With the advent of precision medicine and personalized treatment, targeted therapies have become pivotal in oncology. Noninvasive molecular imaging, especially immunoPET/SPECT, plays a crucial role in refining cancer diagnostics and treatment monitoring by visualizing biological processes at the molecular level. This review explores the dynamic field of immunoPET/SPECT imaging using Fab and F(ab')₂ fragments, characterized by advantageous pharmacokinetics and swift clearance from the bloodstream, making them suitable for same-day imaging procedures. We examine contemporary strategies for radiolabeling these fragments with PET and SPECT radionuclides and discuss potential advancements and the challenges anticipated in the further development of Fab and F(ab')₂ fragments. Despite the complexities involved in their development, these fragments hold significant promise for advanceing personalized cancer treatment. Keys to this advancement are innovative radiolabeling techniques, site-specific conjugation chemistries, and short-lived radionuclides, all of which are crucial for overcoming existing limitations and enhancing the clinical utility of these imaging agents. As research progresses, Fab and F(ab')₂ fragments are expected to become central to the future of cancer diagnostics and therapeutic monitoring, thereby improving patient management and contributing significantly to the evolution of personalized medicine.

Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.
Humans ; Female ; Blood Platelets/pathology* ; Biomarkers, Tumor/genetics* ; Ovarian Neoplasms/pathology* ; China

Objective: To investigate the association between the distribution of tumor infiltrating lymphocytes (TIL) in EBV associated lymphoepitheliomatoid carcinoma (LELC) and the pathological subtypes of LELC, as well as the clinical significance of TIL distribution. Methods: The LELC patients with sufficient tumor tissues, complete clinical data and positive EBER, who visited Zhejiang Cancer Hospital, Hangzhou, China from January 2006 to October 2018, were selected. Various immunohistochemical markers (CD20, CD138, CD4, CD8, CD56 and FOXP3) were examined for TIL typing. Two pathologists reviewed the hematoxylin and eosin (HE) staining sections and interpreted the immunohistochemical results. Correlation analysis was used to evaluate the relationship between the distribution of TIL subgroups and LELC's pathological characteristics. Survival analyses were conducted to study the prognostic values of TIL subgrouping. Results: A total of 102 patients with EBV related LELC were included. 46 of them were classic LELC (c-LELC) with rich interstitial TIL, and 56 were non-classic LELC (n-LELC) with relatively fewer interstitial TIL. The results of TIL analysis showed that all subtypes of c-LELC were rich in TIL, with B lymphocytes as the dominant subgroup. The number of TIL in n-LELC was fewer than that in c-LELC, with T lymphocytes as the dominant subgroup. There was no significant difference in the distribution of plasma cells between the two groups. Survival analysis showed that the total number of TIL, and the infiltrations of CD20⁺B cells, CD4⁺T cells, and FOXP3⁺Treg cells were associated with better overall survivals (P=0.004, 0.003, 0.008 and 0.025, respectively) and disease-free survivals (P=0.011, 0.003, 0.038 and 0.041, respectively) in patients with LELC. Conclusions: The morphologic subtypes of EBV-related LELC have different tumor immune characteristics. The total number of TIL in the stroma of c-LELC is significantly higher than that of n-LELC. Interestingly, B lymphocytes are the dominant TIL in c-LELC, while T lymphocytes are the dominant TIL in n-LELC. The infiltration of TIL, CD20⁺B cells, CD4⁺T cells and FOXP3⁺Treg cells in LELC may suggest a better prognosis.
Humans ; Lymphocytes, Tumor-Infiltrating ; Herpesvirus 4, Human ; Clinical Relevance ; Prognosis ; Carcinoma, Squamous Cell/pathology* ; Forkhead Transcription Factors

Humans ; Lung Neoplasms/pathology* ; Adenocarcinoma/pathology* ; Papilloma/genetics* ; Receptor, Fibroblast Growth Factor, Type 1/metabolism* ; Gene Amplification ; Carrier Proteins ; Cytoskeletal Proteins

Objective: To investigate the evolution and clinical significance of HER2 low expression status in HER2 negative patients in primary and recurrent/metastatic breast cancers. Methods: The data and archived sections of 259 breast cancer patients with recurrence/metastasis and HER2-negative primary foci were collected from January 2015 to January 2022 at the Fourth Hospital of Hebei Medical University, and the HER2 status of primary and recurrence/metastasis foci was determined by immunohistochemistry (IHC), among which IHC 2+patients were subject to fluorescence in situ hybridization (FISH). The HER2 status was classified as HER2-0 group; patients with IHC 1+, IHC 2+and no FISH amplification were classified as HER2 low expression group; and patients with IHC 3+, IHC 2+and FISH amplified were classified as HER2-positive group. The changes of HER2 status in patients with HER2 low expression in primary versus recurrent/metastatic breast cancer foci were compared, and their clinicopathologic characteristics and prognosis were analyzed. Results: The overall concordance rate between primary and recurrent/metastatic HER2 status in breast cancer was 60.6% (157/259, κ=0.178). A total of 102 patients (102/259, 39.4%) had inconsistent primary and recurrent/metastatic HER2 status; 37 patients (37/259, 14.3%) had HER2-0 at the primary foci and HER2-low expression at the recurrent/metastatic; and 56 patients (56/259, 21.6%) had HER2-low expression in the primary foci and HER2-0 in the recurrent/metastatic. The recurrent/metastatic foci became low-expressing compared with the recurrent/metastatic foci which remained HER2-0 patients, with longer overall survival time, higher ER and PR positivity, lower Ki-67 positivity index, and lower tumor histological grade; all with statistically significant differences (all P<0.05). In the primary HER2-low group, patients with recurrent/metastatic foci became HER2-0 while those with recurrent/metastatic foci remained low expression; there were no statistically significant differences in clinicopathological features and overall survival time (all P>0.05). Conclusions: Unstable HER2 status in patients with HER2-0 and low expression in primary versus recurrent/metastatic breast cancer foci, and HER2-0 in the primary foci but low HER2 expression status in recurrence/metastasis is associated with favourable prognosis, and testing HER2 status in recurrence/metastasis can provide more treatment options for such patients.
Humans ; Breast Neoplasms/genetics* ; Clinical Relevance ; In Situ Hybridization, Fluorescence ; Female

Objective: To investigate the clinicopathological features and molecular genetics of diffuse large B-cell lymphomas (DLBCL) with concurrent or secondary to nodal T-follicular helper cell lymphoma, angioimmunoblastic-type (nTFHL-AI). Methods: The clinicopathological features and molecular genetics of DLBCL associated with nTFHL-AI diagnosed between January 2015 and October 2022 at the First Affiliated Hospital of Zhengzhou University were analyzed using histology, immunohistochemistry, PCR, EBV-encoded RNA in situ hybridization and fluorescence in situ hybridization (FISH). Clinical information was collected and analyzed. Results: A total of 6 cases including 3 nTFHL-AI with secondary DLBCL and 3 composite lymphomas were reviewed. There were 4 male and 2 female patients, whose ages ranged from 40 to 74 years (median 57 years). All patients presented with nodal lesions at an advanced Ann Arbor stage Ⅲ/Ⅳ (6/6). Bone marrow involvement was detected in 4 patients. All cases showed typical histologic and immunophenotypic characteristics of nTFHL-AI. Among them, 5 cases of DLBCL with concurrent nTFHL-AI exhibited numerous large atypical lymphoid cells and the tumor cells were CD20 and CD79α positive. The only case of DLBCL secondary to nTFHL-AI showed plasma cell differentiation and reduced expression of CD20. All of cases were activated B-cell (ABC)/non-germinal center B-cell (non-GCB) subtype. Three of the 6 cases were EBV positive with>100 positive cells/high power field, meeting the diagnostic criteria of EBV⁺DLBCL. The expression of MYC and CD30 protein in the DLBCL region was higher than that in the nTFHL-AI region (n=5). C-MYC, bcl-6 and bcl-2 translocations were not detected in the 4 cases that were subject to FISH. Four of the 6 patients received chemotherapy after diagnosis. For the DLBCL cases of nTFHL-AI with secondary DLBCL, the interval was between 2-20 months. During the follow-up period ranging from 3-29 months, 3 of the 6 patients died of the disease. Conclusions: DLBCL associated with nTFHL-AI is very rare. The expansion of EBV-infected B cells in nTFHL-AI may progress to secondary EBV⁺DLBCL. However, EBV-negative cases have also been reported, suggesting possible other mechanisms. The up-regulation of MYC expression in these cases suggests a possible role in B-cell lymphomagenesis. Clinicians should be aware that another biopsy is still necessary to rule out concurrent or secondary DLBCL when nodal and extranodal lesions are noted after nTFHL-AI treatment.
Female ; Male ; Humans ; In Situ Hybridization, Fluorescence ; Lymphoma, Large B-Cell, Diffuse ; B-Lymphocytes ; Biopsy ; T-Lymphocytes, Helper-Inducer

Humans ; Kidney/pathology*

Objective: To investigate the clinicopathological features of glomuvenous malformation (GVM). Methods: Thirty-one cases of GVM diagnosed at the Henan Provincial People's Hospital from January 2011 to December 2021 were collected. Their clinical and pathological features were analyzed. The expression of relevant markers was examined using immunohistochemistry. The patients were also followed up. Results: There were 16 males and 15 females in this study, with an average age of 11 years (range, 1-52 years). The locations of the disease included 13 cases in the limbs (8 cases in the upper limbs, 5 cases in the lower limbs), 9 cases in the trunks, and 9 cases in the foot (toes or subungual area). Twenty-seven of the cases were solitary and 4 were multifocal. The lesions were characterized by blue-purple papules or plaques on the skin surface, which grew slowly. The lumps became larger and appeared to be conspicuous. Microscopically, GVM mainly involved the dermis and subcutaneous tissue, with an overall ill-defined border. There were scattered or clustered irregular dilated vein-like lumens, with thin walls and various sizes. A single or multiple layers of relatively uniform cubic/glomus cells were present at the abnormal wall, with scattered small nests of the glomus cells. The endothelial cells in the wall of abnormal lumen were flat or absent. Immunohistochemistry showed that glomus cells strongly expressed SMA, h-caldesmon, and collagen IV. Malformed vascular endothelial cells expressed CD31, CD34 and ERG. No postoperative recurrence was found in the 12 cases. Conclusions: GVM is an uncommon type of simple venous malformation in the superficial soft tissue and different from the classical glomus tumor. Morphologically, one or more layers of glomus cells grow around the dilated venous malformation-like lumen, which can be combined with common venous malformations.
Male ; Female ; Humans ; Child ; Glomus Tumor/surgery* ; Endothelial Cells/pathology* ; Paraganglioma, Extra-Adrenal/pathology* ; Immunohistochemistry

Humans ; Lymphoma, Large-Cell, Anaplastic/pathology* ; Receptor Protein-Tyrosine Kinases ; Anaplastic Lymphoma Kinase ; Central Nervous System/pathology*

Humans ; Neoplasms/genetics* ; Nuclear Proteins ; Co-Repressor Proteins ; Cell Line, Tumor ; Molecular Chaperones