Cytokine profile of the epidermis is region specific and may determine the characteristics of inflammation.

Recent data indicate that distinct skin areas show different microbial/chemical milieu. Keratinocytes (KC) respond to these stimuli by producing cytokine mediators. Therefore, we aimed to determine KC-derived cytokine expression in distinct healthy skin regions (gland-poor [GP], sebaceous gland-rich [SGR] and apocrine gland-rich [AGR]), and their changes in skin diseases of the given regions (atopic dermatitis [AD], papulopustular rosacea [PPR] and psoriasis). Cytokines were analysed at the mRNA and protein levels, and literature analysis was performed for functional categorization. The three regions showed characteristically different cytokine patterns. GP was featured by an IL-25/IL-33/IL-36RA/IL-38/IL-18 cytokine milieu, SGR was characterized by IL-23/IL-17C/IL-18, and AGR skin exhibited a mixed IL-25/IL-33/IL-23/IL-18 profile. Literature analyses revealed different homeostatic and proinflammatory roles of these cytokine patterns (Th2 related in GP, Th17 related in SGR and mixed Th2/Th17 in AGR). In skin diseases which are primarily epidermal cytokine-driven (AD, PPR), the level of the regionally characteristic cytokines were further elevated, in contrast to the autoantigen-driven psoriasis, where the cytokine pattern was independent from the localization. Healthy skin regions are equipped with different KC-derived cytokine profiles, which may influence each region's capability of mediator production in certain types of dermatoses.

Morphological study of apocrine gland tumors in domestic Richardson's ground squirrels (Urocitellus richardsonii).

The morphology of 58 apocrine tumors from 31 domestic Richardson's ground squirrels (Urocitellus richardsonii) was examined, comparing tumor subtypes with clinical information and histological findings. The squirrels included 23 males (74%) and 8 females (26%). Of the 58 tumors, 36 (62%) were located from the cervical skin to the dorsal skin, 17 (29%) were from the perioral region to the cheek, and the location was unrecorded for the remaining 5 squirrels (9%). Histologically, 49 tumors (84%) were apocrine adenocarcinomas, 6 were apocrine adenomas (10%), and 3 were apocrine cysts (5%). The 49 apocrine adenocarcinomas were subclassified as 16 (33%) cystic papillary type, 16 (33%) tubulopapillary type, 12 (24%) solid type, and 5 (10%) micropapillary invasive type. Fisher's exact test revealed correlations between tumor subtypes and tumor diameters, nuclear atypia, tumor margins, vascular invasion, and periodic acid-Schiff (PAS) positivity. This study showed a predominance of apocrine adenocarcinomas with various histological subtypes. In addition, subclassification of these tumors was useful for predicting the biological behavior of apocrine gland tumors in Richardson's ground squirrels.

Percutaneous Interstitial Nd:YAG Laser Therapy for Axillary Osmidrosis.

BACKGROUND AND OBJECTIVES: To investigate the effects of percutaneous interstitial Nd:YAG laser irradiation on the apocrine glands and molecules involved in odor production (apolipoprotein [ApoD], androgen receptor [AR]) in the subcutaneous tissue of a pig. STUDY DESIGN/MATERIALS AND METHODS: Skin on the back of healthy adult miniature pigs was exposed to pulsed Nd:YAG laser irradiation at 5 or 10 W, or continuous Nd:YAG laser irradiation at 10 W. Samples were taken 1 hour, 1 week, and 1 month after treatment for histology, western blot, and real-time quantitative polymerase chain reaction (qRT-PCR) analysis. RESULTS: One week and 1 month after irradiation, the apocrine glands in pigskin became rounded, glandular cells were shorter, and the glandular cavities were larger compared with controls, but there were no obvious changes in fat cell distribution of collagen around the apocrine glands. One month after irradiation at 10 W in continuous mode, there was a significant decrease in ApoD expression in apocrine cells and ApoD and AR protein and expression levels in pigskin compared with controls. There were also significant differences in ApoD and AR protein and expression levels between treatments. CONCLUSIONS: Percutaneous interstitial Nd:YAG laser irradiation has potential as a safe and efficacious treatment for axillary osmidrosis as it may decrease the production of volatile unsaturated fatty acids, steroids, and associated unpleasant odors in the axilla. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Two cases of Hidradenitis suppurativa and botulinum toxin type a therapy: A novel approach for a pathology that is still difficult to manage.

Hidradenitis suppurativa is a chronic skin disease with an intense inflammatory activation. It typically affects the intertriginous areas with cysts, fistulae, and scarring extremely painful. Patients suffer from severe psychological impact. HS still results in a high unmet medical need with several underdiagnosed cases, probably due to the incomplete knowledge of the pathogenesis of HS. The use of botulinum toxin a has recently been proposed as an effective therapy for HS.

Ultrasound Characteristics of the Hair Follicles and Tracts, Sebaceous Glands, Montgomery Glands, Apocrine Glands, and Arrector Pili Muscles.

OBJECTIVES: To explore the capability of very high-frequency ultrasound (US; 50-71 MHz) to detect the normal morphologic characteristics of the hair follicles and tracts, sebaceous glands, Montgomery glands, apocrine glands, and arrector pili muscles. METHODS: A retrospective study, approved by the Institutional Review Board, evaluated the normal US morphologic characteristics of the hair and adnexal structures in a database of very high-frequency US images extracted from the perilesional or contralateral healthy skin of 1117 consecutive patients who underwent US examinations for localized lesions of the skin and 10 healthy individuals from December 2017 to June 2018. These images were matched with their counterparts from the database of normal histologic images according to the corporal region. The Cohen concordance test and regional mean diameters of the hair follicles and adnexal structures were analyzed. RESULTS: The normal hair follicles and tracts, sebaceous glands, Montgomery glands, apocrine glands, and arrector pili muscles were observed on US images and matched their histological counterparts in all the corporal regions. There was significant US concordance (κ = 0.82; P = .0001) among observers. Regional mean diameters (millimeters) of the hair follicles, sebaceous glands, and apocrine glands are provided. CONCLUSIONS: The hair follicles and tracts, sebaceous glands, Montgomery glands, apocrine glands, and arrector pili muscles are detectable with very high-frequency US, including some regional and anatomic variants. Knowledge of their normal US appearances is a requisite for detecting subclinical changes, understanding the physiopathologic characteristics, and supporting the early diagnosis and management of common dermatologic diseases.

Derivation of marker gene signatures from human skin and their use in the interpretation of the transcriptional changes associated with dermatological disorders.

Numerous studies have explored the altered transcriptional landscape associated with skin diseases to understand the nature of these disorders. However, data interpretation represents a significant challenge due to a lack of good maker sets for many of the specialized cell types that make up this tissue, whose composition may fundamentally alter during disease. Here we have sought to derive expression signatures that define the various cell types and structures that make up human skin, and demonstrate how they can be used to aid the interpretation of transcriptomic data derived from this organ. Two large normal skin transcriptomic datasets were identified, one RNA-seq (n = 578), the other microarray (n = 165), quality controlled and subjected separately to network-based analyses to identify clusters of robustly co-expressed genes. The biological significance of these clusters was then assigned using a combination of bioinformatics analyses, literature, and expert review. After cross comparison between analyses, 20 gene signatures were defined. These included expression signatures for hair follicles, glands (sebaceous, sweat, apocrine), keratinocytes, melanocytes, endothelia, muscle, adipocytes, immune cells, and a number of pathway systems. Collectively, we have named this resource SkinSig. SkinSig was then used in the analysis of transcriptomic datasets for 18 skin conditions, providing in-context interpretation of these data. For instance, conventional analysis has shown there to be a decrease in keratinization and fatty metabolism with age; we more accurately define these changes to be due to loss of hair follicles and sebaceous glands. SkinSig also highlighted the over-/under-representation of various cell types in skin diseases, reflecting an influx in immune cells in inflammatory disorders and a relative reduction in other cell types. Overall, our analyses demonstrate the value of this new resource in defining the functional profile of skin cell types and appendages, and in improving the interpretation of disease data. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Expression of growth hormone-releasing hormone receptors in apocrine adnexal tumours and apocrine glands of the skin.

Encouraged by our previous finding of growth hormone-releasing hormone receptor (GHRH-R) expression in metaplastic and neoplastic apocrine breast epithelium, we examined a small series of skin adnexal tumours with various degrees of apocrine (oxyphilic) differentiation, as well as normal axillary and anogenital apocrine sweat glands, for the expression of GHRH-R. Sections of formalin-fixed paraffin-embedded tissue blocks were immunostained for gross cystic disease fluid protein-15 (GCDFP-15) and androgen receptor (AR), to prove apocrine differentiation and correlate it with areas of GHRH-R expression. All but one of 19 tumours with apocrine epithelium and all five benign apocrine glands stained with both anti-GHRH-R antibodies used, each labelling a different domain of the receptor. Non-apocrine areas of the tumours and four eccrine tumours without oxyphilic features did not stain, but most sebaceous glands and some eccrine glands were labelled. Our data suggest that anti-GHRH-R antibodies highlight apocrine differentiation at extramammary sites also. Although GHRH-R seems to have a sensitivity comparable to classic apocrine markers such as AR and GCDFP-15, it seems to be inferior in specificity. The GHRH-R labelling of apocrine glands and neoplastic epithelium might also interfere with the emerging anti-GHRH targeted treatment of some malignancies acting on these receptors.

Radiation therapy for extramammary Paget's disease: treatment outcomes and prognostic factors.

BACKGROUND: Extramammary Paget's disease (EMPD) is a relatively rare malignancy, and there are few reports related to radiation therapy. In the present study, we investigated the outcome of radiation therapy for EMPD. PATIENTS AND METHODS: Forty-one patients with EMPD in the genitalia underwent radiation therapy with curative intent. Fifteen patients had regional lymph node metastases before radiation therapy, but none had distant metastasis. Total doses of 45-80.2 Gy (median, 60 Gy) were delivered to tumor sites in 23-43 fractions (median, 33 fractions). RESULTS: At a median follow-up period of 41 months, 16 patients had developed recurrences, including 5 with local progression within the radiation field and 12 with lymph node or/and distant metastases outside the radiation field. The local progression-free and disease-free rates were 88% and 55% at 3 years, and 82% and 46% at 5 years, respectively. Nine patients died at 6-73 months after irradiation; the causes of death were tumor progression in five patients, infectious pneumonia in two, renal failure in one and old age in one. The overall and cause-specific survival rates were 93% and 96% at 3 years, and 68% and 84% at 5 years, respectively. Tumor invasion into the dermis and regional lymph node metastasis were significant prognostic factors for both distant metastasis and survival. No therapy-related toxicities of grade ≥3 were observed. CONCLUSIONS: Radiation therapy is safe and effective for patients with EMPD. It appeared to contribute to prolonged survival owing to good tumor control, and to be a promising curative treatment option.

Rare Presentation of Apocrine Hidrocystoma Along the Nasolacrimal Duct.

Hidrocystomas are rare benign cystic tumors of the sweat glands, with no cases of hidrocystoma of nasolacrimal duct previously reported. We present a case of a 28-year-old female with no prior significant medical history presenting with an enlarging mass medial to her right lower eyelid for 2 years. Computed tomography scan showed nodular soft tissue in the middle part of the right nasolacrimal duct. Following complete excision of the cyst, histopathology reported an apocrine hidrocystoma, which is very rare.

Extramammary Paget's disease: Our 15-year experience in a Southeast Asian population.

The treatment of choice for Extramammary Paget's disease (EMPD) is wide excision. However, owing to the tendency of microscopic spread and multi-centricity of the disease, resection margins are hard to determine. Despite the use of adjunctive methods such as mapping biopsy and Moh's micrographic surgery, recurrence rates remain high. We aim to establish treatment guidelines by determining the variables associated with recurrence and the optimal resection margin size. We reviewed 52 patients who underwent wide excision in our institution between 2002 and 2017. A retrospective review of patient demographics, disease characteristics, and resection margins was performed. Most patients were Chinese (n = 39, 75%) male (n = 38, 73.1%). The mean tumor size was 6.73 cm (SD=4.10; range, 1.50-21.0 cm). The mean resection margin was 2.5 cm (SD=1.21; range, 0.20-5.50 cm). Eleven patients (21.2%) had disease recurrence. Nodal involvement significantly correlated with disease recurrence or mortality related to disease (HR=4.645; 95% CI=1.539,14.018; p = 0.0064). Subgroup analysis showed a significant correlation between resection margin size and recurrence rates (p = 0.047). We observed that a smaller resection margin (<2 cm) is acceptable for smaller tumor sizes (<6 cm) to achieve the lowest possible recurrence rates (20%), whereas a larger resection margin (>2 cm) is required for larger tumor sizes (>6 cm) (p = 0.012). Our results suggest that a resection margin recommendation can be made in correlation to the tumor size. This serves as a guideline for surgeons to predict the defect size and provide options for reconstructive surgery while achieving low recurrence rates.

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.

Vulvar Complex Apocrine Carcinoma in a Horse (Equus caballus): A Case Report and Review of Literature.

A 6-year-old Marwari mare presented with recurrent vulvar growth. The growth was surgically excised, fixed and processed routinely. Microscopically, neoplasm showed proliferation of epithelial and myoepithelial cells with tubulopapillary pattern. On immunohistochemistry, myoepithelial cells showed strong immunoreactivity with smooth muscle actin alpha and p63. On basis of histopathology and immunohistochemistry, tumour was diagnosed as complex apocrine carcinoma. This case report describes first confirm vulvar complex apocrine carcinoma in equines.

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.

Surgical Treatment in Hidradenitis Suppurativa.

Hidradenitis suppurativa (HS) is a chronic, progressive inflammatory disorder of follicular occlusion with pubertal onset that presents as painful inflammatory nodules, sinus tracts, and tunnelling in apocrine-gland-rich areas, such as the axilla, groin, lower back, and buttocks. The disease course is complicated by contractures, keloids, and immobility and is often associated with a low quality of life. It is considered a disorder of follicular occlusion with secondary inflammation, though the exact cause is not known. Management can often be unsatisfactory and challenging due to the chronic nature of the disease and its adverse impact on the quality of life. A multidisciplinary approach is key to prompt optimal disease control. The early stages can be managed with medical treatment, but the advanced stages most likely require surgical intervention. Various surgical options are available, depending upon disease severity and patient preference. In this review an evidence-based outline of surgical options for the treatment of HS are discussed. Case reports, case series, cohort studies, case-control studies, and Randomized Clinical Trials (RCT)s available in medical databases regarding surgical options used in the treatment of HS were considered for the review presented in a narrative manner in this article.

Quantification of Canine Apocrine Gland Anal Sac Adenocarcinoma (AGASACA) Tumor Specimen Shrinkage after Formalin Fixation.

The aim was to prospectively measure the shrinkage of primary apocrine gland anal sac adenocarcinoma (AGASACA) tumors after 24 and 48 h of formalin fixation. Dogs that were diagnosed with AGASACA pre-operatively by aspiration cytology were prospectively enrolled in the study. Tumor extirpation was performed in a closed technique. The tumor and associated tissues were examined on the back table away from the patient and the widest dimension of the tumor was measured using a sterile ruler (Medline®; Northfield, IL, USA). This measurement was recorded in mm (t0). The tissue was placed in 10% buffered formalin and stored at room temperature. Two further measurements were taken after 24 (t24) and 48 (t48) hours of formalin fixation. Once the 48 h measurement was taken, the tissue was submitted for histopathology. The percentage of shrinkage between time points was calculated by using the following equation: (1 - [time b/time a]) × 100. Overall, 23 dogs with 23 tumors were enrolled. The mean percentage of shrinkage after 24 and 48 h of formalin fixation was 4.8% and 7.2%, respectively. The median diameter of the tumors reduced by 1 mm over 48 h and was not significantly different at any time point. These data will aid clinicians in interpreting measurements of AGASACA tumors following formalin fixation and shows that minimal change in tumor size is expected following 48 h.

Periocular apocrine adenocarcinoma presenting as an orbital mass: clinicopathological features and management in four patients.

PURPOSE: Apocrine adenocarcinoma is a cutaneous adnexal malignancy which can rarely arise from ocular structures. In this retrospective study, we report our experience with four patients who had primary periocular apocrine adenocarcinoma initially presenting with an orbital tumor. METHODS: Data extracted included demographics, clinical, imaging, and histopathological features, and treatment outcomes. RESULTS: The definitive diagnosis was established after an incisional biopsy in all cases. Two patients were then managed with exenteration. The third patient underwent local resection followed by radiotherapy but had to be exenterated because of new tumor formation 7 years later. The fourth patient had to be managed with oral bicalutamide which kept the tumor stable for 3 years. Recurrence-free survival for the radical surgical treatment group was 10, 6, and 7 years respectively. CONCLUSION: Periocular apocrine adenocarcinoma may insidiously develop as an orbital mass without any clinically detectable primary eyelid skin or conjunctival lesions. This tumor must be in the differential diagnosis of medially located ill-defined orbital masses in patients over 50 years of age. Orbital exenteration appeared as an effective treatment of apocrine adenocarcinoma with orbital extension. Anti-androgenic treatment in an androgen receptor-positive tumor provided temporary local tumor control.

Retroperitoneal Metastatic Apocrine Gland Ductal Adenocarcinoma in a Beagle Dog.

Tumors of sweat glands usually originate from apocrine glands and can develop throughout the body but are rare in dogs. This report describes the retroperitoneal metastasis of primary cutaneous apocrine adenocarcinoma. An 8-year-old, spayed female beagle dog, weighing 11.7 kg, presented with a history of anorexia, hypodynamia, and weight loss. Clinical examination, radiography, ultrasonography, and computed tomography revealed a skin mass on the dorsum of the right metatarsal region, an enlarged ipsilateral popliteal lymph node, and a retroperitoneal mass. Fine-needle aspiration cytology of the popliteal lymph node suggested metastasis of an apocrine sweat gland tumor. Surgical excision of the skin mass, popliteal lymph node, and retroperitoneal mass was performed. The retroperitoneal mass was diagnosed as a metastasis of primary cutaneous apocrine adenocarcinoma. Immunohistochemistry revealed that the tumor cells were positive for cytokeratin 7 but negative for cytokeratin 20 and S100 proteins. There were no postoperative complications, except for temporary hindlimb edema, including local recurrence or metastasis, in the 6-month postoperative follow-up period. This case illustrates that although malignant apocrine gland tumors are rare in dogs, a wide resection of primary cutaneous apocrine gland adenocarcinomas is recommended because of the risk of local invasion or distant metastasis.

Canine Apocrine Gland Anal Sac Adenocarcinoma: A Review.

Apocrine gland anal sac adenocarcinoma (AGASAC) is a relatively uncommon tumor in the dog and comprises approximately 17% of perianal malignancies; however, it is one of the most common causes of paraneoplastic hypercalcemia. Clinical signs in affected dogs most commonly are associated with mechanical obstruction caused by the primary tumor or enlarged regional metastatic lymph nodes and the effects of paraneoplastic hypercalcemia when present. Surgical excision of the primary tumor and metastasectomy of affected locoregional lymph nodes is the preferred initial treatment option for most dogs, although radiation therapy and adjuvant chemotherapy are commonly incorporated into multi-modality treatment plans. A significant role for the use of adjuvant chemotherapy has not been clearly demonstrated. Prolonged survival times are possible, especially for dogs with smaller primary tumors and for dogs that undergo further treatments for recurrent disease. In this article, we review the clinical signs, diagnosis, staging, treatment, and prognosis of AGASAC in the dog.

Association Between Earwax-Determinant Genotypes and Acquired Middle Ear Cholesteatoma in a Japanese Population.

OBJECTIVE: A single-nucleotide polymorphism 538G>A in the human ABCC11 gene is a determinant of the earwax morphotype. ABCC11 538GG and GA correspond to wet earwax and 538AA to dry earwax. Despite a putative positive correlation between the frequency of the 538G allele and the prevalence of cholesteatoma, minimal clinical information is currently available. We aimed to evaluate this association between the ABCC11 genotypes and acquired middle ear cholesteatoma. STUDY DESIGN: Case-control study. SETTING: Single-center academic hospital. METHODS: We recruited 67 Japanese patients with acquired middle ear cholesteatoma (cholesteatoma group) and 100 Japanese controls with no history of middle ear cholesteatoma. We assessed the ABCC11 genotypes for all participants. Clinical information was collected from the cholesteatoma group. The genotype data of 104 Japanese people from the 1000 Genomes Project who represent the general population were used. RESULTS: The proportion of participants with ABCC11 538GG or GA was significantly higher in the cholesteatoma group than in the control group or general Japanese population (P < .001). The ABCC11 538G allele frequency was also significantly higher in the cholesteatoma group than in the control group or general Japanese population (P < .001). Multivariate logistic regression analyses revealed a significant association between the ABCC11 genotype and acquired middle ear cholesteatoma (odds ratio, 5.49; 95% CI, 2.61-11.5; P < .001). CONCLUSION: Our results suggest that the ABCC11 genotypes could be associated with the development of acquired middle ear cholesteatoma among Japanese people.

Updated Concepts in Oncologic Surgery: Apocrine Gland Anal Sac Adenocarcinoma and Mast Cell Tumors.

Advancements within the field of veterinary surgical oncology are constantly presenting themselves, especially with continued development of comprehensive cancer programs. With the use of more advanced imaging techniques within veterinary medicine, tumor staging is improving and techniques novel to veterinary medicine are being evaluated for potential clinical application. Recommended tumor staging and treatment approach for apocrine gland anal sac adenocarcinoma in dogs has evolved, with the anticipation of good long-term patient outcomes. Preoperative staging for mast cell tumors and recommendations for surgical margins to obtain for wide surgical excision is being reassessed by surgeons.