Lacrimal gland adenoid cystic carcinoma (LGACC), the most prevalent malignant epithelial tumor of the lacrimal gland, exhibits high invasiveness and poor prognosis. Despite aggressive local therapies, the 5-year and 10-year survival rates remain at 50% and 20% respectively. This review comprehensively synthesizes histopathological features, molecular mechanisms, and therapeutic advances in LGACC. Histopathological analysis highlights three classical subtypes (tubular, cribriform, and solid) with distinct prognostic implications, particularly emphasizing the detrimental survival impact of tumors undergoing high-grade transformation. At the molecular level, in-depth elucidation reveals the pivotal roles of NOTCH pathway mutations and MYB overexpression in driving oncogenesis through hyperactivation of receptor tyrosine kinase, PIP3/AKT, and ATR/BRCA signaling cascades. Current evidence demonstrates persistent therapeutic challenges: expanded surgical resection fails to significantly improve survival outcomes, while local excision combined with adjuvant therapies still faces substantial recurrence (80% at 5 years) and metastasis rates (66.9%). Emerging breakthroughs in targeted therapies warrant attention, including antisense oligonucleotides targeting MYB-NFIB fusion genes, clinical trial data of NOTCH inhibitors (e.g., AL101), and PARP inhibitor-based combinatorial regimens leveraging DNA damage repair mechanisms. By integrating fundamental research and clinical translational evidence, this review provides a theoretical framework for optimizing LGACC diagnosis and treatment paradigms.

This issue of the Chinese Journal of Tuberculosis and Respiratory Medicine published a manuscript on Mechanisms and therapeutic strategies of small cell lung cancer transformation from non-small cell lung cancer after EGFR-TKI treatment. The exploration of relevant mechanisms, diagnosis, and selection of follow-up therapeutic strategies for such patients are practical problems faced by clinician. With the widespread application of targeted therapy with TKIs for non-small cell lung cancer, small cell lung cancer transformation is one of the important resistance mechanisms after TKI treatment. In recent years, the understanding and importance of its pathogenesis, diagnosis, and treatment strategies in clinical practice have been increasing year by year, and new mechanisms for transformation have been explored in depth to further develop precise intervention strategies for patients.

Lung cancer remains a leading cause of cancer-related mortality. In non-small cell lung cancer (NSCLC) treated with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), histological transformation to small cell lung cancer (SCLC) can occur, leading to EGFR-TKI resistance. SCLC transformation not only challenges existing treatment strategies but also severely impacts patients prognosis. Here, we explore the underlying mechanisms of SCLC transformation, focusing on RB1/TP53 genes, MYC gene, and the Notch and Wnt/β-catenin signaling pathways. We propose a hypothesis for SCLC transformation: co-mutation of RB1/TP53 genes serves as a prerequisite, while combined abnormalities, such as aberrant MYC activation and dysregulated Notch or Wnt/β-catenin signaling, will further drive the transformation process. Currently, therapies for transformed SCLC are still exploratory. We discuss multimodal strategies, including chemotherapy, chemotherapy combined with EGFR-TKIs, chemotherapy combined with anti-angiogenic therapy, chemotherapy combined with immunotherapy, and radiotherapy. Finally, we outline future research directions. Future studies should unravel transformation mechanisms, conduct rigorous randomized trials, and develop precision interventions, paving new avenues for improved patient outcomes.​.

Intravascular large B-cell lymphoma (IVLBCL) represents a rare subtype of extranodal lymphoma characterized by the proliferation of B-cells within the lumen of blood vessels. Pulmonary involvement occurs in approximately 60% of cases. Diagnosis of IVLBCL can be challenging as the clinical manifestations are usually nonspecific. We report a case of IVLBCL presenting with fever and dyspnea. CT scan revealed bilateral diffuse pulmonary ground-glass opacities with gravity-dependent distribution. The diagnosis was established through transbronchial lung biopsy. This case report aimed to heighten clinical awareness and sharpen diagnostic skills regarding pulmonary involvement in IVLBCL.

Objective: To investigate the clinicopathological features, immunophenotype and molecule characteristics of EWSR1::CREM fusion malignant epithelioid neoplasm in soft tissue. Methods: The clinical and pathological data of 2 cases of EWSR1::CREM fusion malignant epithelioid neoplasm in soft tissue diagnosed at the Department of Pathology, Beijing Jishuitan Hospital, Beijing, China from May 2023 to May 2024 were analyzed. Immunohistochemical study, fluorescence in situ hybridization (FISH) and next generation sequencing (NGS) were performed. Relevant literature was reviewed. Results: There were one male and one female patients, aged 35 and 29 years, respectively. The tumors developed in the somatic soft tissue, including calf and chest wall, and were 6.0 and 6.2 cm in size, respectively. The imaging studies suggested space-occupying lesions in muscle tissue. Case 1 did not involve the bone, while Case 2 showed fracture of the 8th rib. Microscopically, a fibrous pseudocapsule surrounded by lymphocytes and plasma cells was identified. The tumors were composed of small to medium-sized round and short spindle-shaped cells, showing nodular or sheet-like pattern. The tumor cells showed round nuclear outline, coarse chromatin with prominent nucleoli. Immunohistochemically, tumor cells showed diffuse positivity of ALK (D5F3), MUM1 and Syn, focal or patchy positivity of CKpan, EMA, S-100, NSE, WT-1 and SMA, and a high Ki-67 index (20%-30%). FISH demonstrated break-apart signals of EWSR1 gene in the 2 cases. NGS revealed EWSR1::CREM gene fusion. Case 2 showed an ATRX gene mutation. The two patients were free of recurrence or metastasis at the 10-month and 1-month follow-up, respectively. Conclusions: EWSR1::CREM fusion malignant epithelioid neoplasm is rare and lacks distinctive morphological and immunohistochemical features. FISH and NGS can help make a definitive diagnosis.

Objective: To investigate the expression of keratin 1 (KRT1) and sialyl-Tn antigen (sTn) in cervical squamous cell carcinoma and its possible mechanism. Methods: Six cervical squamous cell carcinoma specimens were collected at the First Affiliated Hospital of Soochow University, Suzhou, China from 2022 to 2023. Spatial transcriptomics analysis was performed on the paraffin sections of 6 patients to analyze the transcriptomes of invasive squamous cell carcinoma and adjacent normal cervical squamous epithelium. The differential gene KRT1 was selected. Kaplan-Meier survival analysis was used to examine the prognostic value of KRT1 in cervical squamous cell carcinoma patients using the TCGA database. The possible downstream molecule sTn was identified according to literature research. Immunohistochemistry was carried out to investigate the expression of KRT1 and sTn proteins in the primary tumor and metastases of cervical squamous cell carcinoma (40 cases with pelvic lymph node metastasis and 30 cases without). Spearman correlation analysis was conducted to analyze the correlation of their expression. Results: The spatial transcriptomic results of the 6 specimens indicated that the level of KRT1 mRNA significantly decreased in cervical squamous cell carcinoma (compared with that in adjacent normal cervical squamous epithelium), while Kaplan-Meier survival analysis revealed that cervical squamous cell carcinoma patients with low KRT1 mRNA levels (versus high) had a worse prognosis. Immunohistochemistry proved that KRT1 expression was significantly lower in cervical squamous cell carcinoma than in adjacent normal squamous epithelium (P<0.05), but sTn showed the opposite change (increased in carcinoma, P<0.05). The expression changes of KRT1 and sTn were inversely correlated (r=-0.217, P<0.05). In addition, the expression levels of KRT1 and sTn in lymph node metastases were not significantly different from those in primary tumors. Conclusions: The decreased expression of KRT1 in primary cervical squamous cell carcinoma and lymph node metastasis may promote tumor cell proliferation and inhibit apoptosis by upregulating sTn, contributing to the poor prognosis of advanced cervical squamous cell carcinoma.

Objective: To investigate clinicopathologic characteristics and molecular genetic profiles of embryonal rhabdomyosarcoma (ERMS) of the middle ear. Methods: A total of 11 cases of primary middle ear ERMS diagnosed and treated at the Fudan University Affiliated Eye and ENT Hospital between January 2016 and June 2024 were collected. Their clinicopathologic features, immunophenotypes, and molecular genetic alterations were analyzed. Relevant literature was reviewed. Results: There were 8 male and 3 female children. The mean age was 6 years, median age, 6 (5, 7) years, with a range of 1 to 11 years. Clinical manifestations included otorrhea, ear pain, ear fullness, tinnitus, and hearing loss, with some patients also presenting with facial paralysis, hoarseness, and choking on drinking. Otoscopic examination revealed granulomatous neoplasms in the external auditory canal. Imaging studies showed irregular soft-tissue masses in the middle ear region, accompanied by bony destruction and invasion of adjacent structures. Histologically, 10 of the tumors were composed of primitive small round cells, stellate cells, and short spindle-shaped cells, with an alternating loose and dense distribution pattern, and varying degrees of rhabdomyoblastic differentiation in some areas. One tumor exhibited the classic botryoid subtype morphology. Immunohistochemistry supported the diagnosis of rhabdomyosarcoma, and the Ki-67 proliferation index ranged from 40% to 80%. Next-generation sequencing (DNA-seq) was performed on 9 cases, revealing copy number variations of chromosome 7 in 4 cases, PDE4DIP mutations in 5 cases, and C19orf69::TPM3 gene fusions in 6 cases. HPV PCR testing showed HPV11 positivity in 2 cases. All 11 patients underwent surgical treatment, with 4 patients receiving adjuvant chemoradiotherapy. Follow-up until February 2025 revealed 8 deaths, among which 4 cases harbored both C19orf69::TPM3 fusions and PDE4DIP mutations and one had C19orf69::TPM3 fusions alone. Conclusions: ERMS of the middle ear is a rare type of malignant tumor with a relatively poor prognosis. Our study indicates that the concurrence of PDE4DIP mutation and C19orf69::TPM3 gene fusion may indicate poor prognosis in middle ear EMRS, providing a potential target for subsequent individualized treatment.

Objective: To investigate the clinicopathological features, immunophenotype, and gene rearrangement status of hyalinizing clear cell carcinoma (HCCC) of the salivary glands, in order to better understand this rare tumor and improve its precision diagnosis and treatment. Methods: A total of 65 cases of salivary gland HCCC diagnosed at the Peking University School and Hospital of Stomatology, Beijing, China between January 2001 and May 2024 were collected. Clinical features, pathological characteristics, EWSR1 gene rearrangement, and follow-up data were analyzed. Results: There were 33 males and 32 females. The age of the patients ranged from 22 to 85 years, with a median age of 54.0 (40.0, 63.5) years. 93.8% (61/65) of the tumors occurred in the minor salivary glands, most commonly in the palate. Microscopically, the tumors were mainly composed of clear tumor cells. Squamous differentiation was observed in 66.2% (43/65) of the tumors, and mucinous cells in 36.9% (24/65). The tumor stroma showed delicate fibrous septa or hyalinized sheets between tumor nests. Lymph node metastasis occurred in 12.3% (8/65) of the cases, and high-grade transformation was observed in 6.2% (4/65). Tumor cells were all positive for p40 and p63, while SOX10 was positive in 12.3% (8/65) of them. Myoepithelial markers were negative. EWSR1 gene rearrangement was detected in 96.6% of the tumors. Follow-up data showed a 5-year overall survival rate of 93.8%, a local recurrence rate of 9.2%, and a distant metastasis rate of 4.6%. Conclusions: HCCC predominantly arises in minor salivary glands and generally has a favorable prognosis. However, a small proportion of the cases may show high-grade transformation, lymph node metastasis, local recurrence, or distant metastasis. It thus requires long-term and regular follow-up. Accurate diagnosis should be based on a comprehensive assessment of histopathological features, immunophenotype, and gene fusion status.