Q1: Probable Diagnosis

Q2: Histological Features

General Histology of Acute Viral Hepatitis

1. Panlobular mononuclear cell infiltration - predominantly small lymphocytes, with occasional plasma cells and eosinophils
2. Hepatocellular necrosis and dropout - spotty/focal necrosis throughout the lobule; cell dropout creates gaps in the parenchyma
3. Ballooning degeneration of hepatocytes - swollen, pale hepatocytes with disrupted cytoplasm
4. Acidophilic (Councilman/apoptotic bodies) - eosinophilic rounded remnants of dead hepatocytes; a hallmark of viral hepatitis
5. Kupffer cell hyperplasia - reactive enlargement of the resident liver macrophages
6. Variable cholestasis - bile pigment in hepatocytes and canaliculi (explains jaundice and dark urine); hepatitis A can occasionally show a prominent cholestatic variant
7. Hepatocyte regeneration - mitotic figures, multinucleated cells, and "rosette" or "pseudoacinar" formation reflecting regeneration
8. Preserved reticulin framework - in uncomplicated acute hepatitis (no bridging necrosis)
9. Portal tract inflammation - mononuclear infiltrate expanding the portal tracts

Severe/Fulminant Cases May Show

• Bridging hepatic necrosis (portal-to-portal or portal-to-central): confluent necrosis with collapse of the reticulin framework; associated with subacute liver failure
• Massive hepatic necrosis (fulminant hepatitis): widespread lobular dropout, shrunken liver ("acute yellow atrophy")

Note: In hepatitis A specifically, a cholestatic variant with marked cholestasis on biopsy has been described. HAV does NOT cause chronic hepatitis or cirrhosis - complete recovery is the rule (~99%).

Q1: Probable Diagnosis - Multiple Myeloma

1. Osteolytic "punched-out" lesions on skull X-ray - Multiple myeloma classically causes multifocal lytic bone lesions (1-4 cm in diameter) in the axial skeleton (vertebrae, skull, pelvis, ribs). The lesions arise in the medullary cavity, erode cancellous bone, and destroy the cortex - producing the characteristic "punched-out" appearance. These result from myeloma-derived factors that upregulate RANKL, activating osteoclasts while inhibiting osteoblasts, causing net bone resorption and pathologic fractures.
2. Bence Jones proteinuria (urine protein ++ precipitated on heating at 60°C) - Myeloma plasma cells secrete excess free immunoglobulin light chains (κ or λ), which appear in the urine as Bence Jones proteins. These have the characteristic property of precipitating on heating to 45-60°C and redissolving at 100°C. This is virtually pathognomonic for multiple myeloma.

• Age 50 years, male (median diagnosis age ~70, more common in males)
• Bone pain + pathologic fracture of humerus
• Anemia (Hb 8 gm% - normocytic normochromic anemia from marrow replacement)

Q2: Two Other Diagnostic Tests

1. Serum Protein Electrophoresis (SPEP) / Immunofixation - Detects the monoclonal "M protein" (a homogeneous band in the γ or β region). IgG is the most common (60%), followed by IgA (20-25%). This quantifies the paraprotein and monitors response to treatment.
2. Bone Marrow Biopsy (Trephine/Aspiration) - The definitive diagnostic test. Shows >10% (often >30%) clonal plasma cells. Myeloma cells may show abnormal features: prominent nucleoli, clock-face chromatin, eccentric nucleus, and Russell bodies (cytoplasmic inclusions of accumulated immunoglobulin). This is required for definitive diagnosis.

Q3: ESR Finding and Reason