Introduction: Lipid metabolic reprogramming is gaining attention as a hallmark of cancers. Recent mounting evidence indicates that the malignant behavior of breast cancer (BC) is closely related to lipid metabolism. Here, we focus on the estrogen receptor-positive (ER+) subtype, the most common subgroup of BC, to explore immunometabolism landscapes and prognostic significance according to lipid metabolism-related genes (LMRGs).Methods: Samples from The Cancer Genome Atlas (TCGA) database were used as training cohort, and samples from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), Gene Expression Omnibus (GEO) datasets and our cohort were applied for external validation. The survival-related LMRG molecular pattern and signature were constructed by unsupervised consensus clustering and least absolute shrinkage and selection operator (LASSO) analysis. A lipid metabolism-related clinicopathologic nomogram was established. Gene enrichment and pathway analysis were performed to explore the underlying mechanism. Immune landscapes, immunotherapy and chemotherapy response were further explored. Moreover, the relationship between gene expression and clinicopathological features was assessed by immunohistochemistry.Results: Two LMRG molecular patterns were identified and associated with distinct prognoses and immune cell infiltration. Next, a prognostic signature based on nine survival-related LMRGs was established and validated. The signature was confirmed to be an independent prognostic factor and an optimal nomogram incorporating age and T stage (AUC of 5-year overall survival: 0.778). Pathway enrichment analysis revealed differences in immune activities, lipid biosynthesis and drug metabolism by comparing groups with low- and high-risk scores. Further exploration verified different immune microenvironment profiles, immune checkpoint expression, and sensitivity to immunotherapy and chemotherapy between the two groups. Finally, arachidonate 15-lipoxygenase (ALOX15) was selected as the most prominent differentially expressed gene between the two groups. Its expression was positively related to larger tumor size, more advanced tumor stage and vascular invasion in our cohort (n = 149).Discussion: This is the first lipid metabolism-based signature with value for prognosis prediction and immunotherapy or chemotherapy guidance for ER+ BC.

Fibroadenomas (FAs) are the most common breast tumors in women. No pharmacological agents are currently approved for FA intervention owing to its unclear mechanisms and a shortage of reproducible human models. Here, using single-cell RNA sequencing of human FAs and normal breast tissues, we observe distinct cellular composition and epithelial structural changes in FAs. Interestingly, epithelial cells exhibit hormone-responsive functional signatures and synchronous activation of estrogen-sensitive and hormone-resistant mechanisms (ERBB2,BCL2andCCND1pathways). We develop a human expandable FA organoid system and observe that most organoids seem to be resistant to tamoxifen. Individualized combinations of tamoxifen with ERBB2, BCL2 or CCND1 inhibitors could significantly suppress the viability of tamoxifen-resistant organoids. Thus, our study presents an overview of human FA at single-cell resolution that outlines the structural and functional differences between FA and normal breast epithelium and, in particular, provides a potential therapeutic strategy for breast FAs.

Objectives: Cancer metastasis to the kidney is a rare event. We retrospectively analyzed clinicopathologic characteristics in 6 cases of diagnosed renal metastases from primary lung cancer. We also provide clinical follow-up data and brief review of the literature. Methods: Immunohistochemistry was used to evaluate the expression of TTF-1, NapsinA, CK7, CK(AE1/AE3), P63, P40, CgA, PAX-8, GATA3 and Ki-67 in primary tumor and metastases. Additionally, the clinical characteristics, imaging features, diagnosis, and treatment were analyzed. Results: With the help of immunohistochemistry and combined clinical history, we found four cases were lung adenocarcinomas, one case was lung squamous cell carcinoma, and the other case was lung small cell carcinoma metastases to the kidney.The patients were all male by gender and had a mean age of 62 years, and metastasis to the left kidney were more universal. Most of the tumors histological grade originating from the lung were poorly-moderately differentiated, and the time to metastasis to the kidney was relatively short for squamous lung cancer and small cell lung cancer, while the time to metastasis for lung adenocarcinoma was related to its degree of differentiation. Overall, we found the prognosis of lung cancer patients with renal metastases were poor especially with multi-site metastases. Conclusions: Distinguishing primary and secondary tumors of the kidney is essential to guide treatment and prevent unnecessary surgery, so clinical information, radiology, histological correlation of the primary tumor, and immunohistochemical findings help the pathologist determine correct diagnosis.

Composite lymphoma (CL) involving B-cell lymphoma and T-cell lymphoma is extremely rare. Herein, we report three such cases using immunohistochemistry, flo

Gastric SMARCA4-deficient undifferentiated tumors are rare and have a poor prognosis. We analyzed two cases of gastric SMARCA4-deficient undifferentiated tumors with clinicopathologic characteristics, treatment and flow-up. Immunohistochemistry was used to evaluate the expression of BRG1 (SAMRCA4), SMARCB1 (INI-1), CKpan, Ki-67, CD3, CD20, CD163, PD-1, and PD-L1 in gastric SMARCA4-deficient undifferentiated tumors. Additionally, the clinical characteristics, imaging features, diagnosis, and treatment were analyzed. Two elderly male patients (69 and 61 years old) with a large ulcerated mass located in the gastric fundus and cardia. Histologically, the tumor is of low adhesion, diffusely infiltrating lamellar growth, without any percentage of epithelial differentiation zones, and with little stromal component. Tumor cells round, oval, a small amount of irregular shape, easy to see mitotic figures. Some of them had obvious nucleoli, and a few had multiple nucleoli. The cytoplasm varies, and some cells are more abundant. Significant vascular and neural invasion. BRG1(SMARCA4) was absent, INI-1 was present, and Ki-67 proliferation index was highly expressed (≥ 80%). The remaining sarcoma-specific markers were negative. In case 1, the epithelial markers were negative and the PD-L1 combined positive score was 5. In case 2, CKpan was weakly expressed in only a dozen cells, and the PDL1 CPS was 10. The two patients received chemotherapy and anti-PD1 immunotherapy after radical gastrectomy for gastric cancer. The postoperative follow-up time of the two patients was 16 (case 1) and 3 months (case 2), respectively. The general condition was good, no recurrence or metastasis was observed, and the plasma tumor markers were in the normal range. Large SMARCA4-deficient tumors are more likely to have massive necrosis on the surface, leading to negative biopsy results. This tumor has a diffuse lamellar growth and needs to be differentiated from a variety of tumors with similar morphology, such as lymphoma, malignant melanoma, neuroendocrine carcinoma and undifferentiated sarcoma. The tumor cells were negative or only slightly positive for CKpan increases the difficulty of pathological diagnosis of this disease. However, loss of BRG1 (SMARCA4) expression can confirm the diagnosis. Chemotherapy combined with anti-PD1 treatment may have potential benefits in the management of gastric SMARCA4-deficient undifferentiated tumors. However, given the rarity of these tumors and the limited number of cases in our study, further research with larger cohorts is needed to validate these preliminary results.

Breast neuroendocrine carcinoma (NECB) is a rare type of breast tumor. Large-cell neuroendocrine carcinomas of the breast (LCNECB) are a special and rare histological subtype of NECB. Here, we present a case of a 59-year-old woman who was diagnosed with an LCNECB. A mass in the upper outer quadrant of the right breast was revealed via imaging. A histological examination showed the tumor cells were composed of clusters of large cells with obvious atypia that were polygonal or irregularly shaped. The patient underwent a right-breast-conserving radical surgery and sentinel lymph node biopsy (SLB). A histopathological examination revealed that the tumor of the right breast was 2.5 × 2 cm in size with vascular invasion, and the sentinel lymph node was negative. The immunohistochemical results showed that the tumor cells were diffuse and positive for chromogranin A (CgA), synaptophysin (Syn), and INSM1. The patient successfully completed chemotherapy and radiotherapy and is currently undergoing endocrine therapy.