P1 CLINICAL MICROSCOPY

CASE 1

High-Grade Serous Ovarian Adenocarcinoma (HGSC) with Peritoneal Carcinomatosis and

Right-Sided Malignant Pleural Effusion

PATIENT OVERVIEW

Name: Ma. Ana Tee

Age/Sex: 65-year-old female (Postmenopausal woman – high-risk group for epithelial ovarian cancer,
especially high-grade serous carcinoma (HGSC))
Presenting Complaints (2 weeks):

• Progressive shortness of breath

• Increasing abdominal swelling

Relevant History:

• No TB or liver disease
• Only mild hypertension
• No history of chronic infections

PHYSICAL EXAMINATION FINDINGS

• Vitals: Stable (BP: 130/80, RR: 20, SpO₂: 96%)

• Lungs: ↓ breath sounds on right lower lung → suggests pleural effusion
• Abdomen: Distended with shifting dullness → indicates ascites
• No signs of:
o Hepatosplenomegaly
o Edema
o Rash
o Lymphadenopathy
o Liver disease stigmata

Interpretation: Suggests serous fluid accumulations (ascites, pleural effusion) due to malignancy
or systemic illness

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LABORATORY FINDINGS

1. Serum Chemistry

Test Result Interpretation

CA-125 1300 U/mL (↑↑) Tumor marker for epithelial ovarian cancer, esp. HGSC
Electrolytes, LFTs Normal Rules out hepatic cause of ascites
LDH 220 U/L Borderline; may reflect tumor lysis or turnover

2. CBC & ESR

Test Result Interpretation

Hemoglobin 10.5 g/dL Anemia of chronic disease (likely from malignancy)
ESR 60 mm/hr (↑↑) Nonspecific but consistent with chronic inflammation or cancer

FLUID ANALYSES

1. Pleural Fluid (Right Thoracentesis)

Parameter Result Interpretation

Appearance Cloudy yellow Exudative pattern
Total
4.2 g/dL >3.0 → Exudate
Protein
LDH 350 U/L >200 → Exudate
Mildly ↓ → seen in TB,
Glucose 55 mg/dL
malignancy
WBC Count 1,200/uL ↑ → Exudate
Differential 80% lymphocytes Typical of malignancy or TB
ADA 12 U/L <40 → rules out TB
Cytology Atypical glandular cells → adenocarcinoma
CK7+, CK20-, PAX8+, WT1+, p53+ → Müllerian
IHC
(ovarian) origin

Interpretation: Pleural fluid consistent with malignant effusion, most likely from high-grade serous
ovarian carcinoma

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2. Ascitic Fluid (Paracentesis)

Parameter Result Interpretation

Appearance Cloudy Exudate (suspicious for malignancy)
Protein 3.8 g/dL >2.5 → Exudate
Albumin 2.0 g/dL SAAG: 1.8 → portal hypertension not likely primary
WBC 950/uL Elevated
Differential 75% lymphocytes Suggests malignancy
ADA 9 U/L <30 → rules out TB
Cytology Suspicious cells, awaiting IHC Suggestive of malignancy

Interpretation: Ascitic fluid also consistent with peritoneal carcinomatosis from ovarian origin

IMAGING STUDIES

1. Chest X-ray

• Right-sided moderate pleural effusion

• Blunting of costophrenic angle

2. Abdominal Ultrasound

• Complex right adnexal mass (~6 cm) with internal septations

• Moderate ascites

3. CT Abdomen

• Peritoneal thickening
• Omental caking/nodularity → classic for peritoneal carcinomatosis

Interpretation: All imaging is consistent with advanced-stage ovarian malignancy with peritoneal
and pleural spread

PATHOGENESIS OF HIGH-GRADE SEROUS OVARIAN CARCINOMA (HGSC)

1. Site of Origin: Likely from fimbrial end of fallopian tube

2. Mutation in TP53 → Loss of tumor suppression
3. STIC Lesions (Serous Tubal Intraepithelial Carcinoma) → spreads to ovary & peritoneum
4. Tumor cells exfoliate into peritoneum → causes ascites
5. Lymphatic/diaphragmatic spread to right pleural space
6. ↑VEGF & cytokines → ↑vascular permeability → ascites and pleural effusion

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DIFFERENTIAL DIAGNOSIS EXCLUDED

Diagnosis Ruled Out By

ADA <40, no TB history, negative
TB
cultures
No GI mass, no GI symptoms, IHC
GI Malignancy
profile not GI-type
No edema, exudative effusion (not
Heart Failure
transudate), normal BNP
Normal LFTs, no hepatomegaly, no
Liver Cirrhosis
stigmata of liver disease

FINAL DIAGNOSIS: CONFIRMED

• Clinical
• Imaging
• Cytology
• Immunohistochemistry
• Tumor markers (CA-125 ↑↑)

All point to High-Grade Serous Ovarian Carcinoma with peritoneal and pleural metastasis (FIGO
Stage IV)

TREATMENT PLAN

Neoadjuvant Chemotherapy

• Carboplatin + Paclitaxel ± Bevacizumab

• Goal: Shrink tumor pre-surgery

Interval Debulking Surgery

• TAHBSO, omentectomy, peritoneal cytoreduction

Adjuvant Chemotherapy

• Post-surgery, continue same regimen for 3-4 cycles

Maintenance Therapy

• PARP inhibitors (e.g., Olaparib) especially for BRCA mutation carriers

Symptom Management

• Thoracentesis (pleural)
• Paracentesis (ascites)
• Iron for anemia
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MONITORING

• CA-125 levels
• Imaging (US, CT, PET)
• CBC, LFTs, Renal function
• Genetic testing (BRCA, HRD)

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CASE 2

Uric Acid Nephrolithiasis with Acute Gouty Arthritis

PATIENT OVERVIEW

• Name: [Not Specified]

• Age/Sex: 66-year-old Male
• Ethnicity: Filipino
• BMI: 30 kg/m² (Obese)
• Medical History:
o Type 2 Diabetes Mellitus (on Metformin)
o Chronic alcohol consumption (3–4 drinks/day)
o Ketogenic diet
o No smoking or illicit drug use

PRESENTING COMPLAINTS

Brought to the ER with:

• Right-sided flank pain

• Hematuria
• Three episodes of vomiting
• Painful, swollen left knee (onset: 1 day prior; initially attributed to trauma)

Denied:

• Fever
• Dyspnea
• Diarrhea
• Constipation
• History of trauma

PHYSICAL EXAMINATION

• General: Obese, hypertensive

• Vital Signs:
o BP: 160/110 mmHg (Elevated)
o HR: 102 bpm (Mild tachycardia)
o Temp: 36.7°C (Normal)
o RR: 20, SpO₂: 97% (Normal)
• Joint Exam (Left knee):
o Erythematous, warm, tender to palpation
• Abdominal/Flank:
o Right flank tenderness
o No hepatosplenomegaly
• Cardiopulmonary: Normal S1/S2, lungs clear

Interpretation: Findings are consistent with nephrolithiasis and acute monoarthritis; no evidence
of sepsis or generalized inflammation.

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LABORATORY & DIAGNOSTIC FINDINGS

1. Urinalysis

Finding Interpretation
Acidic urine → favors uric acid stone
pH: 5.0
formation
Blood: 2+ Hematuria, likely from stone
Protein: 2+ Mild proteinuria
WBCs: 5–10/HPF Mild inflammation
RBCs: 25–30/HPF Suggests gross hematuria
Crystals: Uric acid Diagnostic of uric acid nephrolithiasis
Ketones: 2+ From ketogenic diet (acidifies urine)

Interpretation: Acidic urine with uric acid crystals and gross hematuria confirms a uric acid stone
etiology; ketones are consistent with ketogenic diet.

2. 24-Hour Urine Collection

Parameter Result Interpretation

Uric Acid 1,200 mg/day (↑) Hyperuricosuria → stone risk
Citrate 150 mg/day (↓) Hypocitraturia → ↓ inhibition of stone formation
Volume 1,100 mL Low-normal → insufficient dilution
Calcium, Oxalate, Creatinine Normal

Interpretation: Hyperuricosuria and low citrate levels significantly increase the risk of uric acid
stone formation; suboptimal urine volume reflects poor hydration.

3. Synovial Fluid Analysis (Left Knee Arthrocentesis)

Finding Interpretation
WBC: 25,000/mm³ Inflammatory arthritis
Differential: 75% Neutrophils Typical of gout
Crystals: Needle-shaped, negatively birefringent Monosodium urate crystals → confirms gout
Color: Milky; Clarity: Cloudy Suggests inflammatory process
Culture/Gram Stain: No organisms Rules out septic arthritis

Interpretation: Findings are diagnostic of acute gouty arthritis, confirmed by the presence of
monosodium urate crystals and neutrophilic inflammation; infection ruled out.

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4. Serum Chemistry

Test Result Interpretation

Serum Uric Acid 7.6 mg/dL (↑) Hyperuricemia
BUN 22 mg/dL (↑) Mild renal stress
Creatinine 1.1 mg/dL Normal
Mildly reduced kidney
eGFR 76 mL/min
function
Ketosis (from ketogenic
β-Hydroxybutyrate 46.8 mg/dL (↑↑)
diet)
Ca²⁺, Mg²⁺ Low Risk factor for stones
Slightly decreased
K⁺ 3.3 mmol/L
(vomiting?)

Interpretation: Hyperuricemia supports gout diagnosis; ketosis from ketogenic diet contributes to
acidic urine; mild renal function impairment and electrolyte disturbances increase nephrolithiasis risk.

5. Lipid Panel

Test Result Interpretation

Total Cholesterol 260 mg/dL High
Triglycerides 220 mg/dL High
HDL 36 mg/dL Low
LDL 181 mg/dL Very high

→ Suggestive of metabolic syndrome → gout

& nephrolithiasis risk factor

Interpretation: Dyslipidemia consistent with metabolic syndrome, which is a shared risk factor for
both uric acid stones and gout.

6. Imaging

A. X-ray KUB

• No calcification seen
→ Interpretation: Uric acid stones are radiolucent → often missed

B. Ultrasound KUB

• Both kidneys: Normal size, no hydronephrosis

• No stones seen
→ Interpretation: Uric acid stones are not visible on US

Interpretation: Radiolucent uric acid stones are often missed on ultrasound and X-ray,
validating the need for CT imaging.

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C. Non-Contrast CT Scan (Gold Standard)

• Oblong hyperdense stone in right renal pelvis

• Mild periureteral stranding (likely inflammation)
• No hydronephrosis

Interpretation: CT findings confirm uric acid nephrolithiasis with partial obstruction; CT is the gold
standard for visualizing radiolucent uric acid stones.

PATHOPHYSIOLOGY SUMMARY

Uric Acid Nephrolithiasis

• Occurs due to:

o Hyperuricosuria (↑ uric acid in urine)
o Low urinary pH (<5.5)
o Low urine volume & hypocitraturia
• Triggered by:
o Ketogenic diet
o T2DM
o Alcohol use
o Obesity
• Leads to:
o Stone formation → flank pain, hematuria, vomiting

Acute Gouty Arthritis

• Triggered by:
o Ketosis, alcohol, purine-rich diet
• Pathogenesis:
o Excess uric acid → MSU crystal deposition in joints
o Initiates intense inflammatory response
• Classic features:
o Acute monoarthritis, erythema, swelling
o Left knee involvement

DIFFERENTIAL DIAGNOSES EXCLUDED

Condition Ruled Out By

No calcifications on imaging; uric acid
Calcium nephrolithiasis
crystals seen
Acute pyelonephritis Afebrile, no leukocytosis, sterile urine
Gram stain/culture negative, classic gout
Septic arthritis
crystals present
No trauma history, inflammatory profile
Trauma-induced arthritis
matches gout

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FINAL CLINICAL IMPRESSION

Uric Acid Nephrolithiasis with Acute Gouty Arthritis

Well-substantiated by:

• CT confirmation of renal stone

• Urinalysis and 24-hr urine findings
• Synovial fluid analysis
• Serum uric acid elevation
• Compatible clinical presentation

TREATMENT & MANAGEMENT PLAN

1. Acute Gout Management

• Colchicine
• NSAIDs (if renal function allows)
• Corticosteroids (if NSAIDs contraindicated)

2. Chronic Uric Acid Management

• Allopurinol or Febuxostat (urate-lowering therapy)

• Potassium citrate or Sodium bicarbonate to alkalinize urine
• Target urine pH: >6.0

3. Lifestyle & Diet

• Stop/reduce alcohol
• Stop ketogenic diet
• Hydration: >2.5L/day fluid intake
• Low-purine, low-sodium balanced diet

COMPLICATIONS TO WATCH FOR

Complication Risk Factor/Mechanism

Recurrent stone formation or
Chronic Kidney Disease
urate nephropathy
Hydronephrosis Obstructive stones if untreated
From T2DM and recurrent renal
Diabetic Nephropathy
injury
From metabolic syndrome and
Cardiovascular Disease
dyslipidemia
Recurrent Gout Flares If uric acid remains uncontrolled

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CASE 3

End-Stage Renal Disease (ESRD) STAGE 5

Secondary to long-standing Hypertensive nephrosclerosis

PATIENT OVERVIEW

• Age/Sex: 62-year-old male

• Medical History: Long-standing hypertension with poor medication adherence
• No history of diabetes, autoimmune disease, or nephrotoxin use

PRESENTING COMPLAINTS

• Progressive fatigue
• Reduced exercise tolerance
• Bilateral pedal edema

Additional symptoms:

• Muscle cramps
• Poor appetite
• Metallic taste
• Mild pallor

Interpretation: These symptoms are consistent with chronic uremia and fluid retention commonly
seen in advanced kidney failure.

PHYSICAL EXAMINATION

• BP: 180/110 mmHg (Severely elevated)

• Pallor: Mild
• Extremities: Bilateral pitting edema
• Cardiopulmonary exam: Unremarkable

Interpretation: Severe hypertension with volume overload and anemia suggests systemic
complications of chronic kidney disease (CKD), likely progressed to ESRD.

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CLINICAL CHEMISTRY

Parameter Result Reference Interpretation

Markedly elevated, reflecting severe reduction in
Serum Creatinine 3.9 mg/dL 0.9–1.3
renal clearance
14
eGFR mL/min/1.73 75–116 Severely reduced; Stage 5 CKD = ESRD
m²
Slightly low, suggests protein-energy wasting or
Serum Albumin 3.4 g/dL 3.5–5.0
nephrotic-range loss
Hyperkalemia, common in ESRD due to impaired
Potassium 5.8 mmol/L 3.5–5.1
excretion
Hyperphosphatemia → reflects impaired
Phosphate 6.1 mg/dL 2.4–4.4
phosphate excretion
Hypocalcemia → often due to phosphate retention
Calcium 7.8 mg/dL 8.6–10.0
and ↓ vitamin D
Markedly elevated → secondary
Parathyroid
520 pg/mL 11–54 hyperparathyroidism due to CKD-MBD (mineral
Hormone (PTH)
bone disorder)
Bicarbonate 17 mmol/L 23–29 Metabolic acidosis, due to inability to excrete H⁺

HEMATOLOGY

Parameter Result Reference Interpretation

Anemia of CKD → reduced EPO
Hemoglobin 10.0 g/dL 13.5–18.0
production
Hematocrit 30% 40–54% Consistent with anemia
RBC Count 3.5 × 10¹²/L 4.2–6.0 Decreased
Normocytic, Indicates non-nutritional anemia,
MCV, MCH, MCHC -
normochromic typical of CKD
11.5–
RDW 14.9% Slightly increased → mild anisocytosis
14.5%
WBC/Platelet
Within normal - No active infection or thrombocytopenia
Count/MPV

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URINALYSIS

Parameter Result Interpretation

Yellow, slightly Suggests some particulate matter, mild
Color/Clarity
turbid abnormality
Isosthenuria — inability to concentrate urine,
Specific Gravity 1.010
typical of advanced CKD
pH 6.0 Normal
Protein 3+ Proteinuria, confirms glomerular damage
Suggests microscopic hematuria, may reflect
Blood Trace
damaged glomeruli
Other (Glucose, Ketones, Nitrites,
Negative No infection or glycosuria
Leukocyte esterase)

Microscopy:

• Microscopic RBCs: 5–10/HPF → Abnormal

• Casts: Granular & broad waxy → hallmark of chronic kidney damage
• Epithelial Cells/Crystals: Few or none → Non-specific

Interpretation: Presence of broad waxy casts and proteinuria is highly suggestive of ESRD with
chronic glomerular damage.

RENAL ULTRASOUND WITH DOPPLER

• Both kidneys small:

o Right: 8.05 cm
o Left: 8.01 cm
• Diffuse cortical hyperechogenicity
• Thinned cortex (<0.8 cm)
• Poor corticomedullary differentiation
• RRI = 0.72 bilaterally (↑)
• No hydronephrosis, stones, or masses

Interpretation: Bilateral renal atrophy, echogenicity, and elevated resistive index confirm
irreversible chronic kidney damage, consistent with ESRD.

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DIFFERENTIAL DIAGNOSES CONSIDERED

Ruled In /
Condition Interpretation
Out
ESRD Ruled In Classic lab and imaging findings + long-standing HTN
Nephrotic Syndrome Ruled Out No massive edema, normal albumin is only slightly low
No hematuria with dysmorphic RBCs, no active
Nephritic Syndrome Ruled Out
inflammation
Acute Kidney Injury
Ruled Out No recent insult; kidney atrophy on imaging = chronicity
(AKI)
Cardiopulmonary exam normal; no cardiomegaly, JVD,
CHF Ruled Out
crackles

FINAL CLINICAL IMPRESSION

End-Stage Renal Disease (ESRD)

Due to long-standing uncontrolled hypertension (hypertensive nephrosclerosis)

Interpretation: The patient meets multiple KDIGO criteria for ESRD:

• eGFR <15 mL/min/1.73 m²

• Proteinuria
• Abnormal urine microscopy
• Abnormal imaging (shrunken, echogenic kidneys)

TREATMENT PLAN

1. Renal Replacement Therapy

• Hemodialysis: To manage uremia, volume overload, and electrolyte imbalance

• Peritoneal Dialysis: Alternative for suitable patients
• Kidney Transplant: Definitive treatment if eligible

2. Medical Management

• Antihypertensives (e.g., ACE inhibitors)

• Erythropoietin-stimulating agents (ESA) for anemia
• Phosphate binders + vitamin D for bone disorder
• Sodium bicarbonate for acidosis
• Dietary protein, potassium, phosphate restriction

3. Lifestyle and Supportive Measures

• Fluid & salt restriction

• Patient education & counseling
• Nutritional support
• Palliative care if dialysis not chosen

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