TEC

In the evaluation of a recent case, a pediatric patient with a history of relapsed Hodgkin lymphoma who was status post stem cell transplantation presented with an acute eruption with small follicular papules. A punch biopsy demonstrated vacuolar interface dermatitis with a sparse lymphocytic infiltrate and subtle hyperkeratosis. Interestingly, the vacuolar change extensively involved follicular epithelium, and concomitant infundibular plugging was also noted. Given the combination of recent transplantation jointly with adnexal vacuolar change, the diagnosis of graft-vs.-host disease (GVHD) seemed apropos and tempting. However, correlation with the clinical situation clarified that the transplant was autologous and additionally revealed that there had been recent busulfan administration. A medication-induced phenomenon was suspected clinically. In another recent case, an adult patient who was two weeks status post bone marrow transplantation for myelodysplasia developed a widespread erythematous eruption that was both truncal and acral in its distribution. A bisected punch biopsy from the back demonstrated subacute vacuolar interface dermatitis with a sparse infiltrate, modest hyperkeratosis, and remarkable epithelial dysmaturation. Additionally, both acantholysis and dyskeratosis were focally apparent in one of the two cross sections within the prepared slide. This created a configuration vaguely resembling an actinic keratosis, given the combination of focal acantholysis and a jumbled epithelium that included enlarged keratinocytes in outer epithelial layers. However, the presentation as an extensive dermatitis at a sun-protected site, with vacuolar change seen microscopically, indicated the eruption was non-neoplastic in nature. What is the interrelationship between the adolescent and the adult briefly mentioned above? Both represent examples of toxic erythema of chemotherapy (TEC)1, a designation that unifies a broad and heterogeneous disorder that has steadily evolved in the realm of dermatology, dermatopathology, and oncology over the last three decades. [Editor’s note: if one has not recently read the remarkable thesis on the subject by Bolognia, Cooper, and Glusac recently, or if one has not ever reviewed it, the time is now. The paper represents a brilliant and compelling distillation of the matter.] First recognized as a ‘peculiar acral erythema’ by Burgdorf and colleagues2, the designations ‘chemotherapy-associated acral erythema’ and ‘hand-foot syndrome’ emerged as diagnostic terms, subsequently, for the iatrogenic malady that has now been consolidated as TEC.3– 6 Independently, it was recognized that the administration of chemotherapy could evoke neutrophilic eccrine hidradenitis (NEH) and syringosquamous metaplasia (eccrine squamous syringometaplasia).7 Both are typified by a papular erythematous eruption that develops within a few days to a few weeks of the delivery of any of a variety of antineoplastic medications. The distribution may be accentuated within acral skin but is not uncommonly widespread.7,8 Because of partially overlapping histopathologic findings and an affinity for the eccrine gland, the fact that NEH and syringosquamous metaplasia represent different parts of the same disease spectrum was grasped relatively soon after their description.7 Appreciation of the fact that there is only one iatrogenic disease here, namely TEC, and awareness that that disorder encompasses the spectrum seminally described as acral erythema, NEH, and syringosquamous metaplasia, dawned more slowly.1 What are the histopathologic principles that facilitate the objective and accurate microscopic diagnosis of TEC? Most crucial is cognizance that TEC may involve any epithelial component of the skin, be it the epidermis, the eccrine duct and gland, or the folliculosebaceous-apocrine unit. It makes intuitive sense that antimetabolite effects might conspicuously influence eccrine epithelium, as medication byproducts may be concentrated and/or secreted within the eccrine apparatus, but TEC represents a pan-epithelial toxic disorder. Because