Microcalcifications are among the most reliable mammographic signs of breast cancer, particularly of non-palpable and in situ disease, yet for decades they were regarded as inert by-products of cellular degeneration-a view that delayed inquiry into their biology. A growing body of in vitro, ex vivo, and tissue-based evidence now reframes breast microcalcification as a process that can be actively regulated and cell-driven, recapitulating physiological and pathological mineralization elsewhere in the body. In this review, we synthesize the mechanistic basis of this paradigm shift and argue that mineral formation is not a passive marker but a participant in tumor biology. Two mineral species-calcium oxalate and calcium hydroxyapatite-carry different biological meaning and are separable on routine histopathology by birefringence and histochemistry. Hydroxyapatite can promote proliferation, matrix remodeling, and invasion, yet it is also the mineral of most benign calcifications, so its significance lies in composition and cellular origin, not presence alone. We discuss the osteomimetic program through which mammary tumor cells acquire bone-like mineralizing capacity, including the roles of alkaline phosphatase activity, ion transport, and PI3K-Akt signaling, and we distinguish osteomimicry-a phenotype of the tumor cell-from the bone metastatic niche that such cells may exploit. We then consider how mineral composition and microstructure encode the surrounding microenvironment and connect to clinical observations: association with HER2-positive disease, behavior under neoadjuvant chemotherapy, prognostic associations, and an emerging link with bone metastasis. We close with an integrated framework and a research agenda positioning mineral biology at the interface of the tumor microenvironment and metastatic progression.

Acral metastases are an exceptionally uncommon manifestation of bone dissemination, with renal cell carcinoma (RCC) serving as a particularly rare primary source. Historically, these lesions signified terminal disease managed with palliative amputation, although most data predate modern immunotherapy. A man in his 50s presented with newly diagnosed clear cell RCC, an inferior vena cava tumor thrombus, and bilateral lung metastases. He repeatedly declined systemic immunotherapy. Nine months later, he developed a painful swelling of the right ring fingertip. Imaging revealed an osteolytic lesion of the distal phalanx. Amputation was performed, and histopathology confirmed metastatic RCC. This case illustrates an atypical acral metastasis secondary to untreated, naturally progressing systemic disease. It highlights the challenges of patient autonomy and traditional medicine preferences. It emphasizes the role of local surgery for symptom relief and histological verification and underscores the necessity of a highly individualized, multidisciplinary approach to managing rare metastatic presentations.

Bone and soft tissue sarcomas are highly heterogeneous malignant tumors originating from mesenchymal tissues. 20%-25% of bone and 10%-15% of soft tissue sarcoma patients present with metastases at diagnosis, with another 30%-50% progressing during treatment. Currently, chemotherapy remains the primary first-line treatment for advanced disease. However, standard protocols for second-line and subsequent treatments are lacking, and immunotherapy is effective only in limited subtypes. Anti-angiogenic tyrosine kinase inhibitor (TKI), by inhibiting angiogenesis and remodeling the tumor microenvironment, has demonstrated promising clinical prospects, expanding their application scope from second-line and subsequent therapies to first-line combination TKI, maintenance, and neoadjuvant settings. To standardize the clinical application of TKI, the Sarcoma Expert Committee of the Chinese Society of Clinical Oncology (CSCO) organized 51 experts and developed this consensus based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system, systematically integrating domestic and international evidence-based medical data up to October 2025, combined with expert clinical experience. This consensus focuses on the application of TKI in bone and soft tissue sarcomas, identifies the 8 core clinical questions and formulates 12 recommendations covering indication selection, timing of administration, combination strategies, perioperative management, and adverse event management, aiming to provide scientific guidance for Chinese clinicians to standardize their use in sarcoma treatment, enhance therapeutic efficacy, and improve patient prognosis.

For metastatic colonization to occur, disseminated tumor cells must survive, adapt to, and remodel distant microenvironments in an organ-specific manner. We established a human multitissue model of cancer spread, with engineered bone and lung linked by vascular flow containing circulating cancer cells. Parental MDA-MB-231 cells extravasated toward both tissues, remodeled their niches, and acquired transcriptional programs reflecting adaptation to the local microenvironment, particularly upon homing to bone. Tissue-specific colonization by the bone- and lung-tropic MDA-MB-231 derivatives was quantified in independently perfused bone or lung platforms. Consistent with in vivo behavior, bone-tropic cells showed stronger bone colonization than lung-tropic cells and induced more pronounced osteolysis. In contrast, lung-tropic cells caused greater epithelial disruption in lung tissue and only modest colonization of bone. Distinct patterns of tissue colonization and secreted factors demonstrate that this device recapitulates key features of organ-specific metastasis observed in vivo for this family of cell lines.

Osteosarcoma remains difficult to cure once it metastasizes, recurs, or becomes resistant to chemotherapy. Surgery combined with multi-drug chemotherapy improves outcomes in localized disease, but outcomes for high-risk patients have plateaued, prompting renewed interest in immunotherapy. However, immune checkpoint blockade has limited efficacy in unselected osteosarcoma patients: in SARC028, one objective response was observed among 22 patients with osteosarcoma treated with pembrolizumab. This limited response is consistent with antigen heterogeneity, enrichment of immunosuppressive myeloid populations, insufficient cytotoxic lymphocyte infiltration, matrix-associated immune exclusion, and metastatic immune adaptation. Gene-based immunotherapy offers a complementary strategy. When endogenous immune priming is inadequate, these platforms may initiate, reshape, or amplify antitumor immunity by promoting oncolytic antigen release, local cytokine or chemokine expression, engineered immune-cell recognition, or non-viral delivery of immunomodulatory payloads. This article discusses oncolytic vectors, cytokine-armed vectors, CAR-T and CAR-NK cells, TCR- or neoantigen-directed strategies, and non-viral gene delivery systems as potential approaches for reshaping osteosarcoma immunity. It also examines combination strategies and translational challenges in pediatric and adolescent patients. Beyond summarizing platform-level evidence, we distinguish findings generated directly in osteosarcoma from evidence extrapolated from other tumor types, identify the principal unresolved knowledge gaps for each platform, and summarize the current osteosarcoma-specific clinical trial landscape to clarify the translational maturity of these strategies.

Therapy-related chronic myeloid leukaemia (t-CML) is an extremely rare myeloid neoplasm. Here, we report a first case of CML developing during long-term treatment with alectinib, a highly selective tyrosine kinase inhibitor (TKI) targeting anaplastic lymphoma kinase (ALK). A 53-year-old never-smoking woman with ALK-positive non-small cell lung cancer (NSCLC) developed mediastinal lymph node and brain metastases after curative surgery. Alectinib therapy achieved sustained systemic and intracranial disease control for nearly 3 years without serious adverse events. However, 3 years and 1 month after initiating alectinib, progressive leukocytosis with marked basophilia and circulating immature myeloid cells was observed. Bone marrow analysis confirmed the diagnosis of CML with BCR-ABL1 fusion. Nilotinib was initiated while alectinib was continued, resulting in a rapid hematologic response without serious adverse events. Further accumulation of cases is needed to clarify the potential leukemogenic risk of ALK-TKIs and to establish the safety and clinical utility of combined ALK-TKI and BCR-ABL-TKI therapy.

Intense bowel activity on 99mTc-MDP bone scintigraphy is often dismissed as urinary contamination or radiopharmaceutical instability, but persistent uptake should prompt an anatomic search. A 68-year-old woman with metastatic cervical squamous cell carcinoma after radical pelvic surgery underwent bone scintigraphy for suspected left-foot metastasis. Images showed sacral/pelvic metastases, benign-appearing calcaneal uptake, and organized colonic activity. Contrast-enhanced CT revealed a complex fistulous tract connecting the left distal ureter, vaginal stump, rectum, and sigmoid colon. Follow-up pelvic SPECT/CT localized persistent activity to the rectosigmoid lumen, confirming fistula-related intraintestinal urine. Recognition redirected interpretation from artifact to actionable urinary-enteric fistula with clinical implications.

We present a 55‑year‑old woman with adnexal masses and elevated CEA. Malignancy workup, adnexal biopsy, and intraoperative assessment revealed the appendix as the primary site, with pathology confirming mucinous adenocarcinoma. While mucinous tumors often show limited avidity on 18F‑FDG PET/CT due to low cellularity, this case demonstrates the utility of fibroblast activation protein inhibitor (FAPI) imaging. 99mTc‑FAPI SPECT/CT successfully identified widespread skeletal metastases, initially detected on bone scan, and extensive soft‑tissue involvement in the peritoneum, appendiceal region, and pleura, highlighting its potential as a superior staging modality for mucinous neoplasms and suggesting the feasibility of FAPI‑targeted theranostics in advanced disease.