Cutaneous Adenocarcinoma Research Articles

Phase II clinical trial of docetaxel and trastuzumab for HER2-positive advanced extramammary Paget's disease (EMPD-HER2DOC).

No consensus has been reached regarding the optimal chemotherapy for metastatic extramammary Paget's disease (EMPD), a rare cutaneous adenocarcinoma, because of the lack of solid evidence from prospective trials. However, the immunohistochemical profile of EMPD reportedly resembles that of breast cancer, particularly in terms of human epidermal growth factor receptor 2 (HER2) expression, suggesting that HER2 is a promising therapeutic target for advanced HER2-positive EMPD. In this phase II single-arm trial, 13 Japanese patients received intravenous trastuzumab (loading dose of 8 mg/kg and maintenance dose of 6 mg/kg) and docetaxel (75 mg/m2) every 3 weeks for up to 2 years. The docetaxel dose was reduced or discontinued according to its toxicity. The primary trial endpoints were objective response rate (ORR) after 3 cycles of treatment and safety throughout the study period. All 13 patients completed 3 cycles of combination therapy. The median follow-up was 27.9 months. The ORR was 76.9% (n = 10/13; 90% CI, 50.5-93.4). Frequently observed adverse events were neutropenia (100%), hypoalbuminemia (84.6%), and mucocutaneous infection (84.6%), all of which were well tolerated. The combination of docetaxel and trastuzumab demonstrated a favorable clinical effect and acceptable tolerability, which makes it a good treatment option for HER2-positive metastatic EMPD (ClinicalTrials.gov Identifier: UMIN000021311, jRCTs031180073).

Vulvar Paget’s Disease: A Systematic Review of the MITO Rare Cancer Group

Vulvar Paget's disease (VPD) is a rare form of cutaneous adenocarcinoma of the vulva, which accounts for about 1-2% of all vulvar neoplasms and mainly affects post-menopausal women. The clinical presentation is usually non-specific and mimics chronic erythematous skin lesions; therefore, the diagnosis is often difficult and delayed. Although VPD is typically diagnosed at a locally advanced stage and has a high recurrence rate, the prognosis is overall favorable with a 5-year survival of nearly 90%. Due to the limited and poor-quality evidence, there is no global consensus on optimal management. Therefore, we performed a systematic review of the literature through the main electronic databases to deepen the current knowledge of this rare disease and discuss the available treatment strategies. Wide surgical excision is recommended as the standard-of-care treatment and should be tailored to the tumor position/extension and the patient's performance status. The goal is to completely remove the tumor and achieve clear margins, thus reducing the rate of local recurrences. Non-surgical treatments, such as radiotherapy, chemotherapy, and topical approaches, can be considered, especially in the case of unresectable and recurrent disease. In the absence of clear recommendations, the decision-making process should be individualized, also considering the new emerging molecular targets, such as HER2 and PD-L1, which might pave the way for future targeted therapies. The current review aims to raise awareness of this rare disease and encourage international collaboration to collect larger-scale, high-quality evidence and standardize treatment.

Mohs micrographic surgery in rare cutaneous tumors: a retrospective study at a Brazilian tertiary university hospital

BackgroundMohs micrographic surgery is an established technique in the treatment of cutaneous neoplasms. It offers higher cure rates and the main indications are non-melanoma malignant skin tumors. Few studies have been performed on the treatment of rare tumors through this technique. ObjectiveTo study rare skin tumors and rare variants of basal cell carcinoma and squamous cell carcinoma submitted to Mohs micrographic surgery in a tertiary service in relation to frequency, disease-free evolution, and applicability of this surgical procedure for this group of tumors. MethodsThis was a retrospective observational study including rare skin tumors and less common variants of basal cell carcinoma and squamous cell carcinoma treated using Mohs micrographic surgery, between October 2008 and April 2021. ResultsDuring the study period, 437 tumors were treated using Mohs micrographic surgery, and 22 (5%) rare skin tumors were selected. The tumors comprised three dermatofibrosarcomas protuberans, two atypical fibroxanthomas, two spiradenomas, two hypercellular fibrohistiocytomas, one primary cutaneous adenocarcinoma, one trichoblastoma, one porocarcinoma, one chondroid syringoma, one cutaneous angiosarcoma, one Merkel cell carcinoma, and one sebaceous carcinoma. Six other cases of rare basal cell carcinoma variants with trichoepitheliomatous differentiation, metatypical basal cell carcinoma, and clear cell squamous cell carcinoma were included. There were no cases of recurrence after an average of six years of follow-up. Study limitationsThis is a retrospective study on rare neoplasms carried out in a single referral center, and this surgical technique isn’t widely available in the public service. ConclusionThis retrospective case series showed that Mohs micrographic surgery is an appropriate treatment for rare skin tumors. They corresponded to 5% of the tumors treated by the technique during a 12-year-period, with no recurrences identified.

Serum Cytokeratin 18 as a Metastatic and Therapeutic Marker for Extramammary Paget's Disease.

Extramammary Paget's disease (EMPD) is a rare cutaneous adenocarcinoma with unfavourable prognosis once it becomes invasive. A tumour marker that reflects disease progression is required for adequate management of EMPD. Cytokeratin 18 is highly expressed in many types of cancer and its soluble forms are detected by M30 (for caspase-cleaved form) and M65 (for both caspase-cleaved and intact forms) assays. We report here that tumour cells of EMPD in both lesional skin and lymph node metastasis are immunohistochemically positive for CK18, and the baseline serum M30 and M65 levels in patients with metastatic EMPD are significantly higher than those in non-metastatic patients. In addition, serial serum M30 and M65 levels might reflect recurrence of EMPD and response to chemotherapy. These results suggest that serum CK18 levels may be a useful tumour marker for advanced EMPD.

Development and Validation of an Artificial Intelligence-Based Image Classification Method for Pathological Diagnosis in Patients With Extramammary Paget's Disease.

Extramammary Paget’s disease (EMPD) is a rare, malignant cutaneous adenocarcinoma with a high recurrence rate after surgical resection. Early diagnosis of EMPD is critical as 15%–40% of cases progress into an invasive form and resulting in a dismal prognosis. However, EMPD can be a diagnostic challenge to pathologists, especially in the grassroots hospital, because of its low incidence and nonspecific clinical presentation. Although AI-enabled computer-aided diagnosis solutions have been extensively used in dermatological pathological image analysis to diagnose common skin cancers such as melanoma and basal cell carcinoma, these techniques have yet been applied to diagnose EMPD. Here, we developed and verified a deep learning method with five different deep convolutional neural networks, named ResNet34, ResNet50, MobileNetV2, GoogLeNet, and VGG16, in Asian EMPD pathological image screening to distinguish between Paget’s and normal cells. We further demonstrated that the results of the proposed method are quantitative, fast, and repeatable by a retrospective single-center study. The ResNet34 model achieved the best performance with an accuracy of 95.522% in pathological images collected at a magnification of ×40. We envision this method can potentially empower grassroots pathologists’ efficiency and accuracy as well as to ultimately provide better patient care.

Cutaneous metastasis of cecum cancer with MSI-high and BRAFV600E mutation: a case report

BackgroundCutaneous metastases of colorectal cancer (CRC) are rare, occurring in 0.7% to 5% of cancer patients. Furthermore, the molecular subtypes of cutaneous metastasis of CRC are unclear. Here, we present a rare case of cutaneous metastasis of high-frequency microsatellite instability (MSI-high)/BRAFV600E-mutant cecum cancer.Case presentationA 77-year-old woman presented at the outpatient clinic with a subcutaneous mass on her left back. An excisional biopsy was performed and metastatic cutaneous adenocarcinoma was diagnosed. A computed tomography scan of the thorax and abdomen showed thickening of the cecum wall, the presence of pericolic lymph nodes, multiple masses in the liver, and a single nodule in the right lung. Right colectomy with D2 lymphadenectomy and functional end-to-end anastomosis was performed because of the almost-complete intestinal obstruction. The expression of KRAS wild type, BRAFV600E mutation, and MSI-high was detected in the cecum cancer using molecular pathological examination. She received chemotherapy with XELOX + BEV regimen (capecitabine + oxaliplatin + bevacizumab). After four administrations, a computed tomography scan showed reduction of distant metastases, which suggested partial response.ConclusionsWe encountered a rare case of cutaneous metastasis of MSI-high and BRAFV600E-mutant cecum cancer. In the future, it will be necessary to accumulate more cases to identify clinical features and more effective treatments for CRCs with cutaneous metastasis.

Basic Pan-Cancer Analysis of the Carcinogenic Effects of Cyclin-Dependent Kinase 4 (CDK4) in Human Surface Tumors.

Although the evidence based on current human, animal, or molecular biology can explain some of the relationships between CDK4 and cancer, there is no pan-cancer analysis of the gene CDK4 in human skin tumors. Therefore, the potential carcinogenic effects of CDK4 in 33 tumors were initially explored in the datasets of the GEO (Gene Expression Omnibus) and the CGA (Cancer Genome Atlas). We found that CDK4 was highly expressed in most cancers and that CDK4 performance levels significantly correlated with the prognosis of cancer patients. These were found in our preliminary exploration. In addition, we used the dataset in tumors such as cutaneous melanoma or lung adenocarcinoma and found increased levels of phosphorylation of r24 l/C/h/s. In addition, fibroblast infiltration associated with CDK4 cancer was observed in head and neck, sarcoma, and melanoma skin. Using this pan-cancer study, our group has provided a comprehensive preliminary demonstration of the oncogenic effects of the CDK4 gene on different human skin tumors.

Abstract 243: Identification of novel epitopes of NY-ESO-1 for solid malignancies by Kiromic proprietary search engine Diamond

Abstract Adoptive cell therapy has been proven a powerful approach for the cure of cancer and other diseases. In particular, the selection of appropriate immunogenic targets has been key to positive outcomes in clinical settings. The availability of RNA-Seq analysis, the accessibility to large data repositories such as TCGA and GTEx, and the creation of new bioinformatic tools have accelerated the process of neoantigen discovery. However, most of the current algorithms are encumbered by the intrinsic complexity of predicting antigen immunogenicity. Diamond™ is a novel artificial intelligence and cognitive machine and deep learning platform to predict peptide processing, HLA binding, and T cell activation. To validate the predictive value of DIAMOND algorithms, the meta-analyses of expression data of cancer-testis antigen New York Esophageal Squamous Cell Carcinoma 1 (NY-ESO-1) and predictions for the immunogenic peptides were compared to experimental data in the literature. In agreement with published clinical observations, DIAMOND metanalysis showed NY-ESO-1 genic overexpression in skin cutaneous melanoma, lung adenocarcinoma, and sarcoma. Moreover, DIAMOND predicted an MHC binding affinity of 0.289 with Supertype A2 for a new NY-ESO-1 peptide, which has been successfully targeted in clinical trials for patients with HLA-A*02:01, as well as it mirrored published data in its prediction of peptide affinity binding in NY-ESO-1–specific MHC II–restricted T cell receptors. Taken together these data support DIAMOND as a reliable platform for the discovery of new immunogenic targets for cancer therapy. Citation Format: Lucia Piccotti, Leonardo Mirandola, Maurizio Chiriva-Internati. Identification of novel epitopes of NY-ESO-1 for solid malignancies by Kiromic proprietary search engine Diamond [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 243.

DNA Damage Repair Gene Set as a Potential Biomarker for Stratifying Patients with High Tumor Mutational Burden

Simple SummaryImmunotherapy has been a promising therapeutic approach for cancer treatment in recent years. Although cancer immunotherapy has achieved remarkable success, treatment response is only observed in a small number of patients. As nonresponders need to endure high treatment costs and toxicities with little benefit from treatment, identifying potential predictive biomarkers is critical to optimize the benefits of immunotherapy in patients. The total number of mutations in the tumor genome is a useful biomarker. Patients with a large number of mutations tend to respond better to cancer immunotherapy. However, assessment of the total number of mutations may not be easy. In this study, we identified gene sets with only a small number of genes whose mutations serve as an indicator of the total number of mutations. These cancer-specific gene sets can be used as a cost-effective approach to stratify patients with a large number of mutations in clinical practice.Tumor mutational burden (TMB) is a promising predictive biomarker for cancer immunotherapy. Patients with a high TMB have better responses to immune checkpoint inhibitors. Currently, the gold standard for determining TMB is whole-exome sequencing (WES). However, high cost, long turnaround time, infrastructure requirements, and bioinformatics demands have prevented WES from being implemented in routine clinical practice. Panel-sequencing-based estimates of TMB have gradually replaced WES TMB; however, panel design biases could lead to overestimation of TMB. To stratify TMB-high patients better without sequencing all genes and avoid overestimating TMB, we focused on DNA damage repair (DDR) genes, in which dysfunction may increase somatic mutation rates. We extensively explored the association between the mutation status of DDR genes and TMB in different cancer types. By analyzing the mutation data from The Cancer Genome Atlas, which includes information for 33 different cancer types, we observed no single DDR gene/pathway in which mutation status was significantly associated with high TMB across all 33 cancer types. Therefore, a computational algorithm was proposed to identify a cancer-specific gene set as a surrogate for stratifying patients with high TMB in each cancer. We applied our algorithm to skin cutaneous melanoma and lung adenocarcinoma, demonstrating that the mutation status of the identified cancer-specific DDR gene sets, which included only 9 and 14 genes, respectively, was significantly associated with TMB. The cancer-specific DDR gene set can be used as a cost-effective approach to stratify patients with high TMB in clinical practice.

A rare case of cutaneous apocrine adenocarcinoma on the axilla that metastasized to the cervical lymph node 12 years after surgery

A rare case of cutaneous apocrine adenocarcinoma on the axilla that metastasized to the cervical lymph node 12 years after surgery

Successful treatment of cutaneous solid type adenocarcinoma with cryosurgery in a Pekingese dog

The aim of this study is to defined the treatment of cutaneous solid type adenocarcinoma in a Pekingese dog using cryotherapy. A 3.5 years old intact female Pekingese dog was referred to the small animal surgery clinic. The first neoplasm localization was dorsal to the vulva and the others were bilateral to the vulva. The shape of the nodules were circular. The nodule diameters were 1.8, 1.5, and 1.2 cm. In cross section, the nodules were whitish-yellow in colour, of solid consistency, and characterized by thickening of the skin. The probe-based cryosurgical system was used for cryoablation, using local anesthetic as the interface for uniform freezing. Based on histopathological features, the dog was diagnosed with solid type perianal adenocarcinoma. In conclusion, cryosurgery can be a potent alternate treatment for pleasant, nodular perianal cutaneous adenocarcinoma in animals, particularly those not suited for operation, or whose owners refuse to have them undergo operation.

Extramammary Paget disease shows differential expression of B7 family members B7-H3, B7-H4, PD-L1, PD-L2 and cancer/testis antigens NY-ESO-1 and MAGE-A.

Extramammary Paget disease (EMPD) is a rare cutaneous adenocarcinoma of the anogenital region most commonly treated with surgical excision. Surgical margin clearance is often problematic and recurrence rates remain high indicating the need for additional therapeutic options. Topical immunomodulators have been used with reported success suggesting EMPD may respond to other immunotherapies. This study investigates EMPD protein expression of targetable B7 family members and cancer/testis antigens (CTAs) B7-H3, B7-H4, PD-L1, PD-L2, MAGE-A, and NY-ESO-1 and components of antigen presenting machinery B2M and MHC-I. Fifty-seven specimens from 48 patients (31 female and 17 male), representing in situ, invasive, and metastatic disease of primary and secondary origin were stained and scored (627 total slides). The percentage of cases expressing each immune regulatory molecule in the in situ followed by invasive tumor components was: B7-H3 (94, 90), B7-H4 (82, 78), PD-L1 (6, 10), MAGE-A (39, 50), NY-ESO-1 (16, 20), B2M (100, 89), and MHC-I (78, 79). PD-L2 was negative in all cases. There was high correlation between marker expression within the in situ and invasive tumor components of the same case. B7-H4 was preferentially expressed in primary cutaneous EMPD. Co-expression of B7 family members B7-H3 and B7-H4 was found within the in situ and invasive tumor components of 74% and 48% of cases, respectively. These findings provide an initial characterization of EMPD tumor cell expression of B7-H3, B7-H4, PD-L1, PD-L2, MAGE-A, and NY-ESO-1 and indicate the potential for new immunotherapeutic options for patients with EMPD.

Extramammary Paget's disease

Extramammary Paget's disease (EPD) is arare, slowly growing, cutaneous adenocarcinoma with an incidence of 0.1-2.4 per 1,000,000 inhabitants. Histologically, EPD is characterized by the presence of epidermal Paget's cells, similarly to mammary Paget's disease. The EPD is typically divided into primary EPD (typeI) and secondary EPD (typeII associated with colorectal carcinoma and typeIII associated with urogenital carcinoma). From aclinical point of view, EPD is unspecific commonly mimicking chronic inflammatory skin disorders. This unspecific clinical picture can impede and delay the diagnosis of EPD. The treatment of choice for local EPD is the micrographically controlled excision. The extent of the infiltration of adnexal structures should be histologically determined prior to topical therapies, such as imiquimod and superficial ablative therapy. The complete excision of the tumor can be challenging due to ill-defined borders. In the metastatic stage the EPD has apoor prognosis. Controlled clinical trials for systemic treatment are still lacking.

Combination Cisplatin-Epirubicin-Paclitaxel Therapy for Metastatic Extramammary Paget's Disease.

Extramammary Paget's disease (EMPD) is a rare cutaneous adenocarcinoma that clinicopathologically resembles breast cancer. The prognosis of metastatic EMPD is poor. Although several chemotherapies have been tried, the effects are temporary; better drugs and combinations are required.In the present study, we retrospectively analyze the efficacy and safety of combination of cisplatin, epirubicin, and paclitaxel in five metastatic EMPD cases. The efficacy was better than that for previously reported regimens: 80% partial responses, including two patients who were refractory to taxane- and/or platinum-based regimens. In terms of safety, four patients who were able to continue treatment exhibited acceptable tolerability.This is the first regimen to combine taxane and anthracycline. When treating breast cancer, anthracycline is regarded as the key cytotoxic agent, and anthracycline in combination with taxane constitutes a key chemotherapeutic regimen. Given our results, we speculate both drugs are critical chemotherapeutic agents for the treatment of metastatic EMPD.

Abstract 5438: XPNPEP3: A novel transcriptional target of canonical Wnt/β-catenin signalling

Abstract Canonical Wnt/β-catenin signalling plays pivotal roles during embryonic development and adult tissue regeneration. Its aberrant activation however drives expression of a panoply of genes to facilitate colorectal tumorigenesis. Hence, it is imperative to delineate the complete β-catenin transcriptome. We performed genome-wide mRNA profiling of sporadic rectal cancer samples stratified by Wnt status. Results revealed significant up-regulation of XPNPEP3 transcript levels along with that of canonical Wnt targets AXIN2 and EPHB2 in Wnt+ samples. The differential expression of XPNPEP3 was further validated by quantitative PCR (Q-PCR) in additional samples. Nuclear stabilization of β-catenin achieved through LiCl treatment in three colorectal cancer (CRC) cell lines followed by Q-PCR and promoter-luciferase assays confirmed up-regulation of XPNPEP3. XPNPEP3 encodes X-prolyl aminopeptidase 3 which functions to remove the penultimate N-terminal Proline residue from nascent proteins and appears to play a role in ciliary function. Immunohistochemistry based expression analysis using a CRC tissue microarray revealed significant correlation between XPNPEP3 levels and β-catenin nuclear localization as well as increased XPNPEP3 expression in tumor compared to matched normal samples. Survival analysis of The Cancer Genome Atlas (TCGA) breast invasive carcinoma, skin cutaneous melanoma and lung adenocarcinoma data sets revealed poor survival among patients having perturbed XPNPEP3 expression. Characterization of possible oncogenic function of XPNPEP3 in CRC cells and in mice tumor xenografts is currently underway. Altogether, our results suggest XPNPEP3 to be a novel transcriptional target of Wnt/β-catenin signalling having a possible significance in CRC tumorigenesis. Citation Format: Raju Kumar, Ashmala Naz, Viswakalyan Kotapalli, Swarnalata Gowrishankar, Satish Rao, Jonathan R. Pollack, Murali Dharan Bashyam. XPNPEP3: A novel transcriptional target of canonical Wnt/β-catenin signalling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5438.

Abstract 2263: The dysregulation of circadian genes across cancers

Abstract As the daily oscillation in physiological processes, circadian is critical for health while disruption of the circadian rhythm has been associated with cancer in humans. Generally, circadian rhythm was proposed to play important roles in tumor suppression, while there were also evidences that disruption of canonical circadian pathway have anti-cancer effects. In this study, we systematically analyzed the aberrances including mutation, somatic copy number alternation, differential DNA methylation and differential expression of circadian genes across cancers based on TCGA data. It is observed that core circadian network genes (CCNGs) such as PER1/2/3, CLOCK, CRY1/2, ARNTL were highly mutated in a number of cancers such as uterine corpus endometrial carcinoma, skin cutaneous melanoma, stomach adenocarcinoma and colon adenocarcinoma. Generally, the expression for the majority of CCNGs was down regulated in a variety of the cancers such as bladder urothelial carcinoma, head and neck squamous cell carcinoma, breast invasive carcinoma, cervical and endocervical cancers, prostate adenocarcinoma, glioblastoma multiforme and stomach adenocarcinoma, while the expression of a number of CCNGs were related with overall survival in various cancers. The alternations of somatic copy number and DNA methylation were observed to be consistent with the differential expression of these CCNGs. Furthermore, the PCA based circadian gene expression signature was found to be related with the overall survivals and immunophenotypes among cancers, which indicated that circadian rhythm might play critical roles in regulation of immune signaling state in tumor environment. Taken together, our study provided comprehensive analyses of the aberrances and functional roles of circadian genes in cancer, while the results should be helpful for further investigation of the molecular mechanisms and therapy development for cancer. Citation Format: Zexian Liu, Huan Lin, Zekun Liu, Kai Yu, Qi Zhao, Xiaolong Zhang, Yan Wang, Zhixiang Zuo. The dysregulation of circadian genes across cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2263.

Metastatic Extramammary Paget's Disease: Pathogenesis and Novel Therapeutic Approach.

Extramammary Paget’s disease (EMPD) is a rare, slow-growing, cutaneous adenocarcinoma that usually originates in the anogenital area and axillae outside the mammary glands. EMPD mostly progresses slowly and is often diagnosed as carcinoma in situ; however, upon becoming invasive, it promptly and frequently metastasizes to regional lymph nodes, leading to subsequent distant metastasis. To date, several chemotherapy regimens have been used to treat metastatic EMPD; however, they present limited effect and patients with distant metastasis exhibit a poor prognosis. Recently, basic and translational investigative research has elucidated factors and molecular mechanisms underlying the promotion of metastasis, which can lead to targeted therapy-based emerging treatment strategies. Here, we aim to discuss current therapies and their limitations; advancements in illustrating mechanisms promoting invasion, migration, and proliferation of EMPD tumor cells; and future therapeutic approaches for metastatic EMPD that may enhance clinical outcomes.

Poorly differentiated cutaneous adenocarcinoma masquerading as scrofuloderma

We report the case of a 60-year-old male presented with axillary swelling of 18 months duration with ulceration and cervical lymphadenopathy of 3 months duration with a clinical diagnosis of scrofuloderma. Histopathology showed dermis infiltrated by sheets, nests, and clusters of polygonal cells with markedly pleomorphic mitotically active nuclei suggestive of a more sinister condition, poorly differentiated cutaneous adenocarcinoma either primary or metastasis from breast. The condition is reported for its rarity from male breast and the need to consider it as a differential diagnosis in similar clinical presentation.

Imiquimod use for the treatment of extramammary Paget disease: series of four cases

INTRODUCTION: Extramammary Paget disease consists of a cutaneous adenocarcinoma in areas of apocrine glands. It is a rare neoplasia, and its surgical treatment yields satisfactory results. However, due to the high recurrence rates, surgeries are potentially disfiguring. Imiquimod is a topical immune-stimulant used for the treatment of anogenital warts and in situ carcinomas. Its use has been described in the scientific literature for the treatment of Extramammary Paget disease with satisfactory results. OBJECTIVE: Describe the course of four cases of Extramammary Paget disease treated with imiquimod, to evaluate evolution and therapeutic response. METHODS: A retrospective study was performed in a service of dermatology in the city of São Paulo, with the review of medical records of all patients diagnosed with Extramammary Paget disease and treated with imiquimod from January 2011 to July 2018. RESULTS: Four patients were included, three with vulvar lesion and one with scrotal lesion. Two women presented completed resolution of the disease, one did not respond and the man progressed with 70% regression of the lesion, having undergone surgical excision of a considerably smaller area than the initial lesion. CONCLUSIONS: Imiquimod presents as a valid therapeutic modality for the treatment of Extramammary Paget disease.

Sox10 and DOG1 Expression in Primary Adnexal Tumors of the Skin

Primary skin adnexal tumors can be challenging to classify and must be discerned from cutaneous adenocarcinoma metastases from various sites. We evaluated expression of Sox10 and DOG1 in normal cutaneous adnexa and in 194 primary skin adnexal tumors, and compared their performance in discriminating primary skin adnexal tumors from cutaneous metastatic adenocarcinomas with that of p40 and p63. In normal skin adnexa, we noted Sox10 expression in both the secretory and myoepithelial cells in eccrine glands, but only in myoepithelial cells in apocrine glands. DOG1 demonstrated canalicular expression in eccrine glands, and weak expression in myoepithelial cells of apocrine glands, germinative cells of sebaceous glands, and outer root sheath of follicular infundibulum. Sox10 was expressed in 100% of cylindromas and spiradenomas, and in variable frequency in other benign and malignant tumors of sweat glands. DOG1 was positive in most cylindromas (87.5%), in only 10.5% of spiradenomas, and was variably expressed in other benign and malignant tumors of sweat glands. All syringomas (n = 20) were negative for Sox10 and DOG1. One out of the 33 follicular neoplasms was positive for Sox10 and DOG1 (3%). All sebaceous neoplasms were negative for Sox10, and 28.1% of them were positive for DOG1. Sox10 was specific (91.9%) but not sensitive (28.4%) for primary skin origin, and was far less accurate (38.5%) than p63 or p40 (95.5% accuracy). Combining Sox10 with p63 or p40 showed only very minimal gain in accuracy (96%). DOG1 expression in tumors showed low sensitivity and specificity for skin adnexal origin.