A research team develops a new monoclonal antibody checkpoint inhibitor for advanced melanoma that has shown promise in animal studies as well as high efficacy and low toxicity in early phase human clinical trials. The research team would now like to compare this drug to existing standard of care immunotherapy for advanced melanoma. The research team decides to conduct a non-randomized study where the novel drug will be offered to patients who are deemed to be at risk for toxicity with the current standard of care immunotherapy, while patients without such risk factors will receive the standard treatment. Which of the following best describes the level of evidence that this study can offer?
Q2
A 49-year-old male presents to his primary care physician for the first time in twelve years. His chief complaint is a new onset of diarrhea, which nothing seems to improve. He first noticed this diarrhea about a month ago. He complains of greasy stools, which leave a residue in his toilet bowl. Review of systems is notable for alcohol consumption of 12-16 cans of beer per day for the last two decades. Additionally, the patient endorses losing 12 lbs unintentionally over the last month. Vital signs are within normal limits and stable. Exam demonstrates a male who appears older than stated age; abdominal exam is notable for epigastric tenderness to palpation. What is the next step in diagnosis?
Q3
A 58-year-old male undergoes a surveillance colonoscopy in which a 2 cm adenoma is identified and removed. Had this adenoma not been excised, the patient would have been at risk of progression to carcinoma. Which of the following is the final mutational step in the progression from adenoma to carcinoma?
Q4
A 5-year-old African-American boy is brought to the physician because of fatigue and night sweats for the past month. During this time, he has also lost 3 kg (6.6 lbs). Before the onset of symptoms, he had been healthy except for a febrile seizure as an infant. His brother had chickenpox 2 months ago. He is at the 75th percentile for height and 50th percentile for weight. He appears markedly fatigued. His temperature is 38°C (100.4°F), pulse is 95/min, respirations are 19/min, and blood pressure is 100/60 mm Hg. Lung and cardiac examination is normal. There are enlarged, nontender lymph nodes bilaterally in the neck. The abdomen is soft and nontender. A complete blood count shows:
Leukocyte count 8,000/mm³
Hemoglobin 9.1 g/dL
Hematocrit 26.9%
Platelet count 34,000/mm³
Serum
Na+ 135 mEq/L
K+ 4.5 mEq/L
Cl- 101 mEq/L
HCO3- 27 mEq/L
Urea nitrogen 9 mg/dL
Creatinine 0.7 mg/dL
Ca2+ 8.8 mg/dL
PCR testing demonstrates a 9:22 chromosomal translocation. The patient is diagnosed with Philadelphia chromosome-positive acute lymphoblastic leukemia. Which of the following is the most appropriate targeted therapy component?
Q5
A 43-year-old woman presents to your clinic for the evaluation of an abnormal skin lesion on her forearm. The patient is worried because her mother passed away from melanoma. You believe that the lesion warrants biopsy for further evaluation for possible melanoma. Your patient is concerned about her risk for malignant disease. What is the most important prognostic factor of melanoma?
Q6
A 40-year-old man presents with an episode of rectal bleeding. He is concerned because his mother died of colorectal cancer at 50 years of age. He has no further information about his family history. Physical examination and digital rectal examination are normal. He undergoes a colonoscopy and is found to have innumerable adenomas in the left side of the colon ranging in size from 4–15 mm. Which of the following is the most likely underlying mechanism of this patient illness?
Q7
A pathologist receives a patient sample for analysis. Cells in the sample are first labeled with fluorescent antibodies and then passed across a laser beam in a single file of particles. The light scatter and fluorescent intensity of the particles are plotted on a graph; this information is used to characterize the sample. This laboratory method would be most useful to establish the diagnosis of a patient with which of the following?
Q8
A 51-year-old woman comes to the physician because of a persistent cough and a 5-kg (11-lb) weight loss over the past 2 months. Yesterday, she coughed up bloody sputum. She does not smoke. Pulmonary examination shows decreased breath sounds over the right upper lobe. A CT scan of the chest shows a mass in the periphery of the right upper lobe. Histopathologic examination of a specimen obtained on CT-guided biopsy shows glandular cells with papillary components and signet ring cells that stain positive for mucin. An alteration in which of the following genes is most likely to have occurred in this patient?
Q9
An investigator studying targeted therapy in patients with gastrointestinal stromal tumors requires a reliable test to determine the spatial distribution of CD117-positive cells in biopsy specimens. Which of the following is the most appropriate test?
Q10
A 75-year-old man comes to his primary care physician because he has been having diarrhea and difficulty breathing. The diarrhea has been intermittent with frequent watery stools that occur along with abdominal cramps. Furthermore, the skin on his face and upper chest feels hot and changes color in episodes lasting from a few minutes to hours. Finally, the patient complains of loss of appetite and says that he has unexpectedly lost 20 pounds over the last two months. Based on clinical suspicion, magnetic resonance imaging is obtained showing a small mass in this patient's lungs. Which of the following is associated with the most likely cause of this patient's symptoms?
Gastrointestinal stromal tumors US Medical PG Practice Questions and MCQs
Question 1: A research team develops a new monoclonal antibody checkpoint inhibitor for advanced melanoma that has shown promise in animal studies as well as high efficacy and low toxicity in early phase human clinical trials. The research team would now like to compare this drug to existing standard of care immunotherapy for advanced melanoma. The research team decides to conduct a non-randomized study where the novel drug will be offered to patients who are deemed to be at risk for toxicity with the current standard of care immunotherapy, while patients without such risk factors will receive the standard treatment. Which of the following best describes the level of evidence that this study can offer?
A. Level 1
B. Level 3 (Correct Answer)
C. Level 5
D. Level 4
E. Level 2
Explanation: ***Level 3***
- A **non-randomized controlled trial** like the one described, where patient assignment to treatment groups is based on specific characteristics (risk of toxicity), falls into Level 3 evidence.
- This level typically includes **non-randomized controlled trials** and **well-designed cohort studies** with comparison groups, which are prone to selection bias and confounding.
- The study compares two treatments but lacks randomization, making it Level 3 evidence.
*Level 1*
- Level 1 evidence is the **highest level of evidence**, derived from **systematic reviews and meta-analyses** of multiple well-designed randomized controlled trials or large, high-quality randomized controlled trials.
- The described study is explicitly stated as non-randomized, ruling out Level 1.
*Level 2*
- Level 2 evidence involves at least one **well-designed randomized controlled trial** (RCT) or **systematic reviews** of randomized trials.
- The current study is *non-randomized*, which means it cannot be classified as Level 2 evidence, as randomization is a key criterion for this level.
*Level 4*
- Level 4 evidence includes **case series**, **case-control studies**, and **poorly designed cohort or case-control studies**.
- While the study is non-randomized, it is a controlled comparative trial rather than a case series or retrospective case-control study, placing it at Level 3.
*Level 5*
- Level 5 evidence is the **lowest level of evidence**, typically consisting of **expert opinion** without explicit critical appraisal, or based on physiology, bench research, or animal studies.
- While the drug was initially tested in animal studies, the current human comparative study offers a higher level of evidence than expert opinion or preclinical data.
Question 2: A 49-year-old male presents to his primary care physician for the first time in twelve years. His chief complaint is a new onset of diarrhea, which nothing seems to improve. He first noticed this diarrhea about a month ago. He complains of greasy stools, which leave a residue in his toilet bowl. Review of systems is notable for alcohol consumption of 12-16 cans of beer per day for the last two decades. Additionally, the patient endorses losing 12 lbs unintentionally over the last month. Vital signs are within normal limits and stable. Exam demonstrates a male who appears older than stated age; abdominal exam is notable for epigastric tenderness to palpation. What is the next step in diagnosis?
A. Endoscopic retrograde cholangiopancreatography (ERCP)
B. Somatostatin receptor scintigraphy
C. d-Xylose absorption test
D. CT abdomen with IV contrast (Correct Answer)
E. EGD with biopsy of gastric mucosa
Explanation: ***CT abdomen with IV contrast***
- Given the patient's history of **heavy chronic alcohol intake**, **weight loss**, **new-onset diarrhea**, **greasy stools (steatorrhea)**, and **epigastric tenderness**, **chronic pancreatitis** with **exocrine pancreatic insufficiency** is highly suspected.
- A **CT scan of the abdomen with IV contrast** is the initial diagnostic test of choice to evaluate the pancreas for changes consistent with chronic pancreatitis, such as **calcifications**, **ductal dilation**, or **atrophy**, and also to rule out other causes like pancreatic tumors.
*Endoscopic retrograde cholangiopancreatography (ERCP)*
- **ERCP** is an **invasive procedure** primarily used therapeutically for conditions like **bile duct stones** or **strictures**, or sometimes for detailed pancreatic duct imaging.
- It is generally **not the first-line diagnostic test** for suspected chronic pancreatitis due to its invasive nature and risk of complications like pancreatitis.
*Somatostatin receptor scintigraphy*
- This imaging technique is primarily used to detect **neuroendocrine tumors (NETs)**, particularly those that express somatostatin receptors.
- While diarrhea can be a symptom of certain NETs (e.g., **VIPoma**), the patient's strong history of chronic alcohol abuse and steatorrhea points more directly to pancreatic exocrine insufficiency, making a CT scan a more appropriate initial investigation.
*d-Xylose absorption test*
- The **d-xylose absorption test** is used to assess **small bowel mucosal function** and differentiate between primary mucosal disease and pancreatic insufficiency as causes of malabsorption.
- In this case, with strong indicators for pancreatic dysfunction (greasy stools, chronic alcohol use), directly evaluating the pancreas via imaging is a more targeted next step.
*EGD with biopsy of gastric mucosa*
- **Esophagogastroduodenoscopy (EGD)** with biopsy is indicated for evaluating upper gastrointestinal symptoms, such as **dysphagia**, **gastric ulcers**, or **celiac disease**.
- While it could evaluate for celiac disease, the patient's history of heavy alcohol use and greasy stools makes **pancreatic insufficiency** a more probable cause of malabsorption, and EGD would not directly assess pancreatic function or structure.
Question 3: A 58-year-old male undergoes a surveillance colonoscopy in which a 2 cm adenoma is identified and removed. Had this adenoma not been excised, the patient would have been at risk of progression to carcinoma. Which of the following is the final mutational step in the progression from adenoma to carcinoma?
A. p53 inactivation (Correct Answer)
B. APC mutation
C. COX-2 overexpression
D. SMAD 2/4 loss
E. K-ras mutation
Explanation: ***p53 inactivation***
- **p53 loss of function** is typically the final genetic event in the **adenoma-to-carcinoma sequence**, facilitating unrestricted cell growth and preventing apoptosis in dysplastic cells.
- The **p53 tumor suppressor gene** normally checkpoints cell division and induces programmed cell death, making its inactivation critical for malignant transformation.
*APC mutation*
- **APC (adenomatous polyposis coli) mutation** is often the **initiating event** in colorectal adenoma formation, leading to aberrant crypt foci and polyp formation.
- While critical for early tumor genesis, it does not represent the final step in progression to invasive carcinoma.
*COX-2 overexpression*
- **Cyclooxygenase-2 (COX-2) overexpression** leads to increased prostaglandin production, which can promote cell proliferation, angiogenesis, and inhibit apoptosis.
- It is an important factor in tumor growth and progression but occurs earlier in the sequence and is not the terminal mutational step for carcinoma.
*SMAD 2/4 loss*
- **SMAD 2/4 loss of function** disrupts the **TGF-β signaling pathway**, which normally inhibits cell growth and promotes differentiation.
- This event typically occurs in the late adenoma stage, contributing to dysplasia, but **p53 inactivation** is considered the final critical step for full malignant transformation.
*K-ras mutation*
- **K-ras mutation** is a well-known event in the **adenoma-to-carcinoma sequence**, occurring earlier than p53 inactivation, usually in intermediate-sized adenomas.
- It leads to constitutive activation of the RAS/MAPK pathway, promoting cell growth and survival, but generally before full malignant transformation.
Question 4: A 5-year-old African-American boy is brought to the physician because of fatigue and night sweats for the past month. During this time, he has also lost 3 kg (6.6 lbs). Before the onset of symptoms, he had been healthy except for a febrile seizure as an infant. His brother had chickenpox 2 months ago. He is at the 75th percentile for height and 50th percentile for weight. He appears markedly fatigued. His temperature is 38°C (100.4°F), pulse is 95/min, respirations are 19/min, and blood pressure is 100/60 mm Hg. Lung and cardiac examination is normal. There are enlarged, nontender lymph nodes bilaterally in the neck. The abdomen is soft and nontender. A complete blood count shows:
Leukocyte count 8,000/mm³
Hemoglobin 9.1 g/dL
Hematocrit 26.9%
Platelet count 34,000/mm³
Serum
Na+ 135 mEq/L
K+ 4.5 mEq/L
Cl- 101 mEq/L
HCO3- 27 mEq/L
Urea nitrogen 9 mg/dL
Creatinine 0.7 mg/dL
Ca2+ 8.8 mg/dL
PCR testing demonstrates a 9:22 chromosomal translocation. The patient is diagnosed with Philadelphia chromosome-positive acute lymphoblastic leukemia. Which of the following is the most appropriate targeted therapy component?
A. Cladribine
B. Imatinib (Correct Answer)
C. Hydroxyurea
D. All-trans retinoic acid
E. Transfuse platelets
Explanation: ***Imatinib***
- The patient has **Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL)**, indicated by the **9:22 chromosomal translocation** (BCR-ABL fusion gene).
- **Imatinib** is a tyrosine kinase inhibitor (TKI) that specifically targets the **BCR-ABL fusion protein**, making it the most appropriate targeted therapy for Ph+ ALL.
*Cladribine*
- **Cladribine** is a purine analog primarily used in the treatment of **hairy cell leukemia** and some forms of lymphoma.
- It is not a targeted therapy for the **BCR-ABL fusion gene** in Ph+ ALL.
*Hydroxyurea*
- **Hydroxyurea** is a myelosuppressive agent used to rapidly lower high blood counts in conditions like **chronic myeloid leukemia (CML)** or **myeloproliferative neoplasms**.
- It does not target the specific genetic abnormality of Ph+ ALL.
*All-trans retinoic acid*
- **All-trans retinoic acid (ATRA)** is a form of vitamin A used in the treatment of **acute promyelocytic leukemia (APL)**.
- ATRA induces differentiation of promyelocytes and is not effective for Ph+ ALL.
*Transfuse platelets*
- While the patient has **thrombocytopenia** (platelet count 34,000/mm³), **platelet transfusion** is a supportive measure, not a targeted therapy for leukemia.
- It addresses a complication of the disease rather than the underlying oncogenic driver.
Question 5: A 43-year-old woman presents to your clinic for the evaluation of an abnormal skin lesion on her forearm. The patient is worried because her mother passed away from melanoma. You believe that the lesion warrants biopsy for further evaluation for possible melanoma. Your patient is concerned about her risk for malignant disease. What is the most important prognostic factor of melanoma?
A. Depth of invasion of atypical cells (Correct Answer)
B. S-100 tumor marker present
C. Evolution of lesion over time
D. Age at presentation
E. Level of irregularity of the borders
Explanation: ***Depth of invasion of atypical cells***
- The **Breslow depth**, which measures the vertical thickness of the melanoma from the granular layer of the epidermis to the deepest part of the tumor, is the **single most important prognostic factor** for localized melanoma.
- A greater depth of invasion correlates directly with a higher risk of **metastasis** and a poorer prognosis due to increased likelihood of reaching dermal lymphatics or blood vessels.
*S-100 tumor marker present*
- While **S-100 protein** is a marker expressed in melanoma cells and can be used to detect metastatic disease (e.g., in lymph nodes), its mere presence does not serve as the primary prognostic indicator for the primary lesion itself.
- S-100 reflects the presence of melanoma cells but does not provide information about the **depth or biological aggressiveness** of the initial tumor.
*Evolution of lesion over time*
- The **evolution or change** in a lesion (e.g., in size, shape, color, new symptoms) is a crucial diagnostic criterion for identifying suspicious lesions for biopsy.
- While important for diagnosis, it is not a direct prognostic factor once melanoma is confirmed; the **pathological features** after biopsy, particularly depth, determine prognosis.
*Age at presentation*
- **Age** can influence treatment decisions and overall health status, but it is not the most important independent prognostic factor for melanoma.
- Prognosis is primarily driven by tumor-specific characteristics rather than the patient's age.
*Level of irregularity of the borders*
- **Border irregularity** is one of the ABCDE criteria (Asymmetry, Border irregularity, Color variation, Diameter >6mm, Evolving) used to identify suspicious pigmented lesions.
- It is a diagnostic indicator that warrants further investigation but does not independently determine **prognosis** as definitively as the Breslow depth after biopsy.
Question 6: A 40-year-old man presents with an episode of rectal bleeding. He is concerned because his mother died of colorectal cancer at 50 years of age. He has no further information about his family history. Physical examination and digital rectal examination are normal. He undergoes a colonoscopy and is found to have innumerable adenomas in the left side of the colon ranging in size from 4–15 mm. Which of the following is the most likely underlying mechanism of this patient illness?
A. Mutation in DNA mismatch repair genes
B. Inactivation of RB1 gene
C. Alterations in STK11 gene
D. Inactivation of BRCA1 and BRCA2 genes
E. Mutations of the APC gene (Correct Answer)
Explanation: ***Mutations of the APC gene***
- The description of **innumerable adenomas** in the colon, particularly at a relatively young age and with a family history of early-onset colorectal cancer, is highly suggestive of **familial adenomatous polyposis (FAP)**.
- FAP is an autosomal dominant condition caused by germline mutations in the **adenomatous polyposis coli (APC) gene**, a tumor suppressor gene, leading to the development of hundreds to thousands of adenomatous polyps and an almost 100% lifetime risk of colorectal cancer.
*Mutation in DNA mismatch repair genes*
- Mutations in **DNA mismatch repair genes** (e.g., MLH1, MSH2, MSH6, PMS2) are associated with **Lynch syndrome (hereditary nonpolyposis colorectal cancer)**.
- Lynch syndrome typically presents with fewer polyps (though an increased risk of colorectal cancer, especially right-sided) and other extracolonic cancers, which is less consistent with "innumerable adenomas."
*Inactivation of RB1 gene*
- The **RB1 gene** is a tumor suppressor gene primarily associated with **retinoblastoma** and has a role in other cancers like osteosarcoma.
- It is not the primary genetic mechanism for the development of multiple colonic adenomas described in this patient.
*Alterations in STK11 gene*
- Alterations in the **STK11 gene** are associated with **Peutz-Jeghers syndrome**, an autosomal dominant disorder characterized by the development of multiple **hamartomatous polyps** mainly in the gastrointestinal tract, especially the small intestine, and characteristic **mucocutaneous pigmentation**.
- These polyps are hamartomatous, not adenomatous, and while they carry a cancer risk, the presentation of innumerable adenomas points away from Peutz-Jeghers syndrome.
*Inactivation of BRCA1 and BRCA2 genes*
- **BRCA1 and BRCA2 genes** are critical tumor suppressor genes primarily associated with an increased risk of **breast cancer** and **ovarian cancer**, as well as some other cancers like prostate and pancreatic cancer.
- While these genes are important in cancer development, they are not directly implicated in the pathogenesis of familial adenomatous polyposis or the significant number of colonic adenomas described.
Question 7: A pathologist receives a patient sample for analysis. Cells in the sample are first labeled with fluorescent antibodies and then passed across a laser beam in a single file of particles. The light scatter and fluorescent intensity of the particles are plotted on a graph; this information is used to characterize the sample. This laboratory method would be most useful to establish the diagnosis of a patient with which of the following?
A. Ventricular septal defect and facial dysmorphism with low T-lymphocyte count
B. Painless generalized lymphadenopathy with monomorphic cells and interspersed benign histiocytes on histology
C. Pancytopenia and deep vein thrombosis with intermittent hemoglobinuria (Correct Answer)
D. Multiple opportunistic infections with decreased CD4 counts
E. Vesicular lesions with dermatomal distribution and dendritic corneal ulcers
Explanation: ***Pancytopenia and deep vein thrombosis with intermittent hemoglobinuria***
- The described laboratory method is **flow cytometry**, which is the **gold standard for diagnosing paroxysmal nocturnal hemoglobinuria (PNH)** by detecting the absence of **CD55** and **CD59** on red blood cells due to impaired GPI anchor synthesis.
- PNH classically presents with **pancytopenia**, **hemolytic anemia** (leading to hemoglobinuria), and a high risk of **thrombosis** (e.g., deep vein thrombosis).
*Ventricular septal defect and facial dysmorphism with low T-lymphocyte count*
- This clinical picture suggests **DiGeorge syndrome**, which involves a developmental defect of the **third and fourth pharyngeal pouches**, leading to thymic hypoplasia and **T-cell deficiency**.
- While flow cytometry is used to quantify T-lymphocyte subsets (e.g., CD3, CD4, CD8), the primary method for diagnosing DiGeorge syndrome is **fluorescent in situ hybridization (FISH)** for a **22q11 deletion**, making it less ideal for flow cytometry diagnosis.
*Painless generalized lymphadenopathy with monomorphic cells and interspersed benign histiocytes on histology*
- This description with "**monomorphic cells**" is more consistent with certain **non-Hodgkin lymphomas** (e.g., Burkitt lymphoma) rather than Hodgkin lymphoma, which typically shows a **polymorphic** cellular infiltrate.
- While flow cytometry can be useful in characterizing lymphomas by identifying cell surface markers, the diagnosis is primarily established by **lymph node biopsy and histopathology** with **immunohistochemistry**, making flow cytometry a supplementary rather than primary diagnostic tool.
*Multiple opportunistic infections with decreased CD4 counts*
- This presentation is highly suggestive of **HIV infection leading to AIDS**. The "decreased CD4 counts" are a key diagnostic and prognostic marker.
- While flow cytometry is used to **monitor CD4 cell counts** in HIV patients, the initial diagnosis of HIV is established via **antibody/antigen combination tests** and confirmed by **Western blot** or **PCR for viral load**, not by flow cytometry.
*Vesicular lesions with dermatomal distribution and dendritic corneal ulcers*
- This clinical presentation points to **herpes zoster ophthalmicus** (shingles affecting the eye due to **varicella-zoster virus** reactivation).
- Diagnosis is primarily **clinical** based on the characteristic rash and eye findings, although **PCR** of vesicular fluid can confirm VZV infection. Flow cytometry has no role in this diagnosis.
Question 8: A 51-year-old woman comes to the physician because of a persistent cough and a 5-kg (11-lb) weight loss over the past 2 months. Yesterday, she coughed up bloody sputum. She does not smoke. Pulmonary examination shows decreased breath sounds over the right upper lobe. A CT scan of the chest shows a mass in the periphery of the right upper lobe. Histopathologic examination of a specimen obtained on CT-guided biopsy shows glandular cells with papillary components and signet ring cells that stain positive for mucin. An alteration in which of the following genes is most likely to have occurred in this patient?
A. TP53
B. SMAD4 (DPC4)
C. APC
D. MYCL1
E. ALK (Correct Answer)
Explanation: ***ALK***
- The patient's presentation with **adenocarcinoma** (glandular cells, mucin, peripheral location) in a **non-smoker** suggests a higher likelihood of specific driver mutations, such as **ALK rearrangements**.
- **ALK gene rearrangements** are characteristic oncogenic drivers in a subset of lung adenocarcinomas, particularly in younger patients and non-smokers.
*TP53*
- **TP53** is a tumor suppressor gene frequently mutated in many cancers, including lung cancer, but its mutation is not as specific to the clinical and histopathological findings of this patient's adenocarcinoma presenting in a non-smoker.
- While common in lung cancer overall, **TP53 mutations** are more strongly associated with squamous cell carcinoma or small cell lung cancer, or with smoking-related adenocarcinoma.
*SMAD4 (DPC4)*
- **SMAD4** is a tumor suppressor gene primarily associated with **pancreatic cancer** and **colorectal cancer**, playing a key role in the TGF-β signaling pathway.
- Its mutation is not a common or characteristic driver in lung adenocarcinoma, especially with the features described.
*APC*
- The **APC gene** is a tumor suppressor gene centrally involved in the **Wnt signaling pathway** and is primarily associated with **colorectal cancer**, particularly **familial adenomatous polyposis**.
- APC mutations are not typically found as primary drivers in lung adenocarcinoma.
*MYCL1*
- **MYCL1 (L-MYC)** is an oncogene belonging to the MYC family, implicated in cell proliferation and apoptosis.
- While MYC family genes can be amplified in various cancers, **MYCL1 amplification** is more characteristic of **small cell lung cancer**, not adenocarcinoma, and does not align with the glandular and papillary features described.
Question 9: An investigator studying targeted therapy in patients with gastrointestinal stromal tumors requires a reliable test to determine the spatial distribution of CD117-positive cells in biopsy specimens. Which of the following is the most appropriate test?
A. Northern blot
B. Immunohistochemistry (Correct Answer)
C. Flow cytometry
D. Fluorescence in-situ hybridization
E. Western blot
Explanation: ***Immunohistochemistry***
- **Immunohistochemistry (IHC)** uses **antibodies** to target specific antigens (like **CD117**) within tissue sections, allowing for **visualization of their spatial distribution** under a microscope.
- This technique is ideal for identifying the precise location and quantity of **CD117-positive cells** within a biopsy, which is crucial for assessing targeted therapy in gastrointestinal stromal tumors.
*Northern blot*
- **Northern blot** is used to detect and quantify specific **RNA** sequences in a sample.
- It does not provide information about **protein expression** or the **spatial distribution of cells** within tissue.
*Flow cytometry*
- **Flow cytometry** is used for analyzing and sorting cells based on their **surface or intracellular markers** by passing them in a fluid stream through laser light.
- While it can quantify **CD117-positive cells**, it requires cells to be in suspension and thus **destroys the tissue architecture**, preventing analysis of spatial distribution.
*Fluorescence in-situ hybridization*
- **Fluorescence in-situ hybridization (FISH)** uses **fluorescent probes** to detect and locate specific **DNA or RNA sequences** on chromosomes or in cells.
- FISH is primarily used for genetic analysis and **does not directly assess protein expression** or cellular distribution in the context of targeted therapy.
*Western blot*
- **Western blot** is used to detect and quantify specific **proteins** from a sample by separating them by size, but it is performed on **tissue homogenates**.
- This technique provides information on the **total protein content** but **does not preserve the spatial arrangement** of cells within the original tissue.
Question 10: A 75-year-old man comes to his primary care physician because he has been having diarrhea and difficulty breathing. The diarrhea has been intermittent with frequent watery stools that occur along with abdominal cramps. Furthermore, the skin on his face and upper chest feels hot and changes color in episodes lasting from a few minutes to hours. Finally, the patient complains of loss of appetite and says that he has unexpectedly lost 20 pounds over the last two months. Based on clinical suspicion, magnetic resonance imaging is obtained showing a small mass in this patient's lungs. Which of the following is associated with the most likely cause of this patient's symptoms?
A. It also arises in the GI tract (Correct Answer)
B. Stains positive for vimentin
C. Has keratin pearls and intercellular bridges
D. Most common lung cancer in non-smokers and females
E. Contains psammoma bodies
Explanation: ***Correct: It also arises in the GI tract***
- The patient's symptoms (diarrhea, flushing, difficulty breathing, weight loss) are highly suggestive of **carcinoid syndrome**, often caused by a **neuroendocrine tumor (NET)** in the lung or gastrointestinal tract that metastasizes to the liver.
- While a lung mass is identified here, **carcinoid tumors** (a type of NET) most commonly originate in the **gastrointestinal tract** (especially the appendix, small intestine, and rectum), making this option strongly associated with the likely cause.
- Carcinoid syndrome typically occurs when liver metastases allow serotonin and other vasoactive substances to bypass hepatic metabolism and enter systemic circulation.
*Incorrect: Stains positive for vimentin*
- **Vimentin** is an intermediate filament typically found in **mesenchymal cells** and is often positive in sarcomas, lymphomas, and melanomas.
- Neuroendocrine tumors, including carcinoid, typically stain positive for **chromogranin** and **synaptophysin**, not vimentin.
*Incorrect: Has keratin pearls and intercellular bridges*
- **Keratin pearls** and **intercellular bridges** are characteristic histological features of **squamous cell carcinoma**, which is a type of non-small cell lung cancer.
- While the patient has a lung mass, his symptoms of carcinoid syndrome point away from squamous cell carcinoma and towards a neuroendocrine tumor.
*Incorrect: Most common lung cancer in non-smokers and females*
- **Adenocarcinoma** is the most common type of lung cancer, particularly prevalent in non-smokers and females.
- However, adenocarcinoma does not typically cause carcinoid syndrome, which is a key clinical presentation in this case.
*Incorrect: Contains psammoma bodies*
- **Psammoma bodies** are concentric, laminated calcified structures seen in certain tumors, such as papillary thyroid carcinoma, meningioma, and serous papillary ovarian cancer.
- They are not characteristic features of neuroendocrine tumors or carcinoid tumors.
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