Crimson Tears: A Rare Case of Hematohidrosis.

Hematohidrosis is a rare clinical disorder characterized by oozing blood from intact skin and mucous membranes in the absence of a bleeding disorder. Most of the cases reported are from Asia. Although etiopathogenesis is unclear, it has been strongly linked to psychological stress. A nine-year-old girl was brought to the hospital with multiple episodes of painless bleeding from her nose and mouth for four days and eyes for three days, lasting four to five minutes each. Her symptoms and a thorough but unrevealing workup, including brain imaging, led to a clinical diagnosis of hematohidrosis, with parental disharmony as the underlying stress factor. Family therapy was recommended, and parent management training regarding the positive and negative reinforcement techniques was given. A significant improvement was observed at her one-month follow-up. This case adds to the current limited literature on hematohidrosis, highlighting its association with psychological stress and the importance of a multidisciplinary approach to management. Future research is warranted to elucidate molecular pathways involved in stress-induced vascular dysfunction and explore targeted therapeutic interventions.

Chromhidrosis Linked to Personal Care Products.

Eccrine chromhidrosis (CH) is a rare condition characterized by the excretion of colored sweat from eccrine glands. This case report contributes to the medical literature by highlighting two instances of eccrine CH linked to over-the-counter personal care products, an association not previously documented. These products contained FD&C Blue No. 1, D&C Red No. 33, and Ext. D&C Violet No. 2, which are known colorants in various consumer items. These cases underscore the potential for personal care products containing colored dyes to cause eccrine CH. The medical community and consumers must be vigilant about product ingredients to facilitate an accurate diagnosis and promote informed usage. Healthcare professionals should consider the role of colored personal care products in their differential diagnosis of CH to recognize and address potential risks effectively. These cases emphasize the need to actively include colored personal care products in medical considerations to ensure that healthcare practices and consumer awareness properly recognize and address potential risks associated with these products.

FGF7 and FGF10 Promote Fate Transition of Human Epidermal Cell-derived Organoids to an Eccrine Gland Phenotype.

Rationale: Reconstruction of hair follicles (HFs) and eccrine sweat glands (ESGs) is essential for functional skin regeneration. In skin reconstruction research, we found that foreskin-derived epidermal cells reconstructed HF organoids unidirectionally, but not ESG organoids. Methods: To investigate key genes and pathways influencing the fate of ESG and HF, a transcriptome profiling of ESG placode-containing skin and HF placode-containing skin was employed, and key DEGs were identified and validated by RT-qPCR and immunofluorescence staining in mice and rats. Subsequently, adult human epidermal cell-derived organoids were reconstructed to probe functional roles and mechanisms of FGF7 and FGF10 by series of approaches integrating RT-qPCR, immunofluorescence-staining, WB, apoptosis assay, and pathway interference assay. Results: All members of FGF7 subfamily were among the key DEGs screened, the differential expression of FGF7 and FGF10 and their receptors FGFR1/FGFR2 was verified between ESG placode-containing skin and HF placode-containing skin. In vivo and in vitro Matrigel plug models showed that both FGF7 and FGF10 promoted fate transition of human epidermal cell-derived organoids to ESG phenotype organoids, FGF7 and FGF10 had a synergistic effect, and mainly function through the FGFR1/2-MEK1/2-ERK1/2 pathway. Conclusions: Adult epidermal cells can be manipulated to reconstruct personalized HF and ESG to meet different needs.

Poroid Neoplasms: A Clinicopathological Study of 13 Cases.

Introduction: Poroid neoplasms (PN) are a heterogeneous group of tumors deriving from sweat glands and folliculo-sebaceous units. Their histological classification and clinical features are challenging. Our aim was to report clinicopathological features of poroid neoplasms. Methods: It is a retrospective study including all cases of poroid neoplasms registered at our Pathology laboratory of Niamey National Hospital (February 2020-February 2024). Results: We registered 13 cases of benign poroid neoplasms: 10 classic poromas (CP) (76.9%), 2 poroid hidradenomas (PH) (15.4%) and 1 dermal duct tumor (DDT) (7.7%). Nine cases (69.2%) had preoperative clinical diagnosis of malignancy. The mean age was 41.1 years (range of 12-70 years) with a slight female predominance. Only 4/13 cases (30.8%) had classical palmoplantar locations. The tumors mean size was 3.7 cm (range of 0.4-8 cm). Clear cells were present in 7 cases (53.8%), apocrine ductal differentiation (mixed or pure) in 6 cases (46.2%), keratin horns in 2 cases (15.4%), squamous eddies in 6 cases (46.2%), melanin pigments in 1 case (7.7%) and sebaceous differentiation in 2 cases (15.4%). Conclusions: Unlike what is classically reported, our study shows that apocrine ductal differentiation, younger age and non-palmoplantar locations are common in poroid neoplasms.

Ontogeny of Skin Stem Cells and Molecular Underpinnings.

Skin stem cells (SCs) play a pivotal role in supporting tissue homeostasis. Several types of SCs are responsible for maintaining and regenerating skin tissue. These include bulge SCs and others residing in the interfollicular epidermis, infundibulum, isthmus, sebaceous glands, and sweat glands. The emergence of skin SCs commences during embryogenesis, where multipotent SCs arise from various precursor populations. These early events set the foundation for the diverse pool of SCs that will reside in the adult skin, ready to respond to tissue repair and regeneration demands. A network of molecular cues regulates skin SC behavior, balancing quiescence, self-renewal, and differentiation. The disruption of this delicate equilibrium can lead to SC exhaustion, impaired wound healing, and pathological conditions such as skin cancer. The present review explores the intricate mechanisms governing the development, activation, and differentiation of skin SCs, shedding light on the molecular signaling pathways that drive their fate decisions and skin homeostasis. Unraveling the complexities of these molecular drivers not only enhances our fundamental knowledge of skin biology but also holds promise for developing novel strategies to modulate skin SC fate for regenerative medicine applications, ultimately benefiting patients with skin disorders and injuries.

Skin Development and Disease: A Molecular Perspective.

Skin, the largest organ in the human body, is a crucial protective barrier that plays essential roles in thermoregulation, sensation, and immune defence. This complex organ undergoes intricate processes of development. Skin development initiates during the embryonic stage, orchestrated by molecular cues that control epidermal specification, commitment, stratification, terminal differentiation, and appendage growth. Key signalling pathways are integral in coordinating the development of the epidermis, hair follicles, and sweat glands. The complex interplay among these pathways is vital for the appropriate formation and functionality of the skin. Disruptions in multiple molecular pathways can give rise to a spectrum of skin diseases, from congenital skin disorders to cancers. By delving into the molecular mechanisms implicated in developmental processes, as well as in the pathogenesis of diseases, this narrative review aims to present a comprehensive understanding of these aspects. Such knowledge paves the way for developing innovative targeted therapies and personalised treatment approaches for various skin conditions.

Establishment of a conditionally reprogrammed primary eccrine sweat gland culture for evaluation of tissue-specific CFTR function.

BACKGROUND: Sweat chloride concentration is used both for CF diagnosis and for tracking CFTR modulator efficacy over time, but the relationship between sweat chloride and lung health is heterogeneous and informed by CFTR genotype. Here, we endeavored to characterize ion transport in eccrine sweat glands (ESGs). METHODS: First, ESGs were microdissected from a non-CF skin donor to analyze individual glands. We established primary cultures of ESG cells via conditional reprogramming for functional testing of ion transport by short circuit current measurement and examined cell composition by single-cell RNA-sequencing (scRNA-seq) comparing with whole dissociated ESGs. Secondly, we cultured nasal epithelial (NE) cells and ESGs from two people with CF (pwCF) to assess modulator efficacy. Finally, NEs and ESGs were grown from one person with the CFTR genotype F312del/F508del to explore genotype-phenotype heterogeneity. RESULTS: ESG primary cells from individuals without CF demonstrated robust ENaC and CFTR function. scRNA-seq demonstrated both secretory and ductal ESG markers in cultured ESG cells. In both NEs and ESGs from pwCF homozygous for F508del, minimal baseline CFTR function was observed, and treatment with CFTR modulators significantly enhanced function. Notably, NEs from an individual bearing F312del/F508del exhibited significant baseline CFTR function, whereas ESGs from the same person displayed minimal CFTR function, consistent with observed phenotype. CONCLUSIONS: This study has established a novel primary culture technique for ESGs that allows for functional ion transport measurement to assess modulator efficacy and evaluate genotype-phenoytpe heterogeneity. To our knowledge, this is the first reported application of conditional reprogramming and scRNA-seq of microdissected ESGs.

Pretreatment of microneedles enhances passive transdermal administration of pilocarpine and pilocarpine-induced sweat production in humans.

The development of an effective transdermal drug delivery protocol to eccrine sweat glands is important for the advancement of research on the human sweating response. We investigated whether microneedle treatment prior to the application of pilocarpine, a hydrophilic and sudorific agent that does not induce sweating due to a limited percutaneous passive diffusion by skin application alone, augments sweat production. We applied three microneedle arrays to forearm skin sites simultaneously (n = 20). Upon removal of the microneedles, 1 % pilocarpine was applied to each site for 5-, 15-, and 30-min for the assessment of sweat gland function. In parallel, pilocarpine was administered by transdermal iontophoresis (5-min) at a separate site. Sweat rate was assessed continuously via the ventilated capsule technique. Pilocarpine augmented sweat rate at the 15- and 30-min periods as compared to the application at 5-min. The sweating responses induced by the 15- and 30-min application of pilocarpine were equivalent to âˆ¼ 80 % of that measured at the iontophoretically treated sites. Notably, we observed a correlation in sweat rate between these two transdermal drug delivery methods. Altogether, our findings show that pre-treatment of microneedle arrays can enhance transdermal delivery efficiency of pilocarpine to human eccrine sweat glands.

Morphology of sweat glands in the skin of Saimaa (Pusa hispida saimensis) and Baltic ringed (Pusa hispida botnica) seals.

The endangered Saimaa ringed seal (Pusa hispida saimensis) is an endemic freshwater subspecies inhabiting Lake Saimaa in Finland. The Baltic ringed seal (Pusa hispida botnica) inhabits the brackish Baltic Sea, which is almost entirely landlocked. Recent research shows that Saimaa and Baltic ringed seals may be genetically even further apart from each other than from other ringed seal subspecies. We documented histologically the integument microstructure of Saimaa and Baltic ringed seals to determine whether the geographic and genetic isolation was manifested as variation in the integument microstructure of these subspecies adapted to icy aquatic environments. The skin structures of these subspecies were similar to those of other phocids. The association of the sweat glands with hair follicles in both subspecies suggested that they were small apocrine sweat glands described previously in terrestrial or aquatic mammals. None of the apocrine glands had large lumina, and some of the ducts were relatively straight and short. Further studies analysing the mode of secretion, for example, apocrine versus eccrine, in the sweat glands are necessary to confirm the types of sweat glands in seals.

Subclinical effects of botulinum toxin A and microwave thermolysis for axillary hyperhidrosis: A descriptive study with line-field confocal optical coherence tomography and histology.

Botulinum toxin A (BTX) and microwave thermolysis (MWT) are standard axillary hyperhidrosis treatments, but comparison of their subclinical effects is lacking. Line-field confocal optical coherence tomography (LC-OCT) is a promising non-invasive imaging tool for visualizing tissue-interactions. This study aimed to describe subclinical effects of BTX and MWT for axillary hyperhidrosis with LC-OCT-imaging compared to histology. This study derived from an intra-individual, randomized, controlled trial, treating axillary hyperhidrosis with BTX versus MWT. Subclinical effects based on LC-OCT images from baseline and 6-month follow-up (n = 8 patients) were evaluated and compared to corresponding histological samples. At baseline, LC-OCT visualized eccrine pores at the skin surface and ducts in the upper dermis (500 µm), but not deeper-lying sweat glands. Histology identified entire sweat glands. Six months post-treatment, LC-OCT revealed no detectable morphology changes in any BTX-treated axillae (100%), while recognizing obstructed eccrine pores and atrophy of eccrine ducts in most MWT-treated axillae (75%). Histology corroborated LC-OCT findings, while also showing substantial changes to entire sweat glands. LC-OCT enabled visualization of subclinical alterations of superficial eccrine ducts after MWT and unchanged morphology after BTX. LC-OCT is a promising tool for non-invasive assessment of treatment-specific tissue-interactions that can be complementary to histology.

Primary cutaneous apocrine carcinoma: A challenging case report.

INTRODUCTION: Primary cutaneous apocrine carcinomas of the axilla represents an extremely rare entity, with <200 cases reported in the literature. It can be challenging, even almost impossible, to distinguish histologically from metastases of breast origin. We herein present the first case of an axillary cutaneous apocrine adenocarcinoma followed and treated in our institute. CASE PRESENTATION: A 58-year-old man with a history of myopathy, presented for a right axillary swelling. Physical examination revealed the presence of a 10 cm right axillary mass, no palpable adenopathy, and bilateral gynecomastia. A biopsy of the mass was performed, showing a pattern consistent with a secondary localization of mammary neoplasia. Breast and distant radiological examinations were negative. The tumor markers' levels were not raised. Therefore, the patient underwent surgery with a large excision, a right axillary lymph node dissection, covered with a pedicled pectoralis major flap. Histological and immunohistochemical examinations showed a high expression of CK7 with a negative expression of TTF1, RH, PSA, and CK20. The diagnosis of an apocrine adenocarcinoma from cutaneous origin was confirmed. CLINICAL DISCUSSION: Primary cutaneous apocrine carcinomas are a group of uncommon malignant adnexal tumors, whose diagnosis is almost impossible to confirm preoperatively. Wide, local excision with clear margins, with or without lymph node dissection is the standard treatment. CONCLUSION: This case illustrates the importance of clinico-pathological correlation of skin cancers, especially apocrine ones. Clinical particularity and careful histological analysis are used to guide the diagnostic approach.

Pregnancy-Related Eccrine Angiomatous Hamartoma: Case Report.

Eccrine angiomatous hamartoma is rare, slow-growing, and benign neoplasm that is diagnosed based on clinical characteristics and histological findings. It usually presents as a solitary nodule on the extremities and may arise at birth or in childhood. Although it is usually asymptomatic, in some cases it can cause pain and hyperhidrosis. From a histological perspective, it is characterized by an increase in the number of eccrine glands and a proliferation of vascular channels. We present the case of a 26-year-old woman who developed an eccrine angiomatous hamartoma in her right leg. The rapid growth of the lesion during pregnancy coupled with the challenges posed by a superficial biopsy, complicated the differential diagnosis.

Primary cutaneous mucinous carcinoma of the scalp masquerading as a benign dermatological mass - A case report.

INTRODUCTION AND IMPORTANCE: Primary cutaneous mucinous carcinoma (PCMC) is a rare low-grade malignant neoplasm derived from the sweat glands. Local recurrence of PCMC occurs frequently, but these lesions rarely metastasize. Due to the absence of classical demographic and clinical characteristics, PCMCs masquerade as sebaceous cyst, lipoma, pilomatrixoma, chalazion, or squamous cell carcinoma. This misdiagnosis frequently leads to incomplete surgical excision which necessitates further surgical therapy for a curative intent. CASE PRESENTATION: We present a case of PCMC in a 45-year-old woman which presented as a slow- growing and symptomless nodule in the scalp. After clinical evaluation, the patient had a typical surgical excision for a benign-looking lesion. Histological evaluation of the specimen confirmed a localized PCMC in the scalp with involved surgical margins. CLINICAL DISCUSSION: A thorough oncological assessment by PET-CT scan and radionuclide scintigraphy was performed. Later, a wide local excision using a gamma probe for intra-operative radionuclide localization of the tumor area and sentinel lymph nodes was done. CONCLUSION: The patient did not have any regional or distant metastases and remained stable at the time of reporting this case.

Development of Physiologically Relevant Skin Organoids from Human Induced Pluripotent Stem Cells.

The development of skin organs for studying developmental pathways, modeling diseases, or regenerative medicine purposes is a major endeavor in the field. Human induced pluripotent stem cells (hiPSCs) are successfully used to derive skin cells, but the field is still far from meeting the goal of creating skin containing appendages, such as hair follicles and sweat glands. Here, the goal is to generate skin organoids (SKOs) from human skin fibroblast or placental CD34+ cell-derived hiPSCs. With all three hiPSC lines, complex SKOs with stratified skin layers and pigmented hair follicles are generated with different efficacies. In addition, the hiPSC-derived SKOs develop sebaceous glands, touch-receptive Merkel cells, and more importantly eccrine sweat glands. Together, physiologically relevant skin organoids are developed by direct induction of embryoid body formation, along with simultaneous inactivation of transforming growth factor beta signaling, activation of fibroblast growth factor signaling, and inhibition of bone morphogenetic protein signaling pathways. The skin organoids created in this study can be used as valuable platforms for further research into human skin development, disease modeling, or reconstructive surgeries.

Epidermal and dermal cells from adult rat eccrine sweat gland-containing skin can reconstruct the three-dimensional structure of eccrine sweat glands.

BACKGROUND: Previously, we have demonstrated that eccrine sweat gland cells (ESGCs) can reconstruct the three-dimensional (3D) structure of eccrine sweat glands (ESGs). However, there is still a need to explore source cells capable of regenerating ESG to address the issue of ESG regeneration in ESGC-deficient conditions, such as severe burns. METHODS: The epidermal cells and dermal cells in adult rat ventral foot skin (ESG-bearing) were isolated. The isolated single epidermal cells and dermal cells were mixed with Matrigel, and then the mixture was implanted into the axillary/inguinal fat pads of nude mice. Five weeks after implantation, the Matrigel plugs were harvested and the morphology and differentiation of the cells were examined by H&E staining and fluorescent immunohistochemical staining for ESG markers, such as Na+ -K+ -2Cl- cotransporter 1 (NKCC1), Na+ -K+ -ATPase (NKA), Foxa1 and K14. RESULTS: The epidermal cells and dermal cells of adult rat ventral foot skin can reconstruct 3D structure and express specific markers of ESGs in skin, such as NKCC1, NKA and Foxa1, indicating the ESG-phenotypic differentiation of the 3D structures. Double immunofluorescence staining showed that some 3D structures expressed both the myoepithelial cell marker alpha-SMA and the common marker K14 of duct cells and myoepithelial cells, while some 3D structures expressed only K14, indicating that ESG-like 3D structures differentiated into duct-like and secretory coiled cells. CONCLUSION: Epidermal and dermal cells from adult ESG-bearing skin can be used as a cell source for ESG regeneration.

Primary Cutaneous Apocrine Carcinoma and Syringocystadenoma Papilliferum Arising in Nevus Sebaceus: A Case Report and Review of the Literature.

Nevus sebaceus is a hamartomatous lesion characterized by epidermal, follicular, sebaceus, and apocrine gland abnormalities. Approximately 25% of affected individuals may develop benign or malignant secondary neoplasms within the preceding nevus sebaceus. Primary cutaneous apocrine carcinoma (PCAC) is a rare malignant skin tumor affecting elderly adults in their sixth decade of life. Histologically, PCAC appears as a dermal tumor displaying apocrine differentiation with decapitation secretion and malignant features. Secondary malignancy arising from nevus sebaceus is a rare complication, especially for apocrine carcinoma. To date, approximately 200 cases of PCAC have been reported in the literature, and only a few cases have developed PCAC on the scalp. Very few cases (approximately only 12) of PCACs developing in nevus sebaceus have been reported. Here, we report an extremely rare case of the coexistence of PCAC and syringocystadenoma papilliferum arising within nevus sebaceus of the scalp.

Epithelial polarity-driven membrane separation but not cavitation regulates lumen formation of rat eccrine sweat glands.

BACKGROUND: Each eccrine sweat gland (ESG) is a single-tubular structure with a central lumen, and the formation of hollow lumen in the initial solid cell mass is a key developmental process. To date, there are no reports on the mechanism of native ESG lumen formation. METHODS: To investigate the lumen morphogenesis and the lumen formation mechanisms of Sprague-Dawley (SD) rat ESGs, SD rat hind-footpads at E20.5, P1-P5, P7, P9, P12, P21, P28 and P56 were obtained. The lumen morphogenesis of ESGs was examined by HE staining and immunofluorescence staining for polarity markers. The possible mechanisms of lumen formation were detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) apoptosis assay and autophagy marker LC3B immunofluorescence staining, and further explored by ouabain intervention experiment. RESULTS: In SD rat ESGs, the microlumen was formed at P1, and the small intact lumen with apical-basal polarity appeared at P3. The expression of apical marker F-actin, basal marker Laminin, basolateral marker E-cadherin was consistent with the timing of lumen formation of SD rat ESGs. During rat ESG development, apoptosis and autophagy were not detected. However, inhibition of Na+-K+-ATPase (NKA) with ouabain resulted in decreased lumen size, although neither the timing of lumen formation nor the expression of polarity proteins was altered. CONCLUSIONS: Epithelial polarity-driven membrane separation but not cavitation regulates lumen formation of SD rat ESGs. NKA-regulated fluid accumulation drives lumen expansion.

Genetics of adnexal tumors: An update.

Cutaneous adnexal tumors form a vast heterogeneous group that include frequent entities that are mostly benign, as well as rare tumors that are occasionally malignant. In contrast to cutaneous tumors arising from the interfollicular epidermis that develop as a result of accumulation of UV-induced DNA damage (basal cell carcinoma, squamous cell carcinoma), the oncogenesis of adnexal tumors is related to a broad spectrum of genetic mechanisms (e.g., point mutation, fusion genes, viral integration, etc.). In this setting, specific and recurrent genetic alterations have been progressively reported, and these allow better classification of these entities. For certain of them, immunohistochemical tools are now available, enabling precise integrated histological and molecular diagnosis since certain entities are linked to well-defined alterations. In this context, we aim in this review to summarize the main molecular tools currently available for the classification of adnexal tumors.