Search Results (113)

Granular cell tumors are uncommon neoplasms of neural origin that may involve the skin and often present with nonspecific clinical features, making diagnosis challenging. Cutaneous granular cell tumors rarely exhibit overlying hypertrichosis, a finding that may obscure their clinical recognition. In this report, we describe a rare case of a primary cutaneous granular cell tumor with prominent overlying terminal hair growth in an adult patient. A 27-year-old woman presented with a slowly enlarging, firm, pigmented plaque on the upper back associated with pruritus and increased hair growth. Histopathologic examination revealed sheets of large polygonal cells with abundant granular eosinophilic cytoplasm, and immunohistochemical staining was positive for S100, SOX10, CD68, and calretinin, confirming the diagnosis. The lesion was completely excised with no evidence of malignancy. To our knowledge, this represents the second reported instance of a cutaneous granular cell tumor associated with hypertrichosis and the first described in an adult. It underscores the importance of clinicopathologic correlation in evaluating unusual cutaneous lesions and expands the spectrum of recognized presentations of cutaneous granular cell tumors. Full article

Background: Multiple myeloma (MM) is a clonal plasma cell neoplasm representing the second most common hematological malignancy. The combination of daratumumab, lenalidomide and dexamethasone (D-Rd) was first approved by the EMA (European Medicines Agency) for the treatment of relapsed/refractory multiple myeloma (RRMM) patients, and was subsequently approved for first-line therapy, based on the results of POLLUX and MAIA trials, respectively. Methods: In this survey, we retrospectively collected data from 96 consecutive transplant-ineligible newly diagnosed multiple myeloma (TIE-NDMM) patients treated with the D-Rd combination. Results: The median age was 73 years; the median progression free survival (mPFS) and median overall survival (mOS) were not reached (NR); the overall response rate (ORR), defined as patients who obtained at least a partial response (PR), was 90%; 59% of patients achieved a very good partial response (VGPR) or better. A strong negative correlation was observed between treatment response and elevated beta-2-microglobulin levels. Conclusions: This study confirms the efficacy of the D-Rd combination as first-line therapy for TIE-NDMM patients, suggesting that achieving at least a PR—and particularly a VGPR—may represent a strong predictor of long-term remission and survival, even in the era of new combinations based on the use of quadruplets. Full article

CD19-directed chimeric antigen receptor (CAR) T-cell therapies have been instrumental in improving outcomes of refractory or relapsed B-cell malignancies. However, there have been safety concerns due to recent reports of second primary malignancies (SPMs) related to CAR T-cell therapies. We reviewed articles from Embase, PubMed, and Cochrane Library records and included SPM case reports as well as cohort studies. Across published cohorts, secondary cutaneous or peripheral T-cell lymphoma (PTCL) after diffuse large B-cell lymphomas (DLBCLs) have been reported at low incidence (generally in the low single-digit percentage range). While CAR T-cell therapy is associated with these rare secondary malignancies and lineage-switch events primarily described in acute leukemia, they are clinically significant and have resulted in increased surveillance. The currently available evidence suggests that most secondary malignancies after CAR T-cell therapy are due to background risk and prior treatment exposures rather than direct CAR T-cell therapy induced oncogenesis. However, rare CAR T-cell therapy-associated second primary T-cell malignancies have been reported. To properly define incidence, mechanisms, and risk factors for CAR T-cell therapy-associated malignancies, continued prospective registry follow-up and additional research will be needed. Full article

Multiphoton endomicroscopy (MPEM) has recently become a key development in optical biomedical diagnostics, providing histologically relevant in vivo images that are eliminating both the need for tissue damage during biopsy sampling and the need for dye injections. Due to its ability to visualize structures at the epithelial, extracellular matrix, and subcellular levels, MPEM offers a promising diagnostic method for precancerous conditions and early forms of gastrointestinal (GI) cancer. The high specificity of multiphoton signals—the two-photon fluorescence response of endogenous fluorophores (NADH, FAD), the second-harmonic generation signal from collagen, and others—makes this method a promising alternative to both traditional histology and confocal endoscopy, enabling real-time assessment of metabolic status, intestinal epithelial cell status, and stromal remodeling. Despite the promising prospects of multiphoton microscopy, its practical implementation is progressing extremely slowly. The main factors here include the difficulty of delivering ultrashort pulses with high peak power, which is necessary for multiphoton excitation (MPE), and obtaining these pulses at the required wavelengths to activate the autofluorescence mechanism. One of the most promising solutions is the use of specialized multimode optical fibers that can both induce beam self-cleaning (BSC), which allows for the formation of a stable beam profile close to the fundamental mode, and significantly broaden the optical spectrum, which can ultimately cover the entire region of interest. This review presents the biophysical foundations of multiphoton microscopy of GI tissue, existing endoscopic architectures for MPE, and an analysis of the potential for using novel nonlinear effects in multimode optical fibers, such as the BSC effect and supercontinuum generation. It is concluded that the use of optical fibers in which the listed effects are realized in the tracts of multiphoton endomicroscopes can become a key step in the creation of a new generation of high-resolution instruments for the early detection of malignant neoplasms of the GI tract. Full article

Background: Pancreatic cancer (PC) is expected to be the second leading cause of cancer-related death by 2030. Surgical resection with R0 margins remains the only available treatment capable of improving the overall survival of the patients; thus, appropriate characterization of pancreatic tumors is mandatory for the correct assessment of PC resectability. Despite advances in pancreatic surgery, POPF remains a frequent and dreaded complication that impacts the morbidity and mortality of PC patients, entailing both clinical and economic consequences. Soft pancreatic texture is known as an independent risk factor for POPF occurrence in pancreatic surgery. Intraoperative exploration of the pancreas is most frequently assessed subjectively, through the surgeon’s palpation. Intraoperative elastography is a modern ultrasound technique suitable to replace the surgeon’s intraoperative palpation to better evaluate pancreatic lesions, pancreatic texture, and improve surgical management. Thus, intraoperative elastography could provide quantifiable and reproducible information in pancreatic parenchyma characterization. Real-time intraoperative assessment of pancreatic texture through an objective method could improve surgical decisions. This systematic review analyzes the role of intraoperative elastography in differentiating benign from malignant pancreatic tumors and the efficacy of this technique in the assessment of pancreatic texture as a predictor of postoperative pancreatic fistula (POPF). Methods: We conducted a comprehensive systematic literature research on PubMed, Google Scholar, Scopus, Web of Science, Embase and Cochrane Library Database using PRISMA framework guided by the words “intraoperative elastography” or “intraoperative elasticity imaging” or “intraoperative shear wave elastography” or “intraoperative strain elastography” and “pancreatic cancer” or “pancreatic neoplasm” or “pancreatic adenocarcinoma” or “pancreatic tumor” or “pancreatic fistula” or “postoperative pancreatic fistula” or “pancreatic leak”. Articles that were listed between 2000 and 2025 and written in the English language were screened for potentially relevant articles. The primary outcome was to evaluate the use of intraoperative elastography in differentiating between benign and malignant lesions of the pancreas. The second outcome was to assess the role of intraoperative elastography in the evaluation of pancreatic texture as a predictive factor for the occurrence of postoperative pancreatic fistula. Results: From a total of 17 publications, 2 scientific articles were considered relevant for the role of intraoperative elastography in differentiating benign from malignant pancreatic lesions, while 4 articles analyzed the role of intraoperative pancreatic elastography as a predictor of postoperative pancreatic fistula (POPF). Based on the results, detection of pancreatic cancer through intraoperative SWE is possible at cut-off values of 3 m/s and 28.7 kPa, and values of 2.2 m/s or less obtained after intraoperative elastography of the pancreas are considered an independent risk factor for POPF in pancreatic surgery. Reported cut-off values should, however, be interpreted as exploratory and should represent a starting point for further studies aimed at validating their clinical implementation. Conclusions: Intraoperative elastography can be a promising tool in pancreatic tumor characterization and could differentiate between benign and malignant pancreatic tumors and predict the risk of POPF, but further prospective studies are required before cut-off values can be routinely applied in clinical practice. Full article

Background/Objectives: Prostate cancer is the second most common cause of cancer-related mortality among the male population worldwide. It is among the leading reasons for the increasing number of years of life lost, working years of life lost, and gross domestic product (GDP) loss in Bulgaria. The primary objective of this study is to evaluate the burden of prostate cancer in Bulgaria, including calculating years of life lost (YLL), years of working life lost (YWLL), and the associated indirect costs. Methods: An observational time-series study was conducted using official national data from the National Statistical Institute (NSI), the INFOSTAT database, and the National Social Security Institute. The study covered the period 2008–2023 and included all registered male deaths attributed to malignant neoplasm of the prostate (ICD-10: C61). YLL, YWLL, and indirect costs were calculated using the human capital approach. Due to restricted access to age-specific mortality files, additional mortality records were obtained through formal data requests to NSI. Results: Prostate cancer led to 127,457 YLL and 6345 YWLL, with productivity losses reaching €88.2 million. Mortality showed an overall increasing trend up to 2020, while YWLL declined due to deaths shifting to older age groups. Conclusions: Despite the advancements in prostate cancer diagnosis and treatment, our findings demonstrate a negative trend regarding YLL, YWLL, and indirect costs associated with the disease, in contrast to other European countries. Strengthening early screening, reducing diagnostic delays, and improving national cancer registry capacity are critical to mitigating future health and economic losses. Full article

Intrahepatic cholangiocarcinomas (iCCAs) are histologically subdivided into small duct-type (SD-iCCA) and large duct-type (LD-iCCA). LD-iCCA versus SD-iCCA may differ in the molecular/genetic profiles and oncogenesis, including precursor lesions. While several precursors, such as high-grade biliary intraepithelial neoplasm (BilIN) and intraductal papillary neoplasm of bile duct (IPNB), have been proposed for LD-iCCA, the potential SD-iCCA precursors remain to be identified. Amid growing interests in the precursors of SD-iCCA, benign “biliary lesions/neoplasms developing in the hepatic parenchyma (BLNP)” such as von Meyenburg complexes (VMCs), bile duct adenomas (BDAs), and biliary adenofibroma (BAF), have been noted to determine whether they have the potential for precursor of SD-iCCA. Herein, these BLNPs were reviewed. BLNP can be classified into three categories. First, traditional VMC and BDA in normal livers which lack atypical features are categorized as “traditional BLNP”. Second, a constellation of several lesions such as VMC and BDA detectable in the background livers of SD-iCCA and in chronic liver disease (unusual VMC and BDA), VMC with dysplastic features, BDA located in the deep hepatic parenchyma, multiple BDA, BDA presenting the BRAF V600E mutation, and BAF harboring variable dysplasia or in situ carcinomas, which may include neoplastic lesions but do not show invasive growth, are categorized as “unusual/dysplastic BLNP”. Third, tubulocystic carcinoma with BAF-like features (AI-TCC) and SD-iCCA with ductal plate malformation (DPMP) which share overlapping features and show relatively good post-operative outcomes and retained features of VMC or DPM, and BDA and BAF, are categorized as “low-grade malignant BLNP”. While the first category is benign and may not be related to SD-iCCA, some of the second category may be related to SD-iCCA, and the third category is malignant and shows invasive growth. The latter two categories may form a common biliary tumorigenic spectrum involving BLNP. Precursors of SD-iCCA, if they exist, may be included in the second category, and the third category may represent unique carcinomas possibly associated with or followed by conventional SD-iCCA. In conclusion, this novel approach to categorize BLNPs into three categories guarantees further studies of precursors of and their progression to conventional SD-iCCA. Full article

Cutaneous lymphomas are a heterogeneous group of extranodal non-Hodgkin lymphomas with distinct clinical and biological features, broadly classified into cutaneous T-cell lymphomas (CTCL) and cutaneous B-cell lymphomas (CBCL). With improved survival due to early detection and therapeutic advances, the emergence of second primary malignancies (SPMs) has become a clinical concern. SPMs, defined as new, distinct malignant neoplasms arising synchronously or metachronously with the index cancer, can significantly impair prognosis and quality of life. In this narrative review, we meticulously examine the current literature, to synthesize evidence on SPMs’ incidence and risk factors in patients with primary cutaneous lymphomas. Evidence from population-based and institutional studies consistently demonstrates elevated risks of hematologic and solid tumors in CTCL. By contrast, data on CBCL remain limited, though recent population-based analyses suggest increased risks of certain hematologic malignancies and solid tumors. We further propose development mechanisms for SPMs, including treatment-related mutagenesis, shared genetic susceptibilities, chronic antigenic stimulation, and immune dysregulation. Lastly, we highlight the clinical implications of these findings, underscoring the need for vigilant surveillance, patient education, and tailored screening strategies. Future research should prioritize large-scale, prospective, and molecularly integrated studies to refine risk stratification and guide personalized survivorship care of this vulnerable population. Full article

Pancreatic neuroendocrine neoplasms (pNENs) are the second most common type of pancreatic cancer after pancreatic ductal adenocarcinoma. Germline mutations in DNA repair genes drive several hereditary and sporadic cancers; however, their role in pNENs remains poorly defined. This pilot study aimed to assess the frequency and clinical relevance of germline DNA repair gene mutations in patients with pNENs, both with and without a family history of cancer. Germline DNA from 57 Polish patients with pNENs was analyzed using targeted next-generation sequencing to identify variants in a panel of DNA repair genes. Variant classification followed the American College of Medical Genetics and Genomics/Association for Molecular Pathology guidelines. Germline mutations were identified in 14 patients (24.6%), both with and without a family history of malignancy. Two patients carried pathogenic variants in BRCA2 and CHEK2, while seven carried variants of uncertain significance (VUS). The identified variants have been implicated in various cancer types, including breast, ovarian, prostate, gastric, colorectal, and pancreatic cancers. These findings indicate that germline mutations in DNA repair genes may contribute to the pathogenesis of pNENs, even in patients without a family history. Broader germline testing and population-specific studies are needed to clarify the genetic landscape and clinical implications of these alterations. Full article

Over the last few decades, due to improvement in imaging techniques, the increased detection of adrenal incidentalomas is observed. Non-aldosterone producing adrenal adenomas (NAPACAs) often co-exist with second benign or malignant lesions. In the present study, we aimed to assess the presence of second neoplasms, both benign and malignant, in patients with NAPACAs, and to investigate possible correlations with clinical parameters, hormonal characteristics and the emergence of comorbidities. A total of 130 NAPACA patients were included in this single-center retrospective study. In this cohort, 35.4% of NAPACA patients carried any second neoplasm (either benign or malignant) whereas, 26.9% had a second malignant neoplasm. Cortisol levels after 1 mg overnight dexamethasone suppression test (F-ODS) were significantly higher in patients without a second neoplasm (p = 0.02), and this finding was consistent even when categorizing patients with and without malignancies (p = 0.02). In line with this observation, ACTH/F-ODS levels were significantly higher in patients with second malignancies (p < 0.05). Interestingly, the presence of mild autonomous cortisol secretion tended to be lower in patients with second malignancies (p = 0.08). No remarkable differences in the comorbidities of NAPACA patients with and without a second neoplasm were documented. Further prospective studies will be needed to elucidate the role of mild hypercortisolemia on the development of these second tumors in NAPACA patients. Full article

DICER1 syndrome is a hereditary cancer predisposition syndrome, characterized by a large range of benign and malignant neoplasms. Patients with DICER1 syndrome have a broad phenotype, with pleuropulmonary blastoma, Sertoli–Leydig cell tumor, cystic nephroma, cervical embryonal rhabdomyosarcoma, cystic lung lesions, and thyroid follicular nodular disease being the most prevalent manifestations. The syndrome is caused by loss-of-function germline variants in the DICER1 gene, and DICER1-related tumors are characterized by second somatic hotspot variants in the RNase IIIb domain of DICER1. DICER1 encodes an endoribonuclease, which is important for RNA interference. This review describes the molecular mechanism of DICER1 function and the pathogenetic mechanisms of tumorigenesis. The purpose of this review is to describe the pathogenesis, genotype–phenotype correlation and tissue specificity of DICER1 syndrome. We conclude that there is a lack of knowledge about the exact molecular mechanisms of DICER1 function and more research is needed to determine the exact role of this altered protein in relation to pathogenesis. Full article

Background: Endometrioid ovarian carcinoma is a subtype of epithelial ovarian carcinoma and is the second most common type of malignant ovarian neoplasm. Studies investigating delayed treatment of ovarian cancer have identified significant impacts on overall survival rates. This study utilizes the Surveillance, Epidemiology, and End Results (SEER) database to identify cases of endometrioid ovarian carcinomas and factors associated with delays in time to treatment (TTT) greater than one month. Methods: The SEER database was queried to identify females with biopsy-confirmed cases of ovarian endometrioid carcinoma from 2010 to 2015. Chi-square tests, two-sided Fisher’s exact tests, and multivariable binary logistic regressions were completed using SPSS version 29.0.2. Statistical significance was confirmed when p < 0.05. Results: A total of 11,235 relevant patients were identified within the SEER database. A majority were Non-Hispanic White (69.2%), aged 50–59 (30.1%), had an annual income of $75,000+ (58.9%), resided in urban communities (90.0%), and were diagnosed with AJCC stage 1 disease (62.0%). When investigating treatment, 94.9% of patients received treatment within 1 month of diagnosis, while 5.1% experienced a delay of over 1 month before starting treatment. Multivariable binary logistic regression analysis demonstrated that American Indian and Alaksa Native (AIAN) patients independently experienced a +376% increased likelihood of treatment delays exceeding 1 month (aOR 4.76; 95% CI 1.32–17.08; p = 0.017). Patients diagnosed at AJCC stage III (aOR 1.88; 95% CI: 1.22–2.91; p = 0.004) or stage IV (aOR: 4.50; 95% CI: 2.75–7.38; p < 0.001) additionally had +88% and +350% higher odds of treatment delays greater than 1 month, respectively. Conclusions: AIAN patients and those presenting with later stage disease for endometrioid ovarian carcinoma face significantly longer TTT, indicating disparities in timely care. Our findings demonstrate an urgent need for targeted interventions to address systemic barriers contributing to delayed treatment in these populations. Full article

Purpose/Objective(s): Peritoneal carcinosis can occur in several gastrointestinal or gynecological malignancies and its prognosis is usually poor. With the advent of more effective systemic agents, the overall survival of metastatic patients has been revolutionized and isolated peritoneal or abdominal wall metastases might benefit from local treatments; Stereotactic Body Radiotherapy (SBRT) might be considered in selected patients with oligometastatic presentation. Materials/Methods: Oligometastases were defined according to recent ESTRO/EORTC consensus. Inclusion criteria were as follows: ECOG PS ≤ 2, written informed consent, up to five lesions to be treated at the same time, patients treated with radiotherapy schedules applying minimum 6 Gy per fraction. The primary endpoint of the study was local control (LC); acute and late toxicity, distant progression-free survival (DPFS), time-to-next systemic treatment (TNST), polymetastatic-free survival (PMFS) and overall survival (OS) were secondary endpoints. Toxicity was assessed according to CTCAE criteria v5.0. Statistical associations between clinical variables and outcomes were assessed using Fisher’s exact test, and Kruskal–Wallis test, as appropriate. Survival outcomes were estimated using the Kaplan–Meier method and compared using the log-rank test. Results: Between April 2020 and September 2024 a total of 26 oligometastatic lesions located in the peritoneum or in the abdominal wall detected in 20 patients received SBRT with Helical Tomotherapy. All cases have been assessed by a multidisciplinary team. Only in three patients out of twenty did more than one lesion receive SBRT: two lesions in two patients, and five lesions in a single case of colorectal cancer with ongoing third-line systemic treatment. Median total dose was 30 Gy (27–35 Gy) in five fractions (3–5). The most frequent primary neoplasm was ovarian cancer in 14/20, endometrial in 2/20, while the remaining were colorectal, vaginal, pancreatic and non-small cell lung cancer. Four lesions were located in the abdominal wall, while the remaining twenty-two were located in the peritoneum. Concurrent systemic therapy was administered in 18/20 patients. With a median follow-up of 15 months (range, 6–59), our 1-year LC was 100%, while 1-year DPFS, PMFS, TNTS and OS rates were 54%, 69%, 61% and 83%, respectively. Abdominal wall location and treatment of a subsequent oligometastatic recurrence with a second course of SBRT were both significantly associated with improved OS (p = 0.03 and p = 0.04, respectively). No G ≥ 3 adverse events occurred. Conclusion: Our preliminary data support the use of SBRT in selected cases of oligometastatic disease located in the peritoneum or in the abdominal wall with excellent results in terms of tolerability and promising clinical outcomes. Full article

Goblet cell adenocarcinomas (GCAs) are an exceedingly rare subtype of tumors, almost exclusively occurring in the appendix, and characterized by features overlapping both adenocarcinomas and neuroendocrine tumors (NETs), which has historically led to confusion and varied nomenclature. This study presents a comprehensive review of the literature highlighting particularities of this type of malignancy, starting from a rare case of a 54-year-old female operated on in our clinic for an appendiceal tumor, initially suspected to be a mucinous neoplasm based on colonoscopic biopsy, which was ultimately confirmed to be goblet cell adenocarcinoma on both intraoperative frozen section and definitive pathological examination. Exhibiting signs and symptoms associated with an abdominal mass, she underwent a right hemicolectomy with partial omentectomy for locally advanced, high-grade, invasive goblet cell adenocarcinoma of the appendix with lymphatic macro metastases and epiploic invasion, categorized as AJCC stage IVb carcinomatosis. The patient received FOLFOX adjuvant. Six months later, she required reoperation due to the progression of carcinomatosis, which was again confirmed histopathologically. A second-line oncological protocol comprising irinotecan, capecitabine, and bevacizumab was initiated. Given the rarity of GCAs and the absence of a consensus on nomenclature, classification, and diagnostic criteria, we conducted a comprehensive literature review to highlight current trends related to this entity, including its classification within different systems (Tang, Yozu, WHO, AJCC), as well as the therapeutic surgical approaches—ranging from simple appendectomy to extensive multiorgan resection, cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC), and the use of systemic therapy. Adhering to these recommendations will enhance communication among pathologists, surgeons, and oncologists regarding the natural history and prognosis of this rare malignancy. Full article

Background/Objective: Radiotherapy for leukemia, the most common childhood malignancy, often exposes patients to radiation, increasing the risk of second malignancies, including thyroid cancer. To assess the incidence and survival outcomes of thyroid cancer after childhood acute lymphoblastic leukemia (ALL). Methods: We systematically reviewed articles reporting the incidence of thyroid cancer in childhood leukemia survivors (age at diagnosis < 18 years) published between 2000–2024 in Science Direct, PubMed, Google Scholar, CENTRAL, and EMBASE. The Newcastle Ottawa Scale was utilized to appraise the methodological quality of the included studies. Descriptive statistics and calculations of incidence were performed using Microsoft Excel. Results: The literature search yielded 1265 articles, of which 18 met the inclusion criteria. Data from 135,861 childhood cancer survivors, among whom 102,070 had a confirmed diagnosis of childhood leukemia, including ALL. The crude incidence of secondary malignancies after childhood leukemia was 10.1 per 1000 patients. Among these, 1.5 per 1000 patients developed second thyroid carcinomas. Overall, 14.6% of the second malignancies in childhood leukemia survivors were thyroid carcinomas, mostly of the papillary type. Survival rates after second thyroid cancer were 100% in all 11/18 studies reporting this outcome. Radiotherapy had been used as part of ALL treatments in 17/18 studies. The use of radiotherapy, female sex, and younger age at the diagnosis of primary ALL emerged as important risk factors for thyroid cancer. Conclusions: Thyroid carcinomas account for ~15% of secondary malignancies after childhood leukemia, with radiation remaining a significant risk factor despite its overall reduced use for the treatment of ALL in the last few decades. Importantly, survival rates remain high. Further research is warranted to determine the incidence and outcomes of thyroid cancer in childhood ALL survivors Full article