Florid Follicular Hyperplasia Research Articles

The Sentient Propagation-Reactive B Cell-Rich Lymphoid Proliferation

Reactive B cell-rich lymphoid proliferation is a heterogeneous group of non-neoplastic lymphoid cell proliferation recapitulating diverse B cell lymphomas. The lesion is commonly categorized as nodal and extra-nodal follicular proliferations, nodal and extra-nodal nodular proliferations or nodal and extra-nodal immunoblastic proliferations. Florid follicular hyperplasia is comprised of quantifiably enhanced, disseminated primary and secondary lymphoid follicles with irregular outlines. Hyperplastic Germinal Centres (GCs) are comprised of admixed centroblasts and centrocytes, reactive T cells, Follicular Dendritic Cells (FDCs) and tingible body macrophages. Lymph node architecture depicts lymphoid follicles comprised of cells expressing B cell antigens wherein primary follicles are pre-eminently constituted of small lymphocytes BCL2+, BCL6- and CD10- immune reactivity. Progressive Transformation of Germinal Centre (PTGC) is constituted of singular or few enlarged lymphoid follicles of 4x to 5x magnitude wherein mantle zone cells display extensive invagination into adjacent germinal centres. Hyaline Vascular Castleman’s Disease (HVCD) delineates innumerable lymphoid follicles confined to the lymph node cortex and medulla or diverse extramedullary sites.

Immune Deficiency/Dysregulation Associated Lymphoid Proliferations, EBV+ In Persons Living With HIV.

The 5th edition of the World Health Organization Classification of Hematolymphoid Tumors recently defined immune deficiency/dysregulation (IDD)-associated-lymphoid-proliferations in HIV settings, where information is scarce, often gone under or misdiagnosed. To describe the clinical picture, histopathology, and outcomes of IDD-associated-lymphoidproliferations Epstein-Barr virus+ (EBV) in people living with HIV without organ transplantation, antiretroviral therapy (ART) treated. HIV+ patients diagnosed with IDD-associated-lymphoid-proliferations seen at an academic medical center in Mexico from 2016 to 2019 were included. Immunohistochemical studies, in situ hybridization, and polymerase chain reaction analysis for EBV and LMP1 gene deletions were performed and correlated with clinical data. We included 27 patients, all men who have sex with men, median age 36 years (interquartile range [IQR] 22-54). The median baseline CD4+ T cells were 113/mL (IQR 89-243), the CD4+/CD8+ ratio was 0.15 (IQR: 0.09-0.22), and the HIV viral load was 184,280 copies/mL (IQR: 76,000-515,707). Twenty patients (74.07%) had IDD-associated-lymphoid-proliferations hyperplasia plasma cell type EBV+, 3 (11.1%) had hyperplasia mononucleosis-like type (IM-type), 1 patient (3.70%) had florid follicular hyperplasia, 3 (11.1%) IDD-associated-lymphoid-proliferations polymorphic type, and there were 22 cases (81.4%) of synchronic Kaposi Sarcoma. Two patients were diagnosed with Hodgkin lymphoma following a second positron emission tomography-computed tomography scan-guided biopsy. The median follow-up was 228 weeks (IQR 50-269); 6 patients died (22.2%) of causes unrelated to IDD-associated-lymphoid-proliferations related. IDD-associated-lymphoid-proliferations EBV+ occured in severely immunosuppressed HIV+ patients, a high percentage of whom had concomitant Kaposi sarcoma. The prognosis was good in patients treated only with ART.

Florid follicular lymphoid hyperplasia of the palate: review of the literature and report of an illustrative case.

The aim of this report was to review oral follicular lymphoid hyperplasia, with emphasis on palatal lesions. A comprehensive search was performed on PubMed for case reports and case series of palatal follicular lymphoid hyperplasia published in the English language literature. Relevant data from collated articles was sought, including patient demographics, clinical manifestations, imaging modalities and findings, comorbidities, etiopathogenesis, lesional management, and lesional outcome. A new palatal case has also been provided to illustrate several features of this lesion. In total, 32 cases were assembled to establish clinicopathologic correlations, representing the largest aggregation of published cases. Most of the affected patients were at least 60 years old and with a decisive female predilection. The majority of lesions were ≤ 3 cm, appearing as normal color, purple-red or red, and varied from soft to firm. Notably, 32% of palatal follicular lymphoid hyperplasias were associated with denture wear, and lesional recurrence was recorded in 16% of cases. To date, none of the reported cases of palatal follicular lymphoid hyperplasia has undergone malignant transformation. Palatal follicular lymphoid hyperplasias often arise as a reactive process. Critical histopathologic and histochemical assessments are necessary to establish benignity. Postoperatively, clinicians should follow patients for at least 5 years for recurrence and remain vigilant for neoplastic change as several published accounts of non-oral follicular lymphoid hyperplasias have undergone malignant transformation, usually to lymphoma.

POEMS-associated Multicentric Castleman Disease: A diagnostic and Therapeutic Conundrum

Abstract Introduction/Objective A rare multisystemic, paraneoplastic hematologic disorder, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes) is associated with an overproduction of pro-inflammatory cytokines caused by a plasma cell proliferative disorder. Castleman disease is a rare clinical entity described as a polyclonal lymphoid proliferation, that leads to generalized lymphadenopathy. It is rarely presented in association with POEMS Syndrome. Methods/Case Report A 55-year-old hispanic male, when being evaluated for liver mass, revealed bile duct thickening and a pancreatic head mass. Endoscopic fine needle aspiration biopsies were negative; however, the cross sectional imaging identified enlarged left axillary lymph nodes. His excisional lymph node biopsy showed human herpese virus-8 (HHV-8) negative multicentric Castleman disease (MCD). Several features of POEMS syndrome were noted. The axillary lymph node biopsy demonstrated florid follicular hyperplasia, scattered regressed germinal centers and concentric rings of mantle zone lymphocytes. CD138, kappa-ISH, and lambda-ISH highlight scattered polytypic plasma cells. Our case fulfills the mandatory criteria of POEMS syndrome with the presence of neuropathy and a constellation of other major and minor criterion including, axillary Castleman, splenomegaly, hepatomegaly, skin changes, ascites and bilateral renal cortical lesions. Furthermore the patient also has a history of cerebrovascular accident and chronic cough favoring POEMS syndrome. Results (if a Case Study enter NA) NA Conclusion The complexity and multi-organ involvement, leads to frequent misdiagnosis of POEMS disease. In addition significant overlap of symptoms of POEMS syndrome makes it difficult to differentiate from other plasma cell disorders associated with MCD. Our study includes a brief review of the literature delineating the characteristics and overlap between POEMS syndrome and other diseases.

Kimura's disease: A clinicopathological study of 23 cases.

Kimura's disease (KD) is an uncommon lymphoproliferative fibroinflammatory disorder. Patients present with head and neck subcutaneous nodules with or without lymphadenopathy. Peripheral blood eosinophilia and elevated serum immunoglobulin E (IgE) levels are typical. This study was designed to delineate the clinicopathological features, pattern of care, and disease course of 23 Taiwanese patients with KD. We retrospectively analyzed the clinical data of 23 consecutive cases (16 male and 7 female; age at diagnosis: 12-77 years) of KD diagnosed at our institution from 2015 to 2020. The median time from presentation to diagnosis was 1 month. Twenty-one patients presented with unilateral or bilateral head and neck masses. The remaining two presented with right flank and right arm lesions, respectively. Peripheral blood eosinophilia was observed in nine, and elevated IgE levels were observed in four. All were diagnosed using either excisional or core-needle biopsy. Seven patients underwent fine needle aspiration without a diagnostic yield. Salivary gland and lymph node involvement was observed in three and seven patients, respectively. Most lesions showed tissue eosinophilia (100%) and florid follicular hyperplasia (78.26%). Three cases had histological KD-IgG4-RD overlap and three had comorbid IgG4-RD were recognized. Thirteen patients underwent surgical resection, one received adjuvant therapy, and two received prednisolone monotherapy. KD should be considered in patients with subcutaneous masses, eosinophilia, and elevated IgE levels. Biopsy remains the gold standard of diagnosis. Increased recruitment of IgG4+ plasma cells is a common feature. Consideration of IgG4-RD in all KD patients may be prudent.

GRANULOMATOUS REACTION TO A MEDIASTINAL SEMINOMA

GRANULOMATOUS REACTION TO A MEDIASTINAL SEMINOMA

Mutations in JAK/STAT and NOTCH1 Genes Are Enriched in Post-Transplant Lymphoproliferative Disorders.

Post-transplant lymphoproliferative disorders (PTLD) are diseases occurring in immunocompromised patients after hematopoietic stem cell transplantation (HCT) or solid organ transplantation (SOT). Although PTLD occurs rarely, it may be associated with poor outcomes. In most cases, PTLD is driven by Epstein-Barr virus (EBV) infection. Few studies have investigated the mutational landscape and gene expression profile of PTLD. In our study, we performed targeted deep sequencing and RNA-sequencing (RNA-Seq) on 16 cases of florid follicular hyperplasia (FFH) type PTLD and 15 cases of other PTLD types that include: ten monomorphic (M-PTLD), three polymorphic (P-PTLD), and two classic Hodgkin lymphoma type PTLDs (CHL-PTLD). Our study identified recurrent mutations in JAK3 in five of 15 PTLD cases and one of 16 FFH-PTLD cases, as well as 16 other genes that were mutated in M-PTLD, P-PTLD, CHL-PTLD and FFH-PTLD. Digital image analysis demonstrated significant differences in single cell area, major axis, and diameter when comparing cases of M-PTLD and P-PTLD to FFH-PTLD. No morphometric relationship was identified with regards to a specific genetic mutation. Our findings suggest that immune regulatory pathways play an essential role in PTLD, with the JAK/STAT pathway affected in many PTLDs.

Axillary lymph nodes on PET in Hodgkin lymphoma after COVID-19 vaccination.

A 21-year-old woman presented with nodular sclerosis Hodgkin lymphoma stage IIIA, IPS 2 with a baseline 18F-fluorodeoxyglucose positron emission tomography and computed tomography (FDG PET/CT) showing initial involved lymph nodes in both sides of the neck, left axilla, mediastinum, hili, para-aortic, left iliac, and involvement of the spleen. After one course of BrAVD (brentuximab-vedotin, adriamycine, vinblastine, dacarbazine), the interim FDG PET/CT scan was negative, classified as a complete metabolic response. A third FDG PET/CT scan was performed after completion of her chemotherapy consisting of six courses of BrAVD. This scan showed a reappearance of FDG avid lymph nodes, with a Deauville score of 5, in the original sites in the left axilla and neck. The most FDG avid lymph node was excised and revealed florid follicular hyperplasia instead of recurrence of Hodgkin lymphoma. In hindsight, she received a COVID-19 vaccination in her left arm several weeks prior to the last FDG PET/CT scan. In the meantime, various articles were published that relate the occurrence of FDG avid ipsilateral axillary and neck lymph nodes to COVID-19 vaccination of several manufacturers. We, therefore, concluded all FDG avid lymph nodes to be triggered by the vaccination. FDG PET/CT scan is valuable in steering therapy in Hodgkin lymphoma patients. However, enhanced FDG uptake only indicates that enhanced glucose metabolism and false positive results are possible, necessitating good clinical correlation. Documentation of the vaccination status including date(s), side, and manufacturer is of importance. In cancer patients, the side and timing of the vaccination should be discussed with the patient to prevent concern of recurrence and avoid unnecessary diagnostics and as in our case.

Primary mediastinal seminoma with florid follicular lymphoid hyperplasia: a case report and review of the literature

BackgroundFirst described in 1955 Primary mediastinal seminomas are rare. Only 1–4% of mediastinal tumours are germ cell tumors; majority of which are teratomas. They typically present in men aged between 20 and 40 years. Very few cases are reported in the literature. Florid follicular lymphoid hyperplasia can obscure the malignant cells and is a rarer finding still. We present a rare case of a 48 year old man with a primary mediastinal seminoma with florid follicular lymphoid hyperplasia; found following excision of a clinically presumed thymoma.Case presentationA 48 year old man was referred for excision of a thymic mass. The presumed diagnosis was a thymoma; following preoperative investigations. The mass was incidentally found on a radiological imaging. However, the patient did report mid-sternal discomfort on lying flat and breathlessness. The patient underwent a thymectomy via a partial median sternotomy with good recovery. Histological assessment was that the mass was in fact a primary mediastinal seminoma with florid follicular lymphoid hyperplasia. A primary testicular malignancy was excluded and the patient required no further oncological treatment.ConclusionsOnly 11 cases have previously been reported of primary mediastinal seminoma with florid follicular lymphoid hyperplasia. Although rare, a primary mediastinal seminoma should be considered as a differential diagnosis for presentations with a thymic mass. Tumour markers can be helpful, however are only positive in third of cases. Ultrasound imaging of the gonads is essential to exclude a primary gonadal lesion. Pure seminomas are radiotherapy and chemotherapy sensitive however the mainstay treatment of primary mediastinal seminomas remains surgical excision. Radiotherapy is reserved postoperatively for incomplete surgical margins.

Graves’ Disease, a Late Complication of Chronic Graft vs Host Disease

Introduction: Graft-versus-host disease (GVHD), a complication of bone marrow transplant (BMT), occurs when the donor white blood cells attack the recipient’s host cells and can occur acutely or chronically several years post-transplant. It is very rare for chronic GVHD to cause hyperthyroidism due to Grave’s disease and thyrotoxicosis years after BMT. Hyperthyroidism after BMT is thought to occur by GVHD or by donor’s auto-reactive lymphocytes transferred to recipient, with majority of cases occurring with donors that have an underlying autoimmune thyroid condition. Case Report: We report a 62 year old male who presented with palpitations, tremors, sweating, weight loss, and anxiety for 3 weeks. Past medical history was significant for allogenic BMT due to AML 14 years ago, which was further complicated by GVHD of eye, liver and skin. Physical exam was negative for thyromegaly or thyroid tenderness. Initial work up showed TSH 0.03 (normal 0.4-5.0 MUI/l), free T4 3.32 (normal 0.6-1.2 ng/dl), TSI 194 % (normal <140 %). Ultrasound revealed a diffuse hypervascular thyroid gland with numerous avascular cystic areas in both lobes and increased homogenous, symmetrical uptake consistent with Graves’ disease was noted on radioactive iodine uptake scan. With clinical suspicion of GVHD leading to Graves’ disease with subsequent thyrotoxicosis, he was started on methimazole. However, due to persistent increase in transaminases, concern for agranulocytosis with methimazole, and risk of developing worsening GVHD of the skin or eye with radioactive iodine therapy, he underwent total thyroidectomy. His pathology showed bilateral lymphoepithelial lesions with florid follicular hyperplasia, marked monocytoid hyperplasia, and Germinal B cells positive for CD10 and negative for BCL2. Lymphoepithelial lesions can be seen in chronic lymphocytic thyroiditis due to persistent inflammation. Conclusion: This case raises the question on the etiology of thyroid nodules and Graves’ disease occurring after BMT. We believe that his pathology findings may be due to chronic GVHD. Hyperthyroidism after BMT is extremely rare, with only a few case reports documenting this phenomenon. We believe that our patient developed hyperthyroidism 14 years after BMT most likely as a sequela of chronic GVHD with underlying immune dysregulation leading to formation of TSI and thyroiditis due to cellular invasion. This suggest a multifactorial etiology of hyperthyroidism in patients with GVHD. However, more prospective studies are required to the explain etiology of hyperthyroidism in GVHD. Moreover, such patients should be closely monitored for development of thyroid dysfunction or thyroid nodules.

2007 Post Transplant Lymphoproliferative Disorder: A Rare Cause of Gastrointestinal Blood Loss Anemia

INTRODUCTION: Post transplant lymphoproliferative disorder (PTLD) is a rare complication after solid organ or stem cell transplant. Gastrointestinal tract is a common site of PTLD proliferation but PTLD related GI bleeding is rare. WE here by present a young Caucasian male on chronic immunosuppression for disease donor kidney transplant who presented with severe iron deficiency anemia related to GI blood loss from PTLD. CASE DESCRIPTION/METHODS: A 33-year-old Caucasian male with H/O Alport syndrome with ESRD S/P kidney transplant in 2012 on chronic immunosuppression with azathioprine and tacrolimus presented with 3 months of abdominal pain and intermittent melena. Hb was 5.4 g/dl, iron 7 mg/dl, ferritin 5 ng/ml. CT abdomen with dilated ileal loop with wall thickening and lobular contour. After resuscitation, patient underwent EGD and colonoscopy. EGD was unremarkable and colonoscopy revealed normal colon but nodular pattern in the terminal ileum (Figure 1). Multiple biopsies were taken. Histopathology and immunohistochemical staining were noted as florid follicular hyperplasia and rare EBV-positive cells, compatible with non-destructive PTLD (Figure 2) and positive CD 20 and high KI-67 proliferation index (Figure 3). Patients was discharged with reduction of his immunosuppressant therapy along with weekly rituximab. DISCUSSION: Gastrointestinal tract is the most common extranodal location of PTLD. EBV is a risk factor for PTLD and is associated with more than 80% of cases. Uncontrolled proliferation of EBV transformed B cells in the setting of compromised T cell mediated immunity due to immune suppression is involved in the pathogenesis if PTLD. Gastrointestinal manifestations may include obstruction, perforation and, very rarely, bleeding. Endoscopic manifestation include ulcers or nodular lesions with or without central ulceration and histologically lymphoid hyperplasia to lymphoma with nearly 80% positive EBV staining. Management is reduction of immune suppression; R-CHOP is an alternative in high risk patients. Early diagnosis and prompt treatment is cornerstone of PTLD gastrointestinal involvement.

Clinical Characteristics and Outcomes of an Analysis of a Single Institution Experience of the 2017 World Health Organization (WHO) Classification of Post-Transplant Lymphoproliferative Disorders (PTLD)

Background: PTLD is the most common malignancy, other than non-melanoma skin cancer, complicating solid organ transplantation (SOT) and has been one of the most commonly observed fatal consequences in SOT. The clinical presentations, management strategies, histologies, causes of death and outcomes are diverse (Dierickx D, Habermann TM. N Engl J Med 2018;378:549-62). The 2017 WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues has redefined the categories as non-destructive PTLDs (plasmacytic hyperplasia, infectious mononucleosis, and florid follicular hyperplasia), polymorphic PTLD, monomorphic PTLD: B-cell neoplasms (diffuse large B-cell lymphoma, Burkitt lymphoma, high-grade B-cell lymphoma, plasmablastic lymphoma, plasma cell myeloma, plasmacytoma, and other) and T-cell neoplasms (peripheral T-cell lymphoma NOS, hepatosplenic T-cell lymphoma, other), and classic Hodgkin lymphoma (CHL) PTLD. We report the outcomes and long-term follow-up of patients from a single institution based on these categories whose pathology was retrospectively reviewed and reclassified based on the WHO 2017 classification.Methods: Patients with SOT who were diagnosed with PTLD at Mayo Clinic (Rochester, MN) were identified through the Mayo Clinic Lymphoma Data base and the University of Iowa/Mayo Clinic SPORE Molecular Epidemiology Resource (MER). The histology was re-reviewed in 80% of the cases (RLK) and classified according to the WHO Classification of Tumours of Haematopoietic an Lymphoid Tissues 2017. Cases were considered “PTLD, unclassified” if the histology could not be confidently classified based on pathology material available for review. Indolent small B-cell lymphomas were not included among the PTLDs except for EBV-positive marginal zone lymphoma. Cox proportional hazards models were used to assess the association of clinical factors in overall survival (OS).Results: 233 patients diagnosed with PTLD between 1987 and 2017 were identified. The median age at the time of diagnosis of PTLD was 54 years (range 16 to 84) with 85 patients (36%) over the age of 60. 156 (67%) were male. The transplanted organs were kidney (41%), kidney/pancreas (5%), liver (29%), heart (9%), lung (7%), and other (8%). PTLD occurred late (more than one year after transplantation) in 66%. There were 69 stage I, 19 stage II, 8 stage III, and 128 stage IV patients. 84% presented with extranodal disease. 21% had involvement of the engrafted organ. 64% of the patients developed a PTLD that was EBV positive by in situ hybridization. Initial approaches to management included reduction of immunosuppression (N=55), chemotherapy/immunochemotherapy (N=71), reduction in immunosuppression with rituximab (N=58), single agent rituximab (N=14), and radiation therapy (N=5). At a median follow-up of 87 months (range 9-289), 139 (60%) patients had died. All six CHL-PTLD patients are alive, two of whom had an event. The median overall survival (OS) was 85 months (95% CI: 39-144) in 177 monomorphic B-cell lymphoma PTLD, 95.5 months (95% CI: 40-not reached) in 24 polymorphic PTLD, and 60 months in 8 non-destructive PTLD cases. In contrast, the median overall survival was 12 months (95% CI: 4-200) in 8 monomorphic T cell and 3 months (95% CI: 1-unreached) in 9 unclassified PTLD cases.Conclusion: PTLD is a heterogeneous group of immunodeficiency-associated lymphoproliferative disorders. The overall survival in non-destructive, polymorphic, and monomorphic PTLD were similar. Monomorphic T/NK cell types had inferior outcomes. [Display omitted] DisclosuresMaurer:Morphosys: Research Funding; Nanostring: Research Funding; Celgene: Research Funding. Ansell:Celldex: Research Funding; Merck & Co: Research Funding; Takeda: Research Funding; LAM Therapeutics: Research Funding; Seattle Genetics: Research Funding; Trillium: Research Funding; Bristol-Myers Squibb: Research Funding; Affimed: Research Funding; Regeneron: Research Funding; Pfizer: Research Funding. Cerhan:Celgene: Research Funding; Nanostring: Research Funding; Jannsen: Other: Scientific Advisory Board.

Reexamining post-transplant lymphoproliferative disorders: Newly recognized and enigmatic types.

Post-transplant lymphoproliferative disorders (PTLD) are a known risk for both solid organ transplant and stem cell transplant recipients. Overall transplant recipients have a six fold increase in risk for developing any kind of non-Hodgkin lymphoma and PTLDs occur in up to 10% of SOT recipients. Several new entities have been accepted or renamed in the 2018 update of the WHO classification of tumors of hematopoietic and lymphoid neoplasms, including florid follicular hyperplasia and extranodal marginal zone lymphomas of mucosa-associated lymphoid tissue (MALT-lymphoma) (excluding common locations such as stomach and salivary gland). Other more rare types of PTLD have been reclassified including EBV-positive mucocutaneous ulcer, which is now a recognized diagnosis in its own right and should not be considered polymorphous PTLD. In this paper newly recognized PTLD entities and more unusual PTLDs will be examined.

IgG4-Related Systemic Disease Lymphadenopathy Masquerading as Renal Cell Cancer Recurrence: A Surprising Turn of Events

SESSION TITLE: Pulmonary Manifestations of Systemic Disease 4 SESSION TYPE: Affiliate Case Report Poster PRESENTED ON: Tuesday, October 31, 2017 at 01:30 PM - 02:30 PM INTRODUCTION: Immunoglobulin G4 Related Disease (IgG4-RD) has been recognized in pulmonary and extra-pulmonary inflammatory states. IgG4-RD encompasses a multitude of diseases once thought to be separate entities unto themselves. We herein present a case of IgG4-RD in a 72-year-old man, which was thought to be a recurrence of his distant renal cell carcinoma. CASE PRESENTATION: A 72-year-old man presented to his pulmonologist’s office for an incidental finding of pulmonary opacities with an adjacent axillary solitary lymphadenopathy on a cancer follow-up screening CT of the chest. Further testing with a PET/CT revealed uptake in the both the lymph node and affected lung tissue. Due to concern for distant metastatic disease, an excisional biopsy was performed. Tissue sampling revealed florid reactive follicular hyperplasia with intrafollicular histiocytes and an abundance of IgG4-positive plasma cells, which is the hallmark of IgG4-RD. The patient received corticosteroids, which caused resolution of the pulmonary opacities. The patient returned to the hospital three months later with severe abdominal pain and was diagnosed with acute pancreatitis. At first, he was managed with conservative medical therapy, but his condition worsened. He was then given a course of corticosteroids and his symptoms began to slowly resolve. DISCUSSION: IgG4-RD was termed in 2010 for a systemic fibroinflammatory disease, which presents with tumefactive lesions. A definite diagnosis of IgG4-RD depends on clinical findings such as masses, hematological findings of elevated serum IgG4 levels, and histopathologic findings of lymphoplasmacytic infiltration of IgG4-positive plasma cells, storiform fibrosis, and obliterative phlebitis. Treatment is recommended initially with steroids, and other immunosuppressants such as rituximab can be used as steroid sparing treatment. IgG4-RD has many organ system involvements, among them are autoimmune pancreatitis, Mikulicz’s disease, Riedel’s thyroiditis, multi-organ inflammatory pseudotumors, Ormond’s disease, idiopathic hypocomplementemic tubulointersitital nephritis, and multifocal fibrosclerosis. Pulmonary parenchymal involvement frequently presents radiographically as a mass-like, focal opacity, which may mimic a neoplasm, and may show uptake on PET/CT. CONCLUSIONS: IgG4-RD closely resembles malignancies, and has a favorable response to treatment. Therefore, heightened awareness of IgG4-RD and its early diagnosis may significantly improve patients’ morbidity. Reference #1: Campbell SN, Rubio E, Loschner AL. Clinical review of pulmonary manifestations of IgG4-related disease. Ann Am Thorac Soc 2014;11:1466-75. Reference #2: Wolfson AR, Hamilos DL. Recent advances in understanding and managing IgG4-related disease. F1000Res 2017;6 Reference #3: Khosroshahi A, Stone JH. A clinical overview of IgG4-related systemic disease. Curr Opin Rheumatol. United States 2011:57-66. DISCLOSURE: The following authors have nothing to disclose: Shimshon Wiesel, Anna Gutman, Paul Catella, Phyllis Suen, Abdul Siddiqui, Ali Abou Yassine, Dany El-Sayegh No Product/Research Disclosure Information

High frequency of Bob1lo T follicular helper cells in florid reactive follicular hyperplasia

Florid reactive follicular hyperplasia (FRFH), which is characterized by large germinal centers (GCs) within normal lymphoid follicles, is often observed in benign lesions of lymph nodes and other tissues. Because of the histologic similarity of FRFH to tumorous lesions such as follicular lymphoma, careful pathological examination is required to evaluate such lesions; however, little is known about the mechanism underlying the development of FRFH. In this study, we investigated T follicular helper (Tfh) cells in hyperplastic tonsils of patients with obstructive sleep apnea syndrome (OSA), which frequently exhibits typical FRFH. When we analyzed tonsils of OSA and recurrent tonsillitis (RT) as a control, tonsils of OSA were found to harbor Tfh cells with a nearly 3-fold higher ratio in total CD4+ T cells than that in tonsils of RT. Further analysis showed that, in comparison to Tfh cells of RT tonsils, Tfh cells of OSA tonsils were relatively tolerant to CD3-mediated activation-induced cell death (AICD) and also expressed lower levels of a Bob1 transcription coactivator and IL-4, which fosters the development of GC-B cells. Given that Bob1 controls the proliferative activity in response to CD3 stimulation and has been suggested to have a role in the production of IL-4 in Tfh cells, the unique structure of FRFH is possibly associated with the function of Bob1lo Tfh cells.

Thymoma and Synchronous Primary Mediastinal Seminomas with Florid Follicular Lymphoid Hyperplasia in the Anterior Mediastinum: A Case Report and Review of the Literature.

Thymoma is the most common neoplasm of the anterior mediastinum and has malignant potential. Germ cell tumors (GCTs) found in the anterior mediastinum are usually benign, and malignant GCTs, such as seminomas, are rare. Histologically, mediastinal seminoma is indistinguishable from testicular seminoma except for site-associated morphological features such as lymphoid follicular hyperplasia. Therefore, excluding metastasis is very important. Recently, we treated a young adult patient with multiple thymic masses that occurred simultaneously. The patient underwent a thymectomy for the removal of the mediastinal masses, one of which was diagnosed as type B2 invasive thymoma, and two of which were diagnosed as primary mediastinal seminomas with massive follicular hyperplasia. The patient received adjuvant chemotherapy after surgical resection. To our knowledge, this is the first description of a thymoma and a mediastinal seminoma occurring simultaneously in the thymus. We present this case along with a literature review.

Bilateral conjunctival pediatric follicular lymphoma

Follicular lymphoma (FL) is the most common type of B cell non-Hodgkin lymphoma in Western counties. FL is usually seen in adults and is very uncommon in pediatric population. Pediatric follicular lymphoma (PFL) is a rare indolent lymphoma characteristically seen in pediatric population, usually involving cervical lymph nodes, Waldeyer ring, and testis. They pose significant diagnostic challenges due to morphologic overlap with much more common florid follicular hyperplasia and lack of typical t(14;18)IgH/BCL2 fusion and BCL-2 protein expression. We present the case of a 10-year-old male with bilateral conjunctival nodules, showing characteristic morphologic and immunophenotypic features of PFL with demonstrated clonal B cell immunoglobulin heavy chain gene rearrangement. Of note, the neoplastic cells expressed MUM1, MYC, and IgM, suggestive of a different disease pathogenesis from adult FL.

Dasatinib-related Follicular Hyperplasia

Dasatinib, a second-generation tyrosine kinase inhibitor with activity against BCR-ABL1 and other Src family tyrosine kinases, is approved as a first-line treatment option for Philadelphia chromosome-positive chronic myelogenous leukemia (CML) in the chronic phase. Recently, lymphadenopathy with morphologic features of reactive follicular hyperplasia was described in a cohort of patients with CML on long-term dasatinib therapy. However, the complete morphologic and immunophenotypic features of this previously underappreciated adverse effect have not been fully described. Herein, we report 3 cases of unexplained lymphadenopathy resulting in multiple diagnostic procedures in patients with CML and a history of long-term dasatinib therapy. Morphologic examination demonstrated preserved nodal architecture showing hybrid features of progressive transformation of germinal centers and Castleman-type changes in a background of florid follicular hyperplasia. Large germinal centers were disrupted by complex infolding of IgD+ mantle zones arranged as cuffs surrounding perforating capillaries. Other abnormalities variably present included decreased CD20 expression among polytypic B cells and increased Epstein-Barr virus reactivity in scattered paracortical cells and/or individual germinal centers. B-cell clonality studies showed no predominant clonal rearrangements. Consideration of dasatinib-related lymphadenopathy may pre-empt unnecessary repeat diagnostic procedures in patients with CML or other dasatinib-susceptible malignancies and persistent lymphadenopathy.

Unusual initial presentation of herpes simplex virus as inguinal lymphadenopathy.

Genital herpes simplex virus (HSV) infections are a common cause of inguinal lymphadenopathy. However, surgical excision of enlarged inguinal nodes is almost never performed to initially diagnose genital herpes simplex virus, due to the distinct external presentation of genital herpetic vesicles that usually occur with the first symptoms of infection. Therefore, the histologic and immunophenotypic features of HSV-associated inguinal lymphadenopathy are unfamiliar to most pathologists. The current report describes the lymph node pathology of two immunocompetent patients, whose initial HSV diagnosis was established through surgical excision of enlarged inguinal lymph nodes. Histologic examination showed features consistent with viral lymphadenopathy, including florid follicular hyperplasia, monocytoid B-cell hyperplasia, and paracortical hyperplasia without extensive necrosis. Immunohistochemical stains for HSV antigens, using polyclonal anti-HSV I and II antibodies, demonstrate strong immunoreactivity for HSV in a small number of cells in the subcapsular sinuses, especially in areas with monocytoid B-cell hyperplasia. Rare scattered HSV-positive cells also are identified in paracortical areas and germinal centers. We conclude that an initial diagnosis of genital HSV infection may be established by inguinal lymph node biopsy.

Mediastinal seminoma with florid follicular lymphoid hyperplasia: a clinicopathological and immunohistochemical study of six cases.

Seminomas are unusual primary tumors of the anterior mediastinum. Morphologically, they are indistinguishable from their testicular counterparts; however, in the mediastinum, the occurrence of secondary changes such as cyst formation is not uncommon. We now describe six cases associated with florid follicular hyperplasia. The patients were male with an age range from 24 to 31years. Clinically, symptoms included cough, dyspnea, and chest pain. Anterior mediastinal masses were detected on imaging and all patients underwent thymectomy. Macroscopically, all tumors had a fleshy, lobulated cut surface. Histologically, the tumors were composed of round to polygonal cells with indistinct cell borders, clear cytoplasm, and prominent nucleoli. Striking follicular hyperplasia was evident in all cases to a degree whereby the tumor component was nearly obscured. Immunohistochemical studies demonstrated that the germinal centers were largely composed of B lymphocytes, and T cells were the predominant component of the interfollicular areas. Scattered Langerhans cells were noted in between tumor cells, and dendritic cells were seen in the mantle zones. All cases failed to show light chain restriction. Follow-up showed that five patients were alive and well 1-5years after diagnosis, while one was lost to follow-up. Thymic seminomas can be associated with striking lymphoid follicular hyperplasia, likely as a response to specific tumor antigens. Familiarity with this variant of thymic seminoma is important in order not to misdiagnose these cases for reactive conditions or other tumors such as lymphoproliferative neoplasms which may require a different treatment approach.