Hematoporphyrine injection-based photodynamic therapy for Perianal Paget's disease: a case report.

Paget's disease of the perianal skin (PPD) is a rare form of extramammary Paget's disease, which can manifest as either a primary intraepithelial adnexal neoplasm or as a secondary condition resulting from the spread of an underlying colorectal lesion. Surgical resection is the primary treatment for PDD, but it poses risks to the aesthetic appearance and functional integrity of the anus. Moreover, its clinical application is limited, particularly in cases of lesions present in multiple skinfold areas, multiple and recurrent lesions, extensive lesion areas, or in elderly patients with poor health. Hematoporphyrin derivative photodynamic therapy (HpD-PDT) serves as an alternative treatment for patients who are not suitable candidates for surgery and for conditions characterized by extensive and discontinuous disease. Here, we present the case of a 70-year-old man with secondary PPD, presenting perianal skin lesions extending beyond the dentate line into the anal canal. When considering HpD-PDT, it is essential to take into account the preservation of function, patient preferences, and potential adverse effects. Subsequent to HpD-PDT, the lesion was effectively eradicated, and anal function was preserved without any notable proliferative, atrophic scarring, or other side effects. Therefore, HpD-PDT proves to be an effective treatment for PPD, offering aesthetic improvement, minimal functional disruption, and a high level of tolerability.

Invasive acantholytic anaplastic extramammary Paget disease: A previously unreported neoplasm in the vulva and review of the literature.

This report describes the first documented invasive acantholytic anaplastic extramammary Paget disease (AAEMPD) of the vulva. An 87-year-old female presented with a recurrent vulvar lesion refractory to topical imiquimod and treated with multiple wide local excisions (WLE). Microscopic examination of the final WLE specimen revealed unique histologic features, primarily supra-basal intraepidermal acantholysis with epidermal papillomatosis and hyperkeratosis. The epidermis, composed of two distinct cell populations, exhibited full-thickness atypia. Paget cells with high mitotic activity were present in the basal and parabasal layers surrounding benign squamous cells in the mid-squamous mucosa. The histologic features were suspicious of the EMPD involving a warty lesion and/or invasive squamous cell carcinoma. In addition to the intraepidermal component, dermal invasion was also present with lymphovascular space invasion. Immunohistochemical studies (KRT7, HER2, and GATA3 reactivity in Paget cells, p63 negativity, and rare mucin in Paget cells) supported the diagnosis of acantholytic anaplastic EMPD. AAEMPD, a rare variant of EMPD, shares similar prognosis and behavior with the classic Paget disease. Recognition and accurate diagnosis of this subtype is crucial for optimal patient management, given distinct treatment strategies compared with other entities in the differential diagnosis.

Primary nipple melanoma in a patient with breast cancer: A diagnosis to consider.

Melanoma in situ of the nipple is an uncommon diagnosis, with only a few reports in the literature. Due to the variety of pathologies that can affect the nipple-areola complex, the diagnosis can be challenging. In this case report we describe a patient with cosmetic bilateral breast implants who presented with eczema of the left nipple-areola complex and suspicious microcalcifications in the lower inner quadrant of the ipsilateral breast on mammography, subsequently diagnosed with nipple melanoma and concomitant ductal carcinoma in situ.

Non-surgical management of recurrent Paget's disease of the vulva: A case report.

Paget's Disease of the Vulva is a relatively rare condition with a high rate of recurrence. Extensive work-up and treatment is warranted as lesions have the capacity to become invasive and can be associated with underlying malignancy. First line therapy includes surgical resection. For those that are not surgical candidates or who do not desire surgical intervention, non-surgical management options include topical therapy with imiquimod. Unfortunately, irritating side effects often results in poor treatment compliance and premature discontinuation limiting efficacy. Here we present a unique case of extensive, recurrent vulvar Paget's disease with excellent response to a combination therapy of imiquimod and Silver Sulfadiazine. To the best of our knowledge, this is the first documented case illustrating the utility of non-surgical management with combination therapy with topical imiquimod and Silver Sulfadiazine for treatment in patients who do not desire surgical intervention.

Paget's Disease Mimicking Prostate Cancer Metastasis with 68Ga-PSMA PET/CT.

68Ga-prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography imaging successfully detects bone metastases in prostate cancer (PCa). However, assuming that all detected PSMA-avid bone lesions are metastases should be avoided. It is essential to evaluate PCa patients with clinical findings and to consider possible differential diagnoses, especially in low-risk patients. Herein, we present the case of a 62-year-old male patient recently diagnosed with low-risk prostate adenocarcinoma with a PSMA-avid bone lesion corresponding to Paget's disease.

Immunotherapy may be more appropriate for ERBB2 low-expressing extramammary paget's disease patients: a prognosis analysis and exploration of targeted therapy and immunotherapy of extramammary paget's disease patients.

Extramammary Paget's disease (EMPD) is a rare cutaneous malignancy characterized by its uncertain etiology and metastatic potential. Surgery remains the first-line clinical treatment for EMPD, but the efficacy of radiotherapy and chemotherapy remains to be fully evaluated, and new therapies for EMPD are urgently needed. In this study, we initially screened 815 EMPD patients in the Surveillance, Epidemiology, and End Results (SEER) database and analyzed their clinical features and prognostic factors. Using the dataset from the Genome Sequence Archive (GSA) database, we subsequently conducted weighted gene coexpression network analysis (WGCNA), gene set enrichment analysis (GSEA), gene set variation analysis (GSVA), and immune infiltration analyses, grouping the samples based on EMPD disease status and the levels of ERBB2 expression. The prognostic analysis based on the SEER database identified increased age at diagnosis, distant metastasis, and receipt of radiotherapy as independent risk factors for EMPD. Moreover, our results indicated that patients who received chemotherapy had worse prognoses than those who did not, highlighting the urgent need for novel treatment approaches for EMPD. Functional analysis of the GSA-derived dataset revealed that EMPD tissues were significantly enriched in immune-related pathways compared with normal skin tissues. Compared with those with high ERBB2 expression, tissues with low ERBB2 expression displayed greater immunogenicity and enrichment of immune pathways, particularly those related to B cells. These findings suggest that patients with low ERBB2 expression are likely to benefit from immunotherapy, especially B-cell-related immunotherapy.

Causes of Musculoskeletal Pain in Paget's Disease of Bone.

Paget's disease of bone (PDB) is characterised by increased and disorganised bone remodelling leading to various complications, such as bone deformity, deafness, secondary osteoarthritis, and pathological fracture. Pain is the most common presenting symptom of PDB, but it is unclear to what extent this is due to increased metabolic activity of the disease, complications, or unrelated causes. We conducted a cross-sectional study of 168 people with PDB attending secondary care referral centres in the UK. We documented the presence of musculoskeletal pain and sought to determine its underlying causes. Musculoskeletal pain was reported by 122/168 (72.6%) individuals. The most common cause was osteoarthritis of joints distant from an affected PDB site in 54 (44.3%), followed by metabolically active PDB in 18 (14.7%); bone deformity in 14 (11.4%); osteoarthritis of a joint neighbouring an affected site in 11 (9.0%), neuropathic pain in 10 (8.2%), and various other causes in the remainder. Pain was more common in women (p<0.019) and in older individuals (p<0.001). Circulating concentrations of macrophage colony-stimulating factor (M-CSF) were significantly higher in those with pain (p = 0.008), but there was no difference between groups of patients with and without pain in concentrations of interleukin-6 (IL-6) or biochemical markers of bone turnover. Pain is a common symptom in PDB but is most often due to osteoarthritis at an unaffected site. The study illustrates the importance of fully evaluating people with PDB to determine the underlying cause of pain so that management can be tailored appropriately.

Simultaneous Occurrence of Two Ectopic Extramammary Paget Disease Lesions: A Case Report.

Paget disease of the breast is a malignant tumor that occurs primarily on the skin of the nipple, whereas extramammary Paget disease occurs on the skin in regions other than the breast, such as the pubis, perianal area, and axilla. Paget disease can also arise outside these areas; this is referred to as ectopic extramammary Paget disease. In this study, we present a case of a Japanese woman in her 70s who experienced simultaneous occurrence of two ectopic extramammary Paget disease lesions on the skin of the anterior chest and left buttock. Both lesions, exceeding 5 cm in diameter, were surgically excised, and the histopathological examination led to a diagnosis of ectopic extramammary Paget disease without invasion. To the best of our knowledge, this is the third reported case of multiple simultaneous ectopic extramammary Paget disease. Clinically, diagnosis of a patient with ectopic extramammary Paget disease is challenging because of its unusual location; however, the disease may be considered a differential diagnosis for Bowen disease.

Vulvar Paget's disease: A population-based cancer registry descriptive study.

BACKGROUND: Although vulvar Paget's Disease (VPD) is a rare skin cancer associated with an excellent prognosis, high recurrence rates are associated with impaired quality of life. OBJECTIVES: Our objective was to investigate the epidemiological and clinical features of VPD diagnosed in a French administrative area (Franche Comté). METHODS: This retrospective study investigated clinical, histologic, therapeutic and follow-up data of patients with VPD diagnosed between 1981 and 2021, including data from the Doubs cancer registry. RESULTS: Among the 21 patients included (19 intra-epithelial and 2 invasive VPD), the median time to diagnosis was 24 months [0-110 months], with a median age of 72 years [38-88 years]. An associated cancer was present in 6 patients (29 %). At 5 years of follow-up, the recurrence rate was 26 %, but then increased to 42 % after a median follow-up of 145 months [31-503 months]. Among the 14 patients first surgically treated, incomplete resection (positive margins) was observed in all patients (100 %), associated with a postoperative recurrence rate of 86 % which was much higher than the rate observed in patients first topically treated (20 %). Postoperative adjuvant therapy (surgical revision, laser, imiquimod) significantly increased the recurrence-free survival (p < 0.001). CONCLUSIONS: Postoperative recurrence of VPD is frequent, mainly after 5 years, proving the importance of prolonged follow-up. Recurrence-free survival was significantly higher after postoperative adjuvant treatment.

Identification of Biomarkers Associated With Paget's Disease of Bone and Bone Metastasis From Breast Cancer Patients.

BACKGROUND: The bone is among the most frequently chosen sites for the metastatic spread of breast cancer. The prediction of biomarkers for BM (Bone Metastasis) and PDB (Paget's disease of bone) initiated from breast cancer could be critically important in categorizing individuals with a higher risk and providing targeted treatment for PDB and BM. AIMS: This research aims to investigate the common key candidate biomarkers that contribute to BM-BCa (Bone metastasis of breast cancer) and PDB by employing network decomposition and functional enrichment studies. METHODS AND RESULTS: This research analyzed high-throughput transcriptome sequencing (RNA-Seq). For this work, the dataset (GSE121677) was downloaded from GEO (Gene Expression Omnibus), and DEGs were identified using Galaxy and R script 4.3. Using STRING (Search Tool for the Retrieval of Interacting Genes), high-throughput research created a protein-protein interaction network (PPIN). The BM-PDB-interactome was created using Cytoscape 3.9.1 and PDB biomarkers, with the top 3% DEGs from BM-BCa. Functional Enrichment Analysis (Funrich 3.1.3) and DAVID 6.8 performed functional and gene set enrichment analysis (GSEA) of putatively essential biomarkers. TCGA (The Cancer Genome Atlas) validated the discovered genes. Based on our research, we identified 1262 DEGs; among these DEGs, 431 genes were upregulated, and 831 genes were downregulated. During the third growth of the interactome, 20 more genes were pinned to the BM-PDB interactome. RAC2, PIAS1, EP300, EIF2S1, and LRP6 are among the additional 25% of genes identified to interact with the BM-PDB interactome. To corroborate the findings of the research presented, additional functional and gene set enrichment analyses have been performed. CONCLUSION: Of the five reported genes (RAC2, PIAS1, EP300, EIF2S1, and LRP6), RAC2 was identified to function as the common key potential biomarker in the BM-PDB interactome analysis and validated by TCGA in the study presented.

Adenoma of the Nipple: A Case Report.

Nipple adenomas are rare, benign breast lesions that present similarly to breast malignancies, often manifesting with unilateral bloody discharge, a palpable mass, and/or nipple distortion. Imaging techniques have limited specificity in distinguishing nipple adenomas from malignancy; therefore, clinicians must rely on histologic and immunohistochemistry evaluation. Here, we highlight the case of a 69-year-old woman with bilateral nipple adenomas presenting as an enlarging nipple mass with chronic nipple discharge. Complete lesion resection with clear margins stands as the primary route of management and complete avoidance of re-occurrence. However, partial excision with nipple preservation has been reported to be successful in selected cases.

Utility of special AT-rich sequence-binding protein 2 (SATB2) immunohistochemistry as a marker for secondary perianal paget disease.

A panel-based approach using immunohistochemistry (IHC) is currently used for subtyping perianal Paget disease (PPD) in the absence of a synchronous neoplasm. Special AT-rich Sequence Binding Protein 2 (SATB2) has been established as a sensitive and specific marker for lower gastrointestinal tract carcinomas. We evaluated its performance as a marker of secondary PPD. A panel of IHCs including CK7, CK20, GCDFP-15, CDX2, and SATB2 were performed on fifteen cases of PPD (identified between 1991-2001) and seven cases of primary vulvar Paget disease with perianal involvement. Eight cases (53%) were classified as secondary PPD based on the presence of a synchronous (n = 7) or a metachronous neoplasm (n = 1). There was no differential staining for CK7 (positive in 7/7 primary vs. 7/8 secondary PPD; P = 1.00) and CK20 (positive in 4/7 primary vs. 8/8 secondary PPD; P = .08). GCDFP-15 was positive in 5/7 cases of primary PPD while negative in all cases of secondary PPD (P = .01). CDX2 was positive in all cases of secondary PPD (P = .001) while SATB2 was positive in 7/8 cases of secondary PPD (P = .01). Both CDX2 and SATB2 were positive in 1/7 cases of primary PPD. The addition of an IHC panel in conjunction with clinical/imaging findings can help definitively classify PPD as either primary or secondary in most cases. We show that SATB2 has comparable performance to CDX2 and can be a helpful additional tool.

Mammary Paget's Disease Mimicking Benign and Malignant Dermatological Conditions: Clinical Challenges and Diagnostic Considerations.

Mammary Paget's disease (MPD) or Paget's disease of the breast is a rare dermatological malignancy of the nipple-areolar complex that manifests with a spectrum of symptoms spanning from itching and redness to more severe indications such as breast lump, nipple-areolar complex destruction, or nipple discharge. It is predominantly associated with an underlying ductal carcinoma in situ or invasive ductal carcinoma. MPD often masquerades as other benign and malignant dermatological conditions, including eczema, atopic dermatitis, psoriasis, and squamous and basal cell carcinomas, leading to delayed diagnosis and inappropriate treatment. Only one-third of the patients present with a palpable lump; therefore, advanced age with chronic and unilateral lesions should raise concern for MPD. Our review article presents case reports of MPD imitating other skin conditions and underscores the key findings of clinical features and diagnostic workup to help differentiate the condition. A literature review revealed that studies emphasize caution regarding the sole use of mammography and ultrasound in diagnosing MPD, particularly in cases lacking a palpable lump. This highlights the MRI as a superior and more accurate imaging tool. However, any suspicious lesion must be biopsied to allow histopathological and immunohistochemical examination, since there are some cases where MRI findings were negative in the presence of a biopsy-proven MPD. This highlights the need for clinicians to investigate any suspicious lesion of the nipple or breast using the complete triple assessment approach to exclude an underlying malignancy. It is imperative to establish therapeutic guidelines to approach any nipple lesion to minimize the risk of misdiagnosing any underlying cancer, which can be potentially fatal if left alone.

Case report: Pyrotinib in the treatment of advanced scrotal EMPD combined with sweat gland carcinoma.

Extramammary Paget disease (EMPD) is a rare cutaneous intraepithelial adenocarcinoma, which is mostly distributed in areas with sweat gland cells and mainly occurs in the anogenital skin of women. The male genital tract involvement is extremely rare and often occurs with other malignant tumors. Paget's disease in the scrotum with sweat gland carcinoma is even rarer. In the first report of scrotal endocrine sweat gland carcinoma associated with Paget disease by Saidi et al. in 1997, no more than 50 cases have been reported in the relevant research worldwide. Early EMPD combined with sweat gland carcinoma is mainly surgical treatment, and there is no standard treatment plan for advanced EMPD with sweat gland carcinoma. Previous article has reported that chemotherapy such as paclitaxel, fluorouracil, platinum, and vinblastine and molecular targeted therapy based on the genetic test results of patients have certain efficacy. Here, we report a 79-year-old male case diagnosed with human epidermal growth factor receptor 2 (HER-2) overexpression, which was effectively controlled by chemotherapy and anti-HER-2 treatment such as pyrotinib.

The Role of Line-Field Confocal Optical Coherence Tomography in Detecting Extramammary Paget Disease Recurrences: A Pilot Diagnostic Study.

Extramammary Paget disease (EMPD) is an uncommon adenocarcinoma of apocrine gland-rich areas, presenting significant diagnostic challenges due to its nonspecific clinical appearance and frequent misidentification as benign, inflammatory skin conditions. Traditional diagnostic methods such as biopsy are invasive and uncomfortable, often required repeatedly due to high recurrence rates. Dermoscopy and non-invasive imaging techniques have been used but provide limited diagnostic accuracy due to their constraints in depth penetration and resolution. Recent advancements in imaging technologies, such as line-field confocal optical coherence tomography (LC-OCT), show promise in enhancing diagnostic precision while minimizing invasive procedures. LC-OCT merges high-resolution imaging with deep penetration capabilities, capturing detailed horizontal and vertical skin images akin to histopathology. This study evaluated the diagnostic performance of LC-OCT in detecting EMPD and its recurrence in 17 clinically suspicious anogenital regions, belonging to six patients. Data were collected prospectively at the patient's bedside by an LC-OCT expert with poor training for EMPD, and, then, reviewed retrospectively by an independent LC-OCT expert with adequate training for EMPD and no concerns about time. The prospective examination yielded 64.7% accuracy (11 true results out of 17 total cases), 71.4% sensitivity (10 true positives out of 14 actual positives), and 33.3% specificity (1 true negative out of 3 actual negatives). The retrospective analysis achieved 94.1% accuracy (16 true results out of 17 total cases), 100% sensitivity (14 true positives out of 14 actual positives), and 66.7% specificity (2 true positives out of 3 actual positives), with the only false positive case being a difficult-to-diagnose concomitant presentation of a lichen sclerosus et atrophicus. Despite the need for specialized training, our results suggest that LC-OCT represents a valuable tool for accurately identifying EMPD and improving its management by reducing unnecessary biopsies. Further studies are needed to standardize its clinical application.

Modified clock mapping biopsy sec. Della Corte-Bifulco in the preoperative assessment of excisional surgery for vulvar Paget's disease.

We have developed a biopsy technique aimed at preoperative evaluating the extent of Paget's vulvar disease in order to plan subsequent radical vulvar surgery. The aim is to find all possible lesion sites that are not visible macroscopically, to obtain a clear evaluation of the disease spread and to tailor the radical surgical procedure to remove even microscopic lesions, avoiding recurrences and excessively destructive surgery, adopting as conservative an approach as possible. We used this procedure for the first time to establish the radicality of the surgical intervention in a 68-year-old patient initially suffering from a single invasive vulvar Paget's lesion.

Superficial circumflex iliac artery perforator propeller flap for penoscrotal extramammary Paget's disease.

BACKGROUND: Extramammary Paget's disease (EMPD) is a rare intra-epidermal adenocarcinoma, and reconstruction of the penoscrotal region remains a clinical challenge. The superficial circumflex iliac artery perforator (SCIP) flap has been successfully used as a free flap, while its application as a propeller flap in the reconstruction of penoscrotal EMPD defect is rarely reported. The objective was to evaluate the safety and efficacy of the SCIP propeller flap in the reconstruction of penoscrotal defects in EMPD. METHODS: Between September 2010 and August 2022, consecutive patients diagnosed with penoscrotal EMPD were enrolled. All patients underwent penoscrotal EMPD excision and reconstruction with SCIP propeller flap combined with other flaps or skin grafts on individual defects. Demographic information, surgical parameters, postoperative complications, patient satisfaction, and recurrence rates were analyzed. RESULTS: Twenty-four patients (mean age, 73 ± 8.8 years; mean BMI, 23.98 ± 3.62 kg/m2) with 33 SCIP propeller flaps (mean size 120.1 cm2; range, 24-208 cm2) were included, and the mean defect size was 67.4 cm2 (range, 12-255 cm2). The mean operative duration was 385.4 ± 146.8 min. Fifteen patients received autologous full-thickness skin grafts, and four received other flaps simultaneously. All flaps survived without total or partial loss, and all donor sites achieved primary closure, though local hematoma (one case) and limited skin graft necrosis (two cases) were observed. All patients experienced complete wound healing and maintained penoscrotal morphology and function without recurrent lesions over a mean follow-up of 59 months. CONCLUSIONS: The SCIP propeller flap seems a safe and effective reconstructive method for penoscrotal EMPD. LEVEL OF EVIDENCE: IV.