Benign Lymphoproliferative Disorder Research Articles

Myasthenia gravis with Castleman disease: A case report with review of literature.

Myasthenia gravis is an autoimmune disorder caused by the formation of autoantibodies directed against the synapses of neuromuscular junction. It is most commonly associated with other non-thymomatous lesions. Castleman disease is one of them, which is a benign lymphoproliferative disorder of uncertain origin. Only eight cases of myasthenia gravis associated with Castleman disease have been described so far. Here, we take the opportunity to describe a case of myasthenia gravis with Castleman disease simulating thymoma clinically and radiologically along with review of literature of this rare association. Patient developed myasthenic crisis in the immediate post-operative period which is more common in myasthenia gravis with Castleman disease rather than myasthenia gravis with thymoma.

Evaluation of the frequency of benign reactive lymphocytosis and lymphoproliferative disorders by flow cytometry in patients with persistent lymphocytosis in peripheral blood

Introduction: Lymphocytosis is characterized by an elevation in the absolute lymphocyte count (ALC) to over 4000 lymphocytes per microliter among adults. In lymphocytosis, the important matter is whether lymphocytosis is a benign reactive condition or a neoplastic lymphoproliferative disorder (LPD), which can be determined by immunophenotyping methods by flow cytometry. Objectives: Due to the need to use flow cytometry to confirm the diagnosis of patients with lymphocytosis, the purpose of this study was to compare the frequency of benign reactive lymphocytosis and LPDs in patients with persistent lymphocytosis using flow cytometry in the peripheral blood and report the results based on the patient’s demographic characteristics. Materials and Methods: This study was a cross-sectional study and the study population was all peripheral blood samples referred to Seyed Al-Shohada hospital in Isfahan to study the cause of absolute and persistent lymphocytosis by immunophenotyping analysis through flow cytometry between 2015 and 2020. Inclusion criteria were patients over 18 years of age with absolute lymphocytosis in complete blood count (CBC) or peripheral blood smear (PBS) who were examined by flow cytometry. Results: This study involved 222 samples, 139 (62.6%) of the cases were male. The mean age was 60.41 (15.91) years. All samples had absolute lymphocytosis and were divided into two groups: benign, with 62 (27.9%), and malignant, with 160 (72.1%). Conclusion: The relationship between gender and malignancy showed that the male gender was associated with an increased risk of malignancy. The mean age between the two groups of malignant and benign was determined by independent t test, and it was shown that the mean (±standard deviation) age of malignant cases is higher than the mean age of benign cases. It is recommended that cases of suspected lymphoproliferative cases and cases with cell counts below the lymphocytosis threshold be investigated in separate studies.

Localisation intramusculaire d’une maladie de Castleman unicentrique : cas clinique et revue de la littérature

Castleman's disease is a rare and benign lymphoproliferative disorder which can be unicentric (UCD) or multicentric (MCD). UCD usually involves a single lymph node or less frequently a group of lymph nodes. The most common sites of nodal UCD presentation are the mediastinum, neck, abdomen and retroperitoneum. Rarely extranodal involvement has been reported. The intramuscular location is very unusual with only about 10 cases described in medical literature so far. We present a case of atypical localization of Castleman's disease occurring in the right gluteal area in a 40-years-old female patient. The patient was asymptomatic and clinical examination was unremarkable except for a right gluteal palpable mass. The CT scanner-guided needle core biopsy was inconclusive. A surgical excision was then performed that revealed a hyaline-vascular type of Castleman's disease. The patient has an uneventful post-operative course. The present case is instructive in the work-up of primary soft tissue tumors, for which Castleman's disease is extremely rare and not considered in the differential diagnosis of clinicians. Pathologists must be aware of its existence so that it can be evoked in the presence of a lymphoid population on histological examination.

CPC09 New-onset agminated Spitz naevi following hypopigmented pityriasis lichenoides chronica

Abstract A 9-year-old girl presented to dermatology with erythematous scaly patches affecting her legs and arms, and hypo­pigmented patches affecting the trunk. She was otherwise fit and well, with no preceding illness or new medications. Treatment with mometasone 0.1% and an emollient was unsuccessful. Two years later, she had continued to develop new hypopigmented patches, as well as dark clustered naevi on the trunk. An incisional biopsy was taken from a hypopigmented patch of the right abdomen and one of the new naevi from the right hip. Incisional biopsy of the hypo­pigmented patch showed scattered necrotic keratinocytes in the epidermis with mild hydropic degeneration of basal cells and a mild superficial and perivascular lymphohistiocytic infiltrate in the dermis, consistent with pityriasis lichenoides chronica (PLC). Incisional biopsy of an eruptive naevus showed a junctional proliferation of melanocytes with overlying epidermal hyperplasia and hyperkeratosis and transepidermal elimination of melanin. Nests of epithelioid melanocytes were present at the rete tips, with no pagetoid spread and no atypia, consistent with an eruptive Spitz naevus. PLC is a benign lymphoproliferative disorder, typically presenting with erythematous scaly papules that relapse and remit. However, cases of PLC presenting with hypopigmentation alone have also been reported, as in this case, which can be part of a postinflammatory dyspigmentation or active disease (Elbendary A, Abdel-Halim MR, Youssef R et al. Hypopigmented lesions in pityriasis lichenoides chronica patients: are they only post-inflammatory hypopigmentation? Aust J Dermatol 2021; 63:68–73). The clustered pattern of Spitz naevi in this patient is termed agminated Spitz naevus. Eruptive disseminated and agminated Spitz naevi are much rarer than the solitary presentation. Triggers of eruptive Spitz naevi include pregnancy, blistering disorders and topical tacrolimus, and in one case following pityriasis lichenoides et varioliformis acuta (Mazzurco J, Menssen K, Schapiro B et al. Eruptive disseminated Spitz nevi in a 26-year-old African-American woman. Int J Dermatol 2012; 51:1270–1), while agminated Spitz naevi are reported to occur after radiotherapy and sunburn, and to arise in naevus spilus or congenitally hypo- or hyperpigmented patches. No cases of malignancy in agminated or eruptive disseminated Spitz naevi have been reported. In this case, the new onset of agminated Spitz naevi may have been triggered by the inflammatory process of PLC. As far as we can ascertain, there have not been previous cases of this published in the literature. Our patient’s hypopigmented areas have now started to self-resolve and we have planned for ongoing monitoring of the agminated Spitz naevi.

Management of a case of Castleman’s disease coexisting with or occurring after transplanted Hodgkin’s lymphoma

Abstract Castleman’s disease is a benign lymphoproliferative disorder. The coexistence of Hodgkin’s lymphoma and multicentric Castle-man’s disease is a rare phenomenon. We discuss a case of a 48-year-old female patient who had been in the records of the Colentina Hematology Clinic since 2019, with the diagnosis of classic Hodgkin’s Lymphoma, nodular sclerosis type I BNLI, stage IIXB. For this, she underwent 3 courses of ABVD and 2 courses of BEACOPP, without showing complete remission on PET/CT evaluation at the end of treatment. After that, we initiated rescue therapy and performed 4 IGEV courses, followed by autologous stem cell transplantation. For maintenance treatment, we opted for Brentuximab, but it was discontinued after the first administration due to the appearance of adverse reactions. Subsequently, we decided to perform radiotherapy with 20 fractions cumulating a total dose of 36 Gy. Shortly after the radiotherapy, symptoms reappeared which were suspected to be in the context of a relapse of the disease. For confirmatory diagnosis, we performed a new PET-CT which highlighted metabolically active ganglion images. Further, were carried out lymph node biopsy for histopathological and immunohistochemical examinations were carried out. The underlying disease was diagnosed as plasmacytic subtype, HHV8 negative, multicentric Castleman’s disease. For treatment, we relied on administrations of Siltuximab treatment therapy that showed complete remission. Castleman’s disease presents a unique diagnostic challenge, but a confirmatory diagnosis can be based on a biopsy examination, advisable after each relapse.

TNFRSF13B/TACI Mutations in Patients with Chronic Rhinosinusitis with Nasal Polyps.

The pathogenesis of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) remains still inconclusive. Recent studies identified an increased expression of BAFF (a B cell-activating factor) and its receptor TACI (Transmembrane Activator and cAML Interactor) in nasal polyp samples, while TNFRSF13B/TACI mutations have been found in patients with benign lymphoproliferative disorders and primary antibody deficiencies. The aim of our study was to evaluate the possible contribution of TNFRSF13B/TACI mutations in CRSwNP pathogenesis. Forty-four (44) patients with CRSwNP (male/female: 33/11, mean age: 52.5 years, range: 16-83) were analyzed for TNFRSF13B/TACI mutations by PCR-sequencing. No pathogenic TNFRSF13B/TACI mutations were identified in our cohort study of CRSwNP patients. We detected two common missense mutations (p.P251L and p.V220A), along with other common silent mutations and intronic polymorphisms in an identical prevalence to healthy control population. TNFRSF13B/TACI mutations might not play a role in the pathogenesis of CRSwNP.

Castleman Disease: A Wide Spectrum of Thoracic Manifestations

Castleman’s disease is a benign lymphoproliferative disorder affecting both lymph nodes and extranodal loci. Castleman’s disease can occur in practically any part of the body, but it occurs mainly in the thorax (~70%) followed by the abdomen and pelvis, neck and axilla. Clinically, Castleman’s disease can be classified into a unicentric or multicentric form, depending on the number of lymph nodes involved, and histologically into a hyaline vascular variant, plasma cell, mixed cellular or plasmablastic variant. In this mini-review we briefly report and focus on all clinical thoracic manifestations of Castleman’s disease resuming for each of them the possible strategy of treatment.

Transient hypertriglyceridemia: a common finding during Epstein-Barr virus-induced infectious mononucleosis

BackgroundHypertriglyceridemia can occur in lymphoproliferative disorders. Infectious mononucleosis is a self-limiting, benign lymphoproliferative disorder. This study aimed to investigate the serum triglyceride concentrations and their change over time in patients with infectious mononucleosis.MethodsWe evaluated an adult patient with severe hypertriglyceridemia (>1000 mg/dL) during infectious mononucleosis and reviewed the records of 360 patients admitted to our hospital because of infectious mononucleosis (median age, 19 years; range, 15-87 years; 51.4% male). We compared the serum triglyceride concentrations with those of a control sample from the general population (n=75). A second triglyceride measurement, obtained during convalescence (median of 30 days after the initial determination), was available for 160 patients.ResultsThe triglyceride concentrations in the acute phase (median: 156 mg/dL) were significantly higher than those of the controls (median, 76 mg/dL; P<0.001). A total of 194 (53.9%) patients presented with hypertriglyceridemia (>150 mg/dL), which was more common in the patients older than 30 years than in the younger patients (78.6% vs. 50.6%; P<0.001). A significant correlation (P<0.005) was observed between the triglyceride levels and white blood cell counts, total cholesterol levels, and liver damage markers. The triglyceride concentrations decreased during convalescence (P<0.001) and were lower than the initial measurement in 83.7% of the cases. Conversely, the total cholesterol concentrations during the acute phase were lower than those of the controls and increased during convalescence (P<0.001).ConclusionsPatients with severe infectious mononucleosis frequently show mild, transient hypertriglyceridemia. Further studies are needed to elucidate the mechanisms underlying this finding.

Benign lymphoproliferative disorders in the immunosuppressed patient: an update.

Immunosuppressed patients may be affected by a wide range of lymphoproliferative disorders (LPDs) ranging from self-limiting disorders to malignant lymphoid proliferations. These LPDs may be associated with systemic immune disorders, develop following organ transplantation or occur in the background of other forms of iatrogenic immunosuppression. Lymphotropic viruses, including Epstein-Barr virus (EBV) and human herpesvirus-8 (HHV8), have been associated with the pathogenesis of distinct LPDs. The resulting classification of this group of disorders is very complex and inconsistent, with several new and emerging entities. Consequently, the diagnosis of an LPD, especially in an immunosuppressed patient, and its subsequent clinical management usually represent an important pitfall in daily clinical and pathology work. Therefore, the aim of this review was to use the available literature to describe the clinicopathological features of the most important benign LPDs that may be diagnosed in the head and neck region of immunosuppressed patients. Original clinical and microscopic images were used to illustrate some of these entities.

Lymphoid interstitial pneumonitis in a newly diagnosed late presenter of human immunodeficiency virus infection: a case report

BackgroundAn increase has been described throughout the years in the frequency of various uncommon diseases in people living with human immunodeficiency virus (HIV). Particularly late presenters are associated with a significant risk not only for acquired immune deficiency syndrome (AIDS)-defining conditions but also for non AIDS-defining diseases which aggravate the prognosis of patients. Lymphoid interstitial pneumonitis (LIP) is one of these conditions described more often after the onset of HIV epidemic. LIP is a benign polyclonal lymphoproliferative disorder of the lung with not well characterized clinical and radiographic findings.Case presentationWe report the diagnostic approach and clinical progress of a newly diagnosed late presenter of HIV infection with respiratory problems in our HIV unit. The findings of computed tomography indicated the diagnosis of HIV-associated LIP, although this condition is mainly described in a normal range of CD4 cell count.ConclusionThis case presentation highlights the importance of timely diagnosis and initiation of antiretroviral therapy. The increase of CD4 cell count and viral suppression may improve the symptoms of LIP.

Malignant behaviour of primary intracranial Rosai Dorfman disease: A rare presentation of a benign disease

Background and purposeThe Rosai Dorfman disease (RDD) is a rare and usually benign lymphoproliferative disorder of unknown aetiology, typically characterized by head and neck lymphadenopathies. However, it may occasionally present with primary extra-nodal involvement including the central nervous system. We firstly described the potential malignant behaviour and fatal evolution of primary intracranial RDD. Illustrative caseA 69-year-old woman sought clinical attention for recurrent episodes of headache, fever and malaise associated with bilateral proptosis and left lower limb paresis. The brain MRI revealed bilateral retro-bulbar and fronto-parieto-occipital subdural lesions. The body CT did not show extracranial lesions. A right fronto-parietal craniotomy was performed and a subtotal resection was achieved. The histopathological diagnosis was consistent with RDD. Despite the patient was commenced on high-dose corticosteroids, she developed a worsening respiratory distress syndrome and a rapid systemic disease progression with liver and kidney failure. Given the poor general status, adjuvant medical and radiation therapies were not deemed safe and feasible and the patient died of multi-organ failure a month later. ConclusionsWe documented an exceptional case of primary intracranial RDD with malignant behaviour characterized by rapid systemic disease progression and poor prognosis. Although RDD with intracranial location has usually a benign and self-limiting course with good response to adjuvant treatments, it hides a malignant potential that may lead patients to death.

TAFRO syndrome, variant of Castleman's disease: case report.

Multicentric Castleman’s disease is a rare benign lymphoproliferative disorder that involves multiple enlarged lymph nodes in different areas of the body. Recently, a unique clinic pathological variant of this disease called TAFRO syndrome has been described. A 23-year-old male with a history of one year and six months of evolution characterized by generalized lymphadenopathy with, night diaphoresis, dyspnea and weight loss. At the third month, hypertension was diagnosed and 8 months later type 2 diabetes mellitus. After his admission, microcytic anemia, thrombocytopenia, renal dysfunction, pleural effusion and ascites were documented. Based on the findings of the physical examination, a computed tomography scan was performed, where multiple lymph nodes and hepatosplenomegaly were identified. A lymph node biopsy was performed, which reported Castleman’s disease, considering then a diagnosis of TAFRO syndrome due to its association with thrombocytopenia, microcytic anemia, anasarca, fever, renal dysfunction, adenomegaly and hepatosplenomegaly. There are still doubts about whether it corresponds to a different disease or a subtype of the Castleman disease. It is more frequent in women, occurs in the middle-aged and elderly and given its heterogeneous presentation, it usually represents a diagnostic challenge. Although its management is not standardized, therapeutic options include immunosuppressant such as steroids, cyclosporine, rituximab and anti-IL6.

Clinical Spectrum of Ras-Associated Autoimmune Leukoproliferative Disorder (RALD).

Ras-associated autoimmune leukoproliferative disorder (RALD) is a clinical entity initially identified in patients evaluated for an autoimmune lymphoproliferative syndrome (ALPS)-like phenotype. It remains a matter of debate whether RALD is a chronic and benign lymphoproliferative disorder or a pre-malignant condition. We report the case of a 7-year-old girl diagnosed with RALD due to somatic KRAS mutation who progressed to a juvenile myelomonocytic leukemia phenotype and finally evolved into acute myeloid leukemia. The case report prompted a literature review by a search for all RALD cases published in PubMed and Embase. We identified 27 patients with RALD. The male-to-female ratio was 1:1 and median age at disease onset was 2years (range 3months-36years). Sixteen patients (59%) harbored somatic mutations in KRAS and 11 patients (41%) somatic mutations in NRAS. The most common features were splenomegaly (26/27 patients), autoimmune cytopenia (15/16 patients), monocytosis (18/24 patients), pericarditis (6 patients), and skin involvement (4 patients). Two patients went on to develop a hematopoietic malignancy. In summary, the current case documents an additional warning about the long-term risk of malignancy in RALD.

EP33 Sjögren’s and lymphoproliferative disorders

Case report - IntroductionSjögren’s syndrome (SS) is a chronic autoimmune inflammatory condition characterised by lymphocytic infiltration of predominantly exocrine glands as well as other organs involving more commonly in skin, lungs, and neurological system. It is associated with increased risk of both benign and malignant lymphoproliferative disorders.Case report - Case descriptionA 29-year-old woman with 5-year history of Primary SS (ANA, Ro/La positive) was reviewed in a routine follow up. She has mild dry eyes, intermittent vasculitic rash around the ankles, occasional pleuritic chest pain but no cough or dyspnoea initially. She used artificial tears but took no regular mediations. Oxygen saturation at rest was 99% and BP 127/70. Heart sounds were normal, and chest was clear.Blood results showed alanine transaminase (ALT) had risen from 50 (normal 5-45) to 145 over 6 months. Viral screen (hepatitis, HIV, CMV, EBV) and liver ANA panel were negative. C4 was low 0.09 (n 0.15-0.55), C3 normal and DsDNA antibodies 1 (n 0-15.1). Ig G was high, fluctuating between 27 - 33 (n 7.67-15.9). ESR had been mildly elevated at 26 (n 0-19). CRP had always been within normal limits. Ultrasound abdomen showed enlarged spleen (15 cm). CT chest abdomen and pelvis showed multifocal groundless opacification affecting mid to upper zones, bilateral cyst formation, solid nodularity, and mild septal thickening with no pleural effusion. There were multiple prominent bilateral axillary and mediastinal lymph nodes measuring upto15 mm. The spleen measured 15.4 cm. Six months later, she developed mild dyspnoea on exertion. Examination revealed fine basal crackles. Oxygen saturation remained 99% at rest. TLco was mildly reduced and Kco in lower limit of normal. Echocardiogram was normal. Ultrasound guided core biopsy of axillary lymph node showed benign reactive features with follicular hyperplasia and plasmacytosis.The diagnosis of lymphocytic interstitial pneumonitis was made. She was started on a reducing dose of Prednisolone 30 mg and Mycophenolate stepwise increment to 1 gm BD. Chest pain resolved shortly after starting glucocorticoid therapy and exercise tolerance improved.Liver enzyme normalised. Case report - DiscussionThe diagnosis of lymphocytic interstitial pneumonia (LIP) in this patient was incidental from the retrospective investigation of the persistently abnormal unexplained liver function test. Splenomegaly is a recognised manifestation of active systemic SS. The main differential diagnoses are lymphoma and other types of interstitial lung diseases (ILD). Her presentation was insidious and there were no constitutional symptoms. Her ANA, Ro, La and Rheumatoid factor were strongly positive. She has hypergammaglobulinemia which is commonly associated with LIP. Histological findings were typical reactive changes with characteristic polymorphic plasmacytosis. In the absence of malignant lymphoid cells and radiological features of ground glass changes and bilateral cysts formation suggested that the most likely diagnosis was LIP secondary to primary SS.The management strategies vary for different types of ILD based on their etiological conditions. There are no specific guidelines for the treatment of LIP. For initial acute stage, glucocorticoid therapy is usually prescribed for symptomatic improvement. For later stages and cysts, immunosuppressants are used and depending on the severity, azathioprine, cyclosporin, rituximab and cyclophosphamide have been used.Median survival for LIP is 11.2 years. Increased risk of secondary infection because of immunosuppressive therapy is common and there are recommendations for atypical chest infection prophylaxis.Case report - Key learning pointsInterstitial lung disease is commonly associated with SS and predicts a higher mortality rate.Glucocorticoid is the main stay of treatment for ILD acute stage with active inflammatory changes.For refractory cases and chronic cystic stages on radiological findings, further immunosuppression therapy may be required.Standardised treatment guidelines are not available.Secondary chest infections may be seen in those with cystic disease and on immunosuppression.Close monitoring and MDT approach is required in the management of LIP.LIP may transform into lymphoma or co-present with lymphoma associated with SS.

MULTIFOCAL PULMONARY NODULAR HYPERPLASIA IN A PATIENT WITH SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)

SESSION TITLE: Medical Student/Resident Pulmonary Manifestations of Systemic Disease Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Pulmonary nodular lymphoid hyperplasia (PNLH) is a rare lympho-proliferative disorder characterized by benign polyclonal lymphoid proliferation. We describe a case of a 44-year-old woman with biopsy proven multifocal pulmonary nodular lymphoid hyperplasia in the setting of SLE. CASE PRESENTATION: 44-year-old woman presented to the emergency room with complaints of intermittent pleuritic chest pain and exertional dyspnea for 3 months. Review of systems was positive for joint pains and morning stiffness. Physical examination was remarkable for tenderness and swelling at proximal interphalangeal joints. Cardiac work up including electrocardiogram, troponin levels and echocardiogram was unremarkable. CT scan of chest with contrast showed numerous bilateral cavitary ground glass opacities measuring about 1-2 cm in size. Transbronchial biopsy was non-diagnostic. A subsequent video-assisted thoracoscopic surgical biopsy revealed nodular lymphoid hyperplasia. Specimen was negative for malignancy, granulomatous disease or vasculitis. Lymphoma was also ruled out by flow cytometry. AFB, fungal and bacterial stains and cultures were negative. Hepatitis panel and HIV testing was negative. Rheumatologic work up showed negative rheumatoid factor and positive ANA, anti-SSA, anti-dsDNA Ab, anti smith and anti-U1-RNP antibodies. Inflammatory markers, ESR and CRP, were elevated. She was evaluated by rheumatology and further history revealed presence of alopecia and nasal sores in addition to serositis (pleuritis) and arthritis. Her clinical picture and serologies met the diagnostic criteria for SLE. DISCUSSION: Pulmonary lymphoid nodular hyperplasia is a rare benign lymphoproliferative disease. It is relatively more common in women and often an incidental finding on imaging. Most patients are asymptomatic, however symptoms such as cough, chest pain or dyspnea can be present. Diagnosis is made by surgical biopsy. It is essential to rule out malignancy, particularly mucosal associated lymphoid tissue lymphoma and infectious etiologies such as bacterial or fungal pulmonary infections. So far PNLH has been described in patients with Sjogren’s disease, without conclusive association. Most common pulmonary manifestation in SLE is pleurisy. Interstitial lung disease (ILD) is less common in SLE and is seen in patients who have anti–U1-RNP antibodies. Imaging findings are nonspecific; however, ground-glass opacities or consolidations may be present. PNLH has not been described in association to or as a manifestation of SLE in medical literature. There is paucity of data for correlation and larger studies are required to study this potential association. CONCLUSIONS: Pulmonary nodular lymphoid hyperplasia is a rare benign lymphoproliferative disorder. After malignancy and infectious etiology is ruled out autoimmune disease should be considered in patients with PNLH. Further work is warranted to establish this relation. Reference #1: Abbondanzo SL, Rush W, Bijwaard KE, Koss MN. Nodular lymphoid hyperplasia of the lung: a clinicopathologic study of 14 cases. Am J Surg Pathol. 2000;24(4):587–597. Reference #2: Song MK, Seol YM, Park YE, et al. Pulmonary nodular lymphoid hyperplasia associated with Sjögren's syndrome. Korean J Intern Med. 2007;22(3):192–196. doi:10.3904/kjim.2007.22.3.192. Reference #3: Quadrelli SA, Alvarez C, Arce SC, et al: Pulmonary involvement of systemic lupus erythematosus: analysis of 90 necropsies. Lupus 2009; 18: pp. 1053-1060 DISCLOSURES: No relevant relationships by William Han, source=Web Response No relevant relationships by Immad Munawar, source=Web Response No relevant relationships by Theresa Nicol, source=Web Response

Comparison between Conventional Gastric Adenocarcinoma and EBV Associated Gastric Carcinoma

Epstein Barr Virus (EBV or Human herpesvirus 4) belongs to the genus Lymphocryptoviridae, the gamma 1 subtype of the Subfamily Gamma herpes viridae and is one of the most common viruses in humans. It is present in all populations, infecting more than 95% of all individuals within the first four decades of life. In developing countries, infections occur very early in life with no specific characteristics other than the general symptoms of acute viremia. In developed countries however, the infection is usually delayed until adolescence or early childhood years where it causes infectious mononucleosis, a benign self-limiting lymphoproliferative disorder. Though the infection with EBV is benign in the acute stages and latent in the chronic phase in the vast majority of people, the virus has been demonstrated to be involved in the development of many malignancies with the list of such malignancies progressively increasing. The first association was with the endemic Burkitt’s lymphoma. Subsequently, other lymphomas (subtypes of Hodgkin’s and non-hodgkin’s lymphomas) are also known to be associated with EBV infection. Epithelial malignancies such as lymphoepitheliomas of nasopharynx and stomach are included in the list of EBV associated tumors. Tumors arise as a result of genetic and epigenetic alterations produced by the virus, which transforms the normal cell into an immortalized proliferating cell. Since Burke et al first detected EBV in undifferentiated lymphoepithelioma like gastric cancer in 1990, many researches are undertaken to prove the same. EBV expresses latent membrane protein which can be detected immune histochemically. Our study is aimed at detecting the EBV expression in gastric carcinoma cells.

Mesenteric Castleman’s Disease: A Rare Cause of Mesenteric Masses: A Case Report and Literature Review

Castleman’s disease, also known as angiofollicular lymph node hyperplasia or giant lymph node hyperplasia, is a rare benign B-cell lymphoproliferative disorder of unknown etiology. We report a case of a 23-year old woman with mesenteric Castleman’s disease of plasma cell variant presented as a palpable mass in the left iliac fossa.

Pulmonary Nodular Lymphoid Hyperplasia in the Eye of Radial Endobronchial Ultrasound

Pulmonary nodular lymphoid hyperplasia (PNLH) is a rare, benign lymphoproliferative disorder often manifesting as a solitary pulmonary nodule (SPN). Once a malignant cause of SPN is ruled out, it presents a diagnostic dilemma to clinicians due to histopathological overlap with diseases like mucosa-associated lymphoid tissue (MALT) lymphoma and IgG4-related sclerosing disease. We report an adult patient who presented with incidental finding of a SPN, and was subsequently diagnosed with PNLH via a combined technique of radial-endobronchial ultrasound (R-EBUS), virtual bronchoscopic navigation (VBN), and cryobiopsy. We discuss the sonographic appearance and histopathological morphology of PNLH, and the merits of bronchoscopic techniques in averting surgical intervention of SPN. This is the first reported sonographic appearance of PNLH under radial-endobronchial ultrasound (R-EBUS).

Genomic Characterization of a Pediatric Cohort with Non-Malignant Lymphoproliferative Disorders

Introduction: Pediatric non-malignant lymphoproliferative disorders (LPDs) are a clinically and genetically heterogeneous. While transient lymphadenopathy is extremely common and rarely dangerous, long-standing immune dysregulation and lymphoproliferation in children may be life-threatening. Data to guide evaluation and treatment of children with benign LPD are lacking. The primary objective of this study was to define the genomic spectrum and clinical characteristics of a cohort of children with nonmalignant LPD. Identification of the underlying pathogenic mechanisms may facilitate timely interventions and potentially guide optimal therapeutic strategies. Method s: Patients at Texas Children's Hospital and collaborating referral centers who met criteria for non-malignant LPD were offered participation in this study, approved by the Baylor College of Medicine Institutional Review Board. LPD was defined as persistent lymphadenopathy, lymph organ involvement, or lymphocytic infiltration for more than 3 months, with or without chronic or significant EBV infection. Chronic or significant EBV infection was defined as recurrent or persistent EBV viremia more than 3 months, invasive EBV disease, or EBV PCR copies &amp;gt;100,000. All subjects and/or family members provided written informed consent to have their clinical and genetic information published. Genetic testing was performed clinically or through research-based whole-exome sequencing (WES). Results : Fifty-one subjects from 47 different families with non-malignant LPD were identified. Median age at disease presentation was 3.3 years (range 3.9 weeks - 21 years) with nearly equal proportions of males (n = 26) and females (n = 25). Almost half of subjects were Hispanic (49%), and 29% were non-Hispanic white. Fifteen subjects (29%) met HLH-2004 diagnostic criteria for HLH. Twenty-one patients had EBV-associated lymphoproliferative disorders (EBV-LPD) and 6 of the 51 ultimately developed malignancy. Clinical genetic testing was performed in 29 patients, and research-based WES was performed in 44 patients. Potential disease-causing genetic defects were identified in 62% of families. Of these pathogenic variants, targeted therapies may be effective for treatment in at least 10 of the conditions (17 subjects, 33%). Furthermore, genetic results supported potential for curative HSCT in 35% of the patients. Mechanistically, all of the LPD-associated genes could be placed into 1 of 3 categories: 1) defective control of lymphocyte activity; 2) impaired lymphocyte activation, cytoskeletal organization, and apoptosis; and 3) dysregulated inflammation. Ten-year survival for the entire cohort was 72.4% with a median 5.6 years of follow-up (range 0.10 - 26.6). Patients without evidence of a genetic explanation had a lower ten-year survival compared to those patients for whom a genetic explanation was identified (48% versus 82%, respectively, p=0.03). When both EBV-LPD and genetic explanation were considered, the ten-year survival estimate for those with EBV-associated disease and no genetic explanation was significantly worse than those with EBV-associated disease and a genetic explanation (17% vs. 90%; p =0.002). Patients without EBV-associated disease were at lower risk of death than those with EBV-LPD. Evaluating outcomes associated with maximum treatment received, ten-year survival was lowest (25% survival) among those who underwent HSCT. Conclusion s: Pediatric non-malignant LPD represents a group of conditions with high risk of death. WES identified actionable mutations in the majority of LPD cases in this cohort. Early identification of these mutations can guide therapy by confirming diagnosis, revealing molecular targets and/or supporting definitive therapy with stem cell transplant. Disclosures Forbes: Takeda: Consultancy. Jolles:CSL Behring: Consultancy, Honoraria, Research Funding, Speakers Bureau; LFB: Consultancy, Honoraria, Research Funding, Speakers Bureau; UCB Pharma: Consultancy, Other: Drug Safety Committee; Shire/Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; Pharming: Consultancy, Honoraria, Research Funding, Speakers Bureau; Octapharma: Consultancy, Honoraria, Research Funding, Speakers Bureau. Heslop:Marker Therapeutics: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Allovir: Equity Ownership; Gilead Biosciences: Membership on an entity's Board of Directors or advisory committees; Kiadis: Membership on an entity's Board of Directors or advisory committees; Tessa Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Cell Medica: Research Funding. Rouce:Novartis: Consultancy, Honoraria; Tessa Therapeutics: Research Funding; Kite, a Gilead Company: Consultancy, Honoraria.

Castleman Disease in the Buccal Space Mimicking Lymphoma: A Case Report

Castleman disease is a benign lymphoproliferative disorder of unknown etiology, more commonly appearing in the mediastinum. Craniofacial involvement is rare. Surgical excision is the only intervention needed for the unicentric type, while systemic treatment would be necessary for the multicentric type. Here, we report a rare case of unicentric castleman disease of the buccal space of a 23-year-old woman. Additionally, we review the radiological and histopathological features of this lesion.