Potential For Distant Metastasis Research Articles

Mismatch repair protein deficiency and its implications on distant metastasis in colorectal cancer: A comprehensive analysis.

While previous studies have indicated variability in distant metastatic potential among different mismatch repair (MMR) states in colorectal cancer (CRC), their findings remain inconclusive, especially considering potential differences across various ethnic backgrounds. Furthermore, the gene regulatory networks and the underlying mechanisms responsible for these variances in metastatic potential across MMR states have yet to be elucidated. We collected 2058 consecutive primary CRC samples from the South West of China and assessed the expression of MMR proteins (MLH1, MSH2, MSH6, and PMS2) using immunohistochemistry. To explore the inconsistencies between different MMR statuses and recurrence, we performed a meta-analysis. To delve deeper, we employed Weighted Gene Co-expression Network Analysis (WGCNA), ClueGo, and iRegulon, pinpointing gene expression networks and key regulatory molecules linked to metastasis and recurrence in CRC. Lastly, both univariate and multivariate Cox regression analyses were applied to determine the impact of core regulatory molecules on metastasis. Of the samples, 8.2% displayed deficient MMR (dMMR), with losses of MLH1 and PSM2 observed in 40.8% and 63.9%, respectively. A unique 24.3% isolated loss of PMS2 without concurrent metastasis was identified, a result that diverges from established literature. Additionally, our meta-analysis further solidifies the reduced recurrence likelihood in dMMR CRC samples compared to proficient MMR (pMMR). Two gene expression networks tied to distant metastasis and recurrence were identified, with a majority of metastasis-related genes located on chromosomes 8 and 18. An IRF1 positive feedback loop was discerned in the metastasis-related network, and IRF1 was identified as a predictive marker for both recurrence-free and distant metastasis-free survival across multiple datasets. Geographical and ethnic factors might influence peculiarities in MMR protein loss. Our findings also highlight new gene expression networks and crucial regulatory molecules in CRC metastasis, enhancing our comprehension of the mechanisms driving distant metastasis.

De novo male breast metastases from nasopharyngeal carcinoma: a case report

BackgroundNasopharyngeal carcinoma is known for its high potential for regional and distant metastasis. However, breast metastasis is rarely reported.Case presentationA 39-year-old Caucasian male presented with bilateral neck lymph node enlargement. Radiological examination with contrast-enhanced computed tomography scan and breast imaging revealed an enhancing mass lesion in the right breast. Histopathology of the nasopharynx mass was suggestive of undifferentiated nasopharyngeal carcinoma. A breast biopsy confirmed the diagnosis of synchronous breast metastasis from the nasopharyngeal carcinoma. We present this study to illustrate that Nasopharyngeal carcinoma can metastasize to the male breast. Furthermore, the high incidence of nasopharyngeal carcinoma metastasis underscores the pressing need to identify effective and safe strategies, emphasizing the importance of utilizing computed tomography scans for metastasis detection.ConclusionThe present study illustrates the first case of synchronous male breast metastases from nasopharyngeal carcinoma. Thus, it is critical to distinguish between metastatic pathology and coexisting second malignancies to plan appropriate therapy.

Revolutionizing the battle against locally advanced breast cancer: A comprehensive insight into neoadjuvant radiotherapy.

Breast cancer (BC) constitutes one of the most pervasive malignancies affecting the female population. Despite progressive improvements in diagnostic and therapeutic technologies, leading to an increased detection of early stage BCs, locally advanced breast cancer (LABC) persists as a significant clinical challenge. Owing to its poor overall survival (OS) rate, elevated recurrence rate, and high potential for distant metastasis, LABC prominently impacts the comprehensive efficacy of BC treatments. Radiotherapy, encompassing preoperative, intraoperative, and postoperative modalities, is acknowledged as an effective strategy for mitigating BC metastasis and enhancing survival rates among patients. Nevertheless, the domain of preoperative neoadjuvant radiotherapy (NART) remains conspicuously underexplored in clinical studies. Available research suggests that NART can induce tumor volume reduction, provoke fibrotic changes in tumor and adjacent normal tissues, thereby mitigating intraoperative cancer propagation and enhancing the quality of life for LABC patients. This manuscript seeks to provide a review of contemporary research pertaining to LABC and its preoperative radiotherapy.

Relationship Between Metabolic Activity, Cellularity, Histopathological Features of Primary Tumors and Distant Metastatic Potential in Breast Cancer.

The aim of this study was to evaluate the relationship between the types of distant metastatic spread, histopathological features, and imaging features of primary tumor on positron emission tomography/magnetic resonance imaging (PET/MRI) for primary staging in newly diagnosed breast invasive ductal carcinoma (IDC) patients. Data from 289 female patients were retrospectively evaluated. Maximum standardized uptake value, metabolic tumor volume (MTV), total lesion glycolysis (TLG), and minimum apparent diffusion coefficient (ADCmin) values of primary tumors were obtained from PET/MRI. The patients were grouped as non-metastatic, oligometastatic (1-5 metastatic lesions) and multimetastatic (>5 metastatic lesions) disease according to the number of distant metastases, and divided into two groups as isolated bone metastasis (IBM) and mixed/soft tissue metastasis (M-SM) groups according to the sites of metastatic spread. Metabolic parameters had higher values and ADCmin had lower values in the multimetastatic and oligometastatic groups than in the non-metastatic group. MTV was the only parameter that showed significant difference between the multimetastatic and oligometastatic groups. MTV and TLG were significantly higher in the M-SM group than in the IBM group. 18F-fluorodeoxyglucose PET parameters had significantly higher values in grade 3, hormone receptor negative, human epidermal growth factor receptor 2 positive, triple negative, and highly proliferative (Ki-67 ≥14%) tumors. The prediction models that included imaging parameters to predict the presence of distant metastasis had higher discriminatory powers than the prediction models that included only histopathological parameters. Primary tumors with higher metabolic-glycolytic activity and higher cellularity were more aggressive and had higher metastatic potential in breast IDC. Compared with histopathological parameters alone, the combination of imaging parameters and histopathological features of primary tumors may help to better understand tumor biology and behavior.

Metastasis of maxillary sinus adenoid cystic carcinoma to the humerus bone—A rare case report

Adenoid cystic carcinoma accounts for 10 to 12% of all salivary gland malignant neoplasms with an estimated incidence of 3 to 4.5 cases per million per year. Perineural spread and multiple local recurrences are its defining features, although the liver and lung are the most frequent sites for distant metastases. It is extremely uncommon for adenoid cystic carcinoma of the maxillary sinus to spread to distant bones. Few cases of adenoid cystic carcinoma with distant bone metastasis have been reported. Here, we report a known case of the adenoid cystic carcinoma of the maxillary sinus in a 40-yearold male, with isolated metastasis to the left humerus bone presenting 4 years later to the excision of the primary lesion. The fine-needle aspiration cytology, trucut biopsy, and immunocytochemistry of the left humerus osteoexpansile lesion confirmed the diagnosis of metastatic adenoid cystic carcinoma. This rare case report re-emphasizes the distant metastatic potential of adenoid cystic carcinoma.

DS07 (P22) Clinicopathologic characteristics of metastatic cutaneous squamous cell carcinoma: a cohort study

Abstract Cutaneous squamous cell carcinoma (cSCC) is a keratinocyte tumour with excellent prognosis following early-stage surgical treatment. Nevertheless, cSCC possesses an inherent potential for locoregional and distant metastasis in ∼4% of cases, contributing to disease-specific mortality. Recent guidance on cSCC management risk stratifies patients based on clinicopathological factors to identify those patients most at risk of metastasis. A retrospective cohort study identified 3455 cSCCs arising in 2522 patients, via review of histopathological diagnoses of cSCC at a tertiary hospital in Dublin, Ireland, between the years of 2009 and 2019. The aim of the study was to describe adequately a large cohort of patients with metastatic cSCC and investigate factors associated with metastasis. Metastatic disease was identified by histopathological and/or radiological confirmation in 116 patients, with complete data available in 105 cases. Twenty-two (21%) were female. Mean age at primary tumour diagnosis was 74.8 years, and mean time to first metastasis was 0.8 years. Twenty-six (25%) patients were immunosuppressed, the commonest reason for which was haematological malignancy. Median (SD) size of the primary tumour was 36 (21.65) mm, and median depth was 10 (7.43) mm. Eighty-six (82%) tumours were located on the head and neck. Seventeen (16%) of the tumours were recurrent, 58 (55%) were > 20 mm, 38 (36%) demonstrated extension beyond subcutaneous fat, 22 (21%) demonstrated lymphovascular invasion, 24 (23%) demonstrated perineural invasion of nerves > 0.1 mm in diameter, and 41 (39%) tumours were poorly differentiated. Twenty-six patients developed distant metastatic disease in addition to nodal metastasis. In most patients in our cohort, AJCC 8th Edition histopathological high-risk cSCC features were absent, apart from size > 20 mm. Conversely, most patients exhibited at least one clinical high-risk cSCC feature as per the British Association of Dermatologists guidelines for the management of cutaneous squamous cell carcinoma, including advanced age and tumour location (Keohane SG, Botting J, Budny PG et al. British Association of Dermatologists guidelines for the management of people with cutaneous squamous cell carcinoma 2020. Br J Dermatol 2021; 184:401–14). All patients were discussed at a specialist skin multidisciplinary team meeting, with significant variability noted in preoperative imaging, depending on the primary treating specialty. This cohort illustrates the importance of risk stratification of cSCC on clinicopathological features. This facilitates management decisions and ongoing patient surveillance with a view to preventing disease-specific morbidity and mortality.

P22 Clinicopathologic characteristics of metastatic cutaneous squamous cell carcinoma: a cohort study

Abstract Cutaneous squamous cell carcinoma (cSCC) is a keratinocyte tumour with excellent prognosis following early-stage surgical treatment. Nevertheless, cSCC possesses an inherent potential for locoregional and distant metastasis in approximately 4% of cases, contributing to disease-specific mortality. Recent guidance on cSCC management risk stratifies patients based on clinicopathological factors to identify those patients most at risk of metastasis. A retrospective cohort study identified 3455 cSCCs arising in 2522 patients, via review of histopathological diagnoses of cSCC at a tertiary hospital in Dublin, Ireland, between the years of 2009 and 2019. The aim of the study was to describe adequately a large cohort of patients with metastatic cSCC and investigate factors associated with metastasis. Metastatic disease was identified by histopathological and/or radiological confirmation in 116 patients, with complete data available in 105 cases. Twenty-two (21%) were female. Mean age at primary tumour diagnosis was 74.8 years and mean time to first metastasis was 0.8 years. Twenty-six (25%) patients were immunosuppressed, the commonest reason for which was haematological malignancy. Median (SD) size of the primary tumour was 36 (21.65) mm and median depth was 10 (7.43) mm. Eighty-six (82%) tumours were located on the head and neck. Seventeen (16%) of the tumours were recurrent, 58 (55%) were > 20 mm, 38 (36%) demonstrated extension beyond subcutaneous fat, 22 (21%) demonstrated lymphovascular invasion, 24 (23%) demonstrated perineural invasion of nerves > 0.1 mm in diameter and 41 (39%) tumours were poorly differentiated. Twenty-six patients developed distant metastatic disease in addition to nodal metastasis. In most patients in our cohort, AJCC 8th Edition histopathological high-risk cSCC features were absent, apart from size > 20 mm. Conversely, most patients exhibited at least one clinical high-risk cSCC feature as per the British Association of Dermatologists’ guidelines for the management of cutaneous squamous cell carcinoma, including advanced age and tumour location (Keohane SG, Botting J, Budny PG et al. British Association of Dermatologists guidelines for the management of people with cutaneous squamous cell carcinoma 2020. Br J Dermatol 2021; 184:401–14). All patients were discussed at a specialist skin multidisciplinary team meeting, with significant variability noted in preoperative imaging, depending on the primary treating specialty. This cohort illustrates the importance of risk stratification of cSCC on clinicopathological features. This facilitates management decisions and ongoing patient surveillance with a view to preventing disease-specific morbidity and mortality.

Giant cell tumor of clivus: a rare case report and review of literature

Clival giant cell tumors (GCTs) are an extremely rare type of tumor, with only 13 cases reported to date. Despite being histologically considered benign, these tumors can be locally aggressive and have a high rate of local recurrence, as well as the potential for distant metastasis. Due to their rarity and the difficulty of treating them due to their critical location, the ideal treatment protocol for managing clival GCTs remains controversial. The present report describes a 22-year-old female who experienced ptosis on her right eye and visual disturbance for one month. Magnetic resonance imaging (MRI) revealed a large, heterogenous, lobulated mass lesion arising from the clivus, extending anteriorly and compressing the optic chiasm and optic tract, with both parasellar extension and extension into the sphenoid sinus. An endoscopic endonasal trans-sphenoidal procedure was performed to excise the lesion. Post-operative MRI revealed residual disease, so a revision surgery was done using a combined microscopic and endoscopic procedure. Following surgery, the patient was given Denosumab for one year as well as has been symptom-free for the past 18 months of follow-up. This report contributes to the limited literature on the GCTs involving the clivus.

Socioeconomic and demographic factors on academic center accessibility in sebaceous adenocarcinoma: An NCDB analysis.

e21501 Background: Sebaceous adenocarcinoma (SA) is a rare, aggressive adnexal tumor shown to have both local and distant metastatic potential. The 5-year overall survival rate for this cancer is 78% for localized/regional disease and 50% for metastatic disease. Improved survival in other skin malignancies, such as melanoma, has been previously linked to treatment at academic cancer centers. The National Cancer Database (NCDB) was analyzed to determine variables impacting treatment at academic versus non-academic facility types in SA. Methods: A retrospective cohort analysis using the NCDB from 2004 to 2019 included patients diagnosed with histologically confirmed SA (N = 3,378). Socio-demographic factors (sex, age, race, Hispanic status, insurance type, urban/rural designation, facility location, education, income, distance from facility, and Charlson-Deyo score) were analyzed using Pearson Chi-squared tests and multivariate analysis of factors on academic center accessibility (facility type) was performed via binary logistic regression. A significance level of 0.05 was used. Results: The number of cases diagnosed with SA has steadily increased from 2004 to 2019 (152 and 287, respectively, R2 = 0.894). Most patients were male (59.1%), White (89.8%), not Hispanic (89.6%), insured (95.7%), and lived in an urban area (98.4%). There was a statistically significant difference between sex, race, insurance type, urban/rural designation, facility location, education, income, and distance from residence to the facility on academic facility type. Male patients were 1.3 times more likely to access academic centers compared to female patients (p < 0.001, CI = [0.681 - 0.911]). Patients with median household incomes in the top quartile were also 2.2 times more likely than those in the bottom quartile to receive treatment at an academic center (p < 0.001, CI = [1.676 - 2.992]). Conclusions: There has been an upward trend in the diagnosis of SA since 2004 with a predilection for White males. Female patients and patients with a lower income are less likely to receive treatment at an academic center. Given the rarity of the disease, this study serves as a valuable tool for understanding the factors associated with facility-type access. Future studies aim to determine the effect of academic center type on overall survival. Additional research is needed to understand the difference in treatment at academic versus non-academic facilities.

Malignant adipocytic tumours: A 20‑year single‑centre retrospective study.

Adipocytic tumours are the most common soft tissue neoplasms. Among them, liposarcoma is the most frequent malignant neoplasm. However, to the best of our knowledge, no previously published study has assessed the evolution and oncological prognosis of the different subtypes of liposarcoma at the retroperitoneal level compared with at other locations. The present study is a retrospective observational study in which all patients were operated on between October 2000 and January 2020 with a histological diagnosis of liposarcoma. Variables, such as age, sex, location, histological type, recurrence, type of treatment and mortality, among others, were analysed. The patients were divided into two groups: Group A (retroperitoneal location) and group B (non-retroperitoneal location). A total of 52 patients with a diagnosis of liposarcoma (17 women and 35 men) and a mean age of 57.2±15.9 years were assessed. A total of 16 patients were classified into group A and 36 into group B. The OR of recurrence was 1.5 (P=0.02) for R1 vs. R0 resection in group A. The OR of recurrence in group B for R1 vs. R0 resection was 1.8 (P=0.77), whereas for R2 vs. R0 resection, the OR was 69 (P=0.011). In conclusion, 52 cases of malignant adipocytic tumours collected during 2000-2020 were analysed with the new World Health Organization classification (updated 2020). Although its recurrence potential and capacity for distant metastasis depended on each histological type, surgical treatment with unaffected margins was the main prognostic factor for survival. The present study identified differences in relation to the survival of each histological subtype and its location, finding greater survival in dedifferentiated liposarcoma, myxoid liposarcoma and pleomorphic liposarcoma located at the extraperitoneal level than in the retroperitoneal location. Resectability was not influenced by liposarcoma location.

Pathological nodal status as a main predictive factor of survival and treatment outcomes of submandibular salivary gland cancers: A 25-year single center experience

IntroductionAim of this study was to explore the survival predictive factors and treatment outcomes in a cohort of SGC patients treated at a single center over a period of 25 years. Materials and methodsPatients who had received primary treatment for SGC were enroled. Outcomes evaluated were: overall survival (OS), disease specific survival (DSS), recurrence free survival (RFS), locoregional recurrence free survival (LRFS) and distant metastasis free survival (DFS). ResultsA total of 40 patients with SGC were enroled in the study. The most common tumor was the adenoid cystic carcinoma (60% of cases). Cumulative OS for 5-and 10-year follow up period was 81% and 60%, respectively. Thirteen patients (32.5%) developed distant metastases during follow-up. Nodal status, high-grade histology, tumor stage and adjuvant radiation-therapy (RT) were significant variables on multivariate analysis for survival and treatment outcomes. ConclusionsSubmandibular gland carcinomas represent rare and heterogenous tumor group regarding histological appearance and locoregional and distant metastatic potential. Tumor histological grade, AJCC tumor stage and nodal status were the strongest predictive factors for survival and treatment outcomes. RT improved OS and locoregional treatment outcome, but not DFS. Elective neck dissection (END) could be beneficial for selected cases of SGC. Superselective neck dissection of levels I-IIa may be the level of dissection for END. Distant metastases were the main cause of death and treatment failure. Prognostic factors for poor DMFS were AJCC stage III and IV, high tumor grade and nodal status.

Differential Gene Expression Profiling in Alveolar Echinococcosis Identifies Potential Biomarkers Associated With Angiogenesis.

Alveolar echinococcosis (AE) is a worldwide zoonosis caused by Echinococcus multilocularis. Alveolar echinococcosis is a severe chronic parasitic disease that exhibits a tumor-like growth, with the potential for invasion and distant metastasis; however, the molecular mechanism underlying this condition remains unclear. Transcriptome analyses were performed to detect differentially expressed genes (DEGs) in samples from patients with AE with invasion and distant metastasis. The results were further verified by immunohistochemistry. A total of 1796 DEGs were identified, including 1742 upregulated and 54 downregulated DEGs. A subsequent functional analysis showed that the significant DEGs were involved in the angiogenesis process. Immunohistochemical analysis confirmed the reliability of the transcriptomic data. These results suggest that angiogenesis is a possible mechanism underlying the tumor-like biological behavior observed during E multilocularis infection. Genes related to this process may play important roles in AE invasion and distant metastasis.

Paravertebral Pseudoendocrine Sarcoma

Abstract Introduction/Objective Pseudoendocrine sarcoma is a rare and newly described, emerging entity occurring predominantly in middle-aged to elderly males with apredilection for the thoracic paravertebral soft tissue. Pseudoendocrine sarcoma is a recently recognized intermediate-grade sarcoma with CTNNB1 mutations. Methods/Case Report Herein, we present a case of a 66-year-old male with a 10-year history of a progressively enlarging, painful, mid-back lesion. CT scan of the chest demonstrated a right paraspinal soft tissue mass measuring 9.5 x 5.5 x 4.5 cm located at the level of T8-T11. An image-guided biopsy was performed revealing monotonous, epithelioid cells, with round hyperchromatic nuclei, eosinophilic, granular cytoplasm, and indistinct borders arranged in rosettes. Mitoses, necrosis and lymphovascular invasion were not identified.The tumor cells were positive for Beta- catenin, CD56, BCL-2, BCL-6, CD4, CD34 and CD 68, and had a low-proliferative index. The neoplastic cells lacked staining with CK-AE1/AE3, CAM-5.2, NKX3.1, PAX8, Chromogranin, Synaptophysin, NSE, EMA, CD3, CD7, PAX5, and inhibin. The morphology and the immunophenotype support the diagnosis of pseudoendocrine sarcoma. Results (if a Case Study enter NA) N/A. Conclusion To date, few cases have been described in the literature. Recognition of this entity is important due to the potential for local recurrence (43%), and regional and distant metastasis. Complete excision of the lesion as well as adequate patient surveillance is imperative as we gain more understanding of the metastatic potential and prognosis of this emerging entity.

Evaluation of relationship between maximum SUV measured on 18F-FDG PET/CT with tumor pathological types, size, lymph node metastasis and distant metastasis in non-small cell lung cancer

BackgroundLung cancer is the most commonly diagnosed cancer, of which the non-small cell lung cancer (NSCLC) accounts for approximately 80% of the newly diagnosed lung cancer. The prognosis of lung tumors depends on early and accurate staging as well as the histopathological type of the tumor. It is suggested that NSCLC with different histopathological types and primary tumor sizes can elicit variable max.SUV values on 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG) PET/CT with different lymph nodes and distant metastatic potential. In this study, we aim to evaluate the relationship between the maximum SUV measured on (18F-FDG) PET/CT with tumor pathological type, primary tumor size, lymph node metastasis, and distant metastasis in NSCLC.ResultsThis is a cross-sectional analysis of the (FDG-PET/CT) findings of 40 patients with NSCLC. Statistical analysis is used to determine correlation between max.SUV and tumor size, with each pathological type, nodal (N) staging and distant metastasis (M) staging. The primary lung tumors histopathological types were 25 (62.5%) adenocarcinomas, 12 (30%) squamous cell carcinomas and 3 (7.5%) large cell carcinomas. The max.SUV and tumor size of the squamous cell carcinoma group were significantly higher than max.SUV of adenocarcinoma and large cell cancer groups (P = 0.000009). A significant positive correlation was found between the primary tumor max.SUV and tumoral size. Neither lymph node nor distant metastases involvement was correlated with tumor max.SUV.ConclusionsThe tumor size and histologic subtype both strongly influence FDG uptake in lung cancer. Nonetheless, max.SUV cannot be regarded as a predictive of metastases or lymph node involvement.

Comparison of clinical features between patients with bone and soft tissue fibrosarcomas.

Fibrosarcomas predominantly arise in soft tissues, but can also develop in bone. Because of their rarity, whether bone development has an impact on clinical features has not been addressed. We included fibrosarcoma patients diagnosed between 1983 and 2016 in the Surveillance, Epidemiology, and End Results database. Differences in clinical features between fibrosarcoma of bone (FS-B) and fibrosarcoma of soft tissue (FS-ST) were investigated. After excluding patients without information regarding cause of death, site of origin, distant tumor or survival, 1443 patients were included. Of those, 98 patients had FS-B. Patients with FS-B were younger, more frequently male, with fibrosarcomas that more often developed in an extremity and were histologically high-grade. In contrast, no difference in potential to metastasize was observed. Survival was almost equal between FS-B and FS-ST (FS-B/FS-ST: cancer-specific survival, hazard ratio [HR]: 1.2, 95% confidence interval [CI]: 0.8-1.7; overall survival, HR: 1.3, 95% CI: 0.9-1.7). Our results clearly indicated that patient backgrounds differed, such as younger age and greater tendencies to affect males, develop in an extremity and show high-grade tumor in patients with FS-B. In contrast, no differences were observed in distant metastatic potential or survival.

Yield of sentinel lymph node biopsy in sebaceous carcinoma and predictors of advanced disease: A retrospective analysis of the National Cancer Database

To the Editor: Sebaceous carcinoma (SC) is a rare cutaneous malignancy with potential for lymph node or distant metastasis. Most SC presents as localized disease, but periocular SC manifests distinct tumor behavior from extraocular SC with a greater propensity for metastasis. Present guidelines suggest that American Joint Committee on Cancer, Eighth Edition stage T2c periocular or greater tumors can be considered for sentinel lymph node biopsy (SLNB), although SLNB is not recommended for extraocular SC because subclinical nodal metastasis is thought to be uncommon in this setting.

Distinct mutational landscapes characterize melanomas metastatic to different anatomical sites.

9562 Background: Despite revolutionary advances in systemic therapies for melanoma, many patients with metastatic disease have limited treatment options and some sites of disease remain particularly challenging to control, such as brain and liver metastases. We sought to define anatomical site-specific mutational profiles of melanoma metastases from which potentially novel personalized therapeutic opportunities may be developed. Methods: Targeted exome genomic profiling was performed via the FoundationOneCDx platform and known or likely pathogenic variants retained for analysis. PD-L1 immunohistochemistry was performed with the Dako 22C3 assay with PD-L1+ defined as tumor proportion score ≥1. Tumor mutational burden (TMB)-high was defined as TMB ≥10mut/Mb. UV signature was calculated using established algorithms. Aberrations in 23 genes potentially actionable in melanoma ( BARD1, BRAF, BRCA1/2, CDKN2A, DDX3X, FANCC, HRAS, IDH1, KIT, KRAS, MAP2K1, NF1, NRAS, PALB2, PIK3CA, PPP6C, PTEN, RAC1, RAD51C/D, RB1, TP53) were compared across metastatic sites including skin, lymph node, lung, liver, and brain. Results: A total of 4918 cutaneous-type melanoma tumors was evaluated, including 2854 skin lesions (primary/metastasis) and metastases from lymph nodes (n = 858), liver (n = 194), lung (n = 342), and brain (n = 200). The commonly mutated genes were CDKN2A (2220/4918, 45.1%), BRAF (2148/4918, 43.7%), NRAS(1347/4918, 27.4%), NF1 (1038/4918, 21.1%), TP53 (1234/4918, 25.1%) and PTEN (1038/4918, 13.5%). Compared with skin lesions, metastases to the lung were enriched for variants affecting NF1 (OR 2.57, p = 8.99e-13), TP53 (OR 1.65, p = 3.04e-04) and depleted in NRAS (OR 0.49, p = 9.00e-06) and BRAF (OR 0.70, p = 1.13e-02). Lung metastases were associated with higher prevalence of UV signatures, PD-L1 positivity and high TMB. PTEN variants were enriched in both brain (OR 3.00, p = 2.38e-08) and small intestine (OR3.46, p = 6.63e-3) metastases. Brain metastases were also enriched for CDKN2A variants (OR 1.56, p = 4.50e-02). Lymph node metastases had lower rates of UV signatures, NF1 variants, or high TMB, but were associated with PD-L1 positivity. Positional analysis of variants revealed that several, including NRAS, MAP2K1, KRAS, HRAS, IDH1, RAC1, GNA11 and GNAQ were highly restricted to hotspot loci, without definite variation by metastatic site. Conversely, variants affecting CDKN2A, PTEN, TP53 and NF1 were distributed widely across the gene, with high levels of non-hotspot mutations observed in skin lesions, suggesting that such non-hotspot subclones contribute less to distant metastatic potential and are lost during disease evolution. Conclusions: We observed distinct and organ site-specific mutational patterns in patients with metastatic melanoma. These data raise the possibility of metastatic phenotype-directed therapy to improve the personalization and outcomes of treatment for this disease.

Proton therapy for skull-base adenoid cystic carcinomas: A case series and review of literature.

An indolent nature, with a high risk of local recurrence along with the potential for distant metastases, makes the relatively rare adenoid cystic carcinomas (ACCs) of the head-and-neck region, a unique entity. In the base of skull (BOS) region, these cancers require radiation doses as high as 70-72 GyE in proximity to critical structures. Proton therapy (PT) confers physical and radiobiological advantages and local control at 2-5 years exceeding 80% in most series, compared with below 60% with photon-based techniques. We report a case series of ACCs of the BOS, treated with image-guided, intensity-modulated PT (IMPT). During 2019-2020, we treated six patients with skull-base ACC IMPT with on-board, cross-sectional image guidance. Dosimetric data, toxicity, and early outcomes were studied, and a comparative review of literature was done. Three patients underwent PT/proton-photon treatment for residual/inoperable lesions and three patients underwent reirradiation for recurrent lesions. The prescription was 70 GyE in 31-35 fractions, and 95% of the clinical target volume (CTV) received 98% of the prescribed dose in five of the six patients. Grade 3 mucositis and skin reactions were noted in two patients and one patient, respectively. Five of the six patients were controlled locally at a median follow-up of 15 months. The radiobiological and physical characteristics of PT help to deliver high doses with excellent CTV coverage in skull-base ACCs, adjacent to critical neurological structures.

Giant De-Differentiated Liposarcoma of the Ascending Colon – A Rare Entity

Background: Liposarcoma is one of the common malignant mesenchymal tumors of the retroperitoneum and soft tissue of the extremities. Liposarcoma primarily arising from the colon is extremely rare. De-differentiated liposarcoma, a high grade variant has high local recurrence and distant metastatic potential. At present no standard treatment guidelines are established for the colonic liposarcoma in view of the rarity of the condition. Case Presentation: In this article we report a case of 46-year-old female who presented with a large right sided abdominal lump. On cross sectional imaging, she was found to have a large heterogenous exophytic mass arising from the ascending colon. Colonoscopy showed a submucosal lesion of the ascending colon with luminal narrowing. She underwent a right radical hemicolectomy. Histopathology of the resected specimen was reported as a de-differentiated liposarcoma arising from the ascending colon, which is an extremely rare occurrence. Patient made an uneventful recovery and is under follow-up. Conclusion: Liposarcoma is a rare disease of large intestine. It should be considered in the differential diagnosis when there is a large, submucosal colonic swelling with no lymph nodal or peritoneal disease. Complete surgical resection with clear margins is the standard of treatment. Evidence on the benefits of adjuvant chemotherapy and radiotherapy in improving survival in liposarcoma of colon is currently evolving.

High frequency of PIK3CA and TERT promoter mutations in fibromatosis-like spindle cell carcinomas

AimsFibromatosis-like spindle cell carcinomas (FLSCCs) are rare metaplastic breast cancers (MBCs) that are characterised by bland spindle cells in a collagenous stroma. Although some MBCs are highly malignant, FLSCCs have...