Sometimes in our practice as dermatopathologists we face routine H&E sections that appear to show no abnormality on initial examination. The situation gets complicated when we do not have enough clinical data. The first impression that would come to mind in such conditions is that the biopsy site might have been missed and maybe we are looking at normal skin!!!! However, this is not usually the case. There are dermatological conditions that only show subtle histopathological features that can easily pass unnoticed. In case of lack of clinical data we should examine the layers of the skin systematically and carefully looking for clues.

Hyphae or spores in the stratum corneum may be the only clue for Tinea or Candida. An absent stratum granulosum may be the only clue for ichthyosis vulgaris. A cornoid lamella of porokeratosis my not be visible except at the very edge of the biopsy. Subtle vacuolar degeneration of the basal layer may be the only clue for GVHD or dermatomyositis.

Disorders of pigmentation such as vitiligo and other disorders may also be the case in such conditions. One should examine the basal layer for any apparent changes in melanocytes or in basal pigmentation. Special stains may be needed. Also adnexal related pathology must be searched for. The case could be alopecia for example. A subtle lymphohistiocytic infiltrate around the blood vessels and around the sweat glands with some degenerative changes in the sweat glands may be a clue for indeterminate leprosy.

The dermis should be examined carefully for subtle interstitial infiltrate, mucin deposition or connective tissue abnormalities. Also amyloid deposits should be looked for. One should think also of foreign materials such as: argyria, hemochromatosis or a tattoo pigment. Dermal edema may be a clue for urticaria and subtle collections of mast cells around blood vessels may point to telangiectasia macularis eruptive perstans.

Finally tumors might be subtle such as some forms of blue nevi, desmoplastic melanoma or some fibrous tumors. A metastasis in a lymphatic or an intravascular lymphoma may be all what we find in a routine H&E section!!

So whenever you encounter an apparently normal section take your time in examining all layers of the skin, examine the adnexae and examine the blood vessels before dismissing the case with a “no abnormality detected” final comment. You may also need to contact the clinician if he did not send you enough information and you might need to do special stains for melanocytes, melanin or amyloid.