Pagetoid dyskeratosis: a frequent pitfall in dermatopathology

ARTICLE

Auteur(s) : Jean Kanitakis, Viviana Lora

Lab. of Dermatopathology, Ed. Herriot Hospital, 69437 Lyon cedex 03, Lyon, France

Pagetoid dyskeratosis (PD) is an incidental histologic finding that can be observed in skin biopsies from various lesions, including acrochordons [1]. PD has been observed in various locations, such as the hand [2], lips [3], prepuce [4] and nipple [5]. PD cells are keratinocytes with a larger size than normal, usually a round shape, a pale cytoplasm and a pycnotic nucleus surrounded by a clear halo (figure 1). These cells predominate in the upper epidermis, i.e. the granular and upper malpighian layer, but may be found at any level within the malpighian layer. The exact nature of these cells is not known with certainty, although they are felt to result from mechanical irritation (friction). A recent immunohistochemical study of nipple PD cells showed them to express high MW keratins, but no low MW keratins (such as K7), HPV, Epithelial Membrane Antigen (EMA), Carcinoembryonic Antigen or gp100/HMB-45.

PD cells are a frequent casual finding in everyday dermatopathology practice and represent a diagnostic pitfall to the unaware, since they may morphologically mimic Paget’s cells (PC), Toker cells of the nipple (TC) and virally-induced (HPV) koilocytes (VK). PC cells usually predominate in the lower epidermis where they can be grouped to form gland-like structures, and have more or less atypical nuclei. VK are found in the upper epidermal layers (granular/upper malpighian) where they are usually clustered, and contain corse keratohyalin granules. TK are clear cells found in 10% of people of both sexes in the nipple epidermis. In doubtful cases, immunohistochemistry can aid in the differential diagnosis between PC (keratin 7+/EMA+/HPV–), PD (keratin 7–/HPV–/EMA–) and VK (HPV+/high MW keratins). The distinction between TK and PC is more subtle. It appears that (dermato)pathologists are not very familiar with PD, this fact being a cause of erroneous diagnoses. Such an example is the recent case report by Arpaia et al. [6], diagnosed as acral viral wart. This case is histologically typical of PD, as shown in fig. 1b (large vacuolated cells scattered in the upper epidermal layers with pycnotic nuclei surrounded by a clear halo and no keratohyalin granules). On the other hand, neither the macroscopical appearance of the lesion, manifesting as a pigmented macule, nor the dermatoscopical pattern (acral warts usually show an absence of dermatoglyphs) concur to the diagnosis of viral wart. Furthermore, no immunohistochemistry was done for HPV antigens to support the viral origin of the lesion. This case seems therefore very similar to PD manifesting with patchy hyperpigmentation of the hand [2], a condition of uncertain (but not viral) origin.

We certainly agree with authors’ recommendation that “in the case of dermatoscopically and/or clinically suspicious lesions surgical excision is strongly recommended, since only histological examination allows the correct diagnosis” and would like to add “… provided the (dermato)pathologist is aware of microscopic pitfalls such as pagetoid dyskeratosis”.

Acknowledgements

References

2 Wang LC, Medenica MM, Shea CR, Busbey S. Pagetoid dyskeratosis of the hand. J Am Acad Dermatol 2004; 50: 483-4.

3 Garijo MF, Val D, Val-Bernal JF. Pagetoid dyskeratosis of the lips. Am J Dermatopathol 2001; 23: 329-33.

4 Val-Bernal JF, Garijo MF. Pagetoid dyskeratosis of the prepuce. An incidental histologic finding resembling extramammary Paget’s disease. J Cutan Pathol 2000; 27: 385-7.

5 Garijo MF, Val D, Val-Bernal JF. Pagetoid dyskeratosis of the nipple epidermis: an incidental finding mimicking Paget’s disease of the nipple. APMIS 2008; 116: 139-46.

6 Arpaia N, Filotico R, Mastrandrea V, Cassano N, Vena G. Acral viral wart showing a parallel ridge pattern on dermatoscopy. Eur J Dermatol 2009; 19: 381-2.