Clinical recommendations for treatment of localized angiosarcoma: A consensus paper by the Italian Sarcoma Group.

Angiosarcoma (AS) represents a rare and aggressive vascular sarcoma, posing distinct challenges in clinical management compared to other sarcomas. While the current European Society of Medical Oncology (ESMO) clinical practice guidelines for sarcoma treatment are applicable to AS, its unique aggressiveness and diverse tumor presentations necessitate dedicated and detailed clinical recommendations, which are currently lacking. Notably, considerations regarding surgical extent, radiation therapy (RT), and neoadjuvant/adjuvant chemotherapy vary significantly in localized disease, depending on each different site of onset. Indeed, AS are one of the sarcoma types most sensitive to cytotoxic chemotherapy. Despite this, uncertainties persist regarding optimal management across different clinical presentations, highlighting the need for further investigation through clinical trials. The Italian Sarcoma Group (ISG) organized a consensus meeting on April 1st, 2023, in Castel San Pietro, Italy, bringing together Italian sarcoma experts from several disciplines and patient representatives from "Sofia nel Cuore Onlus" and the ISG patient advocacy working group. The objective was to develop specific clinical recommendations for managing localized AS within the existing framework of sarcoma clinical practice guidelines, accounting for potential practice variations among ISG institutions. The aim was to try to standardize and harmonize clinical practices, or at least highlight the open questions in the local management of the disease, to define the best evidence-based practice for the optimal approach of localized AS and generate the recommendations presented herein.

Kaposi's Sarcoma: Evaluation of Clinical Features, Treatment Outcomes, and Prognosis in a Single-Center Retrospective Case Series.

Kaposi's sarcoma (KS) is a rare angioproliferative tumor classified in four different clinical-epidemiological forms. The diagnosis is based on histopathological and immunohistochemical analyses. The treatment is heterogeneous and includes several local and systemic therapeutic strategies. Methods: This is a retrospective cohort study including 86 KS patients treated between 1993 and 2022 at the University Hospital of Padua (AOPD) and at the Veneto Institute of Oncology (IOV). The data were extracted from an electronic database. Survival curves were generated using the Kaplan-Meier method, and Cox regression models were employed to explore associations with overall and disease-free survival. The male sex (89.53%), classical variant (43.02%), and cutaneous involvement (77.9%) were predominant. More than 61.6% of patients received a single treatment. Surgery, antiretroviral therapy, and chemotherapy were the mostly adopted approaches. A persistent response was observed in approximately 65% of patients, with a 22% relapse rate (at least 2 years). The overall survival ranges from 90 to 70% at 2 to 10 years after the diagnosis. Iatrogenic KS demonstrated a higher mortality (52.9%). This study reflects our experience in the management of KS. Comorbidities are very frequent, and treatments are heterogeneous. A multidisciplinary approach involving multiple referral specialists is essential for the appropriate management of this disease during diagnosis, treatment, and follow-up.

Primary vascular tumors of bone: A comprehensive literature review on classification, diagnosis and treatment.

Primary vascular tumors of bone are a heterogeneous group of neoplasms, ranging from benign hemangiomas to frankly malignant epithelioid hemangioendotheliomas and angiosarcomas. Over the years, their classification has been a matter of discussion, due to morphologic similarities and uncertainty regarding biologic behavior. Over the past decade, with the development of next-generation sequencing, there has been a significant improvement in the molecular characterization of these lesions. The integration of their morphologic, immunohistochemical and molecular features has led to a better stratification, with important prognostic and therapeutic implications. Nevertheless, primary vascular bone tumors still represent a challenge for medical oncologists. Given their rarity and heterogeneity, in the last few years, there has been no significant progress in medical treatment options, so further research is needed. Here we present a review of the current knowledge regarding primary vascular tumors of the bone, correlating clinicopathologic features with tumor behavior and therapeutic approaches.

Are IDH1 R132 Mutations Associated With Poor Prognosis in Patients With Chondrosarcoma of the Bone?

BACKGROUND: Because chondrosarcomas vary widely in their behavior, and because anticipating their behavior based on histology alone can be challenging, genetic markers represent an appealing area of inquiry that may help us refine our prognostic approaches. Isocitrate dehydrogenase (IDH) mutations are involved in the pathogenesis of a variety of neoplasms, and recently, IDH1/2 mutations have been found in the tissue of benign cartilage tumors as well as in conventional chondrosarcomas and highly aggressive dedifferentiated chondrosarcomas. However, their association with patient survival is still controversial. QUESTIONS/PURPOSES: (1) What proportion of patients with chondrosarcomas carry IDH mutations, and which IDH mutations can be found? (2) Are any specific IDH mutations associated with poorer overall survival, metastasis-free survival, or local recurrence-free survival? METHODS: Between April 2017 and December 2022, we treated 74 patients for atypical cartilaginous tumors or chondrosarcomas in a musculoskeletal tumor referral center. Patients were considered potentially eligible for the present study if the histologic diagnosis was confirmed by two expert soft tissue and bone pathologists following the current WHO classification, complete preoperative imaging and follow-up data were available, surgical excision was performed by sarcoma orthopaedic surgeons directed by a team leader, and the minimum follow-up was 2 years after surgical treatment unless the patient died. Data including sex, age, diagnosis, grade, type of operation, local recurrence, metastasis, and oncologic follow-up were recorded. Forty-one patients (55%) were eligible for the study. For each patient, DNA was extracted and quantified from paraffin-embedded sections of tumor tissue, and the mutational status of IDH1 (codons 105 and 132) and IDH2 (codons 140 and 172) genes was assessed. Of those, 56% (23 of 41) of patients had adequate DNA for analysis of IDH mutations: 10 male and 13 female patients, with a median age of 59 years (range 15 to 98 years). There were 22 conventional chondrosarcomas (8 atypical cartilaginous tumors, 11 Grade 2, and 3 Grade 3) and 1 dedifferentiated chondrosarcoma. Stage was IA in 3 patients, IB in 5, IIA in 1, IIB in 13, and III in 1, according to the Musculoskeletal Tumor Society classification. At a median follow-up of 3.5 years (range 4 months to 5.6 years), 14 patients were disease-free, 2 were alive with disease, and 7 died (3 within 2 years from surgery). Eight patients had metastases, and 7 developed local recurrence. We determined the proportion of patients who carried IDH mutations, and compared patients with and without those mutations in terms of overall survival, metastasis-free survival, and local recurrence-free survival using Kaplan-Meier curves. RESULTS: Six patients showed wild-type IDH genes, and 17 had IDH mutations (12 had IDH1 R132, 3 had IDH1 G105, and 2 had IDH2 R172). Overall survival at 2 years using the Kaplan-Meier estimator was lower in patients with an IDH mutation than in those with the wild-type gene (75% [95% confidence interval 50% to 99%] versus 100% [95% CI 100% to 100%]; p = 0.002). Two-year metastasis-free survival was also lower in patients with an IDH mutation than in those with the wild-type gene (33% [95% CI 7% to 60%] versus 100% [95% CI 100% to 100%]; p = 0.001), as was 2-year local recurrence-free survival (70% [95% CI 42% to 98%] versus 100% [95% CI 100% to 100%]; p = 0.02). CONCLUSION: We found that IDH1 R132 mutations were negatively associated with the prognosis of patients with bone chondrosarcomas. Nevertheless, more extensive studies (such as multicenter international studies) are needed and advisable to confirm our observations in this preliminary small series. Moreover, evaluating mutational status in fresh samples instead of in paraffin-embedded sections could help to increase the number of patients with adequate DNA for analysis. If our findings will be confirmed, the evaluation of IDH mutational status in biopsy samples or resection specimens could be considered when stratifying patients, highlighting those who may benefit from more aggressive treatment (such as adjuvant chemotherapy) or closer follow-up. LEVEL OF EVIDENCE: Level III, prognostic study.

Desmoid Tumors in the Active Surveillance Era: Evaluation of Treatment Options and Pain Relief in a Single-Center Retrospective Analysis.

In patients with desmoid tumors (DTs), active surveillance has been increasingly preferred over surgery, while treatment (including pharmacological therapy, radiotherapy, and/or surgery) is performed in cases with confirmed disease progression. This study aimed to evaluate event-free survival and pain management according to different treatment strategies. We evaluated event-free survival, including recurrence after initial surgical treatment or changes in the therapeutic management after initial non-surgical treatment and pain management according to different treatment strategies. All patients referred for DT in 2001-2021 at our institutions were stratified into four groups: those treated surgically prior to 2012 (SGPre12) or after 2012 (SGPost12), those treated pharmacologically (MG), and those under active surveillance (ASG). An event was defined as recurrence after initial surgical treatment or a change in therapeutic management. Overall, 123 patients were included in the study: 28 in SGPre12, 41 in SGPost12, 38 in MG, and 16 in ASG. Pharmacological treatment resolved painful symptoms in 16/27 (60%) patients (p = 0.0001). The median follow-up duration was 40 months (IQR 23-74). Event-free survival at 1, 3, and 5 years was: 85%, 70%, and 62% in SGPre12; 76%, 58%, and 49% in SGPost12; 49%, 31%, and 31% in MG; and 45%, 45%, and 45% in ASG. Our findings support the role of active surveillance as initial management, as demonstrated by the fact that about half the patients did not experience any progression, while surgery can be reserved as a first-line approach for selected patients. In terms of pain relief, medical therapy led to symptom resolution in more than half the cases.

Guideline-Based Follow-Up Outcomes in Patients With Gastrointestinal Stromal Tumor With Low Risk of Recurrence: A Report From the Italian Sarcoma Group.

Importance: Gastrointestinal stromal tumor (GIST) follow-up is recommended by international guidelines, but data on the role of follow-up in patients with low relapse risk are missing. For these patients, the potential benefit of anticipating recurrence detection should be weighed against psychological burden and radiologic examination loads in terms of costs and radiation exposure. Objective: To evaluate the outcomes of guideline-based follow-up in low-risk GIST. Design, Setting, and Participants: This multi-institutional retrospective cohort study involving Italian Sarcoma Group reference institutions evaluated patients with GIST who underwent surgery between January 2001 and June 2019. Median follow-up time was 69.2 months. Data analysis was performed from December 15, 2022, to March 20, 2023. Patients with GIST at low risk according to Armed Forces Institute of Pathology criteria were included provided adequate clinical information was available: primary site, size, mitotic index, surgical margins, and 2 or more years of follow-up. Exposures: All patients underwent follow-up according to European Society for Medical Oncology (ESMO) guidelines. Main Outcomes and Measures: The primary outcome was the number of tests needed to identify a relapse according to ESMO guidelines follow-up plan. Secondary outcomes included relapse rate, relapse timing, disease-free survival (DFS), overall survival (OS), GIST-specific survival (GIST-SS), postrelapse OS, secondary tumor rates, and theoretical ionizing radiation exposure. An exploratory end point, new follow-up schedule proposal for patients with low-risk GIST according to the observed results, was also assessed. Results: A total of 737 patients (377 men [51.2%]; median age at diagnosis, 63 [range, 18-86] years) with low-risk GIST were included. Estimated 5-year survival rates were 95.5% for DFS, 99.8% for GIST-SS, and 96.1% for OS. Estimated 10-year survival rates were 93.4% for DFS, 98.1% for GIST-SS, and 91.0% for OS. Forty-two patients (5.7%) experienced disease relapse during follow-up (9 local, 31 distant, 2 both), of which 9 were detected after 10 or more years. This translated into approximately 1 relapse detected for every 170 computed tomography scans performed, with a median radiation exposure of 80 (IQR, 32-112) mSv per patient. Nongastric primary tumor (hazard ratio [HR], 2.09; 95% CI, 1.14-3.83; P = .02), and KIT mutation (HR, 2.77; 95% CI, 1.05-7.27; P = .04) were associated with a higher risk of relapse. Second tumors affected 187 of 737 patients (25%), of which 56 were detected during follow-up and represented the primary cause of death in these patients. Conclusions and Relevance: In this cohort study on patients affected by low-risk GISTs, the risk of relapse was low despite a follow-up across 10 or more years. These data suggest the need to revise follow-up schedules to reduce the anxiety, costs, and radiation exposure of currently recommended follow-up strategy.

Sex Differences in Soft Tissue Sarcoma: Incidence, Clinicopathological Profile, Survival, and Costs.

Background: There are evident sex differences in the incidence of and mortality rates for several tumors. Soft tissue sarcomas (STSs) account for no more than 1% of all malignancies in adults. This study aimed to provide a comprehensive overview of the sex differences in the epidemiology of STSs and the related costs. Methods: This retrospective population-based study draws on epidemiological data regarding cases of STS collected by the cancer registry of the Italian Veneto region for the years 1990-2018. A joinpoint regression analysis was performed to identify significant changes in the trends of the standardized incidence rates in males and females. Bivariate and survival analyses were conducted to assess differences in clinicopathological characteristics and short-term mortality by sex. Direct health care costs incurred over 2 years after a diagnosis of STS were calculated, stratified by sex. Results: The incidence rates of STS at any age were higher for males; only among males the incidence rates showed a tendency to slightly increase. No significant sex differences came to light in short-term mortality or clinicopathological profile, except for the cancer site. Health care costs in the 2 years after a diagnosis of STS were not sex related. Conclusion: The STS incidence was found to be higher for males and showed a rising trend over the last three decades only for males. These findings could result from the occupational exposure to environmental mutagens mainly involving men. Sex did not affect the survival or the clinicopathological STS profile.

Digital pathology world tour.

Objective: Digital pathology (DP) is currently in the spotlight and is rapidly gaining ground, even though the history of this field spans decades. Despite great technological progress, the adoption of DP for routine clinical diagnostic use remains limited. Methods: A systematic search was conducted in the electronic databases Pubmed-MEDLINE and Embase. Inclusion criteria were all published studies that encompassed any application of DP. Results: Of 4888 articles retrieved, 4041 were included. Relevant articles were categorized as "diagnostic" (147/4041, 4%) where DP was utilized for routine diagnostic workflow and "non-diagnostic" (3894/4041, 96%) for all other applications. The "non-diagnostic" articles were further categorized according to DP application including "artificial intelligence" (33%), "education" (5%), "narrative" (17%) for reviews and editorials, and "technical" (45%) for pure research publications. Conclusion: This manuscript provided temporal and geographical insight into the global adoption of DP by analyzing the published scientific literature.

Time for a full digital approach in nephropathology: a systematic review of current artificial intelligence applications and future directions.

INTRODUCTION: Artificial intelligence (AI) integration in nephropathology has been growing rapidly in recent years, facing several challenges including the wide range of histological techniques used, the low occurrence of certain diseases, and the need for data sharing. This narrative review retraces the history of AI in nephropathology and provides insights into potential future developments. METHODS: Electronic searches in PubMed-MEDLINE and Embase were made to extract pertinent articles from the literature. Works about automated image analysis or the application of an AI algorithm on non-neoplastic kidney histological samples were included and analyzed to extract information such as publication year, AI task, and learning type. Prepublication servers and reviews were not included. RESULTS: Seventy-six (76) original research articles were selected. Most of the studies were conducted in the United States in the last 7 years. To date, research has been mainly conducted on relatively easy tasks, like single-stain glomerular segmentation. However, there is a trend towards developing more complex tasks such as glomerular multi-stain classification. CONCLUSION: Deep learning has been used to identify patterns in complex histopathology data and looks promising for the comprehensive assessment of renal biopsy, through the use of multiple stains and virtual staining techniques. Hybrid and collaborative learning approaches have also been explored to utilize large amounts of unlabeled data. A diverse team of experts, including nephropathologists, computer scientists, and clinicians, is crucial for the development of AI systems for nephropathology. Collaborative efforts among multidisciplinary experts result in clinically relevant and effective AI tools.

Low-Grade Uterine Leiomyosarcoma Is Highly Sensitive to Hormonal Treatment.

PURPOSE: According to the World Health Organization classification system, uterine leiomyosarcomas (ULMS) are high-grade. A diagnosis of smooth-muscle tumors of uncertain malignant potential (STUMP) is made when Stanford Criteria for ULMS are not met. When a STUMP recurs, the tumor is diagnosed as ULMS and medical treatment is the same as for ULMS. In recent years, some sarcoma centers valued the less aggressive clinical behavior of several recurring STUMP and, given their expression of estrogen and progesterone receptors, started to treat them with hormonal therapy. EXPERIMENTAL DESIGN: This was a retrospective cohort analysis conducted at three referral centers joining the Leiomyosarcoma Foundation Roundtable. We selected all cases of uterine smooth muscle tumors consistent with STUMP and treated with hormonal therapy. RESULTS: 27 consecutive patients were identified. Median age at diagnosis was 43 years. Stage was IA-IB in more than 70% of patients. In these patients, median time to relapse was 62 months. Sites of first relapses were mostly pelvis and peritoneum (76%). After a median follow-up of 49 months, 14 patients (52%) had a partial response while 10 (37%) had a minor response or stable disease. Median time to progression was not reached. CONCLUSIONS: We observed a response or long-term stability rate on hormonal therapy in the 90% range; in all cases the time to relapse was significantly longer than in ULMS and in most cases the relapse was abdominal. On the basis of these findings, we conclude that a proportion of patients with uterine smooth muscle neoplasms actually present with a "low-grade ULMS."

Indicators of clinical performance in monitoring soft tissue sarcoma management: a population-based perspective.

Background: Soft tissue sarcomas (STS) are rare malignancies which prognosis varies significantly by primary site, histological subtype, and tumor stage. Their low incidence, and the complexity of their clinico-pathological characteristics demand standardized, cancer-tailored diagnostics and therapies managed at high-volume, multidisciplinary care centers. This study evaluates the quality of STS management in north-east Italy (Veneto Region) through a list of ad hoc defined clinical indicators. Methods: This population-based study concerns all incident cases of STS in 2018 (214 cases) recorded in the adult population censored by the Veneto's regional Cancer Registry. Based on the international literature, a multidisciplinary working group of experts identified a set of indicators for monitoring the quality of diagnostic, therapeutic, and end-of-life clinical interventions. The quality of care was assessed by comparing the reference thresholds with the indicators' values achieved in clinical practice. Results: Diagnostic procedures showed poor adherence to the thresholds, with a low percentage of histological diagnoses validated by a second opinion. The indicators relating to the surgical treatment of superficial, small, low-grade STS, or of medium, high-grade STS of the head-neck, trunk, or limbs were consistent with the thresholds, while for intermediate, high-grade (large-sized, deep) and retroperitoneal STS they fell significantly below the thresholds. Conclusion: A critical evaluation of the clinical indicators allowed to uncover the procedures needing corrective action. Monitoring clinical care indicators improves cancer care, confirms the importance of managing rare cancers at highly specialized, high-volume centers, and promotes the ethical sustainability of the healthcare system.

Diagnostic, Prognostic, and Therapeutic Role for Angiogenesis Markers in Head and Neck Squamous Cell Carcinoma: A Narrative Review.

Despite refinements to diagnostic and therapeutic approaches over the last two decades, the outcome of patients with head and neck squamous cell carcinoma (HNSCC) has not shown substantial improvements, especially regarding those with advanced-stage disease. Angiogenesis is believed to be a turning point in the development of solid tumors, being a premise for mass growth and potential distant dissemination. Cancer-induced angiogenesis is a result of increased expression of angiogenic factors, decreased expression of anti-angiogenic factors, or a combination of both. The assessment of angiogenesis has also emerged as a potentially useful biological prognostic and predictive factor in HNSCC. The aim of this review is to assess the level of current knowledge on the neo-angiogenesis markers involved in the biology, behavior, and prognosis of HNSCC. A search (between 1 January 2012 and 10 October 2022) was run in PubMed, Scopus, and Web of Science electronic databases. After full-text screening and application of inclusion/exclusion criteria, 84 articles are included. The current knowledge and debate on angiogenesis in HNSCC presented in the eligible articles are stratified as follows: (i) diagnostic markers; (ii) prognostic markers; (iii) predictive markers; and (iv) markers with a potential therapeutic role. Angiogenesis is a biological and pathological indicator of malignancies progression and has negative implications in prognosis of some solid tumors; several signals capable of tripping the "angiogenic switch" have also been identified in HNSCC. Although several studies suggested that antiangiogenic agents might be a valuable adjunct to conventional chemo-radiation of HNSCC, their long-term therapeutic value remains uncertain. Further investigations are required on combinations of antiangiogenic agents with conventional chemotherapeutic ones, immunotherapeutic and molecularly targeted agents in HNSCC. Additional data are necessary to pinpoint which patients could benefit most from these treatments.

Fusion transcriptome profiling defines the monoclonal origin of multifocal epithelioid haemangioma of bone.

AIMS: Epithelioid haemangioma (EH) of bone remains a highly controversial entity. Indeed, the WHO classifies EHs of soft tissues as benign tumours, whereas bone EHs are considered intermediate-locally aggressive tumours due to common multifocal presentation and local destructive growth. To gain insights into the clinical behaviour and biology of EH of bone we retrospectively analysed 42 patients treated in a single institution from 1978 to 2021. METHODS AND RESULTS: Multifocal presentation was detected in 17 of 42 patients (40%) primarily as synchronous lesions. Patients were treated with curettage (57%), resection (29%) or biopsy, followed by radiotherapy or embolisation (14%). Follow-up (minimum 24 months) was available for 38 patients, with only five local recurrences (13%) and no death of disease. To clarify whether the synchronous bone lesions in multifocal EH represent multicentric disease or clonal dissemination, four cases were profiled by RNA-sequencing. Separate lesions from the same patient, which showed a similar transcriptional profile, expressed the same fusion transcript (involving FOS or FOSB) with identical gene breakpoints. CONCLUSIONS: These results indicate that, in EH of bone, multifocal lesions are clonally related and therefore represent the spread of a same neoplastic clone rather than simultaneous independent tumours. This finding is in apparent contradiction with the benign clinical course of the disease, and suggests that tumour dissemination in bone EH probably reflects a phenomenon of passive spreading, with tumour cells colonising distal sites while maintaining their benign biological nature.

Characterization of Tumor and Immune Tumor Microenvironment of Primary Tumors and Metastatic Sites in Advanced Renal Cell Carcinoma Patients Based on Response to Nivolumab Immunotherapy: Preliminary Results from the Meet-URO 18 Study.

BACKGROUND: Prognostic and predictive factors for patients with metastatic renal cell carcinoma (mRCC) treated with immunotherapy are highly warranted, and the immune tumor microenvironment (I-TME) is under investigation. METHODS: The Meet-URO 18 was a multicentric retrospective study assessing the I-TME in mRCC patients treated with ≥2nd-line nivolumab, dichotomized into responders and non-responders according to progression-free survival (≥12 months and ≤3 months, respectively). The primary objective was to identify differential immunohistochemical (IHC) patterns between the two groups. Lymphocyte infiltration and the expressions of different proteins on tumor cells (CD56, CD15, CD68, and ph-mTOR) were analyzed. The expression of PD-L1 was also assessed. RESULTS: A total of 116 tumor tissue samples from 84 patients (59% were primary tumors and 41% were metastases) were evaluated. Samples from responders (N = 55) were significantly associated with lower expression of CD4+ T lymphocytes and higher levels of ph-mTOR and CD56+ compared with samples from non-responders (N = 61). Responders also showed a higher CD3+ expression (p = 0.059) and CD8+/CD4+ ratio (p = 0.084). Non-responders were significantly associated with a higher percentage of clear cell histology and grading. CONCLUSIONS: Differential IHC patterns between the tumors in patients who were responders and non-responders to nivolumab were identified. Further investigation with genomic analyses is planned.

The Prognostic Role of the Immune Microenvironment in Sinonasal Intestinal-Type Adenocarcinoma: A Computer-Assisted Image Analysis of CD3+ and CD8+ Tumor-Infiltrating Lymphocytes.

The prognostic value of conventional histopathological parameters in the sinonasal intestinal-type adenocarcinoma (ITAC) has been debated and novel variables should be investigated. Increasing evidence demonstrated that the evolution of cancer is strongly dependent upon the complex interactions within tumor microenvironment. The aim of this retrospective study was to assess the features of immune microenvironment in terms of CD3+ and CD8+ cells in a series of ITAC and explore their prognostic role, as well as their relations with clinicopathological variables. A computer-assisted image analysis of CD3+ and CD8+ tumor-infiltrating lymphocytes (TIL) density was conducted on surgical specimens of 51 patients with ITAC that underwent a curative treatment including surgery. ITAC displays variable TIL density, which is associated with OS. In a univariate model, the density of CD3+ TIL was significantly related to OS (p = 0.012), whereas the association with CD8+ TIL density resulted in being non-significant (p = 0.056). Patients with intermediate CD3+ TIL density were associated with the best outcome, whereas 5-year OS was the lowest for intermediate CD8+ TIL density. CD3+ TIL density maintained a significant association with OS in the multivariable analysis. TIL density was not significantly related to demographic and clinicopathological variables. CD3+ TIL density was independently associated with OS in a non-linear fashion and patients with intermediate CD3+ TIL density had the best outcome. Though based on a preliminary analysis on a relatively small series of patients, this finding makes TIL density a potential independent prognostic factor of ITAC.

Uncommon presentation of a giant psoas muscle lipoma: a case report and brief literature review.

Giant retroperitoneal lipomas, particularly within the psoas muscle, are a rare condition. We herein present one such case of a 45-year-old Italian man and a literature review. There are only two case reports published in the literature, thus posing challenges for the appropriate diagnosis and treatment. Our patient was admitted to the emergency department with colicky abdominal pain. Computerized tomography (CT) with contrast enhancement revealed kidney stones and a 19.5×13.6×18 cm mass of adipose tissue with septa located in the right retroperitoneum, in close continuity with the right psoas major muscle. Magnetic resonance imaging showed a voluminous neoformation with predominantly adipose content and a compressive effect on adjacent vascular structures. The CT-guided biopsy indicated spindle cell mesenchymal neoplasm, not otherwise specified. Surgical resection of the retroperitoneal mass with the capsule was performed, and a histopathology examination confirmed the diagnosis of spindle cell lipoma. Despite the fact that CT and MRI are the main diagnostic tools, this case report emphasizes the need for a CT-guided core needle biopsy prior to surgery for appropriate diagnosis.

Accessory spleens recapitulate the immune microenvironment of the main spleen in immune thrombocytopenia.

Accessory spleens (AcS) may play a relevant role in immune thrombocytopenia (ITP) and possibly contribute to ITP relapse following splenectomy. Little is known about the immune microenvironment of AcS in ITP. To address this issue, we compared the histological features of eight matched AcS and main spleen (MS) samples, obtained from adult patients with primary ITP. AcS and MS had overlapping immune architectural features and lymphoid composition, suggesting that similar immunologic events occur in AcS and MS of ITP. These findings may have implications for the potential mechanisms of AcS-mediated ITP relapse. Further studies are needed to confirm these results and to dissect spleen immunity in ITP.

Higher accuracy of surgical over core needle biopsy for the diagnosis of lymphoproliferative disorders.

INTRODUCTION: The diagnosis of lymphoproliferative disorders (LPDs) is based on histological evaluation of representative tissue samples. Despite surgical excision biopsies (SEBs) are reference procedures for such diagnoses, lymph node core needle biopsies (LNCBs) are increasingly performed. The diagnostic yield of LNCB is, however, debated and few studies have compared the reproducibility of LNCB and SEB findings. METHODS: To address the diagnostic value of LNCB and SEB, the present study considered a retrospective series of 43 paired LNCB/SEB samples. After histological revision, concordance rates between matched LNCB/SEB samples were evaluated, assuming SEB as gold standard procedure. The actionability of LNCB and SEB-based diagnoses (i.e., relevance for planning further medical interventions) was also assessed. RESULTS: Overall, LNCB provided actionable diagnoses in 39/43 (90.7%) cases, but a consistent subset of them (7/39 [17.9%]) turned out to be wrong at SEB. The cumulative diagnostic inaccuracy of LNCB (i.e., inadequate samples plus wrong diagnoses) was 25.6% and the mean diagnostic delay in such cases was 54.2 days. CONCLUSIONS: Although limited by selection biases due to its retrospective nature, this study highlights the intrinsic limitations of LNCB for the diagnosis of LPDs. SEB remains the gold standard procedure and should be performed in all suitable cases.