Correspondence

Merkel cell polyomavirus in low levels in folliculotropic mycosis fungoides represents a passenger, not a driver

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There is currently no known causative agent for cutaneous T cell lymphoma (CTCL), although a possible infectious cause has long been suggested. The recent discovery of the etiologic role of Merkel cell polyomavirus (MCPyV) in Merkel cell carcinoma has led to numerous investigations into the role of MCPyV in other tumors. In general these studies have failed to demonstrate a role for MCPyV.1,2 A recent study by Kreuter et al.3 argued against a pathogenic role for polyomaviruses (PyVs) in primary cutaneous lymphoma overall; however, the authors found that six of eight folliculotropic mycosis fungoides (FT-MF) samples harbored MCPyV DNA.3 The present study was conducted to further investigate a role for MCPyV in FT-MF. We identified cases of FT-MF through a database search of biopsy specimens at the University of Pennsylvania. Controls were selected from cases read as folliculitis. Slides were reviewed to confirm the presence of follicular epithelium. Samples were then analyzed by real-time polymerase chain reaction (PCR) for the presence of MCPyV, with DNA quality assessment by b-globin reference gene PCR. DNA sufficient for analysis was present in all nine cases of FT-MF and in four of six controls. We performed PCR utilizing a primer set designed within the small T viral region with MCPyV copy number determination using the Quantification of MCPyV, Small T Region Kit (PrimerDesign Ltd, Southampton, UK), and the StepOne Plus instrument (Applied Biosystems, Foster City, CA, USA). Overall, MCPyV was detected in 77% of specimens (eight of nine cases of FT-MF and two of four controls). Levels of MCPyV were assessed using DNA copy number determination by real-time PCR and did not differ statistically between cases of FT-MF and controls. In all cases, levels of MCPyV (as measured by DNA copy number/ng DNA) were very low (range: 0.03–1.06/ng DNA). MCPyV was detected in 89% of FT-MF cases. However, it is important to note that 50% of control samples were also positive for MCPyV, which is similar to the 40% prevalence of MCPyV reported previously in studies of skin swab specimens from healthy adults.4 Although our results are suggestive of a higher prevalence of MCPyV in FT-MF compared with controls, this study was insufficiently powered to detect a statistically significant difference (P = 0.203, Fisher’s exact test) International Journal of Dermatology 2015, 54, e182–e196

because of its small sample size. Moreover, although we confirmed that FT-MF frequently harbors MCPyV DNA,3 the presence of MCPyV in control follicles and the overall low level of viral copy numbers suggests that MCPyV is widespread and probably represents a passenger rather than a driver in FT-MF. As we seek to better understand viral oncogenesis in CTCL, it is critical to recognize that most viruses detected in tumor samples may not be etiologically relevant. In FT-MF, MCPyV is likely to represent a routine inhabitant of the human hair follicle rather than a true causative agent. Experimental findings are further confounded by the altered immune milieu of FT-MF, which may contribute to greater variety in the types and amounts of bystander viral DNA detected.5 To better understand and elucidate the roles of various viruses in oncogenesis, further studies must establish a more complete understanding of the human viral microbiome. Acknowledgment We are indebted to Katrina Abuabara, MD, MA, Department of Dermatology, University of Pennsylvania, for statistical support. Rachel H. Gormley, MD Ellen J. Kim, MD Alain H. Rook, MD Carrie L. Kovarik, MD Department of Dermatology University of Pennsylvania Philadelphia PA, USA E-mail: [email protected] Alexander Sun, BS Perelman School of Medicine at the University of Pennsylvania Philadelphia PA, USA Peter Rady, MD, PhD Stephen K. Tyring, MD, PhD, MBA Department of Dermatology University of Texas Medical School at Houston Houston TX, USA

ª 2015 The International Society of Dermatology

Correspondence

References 1 Andres C, Puchta U, Sander CA, et al. Prevalence of Merkel cell polyomavirus DNA in cutaneous lymphomas, pseudolymphomas, and inflammatory skin diseases. Am J Dermatopathol 2010; 32: 593–598. 2 Shuda M, Arora R, Kwun HJ, et al. Human Merkel cell polyomavirus infection I. MCV T antigen expression in Merkel cell carcinoma, lymphoid tissues and lymphoid tumors. Int J Cancer 2009; 125: 1243–1249. 3 Kreuter A, Silling S, Dewan M, et al. Evaluation of four recently discovered human polyomaviruses in primary cutaneous B cell and T cell lymphoma. Arch Dermatol 2011; 147: 1449–1451. 4 Schowalter RM, Pastrana DV, Pumphrey KA, et al. Merkel cell polyomavirus and two previously unknown polyomaviruses are chronically shed from human skin. Cell Host Microbe 2010; 7: 509–515. 5 Mirvish JJ, Pomerantz RG, Falo LD Jr, et al. Role of infectious agents in cutaneous T cell lymphoma: facts and controversies. Clin Dermatol 2013; 31: 423–431.

Acne keloidalis nuchae in Latin American women

Acne keloidalis nuchae (AKN) is a chronic inflammatory disease that involves the hair follicles of the occipital base of the head and neck, leading to the formation of keloidal papules or plaques.1 It is caused by the entrapment of hair into the connective tissue, causing a foreign body reaction.2 It affects mostly those of African, Southeast Asian, and Hispanic descent. Its incidence is low, representing 0.45% of all African dermatoses. Few cases in women have been reported.2–5 The following report consists of three cases of AKN in mestizo women and one in an African-American woman. Case 1, a 42-year-old mestizo woman with curly hair, presented with a 10 9 5 cm scarring alopecic plaque studded with firm follicular papules and several hair shafts emerging from them. It was located on the nape of her neck and had evolved over six years. Her physical

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examination was relevant for acanthosis nigricans on her neck and both armpits, keratosis pilaris in the cheeks and lateral arm, and ulerythema ophryogenes in her eyebrows (Fig. 1). Her abdominal circumference measured 90 cm, and body mass index (BMI) was 28.4. Laboratory tests were within normal limits, except for insulin (25 mU/ml) and homeostatic model assessment estimated insulin resistance (HOMA-IR) (5.5). Case 2 is a 20-year-old mestizo female patient with straight hair and Down syndrome. She was evaluated for an alopecic, pruritic area of 7 9 5 cm located in her occiput with follicular papules, which had been present for over six months. She had acanthosis nigricans in flexural areas, striae distensae in arms and thighs, and keratosis pilaris (Fig. 2). The abdominal circumference was 98 cm, and BMI was 31.4. Her laboratory tests revealed cholesterol and triglyceride levels slightly above the upper limit of normal, fasting glucose 89 mg/dl, insulin 20 mU/ml, and HOMA 4.3. Case 3, a 46-year-old mestizo female patient with curly hair, was evaluated for an alopecic plaque that measured approximately 4 9 3 cm with few erythematous follicular papules in the occipital region that had been present for over four years (Fig. 3a). The abdominal circumference was 90 cm and BMI 28. Laboratory tests revealed a fasting glucose of 98 mg/dl, insulin 20.6 mU/ml, and HOMA 5.5. Case 4, a 40-year-old black female patient with curly hair, had a 6-year history of a large, painful, scarring alopecic plaque located in the nape of the neck (Fig. 3b). The abdominal circumference measured 70 cm and BMI 22.3. The laboratory tests were within normal values. AKN is almost exclusively reported in males.1 This suggests a pathophysiological mechanism related to male sex hormones (i.e., increase in testosterone levels, augmented sensitivity of hair follicles to androgens, or high levels of free androgens), occupation, sports, and shaving habits, which are less commonly observed in women. There are a few reports of AKN in women that showed no relation-

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Figure 1 (a) Alopecic area in the neck with follicular papules, through which emerges hair shafts and scar plates. (b) Keratotic follicular papules on erythematous areas located distally in both eyebrows ª 2015 The International Society of Dermatology

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