Breast cancer is the most commonly diagnosed malignancy among women worldwide. While survival outcomes have improved substantially over time, recurrence remains a significant concern, especially in estrogen receptor-positive (ER⁺) disease. Although most recurrences occur within five years of initial treatment, ER⁺ tumors carry a persistent risk of late relapse due to tumor dormancy. Very late recurrences occurring decades after remission are rare and poorly characterized.

We present the case of a 96-year-old female with a history of right-sided breast cancer treated with mastectomy and adjuvant radiation therapy at age 50, who presented 46 years later with a palpable chest wall mass near her prior mastectomy scar. Imaging revealed an irregular hypoechoic lesion extending into the pectoralis muscle (BIRADS-5). Core biopsy demonstrated moderately differentiated infiltrating lobular carcinoma that was strongly ER+, progesterone receptor-negative, and HER2 non-amplified. Staging studies revealed no evidence of distant metastatic disease. Given the patient's advanced age, comorbidities, and prior radiation exposure, surgical and radiation approaches were deferred. Following multidisciplinary tumor board discussion and shared decision-making, primary endocrine therapy with tamoxifen was initiated. The patient demonstrated clinical regression within three months and tolerated therapy well.

This case represents one of the longest reported intervals between initial remission and breast cancer recurrence, highlighting the prolonged biologic potential of dormant ER-positive tumor cells. Clinicians should maintain vigilance for recurrence even decades after treatment, particularly in hormone receptor-positive disease.

T-cell immunoreceptor with immunoglobulin (Ig) and immunoreceptor tyrosine-based inhibitory motif (ITIM) domains (TIGIT) is an immune checkpoint receptor involved in the immune evasion of malignant cells and a putative target for novel immunotherapies. TIGIT is expressed by tumor microenvironment (TME) cells in various types of lymphomas, including classical Hodgkin lymphoma (cHL). However, the TIGIT expression patterns in cHL and their relationship with clinical and laboratory parameters require further elucidation.

We studied the immunohistochemical expression patterns of TIGIT in tissue sections from 55 patients diagnosed with cHL.

TIGIT was not expressed by Hodgkin and Reed-Sternberg (HRS) cells but was expressed in the TME cells of 45/55 (81.8%) cases. Using 10% as a threshold for positivity, TIGIT was expressed in the TME cells in 33/55 (60%) cases. Rosettes of TIGIT-positive TME cells around HRS cells were detected in 12/55 cases (21%). While TIGIT expression patterns showed no association with clinical outcomes, established laboratory parameters such as β2-microglobulin demonstrated a significant impact on overall survival. In summary, cHL exhibits frequent but highly variable TIGIT expression patterns in TME cells.

These findings further support the concept of biological heterogeneity of cHL and encourage further studies assessing the role of TIGIT as a potential target for immunotherapy in cHL.

Irisin, a myokine released during physical activity, has been proposed as a mediator of exercise's protective effects against breast cancer (BC). This review underscores the critical role of irisin in mediating the anticancer effects of exercise and its potential application in BC prevention and prognosis.

Studies published up to 2025 were identified in PubMed, Scopus, and Web of Science databases. Data from experimental models, clinical trials, and observational studies were analyzed with emphasis on exercise-induced irisin secretion and its effects on cancer-related pathways.

Irisin, derived from the precursor FNDC5 upon PGC-1α activation in skeletal muscle, regulates cancer-associated pathways by activating AMP-activated protein kinase (AMPK), inhibiting mammalian target-of-rapamycin (mTOR), modulating phosphoinositide 3-kinase (PI3K)/Akt and nuclear factor kappa B (NF-κB) signaling, and influencing transforming growth factor beta (TGF-β) activity. These actions reduce chronic inflammation, tumor proliferation, angiogenesis, and epithelial-mesenchymal transition, while enhancing apoptosis and metabolic balance. Preclinical studies demonstrate irisin's capacity to limit BC cell viability, migration, and metastasis. Clinically, higher circulating irisin levels correlate with reduced tumor aggressiveness, fewer metastases, and better survival, though tumor may overexpress irisin as a local adaptive response. Regular moderate physical activity appears most effective in stimulating irisin secretion, although optimal exercise parameters remain to be determined.

Irisin exerts multifaceted anticancer effects and holds promise as a biomarker and therapeutic target in BC. Its role as a mediator of exercise benefits supports the inclusion of regular moderate physical activity in BC prevention and prognosis strategies. Further research is needed to define clinical applications and optimal exercise regimens for maximizing irisin potential.

Angioimmunoblastic T-cell lymphoma (AITL) is a rare peripheral T-cell lymphoma characterized by diverse and aggressive clinical manifestations that frequently mimic autoimmune disorders. Cutaneous presentations are common and may lead to diagnostic delay.

A 67-year-old woman first presented with non-blanchable skin rash, with normal platelet count and negative autoimmune markers. The rash improved with corticosteroids but recurred two months later, accompanied by fever, night sweats, limb edema, diarrhea, and cervical lymphadenopathy. Skin biopsy reported vasculitis and panniculitis, as direct immunofluorescence was compatible with IgA vasculitis. Subsequent laboratory tests revealed atypical lymphocytes, Coombs-positive anemia, thrombocytopenia, and detected Epstein-Barr virus DNA. Computed tomography showed new splenomegaly and periaortic lymphadenopathy. Lymph node biopsy confirmed AITL. Although CHOP chemotherapy was planned after staging, the patient rapidly deteriorated and died of septic shock. Serial peripheral blood flow cytometry at admission, post-splenectomy, and follow-up showed dynamic immunophenotypic changes: reductions in exhaustion and senescence markers as well as activated regulatory T cells after splenectomy; and later upregulation of exhaustion markers on naïve T cells.

This case illustrates the misleading presentation as immunoglobulin A (IgA) vasculitis and rapid progression of AITL. While vasculitis is accompanied by cytopenia, lymphadenopathy, or aggressive clinical course, early lymph node biopsy is essential for timely diagnosis.

Although immune checkpoint inhibitors (ICIs) can be remarkably effective in the treatment of unresectable recurrent or metastatic carcinoma of the head and neck, even in cases of a marked response, some lesions may remain partially refractory or new lesions may emerge. However, why ICIs sometimes produce such a patchy pattern of therapeutic effects remains unclear.

A 62-year-old patient with advanced hypopharyngeal squamous cell carcinoma who developed pulmonary metastasis after surgery followed by postoperative chemoradiotherapy presented to our department. After initiating ICI therapy, the patient initially achieved complete remission; however, a new pulmonary lesion subsequently appeared and was surgically removed. The patient has since remained in durable remission with continued long-term ICI therapy. Immunohistochemical analysis comparing the new pulmonary lesion with the original hypopharyngeal tumor revealed that cancer cells in the primary lesion were positive for HLA class I and b2-microglobulin, whereas staining for these antigens was negative in cancer cells of the recurrent pulmonary lesion. Cancer cells in the primary lesion exhibited ectopic expression of HLA class II, but no expression was detected in cancer cells of recurrent lesions.

In the pulmonary lesion that did not respond to ICIs, a loss of HLA class I and b2-microglobulin expression was observed. These findings suggest that the reduced antigen-presenting capacity of cancer cells may contribute to immune escape.

Statins, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, have been reported to exert anti-cancer effects. Recently, sterol regulatory element-binding protein 2 (SREBP2) has been shown to be involved in statin resistance in cancer cells. Inhibiting SREBP2 enhances the anti-cancer effects of statins in several cancer cell lines. Three-dimensional (3D) cultured cells are known to exhibit different drug sensitivities compared to two-dimensional (2D) cultured cells. In this study, we evaluated the cytotoxicity induced by combined treatment with atorvastatin and SREBP2 inhibitors in 2D and 3D cultured colorectal cancer (CRC) cells.

25-Hydroxycholesterol and δ-tocotrienol were used as SREBP2 inhibitors. The viability of 2D and 3D cultured cells was measured using the MTT assay and the CellTiter-Glo^® 3D Cell Viability Assay. Gene expression levels were analyzed by qRT-PCR. Protein levels were determined by western blotting.

3D cultured cells exhibited lower statin sensitivity compared to 2D cultured cells. The expression levels of SREBP2 and its target genes differed between 2D and 3D cultured cells. In 2D cultured cells, SREBP2 inhibitors blocked atorvastatin-induced SREBP2 activation and enhanced the cytotoxicity of atorvastatin. However, in 3D cultured cells, SREBP2 inhibitors failed to enhance atorvastatin-induced cytotoxicity, although they successfully suppressed atorvastatin-induced SREBP2 activation.

The efficacy of a combined statin and SREBP2 inhibitors strategy differs substantially between 2D and 3D cultured CRC cells. 3D cultured cells may possess an SREBP2-independent mechanism of statin resistance that differs from that of 2D cultured cells.

Cancer cell plasticity is tightly linked to therapeutic resistance in urothelial carcinoma (UC). Signal transducer and activator of transcription 3 (STAT3) and CD44 play crucial roles in plasticity, but their potential crosstalk in the therapeutic context has not yet been fully elucidated. This study aimed to unveil the shared and distinct roles of STAT3 and CD44 and obtain a better understanding of targeted therapy in UC.

T24 bladder cancer cells were genetically ablated for STAT3 and CD44 and their plasticity was subsequently assessed. Phosphorylated-STAT3 (pSTAT3) and CD44 expression was determined using tissue microarrays in 16 patients who received pembrolizumab therapy for UC, and the association of their expression levels with patient prognosis was investigated.

Ablation of STAT3 or CD44 expression resulted in the dysregulation of vimentin expression and promotion of cell spheroid viability. Patients with imbalanced pSTAT3 and CD44 expression had significantly shorter progression-free survival and overall survival.

Functional imbalance of STAT3 and CD44 may promote cancer cell plasticity and result in impaired pembrolizumab response in patients with advanced UC.

Ovarian metastases from colorectal carcinoma (CRC) are rare but have significant clinical implications, often resembling primary ovarian tumors. An incorrect diagnosis can result in delayed systemic therapy and surgical planning.

A 56-year-old postmenopausal woman presented with right lower quadrant pain and postmenopausal bleeding. Pelvic ultrasound and computed tomography (CT) scans demonstrated a large, complex adnexal mass with thickening of the ascending colonic wall. She underwent diagnostic laparoscopy and subsequent total abdominal hysterectomy with bilateral salpingo-oophorectomy, omentectomy, tumor debulking, and right hemicolectomy. The postoperative pathology revealed a moderately differentiated adenocarcinoma of the cecum, with bilaterally metastatic involvement of the ovaries, omentum, peritoneal surfaces, and liver serosa. Immunohistochemistry confirmed the colonic origin (CDX2⁺, CK20⁺, CK7^-). She was diagnosed with stage IVc (pT4aN2aM1c) colon adenocarcinoma and subsequently started on systemic treatment with mFOLFIRINOX with bevacizumab.

This case highlights the diagnostic challenge of distinguishing between primary ovarian carcinoma and metastatic colorectal adenocarcinoma, underscoring the need for multidisciplinary collaboration and immunohistochemical confirmation to inform treatment decisions.

Extracellular vesicles (EVs), including exosomes, are abundant in body fluids, and EV surface proteins can be profiled as potential minimally invasive biomarkers. CD147 (EMMPRIN/Basigin) is a tumor-associated surface glycoprotein implicated in cancer progression. CD9 and CD63 are tetraspanin membrane proteins widely used as EV markers. The present study aimed to evaluate the clinical significance of serum EV subsets double-positive for CD9 and CD63, or for CD9 and CD147 in patients with colorectal cancer (CRC) before and after tumor resection.

Sixteen patients with CRC were recruited, and paired pre- and postoperative serum samples were analyzed for CD9⁺ CD63⁺ EVs and CD9⁺ CD147⁺ EVs. Serum EVs were quantified using the ExoCounter system with antibody-conjugated beads. CD147 expression in resected tumor tissue was analyzed by immunohistochemistry.

CD9⁺ CD63⁺ EVs were significantly reduced in postoperative samples compared with preoperative samples (p=0.0151). CD9⁺ CD147⁺ EVs also showed a significant postoperative decrease (p=0.0186). CD147 immunostaining was positive in 13 out of 16 resected tumors (81.3%). In patients with CD147 negative tumors (n=3), serum CD9⁺ CD147⁺ EV levels were low at both pre- and postoperative time points and remained unchanged.

Serum CD9⁺ CD63⁺ and CD9⁺ CD147⁺ EV subsets decreased after CRC surgery, supporting their potential utility as minimally invasive liquid biopsy biomarkers of postoperative tumor burden. Future prospective clinical trials will determine whether these EV subsets are indeed biomarkers of postoperative residual tumor.

Ovarian Sertoli cell tumors (SCTs) are a rare subgroup of gonadal ovarian neoplasms. They typically occur in young patients and are usually benign. We present a case report of an elderly patient with uterine maldevelopment in whom a gigantic ovarian SCT was diagnosed.

A 62-year-old woman presented to the emergency department for treatment of a lower limb infection. She additionally reported abdominal girth, loss of appetite, and a sensation of epigastric fullness. Physical examination revealed an abdominal mass. Imaging showed a massive tumor measuring approximately 19.0×12.0×19.0 cm. Initial differential diagnosis included uterine fibroid or ovarian teratoma. Laparotomy was performed, during which a normal uterus was not identified. The excised tumor had a smooth capsule, a solid lobulated structure, and a grayish-yellow color with fine calcifications. Peritoneal fluid obtained at surgery contained no malignant cells. Follow-up at 16 months showed no clinical or radiological evidence of recurrence. The patient's follow-up is ongoing.

This case underscores the importance of including rare ovarian tumors in the differential diagnosis of pelvic masses, particularly in patients with congenital reproductive tract anomalies.