How do you differentiate atopic dermatitis from mycosis fungoides histologically?

Differentiating mycosis fungoides from any spongiotic process (atopic dermatitis, allergic contact dermatitis, etc.) is extremely difficult and typically requires correlation with clinical features and sometimes molecular findings. Some features that favor mycosis fungoides are:

1. Lymphocytic exocytosis in the setting of minimal to no epidermal spongiosis
2. Intraepidermal lymphocytes that are larger than those in the dermis
3. Clusters of intraepidermal lymphocytes with surrounding haloes
4. Papillary dermal fibroplasia that appears to trap the dermal lymphocytes
5. A predominance of the dermal lymphocytic infiltrate collecting on the epidermal side of the superficial vascular plexus

Immunohistochemical stains can play a role as well with a predominance of CD4+ T cells in the epidermis and loss of CD5 and CD7 expression within the intraepidermal lymphocytic population. It is helpful to remember that some cases of mycosis fungoides can show a predominance of CD8+ instead of CD4+ cells.

Spongtiotic processes are characterized by varying levels of epidermal spongiosis that are out of proportion to the amount of lymphocytic exocytosis. Serum crust, eosinophils, and lack of lymphocytic cytologic atypia are also supportive of spongiotic dermatitis.  

Histology should always be paired with clinical features, however, as most cases do not read the textbook. Some patients need to be followed closely with serial biopsies until a definitive diagnosis can be made.