Pyoderma gangrenosum, acne, and suppurative hidradenitis (PASH) syndrome: a single-institution case series with a focus on management.

BACKGROUND: Pyoderma gangrenosum, acne, and suppurative hidradenitis (PASH) syndrome is a rare condition characterized by clinical features of all three dermatologic conditions. The management of PASH syndrome is difficult, with no consensus on treatment guidelines. Since PASH syndrome can increase morbidity and adversely impact quality of life, better characterization of effective therapies is needed. METHODS: A retrospective cohort study was conducted to identify all patients with pyoderma gangrenosum (PG) treated at The Ohio State University Wexner Medical Center between 2015 and 2021. PG diagnosis was confirmed via PARACELSUS score. Subsequent chart review identified eight patients with concomitant hidradenitis suppurativa (HS) and acne who were clinically diagnosed with PASH syndrome. RESULTS: Eight patients were clinically diagnosed with PASH syndrome based on their clinical presentation at our institution. Seven patients had failed some type of medical therapy prior to presentation, including topical corticosteroids, oral corticosteroids, oral antibiotics, and biologics. One patient had also tried surgical drainage at an outside institution. Six patients were effectively treated with biologics, usually in combination with other therapies. One patient experienced improvement of her skin lesions after diagnosis and treatment of her underlying hematologic malignancy. CONCLUSIONS: Medical management with biologics in combination with corticosteroids and/or antibiotics was effective in the management of most patients. Diagnosis and treatment of an underlying condition should be prioritized in refractory cases. If workup is negative, surgical management may be considered. Further investigation with a greater number of patients is required to develop management guidelines for PASH syndrome.

Primary angiosarcoma of the breast in a 21-year-old female: A case report.

We present a case of primary angiosarcoma, an exceedingly rare malignant breast lesion, in a 21-year-old female patient with unilateral breast enlargement. Primary angiosarcoma is an aggressive form of breast cancer with variable presentation and limited clinical experience due to the rarity of the disease. Despite an initial diagnostic challenge, this report showcases the importance of a systematic diagnostic approach and multidisciplinary management in the context of uncommon breast lesions in young patients. Our patient underwent a mastectomy followed by breast reconstruction, achieving favourable cosmetic outcomes. This case serves as a contribution to our understanding of the diagnostic considerations surrounding angiosarcoma of the breast in a young patient.

Fibroadenoma of the vulva with pseudoangiomatous stromal hyperplasia: A common neoplasm in uncommon site.

Mammary-type tissue in the vulva was first described in 1872 but has been rarely reported in the literature. This tissue was previously considered as ectopic breast tissue that occurs as a result of incomplete regression of the milk line. Similar to native breast tissue, ectopic mammary tissue is hormone-sensitive and can develop benign changes, such as fibroadenoma, as well as malignant changes. A more recent theory suggests that these benign and malignant mammary-type entities arise from mammary-like anogenital glands, which constitute normal vulvar components. We report a case of a 41-year-old woman who presented with a chronic asymptomatic cyst on the left vulva that eventually became uncomfortable, especially on standing. The cyst was located on the labium minus, measuring 1.0 × 0.5 cm, with no identified erythema or other skin abnormalities. Excision of the lesion and subsequent microscopic examination showed a circumscribed mass with a nodular overgrowth of epithelial and stromal components, resembling a mammary fibroadenoma with pseudoangiomatous stromal hyperplasia. We bring to attention this rare diagnosis and the importance of considering it in the presence of a vulvar lesion. The malignant and recurrence potential of mammary-type tissue necessitates excision with clear margins and close monitoring of these patients.

Infra-areolar subcutaneous mastectomy in the surgical treatment of adolescent gynecomastia.

BACKGROUND: Despite being a common condition in puberty, only 5-10% of pubertal gynecomastia need surgical treatment. Here the authors present their experiences with infra-areolar subcutaneous mastectomy in the surgical treatment of adolescent gynecomastia. METHODS: The records of patients who underwent infra-areolar subcutaneous mastectomy for adolescent gynecomastia between January 2004 and December 2021 were reviewed retrospectively. The patients' demographic data, complaints and clinical presentation, physical examination, laboratory and radiological findings, surgical management, and postoperative follow-ups were evaluated. The patients were evaluated according to the localization of the gynecomastia (unilateral/bilateral) and according to the patients' body mass index (BMI) (normal/overweight). RESULTS: A total of 21 boys with a mean age of 15 ± 1.4 years were operated by the senior author and infra-areolar subcutaneous mastectomy by a semilunar incision was performed for adolescent gynecomastia. The mean duration of the complaint was 24.2 ± 10.9 months. Gynecomastia was bilateral in 15 (71.5%) and unilateral in 6 (28.5%) of the patients. Sixteen patients (76.2%) were normal weight, 5 (23.8%) were overweight. Chromosomal anomaly and hypogonadism were detected in two patients. Pseudoangiomatous stromal hyperplasia was detected in the pathology of one patient. The mean follow-up time was 2.7 ± 1 years, seroma developed in 2 patients at the early postoperative period. Their long-term follow-up was uneventful without complication. CONCLUSIONS: The results of infra-areolar subcutaneous mastectomy are very promising in pubertal gynecomastia due to good skin elasticity and without obesity in the adolescent age group. We believe that this method provides an almost invisible incision and a natural pectoral appearance for adolescent patients who have experienced serious emotional problems related to their body images.

Pseudoangiomatous stromal hyperplasia: a rare cause of gynecomastia in men.

A 17-year-old male with chest malformation and left breast enlargement underwent surgery for gynecomastia. Histological examination revealed mammary fibrous stroma with ductal hyperplasia and features of pseudoangiomatous stromal hyperplasia. Postoperative follow-up showed no complications, but 8 months later, the patient experienced a mild recurrence with enlargement of the nipple-areolar complex. Although recommended for secondary glandular resection, the patient declined further surgery.

A Rare Case of Pseudoangiomatous Stromal Hyperplasia in a Male Patient.

Teaching Point: Pseudoangiomatous stromal hyperplasia (PASH) is a rare benign breast condition that can mimic the appearance of breast cancer on imaging studies.

A reciprocal perspective on the differential associations between personality traits and multiple indicators of academic achievement.

OBJECTIVE: This study aims to explore the reciprocal associations between personality traits (conscientiousness and openness to experience) and academic achievement in adolescents, using the Personality Achievement Saturation Hypothesis (PASH). BACKGROUND: Personality traits, especially conscientiousness, and openness, have been identified as strong predictors of academic achievement. The PASH provides a framework for understanding these relationships but has mainly been studied from a unidirectional perspective. This study extends the PASH to examine reciprocal associations and how they vary with different achievement indicators. METHODS: Using large-scale panel data (N = 6482) of secondary school students in Germany, we applied cross-lagged panel models and latent change score models to examine the differential reciprocal associations between personality traits (conscientiousness/openness) and academic achievement (school grades/achievement test scores) in language and math over two years from grades 7 to 9. RESULTS: In line with the PASH, initial levels of conscientiousness were more strongly associated with school grades than with achievement test scores over two years. Simultaneously, prior school grades were more strongly associated with conscientiousness over two years. However, initial levels of openness did not show differential associations with either school grades or achievement test scores over two years. Similarly, prior school grades and achievement test scores were also not differentially associated with openness over two years. CONCLUSIONS: Our findings introduce an innovative lens through which we observe how the PASH can be leveraged to explain the differential reciprocal associations between conscientiousness and academic achievement. Further research is needed to examine if PASH could be similarly extended to disentangle the associations between openness and academic achievement.

Quantification of polycyclic aromatic sulfur heterocycles in fine airborne urban particles (PM2.5) after multivariate optimization of a green procedure.

Polycyclic aromatic sulfur heterocycles (PASHs), such as benzothiophenes (BT), dibenzothiophenes (DBT) and benzonapthothiophenes (BNT), can be emitted from vehicular traffic and deposited in fine particles matter (PM2.5). The presence of these compounds in PM2.5 is an environmental concern due to air pollution and its toxic properties. In this study, a green microscale solid-liquid extraction method was developed to determine twenty-three PASHs in PM2.5. A simplex-centroid mixture design was applied to optimize the extraction solvent. A full factorial design was used for preliminary evaluation of the factors that influence the extraction process (extraction time, sample size, and solvent volume) and then a Doehlert design for the significant parameters. The optimal extraction conditions based on the experimental design were: sample size, 4.15 cm2; 450 µL of toluene:dichloromethane (80:20,v/v); and extraction duration, 24 min. High sensitivity (LOD < 0.66pg m-3 and LOQ < 2.21 pg m-3) and acceptable recovery (82.8-120 %), and precision (RSD 3.6-14.0 %) were obtained. The greenness of the method was demonstrated using the Analytical GREEnness (AGREE) tool. The method was applied for analyzing PASHs in PM2.5 samples collected in three time intervals per day from years with different sulfur contents in the diesel: S-500 (≤500 ppm sulfur) and S-50 (≤50 ppm sulfur). Fourteen PASHs were quantified with the highest concentrations observed for 2,8-DMDBT and 4,6-DMDBT, which are recalcitrant compounds. The ANOVA test indicated significant differences between sampling periods during the day. The reduction of diesel S-500 to S-50 corresponded to a 28 % decrease in the total sum of PASHs (∑PASHs) evaluated. Spearman's rank correlations allowed for verifying that BTs and DBTs were highly correlated, suggesting that they were derived from similar sources. A weak correlation of 2,1-BNT and 2,3-BNT with BTs and DBTs indicates that these compounds are a chemical proxy for the emission of diesel engines during the combustion process.

Pseudoangiomatous stromal hyperplasia of the breast, imaging and clinical perspective: A review.

Pseudoangiomatous stromal hyperplasia (PASH) is a benign breast pathology, which most commonly presents incidentally along with other breast pathologies. The etiology and pathogenesis of PASH are still unknown; however, there is some evidence suggesting PASH is hormone dependent. The clinical history, presentation, and imaging appearance of PASH are variable. Clinically, PASH has a wide spectrum of presentations, from being silent to gigantomastia. On imaging, PASH demonstrates various benign to suspicious features. Here we summarize PASH's clinical presentation, histopathology, imaging features, and management.

Giant juvenile fibroadenomas with and without prominent pseudoangiomatous stromal hyperplasia (PASH)-like change: clinicopathological and molecular characteristics.

AIMS: Juvenile fibroadenomas (JFA) are biphasic fibroepithelial lesions (FEL) usually occurring in adolescent female patients. Giant (G) JFA, like other FEL, may exhibit prominent pseudoangiomatous stromal hyperplasia (PASH)-like change. We sought to determine clinicopathological and molecular characteristics of GJFA with and without PASH. METHODS AND RESULTS: Archives were searched for cases of GJFA (1985-2020). All were stained for androgen receptor (AR), beta-catenin, CD34 and progesterone receptor (PR). Cases were sequenced using a custom 16-gene panel - MED12 (exons 1 and 2), TERT promoter (-124C>T and -146Ctable>T), SETD2, KMT2D, RARA (exons 5-9), FLNA, NF1, PIK3CA (exons 10, 11 and 21), EGFR, RB1, BCOR, TP53, PTEN, ERBB4, IGF1R and MAP3K1. Twenty-seven GJFA from 21 female patients aged 10.1-25.2 years were identified. Size ranged from 5.2 to 21 cm. Two patients had multiple, bilateral and later recurrent GJFA. Thirteen (48%) cases showed prominent PASH-like stroma. All were positive for stromal CD34, negative for AR and beta-catenin and one case showed focal PR expression. Sequencing showed MAP3K1 and SETD2 mutations in 17 samples, with KMT2D, TP53 and BCOR aberrations in 10 (45%), 10 (45%) and seven (32%) cases, respectively. Tumours with a PASH-like pattern had higher prevalence of SETD2 (P = 0.004) and TP53 (P = 0.029) mutations, while those without PASH had more RB1 mutations (P = 0.043). MED12 mutation was identified in one case. TERT promoter mutation was observed in four (18%), including two recurrences. CONCLUSIONS: Gene mutations along more advanced phases of the proposed FEL pathogenetic pathway in GJFA are unusual, and suggest a mechanism for more aggressive growth in these tumours.

Pseudoangiomatous Stromal Hyperplasia: Radiologic-Pathologic Correlation.

Pseudoangiomatous stromal hyperplasia (PASH) is a benign mesenchymal proliferative lesion of the breast. PASH is postulated to be hormonally induced and predominantly occurs in premenopausal women and postmenopausal women on menopausal hormone therapy. Clinical presentation varies from screen-detected lesions to palpable masses. Imaging findings of PASH are nonspecific. The most common mammographic findings are an oval or round circumscribed non-calcified mass or developing asymmetry. On US, PASH is often seen as an oval hypoechoic mass that may be circumscribed and can have an echogenic rim, or, when manifest as mammographic asymmetry, US may show a corresponding non-mass focal area of echogenic tissue. Limited studies have investigated the MRI appearance, with PASH most often manifesting as non-mass enhancement, or, less often, as an oval or irregular mass with persistent kinetics. Histopathologically, PASH can be mistaken for a fibroadenoma or phyllodes tumor and has features overlapping low-grade angiosarcoma. Assessment of radiologic-pathologic concordance is particularly important as PASH is often an incidental finding, adjacent to the targeted lesion at histopathology. Surgical excision or repeat core-needle biopsy is necessary for discordant suspicious cases. After a benign, concordant diagnosis of PASH, the patient may resume routine screening.

A review of pediatric macromastia etiology and indications for reduction mammaplasty.

BACKGROUND: Macromastia in adolescents is both physically and psychologically debilitating during a period in life when individuals are particularly vulnerable to peer pressure and social norms. Early recognition and intervention by both pediatricians and surgeons are critical to avoid unnecessary suffering. While reduction mammaplasty is the gold standard for the management of symptomatic macromastia in adults, the management of macromastia in pediatric patients remains controversial. In particular, there is great discussion regarding the timing of reconstructive breast surgery in pediatric patients. METHODS: A comprehensive review of the literature was performed to identify all articles related to macromastia in patients ≤16 years of age, the age at which full development is typically achieved in the United States. The etiologies of pediatric macromastia, approaches to management, and outcomes are summarized herein. FINDINGS: Pathological breast hypertrophy in pediatric patients is a rare finding and may occur secondary to juvenile hypertrophy of the breast (JHB) and pseudoangiomatous stromal hyperplasia (PASH). While medical management of these pathologies has been attempted with varying success, reduction mammaplasty is safe and effective in pediatric patients. There are, however, a number of pediatric-specific considerations that must be taken into account prior to surgery. We provide an algorithm for approaching pediatric macromastia.

Radiological Spectrum of Pseudoangiomatous Stromal Hyperplasia of Breast-A Case Series.

Pseudoangiomatous stromal hyperplasia (PASH) is a benign mesenchymal tumor-like lesion of the breast. It is commonly seen as incidental background changes of the intralobular stroma in biopsy specimens performed for other breast lesions. Less frequently, it presents as a nodular form that has a benign morphology on imaging, mimicking fibroadenoma or as a diffuse form causing progressive massive gigantomastia. Diagnosis is established by biopsy. Knowledge of the imaging appearance of PASH not only facilitates proper assessment of radiopathological correlation but also helps in deciding further management of these lesions. Occasionally, nodular PASH may have a suspicious appearance on imaging wherein excision biopsy is indicated to exclude a coexisting carcinoma.

Management of Stromal Lesions.

Breast stromal lesions include fibroadenomas, phyllodes tumors, pseudoangiomatous stromal hyperplasia, periductal stromal tumors, and lipomas. Most of these lesions are benign and can be managed with observation or surgical excision. Phyllodes tumors, however, are subcategorized into benign, borderline, and malignant. Benign phyllodes tumors may be removed without a margin of breast tissue while borderline and malignant phyllodes tumors need a wide excision with a greater than 1 cm margin. Because malignant phyllodes tumors have a poor prognosis, efforts should be made to discuss their treatment in a multidisciplinary setting and enrollment in a clinical trial should be considered.

Use of granulocyte and monocyte adsorption apheresis in dermatology (Review).

Adsorptive granulocyte and monocyte apheresis (GMA) is an extracorporeal treatment that selectively removes activated myeloid lineage leukocytes from peripheral blood. This technique consists of a column with cellulose acetate beads as absorptive leukocytapheresis carriers, and was initially used to treat ulcerative colitis. A literature search was conducted to extract recently published studies about the clinical efficacy of GMA in patients with different skin disorders, reporting information on demographics, clinical symptoms, treatment and clinical course. Dermatological diseases, in which GMA has been performed, include generalized pustular psoriasis, pyoderma gangrenosum, palmoplantar pustular psoriasis, Behcet's disease, Sweet's syndrome, adult-onset Still's disease, impetigo herpetiformis, reactive arthritis, acne and hidradenitis suppurativa syndrome, cutaneous allergic vasculitis and systemic lupus erythematosus. In most patients, GMA was started after the failure of conventional therapeutic options and it was helpful in the majority of cases. Based on the information summarized, GMA could be considered a valid non-pharmacological treatment option for patients with several dermatological conditions, which are difficult to treat with other pharmacological preparations.

Pyoderma Gangrenosum, Acne, and Hidradenitis Suppurativa Syndrome: A Case Report and Literature Review.

Pyoderma gangrenosum, acne, and hidradenitis suppurativa syndrome is a rare inflammatory disease characterized by pyoderma gangrenosum (PG), mild to severe facial acne, and hidradenitis suppurativa (HS). It only affects the skin and represents cutaneous characteristics of a spectrum of autoinflammation. Lack of pyogenic sterile arthritis (PA) distinguishes the pyoderma gangrenosum, acne, and hidradenitis suppurativa (PASH) syndrome from pyogenic arthritis, pyoderma gangrenosum, acne, and hidradenitis suppurativa (PA-PASH), pyoderma gangrenosum, acne, hidradenitis suppurtiva, and ankylosing spondylitis (PASS), and pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) syndromes. The exact etiology and pathogenesis of PASH syndrome remain unknown. Both PG and HS are contained in the spectrum of neutrophilic dermatitis, which is considered as an autoinflammatory syndrome. From a pathophysiological point of view, they show similar mechanisms, including neutrophil-rich cutaneous infiltration and overexpression of the interleukin-1 (IL-1) family. These findings provide guidance for these intractable diseases. In this review, we described a case of PASH syndrome in a patient who initially failed to respond to immunosuppressive treatment but responded to a combination of colchicine and thalidomide. We reviewed the relevant literature that focuses on PASH syndrome management.

Variant Enrichment Analysis to Explore Pathways Functionality in Complex Autoinflammatory Skin Disorders through Whole Exome Sequencing Analysis.

The challenge of unravelling the molecular basis of multifactorial disorders nowadays cannot rely just on association studies searching for potential causative variants shared by groups of patients and not present in healthy individuals; indeed, association studies have as a main limitation the lack of information on the interactions between the disease-causing variants. Thus, new genomic analysis tools focusing on disrupted pathways rather than associated gene variants are required to better understand the complexity of a disease. Therefore, we developed the Variant Enrichment Analysis (VEA) workflow, a tool applicable for whole exome sequencing data, able to find differences between the numbers of genetic variants in a given pathway in comparison with a reference dataset. In this study, we applied VEA to discover novel pathways altered in patients with complex autoinflammatory skin disorders, namely PASH (n = 9), 3 of whom are overlapping with SAPHO) and PAPASH (n = 3). With this approach we have been able to identify pathways related to neutrophil and endothelial cells homeostasis/activations, as disrupted in our patients. We hypothesized that unregulated neutrophil transendothelial migration could elicit increased neutrophil infiltration and tissue damage. Based on our findings, VEA, in our experimental dataset, allowed us to predict novel pathways impaired in subjects with autoinflammatory skin disorders.