Digital Papillary Adenocarcinoma: Case of a Rare Malignant Cutaneous Tumor of the Eccrine Sweat Gland

Digital papillary adenocarcinoma (DPA) is a rare cutaneous tumor originating from the eccrine sweat glands. These lesions occur almost exclusively on the digits of the hands and feet, where there is a high concentration of eccrine glands. The diagnosis is made histologically, and the course of the malignancy tends to be very aggressive with high rates of recurrence and early metastasis at the time of diagnosis. Due to the low incidence of these lesions, there have been minimal objective data from clinical studies to recommend specific treatment strategies. Wide local excision versus digital amputation proximal to the lesion has been debated for primary treatment, while there are no data to support routine implementation of adjuvant chemotherapy or radiation, despite its metastatic nature. This article presents a case of long-standing, previously undiagnosed DPA. The lesion appeared more inconspicuous on gross examination than other reports in the literature, and diagnosis was made with punch biopsy and confirmed postsurgically. To date, the patient has not had recurrence, although she is being monitored for potential metastatic deposits in her lungs. Clinical dermatologists should be aware of the high mortality burden this lesion may inflict if left undiagnosed or mistreated.

Eccrine Sweat Gland and Its Regeneration: Current Status and Future Directions

Eccrine sweat glands (ESGs) play an important role in temperature regulation by secreting sweat. Insufficiency or dysfunction of ESGs in a hot environment or during exercise can lead to hyperthermia, heat exhaustion, heatstroke, and even death, but the ability of ESGs to repair and regenerate themselves is very weak and limited. Repairing the damaged ESGs and regenerating the lost or dysfunctional ESGs poses a challenge for dermatologists and bum surgeons. To promote and accelerate research on the repair and regeneration of ESGs, we summarized the development, structure and function of ESGs, and current strategies to repair and regenerate ESGs based on stem cells, scaffolds, and possible signaling pathways involved.

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.

Carcinoma del conducto ecrino recidivante. A propósito de un caso.

Eccrine sweat glands are widely distributed throughout the body and regulate body temperature in respond to cholinergic stimuli. Eccrine sweat gland carcinomas are rare and were first described by Cornil in 1865. Their incidence is 1% of all cutaneous malignancies, and the wide range of histological appearances and their similarity to metastatic carcinomas have generated uncertainties and controversies for many years regarding its diagnosis, biological behavior, and treatment. We present the case of a patient with eccrine duct carcinoma of the knee that recurred four years after her first excision. Key words: case report, eccrine sweat glands, eccrine duct carcinoma, cutaneous malignancies

An Engrailed1 enhancer underlies human thermoregulatory evolution

SummaryHumans rely on sweating to cool off and have the highest eccrine sweat gland density among mammals. We investigated whether altered regulation of the Engrailed 1 (EN1) gene, the levels of which are critical for patterning eccrine glands during development, could underlie the evolution of this defining human trait. First, we identify five EN1 candidate enhancers (ECEs) using comparative genomics and validation of enhancer activity in mouse skin. The human ortholog of one ECE, hECE18, contains multiple derived substitutions that together dramatically increase the activity of this enhancer in keratinocytes. Targeted repression of hECE18 reduces EN1 expression in human keratinocytes, indicating hECE18 upregulates EN1 in this context. Finally, we find that hECE18 increases ectodermal En1 in a humanized knock-in mouse to increase eccrine gland number. Our study uncovers a genetic basis for the evolution of one of the most singular human adaptations and implicates the recurrent mutation of a single enhancer as a novel mechanism for evolutionary change.

A two years study of histopathological spectrum of skin adnexal tumors in a tertiary care centre of Southern Assam, India

Background: Skin adnexal tumors (SAT) encompass a wide spectrum of benign and malignant tumors that differentiate toward one or more adnexal structures found in normal skin. Overall incidence of SATs is low yet they can be challenging to diagnose. Our study aims at analysis of histopathological spectrum of various SATs according to age, sex and anatomic locations along with histopathological features.Methods: It was a retrospective cross-sectional study conducted over a period of 2 years from June 2017 to May 2019. All cases were retrieved from department registries and analyzed.Results: Out of the total 4013 biopsies, 25 cases were diagnosed as SATs comprising 44% of tumors with eccrine sweat gland differentiation followed by tumors showing hair follicle differentiation (32%), sebaceous differentiation (16%) and apocrine gland differentiation (8%). The age ranged from 4 years to 68 years and male: female ratio was 1:1.5. Most of the tumors were benign (84%) while only 16% were malignant. Pilomatricoma (19%) was the most common benign tumor while sebaceous carcinoma (75%) was the most common malignant tumor.Conclusions: Skin adnexal tumors are relatively rare neoplasm. Malignant cases are less common than benign ones. Histopathology is quite essential for diagnostic point of view.