Locoregional Lymphadenopathy Research Articles

A rare incidence of signet ring cell carcinoma of the rectosigmoid junction: a case report

Introduction and importance: Signet ring cell carcinoma (SRCC) is a rare type of adenocarcinoma. SRCC comprises 1.0% of all colon cancer and 0.7% of all rectal cancer. The SRCC spreads both hematologically and through lymph nodes making it highly invasive. The pathophysiology of the colorectal SRCC involves an alteration in the function of the RNF43, CDH-1, and SMAD4 genes as well as TGF-B signaling pathways, which are responsible for epithelial-mesenchymal transitions and stem cell properties. This also shows a higher rate of BRAF mutation, microsatellite instability-high (MSI-H) and CpG island methylator phenotype positivity Case presentation: A 17-year-old female patient with no known comorbidities presented with copious, bright red colored per rectal bleeding along with painful defecation. Colonoscopy revealed an eccentric growth that led to luminal narrowing. Multiple biopsies confirmed a 4 cm × 6 cm neoplastic lesion with locoregional lymphadenopathy, but no metastasis. The patient underwent anterior resection of the rectum, colostomy, and rectal stump closure. The sigmoid colon was resected up to the middle up to the third mesorectum followed by multiple re-explorations. Discussion: SRCC presents at an advanced stage with a poor prognosis because signet ring cells infiltrate the mucosa without forming a significant mass, hindering early diagnosis of this carcinoma. Among the previously published large-scale studies, SRCC involves the proximal colon, i.e., the cecum, ascending, and transverse colon. However, our case presents a less common left-sided presentation in a less-commonly presented demographic, a 17-year-old girl. The patient’s non-specific symptoms contributed to a delayed diagnosis. Despite this, the absence of metastasis in our late-diagnosed case is atypical of SRCC. Conclusion: SRCC should be considered as a differential diagnosis for young adults presenting with per-rectal bleeding and other common symptoms often seen in frequently diagnosed conditions. Therefore, early diagnosis along with appropriate surgical intervention combined with supportive treatment are important for better patient outcomes.

Peripheral lymphadenopathy of unknown origin in adults: a diagnostic approach emphasizing the malignancy hypothesis.

The term lymphadenopathy refers to an abnormality in size, consistency or morphological aspect of one or several lymph nodes. Although lymphadenopathies are commonly observed in everyday clinical practice, the difficulty of differentiating benign and malignant disease may delay therapeutic approaches. The present review aims to update diagnostic algorithms in different clinical situations based on the currently available literature. A literature review was performed to assess current knowledge of and to update the diagnostic approach. A short clinical vignette was used as an example of a typical clinical presentation. This case of metastatic lymphadenopathy with incomplete patient history demonstrates how misleading such lymphadenopathy may be, leading to a delayed diagnosis and even a fatal outcome. Any lymphadenopathy persisting for more than 2 weeks should be considered suspicious and deserves further investigation. Precise clinical examination, meticulous history-taking and a search for associated symptomatology are still cornerstones for diagnosing the origin of the condition. The next diagnostic step depends on the anatomical region and the specific patient's situation. Imaging starts with ultrasound, while computed tomography (CT) and magnetic resonance imaging (MRI) allow assessment of the surrounding structures. If the diagnosis remains uncertain, tissue sampling and histological analyses should be performed. Except for head and neck loco-regional lymphadenopathy, there are no methodical guidelines for persistent lymphadenopathy. The present review clarifies several confusing and complex situations. The accuracy of fine needle aspiration cytology could be increased by using core needle biopsy with immunocytologic and flow cytometric methods. Notably, except in the head and neck area, open biopsy remains the best option when lymphoma is suspected or when inconclusive results of previous fine needle aspiration cytology or core needle biopsy are obtained. The incidence of malignant lymphadenopathy varies with its location and the various diagnostic strategies. In metastatic lymphadenopathy of unknown primary origin, European Society for Medical Oncology (ESMO) guidelines and modern methods like next-generation sequencing (NGS) may help to manage such complex cases.

Impact of bulky loco-regional lymphadenopathy in esophageal adenocarcinoma on survival: a retrospective single center analysis.

The relationship between 'bulky' locoregional lymphadenopathy and survival has not been investigated in the setting of esophageal adenocarcinoma (EAC). This study aimed to explore whether bulky regional lymphadenopathy at diagnosis affected survival outcomes in patients with EAC treated with neoadjuvant chemotherapy and en bloc resection. A single-center retrospective review of a prospectively maintained upper GI cancer surgical database was performed between January 2012 and December 2019. Patients with locally advanced EAC (cT2-3, N+, M0) treated with neoadjuvant docetaxel-based chemotherapy and transthoracic en bloc esophagogastrectomy were identified. Computed tomography scans from before the initiation of treatment were reviewed, and patients were stratified according to whether bulky loco-regional lymph nodes were present. This was defined as lymphadenopathy >2cm in any axis. Overall survival was compared, and a Cox multivariate regression model was calculated. Two hundred twenty-five of the eight hundred seventy patients identified met the inclusion criteria. Forty-eight (21%) had bulky lymphadenopathy, leaving 177 allocated to the control group. More patients with bulky lymphadenopathy had ypN3 disease (18/48, 38% vs. 39/177, 20%, P = 0.025). Among patients with bulky lymphadenopathy, overall survival was generally worse (32.6 vs. 59.1months, P = 0.012). However, among the 9/48 (19%) patients with bulky lymphadenopathy who achieved ypN- status survival outcomes were similar to those with non-bulky lymphadenopathy who also achieved lymph node sterilization. Poor differentiation (HR 1.8, 95% CI 1.0-2.9, P = 0.034), ypN+ (HR 1.9, 95% CI 1.1-3.6, P = 0.032), and bulky lymphadenopathy were independently associated with an increased risk of death (HR 1.7, 1.0-2.9, P = 0.048). Bulky regional lymphadenopathy is associated with a poor prognosis. Efforts to identify the ideal treatment regimen for these patients are urgently required.

THU503 An Unusual Case Of Ectopic ACTH Syndrome Secondary To Non-small Cell Lung Cancer

Abstract Disclosure: N. Hernandez: None. E. Askar: None. J.R. Fredrick: None. R.C. Schulman-Rosenbaum: None. Background: Cushing syndrome (CS) is a clinical entity characterized by HTN, DM, peripheral edema, hypokalemia, metabolic alkalosis, and myopathy. CS can be clinically classified into Corticotropin-dependent vs Corticotropin-independent processes. Those categorized as corticotropin dependent can further be subclassified into Eutopic CS (i.e. from the pituitary) vs Ectopic CS (i.e. extra-pituitary). The extra-pituitary source of ACTH most often comes from intra-thoracic neoplasms, of which small cell lung cancer (SCLC) is the most prevalent. However, here we present a case of a patient with Ectopic ACHT Syndrome (EAS) due to non-small cell lung cancer. Clinical Case: 87-year-old woman with pmhx of RA and HTN was admitted for 2-week history of constipation and lower abdominal pain. Physical exam was notable for hypertension and tachycardia, along with lower abdominal tenderness. Laboratory results showed WBCs of 32,000 (3,800-10,500), K of 2.7 mmol/L (3.5-5.5 mmol/L) and HCO3 was 38 mmol/L (22-29 mmol/L). CT chest and abdomen showed a left perihilar necrotic mass 6.6 X 6.0cm, with loco-regional lymphadenopathy with destructive osseous lesion on the right pedicle of L1 and metastatic disease to the liver and adrenal glands. Paraneoplastic ACTH production was suspected in the setting of metastatic lung cancer. Serum ACTH level was 105 pg/mL (7.2-63.6 pg/mL). Initial 8AM cortisol was 41 ug/dL (6.8-18.4 ug/dL) and 24 hr urine cortisol was 2327 mcg/24 h (3.5-45 mcg/24 h) which proved the diagnosis of ACTH-dependent hypercortisolemia. The AM cortisol was 62.3 ug/dL (6.0-18.4 ug/dL) after the 1mg dexamethasone test consistent with hypercortisolemia secondary to ectopic ACTH. IR biopsy of the right axillary LN showed poorly differentiated non-small cell carcinoma with squamous differentiation. The patient was started on chemotherapy, as well as, mifepristone 300 mg daily and ketoconazole 200 TID for hypercortisolism. She was also considered for Metyrapone. However, cortisol levels did not improve despite optimized therapy due to the aggressive nature of the cancer. Later chemotherapy was discontinued and was discharged on hospice with ketoconazole and mifepristone. Conclusion: EAS is associated with neuroendocrine tumors of which up to 50% are caused by SCLC and rarely with adenocarcinoma. However, our case is novel as the source of ACTH was a lung tumor of squamous cell origin. Treatment strategies for ACTH secreting tumors combine chemotherapy as well as medications that target the hormonal imbalance such as steroidogenesis inhibitors and cortisol receptor blockers. Unfortunately, patients with ACTH producing tumors tend to have low median survival rates which limits our ability as clinicians to determine the effectiveness of such interventions. Given the uniqueness of her case, it would be even harder to predict the type of clinical response obtained from such treatment. Presentation: Thursday, June 15, 2023

Polyostotic DLBCL Is Characterized By a NF-Κb Pathway Affecting Molecular Profile and Superior Survival

Introduction Polyostotic diffuse large B-cell lymphoma (DLBCL) is a rare extranodal disease with only multifocal bone localizations that has not extensively been studied. Other known bone DLBCL comprises primary bone (PB-)DLBCL with a single bone localization with(out) locoregional lymphadenopathy and disseminated-DLBCL with ≥1 bone lesion(s) and ≥1 (extra) nodal localization(s). Recently (PMID: 34478526, de Groen et al.), we demonstrated a germinal center B-cell (GCB)-subtype with a centrocyte-like phenotype and a unique corresponding molecular profile, reflecting favorable prognosis for PB-DLBCL compared to non-bone DLBCL with a GCB-subtype. Here, the molecular characteristics of polyostotic-DLBCL were assessed and compared to PB-DLBCL, disseminated-DLBCL, and nodal DLBCL-GCB, using an extensive targeted next-generation sequencing (tNGS) panel. Methods This retrospective multicenter study analyzed 14 polyostotic-DLBCL, 44 PB-DLBCL, 26 disseminated-DLBCL, and 36 nodal DLBCL-GCB cases (selection based on PET/CT-scan), including well-annotated histological and clinical data. Cases were diagnosed with immunohistochemistry following the revised WHO classification of 2016. Cell-of-origin (COO) was determined by Hans' algorithm. Presence of MYC/BCL2/BCL6-rearrangements were identified through fluorescent in situ hybridization (FISH) and break-apart probes. High-grade B-cell lymphomas (double/triple hit) were excluded. As described (PMID: 34478526), tNGS was performed, using an extended panel consisting of 128 (LYMFv2, mostly used) or 52 (LYMFv1) B-cell lymphoma relevant genes. Results Our cohort consisted of 120 patients (78 males, 65%) with a median age at diagnosis of 61 (range 13-91). Half of the polyostotic-DLBCL cases belonged to a GCB phenotype (8/14, 57%), while a GCB phenotype was more frequently identified in PB-DLBCL (31/44, 70%) and disseminated-DLBCL (18/26, 69%). Using tNGS with LYMFv2 and LYMFv1, respectively 57 and 36 cases were successfully analyzed, elucidating (in)activating pathogenic mutations in 124 different genes. In polyostotic-DLBCL, frequent mutations in f.e.CARD11 and MYD88 demonstrated a unique mutational profile affecting the NF-κB pathway characteristic of ABC-genotypes (Figure 1, P=0.018), compared to PB-DLBCL, disseminated-DLBCL and nodal DLBCL-GCB. In contrast, an exclusive immunomodulatory profile with frequent mutations in B2M, IRF8 and TNFRSF14 was identified for PB-DLBCL (P=0.029). Focusing on GCB-associated epigenetic genes (CREBBP, EP300, EZH2, KMT2D, etc.), no significant difference was found between the mentioned DLBCL subgroups. Mutational profiles of disseminated-DLBCL revealed a broad spectrum of abnormalities (BCL2, CREBBP, TNFRSF14, and TP53), partially consistent with either an immunomodulatory or an epigenic genotype. Nodal DLBCL-GCB was specifically characterized by frequent aberrations in BCL2 and MYC and lacked an immunomodulatory or NF-κB activating genotype. Given >1 extranodal localizations, polyostotic-DLBCL is classified as high-risk disease with Ann Arbor stage IV. Compared to disseminated-DLBCL with similar stage III/IV disease, polyostotic-DLBCL demonstrated a superior 3-year overall survival (Figure 2, log-rank, p<0.001, HR: 4.76, CI: 1.4-15.9). Conclusion Polyostotic-DLBCL showed a unique mutational profile with frequent NF-κB-activating mutations, in contrast to PB-DLBCL, disseminated-DLBCL and nodal DLBCL-GCB. Despite this ABC-associated profile of polyostotic-DLBCL and its high Ann Arbor stage, a favorable prognosis was identified especially compared to similar high Ann Abor stage disseminated-DLBCL. To study COO and tumor microenvironment in more detail to evaluate polyostotic-DLBCL as a separate biological disease entity, gene-expression profiling with the BLYM777 panel (PMID: 35454765) will be presented at the meeting. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Real‐world staging computed tomography scanning technique and important reporting discrepancies in pancreatic ductal adenocarcinoma

BackgroundComputed tomography (CT) is the first‐line staging imaging modality for pancreatic ductal adenocarcinoma (PDAC) which determines resectability and treatment pathways.MethodsBetween January 2016 and December 2019, prospectively collated data from two Australian cancer centres was extracted from the PURPLE Pancreatic Cancer registry. Real‐world staging CTs and corresponding reports were blindly reviewed by a sub‐specialist radiologist and compared to initial reports.ResultsOf 131 patients assessed, 117 (89.3%) presented with symptoms, 74 (56.5%) CTs included slices ≤3 mm thickness and CT pancreas protocol was applied in 69 (52.7%) patients. Initial reports lacked synoptic reporting in 131 (100%), tumour identification in 2 (1.6%) and tumour measurement in 13 (9.9%) cases. Tumour‐vascular relationship reporting was missing in 69–109 (52.7–83.2%) for regarding the key arterial and venous structures that is required to assess resectability. Initial reports had no comment on venous thrombus or venous collaterals in 80 (61.1%) and 109 (83.2%) and lacked locoregional lymphadenopathy interpretation in 13 (9.9%) cases. Complete initial staging report was present in 72 (55.0%) patients. Sub‐specialist radiological review resulted in down‐staging in 16 (22.2%) and up‐staging in 1 (1.4%) patient. Staging discrepancies were mainly regarding metastatic disease (12, 70.6%) and tumour‐vascular relationship (5, 29.4%).ConclusionReal‐world staging imaging in PDAC patients show low proportion of dedicated CT pancreas protocol, high proportion of incomplete staging reports and no synoptic reporting. The most common discrepancy between initial and sub‐specialist reporting was regarding metastases and tumour‐vascular relationship assessment resulting in sub‐specialist down‐staging in almost every fifth case.

Synovial sarcoma of the popliteal fossa

Soft tissue sarcomas are heterogeneous group of neoplasms making up to 1% of all malignant tumors in the adult population. The tumor generally appears on the extremities near large joints of middle-aged patients, especially in the popliteal fossa. Our patient presented in February 2014 due to a slowly enlarging, darker-colored swelling in the left popliteal fossa. Upon physical examination, a somewhat nodular, immobile, tender subcutaneous mass was observed. There was no locoregional lymphadenopathy. Patohistological findings showed a high-grade primary malignant mesenchymal tumor, biphasic synovial sarcoma type. The patient underwent surgery with wide surgical excision, followed by radiotherapy treatment. Magnetic resonance imagining follow up after one year revealed tumor recurrence. Neurovascular bundle involvement was detected, but without adjacent bone and muscular invasion and above-the-knee partial amputation of the left leg was performed. The intervention resulted in a remission of the neoplastic process and the patient was scheduled for regular check-ups. Broad surgical resection of the tumor with negative margins was the primary treatment in this case. Mutilating operations are necessary when anatomical structures around the tumor do not allow complete reintervention.

European guideline for imaging in paediatric and adolescent rhabdomyosarcoma \u2014 joint statement by the European Paediatric Soft Tissue Sarcoma Study Group, the Cooperative Weichteilsarkom Studiengruppe and the Oncology Task Force of the European Society of Paediatric Radiology

Appropriate imaging is essential in the treatment of children and adolescents with rhabdomyosarcoma. For adequate stratification and optimal individualised local treatment utilising surgery and radiotherapy, high-quality imaging is crucial. The paediatric radiologist, therefore, is an essential member of the multi-disciplinary team providing clinical care and research. This manuscript presents the European rhabdomyosarcoma imaging guideline, based on the recently developed guideline of the European Paediatric Soft Tissue Sarcoma Study Group (EpSSG) Imaging Committee. This guideline was developed in collaboration between the EpSSG Imaging Committee, the Cooperative Weichteilsarkom Studiengruppe (CWS) Imaging Group, and the Oncology Task Force of the European Society of Paediatric Radiology (ESPR). MRI is recommended, at diagnosis and follow-up, for the evaluation of the primary tumour and its relationship to surrounding tissues, including assessment of neurovascular structures and loco-regional lymphadenopathy. Chest CT along with [F-18]2-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET)/CT or PET/MRI are recommended for the detection and evaluation of loco-regional and distant metastatic disease. Guidance on the estimation of treatment response, optimal long-term follow-up, technical imaging settings and standardised reporting are described. This European imaging guideline outlines the recommendations for imaging in children and adolescents with rhabdomyosarcoma, with the aim to harmonise imaging and to advance patient care.

Diagnostic performance of preoperative CT in differentiating between benign and malignant origin of suspicious gallbladder lesions

PurposeTo determine diagnostic performance of preoperative CT in differentiating between benign and malignant suspicious gallbladder lesions and to develop a preoperative risk score. MethodAll patients referred between January 2007 and September 2018 for suspicion of gallbladder cancer (GBC) or incidentally found GBC were retrospectively analyzed. Patients were excluded when preoperative CT or histopathologic examination was lacking. Two radiologists, blinded to histopathology results, independently reviewed CT images to differentiate benign disease from GBC. Multivariable analysis and internal validation were used to develop a risk score for GBC. Model discrimination, calibration, and diagnostic performance were assessed. ResultsIn total, 118 patients with 39 malignant (33 %) and 79 benign (67 %) lesions were included. Sensitivity of CT for diagnosing GBC was 90 % (95 % confidence interval [CI]: 76–97). Specificity rates were 61 % (95 % CI: 49–72) and 59 % (95 % CI: 48–70). Three predictors of GBC (irregular lesion aspect, absence of fat stranding, and locoregional lymphadenopathy) were included in the risk score ranging from -1 to 4. Adequate performance was found (AUC: 0.79, calibration slope: 0.89). In patients allocated >0 points, the model showed higher performance in excluding GBC than the radiologists (sensitivity 92 % [95 % CI: 79–98]). Moreover, when allocated >3 points, the risk score was superior in diagnosing GBC (specificity 99 % [95 % CI: 93–100]). ConclusionsSensitivity rates of CT for differentiation between benign and malignant gallbladder lesions are high, however specificity rates are relatively low. The proposed risk score may facilitate differentiation between benign and malignant suspicious gallbladder lesions.

Failed Total Hip Arthroplasty: Diagnostic Performance of Conventional MRI Features and Locoregional Lymphadenopathy to Identify Infected Implants.

Very little has been published about the diagnostic performance of MRI in total hip arthroplasty (THA) infection. To determine the diagnostic performance of conventional MRI features and of new lymph nodal indices to identify infection in patients with failed THA. Retrospective. In all, 119 patients (66 females; age 66.9 ± 12.4 years) with failed THA. Metal artifact reduction sequence (MARS) protocol including short tau inversion recovery and turbo spin-echo T1 - and T2 -weighted sequences at 1.5T. Patients underwent pelvis MRI prior to failed THA revision. MRIs were reviewed to identify periprosthetic bone destruction, soft-tissue mass, effusion, synovitis, lamellated synovitis, extracapsular edema, fibrous periprosthetic membrane, bone edema, and extracapsular collection/sinus tract. The number and maximum diameter of inguinal, obturator and iliac lymph nodes of the affected hip were assessed and normalized to those of the unaffected hip to calculate the ratio of nodal size (RNS), ratio of node number (RNN), difference of nodal size (DNS), and difference of node number (DNN). The Mann-Whitney U-and chi-square test were used. Diagnostic performance of indices and odds ratios (OR) were calculated. RNS, RNN, DNS, and DNN indices were significantly different (P = 0.000) between infected and noninfected THA, with accuracies ranging from 84.8% (RNS) and 93.1% (RNN). All other MRI features were significantly more prevalent in infected THA (P ≤ 0.002), except bone destruction, periarticular soft-tissue mass, and fibrous membrane (P ≥ 0.031). Sensitivities ranged from 7.9% (soft-tissue mass) to 76.3% (effusion/bone edema), specificity from 45.7% (bone destruction) to 97.5% (synovitis/lamellated synovitis), accuracy from 49.6% (bone destruction) to 81.5% (synovitis), OR from 0.261 (soft-tissue mass) to 35.550 (synovitis). Conventional MRI features have limited accuracy to differentiate septic and aseptic THA failure. Lymph nodal indices, particularly those related to nodal number, may represent biomarkers of THA infection. 3 TECHNICAL EFFICACY STAGE: 2.

T cell/histiocyte rich large B cell lymphoma of ascending colon: a rare entity

Colonic T cell/histiocyte rich large B cell lymphoma (THRLBCL) is a very unusual occurrence never described before. A 41-year anaemic male presented with loss of weight and appetite for 7 months and fever with Malena for 1 month. Abdominal examination revealed a 4×6 cm retroperitoneal lump in the right iliac fossa. Radiological investigations (USG and CECT whole abdomen) reported an asymmetrical ill-defined growth in ascending colon and caecum with loco-regional lymphadenopathy. Surgical exploration revealed an ascending colon mass with retroperitoneal lymphadenopathy. Right hemi-colectomy with end ileostomy was done and specimen was sent for histopathology which diagnosed it to be a case of THRLBCL of colon. Patient was followed up after 2 weeks and was planned for chemotherapy.

ROLE OF GENERAL PRACTICE DOCTOR IN THE TREATMENT OF SIGNET RING CELL CARCINOMA

&amp;lt;p&amp;gt;Introduction: Stomach cancer is the second in mortality and the fourth most frequent of all cancers in the world. In the recent decades, the number of patients with Signet ring cell carcinoma type has been growing. Unknown etiology with proven risk factors such as smoked and salted foods, smoking, metabolic syndrome, alcohol abuse and Helicobacter pylori infection. Five-year span survival is 20%-40%.&amp;lt;/p&amp;gt; &amp;lt;p&amp;gt;Case outline: Patient, 70 years old, in good health, came to the GP, because of pain she had been feeling in the lower back area for a couple of months. Sometimes she wakes up because of the pain below the chest. Belch, acid, lost three kilograms. Didn&amp;#039;t pay any attention to the problem because earlier, due to severe osteoporosis, she had obtained a compression fracture of two vertebrae. Occult bleeding negative. Laboratory normal. Tenderness on palpation of epigastrium, the tumor mass is not palpable. Addressed immediate to esophagogastroduodenoscopy. Diagnosis: Ulcer ventriculi, region antrum. Histopathological findings: Gastric Adenocarcinoma, diffuse type, Signet ring cell. Computed tomography showed locoregional lymphadenopathy so responsible Consilium decided radical surgery and chemotherapy. Despite being treated, the patient pass away two years after the onset of the illness.&amp;lt;/p&amp;gt; &amp;lt;p&amp;gt;Conclusion: Primary health care workers have a big responsibility, because of nonspecific symptoms, in detection of gastric cancer. Good evaluation of patients who should be referred for esophagogastroduodenoscopy is essential. The doctor should keep in mind in the further course of treatment early postoperative complications, Dumping syndrome, appears ventral anastomosis, subocclusive disorders, gallbladders calculus formation, educate patients about nutrition, vitamins, monitor vitamin B12 and iron because patients are prone to vitamin deficiency and pernicious anemia. Psychological support for patients and their families is also very significant, through a concrete doctor-patient relationship.&amp;amp;nbsp;&amp;lt;/p&amp;gt;

High Frequencies of Mutated EZH2 and IRF8 and Other Epigenetic Genes in Primary Bone Lymphomas Are Indicative of GCB-Phenotype

Introduction Primary bone diffuse large B-cell lymphoma (PB-DLBCL) is a rare extranodal lymphoma comprising 1-2% of all malignant lymphomas. This study aims to elucidate the genetic background of a homogeneous cohort of PB-DLBCL. Methods This retrospective study consists of primary DLBCL-patients with bone localization(s) of which pretreatment fresh frozen or formalin-fixed paraffin-embedded bone tissue samples were available. Patients were diagnosed (2003-2019) at Leiden University Medical Center (LUMC), a center of expertise for bone tumors, Amsterdam University Medical Center (AUMC), Erasmus MC and affiliated Dutch hospitals. Based on strict definitions regarding radiological assessment of anatomical disease localizations at diagnosis three subgroups were categorized: solely osseous involvement (single or multiple bone lesions; PB-DLBCL), osseous involvement and locoregional lymphadenopathy (locoregional disease), and osseous and (multiple) extra-osseous localizations (disseminated disease). Cell-of-origin (COO) was determined by immunohistochemistry (BCL6, CD10, and MUM1) and classified according to the Hans' algorithm. Additionally, COO was confirmed with NanoString and the Lymph2Cx assay (Scott et al., Blood 2014), in a subset of patients. With similar procedures (Vermaat et al., Haematologica 2019), molecular profiles were determined with an in-house developed and validated targeted next-generation sequencing (tNGS) panel, comprising 52 DLBCL-specific genes, for sequencing with the Ion S5TM System. Obtained results were compared to sequencing data of (1) an independent 'in-house' cohort of 23 primary GCB (Germinal Center B-Cell)-DLBCL patients without bone localization ('non-osseous') and (2) pooled data of 651 GCB-DLBCL patients from literature (Chapuy et al., Nature Medicine 2018, Karube et al., Leukemia 2018, Reddy et al., Cell 2017, Schmitz et al., NEJM 2018). Results Our cohort contained 56 patients (males, N=33, (59%)) with a median age at diagnosis of 62 years (range 13-92). Twenty-four patients had PB-DLBCL (45%), 8 had locoregional disease (14%), and 23 had disseminated disease (41%). In general, immunohistochemistry and Lymph2Cx identified a GCB subtype for the majority of all DLBCL with bone localizations (Figure-1A) and these results for the hitherto unperformed cases will follow shortly. tNGS identified 48 genes with 'pathogenic' mutations, with on average four mutated genes per patients (range 0-10; Figure-1A). Overall, high mutation frequencies were observed in TNFRSF14 (33%), KMT2D (27%), EZH2 (25%), CREBBP (22%), B2M (22%), and TP53 (20%) in DLBCL with bone localizations and mainly genes involved in epigenetic machinery. In PB-DLBCLs, high frequency of mutated EZH2 (38%) and IRF8 (25%) were identified. Both are epigenetic genes that regulates tumor suppression and type I interferon, respectively. In four PB-DLBCLs EZH2 and IRF8 were concomitantly mutated. Locoregional disease showed a similar molecular profile as PB-DLBCL. Association with clinical characteristics will be performed shortly. Compared to our cohort of non-osseous GCB-DLBCL (Figure-1B) and pooled data of GCB-DLBCL in large sequencing studies (Figure-1C), EZH2 (Chi-square; P=0.046 and P=0.005, respectively) was significantly more frequently mutated in PB-DLBCL, though IRF8 did not attain this significance (Chi-square; P=0.121 and P=0.111, respectively; Figure-1D). Conclusion This study is the first that provides integrative analyses of immunohistochemistry, Lymph2Cx, and tNGS of a homogeneous cohort of PB-DLBCL, demonstrating the importance of epigenetic genes in lymphomagenesis. In contrast to (non-osseous) GCB-DLBCLs, the molecular profile of PB-DLBCL is characterized by significantly frequent mutations in EZH2 and frequent mutations in IRF8 and other epigenetic genes, which is indicative for a GCB phenotype (Scherer F. et al., Sci Transl Med 2016) and supported by immunohistochemistry and Lymph2Cx data. These results suggest that PB-DLBCL is a specific DLBCL-entity with a unique molecular profile and provide a rationale for exploration of novel targeted treatment with EZH2 (and IRF8) inhibitors for PB-DLBCL patients. Disclosures Lugtenburg: Genmab: Consultancy, Honoraria; Servier: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding, Speakers Bureau; BMS: Consultancy; Celgene: Consultancy, Honoraria; Janssen Cilag: Honoraria; Takeda: Consultancy, Honoraria, Research Funding. Kersten:Gilead: Honoraria; Mundipharma: Honoraria, Research Funding; Roche: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Takeda Oncology: Research Funding; Miltenyi: Honoraria; Kite Pharma: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Novartis: Honoraria.

Salvage Lymph-Node Percutaneous Cryoablation: Safety Profile and Oncologic Outcomes.

This is a retrospective study of all patients who underwent percutaneous CA of LN metastases (May 2014-April 2019). Eighteen patients with a total of 27 LNs were treated with CT-guided CA (Galil Medical, Israel). One patient was excluded since no follow-up was available. The mean LN diameter was 11mm (range 4-28mm). Thirteen patients had a history of previous treatment for locoregional lymphadenopathy. In 21 LNs, a supplementary thermal insulation-displacement technique was used (hydrodissection = 12; carbodissection = 6; both = 3). According to the RECIST criteria, 8 LNs had a complete response, 8 stable disease, 8 partial response and 1 progressive disease. In the subgroup of patients with prostate cancer relapse, the mean PSA level before treatment was 5.5ngr/ml (range 0.6-36ngr/ml) and reduced to 0.32 (range 0-1.1ngr/ml) and 0.3 (range 0-0.6ngr/ml) at 3- and 6-month follow-up, respectively. Six patients presented distant tumor deposits on follow-up that were further treated with systemic (5 patients: hormone/chemo/immunotherapy) and local therapies (1 patient: CA of bone oligometastatic disease). No major complication was noted. Two patients with obturator LN presented transient obturator nerve paresis. Mean follow-up was 15months (range 1-56months). In this series of patients, we have shown that metastatic LNs can be safely treated with image-guided CA. Caution should be paid, and additional measures should be taken when treating LNs near thermal-sensible structures.

PF519 MOLECULAR PROFILING OF PRIMARY BONE LYMPHOMA'S REVEALS FREQUENT MUTATIONS IN EZH2 AND OTHER EPIGENETIC GENES: IMPLICATIONS FOR TARGETED TREATMENT

Background:Primary bone diffuse large B‐cell lymphoma (PB‐DLBCL) is a rare extranodal lymphoma comprising 1–2% of all malignant lymphomas. Large next‐generation sequencing (NGS) studies identified genetic drivers in nodal diffuse large B‐cell lymphomas (DLBCLs), resulting in novel targeted therapeutic opportunities. However, the genetic constitution of PB‐DLBCL is still unclear and extensive sequencing studies have yet been performed.Aims:We aim to determine mutational profiles in a unique large cohort of PB‐DLBCL patients in correlation with clinicopathological characteristics.Methods:This retrospective cohort study consisted of 38 patients with bone localization of DLBCL, of which pretreatment fresh frozen or formalin‐fixed paraffin‐embedded bone tissue samples were available. Patients were diagnosed between 2003 and 2019 at Leiden University Medical Center (LUMC), a center of expertise for bone tumors, and affiliated hospitals in the Netherlands. Strict definitions, based on radiological assessment of anatomical disease localizations at diagnosis were applied, categorizing 3 different subgroups (figure 1A): patients with osseous involvement only (single or multiple bone lesions) (PB‐DLBCL), patients with osseous involvement and locoregional lymphadenopathy (locoregional disease), and patients with osseous and multiple extraosseous localizations (disseminated disease). An in‐house developed and validated targeted NGS panel comprising 52 B‐cell lymphoma‐specific genes was used for sequencing with the Ion S5TM System.Results:Our cohort contained 38 patients, 22 (58%) were male, and the median age at diagnosis was 61 years (range 13–92). Twenty patients had PB‐DLBCL (53%), 4 had locoregional disease (10%), and 14 had disseminated disease (37%). NGS analysis identified 32 genes with ‘pathogenic’ mutations, with on average 2.3 mutated genes per patient (figure 1B). No mutations were detected in 4 patients with disseminated disease. Overall, in patients with bone localization of DLBCL, high mutation frequencies were observed for EZH2 (31.6%), TP53 (21.1%), B2 M (15.8%), and TNFRSF14 (15.8%), belonging to epigenetic (63.2%), DNA damage response (21.1%), and immunity (26.3%) pathways, respectively. In PB‐DLBCL, EZH2 (35%) and TP53 (25%) mutations were considerably more frequently detected compared to disseminated disease (21% and 14%, respectively). In context, previous studies reported substantial lower incidences of mutated EZH2 (11–22%) and TP53 (12–20%) in DLBCLs with germinal center B‐cell (GCB) subtype (Reddy A. et al. 2017; Karube K. et al. 2018; Schmitz R. et al. 2018; and Chapuy B. et al. 2018). Although a small patient group, locoregional disease also demonstrated frequent mutations in EZH2 (50%, 2/4), TNFRSF14 (50%, 2/4), B2 M (50%, 2/4), and TP53 (25%, 1/4).Taken together, these findings demonstrate that the epigenetic pathway is affected most commonly in PB‐DLBCL and locoregional disease (75%), with a substantial lower frequency in disseminated disease (43%) (figure 1C). Correlation of genetic aberrations with gene‐expression profiling and clinicopathological characteristics will follow shortly.Summary/Conclusion:To our knowledge, this is the first study reporting a higher frequency of epigenetic mutations in patients with bone localization of DLBCL, thereby strengthening the concept that DLBCLs with bone location belong to the GCB subtype. Furthermore, the high incidence of mutated EZH2 in PB‐DLBCL patients provides a rationale for exploration of novel targeted treatment with EZH2 inhibitors to improve survival outcomes in these patients.image

99mTc-MIBI single photon emission computed tomography/computed tomography for the incidental detection of rare parathyroid carcinoma.

This study aimed to evaluate the characteristics of parathyroid carcinoma and to validate the diagnostic value of 99mTc-methoxyisobutylisonitrile (MIBI) single photon emission computed tomography/x-ray computed tomography (SPECT/CT) for differentiating between parathyroid carcinoma and hyperparathyroidism. Four consecutive patients with suspected primary hyperparathyroidism were enrolled in this study and underwent 99mTc-MIBI SPECT/CT, ultrasonography, enhanced CT, and MRI. Serum parathyroid hormone (PTH) and calcium were measured. All primary and recurrent lesions showed high focal uptake on 99mTc-MIBI image, whereas metastatic lymph nodes gave false negative results. The serum PTH was 165.14 ± 90.26 pmol/L, which declined rapidly after surgery. One patient with a persistently high PTH (147.5 pmol/L) after surgery presented with multiple lymphadenopathy in the neck. Higher expression of chromogranin A (CgA) further confirmed parathyroid carcinoma as a rare endocrine tumor. Parathyroid carcinoma is thus usually diagnosed incidentally based on nonspecific multiorgan symptoms of hypercalcemia and hyperparathyroidism. 99mTc-MIBI SPECT/CT may help to localize the parathyroid carcinoma, while MRI is valuable for detecting metastasis. Serum PTH and CgA serve as circulating biomarkers in parathyroid carcinoma, and raised levels of PTH and CgA together with locoregional lymphadenopathy may indicate parathyroid carcinoma. Further studies are needed.

A case of rectal hepatoid adenocarcinoma in a patient with inflammatory bowel disease: case report and review of literature

Hepatoid adenocarcinoma is a rare extrahepatic malignancy with histological features and biochemical profile similar to hepatocellular carcinoma. A 38-year-old male with a 10-year history of ulcerative colitis on treatment was found to have a large rectal mass with locoregional lymphadenopathy and distant spread to peri-portal nodes, hepatic parenchyma, and portal vein. Based on elevated serum AFP levels and immunohistochemical staining of rectal tissue, he was diagnosed with metastatic hepatoid adenocarcinoma and was treated with ten cycles of palliative folinic acid, fluorouracil and oxaliplatin (FOLFOX). Following an excellent response to FOLFOX, he was treated with curative intent with 5-fluorouracil (5-FU)-based neoadjuvant chemoradiation followed by proctocolectomy for local cancer control and ulcerative colitis treatment. This was followed by stereotactic body radiation therapy (SBRT) to the liver. The patient had no evidence of relapse three months after his last day of SBRT. This is the first report of comprehensive genomic testing in a patient with hepatoid adenocarcinoma. Genomic testing revealed a TP53 mutation with wild-type K-RAS. The tumor also revealed low (5-10%) expression of programmed death-ligand 1 (PD-L1) and stable microsatellite instability. Though the patient had metastatic disease, he was treated with curative intent with excellent response. This case highlights the fact that aggressive management might lead to good response in this highly aggressive malignancy.

Elevated serum IgG4 levels in diagnosis and treatment response in patients with idiopathic retroperitoneal fibrosis.

Idiopathic retroperitoneal fibrosis (iRPF) may be a manifestation of IgG4-related disease. Measuring serum IgG4 (sIgG4) may be of value in monitoring iRPF, but this has scarcely been evaluated. It is unknown if tamoxifen (TMX) affects sIgG4 levels. We performed a prospective inception cohort study of 59 patients with untreated (re)active iRPF stratified by elevated (>1.4g/L) or normal sIgG4 level. Changes in sIgG4 levels following TMX initiation and, if treatment failed, during subsequent corticosteroid (CS) treatment were analyzed. The median sIgG4 level was 1.1g/L (interquartile range (IQR) 0.4-2.2); 24 patients (40%) had elevated sIgG4 level. Patients with elevated sIgG4 tended to present with higher ESR (46 vs. 34mm/h; P=0.08) and more frequent locoregional lymphadenopathy adjacent to the mass (41.7 vs. 20.0%; P=0.08). sIgG4 also correlated with ESR (ρ=0.26; P=0.05) and serum creatinine (SC) (ρ=0.26; P=0.04). Following TMX initiation, sIgG4 level decreased, particularly when achieving treatment success (P<0.01). Odds ratio for TMX treatment success in patients with elevated sIgG4 level was 0.77 (95% CI 0.53-1.14; P=0.19). After adjusting for age, sex, and SC, the odds ratio was 0.78 (95% CI 0.51-1.18; P=0.24). ROC curve analyses of sIgG4 on a continuous scale and treatment success showed an AUC of 0.62. Treatment success and concurrent sIgG4 decrease (P<0.01) were achieved in 78% of patients who converted to CS therapy. Patients with elevated sIgG4 level may be more inflammatory than patients with normal sIgG4 level, but this needs further study. TMX affects sIgG4 levels, but to a lesser extent than CSs. sIgG4 cannot be used as an outcome prediction tool, irrespective of which cutoff value was chosen.

Kimura’s Disease- A Diagnostic Challenge

Kimura’s disease is a rare, benign, chronic inflammatory disease with an unknown etiology, which predominantly affects Asian males. It has predilection for the head and neck region, and primarily involves the major salivary glands and is accompanied with loco-regional lymphadenopathy. It is therefore often misdiagnosed for a salivary gland tumor or lymphadenopathy secondary to metastases, lymphoma or tuberculosis. We present a case of Kimura’s disease in a middle aged Chinese male patient manifesting as painless lumps over the left jaw and neck. Based on the CT scan, the differential diagnoses of lymphomatous/metastatic adenopathy affecting the left cervical and parotid nodes or a primary left parotid malignancy with ipsilateral metastatic adenopathy were considered. However, a fine needle aspiration biopsy of the left sided adenopathy yielded the diagnosis of Kimura’s disease. The triad of subcutaneous masses in head and neck region, regional lymphadenopathy and masses in one or more of the major salivary glands should raise the suspicion of Kimura’s disease.

Absence of Maternal Microchimerism in Regional Lymph Nodes of Children With Biliary Atresia.

Maternal lymphocytes have been cited as a potential cause of infantile biliary atresia (BA). When hepatoportoenterostomy is performed, locoregional lymphadenopathy is frequently encountered. We screened enlarged nodes from 6 consecutive nonsyndromatic BA patients (age: 68 days ± 18.9 days) for maternal elements using DNA fingerprinting with short tandem repeat analysis and quantitative real-time polymerase chain reaction for allelic (single nucleotide) sequence polymorphisms. Although being partly positive in infants' peripheral blood, no maternal microchimerism could be demonstrated in any of the lymph nodes. This result challenges the hypothesis that maternal cells play a role in hilar lymphadenopathy of children with BA.