Focal Involvement Research Articles

A Rare Case of Diffuse Large B Cell Lymphoma Co-occurring with Small Lymphocytic Leukemia: De Novo Process or Richter’s Syndrome?

Abstract Introduction/Objective Diffuse large B-cell lymphoma (DLBCL) is the most prevalent subtype of lymphoma and can arise either de novo or through transformation from indolent lymphomas, such as Chronic Lymphocytic Leukemia (CLL), known as Richter syndrome (RS). DLBCL derived from RS tends to exhibit more aggressive behavior compared to de novo DLBCL. Methods/Case Report We present a case of a 57-year-old female with no significant medical history, who initially presented with antibiotic and prednisone-resistant sinusitis, progressing to bilateral neck pain and eye congestion. Computed tomography (CT) imaging revealed a 3 cm mass in the right nasal cavity extending to the right maxillary sinus and medial right orbit. Histopathological examination showed diffuse sheets of intermediate to large cells with irregular nuclear contours, dispersed chromatin, variably conspicuous nucleoli, and moderate cytoplasm. Additionally, scattered foci of monotonous, atypical lymphoid cells with lower grade morphology, including small size and condensed chromatin, were also present. Immunohistochemical analysis revealed differential staining patterns between the two cell populations. The larger atypical cells expressed CD20, PAX5, CD10, BCL-6, MUM1, BCL-2, MYC, CD19 (dim), and exhibited a high Ki-67 proliferation index (>80%). In contrast, the smaller atypical cells were positive for CD5, CD19, CD20, PAX5, BCL-2, and CD23 (subset), with a lower Ki-67 proliferation index (<5%). Flow cytometry analysis of tissue samples revealed two distinct clones: Surface Kappa-restricted CD19 dim B cells (38.9%) with CD5- CD10 dim CD20+ and surface Lambda-restricted CD19+ B cells (58.7%) with CD5+ CD10- CD20+. FISH analysis revealed no gene rearrangements. The final diagnosis was Diffuse large B-cell lymphoma, germinal center B- cell phenotype, with aggressive features and focal involvement by small lymphocytic lymphoma/chronic lymphocytic leukemia. Results (if a Case Study enter NA) NA Conclusion The relationship between the large B-cell lymphoma and SLL/CLL remains uncertain; however, given the different immunophenotype and light chain expression observed by flow cytometry, they are likely to represent separate processes.

Uncovering underlying cause for heart failure in a 51-year-old woman with fibromuscular dysplasia

Abstract Introduction/Objective Arrhythmogenic cardiomyopathy is a rare disorder characterized by the replacement of the myocardium with fibroadipose tissue, usually affecting the right ventricle and rarely affecting the left. Methods/Case Report We present the case of a 51-year-old woman with past medical history including fibromuscular dysplasia of the internal carotid arteries and suspected ischemic cardiomyopathy with reduced ejection fraction awaiting heart transplant. The patient suffered a spontaneous coronary artery dissection eight years prior, which was the inciting factor that led to the decline in her cardiac function. After transplant, gross examination of the explanted heart showed a moderate amount of epicardial fat and visible intramural ventricular adipose tissue deposits in the myocardium. On histology, both the right and left ventricle walls showed extensive microscopic fatty infiltration along with focal involvement of the interventricular septum. These findings supported the final diagnosis of arrhythmogenic cardiomyopathy of the right and left ventricle, as well as involvement of the interventricular septum making this case especially rare. There were no signs of infarct or ischemic damage, contrary to what was expected given her diagnosis of ischemic cardiomyopathy. Results (if a Case Study enter NA) NA Conclusion The pathological work-up of this case shed light on the true nature of the patient’s cardiomyopathy and has prompted further genetic testing, as arrhythmogenic cardiomyopathy can be caused by several different genetic mutations. In addition to this work-up, a thorough literature review was performed looking for connections between arrhythmogenic cardiomyopathy and fibromuscular dysplasia, as arrhythmogenic cardiomyopathy is not often seen in this setting. Although no direct connection between the two was uncovered, it was found in the literature that a polymorphism in the Phosphatase and Actin Regulator 1 (PHACTR1) gene has been identified as a genetic component of fibromuscular dysplasia. This variant has been linked to spontaneous coronary artery dissection, which our patient experienced at the young age of 43. This could prompt further genetic investigation into her fibromuscular dysplasia in addition to the genetic work up already being done for her arrhythmogenic cardiomyopathy. This case highlights how rare etiologies can be uncovered through diligent histological analysis, and how further analysis using laboratory techniques such as genetic testing can help patients understand the full breadth of their conditions.

Experience in treating patients with autoimmune pancreatitis

Objective — to establish the main diagnostic signs of autoimmune pancreatitis and aspects of patient treatment. Materials and methods. The study analyzed the results of examination and treatment of 17 patients with autoimmune pancreatitis (AIP) from 2010 to 2022. Among the total number of patients with AIP, there were 11 men (65%) and 6 women (35%). The average age of the patients was 52.4 years. Among all patients with AIP, focal involvement of the pancreas was found in 3 (18%) patients, with a predominant involvement of the head of the pancreas. Segmental form of AIP was diagnosed in 6 (35%) patients, while diffuse form was found in 8 (47%) patients. Type 1 AIP was identified in 13 (76%) patients, and type 2 AIP in 4 (24%) patients. For all patients suspected of AIP, the HISORt criteria were assessed: instrumental visualization, serological and histological verification, determination of the volume of pancreatic involvement, and response to steroid therapy. Results. Recurrence of AIP was observed in 8 (47.0%) patients with type 1 AIP and 1 (5.8%) patient with type 2 AIP. AIP recurred in patients with proximal bile duct involvement, diffuse pancreatic involvement, persistently elevated IgG4 levels after steroid induction, delayed radiological remission, and damage to more than two organs. Increased serum levels of IgG, IgG4, apnd eosinophilia indicated a recurrence of IgG4‑RD. A repeat induction of steroids was performed in patients with recurrent AIP, which proved to be very effective, resulting in high remission rates, specifically in 7 (70%) patients with type 1 AIP and in 1 (100%) patient with type 2 AIP. Among all AIP patients that were operated on, 3 (40%) underwent Roux‑en‑Y hepaticojejunostomies, 1 (20%) pancreaticoduodenectomy, and 1 (20%) a Frey procedure. Conclusions. The low incidence of AIP necessitates the use of a clear diagnostic algorithm, and the peculiarities of the disease’s course require compliance with all the principles of conservative treatment and surgical interventions in case of surgical complications.

Evaluation of Risk Factors Determining Focal Organ Involvement in Patients Diagnosed with Brucellosis

Evaluation of Risk Factors Determining Focal Organ Involvement in Patients Diagnosed with Brucellosis

Determining the frequency of thyroid involvement in chest CT scans of COVID-19 patients and its correlation with the severity of lung involvement and survival of patients in 2020.

This study aimed to determine the frequency of thyroid gland involvement in chest CT scans of patients with COVID-19 admitted to university-affiliated hospitals and assess its relationship with the severity of lung involvement and patient survival in 2020. In this retrospective cross-sectional study, 1000 PCR-positive patients with COVID-19 who were referred to University-affiliated Hospital in 2020 and had chest CT performed within 72 hours of admission to the hospital were examined. The data was collected by patient file information and CT findings recorded in the PACS system, including thyroid involvement, the severity of lung involvement, and findings related to the death and recovery of patients. The mean age of the examined patients was 56 years. 525 people (52.5%) were men, and 475 (47.5%) were women. 14% had severe pulmonary involvement, and 9.3% had very severe involvement. Moreover, 15.9 percent of them had deceased. 19.7% had focal thyroid involvement, 14% had diffuse involvement, and 66.3% were healthy subjects. Male gender and older age showed a significant relationship with thyroid gland involvement. The severity of lung involvement, the death rate in patients, and hospitalization in ICU were also significantly related to thyroid gland involvement in patients with COVID. This study highlights the importance of considering thyroid-gland involvement in the comprehensive management of COVID-19 patients. Routine screening and monitoring of thyroid-function may facilitate earlier detection and appropriate management of thyroid-related complications, potentially improving clinical outcomes. This study suggests that in COVID-19 infection the monitoring of thyroid function is prudent, particularly in cases of more serious disease.

An Extensive Analysis and Comparison of Bone Marrow Aspiration and Bone Marrow Trephine Biopsy at a Tertiary Care Hospital in Jharkhand for Various Hematological and Non-hematological Illnesses.

Background Bone marrow examination (BME) is an indispensable diagnostic tool to evaluate various hematological and non-hematological disorders. Bone marrow aspirate cytology and bone marrow trephine biopsy, even though performed simultaneously, are assessed at different points in time due to different processing methods. Aims and objective This study aims to assess and compare the role of bone marrow aspiration and trephine biopsy to formulate an effective and rapid method for diagnosing a wide spectrum ofvarious hematological and non-hematological disorders. Materials and methods The approach of our study was a hospital-based prospective study conducted on 200 patients over a period of 1 year. The role of bone marrow aspiration and a trephine biopsy is to formulate an effective and rapid method for diagnosing a wide spectrum of hematological and non-hematological disorders. Results In our study, a total of 200 cases were studied, of whom 119 patients were male and 81 were female. The most common finding was erythroid hyperplasia, comprising 40 (20%) cases, followed by hypoplastic marrow, comprising 28 (14%) cases. Subsequently, there were 19 (9.5%) cases of acute leukemia, while 15 (7.5%) cases of chronic myeloid leukemia (CML) in the chronic phase were found. In our study, bone marrow aspirate and bone marrow trephine biopsy were found to positively correlate in 137 (68.5%) of the cases. Conclusion Bone marrow aspiration alone is sufficient for the diagnosis of megaloblastic anemia and most of the hematological malignancies. Bone marrow trephine biopsy is more appropriate for the detection of disorders of focal marrow involvement such as lymphoproliferative disorders and staging of lymphomas, metastatic cancers, granulomatous lesions, and hypoplastic marrow. However, it is strongly recommended that both procedures should be done simultaneously to ensure maximum diagnostic accuracy.

Abstract PO2-23-01: Selective cavity margin shaving: effective method to maintain balance between cosmesis and negative margin in breast conserving surgery

Abstract Background: Breast conserving surgery (BCS), which became the mainstay of breast cancer surgery, both cosmesis and margin negativity are significant issues. Firstly, it is well known that negative resection margin is crucial for reducing local recurrence after BCS. Therefore, there has been numerous attempts to secure negative margin, such as specimen mammography, frozen section margin analysis, and cavity margin shaving. Regarding cosmesis, wider excision to secure negative margin could disrupt cosmesis especially in Asian patients with relatively smaller breast, and minimizing excision volume is necessary for optimal cosmetic outcome. Our center adopted the concept of selective cavity margin shaving (SCMS) to achieve negative margin while optimizing cosmetic result. Method: 606 female patients with non-metastatic, unilateral breast cancer were prospectively collected and underwent BCS with SCMS from October, 2012 to December, 2020. The medical record was retrospectively reviewed, and we assessed positive margin rate and local recurrence. During BCS, the surgeon excised gross margin of 1~2cm around the cancer, and assessed the proximity of the margin through gross examination. If sufficient margin was not obtained, cavity shaving was performed in the close margin, while shaving from retrieved specimen was conducted on the sufficient margin side. Additionally, circumferential margin frozen analysis was carried out, and further excision was performed until a negative margin was achieved or when only focal DCIS involvement remained. Result: The mean ± SD age of the patients was 52.47 ± 9.92 years and mean follow-up period was 59.98 ± 26.59 months. 56 patients (9.24%) received neoadjuvant chemotherapy. 123 patients (20.29%) got positive margin for invasive cancer or DCIS in frozen section margin analysis and 97 patients (16.01%) underwent intraoperative re-excision. There was discordance between frozen and permanent section margin analysis in 48 patients (7.92%), and 7 patients (1.16%) underwent post-operative re-excision operation. Local recurrence occurred in 11 patients (1.82%), which is significantly lower compared to previously reported outcomes after BCS. Presence of lympho-vascular invasion, neoadjuvant chemotherapy, and margin involvement of invasive cancer in permanent section analysis were strongly related with local recurrence. Conclusion: In conclusion, SCMS and frozen section margin analysis demonstrated low positive margin rate and reduced re-excision rate. The local recurrence was also lower compared to conventionally reported rate after BCS. Selective cavity margin shaving is an oncologically safer and effective surgical method with minimized cosmetic deformity. Table 1. Baseline patient characteristics Table2. Univariate and multivariate analysis of factors associated with local recurrence Table2. Univariate and multivariate analysis of factors associated with local recurrence by Cox proportional hazard model. Citation Format: Dabin Kim, Zisun Kim, Sung Mo Hur, Cheol wan Lim. Selective cavity margin shaving: effective method to maintain balance between cosmesis and negative margin in breast conserving surgery [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-23-01.

The effect of steroid therapy on pancreatic exocrine function in autoimmune pancreatitis

Background/objectivesAutoimmune pancreatitis (AIP) is a steroid-responsive inflammatory disease of the pancreas. Few studies investigated pancreatic exocrine function (PEF) in patients suffering from AIP and no definitive data are available on the effect of steroids in PEF recovery. Aim of the study is the evaluation of severe pancreatic insufficiency (sPEI) prevalence in AIP at clinical onset and after steroid treatment. Methods312 Patients with diagnosis of AIP between January 1st, 2010 and December 31st, 2020 were identified in our prospectively maintained register. Patients with a pre-steroid treatment dosage of fecal elastase-1 (FE-1) were included. Changes in PEF were evaluated in patients with available pre- and post-treatment FE (between 3 and 12 months after steroid). ResultsOne-hundred-twenty-four patients were included, with a median FE-1 of 122 (Q1-Q3: 15–379) μg/g at baseline. Fifty-nine (47.6 %) had sPEI (FE-1<100 μg/g). Univariable analysis identified type 1 AIP, radiological involvement of the head of the pancreas (diffuse involvement of the pancreas or focal involvement of the head), weight loss, age and diabetes as associated with a greater risk of sPEI. However, at multivariable analysis, only the involvement of the head of the pancreas was identified as independent risk factor for sPEI. After steroids, mean FE-1 changed from 64 (15–340) to 202 (40–387) μg/g (P = 0.058) and head involvement was the only predictor of improvement of sPEI. ConclusionThe inflammatory involvement of the head of the pancreas is associated with PEF severity, as well as PEF improvement after treatment with steroids in patients with AIP.

Diagnostic Utility of Bone Marrow Aspiration, Trephine Biopsy, and Flow Cytometry in the Evaluation of Various Haematological and Non Haematological Disorders: A Cross-sectional Study from Northern India

Introduction: The spectrum of haematological and non haematological disorders is vast in various age groups. Complete blood counts and other routine laboratory tests are not always sufficient to diagnose these diseases. Bone marrow examination plays an important role in diagnosing their underlying causes. Aim: To analyse the spectrum of various haematological and non haematological disorders reported in Bone Marrow Aspiration (BMA) and compare them with Bone Marrow Trephine Biopsy (BMB) and Flow Cytometry (FCM) findings where applicable. Materials and Methods: A one-year cross-sectional study was conducted in the Department of Clinical Pathology, PGIMS, Rohtak, Haryana, India from April 2022 to March 2023. A total of 518 consecutive BMA samples were morphologically analysed. Comparative evaluations were performed among BMA, BMB, and FCM where applicable. Diagnostic accuracy was calculated, and the findings of discordant cases were tabulated. Definitive diagnosis of lymphoma/leukaemia and Paroxysmal Nocturnal Haemoglobinuria (PNH) cases were made using FCM. Results: The patients’ ages ranged from three months to 86 years, with a mean age of 38.4 years. The male to female ratio was 1.3:1, with a slight male predominance. The highest number of cases were of anaemia {183 (35.3%) and 164 (31.7%), respectively} and leukaemia {128 (24.7%) and 134 (25.9%), respectively}, followed by normal marrow studies {39 (7.5%) and 32 (6.2%), respectively} and megakaryocytic thrombocytopenia {24 (4.6% in each} in both BMA and biopsy. Among anaemia cases {183 and 164 cases in BMA and BMB}, the majority were of the megaloblastic type {62 (33.8%) and 54 (32.9%), respectively}, followed by hypoplastic/aplastic type {40 (21.8%) and 50 (30.5%), respectively}. In cases of leukaemia (128 and 134 cases in BMA and BMB), acute leukaemia cases (76 (59.4%) and 82 (61.2%), respectively} outnumbered chronic leukaemia cases {52 (40.6%) and 52 (38.8%), respectively} in both BMA and BMB. The concordance and discordance rate between BMA and BMB were 87.6% (419 cases) and 12.4% (59 cases), respectively. Diagnosis was exclusively made by BMB in cases of myelofibrosis, granulomatous disease, and Hodgkin’s lymphoma. Conclusion: BMA cytology is a relatively safe and mildly invasive technique for evaluating various haematological and non haematological disorders with better preservation of cellular morphology. However, in cases with dry/blood taps and focal marrow involvement, BMB should be performed, as it shows well-preserved marrow architecture with all its cellular and stromal components. FCM is a definitive diagnostic modality for further categorisation of acute leukaemia and Chronic Lymphoproliferative Disorders (CLPD).

Chapter 16 - Focal inflammatory neuropathies

This chapter focuses on neuropathies that present with focal involvement of nerve roots, plexus, and/or peripheral nerves associated with autoimmune and inflammatory mechanisms that present with focal involvement of nerve roots, plexus and/or peripheral nerves. The clinical presentation, diagnosis, and treatment of focal autoimmune demyelinating neuropathies, focal nonsystemic vasculitic disorders (diabetic and nondiabetic radiculoplexus neuropathies, postsurgical inflammatory neuropathy, and neuralgic amyotrophy), and focal neuropathies associated with sarcoidosis and bacterial and viral infections are reviewed.

Imaging Features of Pediatric Sarcoidosis.

Sarcoidosis is a granulomatous inflammatory disease of uncertain cause. It occurs most commonly in young and middle-aged adults and less frequently in children; therefore, few data on pediatric sarcoidosis exist in the literature. The diagnosis and management of sarcoidosis remain challenging because of diverse and often nonspecific clinical and imaging findings. In addition, the clinical picture varies widely by age. Prepubertal and adolescent patients often present with adult-like pulmonary disease; however, early-onset sarcoidosis is typically characterized by the triad of arthritis, uveitis, and skin rash. Sarcoidosis is mostly a diagnosis of exclusion made by demonstrating noncaseating granulomas at histopathologic examination in patients with compatible clinical and radiologic findings. Although sarcoidosis often affects the lungs and thoracic lymph nodes, it can involve almost any organ in the body. The most common radiologic manifestation is pulmonary involvement, characterized by mediastinal and bilateral symmetric hilar lymphadenopathies with perilymphatic micronodules. Abdominal involvement is also common in children and often manifests as hepatomegaly, splenomegaly, and abdominal lymph node enlargement. Although neurosarcoidosis and cardiac sarcoidosis are rare, imaging is essential to the diagnosis of central nervous system and cardiac involvement because of the risky biopsy procedure and its low diagnostic yield due to focal involvement. Being familiar with the spectrum of imaging findings of sarcoidosis may aid in appropriate diagnosis and management. ©RSNA, 2023 Test Your Knowledge questions are available in the supplemental material.

Demographic characteristics, laboratory features and complications in 346 cases of brucellosis: A retrospective study from Qatar

ObjectivesTo study the epidemiology and laboratory findings and outcomes of human brucellosis in the state of Qatar. MethodsA retrospective study involving adult patients with a definitive diagnosis of brucellosis was conducted. ResultsOf the 346 patients 299 were males. The mean age was 39.62 years. 120 patients had history of drinking raw milk and 116 had a history of contact with animals. Fever (89.9%) and myalgia (56.6%) were the most common presenting symptoms observed. Raised C-reactive protein level was the most frequent laboratory finding noted. Alanine aminotransferase and aspartate aminotransferase levels were raised to three times the normal in 39.6% and 37% of patients, respectively. Blood culture was positive in 72.8% whereas Brucella immunoglobulin G antibody and immunoglobulin M antibody titer was positive in 72.5% and 73.1% patients, respectively. Approximately 21.4% had focal involvement and osteoarticular (11.6%) involvement was the most frequently observed focal form. Doxycycline with rifampicin or gentamicin was the common regimen received. Relapse was seen in 7.2% patients. ConclusionHuman brucellosis continues to be a serious health issue in Qatar predominantly affecting healthy young adult men resulting in significant morbidity. Preventive measures and community awareness particularly among high-risk groups will help in decreasing the prevalence of the disease and its aftereffects.

Autoimmune pancreatitis versus pancreatic cancer

Autoimmune pancreatitis (AIP) is classified as a distinct form of pancreatitis according to the guidelines. It is characterized by imaging morphologic and histologic features and is associated with extrapancreatic manifestations in type1 IgG4-associated disease. Symptoms and findings almost always improve with administration of steroids. Differentiation from pancreatic ductal adenocarcinoma is required, particularly in the presence of AIP with focal parenchymal involvement. If AIP is suspected, abdominal ultrasound and/or endosonography, computed tomography (CT), and preferably magnetic resonance imaging (MRI) are indicated. A distinction is made between parenchymal and ductal changes that specifically indicate the presence of AIP. The diagnosis of autoimmune pancreatitis should be made based on the International Consensus Criteria (ICDC), in which the five main features (imaging, serology, histology, other organ involvement, response to steroid medication) are assessed. In type1 AIP, typical imaging changes are sufficient to establish the diagnosis even with negative histology, whereas for type2 AIP, histologic evidence is required. Imaging changes help in the differential diagnosis from pancreatic cancer. The following article addresses and evaluates crucial imaging diagnostic CT and MRI criteria for correct classification of findings, description of results, and differentiation of autoimmune pancreatitis from pancreatic cancer.

Clinico-radiologic subtypes and therapeutic observation of acute Marchiafava-Bignami disease

We aimed to investigate the clinico-radiologic features of acute Marchiafava-Bignami disease (MBD) and its evolutionary process after effective treatment through subgroup comparison. The clinical and MRI data of 23 patients with acute MBD were retrospectively analyzed and divided into type A (12 cases, with entire callosal involvement) and type B (11 cases, with focal callosal involvement). The clinical assessments and MRI findings (before and after treatment) were compared between the two subtypes. Compared with type B, type A had lower MoCA (Montreal Cognitive Assessment) scores at admission (16.50 ± 1.73 vs 18.27 ± 1.68, P = 0.021) and were more common with extracallosal involvement (66.67% vs 18.18%, P = 0.036) and longer illness duration (18.3 ± 2.1 days vs 15.6 ± 2.4 days, P = 0.012). During the treatment, the residual lesion in the splenium was more common in type A (58.33% vs 9.09%, P = 0.027). After treatment, the MoCa scores of both subtypes gradually increased (P < 0.001), and the callosal and extracallasal lesions disappeared completely. Clinico-radiologic typing of acute MBD is related to the severity of early symptoms, but not to the prognosis. Complete clinico-radiologic recovery is possible for both subtypes with combined treatment. The clinico-radiologic reversibility is helpful for accurate diagnosis and therapeutic evaluation.

Clinical and Radiological Parameters to Discriminate Tuberculous Peritonitis and Peritoneal Carcinomatosis.

It is challenging to differentiate between tuberculous peritonitis and peritoneal carcinomatosis due to their insidious nature and intersecting symptoms. Computed tomography (CT) is the modality of choice in evaluating diffuse peritoneal disease. We conducted an ambispective analysis of patients suspected as having tuberculous peritonitis or peritoneal tuberculosis between Jan 2020 to Dec 2021. The study aimed to identify the clinical and radiological features differentiating the two entities. We included 44 cases of tuberculous peritonitis and 45 cases of peritoneal carcinomatosis, with a median age of 31.5 (23.5-40) and 52 (46-61) years, respectively (p ≤ 0.001). Fever, past history of tuberculosis, and loss of weight were significantly associated with tuberculous peritonitis (p ≤ 0.001, p = 0.038 and p = 0.001). Pain in the abdomen and history of malignancy were significantly associated with peritoneal carcinomatosis (p = 0.038 and p ≤ 0.001). Ascites was the most common radiological finding. Loculated ascites, splenomegaly and conglomeration of lymph nodes predicted tuberculous peritonitis significantly (p ≤ 0.001, p = 0.010, p = 0.038). Focal liver lesion(s) and nodular omental involvement were significantly associated with peritoneal carcinomatosis (p = 0.011, p = 0.029). The use of clinical features in conjunction with radiological findings provide better diagnostic yields because of overlapping imaging findings.

A rare case report of non-syndromic unilateral cerebellar dysplasia and hypoplasia: a diagnostic enigma

BackgroundCerebellar malformations are broadly categorized into hypoplasias and dysplasias, which are further divided based on focal or diffuse involvement. Both hypoplasias and dysplasias are usually associated with cerebral involvement or as a part of syndromes. Isolated unilateral cerebellar dysplasia is, however, extremely unusual.Case presentationWe present a rare case of isolated unilateral cerebellar dysplasia, in a 25-year-old male patient, who came to the Neurology clinic with complaints of infrequent seizure episodes since childhood.ConclusionNotable isolated unilateral cerebellar dysplasia is a rare entity requiring symptomatic treatment, with an anomalous development process being the likely aetiology.

Perceptions of Controversies and Unresolved Issues in the 2014 FIGO Staging System for Endometrial Cancer: Survey Results From Members of the International Society of Gynecological Pathologists and International Gynecologic Cancer Society.

Long-standing controversial and unresolved issues in the current "International Federation of Gynecology and Obstetrics" staging system for endometrial cancer are well-recognized by pathologists and clinicians alike and exist primarily as a result of limitations to the existing literature. To guide the design of future outcome-based studies specifically aimed at resolving such gaps, the International Society of Gynecologic Pathologists developed a survey of the current perceptions of pathologists (n = 172) and clinicians (n= 135) from the International Society of Gynecological Pathologists and from the International Gynecologic Cancer Society on areas for potential refinement of the current International Federation of Gynecology and Obstetrics staging system. The highest priority issues for pathologists and clinicians alike were the need to determine whether stage IIIA patients (ovarian/fallopian tube involvement) can be reliably separated into favorable versus unfavorable outcome groups to avoid over-treatment of the former group and to determine whether stage IIIC patients (lymph node metastases) can be separated into favorable versus unfavorable outcome groups based on the size of lymph node metastases. The majority of pathologists and clinicians viewed lymphovascular space invasion as an independent prognostic variable and favored incorporating lymphovascular space invasion into staging, though the level of support did not meet the threshold of 75% in support that we used to define a formal consensus. While pathologists did agree on the prognostic value of reporting the extent of lymphovascular space invasion, there was no consensus on the diagnostic criteria to distinguish focal versus substantial involvement. The majority of pathologists and clinicians viewed that a universally accepted protocol for sentinel lymph node ultra-staging is lacking. Both survey groups conveyed a slight preference for incorporating tumor histotype and molecular classification into staging but the support was short of the 75% threshold for formal consensus. Collectively, this survey permits the International Society of Gynecological Pathologists to develop a pathologist and clinician-driven long-term strategy for prioritizing and designing outcome-based studies specifically targeted to resolving controversial and unresolved issues in the International Federation of Gynecology and Obstetrics staging of endometrial cancer.

#5128 PREDICTIVE FACTORS OF RENAL RECOVERY AND END-STAGE KIDNEY DISEASE IN PATIENTS WITH SEVERE ANCA-ASSOCIATED VASCULITIS WITH GLOMERULONEPHRITIS

Abstract Background and Aims A significant number of patients with anti-neutrophil cytoplasmic antibodies (ANCA) associated vasculitis (AAV) with glomerulonephritis (AAV-GN) still progress to end-stage kidney disease (ESKD, eGFR&amp;lt;15mL/min/1.73m2) despite advances in remission-induction treatment. Method A retrospective cohort study on MPO- or PR3-ANCA positive patients with AAV (MPA or GPA) and ESKD at presentation. Renal recovery, dialysis discontinuation and maintenance in ESKD after standard remission-induction, with or without the use of PLEX were compared. Results We analyzed 166 patients with biopsy proven active kidney involvement and eGFR &amp;lt;15mL/min/1.73m2 at the time of AAV-GN diagnosis. Patients received glucocorticoids with CYC (n = 84) or with RTX (n = 72) for remission-induction, and 49 also received PLEX. The predictors for renal recovery were erythrocyte sedimentation rate, SCr at diagnosis and minimal or mild chronicity changes. We analyzed 71 patients who started dialysis with or without PLEX within 4 weeks from AAV-GN diagnosis. The predictors for dialysis discontinuation were minimal chronicity changes in kidney biopsy at the time of diagnosis (OR 6.138, [95%CI 1.389-27.118],p = 0.017) and focal glomerular involvement (OR 5.017,[95%CI 1.287-19.567],p = 0.020). Predictors for maintenance in ESKD at 12 months included higher serum creatinine (SCr) at the time of diagnosis (IRR 1.086, [95%CI 1.005-1.173],p = 0.037), moderate (IRR 3.797,[95%CI 1.090-13.225],p = 0.036), or severe chronicity changes in kidney biopsy (IRR 5.883,[95%CI 1.542–22.439],p = 0.009). Conclusion In our cohort, kidney recovery, dialysis discontinuation, and maintenance of ESKD in patients with AAV-GN and eGFR&amp;lt;15mL/min/1.73m2 depended on SCr and histologic findings on kidney biopsies at the time of diagnosis and was not affected by the addition of PLEX.

17th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, 13 - 17 June, 2023.

Introduction and Aim: Recently, in an ancillary study of FOLL12 trial (NCT02063685), total Metabolic Tumor Volume (tMTV) assessed before treatment has been demonstrated to be an independent predictor of PFS in patients receiving frontline immune chemotherapy (1). During the segmentation procedure, it has been observed that frequently spleen MTV (sMTV) heavily influenced the tMTV value, particularly in case of diffuse spleen uptake included in tMTV calculation. High tMTV could be a negative prognostic factor as it represents the tumor burden. On this basis, the aim of the current study was to evaluate the effect of the sMTV defined on baseline PET on tMTV calculation and its impact on outcome, particularly 5y-PFS (Progression Free Survival), in follicular lymphoma patients. Methods and Results: Overall, 690 patients with baseline PET were included in the analysis, 48% were older than 60 years, 89% had stage III-IV disease and 40% had a high-risk FLIPI-2 score. Overall, the 5y-PFS was 79% (95% CI, 76%–82%). Among 690 patients 469 (67.9%) did not have spleen involvement while 128 (18.5%) and 93 (13.4%) showed focal and diffuse spleen involvement, respectively. The 5y-PFS (95% CI) according the spleen status was 67% (62–72), 58% (48–67) and 61% (49–61) in patients without, with focal and with diffuse spleen involvement, respectively (p not significant). MTV calculation was performed with a threshold of 41% for segmentation. In the whole population of 690 patients, the tMTV threshold to categorized low and high tumor burden was 224 and 194 ml with and without sMTV, respectively. Assuming 200 ml as a tMTV threshold, only 16/693 pts (2.3%) changed from low to high tumor burden when the sMTV was included in the tMTV. Including sMTV in tMTV, with a threshold of 200 ml, the 5y-PFS in patients with low and high tMTV was 73% (95% CI: 67–78) and 58% (95% CI: 53–64), respectively, with a HR of 1.83 (p < 0.001). Excluding sMTV from tMTV, the 5y-PFS in patients with low and high tMTV was 72% (95% CI: 67–77) and 58% (95% CI: 52–64) with a HR of 1.80 (p < 0.001). In the two groups, HRs values for tMTV >200 ml showed negligible difference, independently from sMTV inclusion. Conclusion: These preliminary data of the FOLL12 trial showed that tMTV correlated with outcome in terms of PFS; on the contrary the metabolic spleen status defined in the baseline PET do not seem to show any prognostic added value, neither in case of focal nor in case of diffuse uptake. Finally, the inclusion/exclusion of the sMTV into the tMTV did not significantly change either the risk classification of the patients or the outcome in terms of PFS. Larger patients population are needed to confirm these data.

Molecular genetic features and clinical manifestations in Chinese familial cerebral cavernous malformation: from a novel KRIT1/CCM1 mutation (c.1119dupT) to an overall view.

Cerebral cavernous malformations (CCMs) are common vascular anomaly diseases in the central nervous system associated with seizures, cerebral microbleeds, or asymptomatic mostly. CCMs can be classified as sporadic or familial, with familial cerebral cavernous malformations (fCCMs) being the autosomal dominant manner with incomplete penetrance. Germline mutations of KRIT1, CCM2, and PDCD10 are associated with the pathogenesis of fCCMs. Till now, little is known about the fCCMs mutation spectrum in the Han Chinese population. In this study, we enrolled a large, aggregated family, 11/26 of the family members were diagnosed with CCMs by pathological or neuroradiological examination, with a high percentage (5/9) of focal spinal cord involvement. Genomic DNA sequencing verified a novel duplication mutation (c.1119dupT, p.L374Sfs*9) in exon 9 of the Krev interaction trapped 1 (KRIT1) gene. The mutation causes a frameshift and is predicted to generate a truncated KRIT1/CCM1 protein of 381 amino acids. All our findings confirm that c.1119dupT mutation of KRIT1 is associated with fCCMs, which enriched the CCM genes' mutational spectrum in the Chinese population and will be beneficial for deep insight into the pathogenesis of Chinese fCCMs. Additionally, with a retrospective study, we analyzed the molecular genetic features of Chinese fCCMs, most of the Chinese fCCMs variants are in the KRIT1 gene, and all these variants result in the functional deletion or insufficiency of the C-terminal FERM domain of the KRIT1 protein.