She does not have pain with intercourse. Eleven years ago, she had LSIL on a routine Pap smear and testing for high-risk HPV strains was positive. Colposcopy showed CIN 1. She has not returned for follow-up Pap smears since then. She is sexually active with her husband only, and they do not use condoms. She has smoked half a pack of cigarettes per day for the past 25 years and does not drink alcohol. On speculum exam, a 1.4 cm, erythematous exophytic mass with ulceration is noted on the posterior wall of the upper third of the vagina. Which of the following is the most probable histopathology of this mass?
Q282
A 55-year-old man comes to the physician because of fatigue and worsening abdominal pain for 4 weeks. He also reports excessive night sweats and a 5.4-kg (12-lb) weight loss during this time. He has a neck swelling for 4 days. Physical examination shows a nontender, enlarged, and fixed supraclavicular lymph node. There is splenomegaly. A CT scan of the thorax and abdomen shows massively enlarged axillary, mediastinal, and cervical lymph nodes. Analysis of an excised cervical lymph node shows lymphocytes with a high proliferative index that stain positive for CD20. Which of the following is the most likely diagnosis?
Q283
A 52-year-old woman comes to the physician because of a 6-month history of generalized fatigue, low-grade fever, and a 10-kg (22-lb) weight loss. Physical examination shows generalized pallor and splenomegaly. Her hemoglobin concentration is 7.5 g/dL and leukocyte count is 41,800/mm3. Leukocyte alkaline phosphatase activity is low. Peripheral blood smear shows basophilia with myelocytes and metamyelocytes. Bone marrow biopsy shows cellular hyperplasia with proliferation of immature granulocytic cells. Which of the following mechanisms is most likely responsible for this patient's condition?
Neoplasia US Medical PG Practice Questions and MCQs
Question 281: A 57-year-old post-menopausal woman comes to the physician because of intermittent, bloody post-coital vaginal discharge for the past month. She does not have pain with intercourse. Eleven years ago, she had LSIL on a routine Pap smear and testing for high-risk HPV strains was positive. Colposcopy showed CIN 1. She has not returned for follow-up Pap smears since then. She is sexually active with her husband only, and they do not use condoms. She has smoked half a pack of cigarettes per day for the past 25 years and does not drink alcohol. On speculum exam, a 1.4 cm, erythematous exophytic mass with ulceration is noted on the posterior wall of the upper third of the vagina. Which of the following is the most probable histopathology of this mass?
A. Basal cell carcinoma
B. Melanoma
C. Adenocarcinoma
D. Sarcoma botryoides
E. Squamous cell carcinoma (Correct Answer)
Explanation: ***Squamous cell carcinoma***
- The patient's history of **LSIL** with **high-risk HPV** and **non-adherence to follow-up Pap smears** strongly suggests a progression to squamous cell carcinoma.
- **Smoking** is a significant risk factor for SCC, and the description of an **erythematous exophytic mass with ulceration** is consistent with this diagnosis.
*Basal cell carcinoma*
- This is a common skin cancer, but it is **extremely rare in the vagina**, typically occurring in sun-exposed areas.
- While it can manifest as an ulcerated lesion, the risk factors and location do not align with this patient's presentation.
*Melanoma*
- Although **vaginal melanoma** can occur, it is rare and typically presents as a **pigmented lesion**, which is not described.
- The patient's risk factors (HPV, smoking) are not primary drivers of melanoma development.
*Adenocarcinoma*
- **Vaginal adenocarcinoma** is rare and often associated with **diethylstilbestrol (DES) exposure** in utero, which is absent in this case.
- While an exophytic mass can occur, the strong history of **HPV-related dysplasia** points away from adenocarcinoma.
*Sarcoma botryoides*
- This is a rare form of **rhabdomyosarcoma** and typically presents in **infants and young children** as a grapelike mass protruding from the vagina.
- It is not seen in post-menopausal women and is histologically distinct from the likely HPV-related malignancy.
Question 282: A 55-year-old man comes to the physician because of fatigue and worsening abdominal pain for 4 weeks. He also reports excessive night sweats and a 5.4-kg (12-lb) weight loss during this time. He has a neck swelling for 4 days. Physical examination shows a nontender, enlarged, and fixed supraclavicular lymph node. There is splenomegaly. A CT scan of the thorax and abdomen shows massively enlarged axillary, mediastinal, and cervical lymph nodes. Analysis of an excised cervical lymph node shows lymphocytes with a high proliferative index that stain positive for CD20. Which of the following is the most likely diagnosis?
A. Hodgkin lymphoma
B. Burkitt lymphoma
C. Follicular lymphoma
D. Adult T-cell lymphoma
E. Diffuse large B-cell lymphoma (Correct Answer)
Explanation: ***Diffuse large B-cell lymphoma***
- The patient presents with rapidly progressing **B symptoms** (night sweats, weight loss, fatigue), widespread **lymphadenopathy** (cervical, axillary, mediastinal, supraclavicular), and **splenomegaly**.
- A lymph node biopsy showing **CD20 positivity** and a **high proliferative index** in lymphocytes is characteristic of Diffuse Large B-cell Lymphoma (DLBCL), a rapidly growing, aggressive non-Hodgkin lymphoma.
*Hodgkin lymphoma*
- While it can present with B symptoms and lymphadenopathy, Hodgkin lymphoma is characterized by the presence of **Reed-Sternberg cells** on biopsy.
- The description of lymphocytes with a high proliferative index staining positive for CD20 points away from Hodgkin lymphoma.
*Burkitt lymphoma*
- Recognized by its characteristic **starry-sky appearance** on microscopy and a **translocation of the _MYC_ gene** on biopsy (often t(8;14)).
- Though highly aggressive with a high proliferative index, it typically presents differently, often with extranodal involvement (e.g., jaw in endemic forms, ileocecal region in sporadic forms).
*Follicular lymphoma*
- This is an **indolent (slow-growing) non-Hodgkin lymphoma** that typically presents with waxing and waning lymphadenopathy and usually lacks prominent aggressive B symptoms.
- The rapid progression of symptoms and high proliferative index are inconsistent with follicular lymphoma.
*Adult T-cell lymphoma*
- Caused by HTLV-1 infection and characterized by **CD4+ T-cell proliferation**. It primarily affects skin, lymph nodes, liver, and spleen, and can cause hypercalcemia.
- The biopsy showing **CD20 positivity** (a B-cell marker) rules out this diagnosis, which would typically show T-cell markers.
Question 283: A 52-year-old woman comes to the physician because of a 6-month history of generalized fatigue, low-grade fever, and a 10-kg (22-lb) weight loss. Physical examination shows generalized pallor and splenomegaly. Her hemoglobin concentration is 7.5 g/dL and leukocyte count is 41,800/mm3. Leukocyte alkaline phosphatase activity is low. Peripheral blood smear shows basophilia with myelocytes and metamyelocytes. Bone marrow biopsy shows cellular hyperplasia with proliferation of immature granulocytic cells. Which of the following mechanisms is most likely responsible for this patient's condition?
A. Cytokine-independent activation of the JAK-STAT pathway
B. Unregulated expression of the ABL1 gene (Correct Answer)
C. Loss of function of the APC gene
D. Overexpression of the c-KIT gene
E. Altered expression of the retinoic acid receptor gene
Explanation: ***Unregulated expression of the ABL1 gene***
- This patient's presentation with **fatigue, weight loss, splenomegaly, elevated white blood cell count (41,800/mm³)**, **basophilia, myelocytes, and metamyelocytes** on peripheral smear, and **low leukocyte alkaline phosphatase (LAP) activity** is highly characteristic of **chronic myeloid leukemia (CML)**.
- CML is defined by the **Philadelphia chromosome (Ph chromosome)**, which results from a **t(9;22) translocation** and leads to the formation of the **BCR-ABL1 fusion gene**. This gene encodes a **constitutively active tyrosine kinase** that leads to unregulated cell proliferation.
*Cytokine-independent activation of the JAK-STAT pathway*
- This mechanism is characteristic of other **myeloproliferative neoplasms (MPNs)**, such as **polycythemia vera**, **essential thrombocythemia**, and **primary myelofibrosis**.
- These conditions often involve mutations in genes like **JAK2** (e.g., V617F), leading to cytokine-independent signaling, but their clinical and hematologic features differ from CML.
*Loss of function of the APC gene*
- Loss of function of the **adenomatous polyposis coli (APC) gene** is primarily associated with **familial adenomatous polyposis (FAP)** and a significant proportion of **sporadic colorectal cancers**.
- It plays a crucial role in the **Wnt signaling pathway** and cell adhesion, but it is not directly involved in the pathogenesis of CML.
*Overexpression of the c-KIT gene*
- **Overexpression or activating mutations of the c-KIT gene** (a receptor tyrosine kinase) are associated with conditions like **gastrointestinal stromal tumors (GISTs)** and some forms of **mastocytosis**.
- While it involves a tyrosine kinase, the specific clinical and hematological picture of this patient does not align with disorders driven by c-KIT dysregulation.
*Altered expression of the retinoic acid receptor gene*
- **Altered expression or fusion genes involving the retinoic acid receptor alpha (RARα) gene** (e.g., PML-RARα fusion) are pathognomonic for **acute promyelocytic leukemia (APL)**.
- APL presents as an **acute leukemia** with a predominance of abnormal promyelocytes and is associated with a high risk of **disseminated intravascular coagulation (DIC)**, which is distinct from the chronic myeloproliferative disorder described.
