Search Results (41)

Extramammary Paget’s disease (EMPD) is a rare adenocarcinoma originating from apocrine glands, primarily affecting the anogenital and axillary regions. Ectopic EMPD, occurring in non-apocrine sites such as the scalp, is exceptionally uncommon. We report a case of ectopic EMPD of the scalp distinguished by its association with an intraosseous atypical meningioma, a previously unreported finding. A 70-year-old female presented with a persistent 15 cm erythematous, alopecic scalp lesion that had been misdiagnosed for a decade. Histopathological analysis confirmed ectopic EMPD, while imaging identified an adjacent intraosseous meningioma. Surgical resection was performed for the meningioma, and radiotherapy was selected as the treatment modality for EMPD. Due to its clinical resemblance to inflammatory dermatoses, ectopic EMPD is often underrecognized, underscoring the critical role of histopathology and immunohistochemical markers in diagnosis. Given its potential association with malignancies, comprehensive systemic evaluation is warranted. The high recurrence rate following surgical excision necessitates consideration of alternative therapeutic approaches, including radiotherapy, Mohs micrographic surgery, or photodynamic therapy. This case highlights the necessity for heightened clinical awareness of atypical scalp lesions and underscores the importance of thorough diagnostic assessment. Further research is needed to clarify the relationship between EMPD and other neoplasms and to optimize management strategies. Full article

Background: Extramammary Paget’s disease (EMPD) is a rare cutaneous carcinoma that typically affects the elderly and is frequently observed in genital and perianal regions. We analyzed the outcomes and prognostic factors for EMPD after radiation therapy (RT). Methods: We analyzed data from 81 patients with non-metastatic EMPD who received either RT alone or in combination with surgery and/or chemotherapy. The median radiation dose was 56 Gy in 28 fractions. Local control (LC), progression-free survival (PFS), and overall survival (OS) rates were calculated using the Kaplan–Meier method. Multivariate analyses were performed using the Cox proportional hazards model. Late adverse events were evaluated by NCI-CTCAE version 5.0. Results: The median age was 78 years, and the median follow-up period was 36 months. The three-year LC, PFS, and OS rates were 75%, 52%, and 80%, respectively. Multivariate analyses identified the presence of lymph node (LN) metastasis, the absence of surgery, and the omission of elective nodal irradiation (i.e., local irradiation only) as significant factors for unfavorable LC (p = 0.01, 0.02, and 0.006) and PFS (p = 0.001, 0.04, and 0.03). LN metastasis was also a significant factor for unfavorable OS (p = 0.005). One patient developed grade 2 skin infection, and another developed grade 3 lymphedema; no grade 4 or higher toxicity was observed. Conclusions: The present results revealed prognostic factors for EMPD after RT and suggest that the absence of surgery and omission of elective nodal irradiation worsened outcomes. A prospective study is needed to establish an optimal treatment strategy for this rare malignancy, which is common in the elderly. Full article

The vulva is a complex anatomical organ that may present with a wide range of pathologies. Even if it can be easily investigated, correctly interpreting vulvar appearance is often challenging. Vulvar ultrasound is an emerging diagnostic technique that may be helpful in different aspects of vulvar pathology. We aimed to summarize the state of the art of vulvar ultrasound, provide the necessary theoretical bases of embryology and anatomy, describe the normal and pathological vulvar sonographic characteristics, and propose a feasible and reproducible methodology for vulvar ultrasound. Vulvar sonographic scan should be performed with a linear probe, preferably > 15 mHz, following a standardized methodology. The sonographic appearance of the normal vulva reflects the different histology of its structures and, thus, their embryogenetic origin. The description of a suspected vulvar lesion should include localization, dimensions, volume, type of growth, shape, appearance of the edges, depth of invasion, echogenicity, and identification of vascularization. Cystic dilatation of obstructed Bartolini ducts is the most common benign finding in the vulva (fluctuant structures in the posterior third of the labia majora containing clear mucous fluid). Malignant vulvar lesions appear as hypoechogenic or heterogeneous solid lesions with irregular margins and a high degree of vascularization. Extramammary Paget Disease presents a homogeneous hypoechogenic creeping area in the epidermis due to neoplastic cells typical of this disease. The potential applications of vulvar ultrasound are examining the content of a vulvar swelling to guide its management and assessing the response to medical treatment in the case of lichen sclerosus. In managing patients affected by vulvar malignancies, it may play a critical role in local staging, stromal invasion determination, measuring the distance from the midline, and assessing the eligibility for sentinel lymph node procedure. Vulvar ultrasound is a minimally invasive and economical test that can be performed with minimal equipment. Further studies will be necessary to validate the clinical applications, quantify the diagnostic performance, and evaluate the agreement between operators. Full article

Fat composition is largely responsible for the technological and rheological properties of cow milk and dairy products. Bovine milk fat is unique in terms of its fatty acid composition and positional distribution, with about 25% of its fatty acids being short- and medium-chain, which are synthesized de novo in the mammary gland and are not present in extra-mammary tissues. With the aim to identify potential genetic factors responsible for the unique composition of bovine milk fat, we extracted genes with GO annotations related to lipid metabolism and performed a gene expression mega-analysis. Overall, different lipogenic tissues (i.e., mammary, liver, and adipose) displayed discerned expression patterns. In a PCA, the liver was significantly separated from adipose and mammary tissues. In a correlation analysis with the fatty acid synthetase (FASN) gene, notable differences among the tissues were found. In the mammary gland, the majority of genes (~70%) were negatively correlated with FASN expression, whereas only 18% were negatively correlated in adipose. Only a few genes were positively correlated with FASN exclusively in the mammary gland, including AGPAT1 and AGPAT6, which also had the highest expression in the mammary gland compared with adipose. Looking at the expression levels in tissues (TPM) revealed significant differences in the expressions of genes responsible for the activation of fatty acids by ligation to CoA, according to their carbon chain length. Notably, the ACSS1 gene, which converts acetate to acetyl-CoA, had the highest expression in the mammary gland, whereas genes responsible for the activation of long-chain fatty acids had lower expressions. The findings of the present study suggest that the unique properties of dairy fat are the results of the distinct expression patterns of genes involved in de novo synthesis of fatty acids and their downstream utilization. Full article

Background/Objectives: Some skin tumors can extend beyond their clinical appearance. This presents an additional challenge, especially when the affected area is the genital region, which is more difficult for both the patient and the physician to access and monitor due to its location and anatomical characteristics. The treatment of these lesions is complex, and literature postulates Mohs surgery as the best therapeutic option. Methods: We describe our experience in two patients with the resection of vulvar lentiginous melanoma and genital extramammary Paget’s disease, using a method of deferred lateral margin control in the surgical treatment. Results: The “spaghetti technique”(ST) initially removing a small strip from all lateral margins of the lesion, which is then closed directly while awaiting the paraffin histological result. In a second stage, the tumors within those margins are removed, and immediate reconstruction is performed. The final oncological and functional result was satisfactory, with no notable side effects. Conclusions: This method is suited for large, poorly defined superficial tumors in the genital, perineal, and perianal regions, where a frozen section study would be slow and burdensome for the patient and surgeon. The ST preserves healthy tissue and can be performed by any surgeon and pathologist without additional training, and is more comfortable for patients, avoiding prolonged open wounds during multiple steps of tumor excision. Full article

TRPS1 (Tricho-rhino-phalangeal syndrome 1) is a GATA transcriptional activator gene encoding for a protein used as a sensitive immunohistochemical marker of breast carcinomas. In dermatopathology, TRPS1 is used as a marker of mammary and extramammary Paget’s disease and is also expressed by a variety of primary cutaneous tumors, mostly of adnexal origin. So far, very limited data exist on the expression of TRPS1 in metastatic skin tumors. We studied the immunohistochemical expression of TRPS1 in 72 cutaneous metastatic tumors from the breast (n: 19) and other origins (n: 53) in order to assess its diagnostic usefulness. The intensity of TRPS1 immunostaining was expressed as a histoscore: the product of the percentage of positive cells (scored semi-quantitatively 0–4) and the staining intensity (scored 0–3). In normal skin, nuclear TRPS1 expression was predominantly observed in cells of adnexal structures (pilosebaceous follicles and sweat glands). Eighteen (18/19, 94.7%) metastatic breast carcinomas showed diffuse and strong TRPS1 positivity (histoscore 12). Lower reactivity was found in some other metastases, including from the lung (11/22), the female genital tract (3/4), and the kidney (2/4), whereas most (20/22) metastases from the digestive system and peritoneum, along with a case of metastatic prostate carcinoma, were negative. These results suggest that a high histoscore for TRPS1 is in favor of the mammary origin of metastatic cutaneous carcinoma. Although TRPS1 is not absolutely specific or sensitive to a particular primary, we consider that it can be added to a panel of other markers when investigating the origin of a cutaneous metastasis, namely when this is the first manifestation of the neoplastic disease. Full article

Breast metastasis originating from a primary lung tumor is exceedingly rare and can present challenges in distinguishing it from primary breast cancer. This case report discusses the management of a 64-year-old woman who initially presented with a nodule in her left breast. A biopsy revealed an infiltrating ductal carcinoma. Despite negative BRCA genetic testing, her significant family history of cancer and the presence of a newly detected right breast lesion led to a bilateral mastectomy. Post-operative imaging identified multiple hypodense nodules and a spiculated pulmonary nodule, necessitating further investigation. An endoscopic lung biopsy confirmed a primary pulmonary carcinoma with histological features similar to the breast carcinoma, suggesting the lung as the primary source. This case highlights the complexity of differentiating breast metastasis originating from a lung tumor and primary breast cancer. It underscores the importance of comprehensive diagnostic evaluations and the consideration of extramammary origins in metastatic cases. The findings emphasize the role of multidisciplinary teams in managing such rare and challenging cases and highlight the necessity for thorough and repeated assessments in atypical breast cancer presentations. Full article

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. Full article

This study shall retrospectively evaluate the efficacy and safety of liquid-nitrogen based CT-guided cryoablation (CA) as a minimal-invasive technique for the curative treatment of primary breast cancer. A total of 45 female patients with 56 tumors were treated by CT-guided CA in analgosedation as an outpatient procedure. We used a liquid-nitrogen based system with a single cryoprobe and performed two freeze cycles with an intermediate thawing. The mean tumor diameter was 1.6 ± 0.7 cm. Follow-up was conducted via contrast-enhanced MR images of the breast. No complications were observed in all 56 ablations. Initial complete ablation was achieved in 100% of cases. Four cases of local tumor progression were reported, resulting in a rate of 8.9%, and 6 cases of intramammary distant recurrence at a rate of 13.3%. The extramammary tumor progression was observed in 7 patients at a rate of 15.6%. The mean overall survival was 4.13 years (95% CI: 3.7–4.5). The mean overall progression-free survival was 2.5 years (95% CI: 1.8–3.2) and the mean local progression-free survival was 2.9 years (95% CI: 2.3–3.6). Cryoablation is a safe and effective treatment for primary breast cancer tumors, which can be performed in analgosedation and as an outpatient procedure. However, potential for improvement exists and further evidence is necessary. Full article

Extramammary Paget’s disease (EMPD) is subclinical in extent and multifocal in nature. There is no global consensus for treatment, so its management represents a challenge in clinical practice. Therefore, we conducted a systematic review through the main electronic databases to assess the effectiveness of topical imiquimod in cutaneous EMPD and to discuss its management. Finally, 24 studies involving a total of 233 EMPD patients treated with topical imiquimod were selected. The topical imiquimod response rate was 67%, and the complete response (CR) rate was 48%. Patients were treated with a three–four times a week regimen in most cases, ranging between 2 to 52 weeks. In addition, imiquimod was applied as an adjunctive treatment in 21 patients, achieving a CR rate of 71%. Consequently, imiquimod therapy could achieve a good response ratio as a first-line treatment, as adjuvant and neo-adjuvant therapy, and as a treatment for recurrent disease. The heterogeneity between studies and the lack of a control arm made it impossible to conduct a meta-analysis. To improve the quality of evidence on EMPD, multicenter studies are essential to collect a larger number of patients and, consequently, obtain high-quality evidence to standardize treatment. The Prospero registration number is CRD42023447443. Full article

To evaluate the effects of amount and profile of amino acid (AA) on milk protein yield (MPY), mammary metabolism, and efficiency of nitrogen use (ENU), ten cows were used in 5 × 5 replicated Latin squares and fed a positive control (16.1% crude protein-CP) or two lower CP diets (14.6 and 13.2%) with or without essential AA (EAA) infusion. The EAA solutions provided predicted limiting EAA in each treatment and were continuously infused into the abomasum of the cows. Milk production and MPY were not affected by treatment (mean 35.4 kg/d and 1.03 kg/d, respectively). Efficiency of nitrogen utilization was increased as dietary CP decreased but was not affected by EAA infusion (p < 0.01). Energy-corrected milk production was increased by EAA infusion into 13.2% CP, but not into 14.6% CP diet (p = 0.09), reaching the positive control value. Infusions increased mammary affinity for non-infused EAA (Ile, Phe, Thr, and Trp), allowing the same MPY despite lower arterial concentrations of these AA. Higher arterial concentrations of infused EAA did not increase their mammary uptake and MPY (p = 0.40; p = 0.85). Mammary metabolism did not fully explain changes in N efficiency, suggesting that it might be driven by less extramammary catabolism as AA supply was reduced. Full article

The human epidermal growth factor receptors (HERs) are expressed abundantly in the human body. The tumorigenic potential of HER2/neu is linked to its overexpression, amplification or somatic mutation. The HER2 gene amplification leading to protein overexpression has been reported in 25–30% of breast cancers and 10–30% of gastric/gastroesophageal cancers. While HER2 is a well-documented predictive, prognostic, and therapeutic marker in breast and gastric/gastroesophageal cancers, its relevance has also been demonstrated in multiple other malignancies. In this article, we will conduct an extensive review of current data pertaining to HER2 amplification, overexpression, or mutation in cancers other than breast and gastric cancers. Full article

The occurrence of more than one primary malignant tumor in a single patient is rare. Multiple primary malignancies can pose difficulties in differential diagnosis between primary tumors and metastasis. Here, we present a case report with multiple primary malignancies. The patient is a 45-year-old female who was diagnosed with cervical mixed squamous neuroendocrine adenocarcinoma, metastasized carcinosarcoma and extramammary vulvar Paget’s disease. The patient was first diagnosed with a microinvasive squamous cervical carcinoma in situ. After a few months, the amputation of a small residual tumor and histological evaluation revealed an IA1-stage poorly differentiated (G3) mixed squamous and neuroendocrine cervical adenocarcinoma. After two years, the disease had progressed and biopsies from altered sites were taken. Histological diagnosis from an ulcerated vulvar region revealed extramammary vulvar Paget’s disease. A biopsy from vagina polyp revealed an earlier diagnosed mixed squamous and neuroendocrine cervical adenocarcinoma. However, histological diagnosis from an inguinal lymph node biopsy was unexpected and revealed carcinosarcoma. It indicated either the development of another primary malignancy, or an unusual spread of metastasis. Clinical presentation as well as diagnostic and treatment challenges are discussed in this case report. This case report shows that multiple primary malignancy cases are difficult to manage both for clinicians and the patient because the therapeutic options can become limited. This complex case was managed by a multidisciplinary team. Full article

Staphylococcus aureus (S. aureus), a major mastitis pathogen in dairy goats, is classified as a contagious pathogen. Although previous research has shown that extramammary body sites can be colonized with S. aureus, it is unknown whether these sites are reservoirs for intramammary infections. The aim of this research was to determine whether extramammary sites can be colonized with mastitis-associated S. aureus strains in dairy goats. Milk samples were collected from 207 primiparous goats and from 120 of these goats, extramammary site samples (hock, groin, nares, vulva and udder) were collected from a large commercial dairy goat herd in the Netherlands during four sampling visits. Extramammary site swabs and milk samples were (selectively) cultured and S. aureus isolates were spa genotyped. The prevalence of colonization of the extramammary sites at goat level was 51.7% and the prevalence of S. aureus intramammary infections was 7.2%. The nares were colonized most frequently (45%), while the groin area was colonized the least (2.5%). Six spa genotypes were identified in this herd and there was no significant difference in the distribution of spa genotypes between the milk or the extramammary sites (p = 0.141). Both in the extramammary sites and in the milk, spa genotypes t544 (82.3% and 53.3%) and t1236 (22.6% and 33.3%) were the dominant genotypes. These results show that in goats, extramammary sites, particularly the nares, are frequently colonized with mastitis-associated S. aureus strains. Extramammary sites may, thus, be a source of S. aureus intramammary infections that are not targeted by the intervention measures aimed at preventing transmission from infected udder glands. Full article

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. Full article