Background:  Cutaneous infectious and inflammatory diseases may contain a significant number of CD30-positive cells, thus mimicking lymphomatoid papulosis (LyP) or anaplastic large cell lymphoma.

Methods:  We reviewed our cases of non-neoplastic skin conditions with large, CD30-positive cells and searched the literature for similar cases.

Results:  A total of 28 cases were included in the study: Milker’s nodule (n = 8), Herpes simplex virus infection (n = 7), lymphomatoid drug reaction (n = 3), molluscum contagiosum (n = 3), nodular scabies (n = 2), leishmaniasis (n = 1), syphilis (n = 1), pernio (n = 1), ruptured infundibular cyst (n = 1) and pseudolymphoma in a scar (n = 1). CD30-positive cells were often arranged in clusters and revealed both Golgi and membrane positivity, similar to what was observed in LyP and CD30+ anaplastic large T-cell lymphoma.

Conclusions:  Analysis of our data and of those published in the literature shows that viruses and drugs are the most common cause for occurrence of large CD30-positive cells in cutaneous pseudolymphomatous infiltrates. Arrangement of these large, CD30-positive cells in small clusters is not unique to cutaneous CD30-positive lymphomas, and in many cases a precise diagnosis can be made only upon accurate clinicopathological correlation or using ancillary methods such as polymerase chain reaction analysis for viral DNA.