Question 1

A 42-year-old man who recently immigrated from Mexico presents to the clinic with fever, a productive cough streaked with blood, back pain, and night sweats. He was found to be HIV-positive 3 years ago but does not know his most recent CD4+ count. With further questioning, the patient notes that he had previously experienced these symptoms when he was in Mexico, but he has no recollection of taking any treatment. Which of the following characteristics would best describe the histology of a lung biopsy specimen obtained from this patient?

Accepted Answer

Epithelioid cells with caseous necrosis surrounded by multinucleated giant cells and lymphocytes. ***Epithelioid cells surrounded by multinucleated giant cells and lymphocytes***
- The patient's symptoms (fever, productive cough with hemoptysis, back pain, night sweats, HIV-positive status, and history of similar symptoms in Mexico) are highly suggestive of **reactivation tuberculosis (TB)**.
- The characteristic histological finding in **tuberculosis** is **caseating granulomas**, which are composed of epithelioid cells (activated macrophages) surrounded by lymphocytes and multinucleated giant cells (Langhans giant cells), with a central area of **caseous necrosis**.

*Cells with increased nuclear-to-cytoplasmic ratio*
- This description is typical of **malignant cells**, such as those seen in carcinoma, which is not the primary presentation given the historical and symptomatic context pointing towards infection.
- While lung cancer could cause some of these symptoms, the history of previous episodes and HIV points more strongly to an infectious etiology like TB.

*Noncaseating granuloma*
- **Noncaseating granulomas** are characteristic of diseases like **sarcoidosis** or **Crohn's disease**, which typically do not present with the described constitutional symptoms (e.g., night sweats) and hemoptysis in this context, especially with a history of HIV and prior infection.
- The presence of caseous necrosis is a key differentiator for tuberculosis granulomas.

*Cellular debris and macrophages followed by cystic spaces and cavitation*
- This describes the histological features of a **lung abscess** or extensive tissue destruction, which can be a complication of TB but is not the primary defining characteristic of the initial granuloma formation.
- While TB can lead to cavitation, the initial and most specific histological feature in active TB is the granulomatous inflammation.

*Macrophage filled with fungal microorganisms*
- This finding would suggest a **fungal infection** such as histoplasmosis or cryptococcosis, which can occur in HIV-positive individuals and present with similar symptoms.
- However, the strong clinical picture of prior similar illness in Mexico (an endemic area for TB), systemic symptoms, and hemoptysis, makes TB a more probable diagnosis, which is characterized by granulomas rather than direct macrophage colonization by fungi. [Practice more Pathology questions on OnCourse]

Question 2

A 48-year-old man comes to the physician because of a 2-day history of fever, flank pain, and hematuria. He has chronic back pain, for which he has been taking meloxicam for the past 2 weeks. His temperature is 38.9°C (102°F). Physical examination shows a diffuse maculopapular rash over his trunk and extremities. Urinalysis shows 10–15 RBC/hpf, 20 WBC/hpf, and numerous eosinophils. Histologic examination of a kidney biopsy specimen is most likely to show which of the following findings?

Accepted Answer

Interstitial T-cell infiltration. ***Interstitial T-cell infiltration***
  - This patient's presentation with **fever**, **rash**, **eosinophiluria**, and acute kidney injury following meloxicam use is highly characteristic of **acute interstitial nephritis (AIN)**.
  - AIN is a **type IV hypersensitivity reaction** characterized by inflammation and edema of the renal interstitium, with a predominant infiltrate of **T lymphocytes and eosinophils**.

*Cortical cyst formation*
  - **Cortical cysts** are typically associated with **polycystic kidney disease**, which is a genetic disorder presenting with multiple cysts in the renal cortex and medulla, often leading to progressive renal failure over time.
  - This condition does not explain the acute onset of **fever, rash, eosinophilia**, and acute kidney injury seen in this patient.

*Glomerular crescent formation*
  - **Glomerular crescent formation** is characteristic of **rapidly progressive glomerulonephritis (RPGN)**, indicating severe glomerular injury often due to autoimmune diseases like **Goodpasture syndrome**, vasculitis, or lupus.
  - While RPGN can present with **hematuria** and acute kidney injury, the presence of **rash, fever**, and especially **eosinophiluria** strongly points away from a primary glomerular disease and towards an interstitial process.

*Mesangial IgA deposition*
  - **Mesangial IgA deposition** is the hallmark of **IgA nephropathy (Berger's disease)**, which typically presents with recurrent episodes of gross or microscopic hematuria, often triggered by an infection.
  - It does not usually involve **fever, rash, or significant eosinophilia**, and the acute kidney injury in this case is more indicative of an allergic drug reaction.

*Papillary necrosis*
  - **Papillary necrosis** is commonly associated with chronic analgesic abuse (**NSAID use**), **sickle cell disease**, or **diabetes mellitus**.
  - While the patient is taking meloxicam, the acute presentation with **fever, rash**, and prominent **eosinophiluria** is a stronger indicator of allergic interstitial nephritis rather than papillary necrosis, which usually presents with chronic pain and hematuria, often with sloughed papillae in the urine. [Practice more Pathology questions on OnCourse]

Question 3

A 3-year-old boy is brought to the physician for follow-up examination 5 days after sustaining a forehead laceration. Examination shows a linear, well-approximated laceration over the right temple. The wound is clean and dry with no exudate. There is a small amount of pink granulation tissue present. Microscopic examination of the wound is most likely to show which of the following?

Accepted Answer

Angiogenesis with type III collagen deposition. ***Angiogenesis with type III collagen deposition***
  - Five days post-laceration, the wound is in the **proliferative phase** of healing, characterized by the formation of **granulation tissue**.
  - **Granulation tissue** consists of new blood vessels (**angiogenesis**) and proliferating fibroblasts that deposit **type III collagen** (which is later replaced by type I collagen).

*Macrophage infiltration and fibrin clot degradation*
  - This describes events characteristic of the **inflammatory phase** (24-48 hours post-injury), where macrophages clean up debris and the initial fibrin clot.
  - While some macrophages may still be present, the dominant microscopic feature at 5 days would be granulation tissue formation.

*Fibroblast hyperplasia with disorganized collagen deposition*
  - Fibroblast proliferation and collagen deposition are indeed key features of the proliferative phase. However, specifying "disorganized collagen deposition" is somewhat less precise than angiogenesis and type III collagen, and **type III collagen** is characteristic of early granulation tissue rather than just general disorganized collagen.
  - This option doesn't fully capture the active angiogenesis component which is prominent in granulation tissue.

*Capillary dilation with neutrophilic migration*
  - This is characteristic of the **acute inflammatory response** occurring within the first 24-48 hours after injury.
  - By day 5, neutrophils have largely been replaced by macrophages, and the inflammatory phase is transitioning into the proliferative phase.

*Acellular tissue with type I collagen deposition*
  - **Type I collagen** deposition and scar maturation (leading to a more acellular tissue) occur much later, during the **remodeling phase** of wound healing, typically weeks to months after the injury.
  - At 5 days, the tissue is highly cellular and vascular. [Practice more Pathology questions on OnCourse]

Question 4

A 9-year-old boy is brought to the hospital by his mother with complaints of fever and right flank pain for the past 3 days. His mom mentions that he has had these symptoms recurrently for the past 4 years. He was treated with antibiotics in the past and got better, but eventually, these symptoms recurred. On physical examination, he is warm to touch and there is tenderness over his right costovertebral angle. The vital signs include a blood pressure of 100/64 mm Hg, a pulse of 100/min, a temperature of 38.0°C (100.4°F), and a respiratory rate of 14/min. Complete blood count results are as follows:
Hemoglobin 12 g/dL
Red blood cell 5.1 million cells/µL
Hematocrit 45%
Total leukocyte count 8,500 cells/µL
Neutrophils 71%
Lymphocyte 24%
Monocytes 4%
Eosinophil 1%
Basophils 0%
Platelets 240,000 cells/µL
Urinalysis results:
pH 6.2
Color turbid yellow
RBC none
WBC 8–10/HPF
Protein trace
Cast WBC casts
Glucose absent
Crystal none
Ketone absent
Nitrite positive
A computed tomography scan shows renal scarring and multiple atrophy sites with compensatory hypertrophy of residual normal tissue. There is additional renal cortical thinning. Which of the following would be the most likely microscopic finding if a renal biopsy were to be done?

Accepted Answer

Chronic interstitial inflammation with tubular atrophy and fibrosis. ***Chronic interstitial inflammation with tubular atrophy and fibrosis***
- The patient's history of recurrent fevers, flank pain, positive nitrites, WBCs, and WBC casts in urine, along with CT findings of renal scarring and atrophy, points towards **chronic pyelonephritis**.
- The hallmark microscopic findings of chronic pyelonephritis include **chronic interstitial inflammation** (lymphocytes and plasma cells infiltrating the interstitium), **tubular atrophy**, and **interstitial fibrosis**.
- These findings reflect the long-standing inflammatory process and structural damage characteristic of this condition.

*Tubules containing eosinophilic casts*
- This describes **thyroidization of tubules**, which is indeed seen in chronic pyelonephritis when dilated tubules become filled with eosinophilic colloid-like material.
- While this is a characteristic finding, it is more specific but less comprehensive than the broader description of chronic interstitial inflammation with tubular atrophy and fibrosis, which encompasses the fundamental pathologic process.

*Sloughed tubular cells within tubular lumen*
- This finding is characteristic of **acute tubular necrosis (ATN)**, typically seen in ischemic or nephrotoxic injury.
- The patient's presentation with recurrent infections and chronic structural changes is not consistent with ATN.

*Normal glomeruli with accumulated lipid in proximal convoluted tubular cells*
- This description is characteristic of **minimal change disease (lipoid nephrosis)**, a cause of nephrotic syndrome with heavy proteinuria and edema.
- The clinical picture of recurrent infections, flank pain, and localized scarring does not align with minimal change disease.

*Segmental sclerosis and hyalinosis*
- These findings are typical of **focal segmental glomerulosclerosis (FSGS)**, a glomerular disease often presenting with nephrotic syndrome.
- The recurrent infections and localized renal scarring with preserved glomerular function are not consistent with FSGS. [Practice more Pathology questions on OnCourse]

Question 5

A 60-year-old man comes to the office because of an 8-month history of cough, night sweats, shortness of breath, and fatigue. He has also had a 9-kg (19.8-lb) weight loss during this time. He appears pale. Abdominal examination shows hepatosplenomegaly. His leukocyte count is 80,000/mm3 and his leukocyte alkaline phosphatase level is increased. A peripheral blood smear shows > 82% neutrophils with band forms and immature and mature neutrophil precursors. An x-ray of the chest shows a 9-mm right hilar nodule. Which of the following is the most likely cause of this patient's laboratory findings?

Accepted Answer

Leukemoid reaction. ***Leukemoid reaction***
  - The combination of **leukocytosis** (>50,000/mm³), **immature granulocytes**, and **elevated leukocyte alkaline phosphatase (LAP) score** in the presence of an underlying inflammatory or infectious process (such as the suspected lung lesion) strongly suggests a leukemoid reaction.
  - A leukemoid reaction is a reactive **increase in white blood cells**, often in response to severe infection or malignancy, mimicking leukemia but distinct from it due to the high LAP score and lack of specific chromosomal translocations.

*Sarcoidosis*
  - Sarcoidosis typically presents with **non-caseating granulomas**, often affecting the lungs and lymph nodes, but does not usually cause such a profound leukocytosis with immature forms.
  - While a **hilar nodule** can be seen, the described hematological findings, especially the high LAP score and pronounced neutrophilia, are not characteristic of sarcoidosis.

*Acute lymphoblastic leukemia*
  - This condition involves a proliferation of **lymphoblasts**, not mature or immature neutrophils; therefore, the peripheral smear would show a predominance of blasts and not mature neutrophil precursors.
  - While it can cause leukocytosis, the specific cell types and the **elevated LAP score** (LAP is typically low in ALL) rule it out.

*Tuberculosis*
  - Tuberculosis can cause fever, night sweats, weight loss, and lung findings, but it typically does not lead to a **leukocyte count of 80,000/mm³** with such a high proportion of immature neutrophils.
  - While it can cause a **leukemoid reaction**, the LAP score and specific granulocyte morphology help differentiate it from other causes, and the primary diagnosis here is the reaction itself, which would be *caused* by something like TB.

*Chronic myeloid leukemia*
  - CML also presents with marked leukocytosis and **immature myeloid cells** but is characterized by a **low leukocyte alkaline phosphatase (LAP) score** and the presence of the **Philadelphia chromosome (BCR-ABL1 fusion gene)**, which contradicts the elevated LAP score found in this patient.
  - While hepatosplenomegaly and constitutional symptoms align, the LAP score is a key differentiating factor. [Practice more Pathology questions on OnCourse]

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