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.

An Update on the Molecular and Clinical Characteristics of Apocrine Carcinoma of the Breast.

Apocrine carcinoma of the breast is a rare malignancy. According to 2019 WHO classification, apocrine cellular features and a characteristic steroid receptor profile (Estrogen receptor (ER)-negative and androgen receptor (AR)-positive) define apocrine carcinoma. Her-2/neu protein expression is reported in ∼30-50% of apocrine carcinomas, while NGS analysis showed frequent PIK3CA/PTEN/AKT and TP53 mutations Followed by deregulation in the mitogen-activated protein kinase pathway components (mutations of KRAS, NRAS, BRAF). A recent miRNA study indicates various miRNAs (downregulated hsa-miR-145-5p and upregulated 14 miRNAs such as hsa-miR-182-5p, hsa-miR-3135b, and hsa-miR-4417) may target the commonly altered pathways in apocrine carcinomas such as ERBB2/HER2 and mitogen-activated protein kinase signaling pathway. Although AR expression is a hallmark of apocrine carcinoma, little is known regarding the efficacy/resistance to antiandrogens. Success of bicalutamide, a non-steroidal anti-androgen, was reported in a case of Her2-negative apocrine carcinoma. Two recent studies, however, described presence of anti-androgen resistance biomarkers (a splice variant ARv7 and AR/NCOA2 co-amplification) in a subset of AR+ apocrine carcinomas, cautioning the use of anti-androgens in AR+ triple-negative breast carcinomas. Apocrine carcinomas rarely show biomarkers predictive of response to immune checkpoint inhibitors (PD-L1 expression, MSI-H status, and TMB-high). Therefore, a comprehensive cancer profiling of apocrine carcinomas is necessary to identify potential therapeutic targets for a truly individualized treatment approach.

Soy Isoflavone Genistein Inhibits an Axillary Osmidrosis Risk Factor ABCC11: In Vitro Screening and Fractional Approach for ABCC11-Inhibitory Activities in Plant Extracts and Dietary Flavonoids.

Axillary osmidrosis (AO) is a common chronic skin condition characterized by unpleasant body odors emanating from the armpits, and its aetiology is not fully understood. AO can seriously impair the psychosocial well-being of the affected individuals; however, no causal therapy has been established for it other than surgical treatment. Recent studies have revealed that human ATP-binding cassette transporter C11 (ABCC11) is an AO risk factor when it is expressed in the axillary apocrine glands-the sources of the offensive odors. Hence, identifying safe ways to inhibit ABCC11 may offer a breakthrough in treating AO. We herein screened for ABCC11-inhibitory activities in 34 natural products derived from plants cultivated for human consumption using an in vitro assay system to measure the ABCC11-mediated transport of radiolabeled dehydroepiandrosterone sulfate (DHEA-S-an ABCC11 substrate). The water extract of soybean (Glycine max) was found to exhibit the strongest transport inhibition. From this extract, via a fractionation approach, we successfully isolated and identified genistein, a soy isoflavone, as a novel ABCC11 inhibitor with a half-maximal inhibitory concentration value of 61.5 µM. Furthermore, we examined the effects of other dietary flavonoids on the ABCC11-mediated DHEA-S transport to uncover the effects of these phytochemicals on ABCC11 function. While further human studies are needed, our findings here about the natural compounds will help develop a non-surgical therapy for AO.

Clinical hypocalcemia following surgical resection of apocrine gland anal- sac adenocarcinomas in 3 dogs.

Three canine patients were presented with marked hypercalcemia secondary to an apocrine gland anal sac adenocarcinoma (AGASCA). Two of the patients underwent treatment for hypercalcemia before surgical resection of their tumors, including diuresis and the administration of bisphosphonates. All dogs developed clinically symptomatic hypocalcemia 2 to 4 days following surgery. Clinical signs included facial rubbing, muscle fasciculations, lameness, and collapse. The dogs each required calcium supplementation and close monitoring of serum ionized calcium, as inpatients and continuing after discharge. Hypocalcemia and associated clinical signs resolved with treatment in all cases.

Hypocalcémie clinique après la résection chirurgicale d'adénocarcinomes du sac de glandes anales aprocrines chez trois chiens. Trois patients canins ont été présentés avec une hypercalcémie marquée secondaire à un adénocarcinome du sac des glandes anales apocrines (ASGAA). Deux des patients ont subi un traitement pour l'hypercalcémie avant la résection chirurgicale de leurs tumeurs, y compris la diurèse et l'administration de bisphosphonates. Tous les chiens ont développé une hypocalcémie cliniquement symptomatique de 2 à 4 jours après la chirurgie. Les signes cliniques incluaient le frottement de la face, des fasciculations des muscles, la boiterie et le collapsus. Les chiens ont tous exigé de la supplémentation au calcium et une étroite surveillance du calcium ionisé sérique, comme patients à l'interne et après le congé. L'hypocalcémie et les signes cliniques connexes se sont résorbés avec le traitement dans tous les cas.(Traduit par Isabelle Vallières).

Verneuil's disease, innate immunity and vitamin D: a pilot study.

BACKGROUND: Verneuil's disease is a chronic inflammatory skin disease of the follicles in apocrine glands rich area of the skin (axillary, inguinal, anogenital) and is associated with a deficient skin innate immunity. It is characterized by the occurrence of nodules, abscesses, fistulas, scars. Recently, vitamin D has been shown to stimulate skin innate immunity. OBJECTIVE: The primary objective of the study was to assess whether Verneuil's disease was associated with vitamin D deficiency. The secondary objective was to determine whether vitamin D supplementation could improve inflammatory lesions. METHODS: First, 25(OH) vitamin D3 serum levels in patients with Verneuil's disease followed at Nantes University Hospital were compared to those of healthy donors from the French Blood Bank. Then, a pilot study was conducted in 14 patients supplemented with vitamin D according to their vitamin D level at baseline at months 3 and 6. The endpoints at 6 months were decreased by at least 20% in the number of nodules and in the frequency of flare-ups. RESULTS: Twenty-two patients (100%) had vitamin D deficiency (level <30 ng/mL) of whom 36% were severely deficient (level <10 ng/mL), having correlation with the disease severity (P = 0.03268) vs. 20 controls with vitamin D deficiency (91%) of whom 14% were severely deficient. In 14 patients, the supplementation significantly decreased the number of nodules at 6 months (P = 0.01133), and the endpoints were achieved in 79% of these patients. A correlation between the therapeutic success and the importance of the increase in vitamin D level after supplementation was observed (P = 0.01099). CONCLUSION: Our study shows that Verneuil's disease is associated with a major vitamin D deficiency, correlated with the disease severity. It suggests that vitamin D could significantly improve the inflammatory nodules, probably by stimulating the skin innate immunity. A larger randomized study is needed to confirm these findings.

Large cutaneous apocrine carcinoma occurring on right thigh aggravated after moxa treatment

Primary cutaneous apocrine carcinoma is a rare adnexal tumor of the skin that occurs mainly in the axilla, anogenital area while the scalp and the lower extremities, especially the thigh, are very unusual sites. However, clinical or pathologic characteristics have not been well established due to a paucity of this tumor. Herein, we report very unusual case of apocrine carcinoma present as a huge mass in the lateral thigh of 77-year-old woman, which was aggravated abruptly after an irritation by moxa treatment, with a brief review of the literature.

Local injection of botulinum toxin A: an alternative therapy for axillary osmidrosis.

The objective of this study was to investigate the efficacy of local injection of botulinum toxin A for treating axillary osmidrosis. One hundred and fifty patients with axillary osmidrosis were randomly divided to receive botulinum toxin A injection treatment (50 U of botulinum toxin A was injected intracutaneously into 6-20 different sites within each axilla, n = 74) or surgical excision of the apocrine glands (n = 76). The patients were followed up for 1-3 months to analyze the therapeutic effect and complications of the two methods. The curative effect in patients with mild and moderate axillary osmidrosis was not significantly different between the botulinum toxin A injection group and operation group. However, for patients with severe axillary osmidrosis, surgery treatment seemed to be superior to botulinum toxin A treatment (P = 0.005). There was also no significant difference in the modified Dermatology Life Quality Index between the two treatments. Two cases showed complications related to hemorrhage and incision infection in the operation group. In conclusion, local injection of botulinum toxin A is a safe, fast and effective treatment for mild and moderate axillary osmidrosis, but the long-term effect remains to be further investigated.

Efficacy of fractional microneedle radiofrequency device in the treatment of primary axillary hyperhidrosis: a pilot study.

BACKGROUND: Fractional microneedle radiofrequency (FMR) devices deliver energy to the deep dermis through insulated microneedles without destroying the epidermis. These FMR devices have been shown to be effective for the treatment of wrinkles, acne scars and large pores. In this study it was postulated that FMR energy could specifically affect the sweat glands, preserving the skin surface even if sweat glands were seated in the deep dermis. OBJECTIVE: To evaluate the efficacy and safety of FMR for primary axillary hyperhidrosis (PAH) treatment and to conduct a histological analysis before and after treatment. METHODS: Twenty patients with PAH had 2 sessions of bipolar FMR treatment at 4-week intervals. Clinical improvement was evaluated using a Hyperhidrosis Disease Severity Scale (HDSS) and photographs were taken using the starch-iodine test at every visit and 2 months after the last treatment. The amount of sweat reduction was indirectly assessed using a Tewameter™. Skin biopsies were obtained from 3 of the enrolled patients before and after treatment. The satisfaction and adverse reactions of the research participants were recorded at every follow-up visit. RESULTS: HDSS scores decreased significantly from a baseline of 3.3 to 1.5 and 1.8 after the first and second months of posttreatment follow-up sessions, respectively (p < 0.001). In response to a subjective assessment at 1 month after the second treatment, 75% of patients (n = 15) had an HDSS score of 1 or 2, and 70% of patients (n = 14) expressed more than 50% improvement in their sweating. The starch-iodine reaction was also remarkably reduced in 95% of patients (n = 19) after FMR treatment. Histological findings showed a decrease in the number and size of both apocrine and eccrine glands 1 month after the final treatment. Side effects were minimal and included mild discomfort, transient swelling and postinflammatory hyperpigmentation. CONCLUSION: FMR treatment was effective for the treatment of PAH without significant adverse reactions due to direct volumetric heating of the lower dermis.

Isolated areolar apocrine chromhidrosis.

A case of isolated areolar apocrine chromhidrosis in an 11-year-old female is presented. This is the youngest case cited in Medline. The goal of this review is to increase awareness of apocrine chromhidrosis among primary care providers and to discuss treatment. Capsaicin cream 0.025% is a proven treatment that may reduce the potential psychological impact and embarrassment that patients experience.

Enfermedad de Lafora / Lafora's disease

El diagnóstico de enfermedad de Lafora se basa en la sintomatología clínica y en la detección histológica de unas inclusiones intracitoplasmáticos PAS positivas denominadas cuerpos de Lafora. A pesar de que esta entidad no cursa con manifestaciones cutáneas, la participación del dermatólogo y del dermatopatólogo es importante, pues la biopsia de la piel axilar es el procedimiento diagnóstico más rentable. En esta localización los cuerpos de Lafora se detectan principalmente en las células periféricas ductales de los conductos ecrinos y en las células mioepiteliales de las glándulas apocrinas. Presentamos este hallazgo en una mujer de 17 años (AU)

Carcinoma verrucoso sobre hidrosadenitis supurativa perianal. Presentación de un caso y revisión bibliográfica / Verrucous carcinoma complicating perianal hidradenitis suppurativa. Case report and literature review

La hidrosadenitis supurativa es una enfermedad inflamatoria crónica que afecta a las glándulas apocrinas. Al igual que en otras enfermedades inflamatorias crónicas de la piel pueden producirse cambios degenerativos. El carcinoma escamoso es la neoplasia maligna descrita con más frecuencia siendo excepcional el hallazgo de su variedad bien diferenciada denominado carcinoma verrucoso. Desde 1988, en nuestro hospital se han intervenido 44 pacientes diagnosticados de hidrosadenitis supurativa, de los cuales 15 presentaban una forma masiva de la enfermedad. Durante este periodo tan solo un paciente atendido en nuestra unidad de coloproctología por afectación perianal presentó degeneración maligna hacia un carcinoma verrucoso. Presentamos este caso y comentamos las peculiaridades clínicas y terapeúticas de esta situación tan poco frecuente (AU)

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Distribution of CA 125 in embryonic tissues and adult derivatives of the fetal periderm.

New murine monoclonal antibodies to a partially purified CA 125 antigen were developed and identified as M 2 and M 11. With immunohistochemical techniques, these new antibodies and OC 125 antibody were used to search for CA 125 in embryonic tissues and adult apocrine sweat glands and mammary glands. The embryonic skin, the periderm, expressed CA 125 antigen and its adult derivatives, the mammary glands and apocrine sweat glands, expressed CA 125 while in the active state of secretion. In a 6-week-old formalin-fixed and paraffin-embedded ectopic embryo specimen, antibodies M 2 and M 11 recognized CA 125 in the periderm, the notochord, the myocardium, the pericardium, the gastroenteric tract, enteric duct remnants in the umbilical cord (vitelline and allantoic ducts), the mesonephric duct, and the amnion. OC 125 staining of these formalin-fixed specimens was either very faint or absent. In a formalin-fixed and paraffin-embedded specimen of apocrine sweat glands from the axilla, antibodies M 2 and M 11 detected CA 125 antigen intracellularly in the secretory cells. Again no staining was observed with OC 125 antibody. In a frozen and acetone-fixed specimen of lactating mammary glands, antibodies M 2 and OC 125 detected CA 125 antigen intraductally. Colostrum and milk collected from 25 mothers at various stages post partum had mean CA 125 levels of 34,213 U/ml in colostrum, 1469 U/ml at 3 to 7 days, and 105 U/ml at 5 to 26 weeks.

[The complete remission of recurrent sweat gland carcinoma by radiotherapy combined with hyperthermia].

The authors describe a case of a sweat gland carcinoma that underwent complete remission after treatment with radiotherapy and hyperthermia. This sweat gland carcinoma had been thought to be unamenable to any therapeutic treatment. Based on this result, the authors feel that radiotherapy combined with hyperthermia may be effective for the treatment of a sweat gland carcinoma.

Treatment of apocrine chromhidrosis with topical capsaicin.

A 30-year-old white woman with facial apocrine chromhidrosis was treated successfully with topical capsaicin once or twice daily. Paired comparison of treated versus untreated sides and active drug-treated versus vehicle-treated sides showed suppression of the chromhidrosis only when capsaicin was used. After treatment was discontinued, the chromhidrosis returned within 2 days.

Treatment of hidradenitis suppurativa with combination hypothalamic-pituitary-ovarian and adrenal suppression. A case report.

A 33-year-old woman with severe familial hidradenitis suppurativa of the vulva and perineum was treated with a combination of dexamethasone and a new synthetic gonadotropin releasing hormone agonist, leuprolide acetate. The clinical improvement paralleled the adrenal and ovarian suppression, as demonstrated by falling blood levels of testosterone, dehydroepiandrosterone sulfate, androstenedione and estradiol.

Humoral hypercalcemia of malignancy in nude mouse model of a canine adenocarcinoma derived from apocrine glands of the anal sac. Biochemical, histomorphometric, and ultrastructural studies.

A serially transplantable tumor line, designated CAC-8, has been developed in nude mice from a spontaneously occurring adenocarcinoma of the anal sac from a hypercalcemic dog. Nude mice with transplanted CAC-8 developed hypercalcemia (mean 16.3 +/- 0.6 mg/dl) and moderate hypophosphatemia without bone metastasis. Urinary excretion of calcium and hydroxyproline were increased 6- and 2.3-fold, respectively. Urinary excretion of cAMP was moderately increased but phosphorus excretion was not significantly altered. Serum 1,25-dihydroxycholecalciferol was increased significantly in tumor-bearing nude mice in proportion to the magnitude of tumor-induced hypercalcemia. Histomorphometric evaluation of lumbar vertebrae from nude mice with CAC-8 revealed decreased total and cortical bone volume, a 3.3-fold increase in bone resorption rate and a 2.5-fold increase in bone formation rate at the tissue level. The transplanted CAC-8 has maintained the histologic pattern of the original carcinoma up to the present sixth passage. Ultrastructural evaluation of transplanted tumor cells revealed 150-250-nm secretory-like granules. The granules did not stain by using an ultrastructural cytochemical (uranaffin) stain specific for neuroendocrine secretory granules. Ultrastructurally, the parathyroid glands of nude mice with CAC-8 appeared inactive with large intracytoplasmic whorl of agranular membranes. These data suggest the transplanted carcinoma secreted a humoral factor which resulted in hypercalcemia. The tumor line (CAC-8) propagated in nude mice represents an animal model of humoral hypercalcemia of malignancy that shares many features with the syndrome described in human patients. Unique features of this transplanted carcinoma associated with hypercalcemia include increased serum dihydroxycholecalciferol, increased rate of bone formation as well as bone resorption, an absence of bone metastases, and evidence of parathyroid gland suppression.