Search Results (173)

Background/Objectives: Anaplastic lymphoma kinase (ALK) fusion is a driver gene translocation detected in 3–5% of patients with non-small-cell lung cancer (NSCLC). Next-generation sequencing (NGS)-based tests are the standard of care for detecting actionable gene alterations; however, false negatives remain a concern. Immunohistochemical staining is another reliable, rapid, and low-cost method for detecting ALK fusions. Previous studies have reported high concordance with NGS, although further studies are needed to draw definitive conclusions. Methods: A retrospective analysis was conducted on consecutive patients with NSCLC who were tested using the Oncomine Dx Target Test (ODxTT), an amplicon-based DNA and RNA NGS test for NSCLC, and ALK-immunohistochemistry (IHC) at our institution between 8 August 2019 and 11 April 2025. Results: Of 919 eligible patients included in this study, ALK fusion was detected in 30 (3.26%) patients, whereas ALK-IHC was positive in 35 (3.80%) patients. The concordance and κ coefficient of the two tests were 99.4% and 0.920, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of ALK-IHC for ODxTT were 100%, 99.4%, 85.7%, and 100%, respectively. Five discordant patients were NGS negative and IHC positive. Among the five discordant cases, one had a false-negative NGS result, whereas the remaining four had false-positive ALK-IHC results, including three patients with neuroendocrine carcinomas. Conclusions: ALK-IHC shows diagnostic accuracy comparable to ODxTT, although prudent interpretation is needed for patients without adenocarcinoma. Our findings suggest the complementary role of ALK-IHC alongside NGS-based testing, particularly in patients with a high pre-test probability of harbouring ALK fusions. Full article

Breast implants are among the most frequently used long-term implantable medical devices in aesthetic and reconstructive surgery. In addition to correcting anatomical deficits, they have significant psychosocial effects, influencing body image, self-esteem, and quality of life, particularly in patients undergoing postmastectomy reconstruction. This review provides a comprehensive overview of the historical development, biological interactions, material characteristics, and clinical outcomes of breast implants. Early reconstructive attempts using foreign materials and injectable substances were associated with severe complications, underscoring the need for safer technologies. The introduction of silicone gel implants in the 1960s marked a pivotal advancement, followed by the development of saline-filled devices and highly cohesive silicone gels with enhanced mechanical stability. Key surgical considerations, including incision type and implant placement plane (subglandular, submuscular, dual-plane, and subfascial), are discussed in relation to aesthetic outcomes and complication risk. Emphasis is placed on the implant–tissue interface and the foreign body response (FBR), a process involving protein adsorption, immune cell activation, fibrous capsule formation, and potential chronic inflammation. Persistent inflammatory stimulation, often associated with bacterial biofilm formation, contributes to capsular contracture, the most common long-term complication. Additional adverse events include implant rupture, silicone gel bleed, granulomatous reactions, infection, hematoma, implant malposition, and rare but clinically significant conditions such as breast implant-associated anaplastic large cell lymphoma (BIA-ALCL). The review also summarizes implant classification according to construction, filling material, shape, and surface topography, highlighting the influence of surface characteristics on host response and clinical outcomes. Advances in biomaterials, cohesive gel formulations, and surface engineering aim to enhance biocompatibility and long-term safety, supported by standardized mechanical and biological testing protocols. Full article

Background and Clinical Significance: Primary cutaneous anaplastic large cell lymphoma (C-ALCL) is a CD30-positive T-cell lymphoproliferative disorder that can clinically resemble various non-melanoma skin cancers, making diagnosis challenging. Although histopathology remains the diagnostic gold standard, non-invasive imaging modalities such as dermoscopy and reflectance confocal microscopy (RCM) are increasingly used as complementary tools to support the differential diagnosis. To date, no data on RCM features of C-ALCL have been described. Case Presentation: We report the case of an 80-year-old man presenting with a rapidly enlarging nodule on the lateral aspect of his right eyelid, providing a detailed account of dermoscopic and RCM findings integrated with clinicopathological correlation. Dermoscopy revealed a red-orange homogeneous background with white streaks, and polymorphic vascular structures, while subsequent RCM (Vivascope 3000 probe) demonstrated marked architectural disarray of the epidermis and dermoepidemal junction, with prominent epidermal involvement characterized by aggregates of highly reflective cells. In the absence of alternative diagnostic patterns, these features raised suspicion for a cutaneous lymphoproliferative disorder, which was later confirmed by histopathological and immunohistochemical analyses. Conclusions: Our findings support the value of RCM as a practical tool in guiding differential diagnosis and biopsy, particularly for rapidly growing lesions located in anatomically sensitive areas. Full article

Background: Anaplastic large cell lymphoma (ALCL) accounts for up to 15% of all pediatric and adolescent non-Hodgkin lymphomas and is characterized by significant clinical, morphological, and immunohistochemical heterogeneity. Expression of T-cell markers on tumor cells is considered as one of the factors in an unfavorable prognosis in ALCL. However, no treatment protocols based on ALCL immunological heterogeneity have been used, yet. Objective: To compare the effectiveness of immunophenotype-oriented chemotherapy in children with ALCL treated according to the ALCL NII DOiG 2003 protocol versus the standard NHL-BFM 95 protocol. Methods: A retrospective–prospective analysis of 100 newly diagnosed ALCL patients, who were treated between 2000 and 2023, was performed across five pediatric oncology and hematology centers in Russia. Patients were divided into two groups: those treated with the NHL-BFM 95 protocol (n = 52) and those treated with the ALCL NII DOiG 2003 protocol (n = 48). Comparative analysis used Kaplan–Meier survival curves constructed for each group, and statistical analysis was performed with IBM SPSS Statistics 21.0. Results: The 10-year overall survival was significantly higher in the ALCL NII DOiG 2003 group (95.3 ± 3.3%) compared to that of the NHL-BFM 95 group (82.0 ± 5.4%, p = 0.037). Event-free survival was also improved (95.3 ± 3.3% vs. 68.6 ± 6.5%, p = 0.001), as well as the relapse-free survival (97.3 ± 2.7% vs. 74.4 ± 6.4%, p = 0.003). Conclusions: The immunophenotype-oriented approach of the ALCL NII DOiG 2003 protocol provides significantly improved long-term outcomes compared to the common NHL-BFM 95. These findings support the benefit of personalized immunologically targeted therapy in pediatric ALCL treatment. Full article

Primary cutaneous anaplastic large cell lymphoma (pcALCL) is a type of cutaneous T-cell lymphoma (CTCL) classified as a CD30+ lymphoproliferative disorder along with lymphomatoid papulosis. Although it is the second most common subtype of CTCL after mycosis fungoides/Sézary syndrome, it remains rare, with an incidence of fewer than 0.5 cases per million person-years. Despite its histologic similarity to systemic anaplastic large cell lymphoma, pcALCL follows a largely indolent course with excellent outcomes, with disease-specific survival rates of 86–95% in contemporary series. This narrative review summarizes the clinical presentation, diagnostic evaluation, and management of pcALCL based on a semi-structured literature search, with emphasis on prospective studies and clinically relevant retrospective data. Diagnosis remains challenging due to overlap with other CD30-positive lymphoproliferative disorders and reactive conditions, requiring careful clinicopathologic correlation and exclusion of systemic disease. While regional lymph node involvement may be present, available evidence suggests it does not significantly impact prognosis, highlighting the importance of avoiding overtreatment. Management strategies are guided by disease extent, with strong evidence supporting skin-directed therapies, particularly radiation, for localized disease. For multifocal or relapsed disease, brentuximab vedotin demonstrates the most robust prospective data and has reshaped the treatment landscape; however, alternative systemic therapies, including methotrexate and retinoids, remain relevant in selected patients. Overall, current management is supported largely by non-randomized data, and key gaps remain in risk stratification, optimal sequencing of therapies, and management of uncommon aggressive variants. Full article

Classic Hodgkin lymphoma (cHL) is a distinctive B-cell malignancy defined by the presence of scarce but pathobiologically dominant Hodgkin Reed-Sternberg (HRS) cells within an inflammatory tumor microenvironment (TME). Although representing less than 10% of total tumor cellularity, HRS cells shape the TME by recruiting and functionally polarizing immune and stromal elements through cytokine- and chemokine-mediated signaling. Morphologically, HRS cells are large, atypical, often binucleated or multinucleated cells with prominent eosinophilic nucleoli and abundant cytoplasm, giving rise to the classic “owl’s eye” appearance. Distinct morphological variants—including lacunar, mummified, mononuclear, and anaplastic forms—contribute to the histopathologic diversity across cHL subtypes such as nodular sclerosis, mixed cellularity, lymphocyte-rich, and lymphocyte-depleted disease. The immunophenotype of HRS cells is equally characteristic, with strong and uniform CD30 expression, frequent CD15 positivity, reduced expression of B-cell markers (CD20, CD79A/B), and partial retention of PAX5, reflecting profound lineage dysregulation. Aberrant expression of activation markers and immune-evasion molecules, including PD-L1 driven by recurrent 9p24.1 amplification, underscores their capacity for immune escape. Genetically, HRS cells display alterations affecting NF-κB, JAK/STAT, and PI3K/AKT pathways, facilitated by somatic mutations, chromosomal gains, and epigenetic remodeling that silence B-cell-defining genes. Despite reprogramming, clonality and somatic hypermutation patterns confirm their origin from germinal center B-cells, even in EBV-associated cases. Collectively, the morphology, phenotype, and genotype of HRS cells reveal a complex pathogenic network in which intrinsic oncogenic pathways and extrinsic TME interactions co-operate to sustain malignant transformation. Understanding these integrated mechanisms provides a biological foundation for current therapeutic strategies. Full article

Objective: Primary extranodal lymphomas of the head and neck region are relatively rare and represent a biologically distinct subset. The diagnosis and differential diagnosis of head and neck lymphomas are important and deserve special attention. The aim of the present study was to retrospectively evaluate patients diagnosed with primary head and neck lymphomas at the Department of Pathology between January 2020 and January 2026. Histopathological subtypes, localization, relative frequencies, and overall survival were analyzed. Materials and Methods: This retrospective study included 31 cases diagnosed with lymphoma involving the head and neck region. Medical records were reviewed. Histopathological slides were re-evaluated under light microscopy by experienced pathologists. All cases were classified according to the current World Health Organization (WHO) classification of tumors of hematopoietic and lymphoid tissues. An extensive immunohistochemical panel was applied. Statistical analysis was performed using SPSS statistical software (version 27.0; IBM Corp., Armonk, NY, USA). Results: The study group included 31 patients with head and neck lymphoma. The most common histological type was diffuse large B-cell lymphoma (DLBCL) (54.8%). Other histological subtypes included follicular lymphoma (FL), mantle cell lymphoma (MCL), extranodal NK/T-cell lymphoma (NKTCL), anaplastic large cell lymphoma (ALCL), and Hodgkin lymphoma (HL). The most common location was the tonsil (38.7%). Other locations included the nasopharynx, oral cavity, nasal cavity, salivary glands, and thyroid. Epstein–Barr virus (EBV) positivity was detected in two patients (6.5%), and human immunodeficiency virus (HIV) infection was identified in two patients (6.5%). At the time of the last follow-up, 27 patients (87.1%) were alive, whereas four patients (12.9%) had died. The mortality rate was 12.9%. The median overall survival was 28 months (95% CI: 10–45). Conclusions: Malignant lymphoma should be considered when evaluating head and neck masses, and histopathological assessment of the affected tissue remains the cornerstone of diagnosis. Full article

Background/Objectives: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is the sentinel implant-associated malignancy, illustrating how long-lived biomaterials can reshape local tissue–immune ecology. Although textured (high-surface-area) implants show the strongest epidemiologic association, the rarity of disease despite widespread exposure suggests additional host modifiers. We synthesize evidence supporting a gene–environment (G × E) framework and critically appraise emerging host-susceptibility signals (including BRCA1/BRCA2 and HLA associations). Methods: We conducted a narrative, evidence-based synthesis of peer-reviewed epidemiologic and registry studies, peri-implant niche biology (biofilm/foreign-body response and cytokine milieu), tumor genomic profiling, and current guidelines/regulatory communications, prioritizing primary studies for key claims. Results: Textured exposure dominates risk attribution, whereas absolute-risk estimates vary with denominators, exposure ascertainment, and follow-up duration. Mechanistic studies support a chronically inflamed capsule niche. Genomic analyses repeatedly converge on JAK/STAT pathway activation with frequent co-alterations in epigenetic regulators and recurrent copy-number changes, consistent with stepwise evolution under sustained selection. Immune-evasion features—including frequent PD-L1 expression and CD274 (9p24.1) copy-number alterations—provide a plausible checkpoint route, while host-susceptibility signals remain preliminary and require multi-center, multi-ancestry replication. Conclusions: BIA-ALCL is a multistep, context-dependent lymphoma in which implant-mediated inflammation intersects with host susceptibility to enable somatic evolution and immune escape. Clinically, prevention currently relies on exposure mitigation, standardized risk communication, and symptom-driven evaluation; precision prevention will require integrative cohorts linking verified device exposure, immunogenetics, microenvironment profiling, and tumor multi-omics. Full article

T-cell malignancies represent a complex spectrum of clinically and biologically heterogeneous diseases. Effective translational research and drug development are critically dependent on preclinical models that faithfully recapitulate this diversity. This review analyzes the current preclinical landscape, identifying a profound disparity between the clinical spectrum of T-cell neoplasms and the available in vitro tools. We demonstrate that the existing armamentarium of cell lines is heavily skewed, with an abundance of models for T-cell lymphoblastic leukemia/lymphoma (T-ALL), cutaneous T-cell lymphoma (CTCL), and anaplastic large cell lymphoma (ALCL). This skew is a direct result of a biological selection bias, as these entities are often driven by potent, TME-independent oncogenes (e.g., NOTCH1 mutations, NPM1-ALK fusions) conducive to immortalization. Conversely, the majority of peripheral T-cell lymphoma (PTCL) subtypes, which are frequently TME-dependent and clinically aggressive, remain “preclinical orphans” with few or no authenticated models. This “preclinical void” constitutes a major bottleneck, impeding mechanistic studies and therapeutic progress. We discuss the limitations of 2D cultures and highlight the necessity of adopting advanced platforms, such as patient-derived xenografts (PDX) and 3D organoid systems. These “avatar” models preserve vital tumor heterogeneity and microenvironmental context, offering superior predictive value. The systematic development and integration of these next-generation models are essential to bridge the translational gap and advance precision medicine for all patients with T-cell malignancies. Full article

Background: Primary cutaneous B-cell lymphomas (CBCLs) are a rare and heterogeneous group of lymphomas, among which the anaplastic variant of diffuse large B-cell lymphoma (A-DLBCL) represents an exceptionally rare entity. Although they typically present as painless and non-ulcerated skin lesions, rare variants may exhibit atypical clinical features. Pyoderma gangrenosum (PG) is a rare inflammatory ulcerative disease that may overlap clinically with other ulcerative dermatoses and pose diagnostic challenges due to the absence of standardized differential algorithms. Methods: An 85-year-old male presented with multiple rapidly progressive, painful, ulcerative lesions, initially misdiagnosed as PG and treated with oral cyclosporine with no clinical response. Skin biopsy specimens underwent detailed histopathological and immunohistochemical evaluation. Results: The analyses revealed dense infiltration of atypical large lymphoid cells, with CD20, CD45, and CD30 positivity, and a Ki-67 proliferation index of approximately 90%, consistent with primary cutaneous A-DLBCL. Owing to the delayed correct diagnosis, the patient’s condition deteriorated rapidly, leading to his death before appropriate therapy could be initiated. Conclusions: The case documents an exceptionally rare cutaneous presentation of A-DLBCL, expanding the extremely limited literature on this enigmatic entity. Furthermore, it underscores the fundamental role of early skin biopsy in the differential diagnosis of non-specific ulcerative lesions, which is critical for ensuring appropriate treatment administration within the therapeutic window in cases of malignancy. Full article

Implant-based breast reconstruction (IBBR) remains the most common form of post-mastectomy reconstruction worldwide, offering patients a reliable and accessible option to restore breast contour. Advances in surgical technique, biomaterials, and implant technology have driven rapid evolution in the field, with the dual goals of improving aesthetic outcomes and minimizing patient morbidity. The prepectoral plane has been popularized due to the eliminated risk of animation deformity and reduced postoperative pain. Some concerns remain regarding mastectomy flap thickness and long-term oncologic and aesthetic outcomes. Concurrently, nipple-sparing mastectomy has improved aesthetic results and enabled surgeons to move beyond just restoring breast form and improve functional recovery as well, as demonstrated by surgical efforts aimed at restoring nipple–areolar complex (NAC) sensation. Adjunctive use of biologic matrices and synthetic meshes has broadened reconstructive options, while next-generation implants seek to further enhance outcomes. Balanced against these innovations are important oncologic and systemic safety concerns, including breast implant-related cancers and the ongoing debate over breast implant illness (BII). This review highlights eight current “hot topics” in implant-based breast reconstruction: (1) prepectoral reconstruction, (2) nipple-sparing mastectomy, (3) oncoplastic techniques, (4) nipple–areolar complex (NAC) neurotization, (5) biologic matrices and synthetic meshes, (6) next-generation implants, (7) optimizing aesthetic outcomes, and (8) implant-associated cancer and systemic concerns. Together, these areas define the current landscape of innovation, controversy, and future directions in implant-based reconstruction. Full article

Background and Objectives: Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL) is a T-cell lymphoma that has shown an interest in the medical community in recent years. Given its emerging clinical relevance, accurate imaging plays a crucial role in diagnosis, staging, and follow-up. This systematic review aims to evaluate the role of Fluorine-18 Fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in the staging and follow-up of patients with BIA-ALCL, focusing on its diagnostic accuracy and clinical impact. Materials and Methods: A systematic search of PubMed and National Center for Biotechnology Information (NCBI) was conducted to identify studies assessing the use of 18F-FDG PET/CT in BIA-ALCL up to and including 15 April 2024, using the following keywords “breast implant-associated anaplastic large cell lymphoma” AND “PET/CT” AND “BIA-ALCL”. Data regarding the role of PET/CT in disease detection, staging, therapeutic guidance, and post-treatment surveillance was analyzed and synthesized in a tabulated format for comparative analysis. Given study heterogeneity, findings were synthesized narratively and diagnostic performance metrics were summarized descriptively, and no formal risk-of-bias assessment was performed due to the descriptive, case-based nature of evidence. Results: A total of 28 studies met the inclusion criteria, comprising 27 individual case reports and one case series that included seven patients. Across these studies, 18F-FDG PET/CT demonstrated diagnostic utility in the evaluation of BIA-ALCL, serving primarily for initial disease staging in 27 cases and for monitoring treatment response in 16 cases. Discussion: The review’s limitations include potential search bias due to variable radiotracer terminology and the restriction to English-language studies, which may limit literature retrieval and generalizability. Conclusions: Thus, 18F-FDG PET/CT demonstrated significant value in early lesion detection, accurate staging, assisting in monitoring treatment response and detecting recurrence. Full article

Background: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a mature T-cell lymphoma linked to textured breast implants. A leading hypothesis suggests that chronic inflammation, combined with immunological and genetic factors, drives its pathogenesis. Two previous studies investigating bacterial biofilms on breast implant capsules have produced conflicting results, particularly regarding the enrichment of Ralstonia spp. Methods: We analyzed the microbiota profiles in seroma samples from 10 BIA-ALCL patients and 12 patients with non-neoplastic effusion, subclassified into acute-, mixed-, and chronic-type based on cellular composition. We used two metagenomic approaches: 16S rRNA gene sequencing and Nanopore sequencing with the “What’s in My Pot?” (WIMP) taxonomic classifier. Our analyses included alpha and beta diversity metrics, as well as comparisons of Gram status and oxygen requirements. Results: Both sequencing methods identified Staphylococcaceae, Propionibacteriaceae, and Bradyrhizobiaceae as the most prevalent bacterial families in both BIA-ALCL and benign seroma samples. Notably, the Burkholderiaceae family was more abundant in some of the benign seromas according to the 16S rRNA sequencing, but Ralstonia spp. were not detected. BIA-ALCL showed higher richness (based on Nanopore data) and higher evenness (based on 16S rRNA data) compared to acute-type seromas, indicating a more homogenous representation of the different taxa identified. BIA-ALCL seromas did not cluster together based on Nanopore data, but they did form a distinct cluster with 16S rRNA data. This cluster was differentiated from the other two clusters by a relatively balanced presence of multiple families without overt dominance. We observed no significant differences in Gram staining between BIA-ALCL and benign samples using either method. However, non-aerobic bacterial families were enriched in BIA-ALCL cases only when analyzed with the Nanopore pipeline. Conclusions: Overall, our findings did not identify a distinctive microbial signature specifically associated with BIA-ALCL. Full article

Background/Objectives: Three-dimensional (3D) in vitro cell culture models have recently stimulated great interest since they may have more pre-clinical value than conventional in vitro 2D models. In fact, 3D culture models may mimic the in vivo biophysical 3D structure of tumors and cell-to-cell interaction, thereby representing a more useful approach to testing drug responses. In this study we have developed a 3D culture model of an EBV+/CD30+cell line, D430B, previously characterized as an Anaplastic Large Cell Lymphoma of B phenotype (B-ALCL), to determine the cytotoxic activity of the antibody–drug conjugate Brentuximab Vedotin. Methods: By using of ultra-low attachment plates, we developed D430B spheroids that appeared particularly homogenous in terms of growth and size. Results: Brentuximab Vedotin treatment (1 to 20 μg/mL) turned out to be significantly cytotoxic to these cells, while the addition of the anti-CD20 chimeric antibody Rituximab (10 μg/mL) appeared almost ineffective, even though these cells express CD20. Moreover, when we co-cultured D430B cells with stromal cells (HS5), to re-create a microenvironment representative of neoplastic cell/mesenchymal cell interactions within the lymph node, we observed a significant, although faint, protective effect. Conclusions: This simple and reproducible method of generating D430B-ALCL spheroids to evaluate their response to Brentuximab Vedotin treatment, as here described, may provide a valuable preliminary tool for the future pre-clinical screening of patients’ primary lymphoma cells or the development of novel therapies for this type of pathology and related diseases. Full article

Combining immune checkpoint inhibitors (ICIs) and anti-angiogenic pharmacologic agents is an encouraging therapeutic approach in the treatment of non-small cell lung cancer (NSCLC). Currently, the only FDA-approved therapy combining an immune checkpoint inhibitor and a vascular endothelial growth factor (VEGF) inhibitor is atezolizumab, bevacizumab, and chemotherapy in first-line metastatic NSCLC patients. However, the combination of nivolumab, a programmed death-1 (PD-1) inhibitor, and bevacizumab has also shown encouraging results in patients with NSCLC with minimal adverse effects, respectively. This communication aims to highlight the efficacy of nivolumab and bevacizumab in NSCLC patients without sensitizing mutations in epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), or ROS proto-oncogene 1 (ROS1). In addition, the combination of nivolumab/atezolizumab and bevacizumab with other therapeutic agents is also discussed. We also underscore the adverse effects and limitations of such combinations in NSCLC patients. Future studies should focus on large-scale trials and biomarker identification to establish the benefits of these combination therapies in NSCLC patients. Full article