Search Results (9)

Background: The glucocorticoid receptor (GR) regulates the transcription of thousands of genes. In cancer, both oncogenic and tumor suppressive roles of GR have been proposed. Methods: A tissue microarray containing 18,527 samples from 147 tumor (sub-)types and 608 samples from 76 normal tissue types was analyzed for GR expression by immunohistochemistry. Results: GR positivity was found in 76.4% of 14,349 interpretable cancers, including 18.5% with weak, 19.6% with moderate, and 38.3% with strong positivity. GR positivity appeared in all 147 tumor types, with at least one strongly positive tumor in 136 types. Of out tumor entities, 77 of the 147 showed GR positivity in 100% of the cases analyzed. Only six tumor types had less than 50% GR-positive cases, including adenomas with low-/high-grade dysplasia (32.5%/21.7%), adenocarcinomas (17%) and neuroendocrine carcinomas (45.5%) of the colorectum, endometrial carcinomas (25.6%), and rhabdoid tumors (25%). Reduced GR staining was associated with grade progression in pTa (p < 0.0001) and with nodal metastasis in pT2-4 (p = 0.0051) urothelial bladder carcinoma, advanced pT stage (p = 0.0006) in breast carcinomas of no special type (NST), and high grade (p = 0.0066), advanced pT stage (p < 0.0001), and distant metastasis (p = 0.0081) in clear cell renal cell carcinoma. GR expression was unrelated to clinico-pathological parameters in gastric, pancreatic, and colorectal adenocarcinoma, and in serous high-grade carcinoma of the ovary. Conclusions: GR expression is frequent across all cancer types. Associations between reduced GR expression and unfavorable tumor features in certain cancers suggest that the functional importance of GR-regulated genes in cancer progression depends on the cell of tumor origin. Full article

Ectopic adrenocorticotropic hormone syndrome (EAS) occurs when a tumor develops neuroendocrine differentiation with the secretion of ACTH resulting in hypercortisolism and possibly Cushing’s syndrome (CS). Only 5–10% of CS cases are attributed to EAS; of these, breast tumors comprise less than 1%. Two known variants of breast neuroendocrine tumors include neuroendocrine-differentiated carcinoma and ductal carcinoma with neuroendocrine features. Currently, guidelines for treatment are limited and EAS is associated with significant morbidity and mortality. A 39-year-old female presented with a rapidly enlarging breast mass. Biopsy demonstrated invasive poorly differentiated breast carcinoma with high-grade neuroendocrine features and necrosis. Staging at diagnosis confirmed metastatic disease of the liver and bone. First-line chemotherapy (Cisplatin/Etoposide/Durvalumab) was initiated with evidence of disease progression after four cycles. Given a poor response to therapy, a simple mastectomy was performed for local control and complete pathologic analysis, demonstrating high-grade neuroendocrine carcinoma with large-cell features. Second-line therapy (Adriamycin/Cyclophosphamide) was initiated for three cycles after which the patient required admission for severe and refractory hypokalemia. Workup confirmed elevated ACTH consistent with paraneoplastic EAS and further evidence of disease progression. Third-line therapy (Nab-Paclitaxel) was initiated, and genetic testing was completed, confirming the PIK3 mutation, for which access to Alpelisib therapy was requested. Given symptoms of progressive severe CS with significant liver disease limiting medical therapies, the patient underwent urgent bilateral laparoscopic adrenalectomy after which she was able to be discharged home while awaiting additional systemic therapy. EAS resulting in CS secondary to breast neuroendocrine carcinoma is a rare and challenging diagnosis. Further research is needed to inform treatment guidelines to improve outcomes. While patient survival is dependent upon the underlying disease process, laparoscopic bilateral adrenalectomy is an accepted, definitive treatment option. Full article

A seven-year-old spayed female dog presented with multiple, small oval-shaped masses on the abdominal skin. The excised tissue was submitted for histopathological evaluation. Routine histology revealed basaloid nodules with stippled chromatin and pleomorphic nuclei. Morphologically, the tumor resembled a solid papillary carcinoma of the breast or an endocrine mucin-producing sweat gland carcinoma (EMPSGC). EMPSGC is a rare neuroendocrine-differentiated neoplasm. This study aimed to compare different immunohistochemical markers for distinguishing between canine sweat gland carcinoma (SGC) and mammary gland carcinoma (MGC). CK19 and Sox9 were useful in identifying SGC. Additionally, the tumor was positive for CK5, AE1/AE3+CK8/18, p63, vimentin, E-cadherin, and synaptophysin, while estrogen receptor staining was negative. The final diagnosis of canine EMPSGC was based on the tumor’s morphological and neuroendocrine immunohistopathological features. Our report provides the first detailed description of a canine EMPSGC, an exceedingly rare tumor in dogs. Full article

MiRNAs have been reported as biomarkers with diagnostic, prognostic, and predictive value for many different diseases. Therapeutic agents targeting some miRNAs are currently being developed. We aimed to compare BC-NEFs (carcinoma of the breast with neuroendocrine features) with IDC (invasive ductal carcinoma) cases without neuroendocrine features in terms of the level of miRNA expression known to show the oncogenic (miR-21) and tumor-suppressor effects (miR-let7f) and the clinicopathological features. A total of 29 patients with a diagnosis of BC-NEFs (15 cases with neuroendocrine differentiation >50% of the whole section of tumor and 14 cases with neuroendocrine differentiation 10–50% of the tumor) and 30 patients with a diagnosis of IDC (no neuroendocrine differentiation) were retrospectively re-evaluated. Expression levels of miR-21 and miR-let7f were determined by the qRT-PCR method in paraffin tissue blocks. MiR-21 expression was significantly higher in the IDC group than in the group with BC-NEFs. miR-let7f expression was significantly lower in the group with BC-NEFs compared to the IDC group. A high expression level of miR-21 was found to be associated with progesterone receptor (PR) negativity. Our findings show that the presence of NEFs in breast carcinomas makes a significant difference in the expression levels of the investigated oncogenic (miR-21) and tumor-suppressor (miR-let7f) miRNAs. These findings suggest that miRNAs may be a potential biomarker in BC-NEFs and would benefit from targeted therapy. Full article

(1) Background: Endocrine Mucin-Producing Sweat Gland Carcinoma (EMPSGC) is a rare, low-grade, neuroendocrine-differentiated, cutaneous adnexal tumor, officially recognized by the World Health Organization (WHO) Skin Tumors Classification in 2018 as a separate entity and homologue of endocrine ductal carcinoma in situ (eDCIS)/solid papillary carcinoma of the breast. Although it is more frequent in the female sex, between 60 and 70 years old, in the peri-orbital region, EMPSGC has also been described in the male sex, in subjects under 60 and over 80, and in extra-eyelid localizations (cheek, temple, scalp), but also in extra-facial localizations (chest and scrotum). (2) Methods: We present the clinical case of a 71-year-old woman with an undated lesion of the scalp, which presented as a nodule, skin-colored, and 2.5 cm in maximum diameter. We also conduct a comprehensive literature review from 1997 to the end of 2022, consulting PubMed, Scopus, Web of Science (WoS), and Google Scholar using the following keywords: “Endocrine mucin-producing sweat gland carcinoma” and/or “EMPSGC” and/or “skin” and “cutaneous neoplasms”. In addition, we followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A total of 253 patients were recorded; 146 were females (57.7%) and 107 were males (42.2%). The vast majority of the lesions were in the eyelids (peri-ocular region), and only a minority of cases involved the cheeks, supra-auricular, retro-auricular, and occipital region, with very rare cases in the scalp, to which the present is also added. (4) Conclusions: The morphological and immunophenotypical features are essential both for the correct diagnosis and to be able to classify this lesion among the corresponding eDCIS/solid papillary carcinoma of the breast, with neuroendocrine differentiation. Recent papers have attempted to shed light on the molecular features of EMPSGC, and much remains to be conducted in the attempt to subtype the molecular profiles of these entities. Future studies with large case series, and especially with molecular biology techniques, will be needed to further add information about EMPSGC and its relationship in the PCMC spectrum. Full article

We aimed to overview the most recent data on sternal metastases from a multidisciplinary approach (diagnosis strategies, outcome, and histological reports). This narrative review based on a PubMed search (between January 2020 and 22 July 2023) using key words such as “sternal”, “manubrium”, and “metastasis” within the title and/or abstract only included original papers that specifically addressed secondary sternal spreading of cancer in adults, for a total of 48 original articles (14 studies and 34 single case reports). A prior unpublished case in point is also introduced (percutaneous incisional biopsy was used to address a 10 cm sternal tumour upon first admission on an apparently healthy male). The studies (n = 14) may be classified into one of three groups: studies addressing the incidence of bone metastases (including sternum) amid different primary cancers, such as prostate cancer (N = 122 with bone metastases, 83% of them with chest wall metastases), head and neck cancers (N = 3620, 0.8% with bone metastases, and 10.34% of this subgroup with sternum involvement); and glioblastoma (N = 92 with bone metastases, 37% of them with non-vertebral metastases, including the sternum); assessment cohorts, including breast cancer (N = 410; accuracy and sensitivity of PET/CT vs. bone scintigraphy is superior with concern to sternum spreading) and bone metastases of unknown origin (N = 83, including a subgroup with sternum metastases; some features of PET/CT help the differentiation with multiple myeloma); and cohorts with various therapeutic approaches, such as palliative arterial embolization (N = 10), thymic neuroendocrine neoplasia (1/5 detected with sternum metastases), survival rates for sternum metastases vs. non-sternum chest wall involvement (N = 87), oligo-metastatic (sternal) breast cancer (3 studies, N = 16 for all of them), oligo-metastatic head and neck cancer (N = 81), conformal radiotherapy (N = 24,215, including an analysis on sternum spreading), and EBRT followed by MR-HIFU (N = 6). Core data coming from the isolated case reports (N = 34) showed a female to male ratio of 1.6; the females’ ages were between 34 and 80 (mean of 57.28) and the males’ ages varied between 33 and 79 (average of 58.78) years. The originating tumour profile revealed that the most frequent types were mammary (N = 8, all females) and thyroid (N = 9, both women and men), followed by bladder (N = 3), lung (N = 2), and kidney (N = 2). There was also one case for each of the following: adenoid cystic carcinoma of the jaw, malignant melanoma, caecum MiNEN, a brain and an extracranial meningioma, tongue carcinoma, cholangiocarcinoma, osteosarcoma, and hepatocellular carcinoma. To our knowledge, this is the most complex and the largest analysis of prior published data within the time frame of our methods. These data open up new perspectives of this intricate, dynamic, and challenging domain of sternum metastases. Awareness is a mandatory factor since the patients may have a complex multidisciplinary medical and/or surgical background or they are admitted for the first time with this condition; thus, the convolute puzzle will start from this newly detected sternal lump. Abbreviations: N = number of patients; n = number of studies; PET/CT = positron emission tomography/computed tomography; EVRT = external beam radiotherapy; MR-HIFU = magnetic resonance-guided high-intensity focused ultrasound; MiNEN = mixed neuroendocrine-non-neuroendocrine tumour. Full article

Background: Breast carcinoma with neuroendocrine features includes neuroendocrine neoplasm of the breast and invasive breast cancer with neuroendocrine differentiation. This study aimed to investigate the clinicopathological features and prognosis of this disease according to the fifth edition of the World Health Organization classification of breast tumors. Materials and Methods: A total of 87 patients with breast carcinoma with neuroendocrine features treated in the First Medical Center, Chinese PLA General Hospital from January 2001 to January 2022 were retrospectively enrolled in this study. Results: More than half of the patients were postmenopausal patients, especially those with neuroendocrine neoplasm (62.96%). There were more patients with human epidermal growth factor receptor 2 negative and hormone receptor positive tumors, and most of them were Luminal B type (71.26%). The multivariate analysis showed that diabetes and stage IV disease were related to the progression-free survival of breast carcinoma with neuroendocrine features patients (p = 0.004 and p < 0.001, respectively). Conclusion: Breast carcinoma with neuroendocrine features tended to be human epidermal growth factor receptor 2 negative and hormone receptor positive tumors, most of them were Luminal B type, and the related factors of progression-free survival were diabetes and stage IV disease. Full article

Breast tumors with neuroendocrine (NE) differentiation comprise an uncommon and heterogeneous group of tumors, including invasive breast cancer of no special type (IBC-NST) with NE features, neuroendocrine tumors (NETs), and neuroendocrine carcinoma (NEC). The most recent World Health Organization (WHO) classification in 2019 defined neuroendocrine neoplasms (NENs) of the breast (Br-NENs) as tumors in which >90% of cells show histological evidence of NE differentiation, including NETs (low-grade tumors) and NEC (high-grade). Due to the low prevalence of these tumors and successive changes in their diagnostic criteria over the years, only limited evidence of these tumors exists, derived mainly from case reports and retrospective case series. Breast tumors with NE differentiation are usually treated like the more commonly occurring IBC-NSTs. Immunohistochemistry (IHC) of breast tumors with NE differentiation usually shows a hormone receptor (HR)-positive and human epidermal growth factor type 2 (HER2)-negative profile, so that hormonal therapy with cyclin-dependent kinase (CDK)4/6 inhibitors or other targeted agents would be reasonable treatment options. Herein, we present a review of the literature on breast tumors with NE differentiation as defined in the latest WHO 2019 classification, and discuss the clinical management of these tumors. Full article

Neuroendocrine breast carcinomas represent a rare subtype of breast cancer. Their definition, prevalence and prognosis remain controversial in the literature. Regarding the presentation, there are no differences from other breast carcinomas and clinical syndromes related to hormone production are extremely rare. Refinement of the classification of neuroendocrine neoplasms of the breast is needed in order to improve the reproducibility of their diagnostic criteria and to define their clinical significance. This article presents the case of a 44-year-old female patient diagnosed with invasive breast carcinoma with neuroendocrine features, according to the 2012 World Health Organization (WHO) definition, with focus on presentation, clinical manifestations, diagnostic approach and differential diagnosis. Full article