The cutaneous histopathology of chemotherapeutic reactions

Abstract

The histological diagnosis of chemotherapy-induced cutaneous reactions is a difficult problem for the dermatopathologist. The initial effort should be directed towards obtaining as much clinical history as possible since the provided information is often incomplete and clinical correlation is usually required. The biopsy should be examined in a systematic fashion to assess the presence of damage to specific cutaneous structures. A recommended approach is to initially examine the epidermis and then proceed to hair follicles, eccrine sweat glands, vessels and dermis. The degree and pattern of damage will usually indicate whether or not a cytotoxic reaction is present. The intensity, pattern, and components of the inflammatory response should be assessed since they provide clues to whether a hypersensitivity reaction or immunomodulating chemotherapeutic reaction is present. In addition to the possibility of a chemotherapeutic reaction, the dermatopathologist must also consider the possibility of an infection since the host is usually immunocompromised and must also exclude the presence of a residual malignancy. After examination of the biopsy specimen and determination of the pathologic process or precesses, the observed findings should be correlated with the clinical history before rendering an interpretation.

Hand-Foot Syndrome (Hand-Foot Skin Reaction, Palmar-Plantar Erythrodysesthesia): Focus on Sorafenib and Sunitinib

“…Both the timing of the eruption, which can occur as early as 24 h after drug administration, and the correlation between HFS and drug dosage observed in most of the series and trials strongly favor a directly toxic mechanism of injury [6,13]. The most common histopathologic pattern observed, a cell-poor lymphocytic interface dermatitis with basilar vacuolar degeneration and dyskeratosis, is also consistent with direct cytotoxic injury to the epidermis [10,22,25,91]. …”

Autologous GVHD?

“…14,[17][18] For example, radiation exposure, drugs and infection produce similar abnormalities in the skin and gut as acute GVHD. [19][20][21][22][23] The time at which these abnormalities are detected may help distinguish acute GVHD from radiation and drug-induced tissue damage, but this is not always so. 14 Several examples of the difficulty in using histological criteria to diagnose acute GVHD are explained below.…”

“…Confounding entities resembling acute GVHD include bacterial, fungal and viral infections, drug reactions, tissue damage from pre-transplant drugs and radiation, and other effects. 7,13,[18][19][20][21][22][37][38] There is no reason a transplant recipient cannot have more than one of these confounders. The bottom line is there are no convincing data to show that persons said to have auto-GvHD really have this disease, or that this disease really exists.…”

Skin Toxic Effects of Polyethylene Glycol–Coated Liposomal Doxorubicin

“…17 The rapid turnover rate of keratinocytes makes these cells most susceptible to cytotoxic damage induced by chemotherapy. 18 The pattern of damage is dictated not only by the inflicting drug but also by the method of administration. Compared with doxorubicin, Doxil has an extremely long circulation time, and it preferably localizes in the skin and deposits a substantial fraction of the administered drug there.…”