Palmar Pagetoid dyskeratosis: A sheep in wolf’s clothing
By Warren R. Heymann, MD, FAAD
Nov. 30, 2022
Vol. 4, No. 47
Furrows are fine, ridges are risky.
I learned that phrase in a stellar lecture given by Jennifer A. Stein, MD, PhD, FAAD, discussing the use of dermoscopy for acral pigmented lesions. It has served me in good stead as I have reassured many patients that their acral nevi appear benign and have identified cases of acral lentiginous melanoma with greater confidence.
A parallel ridge pattern on dermoscopy is highly sensitive and specific for acral lentiginous melanoma on the palms and soles, although it may be observed in other conditions including subcorneal hemorrhages, posttraumatic purpura, congenital nevi, blue nevi, lentigines, acral angiomas, verrucae, chemotherapy-induced hyperpigmentation, fixed drug eruptions, exogenous pigmentation, and ethnic pigmentation. (1,2) Dermatologists should now also add palmar Pagetoid dyskeratosis (PPD) to this list, as there have been an increasing number of reports of this benign disorder. This commentary will focus on Pagetoid dyskeratosis of the hands (PDH), of which PPD is a subset.
What is Pagetoid dyskeratosis (PD)?
PD cells are keratinocytes appearing larger than normal, with a round shape, a pale cytoplasm, and a pyknotic nucleus surrounded by a clear halo, and are distinct from other epidermal “clear” cells as observed in Paget disease, Pagetoid squamous cell carcinoma in situ, epidermotropic metastasis, superficial spreading Pagetoid melanoma, clear cell papulosis, koilocytoses, and Toker cells of the nipple. Immunohistochemical stains demonstrate that PD cells express high-molecular-weight keratins but not the low-molecular-weight types, human papillomavirus, epithelial membrane antigen, carcinoembryonic antigen, or GP100/HMB-45. (3)
Despite being previously recognized by other pathologists, the initial analysis of these intraepidermal clear cells was performed by Mehregan in 15 cases. He attributed these cells to an artifact, although he acknowledged that they were frequently observed in intertriginous regions, suggesting that moisture could be a pathogenic factor. (4) Based on their study of 44 cases of PD, including one case for electron microscopy, Tschen et al stated “we believe that these cells are probably a small part of the normal population of keratinocytes and that under certain circumstances they can be induced;” friction was considered the likely culprit. (5)
In their study of 3,565 biopsies, Santos-Briz et al appreciated PD cells in 80 cases (2.24%). Melanocytic nevi were the commonest skin lesions in which PD was observed, followed by soft fibromas, angiofibromas, and acrochordons. Most lesions were located on the head, neck, and trunk. (3) Tokat et al noted that 8 of 32 cases angiofibromas displayed PD. (6)
Is Pagetoid dyskeratosis (PD) clinically relevant?
Other than being a histologic oddity that could mimic significant pathological disorders, there is one entity where the PD may be a primary finding — PDH and its PPD variant.
In what may have been the first reported case of PDH, Frenk and Delacrétaz present 2 patients with brownish, ill-defined macules on their fingers, in one case also on elbows and knees. Light microscopy revealed identical changes in both cases: scattered, swollen, vacuolated, clear keratinocytes in the suprabasal epidermis and horny layer. Electron microscopy showed alterations that were interpreted as hydropic degeneration of keratinocytes. (7) The term PDH was first utilized by Wang et al who detailed the case of a 26-year-old woman who presented with a 6-year history of intermittent discoloration manifesting as ill-defined, golden-yellow to light-brown patches over the metacarpophalangeal joint of the thumb clinically with PD histologically. (8)
There have now been multiple reports of PDH that involve the palm (PPD) or volar aspect of the fingers; these lesions demonstrate brown pigmentation of the ridges on dermoscopy. (1,2,9,10,11) Most cases have been reported in women, often with a history of repeated friction and trauma, especially with broomsticks. (1) Clinically, the lesions have a linear shape and an orange-brown color. The color has been attributed to the PD cells along the crista cutis, triggering scattered reflection and correlating with the parallel ridge pattern on dermoscopy. (1,2). The clinical differential diagnosis includes tinea nigra, chromhidrosis, exogenous pigmentation, subcorneal hemorrhage, and of course acral lentiginous melanoma. (2) Upon review of these articles, the dermoscopic image of PDH/PPD concerns me more than its clinical appearance. As this is a benign disorder that usually resolves with the elimination of precipitating frictional trauma, no treatment is required. A biopsy should be performed if there is no resolution of the lesions and/or if there is any doubt about the clinical diagnosis. (1)
Point to Remember: Pagetoid dyskeratosis is a benign process that must be recognized by dermatopathologists to avoid the misdiagnosis of extramammary Paget disease, Pagetoid squamous cell carcinoma in situ, and Pagetoid melanoma. Clinicians should recognize that Pagetoid dyskeratosis may present clinically as hyperpigmented patches on acral sites, with dermoscopy revealing a parallel ridge pattern that is reminiscent of acral lentiginous melanoma.
Our expert’s viewpoint
Christopher R. Shea, MD, FAAD
Eugene J. Van Scott Professor in Dermatology
Director, Dermatopathology Fellowship Program
Section of Dermatology
University of Chicago Medicine
Pagetoid dyskeratosis (PD) is a fairly common histopathologic curiosity, but one that may set a trap for inexperienced microscopists, misleading them into erroneously diagnosing sinister conditions such as melanoma, Paget disease of breast, or other epidermotropic malignancies. Despite its alarming name, PD is a benign and asymptomatic disorder of premature keratinization (i.e., dyskeratosis). New research, showing that this innocent and enigmatic condition may also simulate melanoma dermatoscopically, completes the deception.
It remains unclear precisely what mechanism is responsible for the characteristic yellow-brown hyperpigmentation of PD lesions. The process of dyskeratosis might be expected to favor the liberation of melanin pigment from damaged keratinocytes, and its subsequent deposition within dermal melanophages, but such a finding is not seen in PD. Perhaps the explanation is that the dyskeratotic cells in PD are typically located well above the basal layer of the epidermis, and therefore tend to be eliminated transepidermally rather than forming colloid bodies with pigment incontinence in the dermis, as in lichenoid interface dermatitis.
Another potential cause of hyperpigmentation might be hemosiderin deposition, as suggested by the reported association of PD with local trauma to the skin. However, neither iron nor melanin pigments appear to be altered in PD. It has been hypothesized that PD alters the reflectance characteristics of the affected epidermis; this potential explanation for the observed changes in color seems logical but remains speculative. Non-invasive methods of in vivo optical imaging of tissue such as confocal scanning laser microscopy might be fruitfully applied to this problem. More simply, it would be interesting to report the results of examining PD lesions under UVA illumination using Wood’s lamp.
Jennifer A. Stein, MD, PhD, FAAD
Professor, Ronald O. Perelman Department of Dermatology at NYU Grossman School of Medicine
Director, Dermatology Medical Faculty Group Practice
I did not create the mnemonic “furrows are fine, ridges are risky,” but I am a big fan because it is so helpful for remembering that the parallel furrow pattern is a reassuring dermoscopic feature of acral nevi and the parallel ridge pattern is worrisome for melanoma. As a general rule, a new lesion with a parallel ridge pattern should be viewed with a high degree of suspicion for acral melanoma, though there are a few exceptions, such as palmar Pagetoid dyskeratosis (PPD), as described in this excellent article by Dr. Heymann.
A common benign lesion that has pigment on the ridge is subcorneal hemorrhage, though the pigment should be red to black dots and globules or a solid blotch, which is usually distinguishable from melanoma by both the color and pattern. If there is still any uncertainty, the diagnosis can be confirmed by paring off the pigment in the stratum corneum with a 15 blade.
Congenital nevi can sometimes have pigment on the ridge, but usually the pigment is in the form of dots or globules next to the eccrine acrosyringia, rather than a parallel ridge pattern. The history and stable nature should also be reassuring of the diagnosis of congenital nevus. Importantly, acral lesions in Fitzpatrick type V and VI skin can sometimes display pigment on the ridge, which is challenging because acral melanomas account for a larger proportion of melanomas in patients with skin of color. More needs to be understood about the parallel ridge pattern in acral lesions in Fitzpatrick V and VI and it is an active area of research. Other clinical scenarios with pigment on the ridge include dye (should be able to pare off), pigmented macules associated with Peutz-Jeghers syndrome (should be multiple), and drug-induced hyperpigmentation of acral skin (history can confirm).
In his article, Dr. Heymann points out that PPD is another scenario in which one can encounter the parallel ridge pattern on acral skin. As Dr. Heymann notes, although PPD may have a worrisome dermoscopic pattern, its distinctive clinical appearance would not be confused for a melanoma. Although dermoscopy is an important clinical tool, it should never replace your clinical judgement, but should be used in combination with other clinical information to help determine the best diagnosis for the patient.
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