BACKGROUND

Penile squamous cell carcinoma (SCC) is rare in high-income regions but remains a significant oncologic burden worldwide. Nodal involvement is the most important prognostic factor, and early identification is critical.

A 56-year-old circumcised male presented with a six-month history of a progressively enlarging, foul-smelling fungating penile mass and bilateral inguinal lymphadenopathy. Biopsy confirmed moderately differentiated SCC. Imaging showed large bilateral inguinal nodal disease without distant metastasis. Laboratory findings revealed leukocytosis, thrombocytosis, and mildly deranged coagulation parameters. The patient underwent total penectomy with perineali urethrostomy, followed by bilateral inguinal and pelvic lymph node dissection through single-curvilinear incisions. Frozen-section analysis confirmed extensive bilateral nodal metastasis. Postoperatively, a localized left inguinal surgical site infection was treated conservatively. He was discharged on postoperative day seven with drains in situ and was recommended adjuvant chemoradiotherapy in accordance with NCCN Guidelines.

This case highlights the challenges of managing advanced penile SCC with bulky bilateral inguinal metastasis and demonstrates the utility of single-curvilinear inguinal incisions for comprehensive lymphadenectomy. Early recognition, accurate staging, and guideline-based multimodal treatment remain essential for optimizing outcomes.

An elderly Filipino female presented with a 5-year enlarging left nasolacrimal mass initially diagnosed as Inverted Papilloma of the Lacrimal Sac. Repeat biopsy revealed a papillomatous neoplasm with thick and thin papillae, solid invaginating lobules, and anastomosing trabeculae of monomorphic squamotransitional cells, briskly infiltrated by neutrophils. Mucocytes, respiratory epithelium, and microcysts, typical of Inverting Sinonasal Papilloma, are absent. Immunohistochemistry, including a validated AFF2 IHC, confirmed the diagnosis of DEK::AFF2 sinonasal carcinoma. Awareness of this emerging entity is essential to prevent misdiagnosis and prompt surgical management.

Introduction: Pancreatoblastoma is a rare tumor predominantly affecting pediatric population and accounts for 0.5% of all pancreatic tumors. Overlapping histologic features with other neoplasms in a limited sample poses a diagnostic challenge in rendering final diagnosis for appropriate management. Case Description: A 6-year-old female presented with abdominal mass. Imaging revealed a pancreatic mass initially measuring 8.9 cm enlarging to 20.8 cm in the span of 3 months with elevated serum AFP levels. Biopsy and subsequent immunohistochemistry was interpreted as malignant round cell neoplasm. Neoadjuvant chemotherapy was initiated and underwent distal pancreatectomy. Grossly, there was an ill defined, tan, solid mass measuring 10.0 x 8.0 x 8.0 cm and histology revealed lobules separated by dense fibrous bands with acinar and trabecular patterns and featured prominent squamous morules. Patient was discharged stable with normalization of serum AFP and started adjuvant chemotherapy. Discussion: Biopsy showed round cells which are beta-catenin positive and synaptophysin, chromogranin A negative with an impression of solid pseudopapillary neoplasm versus pancreatoblastoma. Thorough sampling of the resection specimen showed lobules of malignant cells positive for pancytokeratin and E-cadherin confirming epithelial differentiation and the diagnostic squamous morules showed CD10 positivity and a distinct pattern of both nuclear and cytoplasmic betacatenin expression supporting the activation of Wnt pathway that is typical of pancreatoblastoma. Conclusion Limited tissues due to large tumor size and core biopsy sampling did not reveal the characteristic squamous morules, thus having a diagnostic challenge. Comprehensive evaluation of the resected specimen addressed this gap by having more tumoral areas and specific tissues subjected to immunohistochemistry studies.
Child ; Pancreatoblastoma ; alpha-Fetoproteins ; Carcinoma, Squamous Cell

OBJECTIVE

To report a case of parotid cholesteatoma and concurrent squamous cell carcinoma of the temporal bone in a 51-year-old woman.

Design: Case Report

Setting: Tertiary Government Training Hospital

Patient: One

A 51-year-old woman with a left parotid mass and ipsilateral external auditory canal mass and chronic bilateral otorrhea had parotid biopsy histological features of cholesteatoma and temporal bone imaging suggestive of middle ear cholesteatoma and possible parotid region abscess. She underwent subtotal petrosectomy, mastoid obliteration and excision of the parotid mass. Histopathological examination of the parotid mass was consistent with cholesteatoma but tissue from the middle ear cavity showed well-differentiated squamous cell carcinoma.

While cholesteatomas typically arise within the temporal bone, they may occasionally present in atypical or distant sites. In cases where a cholesteatoma demonstrates an unusual location, aggressive behavior, or atypical clinical progression, a high index of suspicion should be maintained for the possibility of an underlying or coexisting temporal bone squamous cell carcinoma.

OBJECTIVE: Aloin, the main active component in Aloe vera (L.) Burm. f., has shown promising anti-tumor effects. This study investigated the impact of aloin in lung squamous cell carcinoma (LUSC) and explored its functional mechanism. METHODS: We analyzed the viability, migration, invasion, proliferation, and apoptosis of two LUSC cell lines after treatment with aloin. Target molecules of aloin and downstream target transcripts of nuclear receptor subfamily 3 group C member 2 (NR3C2) were predicted by bioinformatics. The biological functions of NR3C2 and metallothionein 1 M (MT1M) in the malignant properties of LUSC cells were determined. A co-culture system of LUSC cells with monocyte-derived macrophages was constructed. Mouse xenograft tumor models were generated to analyze the functions of aloin and NR3C2 in the tumorigenic activity of LUSC cells and macrophage polarization in vivo. RESULTS: Aloin suppressed malignant properties of LUSC cells in vitro. However, these effects were negated by the silencing of NR3C2. NR3C2 was found to activate MT1M transcription by binding to its promoter. Additional upregulation of MT1M suppressed the malignant behavior of LUSC cells augmented by NR3C2 silencing. Analysis of the M1 and M2 markers/cytokines in the macrophages or the culture supernatant revealed that aloin treatment or MT1M overexpression in LUSC cells enhanced M1 polarization while suppressing M2 polarization of macrophages, whereas NR3C2 silencing led to reverse trends. Consistent findings were reproduced in vivo. CONCLUSION This study demonstrated that aloin activates the NR3C2/MT1M axis to suppress the malignant behavior of LUSC cells and M2 macrophage polarization. Please cite this article as: Chen YN, Lu JY, Gao CF, Fang ZR, Zhou Y. Aloin blocks the malignant behavior of lung squamous cell carcinoma cells and M2 macrophage polarization by modulating the NR3C2/MT1M axis. J Integr Med. 2025; 23(2): 195-208.
Lung Neoplasms/metabolism* ; Humans ; Animals ; Cell Line, Tumor ; Carcinoma, Squamous Cell/metabolism* ; Mice ; Macrophages/drug effects* ; Emodin/analogs & derivatives* ; Metallothionein/genetics* ; Cell Proliferation/drug effects* ; Cell Movement/drug effects* ; Apoptosis/drug effects* ; Receptors, Glucocorticoid/genetics*

Pristimerin, which is one of the compounds present in Celastraceae and Hippocrateaceae, has antitumor effects. However, its mechanism of action in esophageal squamous cell carcinoma (ESCC) remains unclear. This study aims to investigate the efficacy and mechanism of pristimerin on ESCC in vitro and in vivo. The inhibitory effect of pristimerin on cell growth was assessed using trypan blue exclusion and colony formation assays. Cell apoptosis was evaluated by flow cytometry. Gene and protein expressions were analyzed through quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blotting, and immunohistochemistry. RNA sequencing (RNA-Seq) was employed to identify significantly differentially expressed genes (DEGs). Cell transfection and RNA interference assays were utilized to examine the role of key proteins in pristimerin?s effect. Xenograft models were established to evaluate the antitumor efficiency of pristimerin in vivo. Pristimerin inhibited cell growth and induced apoptosis in ESCC cells. Upregulation of Noxa was crucial for pristimerin-induced apoptosis. Pristimerin activated the Forkhead box O3a (FoxO3a) signaling pathway and triggered FoxO3a recruitment to the Noxa promoter, leading to Noxa transcription. Blocking FoxO3a reversed pristimerin-induced Noxa upregulation and cell apoptosis. Pristimerin treatment suppressed xenograft tumors in nude mice, but these effects were largely negated in Noxa-KO tumors. Furthermore, the chemosensitization effects of pristimerin in vitro and in vivo were mediated by Noxa. This study demonstrates that pristimerin exerts an antitumor effect on ESCC by inducing AKT/FoxO3a-mediated Noxa upregulation. These findings suggest that pristimerin may serve as a potent anticancer agent for ESCC treatment.
Forkhead Box Protein O3/genetics* ; Humans ; Apoptosis/drug effects* ; Esophageal Squamous Cell Carcinoma/physiopathology* ; Esophageal Neoplasms/physiopathology* ; Pentacyclic Triterpenes ; Animals ; Cell Line, Tumor ; Proto-Oncogene Proteins c-bcl-2/genetics* ; Mice ; Signal Transduction/drug effects* ; Mice, Nude ; Cell Proliferation/drug effects* ; Triterpenes/pharmacology* ; Xenograft Model Antitumor Assays ; Mice, Inbred BALB C ; Male ; Gene Expression Regulation, Neoplastic/drug effects*

Objective To elucidate the molecular mechanism by which exosomes (Exo) derived from cancer-associated fibroblasts (CAF) carrying HOX transcript antisense intergenic RNA (lncRNA HOTAIR) promote the metastasis of esophageal squamous cell carcinoma (ESCC). Methods CAFs were collected from tumor tissues, and non-cancer associated fibroblasts (NFs) were obtained from adjacent normal tissues at least 5 cm away from the tumor. Exosomes (CAFs-Exo and NFs-Exo) were isolated from conditioned media collected from CAFs or NFs. CAFs-Exo and NFs-Exo were incubated with human ESCC cell line TE-1 for 24 hours, and CCK-8 was used to determine the cell proliferation ability. Scratch test and Transwell test were performed to determine the cell migration and invasion ability. TE-1 cells were divided into the following two groups: NC group and KD group. The NC group and KD group were transfected with control siRNAs or siRNAs targeting HOTAIR respectively. The effects of HOTAIR knock-down on cell proliferation, migration, invasion and glycolysis were determined. Results CAFs-Exo promoted the proliferation of TE-1 cells more significantly than NFs-Exo. Compared with NFs-Exo group, the migration and invasion ability of TE-1 cells treated with CAFs-Exo were improved significantly. In addition, CAFs-Exo treatment inhibited the expression of E-cadherin and enhanced the expression of N-cadherin. The expression of HOTAIR in CAFs was significantly higher than that in NFs. Compared with NFs-Exo, the expression level of HOTAIR in CAFs-Exo increased significantly. Compared with NC group, the proliferation, migration and invasion of TE-1 cells in KD group decreased significantly. Compared with NC group, hexokinase 2 (HK2), extracellular acidification rate (ECAR) and ATP/ADP ratio of TE-1 cells in KD group decreased significantly. Conclusion HOTAIR, an exosome derived from CAFs, may be involved in metastasis and EMT by regulating glycolysis in ESCC cells.
Humans ; RNA, Long Noncoding/metabolism* ; Esophageal Neoplasms/metabolism* ; Cell Movement/genetics* ; Cell Proliferation/genetics* ; Cell Line, Tumor ; Esophageal Squamous Cell Carcinoma ; Exosomes/genetics* ; Neoplasm Metastasis ; Neoplasm Invasiveness ; Gene Expression Regulation, Neoplastic ; Glycolysis/genetics* ; Cancer-Associated Fibroblasts/metabolism* ; Carcinoma, Squamous Cell/metabolism* ; Cadherins/genetics*

The early diagnosis and precise treatment of esophageal squamous cell carcinoma (ESCC) hold significant clinical value in improving patient survival rate. Current diagnostic methods for early-stage ESCC primarily rely on invasive procedures and endoscopy, which can cause discomfort and financial burden for patients. Therefore, non-invasive biomarkers with high sensitivity and specificity present a more suitable alternative for early tumor diagnosis. Tumor associated autoantibodies (TAAb), identified as potential biomarkers, have considerable clinical implications for the early diagnosis, treatment monitoring, and prognosis assessment of ESCC. Here in we aim to summarize recent research on ESCC-related autoantibodies, including their background, types and development, analyze the potential of those autoantibodies in clinical diagnosis, treatment monitoring, and prognosis assessment, and also discuss the limitations of existing research and future directions. The goal is to provide a theoretical foundation for the early diagnosis and personalized treatment of ESCC.
Humans ; Autoantibodies/immunology* ; Esophageal Neoplasms/therapy* ; Esophageal Squamous Cell Carcinoma/immunology* ; Biomarkers, Tumor/immunology* ; Prognosis ; Carcinoma, Squamous Cell/diagnosis* ; Animals

The NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, a high-molecular-weight protein complex in the cytoplasm, is composed of three core components: the sensor protein NLRP3, the adaptor protein apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) and the effector protein caspase-1. It plays a critical role in regulating host immune and inflammatory responses. Studies have shown that the NLRP3 inflammasome has increasingly become a focal point in tumor molecular biology field. A growing body of evidence indicates that the increased expression and activation of the NLRP3 inflammasome is closely associated with the pathogenesis of head and neck squamous cell carcinoma (HNSCC) and the tumor microenvironment (TME). It may promote tumor proliferation, invasion, migration, and other biological behaviors through various regulatory mechanisms while influencing tumor immune evasion and therapy resistance, which holds promise as a prognostic biomarker for patients. This review explores the current effect and mechanism of the NLRP3 inflammasome and its signaling pathways in head and neck cancer, providing insights into clinical targeted drug development and molecular immunotherapy.
Humans ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Inflammasomes/metabolism* ; Head and Neck Neoplasms/pathology* ; Squamous Cell Carcinoma of Head and Neck/metabolism* ; Tumor Microenvironment ; Signal Transduction ; Animals

The standard treatment for locally advanced esophageal squamous cell carcinoma (ESCC) is neoadjuvant chemoradiotherapy, followed by surgery or definitive radiotherapy, but clinical results are unsatisfactory. In recent years, relevant studies have shown that immunotherapy combined with chemoradiotherapy has become a new treatment option for locally advanced ESCC. This article summarizes the current progress of chemoradiotherapy combined with immunotherapy in the treatment of locally advanced ESCC, and provides necessary theoretical basis for the comprehensive understanding and optimization of chemoradiotherapy combined with immunotherapy regimens for ESCC.
Humans ; Esophageal Squamous Cell Carcinoma/therapy* ; Esophageal Neoplasms/radiotherapy* ; Immunotherapy/methods* ; Chemoradiotherapy/methods* ; Combined Modality Therapy