Lymphoma Metastasis Research Articles

Establishing the utility of multi-platform liquid biopsy by integrating the CSF methylome and proteome in CNS tumours.

Liquid biopsy represents a major development in cancer research, with significant translational potential. Similarly, it is increasingly recognized that multi-omic molecular approaches are a powerful avenue through which to understand complex and heterogeneous disease biology. We hypothesize that merging these two promising frontiers of cancer research will improve the discriminatory capacity of current models and allow for improved clinical utility. We have compiled a cohort of patients with glioblastoma, brain metastasis, and primary central nervoussystem lymphoma. Cell-free methylated DNA immunoprecipitation (cfMeDIP) and shotgun proteomic profiling wasobtained from the cerebrospinal fluid (CSF) of each patient and used to build tumour-specific classifiers. We show that the DNA methylation and protein profiles of cerebrospinal fluid can be integrated to fully discriminate lymphoma from its diagnostic counterparts with perfect AUC of 1 (95% confidence interval 1-1) and 100% specificity, significantly outperforming single-platform classifiers. We present the most specific and accurate CNS lymphoma classifier to date and demonstrates the synergistic capability of multi-platform liquid biopsies. This has far-reaching translational utility for patients with newly diagnosed intra-axial brain tumours.

GR.5 Establishing the utility of multi-platform liquid biopsy by integrating the CSF methylome and proteome in CNS malignancy

Background: Liquid biopsy represents a major development in cancer research, with significant translational potential. Similarly, the integration of multiple molecular platforms has yielded novel insights into disease biology and heterogeneity. We hypothesise that applying contemporary multi-omic approaches to liquid biopsies will improve the power of current models. Methods: We have compiled a cohort of 51 patients with glioblastoma, brain metastasis, and primary CNS lymphoma who underwent CSF sampling as part of clinical care. Cell free methylated DNA and shotgun proteomic profiling was obtained from the CSF of each patient and used to build tumour-specific classifiers. Integrated classifiers were compared with single platform classifiers using multiple approaches. Results: In this study, we show that the DNA methylation and protein profiles of cerebrospinal fluid can be combined to fully discriminate lymphomas from their major diagnostic counterparts with perfect AUCs of 1 (95% confidence interval 1-1) and 100% specificity. Each integrated lymphoma classifier significantly outperforms single-platform classifiers, suggesting synergistic biology is obtained using multiple molecular platforms. Conclusions: We present the most specific and accurate CNS lymphoma classifier to date by integrating the methylome and proteome of CSF. This has important implications for the future of cancer diagnostics and generates immediate utility for patients with CNS lymphoma.

Diagnosis and treatment of metastatic uterine lymphoma in a chinchilla (Chinchilla lanigera)

AbstractA 4‐year‐old, entire, female chinchilla (Chinchilla lanigera) presented to an emergency veterinary hospital for laboured breathing, lethargy and hyporexia. Physical exam findings and diagnostic imaging were supportive of uterine disease. An ovariohysterectomy was performed, and histopathology diagnosed incompletely resected uterine lymphoma. A rotating outpatient chemotherapy protocol containing oral prednisolone (0.5 mg/kg), subcutaneous L‐asparaginase (400 iu/kg), oral cyclophosphamide (200 mg/m2) and subcutaneous cytosine arabinoside (50 mg/kg) was initiated. The patient tolerated chemotherapeutics well based on normal behaviour, appetite, exam findings and serial bloodwork values. One hundred two days after initial presentation, the patient was euthanased due to a decline in clinical condition. Postmortem examination and histopathology confirmed metastasis of lymphoma to the brain, mediastinum, mesentery, liver and spleen. No evidence of organ damage due to chemotherapeutics was noted histologically. Postmortem immunohistochemistry confirmed the diagnosis of lymphoma. Further studies are needed to guide chemotherapeutic dosing and treatment of lymphoma in chinchillas.

NIMG-89. CNS-ISOLATED RICHTER’S TRANSFORMATION: THE FALLIBILITY OF NEURO-IMAGING AND THE CRITICAL ROLE OF BRAIN BIOPSY IN A CHALLENGING DIAGNOSIS

Abstract INTRODUCTION An 81-year-old male was admitted for acute encephalopathy and failure to thrive. Workup revealed a lymphocyte-predominant leukocytosis, prominent axillary and mediastinal lymphadenopathy on CT, and multiple supra-tentorial FLAIR-hyperintense lesions that were homogenously contrast-enhancing. Axillary lymph node biopsy demonstrated small lymphocytic lymphoma (SLL), a variant of CLL. Despite concern for CNS malignancy, brain biopsy was initially deferred since the patient’s brain lesions were attributed to SLL metastasis. However on hospital day 15, he developed partial seizures, prompting stereotactic biopsy which revealed DLBCL. DATA/DISCUSSION Our case highlights the pitfalls of relying solely upon neuro-imaging to diagnose Richter’s transformation (RT) isolated to the CNS. First, MRI does not differentiate CNS metastasis of systemic lymphoma from CNS RT. A review of 35 biopsy or LP-proven cases of CNS-isolated RT showed imaging characteristics consistent with primary and metastatic CNS lymphoma. When parenchymal lesions are present, all are T2/FLAIR hyper-intense; 60% are unifocal (40% multifocal); and 95% homogenously enhance. Second, CNS-isolated RT is at least 3 times rarer than CNS metastases of CLL. Among patients with CLL, ~1% will eventually exhibit CNS metastasis but < 0.3% will develop CNS-isolated RT. In patients with known CLL and no evidence of high-grade transformation, it is reasonable to attribute brain lesions to CNS metastasis of CLL as opposed to RT, absent a definitive tissue diagnosis. CONCLUSION These data emphasize the importance of biopsy in the workup of CNS lymphoma, especially since treatment differs based on histopathological subtype. Given its chronic indolent course, SLL is typically managed expectantly, whereas the aggressive nature of DLBCL warrants more intensive chemotherapy. Our case also shows that in patients with suspicious CNS lesions, presence of systemic malignancy does not eliminate the need for brain biopsy, and that clinical deterioration should prompt biopsy if not already performed.

МЕТАБОЛИЧЕСКАЯ ОФЭКТ/КТ с 99mTc-1-Тио-D-ГЛЮКОЗОЙ В ДИАГНОСТИКЕ МЕТАСТАЗИРОВАНИЯ ДИФФУЗНОЙ-В-КРУПНОКЛЕТОЧНОЙ ЛИМФОМЫ ПОЛОВЫХ ОРГАНОВ В ГОЛОВНОЙ МОЗГ (КЛИНИЧЕСКОЕ НАБЛЮДЕНИЕ)

Purpose: To demonstrate a rare clinical case of early recurrence of verified primary genital lymphoma and the possibility of 99mTc-1-Thio-D-glucose (99mTc-TG) SPECT/CT using to brain metastasis diagnosis. Material and methods: A patient with a diagnosis of primary diffuse large B-cell genital lymphoma underwent magnetic resonance imaging (MRI) to assess the extent of the disease. Post-treatment follow-up included 18F-FDG PET/CT. To diagnose brain metastasis, 99mTc-TG SPECT/CT and MRI were performed. Results: A rare case of early recurrence of diffuse large B-cell lymphoma with a primary local lesion in the genital organs is described. The possibility of modern methods of nuclear medicine in the diagnosis of early recurrence of malignant lymphoma has been demonstrated. 99mTc-TG SPECT/CT and MRI, were useful for visualization of a high metabolic brain tumor at the outpatient stage and recommendation of high-dose therapy according to the scheme MT-R was done. Conclusion: The article presents a rare clinical case of early recurrence of diffuse large B-cell genital lymphoma. Possibilities of SPECT/CT with 99mTc-TG for visualization of lymphoma metastasis to the brain were demonstrated.

Differentiation of glioblastoma, brain metastases and central nervous system lymphomas using amount of vasogenic edema and diffusion MR imaging of tumor core and peritumoral zone- Searching for a practical approach

Background/Aim: The differential diagnosis of solitary brain tumors poses challenges for clinicians and radiologists, often leading to invasive biopsy procedures. Therefore, this study aimed to evaluate the variations in edema volume and diffusion characteristics between the tumor core and peritumoral zone in cases of glioblastoma, brain metastasis, and central nervous system lymphoma. The aim was to identify additional parameters for conventional magnetic resonance imaging (MRI) that could aid in the differential diagnosis. Methods: A total of 39 patients (13 with central nervous system lymphoma, 13 with glioblastoma, and 13 with brain metastases) were included in this retrospective cohort study. Apparent diffusion coefficient (ADC) values were calculated from the ADC maps obtained from Brain MRI for both the lesion and peritumoral region. Additionally, the largest diameter of the vasogenic edema-mass complex was measured using T2 sequences. In the contrast-enhanced series, the largest diameter of the metastatic lesion was measured. The edema-mass ratio was determined by dividing the diameter of the edema-mass complex by the diameter of the mass. Results: There was a statistically significant difference in the edema-mass ratio among the tumor types (P=0.008). Further analysis using Bonferroni correction revealed that this difference was primarily due to glioblastoma. Compared to patients with lymphoma and brain metastases, lesions diagnosed as glioblastoma exhibited a lower edema-mass ratio. Additionally, a statistically significant difference was observed in the ADC value measured from the lesion according to the tumor type (P=0.017). It was determined that lesions associated with central nervous system lymphoma had lower ADC values than those with glioblastoma. Conclusion: Including lesional and perilesional ADC values obtained through diffusion-weighted examination and edema mass ratio measurements may enhance the accuracy of differential diagnosis. Utilizing these imaging characteristics in a multiparametric approach, as suggested by this research, can improve the accuracy of diagnosing malignant cancers, thereby enabling better patient management and treatment decisions.

Tumor Microenvironment Mediated Spermidine-Metal-Immunopeptide Nanocomplex for Boosting Ferroptotic Immunotherapy of Lymphoma.

Immunotherapy as an alternative treatment strategy for B-cell lymphoma is undesirable because of tumor heterogeneity and immune surveillance. Spermidine (SPM), as a regulator of the tumor microenvironment (TME), can facilitate the release of damage-associated molecular patterns (DAMPs) from cancer cells, promote immune recognition, and thus alleviate immune surveillance in the TME. Hence, in this work, self-assembled spermidine-based metal-immunopeptide nanocomplexes (APP-Fe NCs; APP is anti-programmed death ligand-1 peptide) with pH-responsive release kinetics were prepared via the flash nanocomplexation (FNC) technique based on the noncovalent interaction between APP-SPM-dextran (DEX) and sodium tripolyphosphate (TPP) and coordination between Fe3+ and TPP. An in vitro study suggested that APP-Fe NCs effectively induce strong oxidative stress and mitochondrial dysfunction and subsequently lead to ferroptosis in cells by interfering with homeostasis in lymphoma cells. Further investigation on lymphoma mice models demonstrated that APP-Fe NCs effectively inhibited the growth and liver metastasis of lymphomas. Mechanistically, by triggering ferroptosis in tumor tissues, these spermidine-containing APP-Fe NCs efficiently facilitated the release of DAMPs and ultimately reshaped TME to enhance immunotherapy efficacy in lymphoma. Combined with its good histocompatibility and facile preparation technique, this pH-responsive APP-Fe NCs with regulation on TME may hold potential for cascade amplification on the combinative immunotherapy of lymphoma in the clinic.

Abstract 2654: Inhibition of lymphoma interactions withangiogenic and lymphangiogenic endotheliumusing αCD20-IgG1-huEndoP125A, an anti-CD20 endostatin fusion protein

Abstract Mantle Cell Lymphoma (MCL) is an aggressive non-Hodgkin’s lymphoma that frequently metastasizes. Lymphoma dissemination into distant sites is the primary cause of cancer mortality. Lymphoma metastasis requires development of supporting vasculature in which the interaction between malignant B cells and the vasculature or lymphatics is critical to tumor cell growth and dissemination. Human umbilical vein endothelial cells (HUVEC) or human lymphatic endothelial cells (HLEC) cultured on Matrigel, in vitro, assemble into networks of capillary like structures (CLS) or lymphatic like structures (LLS). When Mino or Jeko-1 MCL cells are co-cultured with vascular or lymphatic cells they migrate toward and anneal to nascent CLS or LLS. We constructed a novel antibody fusion protein, αCD20-IgG1-huEndoP125A, to inhibit such interactions. αCD20-IgG1-huEndoP125A links an αCD20 human IgG1 targeting domain and a mutant version of human endostatin, huEndoP125A, with enhanced anti-angiogenic properties. αCD20-IgG1-huEndoP125A completely inhibits CLS or LLS formation and prevents the alignment and annealing of MCL to CLS or LLS. αCD20-IgG1-huEndoP125A also significantly reduces both endothelial and MCL migration and invasion in vitro. Cell migration and trafficking is tightly regulated by chemokine interactions with corresponding chemokine receptors. We assayed for the presence of chemokines using a dot blot chemokine array. Jeko-1 and HUVEC cells were cultured on Matrigel, alone or together in co-culture, and either treated with αCD20-IgG1-huEndoP125A or left untreated. CXCL12 was expressed at high levels in HUVEC cultures undergoing CLS formation and expression was further increased in HUVEC and MCL co-cultures. HUVEC or HUVEC/MCL co-cultures treated with αCD20-IgG1-huEndoP125A showed markedly decreased CXCL12 expression. Flow cytometry showed that corresponding chemokine receptor CXCR4 was upregulated on MCL cells compared to normal B cells. CXCR4 was also upregulated on HUVEC undergoing CLS formation, and further increased on HUVEC in co-culture with MCL cells. αCD20-IgG1-huEndoP125A inhibited HUVEC CLS formation, reduced MCL migration to and alignment with nascent CLS or LLS, downregulated CXCL12 levels in HUVEC or coculture supernatants, and reduced CXCR4 expression on both HUVEC and MCL cells. Murine 38c13-huCD20 lymphoma cells were implanted s.c. into C3H mice and mice were treated i.p. with either PBS, Rituximab, or equimolar αCD20-IgG1-huEndoP125A. Mice treated with αCD20-IgG1-huEndoP125A showed significantly reduced tumor growth compared to mice treated with PBS or rituximab. αCD20-IgG1-huEndoP125A ability to inhibit angiogenesis, lymphangiogenesis, and lymphoma association with angiogenic or lymphatic vasculature may be a potent means of preventing lymphoma growth and metastasis. Citation Format: Christian Elledge, Seung-Uon Shin, Rathin Das, Yu Zhang, Hyun-Mi Cho, Sundaram Ramakrishnan, Ankita Sankar, Joseph Rosenblatt. Inhibition of lymphoma interactions withangiogenic and lymphangiogenic endotheliumusing αCD20-IgG1-huEndoP125A, an anti-CD20 endostatin fusion protein [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2654.

Sternal Abnormalities on Thoracic Radiographs of Dogs and Cats.

Evaluation of the sternum is part of the routine examination of small animal thoracic radiographs. However, descriptions on frequency and type of abnormalities are lacking. This retrospective observational study aimed to describe abnormal radiographic findings of the sternum in a cross-section of client-owned dogs and cats undergoing thoracic radiography between 1 January 2019 and 1 January 2021 for reasons unrelated to diseases of the sternum. The study population consisted of 777 dogs (mean age, 7.3 ± 3.9 years) and 183 cats (mean age, 7.3 ± 5.1 years). Sternal abnormalities were observed in 189/777 (24%) dogs and 53/183 (29%) cats, mostly around the intersternebral cartilages, accounting for 32/80 (40%) dogs and 20/35 (57%) cats. This was followed by an abnormal number of sternal segments (8% dogs, range 3-9 sternebrae; 15% cats, range 7-9 sternebra). Pectus excavatum was observed in 6/777 (0.8%) dogs and 6/183 (3%) cats, and pectus carinatum in 18/777 (2%) dogs and 2/183 (1%) cats. Post-traumatic changes, such as subluxation, were observed in nine dogs (1.1%) and three cats (1.6%). Presumed prostatic carcinoma metastasis and malignant lymphoma were observed in two dogs (0.2%). Incidental radiographic sternal abnormalities are common in cats and dogs but mostly of unknown clinical relevance.

Systemic Tumors and Retina

The eyes are a rare site for systemic metastasis. Metastatic tumors of the eye are more common than primary ocular tumors. The choroid is the most common site for ocular metastases whereas retinal metastases are relatively rare. The retina metastasis of Malignant melanoma, pulmonary carcinoma, breast adenocarcinoma, gastrointestinal carcinoma, uterine adenocarcinoma, and lymphoma was reported. Retinal metastases may cause visual symptoms in patients as well as be asymptomatic. Retinal hemorrhage, retinal mass, retinal or vitreous seeding, vascular occlusion, vitreous hemorrhage, and retinal detachment may be seen due to retinal metastasis. The ocular findings of systemic tumors metastasize to the retina and the approach to the patient are discussed in this review.

下唇に発生したメルケル細胞癌の1例

Merkel cell carcinoma (MCC) is a rare and highly aggressive neuroendocrine malignancy of the skin. We report a case of MCC of the lower lip. An 85-year-old woman was referred to our hospital because of a tumor in her lower lip. An extraoral examination revealed a palpable soft tumor measuring 17 × 11mm. A malignant tumor was suspected, and a FDG-PET/CT was performed. Accumulation was observed in the lower lip, the first spinous process, the right side of the second vertebral body, the left seventh rib, and the right pubis. The lip was resected first, because it was considered to be a bone metastasis of non-Hodgkin's lymphoma, the treatment of which had been discontinued in the past. A pubic biopsy was performed after surgery and MCC with multiple bone metastases was diagnosed. The painful pubis and ischium were irradiated (30Gy/10fr), and Avelumab and Denosumab administered. However, brain metastasis and irAE enteritis were observed, and the patient died of this disease one year and eight months after the initial diagnosis.

Contribution of Outpatient Ultrasound Transvaginal Biopsy and Puncture in the Diagnosis and Treatment of Pelvic Lesions: A Bicenter Study.

The use of transvaginal ultrasound guided biopsy and puncture of pelvic lesions is a minimally invasive technique that allows for accurate diagnosis. It has many advantages compared to other more invasive (lower complication rate) or non-invasive techniques (accurate diagnosis). Furthermore, it offers greater availability, it does not radiate, enables the study of pelvic masses accessible vaginally with ultrasound control in real time, and it is possible to use the colour Doppler avoiding puncturing large vessels among others. The main aim of the work is to describe a standardized ambulatory technique and to determine its usefulness. This is a retrospective study of ultrasound transvaginal punctures (core needle biopsies and cytologies) and drainages of pelvic lesions performed on an outpatient basis during the last two years. The punctures were made with local anesthesia, under transvaginal ultrasound guidance with an automatic or semi-automatic 18G biopsy needle with a length of 20-25 cm and a penetration depth of 12 or 22 mm. The material obtained was sent for anatomopathological, cytological and/or microbiological study if necessary. A total of 42 women were recruited in two centers. Fifty procedures (nine punctures, seven drains, and 34 biopsies) were performed. In five cases the punction and drain provided clinical relief in benign pelvic masses. Regarding material of the biopsies performed, 15 were vaginal in women previously histerectomized, finding 10 carcinomas, eight were ovarian tumours in advanced stages or peritoneal carcinomatosis obtaining the appropriate histology in each case, seven were suspicious cervical biopsies finding carcinomas in five of them, three were myometrial biopsies including one breast carcinoma metastasis in the miometrium and a benign placental nodule, and a periurethral biopsy was performed on a woman with a history of endometrial cancer confirming recurrence. The pathological diagnosis was satisfactory in all cases, confirming the nature of the lesion (25 malignant-ten vaginal recurrences of previous gynaecological cancers, eight cases of primary ovarian/peritoneal carcinoma, four new diagnosis of cervical malignant masses, one cervical metastasis of lymphoma, one periurethral recurrence of endometrial carcinoma and one recurrence of breast cancer in the myometrium-and 23 benign). The tolerance was excellent and no complications were detected. The ambulatory ultrasound transvaginal puncture and drainage technique is useful for obtaining a sample for pathological and microbiological diagnosis with excellent tolerance that can be used to rule out the recurrence of malignant lesions or progression of the disease, diagnose masses not accessible to gynecological exploration (vaginal vault, myometrium or cervix) and for early histologic diagnosis in cases of advanced peritoneal carcinomatosis or ovarian carcinoma as well as drainage and cytological study of cystic pelvic masses.

A Deep Learning Model for Preoperative Differentiation of Glioblastoma, Brain Metastasis, and Primary Central Nervous System Lymphoma: An External Validation Study

(1) Background: Neuroimaging differentiation of glioblastoma, primary central nervous system lymphoma (PCNSL) and solitary brain metastasis (BM) represents a diagnostic and therapeutic challenge in neurosurgical practice, expanding the burden of care and exposing patients to additional risks related to further invasive procedures and treatment delays. In addition, atypical cases and overlapping features have not been entirely addressed by modern diagnostic research. The aim of this study was to validate a previously designed and internally validated ResNet101 deep learning model to differentiate glioblastomas, PCNSLs and BMs. (2) Methods: We enrolled 126 patients (glioblastoma: n = 64; PCNSL: n = 27; BM: n = 35) with preoperative T1Gd-MRI scans and histopathological confirmation. Each lesion was segmented, and all regions of interest were exported in a DICOM dataset. A pre-trained ResNet101 deep neural network model implemented in a previous work on 121 patients was externally validated on the current cohort to differentiate glioblastomas, PCNSLs and BMs on T1Gd-MRI scans. (3) Results: The model achieved optimal classification performance in distinguishing PCNSLs (AUC: 0.73; 95%CI: 0.62–0.85), glioblastomas (AUC: 0.78; 95%CI: 0.71–0.87) and moderate to low ability in differentiating BMs (AUC: 0.63; 95%CI: 0.52–0.76). The performance of expert neuro-radiologists on conventional plus advanced MR imaging, assessed by retrospectively reviewing the diagnostic reports of the selected cohort of patients, was found superior in accuracy for BMs (89.69%) and not inferior for PCNSL (82.90%) and glioblastomas (84.09%). (4) Conclusions: We investigated whether the previously published deep learning model was generalizable to an external population recruited at a different institution—this validation confirmed the consistency of the model and laid the groundwork for future clinical applications in brain tumour classification. This artificial intelligence-based model might represent a valuable educational resource and, if largely replicated on prospective data, help physicians differentiate glioblastomas, PCNSL and solitary BMs, especially in settings with limited resources.

An integrative non-invasive malignant brain tumors classification and Ki-67 labeling index prediction pipeline with radiomics approach

BackgroundThe histological sub-classes of brain tumors and the Ki-67 labeling index (LI) of tumor cells are major factors in the diagnosis, prognosis, and treatment management of patients. Many existing studies primarily focused on the classification of two classes of brain tumors and the Ki-67LI of gliomas. This study aimed to develop a preoperative non-invasive radiomics pipeline based on multiparametric-MRI to classify-three types of brain tumors, glioblastoma (GBM), metastasis (MET) and primary central nervous system lymphoma (PCNSL), and to predict their corresponding Ki-67LI. MethodsIn this retrospective study, 153 patients with malignant brain tumors were involved. The radiomics features were extracted from three types of MRI (T1-weighted imaging (T1WI), fluid-attenuated inversion recovery (FLAIR), and contrast-enhanced T1-weighted imaging (CE-T1WI)) with three masks (tumor core, edema, and whole tumor masks) and selected by a combination of Pearson correlation coefficient (CORR), LASSO, and Max-Relevance and Min-Redundancy (mRMR) filters. The performance of six classifiers was compared and the top three performing classifiers were used to construct the ensemble learning model (ELM). The proposed ELM was evaluated in the training dataset (108 patients) by 5-fold cross-validation and in the test dataset (45 patients) by hold-out. The accuracy (ACC), sensitivity (SEN), specificity (SPE), F1-Score, and the area under the receiver operating characteristic curve (AUC) indicators evaluated the performance of the models. ResultsThe best feature sets and ELM with the optimal performance were selected to construct the tri-categorized brain tumor aided diagnosis model (training dataset AUC: 0.96 (95% CI: 0.93, 0.99); test dataset AUC: 0.93) and Ki-67LI prediction model (training dataset AUC: 0.96 (95% CI: 0.94, 0.98); test dataset AUC: 0.91). The CE-T1WI was the best single modality for all classifiers. Meanwhile, the whole tumor was the most vital mask for the tumor classification and the tumor core was the most vital mask for the Ki-67LI prediction. ConclusionThe developed radiomics models led to the precise preoperative classification of GBM, MET, and PCNSL and the prediction of Ki-67LI, which could be utilized in clinical practice for the treatment planning for brain tumors.

S1961 Isolated Cardiac Metastasis as an Initial Presentation of Colorectal Cancer in a Young Male Due to Lymphatic Spread

Introduction: Malignant pericardial effusion is common, reported in 5–15% of cancer patients. It most commonly arises from metastasis of lymphomas and tumors of the lung, breast, and, infrequently, the gastrointestinal tract. We report a rare case of metastatic colon cancer without the direct involvement of other solid organs suggesting a lymphatic spread. Case Description/Methods: A 28-year-old man presented with one day of sudden onset of shortness of breath at rest. Vitals were significant for tachycardia. On examination, the lungs were clear to auscultation with distant heart sounds; the abdomen was soft without tenderness. The clinical presentation was suggestive of pericardial effusion. Laboratory studies revealed microcytic anemia with hemoglobin of 11.7 g/dl. CT angiography chest with contrast revealed moderate to large PEff and subsegmental pulmonary embolism. An ECHO showed large PEff, without any signs of tamponade. He underwent video-assisted thoracoscopic surgery for PEff with a pericardial window. The mediastinal lymph node biopsy and pericardial fluid cytology showed metastatic adenocarcinoma cells. A CT scan of the chest/abdomen/pelvis was performed to find the primary malignancy, which revealed a segmental thickening of the proximal ascending colon and ileum with proximal cecal distension, lymphadenopathy, without liver metastasis. A CF showed a large polypoidal mass in the ascending colon, and biopsy revealed poorly differentiated adenocarcinoma in ascending colon. He was started on palliative chemotherapy with capecitabine, oxaliplatin, and bevacizumab and was discharged with outpatient oncology follow-up (Figure). Discussion: Colorectal cancer (CRC) is the third most common cancer in the United States. It primarily spreads hematogenous via the portal venous system that drains the colon and proximal rectum to the liver and the lungs to the heart. However, cardiac metastasis is rare. In our patient, we assume lymphatic spread of colon cancer due to isolated pericardial involvement in the absence of solid organ involvement. To our knowledge, this is the second reported case of lymphatic spread of colon cancer. Therefore, we emphasize considering pericardial effusions as a marker of occult malignancy to facilitate rapid diagnosis and prompt treatment. However, the prognosis for carcinomatous pericarditis is poor, with a 2-5 months median survival.Figure 1.: A-Echocardiogram: Parasternal short axis view showing large pericardial effusion, no signs of cardiac tamponade. B-Colonoscopy showing a lobulated mass in cecum. C-Computed Tomography (C.T.) scan with PO/IV contrast showing mass vs segmental inflammation in proximal ascending colon (pink arrow). Mild thickening of terminal ileum (white arrow).

A rare case of synchronous multiple primary malignancies of breast cancer and diffuse large B-cell lymphoma that responded to multidisciplinary treatment: a case report

BackgroundMultiple primary malignancies of breast cancer and diffuse large B-cell lymphoma (DLBCL) are rare. Here, we report a case of advanced breast cancer and DLBCL managed with multidisciplinary therapy preceded by surgery with a successful outcome.Case presentationDuring a medical examination, a 71-year-old woman was diagnosed with a right breast mass, enlarged lymph nodes throughout the body, and a splenic tumor. The results of the clinical examination and imaging were suggestive of widely spread breast cancer with lymph node metastasis and malignant lymphoma with systemic metastasis. The histological evaluation of the biopsied breast tissue revealed human epidermal growth factor receptor 2 (HER2)-positive breast cancer, whereas the histological evaluation of the excised inguinal lymph node revealed DLBCL. 18F-FDG PET/computed tomography was performed, and it was determined that both breast cancer and DLBCL were in an advanced stage. Thus, mastectomy was performed, and the axillary lymph nodes showed mixed metastasis of breast cancer and DLBCL. Soon after, the R-CHOP therapy was initiated (375-mg/m2 rituximab, 2-mg/m2 vincristine, 50-mg/m2 doxorubicin, 750-mg/m2 cyclophosphamide, and 125-mg methylprednisolone). After irradiation of the spleen, trastuzumab was administered for 1 year.ConclusionsWe experienced a case of combined breast cancer and DLBCL, which was difficult to treat because both were in advanced stages. Thorough staging of the malignancy and discussion by a multidisciplinary team are necessary to determine the optimal treatment strategy.

Ultrasound-Guided Tru-Cut Biopsy in Gynecological and Non-Gynecological Pelvic Masses: A Single-Center Experience.

Aim: The aim of this study was to evaluate the feasibility of adequacy, accuracy, and safety of ultrasound-guided tru-cut biopsy in managing malignant and benign abdominopelvic masses in a selected population and critically discuss some issues in different situations, which deserve some reflections on those practices. Materials and Methods: This is a retrospective study involving 42 patients who underwent transvaginal or transabdominal tru-cut biopsy between August 2017 and November 2021. The inclusion criteria were poor health status or primary inoperable advanced tumor, suspicion of recurrence or metastasis to the ovaries or peritoneum in gynecological and non-gynecological pelvic malignancies. Tissue samples were considered adequate if it was possible to determine the origin of the tumor, and immunohistochemistry could be performed. Diagnostic accuracy was assessed considering the agreement between tru-cut biopsy histology and final postoperative histology. Results: It total, 44 biopsies were obtained from 42 patients (2 patients had repeat biopsies). The pathologist considered all pathological samples adequate (adequacy 100%). The final histology was consistent with tru-cut biopsy diagnosis in all but 2 cases (diagnostic accuracy 88.2%). If we consider only the cases that have carried out at least two diagnostic samples, accuracy rose to 94.1%. Pathological examinations from tru-cut samples showed 2 benign lesions (4.8%) and 40 malignant tumors (95.2%), divided into 19 advanced primary inoperable ovarian cancers, 7 primary advanced cervical cancers, 4 recurrent endometrial cancers, 3 recurrent cervical cancers, 3 recurrent ovarian cancers, 1 case of primitive peritoneal malignancy (leiomyosarcoma), and 3 non-gynecological cancers with a strong suspicion of metastases at ultrasound (2 cases of ovarian, colorectal cancer metastasis, and 1 case of pelvic site type B lymphoma metastasis). However, one case of minor complication related to the procedure was reported but not significant. Conclusions: The diagnostic adequacy, accuracy of the tru-cut biopsy, and safety were high. Pathological samples are representative of the disease and suitable for histological and immunohistochemical analysis.

Evaluation of the Long noncoding RNA NONHSAT037832 Gene Expression Changes in Patients with Thyroid Carcinoma

Background & Objective: Thyroid cancer is the most common endocrine disorder in the world. One of the main causes of this cancer is genetic changes, in particular mutations in the tumor and oncogene inhibition genes. In addition to mutations, some non-encoding RNAs called lncRNAs play an important role in the progression of tumors. NONHSAT is a lancer and has recently been referred to the role of this gene in various types of cancer. This study aimed to evaluate the lncRNA-NONHSAT037832 gene expression changes in patients with thyroid carcinoma.
 Materials & Methods: A cross-sectional study was conducted on 140 homogeneous samples (70 cancer tissue homogeneous samples and 70 homogeneous healthy tissue samples) from patients with thyroid cancer referred to Alzahra Hospital in Tabriz. Using the Real-Time PCR, changes in the expression of the lncRNA-NONHSAT037832 gene were evaluated. In addition, the relationship between lncRNA-NONHSAT037832 gene expression changes and clinical parameters was investigated.
 Results: The results showed that the expression of lncRNA-NONHSAT037832 gene expression in the tissues of cancer was significantly higher than healthy tissues (P <0.001) and a significant relationship with MTN (P = 0.001) and node metastasis Lymphoma was shown (P = 0.30).
 Conclusion: According to the results, the lncRNA-NONHSAT037832 gene may be used as a prognostic biomarker for thyroid cancer. 

A Deep Learning Model for Preoperative Differentiation of Glioblastoma, Brain Metastasis and Primary Central Nervous System Lymphoma: A Pilot Study.

BackgroundNeuroimaging differentiation of glioblastoma, primary central nervous system lymphoma (PCNSL) and solitary brain metastasis (BM) remains challenging in specific cases showing similar appearances or atypical features. Overall, advanced MRI protocols have high diagnostic reliability, but their limited worldwide availability, coupled with the overlapping of specific neuroimaging features among tumor subgroups, represent significant drawbacks and entail disparities in the planning and management of these oncological patients.ObjectiveTo evaluate the classification performance metrics of a deep learning algorithm trained on T1-weighted gadolinium-enhanced (T1Gd) MRI scans of glioblastomas, atypical PCNSLs and BMs.Materials and MethodsWe enrolled 121 patients (glioblastoma: n=47; PCNSL: n=37; BM: n=37) who had undergone preoperative T1Gd-MRI and histopathological confirmation. Each lesion was segmented, and all ROIs were exported in a DICOM dataset. The patient cohort was then split in a training and hold-out test sets following a 70/30 ratio. A Resnet101 model, a deep neural network (DNN), was trained on the training set and validated on the hold-out test set to differentiate glioblastomas, PCNSLs and BMs on T1Gd-MRI scans.ResultsThe DNN achieved optimal classification performance in distinguishing PCNSLs (AUC: 0.98; 95%CI: 0.95 - 1.00) and glioblastomas (AUC: 0.90; 95%CI: 0.81 - 0.97) and moderate ability in differentiating BMs (AUC: 0.81; 95%CI: 0.70 - 0.95). This performance may allow clinicians to correctly identify patients eligible for lesion biopsy or surgical resection.ConclusionWe trained and internally validated a deep learning model able to reliably differentiate ambiguous cases of PCNSLs, glioblastoma and BMs by means of T1Gd-MRI. The proposed predictive model may provide a low-cost, easily-accessible and high-speed decision-making support for eligibility to diagnostic brain biopsy or maximal tumor resection in atypical cases.

New Insights into LINC00346 and its Role in Disease.

Accumulating evidence has shown that long intergenic non-protein-coding RNA 346 (LINC00346) functions as an oncogene in the tumorigenesis of several cancers. The expression level of LINC00346 has been shown to be obviously correlated with prognosis, lymphoma metastasis, histological grade, TNM stage, tumor size and pathologic stage. LINC00346 has been found to regulate specific cellular functions by interacting with several molecules and signaling pathways. In this review, we summarize recent evidence concerning the role of LINC00346 in the occurrence and development of diseases. We also discuss the potential clinical utility of LINC00346, thereby providing new insight into the diagnosis and treatment of diseases. In addition, we further discuss the potential clinical utility of LINC00346 in the diagnosis, prognostication, and treatment of diseases.