A Recurrent Case of Papillary Eccrine Adenoma.

Papillary eccrine adenoma (PEA) is a rare benign eccrine gland neoplasm presenting as a solitary nodule, primarily in middle-aged African American females. Accurate histological diagnosis is crucial due to its potential to mimic adnexal carcinomas. Complete excision is recommended due to its risk of local aggression and recurrence. A 75-year-old Caucasian male with a history of basal cell carcinoma (BCC) presented with a recurrent pink, scaly nodule on the right medial pretibial leg area. Initial biopsy showed benign PEA. The lesion recurred after one year, and a re-biopsy confirmed a tubulopapillary adenoma within a scar. The lesion was excised with a 2 mm margin. PEA is characterized histologically by dilated ducts lined by a dual layer of tumor cells, often with intraluminal papillae structures. Immunohistochemical staining aids diagnosis, with markers such as S-100, carcinoembryonic antigen (CEA), and epithelial membrane antigen (EMA) indicating eccrine differentiation. Differential diagnoses include adnexal carcinomas and BCC with eccrine differentiation. Complete excision is necessary to prevent recurrence.

Sweat gland development requires an eccrine dermal niche and couples two epidermal programs.

Eccrine sweat glands are indispensable for human thermoregulation and, similar to other mammalian skin appendages, form from multipotent epidermal progenitors. Limited understanding of how epidermal progenitors specialize to form these vital organs has precluded therapeutic efforts toward their regeneration. Herein, we applied single-nucleus transcriptomics to compare the expression content of wild-type, eccrine-forming mouse skin to that of mice harboring a skin-specific disruption of Engrailed 1 (En1), a transcription factor that promotes eccrine gland formation in humans and mice. We identify two concurrent but disproportionate epidermal transcriptomes in the early eccrine anlagen: one that is shared with hair follicles and one that is En1 dependent and eccrine specific. We demonstrate that eccrine development requires the induction of a dermal niche proximal to each developing gland in humans and mice. Our study defines the signatures of eccrine identity and uncovers the eccrine dermal niche, setting the stage for targeted regeneration and comprehensive skin repair.

Adult-Onset Subungual Eccrine Angiomatous Hamartoma on Right Great Toe: A Case Report.

Eccrine angiomatous hamartoma (EAH) is a benign skin nodule characterized by the proliferation of eccrine glands and vascular structures in the dermis. It usually presents as a single papule or nodule on the extremities, and usually arises at birth or in early childhood, but several cases which appeared in adulthood have been reported. A 52-year-old female presented with a tender subungual nodule on the right great toenail for 3 months. Skin biopsy from the lesion showed proliferation of eccrine glands and capillaries in the dermis, and immunohistochemistry confirmed the diagnosis of EAH. We excised it as a treatment, and at the 3-month follow-up, pain by her lesion has resolved without any adverse effects. Our presented case is an adult-onset EAH that occurred as a subungual lesion. Unlike the previous cases, it did not cause any nail deformity or destruction and initially was misinterpreted as some other subungual tender nodule. To the best of our knowledge, we report the first case of adult-onset subungual EAH without nail deformity.

Perianal Linear Syringocystadenoma Papilliferum: A Case Report with Review of the Literature.

Syringocystadenoma papilliferum is a rare benign adnexal tumor that originates from the apocrine and eccrine glands. It mainly manifests as a solitary lesion in the head and neck; however, rarely, it may involve the trunk and limbs, typically with a linear pattern. Here, we report an extremely rare case of congenital linear syringocystadenoma papilliferum on the left buttock near the anus in a 6-year-old girl. This lesion should be considered in the list of differential diagnosis of linear lesions in order to prevent complications with proper diagnosis, treatment or follow-up.

Diagnostic Accuracy of Hyperpigmented Microcircles in Dermatoscopy of Non-Facial Non-Acral Melanomas: A Pilot Retrospective Study using a Public Image Database.

BACKGROUND: Grey perifollicular circles are a dermatoscopic clue to melanoma, especially in facial skin. So far, no other adnexal clues than follicular have been investigated in this diagnosis. OBJECTIVES: The study aimed to analyse the prevalence of hyperpigmented periadnexal microcircles (HMs) in melanoma and its common simulators at non-facial non-acral sites, analyse the relation between the presence of HM, regression and hypopigmentation, and evaluate the diagnostic accuracy of this structure in melanoma. METHODS: International Skin Imaging Collaboration (69,445 images) was searched in April 2020 for the pathology-confirmed dermatoscopic images with metadata including sex, age bin, and declared non-acral non-facial anatomic site. The final study sample (5,408 images, 1,326 of which were melanomas) was evaluated by expert dermatoscopist blinded to the diagnosis and labelled for the presence of ≥3 HM distributed centrally (cHM) or peripherally (pHM), hypopigmentation, and classic dermatoscopic regression structures. A subset of 40 images was labelled by 7 raters (2 residents, 5 experts) to assess interobserver agreement. We compared the presence of pHM with the presence of regression as well as performed a set of independent χ2 tests to evaluate the discriminatory power and its fragility. Performance of the models was assessed using measures of discrimination and calibration. RESULTS: HM were significantly more prevalent in melanomas than in non-melanomas and nevi. Fair/good interobserver agreement for HM was reached for all the raters, and moderate/good for experts only (single rater/average, respectively). Regardless of regression/hypopigmentation status, pHM were significantly more common in melanoma than in non-melanomas or nevi and were observed significantly more often in melanomas on sun-damaged skin (upper extremity, posterior torso). No significant differences between the groups were found for cHM. pHM proved a high odds ratio in the tests as to the classical indicators such as classic dermatoscopic regression structures. CONCLUSION: pHM could be considered a novel dermatoscopic clue to melanoma.

A case of hematohidrosis successfully treated with a beta-blocker.

Hematohidrosis is a rare disorder characterized by bloody sweating on the skin without trauma. The ear, nose, and other facial areas are the most commonly affected sites. This study shows usefulness of beta-blockers in the treatment of hematohidrosis.

Molecular and Physiological Functions of PACAP in Sweat Secretion.

Sweat plays a critical role in human body, including thermoregulation and the maintenance of the skin environment and health. Hyperhidrosis and anhidrosis are caused by abnormalities in sweat secretion, resulting in severe skin conditions (pruritus and erythema). Bioactive peptide and pituitary adenylate cyclase-activating polypeptide (PACAP) was isolated and identified to activate adenylate cyclase in pituitary cells. Recently, it was reported that PACAP increases sweat secretion via PAC1R in mice and promotes the translocation of AQP5 to the cell membrane through increasing intracellular [Ca2+] via PAC1R in NCL-SG3 cells. However, intracellular signaling mechanisms by PACAP are poorly clarified. Here, we used PAC1R knockout (KO) mice and wild-type (WT) mice to observe changes in AQP5 localization and gene expression in sweat glands by PACAP treatment. Immunohistochemistry revealed that PACAP promoted the translocation of AQP5 to the lumen side in the eccrine gland via PAC1R. Furthermore, PACAP up-regulated the expression of genes (Ptgs2, Kcnn2, Cacna1s) involved in sweat secretion in WT mice. Moreover, PACAP treatment was found to down-regulate the Chrna1 gene expression in PAC1R KO mice. These genes were found to be involved in multiple pathways related to sweating. Our data provide a solid basis for future research initiatives in order to develop new therapies to treat sweating disorders.

TRPS1 Is Differentially Expressed in a Variety of Malignant and Benign Cutaneous Sweat Gland Neoplasms.

Neoplasms of sweat glands and the breast may be morphologically and immunophenotypically similar. A recent study showed that TRPS1 staining is a highly sensitive and specific marker for breast carcinoma. In this study, we analyzed TRPS1 expression in a spectrum of cutaneous sweat gland tumors. We stained five microcystic adnexal carcinomas (MACs), three eccrine adenocarcinomas, two syringoid eccrine carcinomas, four hidradenocarcinomas, six porocarcinomas, one eccrine carcinoma-NOS, 11 hidradenomas, nine poromas, seven cylindromas, three spiradenomas, and 10 syringomas with TRPS1 antibodies. All of the MACs and syringomas were negative. Every cylindroma and two of the three spiradenomas demonstrated intense staining in cells lining the ductular spaces, with negative to relatively weak expression in surrounding cells. Of the 16 remaining malignant entities, 13 were intermediate to high positive, one was low positive, and two were negative. From the 20 hidradenomas and poromas, intermediate to high positivity was revealed in 14 cases, low positivity in three cases, and negative staining in three cases. Our study demonstrates a very high (86%) expression of TRPS1 in malignant and benign adnexal tumors that are mainly composed of islands or nodules with polygonal cells, e.g., hidradenomas. On the other hand, tumors with small ducts or strands of cells, such as MACs, appear to be completely negative. This differential staining among types of sweat gland tumors may represent either differential cells of origin or divergent differentiation and has the potential to be used as a diagnostic tool in the future.

Transglutaminase Activity Is Conserved in Stratified Epithelia and Skin Appendages of Mammals and Birds.

The cross-linking of structural proteins is critical for establishing the mechanical stability of the epithelial compartments of the skin and skin appendages. The introduction of isopeptide bonds between glutamine and lysine residues depends on catalysis by transglutaminases and represents the main protein cross-linking mechanism besides the formation of disulfide bonds. Here, we used a fluorescent labeling protocol to localize the activity of transglutaminases on thin sections of the integument and its appendages in mammals and birds. In human tissues, transglutaminase activity was detected in the granular layer of the epidermis, suprabasal layers of the gingival epithelium, the duct of sweat glands, hair follicles and the nail matrix. In the skin appendages of chickens, transglutaminase activity was present in the claw matrix, the feather follicle sheath, the feather sheath and in differentiating keratinocytes of feather barb ridges. During chicken embryogenesis, active transglutaminase was found in the cornifying epidermis, the periderm and the subperiderm. Transglutaminase activity was also detected in the filiform papillae on the tongue of mice and in conical papillae on the tongue of chickens. In summary, our study reveals that transglutaminase activities are widely distributed in integumentary structures and suggests that transglutamination contributes to the cornification of hard skin appendages such as nails and feathers.

Impacts of Skin Eccrine Glands on the Measured Values of Transepidermal Water Loss.

Transepidermal water loss (TEWL) is widely used to assess and quantify skin insensible water loss to assess skin's barrier function integrity. Low TEWL values are normally indicative of intact skin and a healthy functional barrier, whereas an increased TEWL reveals a disturbed or disrupted skin barrier. Because most skin sites at which these measurements are made have eccrine glands present, the contribution of the sweat gland activity to these measurements is variable and, in most cases, unknown. The separation between the contribution of water loss that is reflective of the skin barrier integrity versus that contributed via eccrine activation is not easy and is made more difficult since both components increase with increasing skin and environmental temperature. Endogenous factors that impact eccrine sweat gland activity include sympathetic nervous system activity, emotional stress, physical activity, eccrine gland density, and age. Exogenous factors that impact eccrine gland activity include ambient temperature and humidity and the climate where one resides. The aforementioned variables impact eccrine gland activity positively or negatively and therefore alter TEWL values accordingly. Although it may be theoretically possible to control all these factors, the difficulty in doing so results in only a few being controlled during most TEWL measurements. Such confounding processes may have impacted historical TEWL reference ranges and values previously reported. Thus, the impact of eccrine activation on standardly measured TEWL values is at this juncture unclear and may be a component contributing to some reported variability in TEWL values. To help clarify the issues, a literature review was conducted to investigate and summarize relevant prior research efforts and outcomes with respect to ways to consider eccrine activity in TEWL measurements and estimate the contribution of eccrine gland activity to TEWL values. Online databases such as Excerpta Medica Database (EMBASE), Public/Publisher Medline (PubMed), Elton B. Stephans Company (EBSCO), Google Scholar, and Wiley Online Library were searched with "transepidermal water loss" or "TEWL" in the title combined with "eccrine glands" or "sweat" anywhere in the text. The present findings indicate a multiplicity of biological and environmental variables impacting eccrine gland activity and thereby potentially affecting measured TEWL values. Even if laboratory conditions adhere to various guidelines and recommendations, it is not yet possible to separate the eccrine activation component from the parameter of true interest in the assessment of the skin's physiological barrier function except for full gland deactivation. The amount that such eccrine gland activation impacts the measured value of TEWL is generally not determined using currently available methods and the only sure way to eliminate a confounding effect is to inactivate the glands during such TEWL measurements. Because such eccrine gland deactivating approach is not usually desirable or even possible, other approaches would be recommended. One would be the development of a measuring device that could distinguish between the component of TEWL that is associated with the skin barrier function and the other that is attributable to sweat gland activation. Further research and development along these lines appear warranted.

Effect of PACAP on sweat secretion by immortalized human sweat gland cells.

The process of sweating plays an important role in the human body, including thermoregulation and maintenance of the environment and health of the skin. It is known that the conditions of hyperhidrosis and anhidrosis are caused by abnormalities in sweat secretion and can result in severe skin conditions such as pruritus and erythema, which significantly reduce the patient's quality of life. However, there are many aspects of the signaling mechanisms in the process of sweating that have not been clarified, and no effective therapies or therapeutic agents have yet been discovered. Previously, it was reported that pituitary adenylate cyclase-activating polypeptide (PACAP) promotes sweating, but details of the underlying mechanism has not been clarified. We used immortalized human eccrine gland cells (NCL-SG3 cell) to investigate how sweat secretion is induced by PACAP. Intracellular Ca2+ levels were increased in these cells following their exposure to physiological concentrations of PACAP. Intracellular Ca2+ was not elevated when cells were concomitantly treated with PA-8, a specific PAC1-R antagonist, suggesting that PAC1-R is involved in the elevation of intracellular Ca2+ levels in response to PACAP treatment. Furthermore, immunocytochemistry experiments showed that aquaporin-5 was translocated from the cytoplasm to the cell membrane by PACAP. These results suggest that PACAP acts on eccrine sweat glands to promote sweat secretion by translocation of aquaporin-5 to the cell membrane in response to increased levels of intracellular Ca2+. These findings also provide a solid basis for future research initiatives to develop new therapies to treat sweating disorders.

Stem cell spreading dynamics intrinsically differentiate acral melanomas from nevi.

Early differential diagnosis between malignant and benign tumors and their underlying intrinsic differences are the most critical issues for life-threatening cancers. To study whether human acral melanomas, deadly cancers that occur on non-hair-bearing skin, have distinct origins that underlie their invasive capability, we develop fate-tracing technologies of melanocyte stem cells in sweat glands (glandular McSCs) and in melanoma models in mice and compare the cellular dynamics with human melanoma. Herein, we report that glandular McSCs self-renew to expand their migratory progeny in response to genotoxic stress and trauma to generate invasive melanomas in mice that mimic human acral melanomas. The analysis of melanocytic lesions in human volar skin reveals that genetically unstable McSCs expand in sweat glands and in the surrounding epidermis in melanomas but not in nevi. The detection of such cell spreading dynamics provides an innovative method for an early differential diagnosis of acral melanomas from nevi.

Repeated mutation of a developmental enhancer contributed to human thermoregulatory evolution.

Humans sweat to cool their bodies and have by far the highest eccrine sweat gland density among primates. Humans' high eccrine gland density has long been recognized as a hallmark human evolutionary adaptation, but its genetic basis has been unknown. In humans, expression of the Engrailed 1 (EN1) transcription factor correlates with the onset of eccrine gland formation. In mice, regulation of ectodermal En1 expression is a major determinant of natural variation in eccrine gland density between strains, and increased En1 expression promotes the specification of more eccrine glands. Here, we show that regulation of EN1 has evolved specifically on the human lineage to promote eccrine gland formation. Using comparative genomics and validation of ectodermal enhancer activity in mice, we identified a human EN1 skin enhancer, hECE18. We showed that multiple epistatically interacting derived substitutions in the human ECE18 enhancer increased its activity compared with nonhuman ape orthologs in cultured keratinocytes. Repression of hECE18 in human cultured keratinocytes specifically attenuated EN1 expression, indicating this element positively regulates EN1 in this context. In a humanized enhancer knock-in mouse, hECE18 increased developmental En1 expression in the skin to induce the formation of more eccrine glands. Our study uncovers a genetic basis contributing to the evolution of one of the most singular human adaptations and implicates multiple interacting mutations in a single enhancer as a mechanism for human evolutionary change.

Histopathology of morphea: Sensitivity of various named signs, a retrospective study.

BACKGROUND: Morphea or localized scleroderma is characterized histopathologically by sclerosis, fibrosis, and atrophy of the skin and subcutaneous tissue. Various authors have named the characteristic findings seen in histopathology of morphea and have labeled them as specific signs, including line sign, cookie-cutter sign, and square biopsy sign. Besides, other findings mentioned include high eccrine glands and the presence of interstitial mucin. The present study was undertaken to assess the sensitivity of these tests in the histopathological diagnosis of morphea. METHODS: All cases clinically diagnosed and histopathologically reported as morphea in the last 3 years (September 2016 to August 2019) were included. The slides were reviewed by two independent investigators for the presence of line sign, cookie-cutter sign, square biopsy sign, high eccrine glands, and mucin. The sensitivity of these signs in accurately diagnosing morphea was assessed. Besides, specificity, positive predictive value, and negative predictive value of these signs were assessed using 40 random histopathology slides as controls. RESULTS: The highest sensitivity was of high eccrine glands (82.5%) followed by the presence of mucin in the dermis (77.5%). Cookie-cutter sign and square biopsy signs were seen in 70% and 62.5% patients, respectively. Line sign was least sensitive of all, seen in 45% of biopsy specimens, but was most specific (82.5%). CONCLUSION: A fair number of biopsies of morphea displays the presence of high eccrine glands, mucin, cookie-cutter sign, square biopsy sign, and line sign. These signs thus can be of immense help to the dermatopathology trainees.

Notch Signaling Pathway Expression in the Skin of Leprosy Patients: Association With Skin and Neural Damage.

Introduction: Leprosy is an infectious disease caused by Mycobacterium leprae, a debilitating disease that affects the skin and peripheral nerves. It is possible that tissue changes during infection with leprosy are related to alterations in the activity of the Notch signaling pathway, an innate signaling pathway in the physiology of the skin and peripheral nerves. Methods: This is a descriptive observational study. Thirty skin biopsies from leprosy patients and 15 from individuals with no history of this disease were evaluated. In these samples, gene expressions of cellular components associated with the Notch signaling pathway, Hes-1, Hey-1, Runx-1 Jagged-1, Notch-1, and Numb, were evaluated using q-PCR, and protein expression was evaluated using immunohistochemistry of Runx-1 and Hes-1. Results: Changes were observed in the transcription of Notch signaling pathway components; Hes-1 was downregulated and Runx-1 upregulated in the skin of infected patients. These results were confirmed by immunohistochemistry, where reduction of Hes-1 expression was found in the epidermis, eccrine glands, and hair follicles. Increased expression of Runx-1 was found in inflammatory cells in the dermis of infected patients; however, it is not related to tissue changes. With these results, a multivariate analysis was performed to determine the causes of transcription factor Hes-1 reduction. It was concluded that tissue inflammation was the main cause. Conclusions: The tissue changes found in the skin of infected patients could be associated with a reduction in the expression of Hes-1, a situation that would promote the survival and proliferation of M. leprae in this tissue.

Regional influence of nitric oxide on cutaneous vasodilatation and sweating during exercise-heat stress in young men.

NEW FINDINGS: What is the central question of this study? Do regional differences exist in nitric oxide synthase (NOS)-dependent cutaneous vasodilatation and sweating during exercise-heat stress in young men. What is the main finding and its importance? Exercise-induced increases in cutaneous vasodilatation and sweating were greater on the chest and upper back compared to the forearm, although the NOS contribution to cutaneous vasodilatation was similar across all regions. Conversely, there was a greater NOS-dependent rate of change in sweating on the chest compared to the forearm, with a similar trend on the back. ABSTRACT: While it is established that nitric oxide synthase (NOS) is an important modulator of forearm cutaneous vasodilatation and sweating during an exercise-heat stress in young men, it remains unclear if regional differences exist in this response. In 15 habitually active young men (24 ± 4 (SD) years), cutaneous vascular conductance (CVC) and local sweat rate (LSR) were assessed at three body regions. On each of the dorsal forearm, chest and upper-back (trapezius), sites were continuously perfused with either (1) lactated Ringer solution (control) or (2) 10 Mm Nω -nitro-l-arginine (l-NNA, NOS inhibitor), via microdialysis. Participants rested in the heat (35°C) for ∼75 min, followed by 60 min of semi-recumbent cycling performed at a fixed rate of heat production of 200 W m-2 (equivalent to ∼42% V̇O2peak ). During exercise, the chest and upper-back regions showed higher CVC and LSR responses relative to the forearm (all P < 0.05). Within each region, l-NNA attenuated CVC and LSR relative to control (all P < 0.05). However, the NOS contribution was not different across regions for the rate of change and plateau for CVC or for the LSR plateau (all P > 0.05). Conversely, there was a greater NOS contribution to the rate of change for LSR at the chest relative to the forearm (P < 0.05) with a similar trend for the back. In habitually active young men, NOS-dependent cutaneous vasodilatation was similar across regions while the NOS contribution to LSR was greater on the chest relative to the forearm. These findings advance our understanding of the mechanisms influencing regional variations in cutaneous vasodilatation and sweating during an exercise-heat stress.

A case report of temple squamoid eccrine ductal carcinoma: A diagnostic challenge beneath the tip of the iceberg.

Eccrine carcinomas are a rare tumor entity which originates from eccrine glands and comprise <0.01% of all cutaneous tumors. Eccrine carcinoma subtypes are classified based on their distinct histopathological pattern. Squamoid eccrine ductal carcinoma (SEDC) is a rare subtype, characterized by both squamous and adnexal ductal differentiation, and resembles squamous cell carcinoma on clinical examination. Given the rarity of these tumors, there remains a lack of clear diagnostic criteria or treatment guidelines for the management of SEDC. We report a rare case of SEDC with perineural invasion in an elderly gentleman who was treated with wide local excision.

Tattoos do not affect exercise-induced localised sweat rate or sodium concentration.

OBJECTIVES: Skin tattoos have been shown to reduce localised sweat rate and increase sweat sodium concentration ([Na+]) when sweating is artificially stimulated. This study investigated whether similar responses are observed with exercise-induced sweating. DESIGN: Unblinded, within-participant control, single trial. METHODS: Twenty-two healthy individuals (25.1±4.8 y (Mean±SD), 14 males) with a unilateral tattoo ≥11.4cm2 in size, ≥2 months in age, and shaded ≥50% participated in this investigation. Participants undertook 20min of intermittent cycling (4×5min intervals) on a stationary ergometer in a controlled environment (24.6±1.1°C; 64±6% RH). Resultant sweat was collected into absorbent patches applied at two pairs of contralateral skin sites (pair 1: Tattoo vs. Non-Tattoo; pair 2: Control 1 vs. Control 2 (both non-tattooed)), for determination of sweat rate and sweat [Na+]. Paired samples t-tests were used to determine differences between contralateral sites. RESULTS: Tattoo vs. Non-Tattoo: Neither sweat rate (Mean±SD: 0.92±0.37 vs. 0.94±0.43mg·cm-2·min-1, respectively; p=0.693) nor sweat [Na+] (Median(IQR): 37(32-52) vs. 37(31-45) mM·L-1, respectively; p=0.827) differed. Control 1 vs. Control 2: Neither sweat rate (Mean±SD: 1.19±0.53 vs. 1.19±0.53mg·cm-2·min-1, respectively; p=0.917) nor sweat [Na+] (Median(IQR): 29(26-41) vs. 31(25-43)mM·L-1, respectively; p=0.147) differed. The non-significant differences for sweat rate and [Na+] between Tattoo vs. Non-Tattoo were inside the range of the within participant variability (sweat rate CVi=5.4%; sweat [Na+] CVi=4.4%). CONCLUSIONS: Skin tattoos do not appear to alter the rate or [Na+] of exercise-induced sweating. The influence of skin tattoos on localised sweat responses may have previously been over-estimated.

Comparative evidence for the independent evolution of hair and sweat gland traits in primates.

Humans differ in many respects from other primates, but perhaps no derived human feature is more striking than our naked skin. Long purported to be adaptive, humans' unique external appearance is characterized by changes in both the patterning of hair follicles and eccrine sweat glands, producing decreased hair cover and increased sweat gland density. Despite the conspicuousness of these features and their potential evolutionary importance, there is a lack of clarity regarding how they evolved within the primate lineage. We thus collected and quantified the density of hair follicles and eccrine sweat glands from five regions of the skin in three species of primates: macaque, chimpanzee and human. Although human hair cover is greatly attenuated relative to that of our close relatives, we find that humans have a chimpanzee-like hair density that is significantly lower than that of macaques. In contrast, eccrine gland density is on average 10-fold higher in humans compared to chimpanzees and macaques, whose density is strikingly similar. Our findings suggest that a decrease in hair density in the ancestors of humans and apes was followed by an increase in eccrine gland density and a reduction in fur cover in humans. This work answers long-standing questions about the traits that make human skin unique and substantiates a model in which the evolution of expanded eccrine gland density was exclusive to the human lineage.