```python
def region_totals(grid: list, queries: list) -> list:
    if not grid or not all(grid):
        raise ValueError("Grid must have at least one row with at least one cell.")
    
    rows = len(grid)
    cols = len(grid[0])
    if any(len(row) != cols for row in grid):
        raise ValueError("All rows must have the same number of cells.")
    
    prefix_sum = [[0] * (cols + 1) for _ in range(rows + 1)]
    for i in range(1, rows + 1):
        for j in range(1, cols + 1):
            prefix_sum[i][j] = grid[i - 1][j - 1] + prefix_sum[i - 1][j] + prefix_sum[i][j - 1] - prefix_sum[i - 1][j - 1]
    
    results = []
    for query in queries:
        if len(query) != 4:
            raise ValueError("Each query must be a list of exactly four integers.")
        
        top, left, bottom, right = query
        if not (0 <= top < rows and 0 <= left < cols and top < bottom <= rows and left < right <= cols):
            raise ValueError("Query area out of bounds.")
        
        total = prefix_sum[bottom][right] - prefix_sum[top][right] - prefix_sum[bottom][left] + prefix_sum[top][left]
        results.append(total)
    
    return results
```