A 40-year-old male with a history of chronic alcoholism recently received a liver transplant. Two weeks following the transplant, the patient presents with a skin rash and frequent episodes of bloody diarrhea. A colonoscopy is performed and biopsy reveals apoptosis of colonic epithelial cells. What is most likely mediating these symptoms?
Q2
Twelve days after undergoing a cadaveric renal transplant for adult polycystic kidney disease, a 23-year-old man has pain in the right lower abdomen and generalized fatigue. During the past 4 days, he has had decreasing urinary output. Creatinine concentration was 2.3 mg/dL on the second postoperative day. Current medications include prednisone, cyclosporine, azathioprine, and enalapril. His temperature is 38°C (100.4°F), pulse is 103/min, and blood pressure is 168/98 mm Hg. Examination reveals tenderness to palpation on the graft site. Creatinine concentration is 4.3 mg/dL. A biopsy of the transplanted kidney shows tubulitis. C4d staining is negative. Which of the following is the most likely cause of this patient's findings?
Q3
A 10-year-old girl with previously diagnosed sickle cell anemia presents to the emergency room with a low-grade fever, malaise, petechiae on her arms, and a rash on her face. She regularly takes hydroxyurea and receives blood transfusions to treat her condition. Her blood tests show a hemoglobin of 4.0 g/dL, MCV of 87 fl, and 2% reticulocyte count. An attempted bone marrow biopsy was a dry, empty tap. What is the most likely diagnosis?
Q4
A 43-year-old woman comes to the office with a 5-day history of a rash. She's had a rash across her neck, shoulders, and the palms of her hands for the past five days. She's also had large-volume watery diarrhea for the same period of time. Past medical history is notable for acute myeloid leukemia, for which she received a stem cell transplant from a donor about two months prior. Physical exam reveals a faint red maculopapular rash across her neck, shoulders, and hands, as well as an enlarged liver and spleen. Labs are notable for a total bilirubin of 10. Which of the following is the mechanism of this patient's pathology?
Q5
A 57-year-old woman comes to the clinic complaining of decreased urine output. She reports that over the past 2 weeks she has been urinating less and less every day. She denies changes in her diet or fluid intake. The patient has a history of lupus nephritis, which has resulted in end stage renal disease. She underwent a renal transplant 2 months ago. Since then she has been on mycophenolate and cyclosporine, which she takes as prescribed. The patient’s temperature is 99°F (37.2°C), blood pressure is 172/102 mmHg, pulse is 88/min, and respirations are 17/min with an oxygen saturation of 97% on room air. Labs show an elevation in serum creatinine and blood urea nitrogen. On physical examination, she has 2+ pitting edema of the bilateral lower extremities. Lungs are clear to auscultation. Urinalysis shows elevated protein. A post-void bladder scan is normal. A renal biopsy is obtained, which shows lymphocyte infiltration and intimal swelling. Which of the following is the next best step in management?
Q6
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?
Q7
Two weeks after undergoing allogeneic stem cell transplant for multiple myeloma, a 55-year-old man develops a severely pruritic rash, abdominal cramps, and profuse diarrhea. He appears lethargic. Physical examination shows yellow sclerae. There is a generalized maculopapular rash on his face, trunk, and lower extremities, and desquamation of both soles. His serum alanine aminotransferase is 115 U/L, serum aspartate aminotransferase is 97 U/L, and serum total bilirubin is 2.7 mg/dL. Which of the following is the most likely underlying cause of this patient's condition?
Q8
A 50-year-old man presents to a clinic with oliguria. Four weeks ago, he had a kidney transplant. Postoperative follow-up was normal. He is currently on cyclosporine and admits that sometimes he forgets to take his medication. On physical examination, the vital signs include: temperature 37.1°C (98.8°F), blood pressure 165/110 mm Hg, heart rate 80/min, and respiratory rate 16/min. There is mild tenderness on renal palpation. His serum creatinine level is 4 mg/dL, well above his baseline level after the transplant. Which of the following best describes the histological finding if a biopsy is taken from the transplanted kidney?
Q9
An otherwise healthy 47-year-old woman comes to the physician for the evaluation of a 4-month history of worsening fatigue and constipation. She has also noticed that her cheeks appear fuller and her voice has become hoarse. Her temperature is 36.3°C (97.3°F) and pulse is 59/min. Examination of the neck shows a painless, mildly enlarged thyroid gland. Her skin is dry and cool and her nails appear brittle. Serum studies show antibodies against thyroid peroxidase. A biopsy of the thyroid gland is most likely to show which of the following?
Q10
A 61-year-old woman comes to the physician because of a constant, dull headache and generalized body pains for the past 8 months. She has also had difficulty hearing from her left side, which started a month after the onset of the headaches. Five months ago, she had surgery to correct a fracture of the right femur that occurred without a fall or any significant trauma. Five years ago, she underwent a total thyroidectomy for localized thyroid carcinoma. She takes levothyroxine and calcium supplements, which she started after menopause. Physical examination reveals a prominent forehead and irregular, tender skull surface. Bony tenderness is present over bilateral hip and knee joints, with decreased range of motion of the right hip joint and increased anterior curvature of both tibias. Laboratory studies show a highly elevated level of alkaline phosphatase, with vitamin D, calcium and PTH levels within normal limits. A plain x-ray of the head is most likely to show which of the following findings?
Graft-versus-host disease US Medical PG Practice Questions and MCQs
Question 1: A 40-year-old male with a history of chronic alcoholism recently received a liver transplant. Two weeks following the transplant, the patient presents with a skin rash and frequent episodes of bloody diarrhea. A colonoscopy is performed and biopsy reveals apoptosis of colonic epithelial cells. What is most likely mediating these symptoms?
A. Donor T-cells (Correct Answer)
B. Recipient T-cells
C. Recipient B-cells
D. Recipient antibodies
E. Donor B-cells
Explanation: ***Donor T-cells***
- This clinical presentation of **skin rash**, **bloody diarrhea**, and **colonic epithelial apoptosis** following an allogeneic transplant (like a liver transplant) is classic for **Graft-versus-Host Disease (GVHD)**.
- In GVHD, **immunocompetent T-cells from the donor** recognize the recipient's tissues as foreign and mount an immune attack, causing damage to organs like the skin, gastrointestinal tract, and liver.
*Recipient T-cells*
- **Recipient T-cells** are typically immunosuppressed following an organ transplant to prevent organ rejection.
- Furthermore, if activated, recipient T-cells would target the donor organ (the liver in this case), leading to **rejection**, rather than the systemic symptoms observed (skin rash, bloody diarrhea) which suggest an attack by donor cells on recipient tissues.
*Recipient B-cells*
- While recipient B-cells can be involved in **antibody-mediated rejection** of the transplanted organ, they are not the primary mediators of **cellular GVHD**.
- **Antibody-mediated rejection** would typically involve antibodies targeting the donor liver, leading to liver dysfunction, not the widespread GVHD symptoms described.
*Recipient antibodies*
- **Recipient antibodies** are primarily involved in **antibody-mediated rejection** of the transplanted organ, which would manifest as dysfunction of the transplanted liver.
- They do not mediate the symptoms of **Graft-versus-Host Disease (GVHD)**, which is a cell-mediated immune response.
*Donor B-cells*
- **Donor B-cells** are generally not the primary mediators of GVHD.
- While donor immune cells are crucial for GVHD, the major players are **donor T-cells**, which directly recognize and attack host tissues.
Question 2: Twelve days after undergoing a cadaveric renal transplant for adult polycystic kidney disease, a 23-year-old man has pain in the right lower abdomen and generalized fatigue. During the past 4 days, he has had decreasing urinary output. Creatinine concentration was 2.3 mg/dL on the second postoperative day. Current medications include prednisone, cyclosporine, azathioprine, and enalapril. His temperature is 38°C (100.4°F), pulse is 103/min, and blood pressure is 168/98 mm Hg. Examination reveals tenderness to palpation on the graft site. Creatinine concentration is 4.3 mg/dL. A biopsy of the transplanted kidney shows tubulitis. C4d staining is negative. Which of the following is the most likely cause of this patient's findings?
A. Drug-induced nephrotoxicity
B. Allorecognition with T cell activation (Correct Answer)
C. Irreversible fibrosis of the glomerular vessels
D. Donor T cells from the graft
E. Preformed cytotoxic antibodies against class I HLA
Explanation: ***Allorecognition with T cell activation***
- The patient's symptoms (pain at graft site, fatigue, decreasing urinary output, elevated creatinine) 12 days post-transplant, along with **tubulitis on biopsy** and negative **C4d staining**, are indicative of acute cellular rejection, mediated primarily by **T-cell recognition of donor HLA antigens**.
- **Hypertension** and **fever** also support acute rejection, and the immunosuppressive regimen may not be fully effective in preventing this T-cell mediated response.
*Drug-induced nephrotoxicity*
- While cyclosporine and enalapril can cause kidney injury, the **histological finding of tubulitis** is highly specific for acute cellular rejection, not typically seen with drug-induced nephrotoxicity alone.
- Drug-induced nephrotoxicity usually presents with a more **gradual rise in creatinine** and may lack the systemic signs like fever or the specific pathological features of rejection.
*Irreversible fibrosis of the glomerular vessels*
- This description is more consistent with **chronic allograft nephropathy** or long-term damage, which typically develops months to years after transplantation, not within 12 days.
- The findings described (pain, fever, tubulitis) point to an acute process, not chronic fibrosis.
*Donor T cells from the graft*
- This scenario describes **graft-versus-host disease (GVHD)**, which is rare in solid organ transplantation due to the much smaller lymphocyte load compared to bone marrow transplants.
- GVHD typically affects the skin, liver, and gut, and while it involves T-cell mediated injury, the primary damage in renal transplant rejection is directed at the transplanted kidney by the recipient's immune system.
*Preformed cytotoxic antibodies against class I HLA*
- This describes **hyperacute rejection**, which occurs within minutes to hours of transplantation due to pre-existing antibodies in the recipient against donor antigens.
- The patient's symptoms developing 12 days post-transplant, along with the biopsy showing tubulitis and negative C4d staining (indicating absence of significant antibody-mediated complement activation), rule out hyperacute rejection.
Question 3: A 10-year-old girl with previously diagnosed sickle cell anemia presents to the emergency room with a low-grade fever, malaise, petechiae on her arms, and a rash on her face. She regularly takes hydroxyurea and receives blood transfusions to treat her condition. Her blood tests show a hemoglobin of 4.0 g/dL, MCV of 87 fl, and 2% reticulocyte count. An attempted bone marrow biopsy was a dry, empty tap. What is the most likely diagnosis?
A. Reaction to the blood transfusions
B. Gastrointestinal bleeding
C. Anemia of chronic disease
D. Aplastic crisis (Correct Answer)
E. Sequestration crisis
Explanation: ***Aplastic crisis***
- The combination of **severe anemia** (hemoglobin 4.0 g/dL), **low reticulocyte count** (2%), and a **dry bone marrow tap** confirms a defect in red blood cell production.
- In a patient with **sickle cell anemia**, an aplastic crisis is often triggered by **Parvovirus B19 infection**, which targets erythroid precursors.
*Reaction to the blood transfusions*
- An acute transfusion reaction would typically present with fever, chills, urticaria, or dyspnea, which are not the predominant symptoms here.
- Hemoglobin would likely drop acutely or remain stable, but not necessarily with such a profound reticulocytopenia or bone marrow findings.
*Gastrointestinal bleeding*
- While GI bleeding can cause severe anemia, it would typically be associated with **microcytic anemia** (decreased MCV if chronic) and **elevated reticulocyte count** as the bone marrow tries to compensate, neither of which are observed.
- There is no mention of melena or hematochezia, and the dry bone marrow tap points to a production problem, not blood loss.
*Anemia of chronic disease*
- This condition typically results in **mild to moderate anemia** with a **normal or slightly reduced MCV** and a **low reticulocyte count**.
- However, the hemoglobin level of 4.0 g/dL is too severe for typical anemia of chronic disease, and the dry bone marrow tap is not a characteristic finding.
*Sequestration crisis*
- A sequestration crisis involves the rapid pooling of blood in the spleen or liver, leading to **acute severe anemia** and often **splenomegaly**.
- However, it would be characterized by a **high reticulocyte count** as the bone marrow attempts to compensate for the sudden blood loss, which is contrary to the findings in this case.
Question 4: A 43-year-old woman comes to the office with a 5-day history of a rash. She's had a rash across her neck, shoulders, and the palms of her hands for the past five days. She's also had large-volume watery diarrhea for the same period of time. Past medical history is notable for acute myeloid leukemia, for which she received a stem cell transplant from a donor about two months prior. Physical exam reveals a faint red maculopapular rash across her neck, shoulders, and hands, as well as an enlarged liver and spleen. Labs are notable for a total bilirubin of 10. Which of the following is the mechanism of this patient's pathology?
A. Drug hypersensitivity reaction
B. Host CD8+ T cells against graft antigens
C. Graft T cells against host antigens (Correct Answer)
D. Pre-existing host antibodies against graft antigens
E. Host antibodies that have developed against graft antigens
Explanation: ***Graft T cells against host antigens***
- This patient's symptoms (rash, diarrhea, hepatosplenomegaly, elevated bilirubin) occurring after a stem cell transplant are classic for **graft-versus-host disease (GVHD)**.
- GVHD occurs when **donor T cells** from the graft recognize the recipient's (host's) tissues as foreign and mount an immune attack against them.
*Drug hypersensitivity reaction*
- While drug rashes can occur, the widespread nature, severe GI involvement (large-volume watery diarrhea), and liver dysfunction, especially in the context of a recent stem cell transplant, point away from a simple **hypersensitivity reaction**.
- A drug reaction would typically not cause such severe systemic effects or splenomegaly.
*Host CD8+ T cells against graft antigens*
- This describes **host-versus-graft rejection**, where the recipient's immune system attacks the transplanted cells.
- In a stem cell transplant setting, the host's immune system is typically severely suppressed to prevent this, and the clinical picture here is characteristic of the donor cells attacking the host.
*Pre-existing host antibodies against graft antigens*
- Pre-existing antibodies would cause a **hyperacute or acute rejection** much earlier after transplantation, often within minutes to days.
- This patient's symptoms developed two months post-transplant, which is more typical for acute GVHD, mediated by T cells.
*Host antibodies that have developed against graft antigens*
- The development of host antibodies against graft antigens would lead to **humoral rejection**, which typically manifests differently and less commonly causes the specific constellation of symptoms seen here (skin rash, severe diarrhea, cholestatic hepatitis in the context of stem cell transplant).
- T-cell-mediated responses are the primary drivers of GVHD in this scenario.
Question 5: A 57-year-old woman comes to the clinic complaining of decreased urine output. She reports that over the past 2 weeks she has been urinating less and less every day. She denies changes in her diet or fluid intake. The patient has a history of lupus nephritis, which has resulted in end stage renal disease. She underwent a renal transplant 2 months ago. Since then she has been on mycophenolate and cyclosporine, which she takes as prescribed. The patient’s temperature is 99°F (37.2°C), blood pressure is 172/102 mmHg, pulse is 88/min, and respirations are 17/min with an oxygen saturation of 97% on room air. Labs show an elevation in serum creatinine and blood urea nitrogen. On physical examination, she has 2+ pitting edema of the bilateral lower extremities. Lungs are clear to auscultation. Urinalysis shows elevated protein. A post-void bladder scan is normal. A renal biopsy is obtained, which shows lymphocyte infiltration and intimal swelling. Which of the following is the next best step in management?
A. Add diltiazem
B. Nephrectomy
C. Start intravenous steroids (Correct Answer)
D. Add ceftriaxone
E. Discontinue cyclosporine
Explanation: ***Start intravenous steroids***
- The patient presents with **decreased urine output**, elevated creatinine, and a recent kidney transplant with biopsy showing **lymphocyte infiltration** and **intimal swelling**, all highly suggestive of **acute cellular rejection**.
- **High-dose intravenous steroids** (e.g., methylprednisolone) are the first-line treatment for acute cellular rejection to suppress the immune response and preserve graft function.
*Add diltiazem*
- **Diltiazem** is a calcium channel blocker used to treat hypertension and arrhythmias, and it can also interfere with cyclosporine metabolism, potentially increasing its levels.
- While the patient has elevated blood pressure, adding diltiazem would not address the underlying **immune rejection** and would not be the primary intervention.
*Nephrectomy*
- **Nephrectomy** involves surgical removal of the transplanted kidney. This radical intervention is reserved for **irreversible graft failure** or severe complications like overwhelming infection or malignancy.
- Given the acute presentation and possibility of reversing rejection with immunosuppression, nephrectomy is **premature** and not the next best step.
*Add ceftriaxone*
- **Ceftriaxone** is an antibiotic used to treat bacterial infections.
- There is no clinical evidence in the stem (e.g., fever, signs of infection) to suggest a **bacterial infection** as the cause of her symptoms, making antibiotics inappropriate.
*Discontinue cyclosporine*
- **Cyclosporine** is an immunosuppressant essential for preventing transplant rejection. Discontinuing it would immediately increase the risk of more severe and potentially **irreversible rejection**.
- While cyclosporine can cause nephrotoxicity, the biopsy findings of **cellular infiltration** point more towards rejection rather than primary drug toxicity, and the primary treatment for rejection involves increasing immunosuppression, not withdrawing it.
Question 6: 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 7: Two weeks after undergoing allogeneic stem cell transplant for multiple myeloma, a 55-year-old man develops a severely pruritic rash, abdominal cramps, and profuse diarrhea. He appears lethargic. Physical examination shows yellow sclerae. There is a generalized maculopapular rash on his face, trunk, and lower extremities, and desquamation of both soles. His serum alanine aminotransferase is 115 U/L, serum aspartate aminotransferase is 97 U/L, and serum total bilirubin is 2.7 mg/dL. Which of the following is the most likely underlying cause of this patient's condition?
A. Preformed cytotoxic anti-HLA antibodies
B. Proliferating transplanted B cells
C. Activated recipient T cells
D. Donor T cells in the graft (Correct Answer)
E. Newly formed anti-HLA antibodies
Explanation: ***Donor T cells in the graft***
- The symptoms (rash, GI symptoms, liver dysfunction) after an allogeneic stem cell transplant are classic signs of **acute graft-versus-host disease (GVHD)**. This condition occurs when **immunocompetent T cells from the donor graft** recognize the recipient's tissues as foreign and mount an immune attack.
- The rapid onset within two weeks post-transplant, elevated liver enzymes, jaundice (**yellow sclerae**, **elevated bilirubin**), severe pruritic rash, and GI symptoms (**abdominal cramps**, **profuse diarrhea**) are all characteristic manifestations of acute GVHD.
*Preformed cytotoxic anti-HLA antibodies*
- Preformed antibodies would typically cause **hyperacute rejection**, which occurs within minutes to hours of transplantation and involves widespread thrombosis and necrosis of the graft, not the systemic symptoms seen here.
- This reaction is mediated by the recipient's antibodies attacking donor antigens, leading to immediate graft failure.
*Proliferating transplanted B cells*
- Transplanted B cells can contribute to chronic GVHD through antibody production, but they are not the primary mediators of **acute GVHD**; acute GVHD is predominantly a T cell-mediated process.
- Proliferation of donor B cells is more commonly associated with post-transplant lymphoproliferative disorders (PTLD) or chronic GVHD, not the acute presentation described.
*Activated recipient T cells*
- In an allogeneic transplant, the recipient's immune system is usually heavily suppressed beforehand to prevent host-versus-graft rejection.
- If recipient T cells were active, they would primarily cause **rejection of the donor stem cells** (graft rejection), not the systemic symptoms of GVHD, which is a reaction of the donor cells against the host.
*Newly formed anti-HLA antibodies*
- Newly formed antibodies the recipient develops against the donor's HLA antigens would cause graft rejection, a process often delayed but not presenting as the widespread organ damage of acute GVHD.
- These antibodies are part of the host's attempt to reject the foreign graft, not the donor cells attacking the host.
Question 8: A 50-year-old man presents to a clinic with oliguria. Four weeks ago, he had a kidney transplant. Postoperative follow-up was normal. He is currently on cyclosporine and admits that sometimes he forgets to take his medication. On physical examination, the vital signs include: temperature 37.1°C (98.8°F), blood pressure 165/110 mm Hg, heart rate 80/min, and respiratory rate 16/min. There is mild tenderness on renal palpation. His serum creatinine level is 4 mg/dL, well above his baseline level after the transplant. Which of the following best describes the histological finding if a biopsy is taken from the transplanted kidney?
A. Lymphocytic infiltration of graft vessels and endothelial damage (Correct Answer)
B. Thrombosis and occlusion of vessels
C. Atherosclerosis on angiography
D. Necrosis with granulation tissue
E. Thickening of blood vessels, fibrosis of graft vessels, and parenchymal atrophy
Explanation: ***Lymphocytic infiltration of graft vessels and endothelial damage***
- The patient's presentation with **oliguria**, elevated **creatinine**, and **hypertension** following a recent kidney transplant, especially with a history of non-adherence to **cyclosporine** (an immunosuppressant), strongly indicates **acute rejection**.
- Histologically, acute rejection is characterized by **lymphocytic infiltration** of the graft vessels (often referred to as **vasculitis** or **endotheliitis**) and associated **endothelial damage**.
*Thrombosis and occlusion of vessels*
- This finding is more characteristic of **hyperacute rejection**, which typically occurs within minutes to hours of transplantation, not weeks later.
- Hyperacute rejection is mediated by **pre-formed antibodies** and leads to severe, rapid graft failure due to widespread intravascular thrombosis.
*Atherosclerosis on angiography*
- While post-transplant patients can develop accelerated atherosclerosis (a form of **chronic rejection**), it is typically a long-term complication developing months to years after transplantation.
- The acute presentation with rapid creatinine elevation is not typical for primary atherosclerosis.
*Necrosis with granulation tissue*
- **Necrosis** with **granulation tissue** is a general healing response to significant tissue injury or inflammation.
- While some cellular necrosis can occur in severe rejection, it's not the defining feature, and granulation tissue indicates a more prolonged, subacute process rather than the primary histological hallmark of acute rejection.
*Thickening of blood vessels, fibrosis of graft vessels, and parenchymal atrophy*
- These are classic features of **chronic rejection**, which manifests months to years after transplantation as a gradual decline in graft function.
- **Chronic rejection** involves progressive damage leading to vasculopathy, interstitial fibrosis, and tubular atrophy, rather than the acute inflammatory cellular infiltrate seen here.
Question 9: An otherwise healthy 47-year-old woman comes to the physician for the evaluation of a 4-month history of worsening fatigue and constipation. She has also noticed that her cheeks appear fuller and her voice has become hoarse. Her temperature is 36.3°C (97.3°F) and pulse is 59/min. Examination of the neck shows a painless, mildly enlarged thyroid gland. Her skin is dry and cool and her nails appear brittle. Serum studies show antibodies against thyroid peroxidase. A biopsy of the thyroid gland is most likely to show which of the following?
A. Tall follicular cells, scalloped colloid, and vascular congestion
B. Lymphocytic infiltration, Hürthle cells, and germinal centers (Correct Answer)
C. Large, irregular nuclei, nuclear grooves, and Psammoma bodies
D. Spindle cells, pleomorphic giant cells, and mitotic figures
E. Multinucleated giant cells, macrophages, and degenerated follicular cells
Explanation: ***Lymphocytic infiltration, Hürthle cells, and germinal centers***
- The patient's symptoms (fatigue, constipation, fuller cheeks, hoarse voice, dry and cool skin, brittle nails, bradycardia, mildly enlarged thyroid gland) are classic for **hypothyroidism**. The presence of **anti-thyroid peroxidase antibodies** confirms an autoimmune etiology, specifically **Hashimoto's thyroiditis**.
- **Hashimoto's thyroiditis** is characterized pathologically by extensive **lymphocytic infiltration** of the thyroid parenchyma, the presence of **Hürthle cells** (metaplastic follicular cells with abundant eosinophilic cytoplasm), and the formation of **germinal centers** within the thyroid gland.
*Tall follicular cells, scalloped colloid, and vascular congestion*
- This description is characteristic of **Graves' disease**, an autoimmune cause of **hyperthyroidism**.
- The patient's symptoms and signs (e.g., bradycardia, dry skin, constipation) are consistent with **hypothyroidism**, not hyperthyroidism.
*Large, irregular nuclei, nuclear grooves, and Psammoma bodies*
- These are classic histological features of **papillary thyroid carcinoma**, the most common type of thyroid cancer.
- While thyroid nodules can occur in Hashimoto's, the overall clinical picture points strongly to a benign autoimmune inflammatory process, not malignancy.
*Spindle cells, pleomorphic giant cells, and mitotic figures*
- This describes **anaplastic thyroid carcinoma**, a highly aggressive and undifferentiated thyroid malignancy.
- Anaplastic carcinoma typically presents as a rapidly enlarging, painful neck mass in older individuals, which is not consistent with this patient's chronic, milder presentation.
*Multinucleated giant cells, macrophages, and degenerated follicular cells*
- This histological pattern is characteristic of **subacute granulomatous thyroiditis (de Quervain's thyroiditis)**.
- Subacute thyroiditis typically presents with painful thyroid enlargement and often follows a viral infection, which is not suggested by the patient's symptoms or antibody findings.
Question 10: A 61-year-old woman comes to the physician because of a constant, dull headache and generalized body pains for the past 8 months. She has also had difficulty hearing from her left side, which started a month after the onset of the headaches. Five months ago, she had surgery to correct a fracture of the right femur that occurred without a fall or any significant trauma. Five years ago, she underwent a total thyroidectomy for localized thyroid carcinoma. She takes levothyroxine and calcium supplements, which she started after menopause. Physical examination reveals a prominent forehead and irregular, tender skull surface. Bony tenderness is present over bilateral hip and knee joints, with decreased range of motion of the right hip joint and increased anterior curvature of both tibias. Laboratory studies show a highly elevated level of alkaline phosphatase, with vitamin D, calcium and PTH levels within normal limits. A plain x-ray of the head is most likely to show which of the following findings?
A. Mixed lytic and sclerotic lesions (Correct Answer)
B. Periosteal trabeculations with radiolucent marrow hyperplasia
C. Generalized dense, sclerotic bone
D. Multiple, well-defined, punched out lytic lesions
E. Lytic lesions with no sclerotic margin
Explanation: ***Mixed lytic and sclerotic lesions***
- The patient's symptoms (headache, hearing loss, pathological fracture, bony pain, prominent forehead, enlarged skull, increased tibial curvature, and elevated alkaline phosphatase with normal calcium and PTH) are classic for **Paget's disease of bone**.
- **Paget's disease** is characterized by disorganized bone remodeling, which radiographically appears as a mixture of osteolytic (bone destruction) and osteosclerotic (bone formation) lesions, often described as a "cotton wool" appearance in the skull.
*Periosteal trabeculations with radiolucent marrow hyperplasia*
- This finding is more characteristic of conditions like **myelofibrosis**, where there is marrow replacement and extramedullary hematopoiesis, leading to bony changes.
- While Paget's can affect bone structure, it primarily involves remodeling within the bone itself rather than periosteal trabeculations and marrow hyperplasia as a primary radiological feature.
*Generalized dense, sclerotic bone*
- **Osteopetrosis** (Albers-Schönberg disease) is characterized by excessively dense, brittle bones due to defective osteoclast function, leading to generalized sclerosis.
- The clinical presentation with mixed lytic and sclerotic phases, hearing loss, and characteristic bone deformities points away from uniform bone sclerosis.
*Multiple, well-defined, punched out lytic lesions*
- This finding is most suggestive of **multiple myeloma**, a plasma cell malignancy that causes discrete areas of bone destruction without much osteoblastic (bone-forming) activity.
- The patient's symptoms, particularly the prominent forehead, increased tibial curvature, and highly elevated alkaline phosphatase, are not typical of multiple myeloma.
*Lytic lesions with no sclerotic margin*
- This pattern can be seen in aggressive **metastatic bone disease** (e.g., from renal cell carcinoma or thyroid carcinoma, although the patient had a thyroidectomy 5 years ago for localized cancer, making widespread metastases less likely to present this way).
- While Paget's does have lytic phases, the entire clinical picture and the eventual mixed lytic-sclerotic appearance differentiate it from purely lytic, unsclerofed lesions of aggressive metastatic disease.
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