[This retracts the article DOI: 10.1007/s12253-018-0400-1.].

Pancreatic amphicrine-like carcinoma (ALC) is an exceptionally rare neoplasm characterized by simultaneous exocrine and endocrine differentiation within the same tumour cells. These tumours represent a diagnostic challenge because they must be distinguished from mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs), which consist of morphologically distinct tumour components. We report a case of pancreatic ALC with acinar differentiation harboring a KANK4::RAF1 fusion identified by comprehensive genomic profiling. Histologically, the tumour demonstrated acinar differentiation with expression of trypsin and BCL10 together with neuroendocrine differentiation characterized by synaptophysin and INSM1 expression within the same neoplastic population. Molecular analysis revealed a RAF1 rearrangement, a potentially actionable alteration previously described in a subset of pancreatic acinar carcinomas. The patient showed rapid disease progression despite systemic chemotherapy. Treatment with the MEK inhibitor trametinib was initiated based on the presence of a RAF1 fusion but was discontinued after 1 month because of toxicity, preventing assessment of therapeutic efficacy. This case expands the molecular spectrum of pancreatic ALC with acinar differentiation and highlights the importance of comprehensive molecular profiling in rare pancreatic neoplasms to identify potentially actionable genomic alterations.

Head and neck squamous cell carcinomas (HNSCCs) are mostly associated with smoking, alcohol intake, and/or human papillomavirus HPV16 and/or HPV18 infection. However, most tumors are diagnosed at an advanced stage. In the search for biomarkers of HNSCC, we studied the prognostic role of SPOCK1, a heparan sulfate proteoglycan. In HNSCC, SPOCK1 expression was tested both at in silico mRNA level using the Kaplan-Meier Plotter and at in situ protein level after SPOCK1 immunohistochemistry after whole slide digitalization. Protein expression results were analyzed using H-Scores, both by eye-control testing and with a machine-learning-based automated image analysis tool, DensitoQuant. SPOCK1 mRNA expression was found to be significantly higher in oral carcinomas than in the normal oral mucosa (log-rank p = 5.76e-06). Elevated SPOCK1 mRNA expression was consistently associated with a strongly reduced overall survival (OS; HR = 1.57 (1.2-2.06); log-rank p = 0.001) in HNSCC. This was particularly true for tumors with high (log-rank p = 0.00085) vs. low (log-rank p = 0.55) neoantigen (NeoAG) levels, at median antigen level stratification. Both the Cox-regression analysis and the log-rank test revealed elevated SPOCK1 protein levels in association with significantly reduced OS in our 97 HNSCC patients (both p = 0.002), which was supported by automated image analysis testing (p = 0.008 and p = 0.044, respectively). Our findings suggest that SPOCK1 can be a candidate adverse prognostic biomarker also in HNSCC. Therefore, SPOCK1 overexpression may specify a group of oral cancers with aggressive tumor biology.

Rhabdomyosarcoma is the third most common extracranial solid tumor in childhood. Treatment of patients is multimodal, based on systemic chemotherapy and local therapy by surgery and/or radiotherapy. Although standard therapies result in an overall survival of more than 75% for patients in the low-risk group, the prognosis for high-risk patients remains poor. For this reason, new therapeutic alternatives are needed. One such option is the use of specific Tropomyosin receptor kinase (TRK) inhibitors, which provides the opportunity of targeted therapeutic treatment for patients carrying Neurotrophic Receptor Tyrosine Kinase (NTRK) translocations. As the frequency of these aberrations is not yet known in rhabdomyosarcomas, the aim of this study was to map the pan-TRK expression profile of rhabdomyosarcomas by an affordable method and to investigate the link between the expression and the clinicopathological features. We studied samples of patients diagnosed with rhabdomyosarcoma at the Pediatric Center, Semmelweis University, Budapest, Hungary. Using immunohistochemistry, we found that pan-TRK expression was detected in 38% of the cases studied. The expression was present in a significantly higher proportion of samples in the unfavorable, alveolar histological subtype. However, no NTRK fusion was detected in the 17 TRK expressing samples.

This study provides a comprehensive nationwide analysis of extensive-stage small cell lung cancer (ES-SCLC) in Hungary, examining incidence rates, demographic trends, treatment patterns, and survival outcomes. We used data from the National Health Insurance Fund (NHIF) covering the period of 2013-2022, and we analyzed 8,104 ES-SCLC patients who received first-line (1L) etoposide-platinum (EP) chemotherapy, all of whom were confirmed to not have received concomitant chemoradiotherapy or curative thoracic surgery and had histology results in line with SCLC. We evaluated epidemiology, regional distribution, radiotherapy use, and subsequent treatment pathways. For the efficacy analysis, we narrowed the cohort to 5,576 patients who initiated EP within 1 year of their first C34-coded lung cancer diagnosis between 2013 and 2019, enabling 3-year follow-up. Key endpoints included overall survival (OS) and progression-free survival (PFS), the latter of which was inferred using time to first subsequent therapy (TFST). Our results revealed a shifting age distribution toward the age group above 70 years, while the male-to-female ratio gradually evened out. Treatment patterns showed the increasing use of carboplatin over cisplatin and frequent short course radiotherapy. Among those who underwent subsequent therapy, EP rechallenge was most widespread. Despite high initial response rates, survival outcomes remained poor: median PFS was 6.5 months (6-month: 52.9%, 1-year: 19%, 3-year: 5.2%), and median OS was 9.3 months (6-month: 69.8%, 1-year: 37.5%, 3-year: 9.2%). These results were in line with international real-world evidence and clinical trial data. Our findings highlight the aggressive nature of ES-SCLC and provide insight to the limited efficacy of chemotherapy-based therapies, underscoring the need to improve existing 1L and subsequent-line treatments and to introduce novel options. As Hungary transitions into the immunotherapy era, future studies with extended follow-up that incorporate staging, radiotherapy intent, comorbidities, and progression data will be essential for optimizing therapeutic strategies.

Multigene signatures like Oncotype DX and Prosigna Prediction Analysis of Microarray 50 (PAM50) help estimate distant recurrence risk in patients with luminal breast cancer receiving endocrine therapy. Determining the benefit of adjuvant chemotherapy, tests are costly and not always supported through reimbursement. We aimed to assess the utility of the APIS Breast cancer subtyping kit (BCSK) and its proliferation score (PS), as a potential prognostic assay. We analysed 141 adult patients with early luminal HER2- breast cancer diagnosed between 2020 and 2022 at Cantonal Hospital Basel-Land and Basel University Hospital. All patients had a valid OncotypeDX[®] Recurrence Score (RS) and received at least one line of adjuvant therapy. Molecular subtype and PS were obtained using the APIS BCSK. We performed the Prosigna PAM50 risk of recurrence (ROR) test on a subset of 59 patients. Our findings showed high concordance at the single marker level (estrogen receptor -ESR1, progesterone receptor - PGR, human epidermal growth factor receptor 2 - ERBB2 and marker of proliferation Ki-67 - MKI67), and between the BCSK and PAM50 subtype (overall percent agreement, OPA-71.2%). Notably, BCSK showed stronger agreement with immunohistochemistry (IHC)-based subtypes (OPA: 71.2%) than PAM50 with IHC (OPA: 54.2%). The BCSK PS correlated moderately with Prosigna PAM50 ROR (ρ = 0.4787) and more weakly with Oncotype DX RS (ρ = 0.4006). The correlation between ROR and RS was weak (ρ = 0.2255). In this preliminary comparison, the APIS BCSK and PS demonstrate promising potential as an initial molecular subtyping and risk stratification tool for breast cancer patients.

Glucose is at the center of liver metabolism, and together with NADPH, it is an essential factor in hepatic regulation and adaptation to different metabolic states. The liver plays a fundamental role in the development of obesity. Excess food intake, particularly excess glucose, primarily burdens liver metabolism. The hepatocyte-specific glycogenoreticular system, a functional unit based on the tight interaction between glycogen particles and the ER, is central to the storage and distribution of glucose throughout the body. Additionally, the liver converts excess glucose into ketogenic molecules. The liver is the most important site for glucogenic to ketogenic conversion in the body. However, the escape route offered by unrestricted fatty acid synthesis and deposition takes its toll in the long run. An NADPH pool is also a pivotal connection among intermediary metabolism, redox homeostasis, and drug metabolism in hepatocytes. Preservation and recovery of excess glucose is a commitment, which presents a potential pitfall. Overfeeding can lead to pathological consequences by disrupting regulatory mechanisms. The fulfillment of metabolic goals by the liver plays a significant role in the development of various pathological conditions, such as fatty liver, obesity, insulin resistance, and metabolic syndrome.

Extranodal natural killer/T-cell lymphomas (ENKTCL) are rare, aggressive neoplasms primarily occurring in adults of Asian or Native American descent. Most are associated with Epstein-Barr virus (EBV) and originate in the nasopharyngeal region. We present the case of a fulminant, disseminated, non-nasal, EBV negative, seemingly de novo ENKTCL in an infant who presented with a five-day history of progressive abdominal distention, respiratory distress, irritability, non-bilious emesis, right eye proptosis, and pallor. Initial labs revealed leukocytosis, anemia and thrombocytopenia. Computerized axial tomography revealed densities in the right optic nerve, superior orbits, thymus, posterior mediastinum, pericardium, myocardium, axillary lymph nodes, adrenal glands, kidneys and pancreas. The patient rapidly deteriorated, and despite extensive resuscitation, ultimately died. Autopsy revealed tumors in many organs, displaying vascular damage and tissue necrosis with lymphoid infiltration. The likely diagnosis of EBV-negative ENKTCL was confirmed after further histologic analysis. Pediatric ENKTCL is a particularly uncommon tumor, especially given our patient's very young age and EBV-negative status. Determining the best treatment regimen for these children is challenging due to limited data. Treatment typically consists of combination chemotherapy and radiation, but targeted therapies are being explored with promising results.