# Clinical Cases: Infectious Disease Pathology

## Case 1: Pulmonary Tuberculosis with Caseating Granulomas

### Patient Demographics
- **Age:** 35 years old
- **Sex:** Male
- **Occupation:** Recent immigrant, construction worker

### Chief Complaint
"Cough with blood-tinged sputum, night sweats, and weight loss for 2 months"

### History of Present Illness
A 35-year-old male from the Philippines presents with a 2-month history of productive cough, initially with yellow sputum that has recently become blood-streaked. He reports drenching night sweats requiring him to change his shirt, fevers, and unintentional weight loss of 8 kg. He has mild shortness of breath with exertion. He immigrated to the United States 1 year ago. He has no known HIV risk factors and denies prior TB diagnosis or treatment. He lives in a shared housing arrangement with 5 other individuals.

### Physical Examination
- **Vital Signs:** BP 118/72 mmHg, HR 96 bpm, RR 20/min, Temp 38.4C, SpO2 95% on room air
- **General:** Thin male, appears chronically ill, mild respiratory distress
- **HEENT:** No oral lesions, mild cervical lymphadenopathy
- **Respiratory:** Decreased breath sounds in right upper lobe with bronchial breath sounds, few crackles
- **Cardiovascular:** Tachycardia, no murmurs
- **Abdomen:** Soft, non-tender
- **Extremities:** No clubbing or edema

### Diagnostic Workup

**Laboratory Studies:**
| Test | Result | Reference Range |
|------|--------|-----------------|
| WBC | 11,200/uL | 4,500-11,000/uL |
| Hemoglobin | 11.8 g/dL | 13.5-17.5 g/dL |
| ESR | 85 mm/hr | 0-20 mm/hr |
| HIV antibody | Negative | Negative |
| Albumin | 3.0 g/dL | 3.5-5.5 g/dL |

**Imaging:**
- **Chest X-ray:** Right upper lobe cavitary lesion (3.5 cm) with surrounding infiltrate, additional nodular opacities in right middle lobe
- **CT Chest:** Cavitary lesion in right upper lobe with tree-in-bud nodularity, mediastinal lymphadenopathy with central hypodensity

**Microbiology:**
- **Sputum AFB smear:** 3+ acid-fast bacilli
- **GeneXpert MTB/RIF:** Mycobacterium tuberculosis detected, rifampin resistance not detected
- **Sputum culture:** Pending (Mycobacterium tuberculosis grew at 3 weeks)

**Tuberculin Skin Test:**
- 22 mm induration at 48 hours (strongly positive)

### Pathology Correlation
This case demonstrates the **characteristic pathology of tuberculosis infection**:

**Primary TB vs. Reactivation TB:**

**Primary TB (Ghon Complex):**
- Initial infection, usually childhood
- **Ghon focus:** Subpleural granuloma, typically middle or lower lung
- **Ghon complex:** Ghon focus + involved hilar lymph nodes
- Usually asymptomatic, heals with fibrosis and calcification
- May progress to primary progressive TB in immunocompromised

**Reactivation TB (Secondary TB):**
- Reactivation of latent infection
- Typically involves **apical and posterior segments of upper lobes**
- Higher oxygen tension favors M. tuberculosis growth
- Cavitation common (as in this patient)
- Highly contagious

**Histopathology of TB:**

**Caseating Granuloma:**
1. **Central caseating necrosis** - "cheesy" appearance, acellular, eosinophilic
2. **Epithelioid macrophages** - activated macrophages with elongated, "footprint-shaped" nuclei
3. **Langhans giant cells** - multinucleated giant cells with nuclei arranged in horseshoe/peripheral pattern
4. **Lymphocyte collar** - surrounding rim of lymphocytes and fibroblasts

**Why Caseation?**
- Result of Type IV hypersensitivity (delayed-type) response
- T cells release IFN-gamma activating macrophages
- TNF-alpha mediates granuloma formation
- Central necrosis represents killed bacteria and dead immune cells

**Special Stains:**
- **Ziehl-Neelsen** or **Kinyoun** stain: Acid-fast bacilli (red rods)
- Organisms often sparse in tissue; culture more sensitive

### Clinical Image
![Tuberculosis - Lung Pathology](case_01_image.jpg)

*Gross pathology of pulmonary tuberculosis showing caseating granulomas with characteristic "cheesy" white necrotic centers. The caseous material has a soft, friable consistency. Cavitation may develop when this material is expectorated.*

**Image Source:** Wikimedia Commons - "Tuberculosis pathology"
**License:** CC BY-SA 3.0
**URL:** https://commons.wikimedia.org/wiki/File:Tuberculosis_-_Teknisk_Museum_01.jpg

### Diagnosis
**Pulmonary Tuberculosis, Cavitary, Sputum Smear-Positive**
- Active, infectious disease
- Drug-susceptible (based on molecular testing)

### Treatment
**Initial Phase (2 months):**
- RIPE therapy:
  - **R**ifampin
  - **I**soniazid (+ pyridoxine to prevent neuropathy)
  - **P**yrazinamide
  - **E**thambutol

**Continuation Phase (4 months):**
- Rifampin + Isoniazid

**Public Health:**
1. Respiratory isolation until 3 negative AFB smears
2. Directly Observed Therapy (DOT)
3. Contact investigation for all close contacts
4. Report to public health authorities

### Teaching Points
1. **Caseating granulomas** are the histologic hallmark of TB
2. **Langhans giant cells** with peripheral horseshoe nuclei are characteristic (but not pathognomonic)
3. Reactivation TB typically involves **upper lobes** (higher PO2)
4. **Type IV hypersensitivity** mediates granuloma formation and tissue damage
5. **AFB smear** detects highly infectious patients; culture is gold standard for diagnosis
6. The **tuberculin skin test** detects delayed-type hypersensitivity, not active disease

---

## Case 2: HIV/AIDS with Opportunistic Infections

### Patient Demographics
- **Age:** 38 years old
- **Sex:** Male
- **Occupation:** Graphic designer

### Chief Complaint
"Shortness of breath, fever, and white patches in my mouth for 3 weeks"

### History of Present Illness
A 38-year-old male presents with progressive shortness of breath and dry cough for 3 weeks. He has had low-grade fevers, drenching night sweats, and has lost 7 kg over the past 2 months. He noticed white patches in his mouth that have become painful. He has had intermittent diarrhea for the past month. He was diagnosed with HIV 5 years ago but stopped taking antiretroviral therapy 2 years ago due to side effects and has not followed up with his HIV provider. He has had multiple male sexual partners.

### Physical Examination
- **Vital Signs:** BP 102/68 mmHg, HR 112 bpm, RR 28/min, Temp 38.6C, SpO2 86% on room air
- **General:** Cachectic male in moderate respiratory distress
- **HEENT:** White plaques on oral mucosa and tongue (scrape off), angular cheilitis
- **Respiratory:** Tachypnea, bilateral crackles throughout, no wheezing
- **Lymph nodes:** Diffuse lymphadenopathy
- **Skin:** Seborrheic dermatitis on face, purple nodular lesions on lower extremities
- **Neurologic:** Alert, no focal deficits

### Diagnostic Workup

**Laboratory Studies:**
| Test | Result | Reference Range |
|------|--------|-----------------|
| CD4 count | 45 cells/uL | 500-1500 cells/uL |
| HIV viral load | 450,000 copies/mL | Undetectable on ART |
| WBC | 3,200/uL | 4,500-11,000/uL |
| Hemoglobin | 9.8 g/dL | 13.5-17.5 g/dL |
| LDH | 585 U/L | 140-280 U/L |
| 1,3-beta-D-glucan | 385 pg/mL | <80 pg/mL |

**Imaging:**
- **Chest X-ray:** Bilateral diffuse interstitial infiltrates ("ground glass" appearance)
- **CT Chest:** Bilateral ground-glass opacities with apical sparing, no lymphadenopathy

**Bronchoscopy with BAL:**
- **GMS stain:** Cysts with central dot consistent with Pneumocystis jirovecii
- **Cytology:** No malignant cells

**Oral Scraping:**
- **KOH prep:** Budding yeast with pseudohyphae (Candida)

**Skin Biopsy (leg lesion):**
- Spindle cells forming vascular channels, HHV-8 positive
- Consistent with Kaposi sarcoma

### Pathology Correlation
This case demonstrates **HIV/AIDS pathology** and **opportunistic infections**:

**HIV Pathophysiology:**
1. HIV targets **CD4+ T lymphocytes** via CD4 receptor and CCR5/CXCR4 co-receptors
2. Progressive CD4 depletion over years
3. **AIDS defined:** CD4 <200 cells/uL OR AIDS-defining illness

**Lymph Node Pathology Progression:**
- Early: **Follicular hyperplasia** (robust immune response)
- Late: **Follicular involution and lymphocyte depletion** (immune exhaustion)

**Opportunistic Infections by CD4 Count:**
| CD4 Count | Infections |
|-----------|------------|
| <500 | Oral candidiasis, TB, Kaposi sarcoma |
| <200 | PCP, Toxoplasmosis, Cryptococcus |
| <100 | CMV, MAC, Cryptosporidium |
| <50 | Progressive multifocal leukoencephalopathy |

**Pneumocystis jirovecii Pneumonia (PCP):**
- Most common AIDS-defining illness
- **Histology:** "Foamy" eosinophilic alveolar exudate
- **GMS stain:** Cysts with central dot, crushed cup shapes
- Elevated LDH and beta-glucan
- Ground-glass opacities on imaging

**Kaposi Sarcoma:**
- Caused by HHV-8 (Human herpesvirus 8)
- **Histology:** Spindle cells forming slit-like vascular spaces, red blood cell extravasation
- Can involve skin, mucosa, lungs, GI tract

**Oral Candidiasis (Thrush):**
- **Pseudomembranous form:** White plaques that scrape off
- **Histology:** Budding yeast with pseudohyphae (not true hyphae)

### Clinical Image
![HIV/AIDS Opportunistic Infection](case_02_image.jpg)

*Pathology demonstrating pulmonary involvement in AIDS. Pneumocystis jirovecii pneumonia shows characteristic foamy, eosinophilic alveolar exudate. GMS stain reveals the cup-shaped cysts of Pneumocystis.*

**Image Source:** Wikimedia Commons - "Pneumocystis jirovecii"
**License:** CC BY-SA 3.0
**URL:** https://commons.wikimedia.org/wiki/File:Pneumocystis_jirovecii_01.jpg

### Diagnosis
1. **AIDS** (CD4 = 45 cells/uL with AIDS-defining illnesses)
2. **Pneumocystis jirovecii Pneumonia (PCP)**
3. **Oropharyngeal Candidiasis**
4. **Kaposi Sarcoma**

### Treatment
**PCP:**
1. TMP-SMX (trimethoprim-sulfamethoxazole) - first line
2. Prednisone (if PaO2 <70 or A-a gradient >35)
3. Supplemental oxygen

**Candidiasis:**
1. Fluconazole orally

**Kaposi Sarcoma:**
1. Antiretroviral therapy (primary treatment)
2. Consider chemotherapy if extensive

**HIV:**
1. Initiate antiretroviral therapy (after treating PCP)
2. OI prophylaxis:
   - TMP-SMX (PCP, Toxoplasma) until CD4 >200
   - Azithromycin (MAC) until CD4 >100
3. Adherence counseling
4. Partner notification

### Teaching Points
1. **HIV depletes CD4+ T cells**, leading to progressive immunodeficiency
2. **Opportunistic infections** occur at predictable CD4 thresholds
3. **PCP** is the most common AIDS-defining illness in the US
4. **Kaposi sarcoma** is caused by HHV-8, an AIDS-defining malignancy
5. **Type IV hypersensitivity** is impaired in HIV, explaining susceptibility to intracellular pathogens
6. Effective ART can restore immune function and reduce OI risk