In 1st case, assuming an infinitesimal part of the lump, We consider the universe as the superposition of 1. The rest of the lump and 2. The other masses which we considered them all in a single mass density $\rho$.
The forces of the uniform infinite matter cancel on any infinitesimal part by symmetry. What remains is the force of the rest of the lump.
After integrating over the volume of the lump, The second part also becomes zero as a system can't exert force on itself.
About The second configuration, aside form the fact that the lump can't exert force on itself as we stated above, we must be calculate a thing.
A particle in a uniform sphere of mass density $\rho$, if off-center, WILL feel force. As you say, we assume the lump's in the center (of course it's unclear because if it possesses dimension (it's not a point), It matters which point of it is in the center!).
The gravitational field inside a uniform sphere given by:
$$\mathbf{g}=-4\pi\rho G r\mathbf{\hat r}$$
So the total force due to the big sphere on the lump will be:
$$\mathbf{F}=\int_\text{the lump}\mathbf{g} dm=-4\pi\rho G \int_\text{the lump}\mathbf{r}dm=-4\pi\rho G M \mathbf{r_\text{center of mass}}$$
The last integral is by definition equal to $M \mathbf{r_{center of mass}}$. So,
Whether or not, the lump in the second configuration will feel force depends on the result of Where the center of mass is located. If the center of mass of the lump is in the center of the big sphere, the lump will not feel force.