Clear cell papulosis: Clearly distinctive, clearly underrecognized
By Warren R. Heymann, MD
June 3, 2020
Vol. 2, No. 22
One of my greatest joys in dermatology is diagnosing a disease that I have only read about, but then encounter in life. That “aha moment” is exhilarating! When attending patient presentations at dermatology conferences, I encourage my residents not to look at the protocols first — this way they are unbiased and forced to reach their own conclusions. Last spring, at the Philadelphia Dermatological Society Meeting held at the Philadelphia College of Osteopathic Medicine, a 2-year-old Pakistani girl with suprapubic and lower abdominal hypopigmented papules, confirmed histologically as clear cell papulosis (CCP), was presented. (1) That was my clinical impression — I felt like Irene Cara singing “What a Feeling!”
CCP was first described by Kuo et al in two young brothers whose white papules demonstrated benign Pagetoid clear cells within an acanthotic epidermis displaying decreased pigmentation. These cells contained mucin and stained positive for keratin AE1/AE3, carcinoembryonic antigen (CEA) and epithelial membrane antigen (EMA). (2)
Most cases have been reported in those of Asian descent with a female predominance. CCP characteristically presents in the first year of life, and, with rare exception, after the age of 6 years. Morphologically, CCP presents multiple, asymptomatic, white macules, or papules 2‐10mm in diameter. Distribution is mostly on the lower abdomen but are often arranged along the milk lines. (1) Dermoscopy of CCP presents as an irregularly bordered depigmented structureless lesion. (3) CCP is typically self‐limited as lesions spontaneously resolve with age and is restricted to the skin without systemic symptoms. In a study of 19 patients with CCP, with a median follow-up duration of 11.5 years, regression of skin lesions was observed in 85.7% of patients. Despite the similarity to Paget cells, there is no evidence to suggest that CCP is a potential precursor of mammary/extramammary Paget disease. (3)
The clinical differential diagnosis includes flat warts, epidermodysplasia verruciformis, tinea versicolor, idiopathic guttate hypomelanosis, nevus anemicus, nevus depigmentosus, guttate morphea, lichen sclerosis, Langerhans cell histiocytosis, pityriasis alba, or cutaneous T cell lymphoma. When you review the literature, it is obvious (clear!) how similar these cases are — the correct diagnosis can be made clinically, if you think of it. I would never fault anyone for considering these other entities, but they can easily be ruled out by a KOH exam and biopsy. Aside from the H&E, and stains mentioned above, the CK-7 may be variably positive while stains for Langerhans cells or melanocytes (S100, CD1a and MART-1) are negative. (5)
The pathogenesis of CCP remains to be defined. There may be a genetic predisposition. The differential diagnosis of pale cells in the epidermis includes Toker cells, Paget/extramammary Paget disease, and CCP. The clear cells of CCP share a similar immunohistochemical staining pattern with all 4 conditions: positive for EMA, CEA, AE-1, AE-3, CAM-5.2, and CK-7. Yu et al studied the case CCP in a 1-year-old Asian-American girl finding that the Her2/neu, p53, ER (estrogen receptor), and PR (progestin receptor) staining results were all negative. The authors hypothesized that “both the clear cells of CCP and Paget cells may represent an aberrant differentiation from Toker cells that have lost their PR and ER staining characteristics but acquired the trait of positive staining for mucin.” (6) As melanocytes are present, the hypopigmentation of CCP is presumed to be due to melanocyte dysfunction or aberrant melanogenesis. (3)
Once diagnosed, how should CCP be managed? The answer is clear — reassure the parents that this is an asymptomatic benign process that will abate with time. No treatment is the right treatment. If there was ever a disorder where “first do no harm applies,” CCP is the poster child.
Point to Remember: Clear cell papulosis is a benign, self-limited disorder presenting as hypopigmented macules and papules along the milk line, especially on the lower abdomen and suprapubic region. Recognizing CCP is the key — once the diagnosis is established, reassurance is all that is necessary, clearly.
Our Expert’s Viewpoint
Howard Pride, MD
Clear cell papulosis is purportedly a rare entity that is not found in the index of the major pediatric dermatology text books. It is harmless and tends to go away without incident, so it is likely both underrecognized and underdiagnosed. I wonder how many times I have set eyes on this condition only to shrug it off as a “benign lesion” and move on. It falls well into the category of, “I haven’t seen it, but it has seen me.”
Dorfman CO, Quinn K, McGonagle M, Schwarz E. Clear cell papulosis: A case report of a rare entity. Pediatr Dermatol 2019; 36: 718-719.
Kuo TT, Chan HL, Hsueh S. Clear cell papulosis of the skin. A new entity with histogenic implications for cutaneous Paget’s disease. Am J Surg Pathol 1987; 11: 627-634.
Leerunyakul K, Kanokrungsee S, Rutnin S. Clear cell papulosis: Dermatoscopic findings and literature review. Pediatr Dermatol 2019; 36: 655-657.
Tseng FW, Kuo TT, Lu PH, Chan HL, et al. Long-term follow-up study of clear cell papulosis. J Am Acad Dermatol 2010; 63: 266-273.
Seykora CM, Dalton SR, Brown PJ. Clear cell papulosis: Report and review. Dermatol Online J 2018; 24 (1): 15.
Yu Y, Sukhatme S, Loo DS. Clear cell papulosis: A connection of clear cells to Toker cells or Paget disease. Arch Dermatol 2009; 145: 1066-1068.
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