Spectrum of B-cell neoplasms associated with immunoglobulin G4-related disease.

Immunoglobulin G4-related disease (IgG4-RD) has rarely been associated with lymphoid neoplasms, the spectrum of which remains unclear. B-cell lymphoid neoplasms (LN) associated with IgG4-RD diagnosed in a 4-year period were analysed. There were five men and three women at a median age of 76.5 (52-90) years; three with synchronous IgG4-RD and LN; three with IgG4-RD preceding LN by 2, 3, and 22 years; and two with LN preceding IgG4-RD by 2.5 and 7 years. All patients presented with disseminated lymphadenopathy. Monoclonal gammopathy of undetermined significance (MGUS)/smouldering multiple myeloma (SMM) was found in three patients, all with an IgGκ paraprotein. Levels of IgGκ and IgG4 correlated. Diffuse large B-cell lymphoma (DLBCL) was found in three patients, with one case showing co-existing lymphoma and IgG4-RD in the same lymph node biopsy. The remaining two cases were marginal zone lymphoma (MZL) developing in a lacrimal gland previously involved by IgG4-RD; and nodular lymphocyte predominant Hodgkin lymphoma (NLP-HL) diagnosed in a lymph node with concomitant IgG4-RD. Low-dose continuous prednisolone was given for MGUS/SMM, with both monoclonal IgGκ and IgG4 responding. Combination chemotherapy was given for DLBCL, with two patients achieving complete response and one patient dying from refractory lymphoma. The patient with MZL refused treatment, whereas the case of NLP-HL responded completely to chemotherapy. Our findings together with previous observations suggest that IgG4-RD has an increased risk of B-cell neoplasms. Patients with IgG4-RD presenting with lymphadenopathy require vigorous investigations to exclude lymphoid neoplasms.

Surgical Experience of Video-Assisted Mediastinoscopy for Nonlung Cancer Diseases.

BACKGROUND: Video-assisted mediastinoscopy (VAM) is a valuable method in the investigation of diseases with mediastinal lymphadenopathy or those localized in the mediastinum. The aim of this study was to determine the diagnostic value of VAM in the investigation of mediastinal involvement of nonlung cancer diseases and to describe our institutional surgical experience. METHODS: Clinical parameters such as age, sex, histological diagnosis, morbidity, and mortality of all patients who underwent VAM for the investigation of mediastinal involvement of diseases except lung cancer between January 2006 and July 2018 were retrospectively reviewed, and the diagnostic efficacy of VAM was determined statistically. RESULTS: During the study period, 388 patients underwent VAM, and 536 lymph nodes were sampled for histopathological evaluation of mediastinum due to mediastinal lymphadenopathy or paratracheal lesions. The most common diagnoses were sarcoidosis (n = 178 [45.9%]), tuberculous lymphadenitis (n = 108 [27.8%]), lymphadenitis with anthracosis (n = 72 [18.6%]), and lymphoma (n = 15 [3.9%]). CONCLUSION: The results of the study show that VAM should be used because of its high diagnostic benefit in mediastinal lymphadenopathies, which are difficult to diagnose, or mediastinal lesions located in the paratracheal region. Despite the increase in the number of new diagnostic modalities, VAM is still the most effective method and a gold standard.

Recurrence of periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome after tonsillectomy: case-based review.

Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is a recurrent fever syndrome for which tonsillectomy is a therapeutic option curing the disease in most patients. Recurrence after remission with tonsillectomy is extremely rare. Increasing number of reports on diverse disease manifestations in PFAPA could give us clues about the disease etiopathogenesis. We aimed to describe a patient with recurrence of PFAPA syndrome after tonsillectomy and to review the previous studies including similar cases. We report a 17-year-old boy with PFAPA syndrome who experienced remission for 3 years after tonsillectomy and was later found to harbor an MEFV mutation when the disease relapsed. He responded well to colchicine treatment at relapse. The literature review revealed 14 articles describing 24 similar PFAPA patients. The therapeutic options include single-dose corticosteroids and nonsteroidal anti-inflammatory drugs during attacks, cimetidine, and resurgery. The presented case was the only one heterozygous for an MEFV mutation and treated with colchicine at disease relapse. Albeit rare, the reoccurrence of PFAPA after tonsillectomy could occur. The presence of such patients opposes with the hypothesis that the trigger or immune dysregulation in PFAPA pathogenesis resides in tonsils.

Pediatric Cervical Lymphadenopathy.

Cervical lymphadenopathy affects as many as 90% of children aged 4 to 8 years. With so many children presenting to doctors' offices and emergency departments, a systematic approach to diagnosis and evaluation must be considered. In the following review, we aim to provide the pediatric clinician with a general framework for an appropriate history and physical examination, while giving guidance on initial diagnostic laboratory testing, imaging, and potential need for biopsy. The most common cause of cervical lymphadenopathy in the pediatric population is reactivity to known and unknown viral agents. The second most common cause includes bacterial infections ranging from aerobic to anaerobic to mycobacterial infections. Malignancies are the most concerning cause of cervical lymphadenopathy.The explosion in the use of ultrasonography as a nonradiating imaging modality in the pediatric population has changed the diagnostic algorithm for many clinicians. We aim to provide some clarity on the utility and shortcomings of the imaging modalities available, including ultrasonography, computed tomography, and magnetic resonance imaging.

Treatment of Richter's Syndrome.

OPINION STATEMENT: Based on the available literature, mostly derived from retrospective or non-randomized phase I or II studies, it is difficult to define an optimized treatment approach for patients developing Richter's syndrome (RS). Early recognition of chronic lymphocytic leukemia (CLL) patients presenting clinical features suspected for a transformation is useful to avoid exposing them to multiple lines of therapy that, being targeted to CLL progression, have poor efficacy against RS. Because of the low specificity (~ 50-60%) of clinical signs of RS (such as rapid and discordant bulky localized lymphadenopathies, elevated LDH levels, emergent physical deterioration, and/or fever in the absence of infection), a 18FDG PET/CT and a biopsy are recommended to confirm RS. A 18FDG PET/CT showing low uptake is helpful to rule out RS and avoid unnecessary risks and costs of performing a biopsy. A 18FDG PET/CT showing a high uptake is not diagnostic of RS but may help in the choice of the site where the biopsy is to be performed. In the setting of the diffuse large B-cell lymphoma (DLBCL) variant of RS, the definition of a clonal relationship between RS and the underlying CLL may guide the choice of treatment. If a clonal relationship is confirmed (the most common situation), rituximab-CHOP-like treatment does not guarantee long-lasting remissions, and should be used as induction therapy followed by consolidation with a stem cell transplant in physically fit patients. If the CLL and RS are clonally unrelated (the less common situation), the management should be that of a de novo DLBCL. In the setting of the rare Hodgkin lymphoma variant of RS, which is usually clonally unrelated to the CLL, ABVD with or without radiotherapy may be curative of the aggressive lymphoma.

Demographic, clinical and therapeutic findings in a monocentric cohort of adult patients with suspected PFAPA syndrome.

OBJECTIVES: Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenopathy (PFAPA) syndrome is a non-Mendelian autoinflammatory disorder until now considered to be specifically limited to paediatric age. Recently, an increasing number of reports seems to suggest that PFAPA syndrome, diagnosed by the Marshall criteria revised by Thomas et al., can also affect adults. METHODS: The Marshall/Thomas criteria have been applied to 989 adult patients presenting for recurrent fever episodes: all patients enrolled were reviewed for demographic, clinical, and therapeutic data. Infectious, neoplastic, autoimmune and other autoinflammatory diseases were ruled out. RESULTS: We identified 30 adult patients (19 males, 11 females) with a suspected PFAPA syndrome: their mean age at disease onset was 33.75±14.01 years, mean age at diagnosis 39.1±14.39 years, and mean body temperature peak 39.5±0.7°C. In addition, the mean frequency of febrile episodes was 11.58±8.97 per year. More precisely, patients complained of pharyngitis (77%), cervical adenitis (73%), asthenia (63%), arthralgia (67%), oral aphthosis (50%), myalgia (54%), cephalalgia (43%), abdominal pain (27%), nausea/vomiting (17%), periorbital pain (17%), and arthritis (10%). Six out of 30 (20%) patients had suffered from PFAPA syndrome also during childhood, and the disease had reappeared in adulthood. CONCLUSIONS: We provide the largest monocentric cohort of patients diagnosed with a suspected PFAPA syndrome in adulthood confirming that this syndrome can occur also during adulthood; moreover, due to the medical history of our patients and based on our experience, PFAPA syndrome might relapse during adulthood after a temporary remission reached in the course of paediatric age.

Management Strategies in Rosai-Dorfman Disease: To Do or Not To Do.

Rosai-Dorfman disease or sinus histiocytosis with massive lymphadenopathy is an extremely rare non-Langerhans cell histiocytosis. Orbital involvement is even rarer and may be accompanied by lymph node involvement. Treatment options range from systemic steroids and immunosuppressants to radiation and debulking. We present a rare case of bilateral orbital sinus histiocytosis with massive lymphadenopathy with cervical and circumaortic lymphadenopathy.

A retrospective evaluation of lymphadenopathy in children in a single center's experience.

OBJECTIVE: To determine the causes of lymphadenopathies in children living in our region, and detect the frequency of malignant disease. METHODS: Our study evaluated demographic characteristics, lymph node involvement sites, tests, and viral serologiesperformed to search for the presence of infection, and ultrasonographic, and histologic findings of 1700 children who were referred to the outpatient clinics of the Paediatric Diseases and Paediatric Surgery between January 2012, and January 2015. RESULTS: Our study population consisted of 1003 (59 %) boys, and 697 (41 %) girls aged less than 18 years.Definitive diagnosis of43 (8.68 %) patients with unilateral, and 452 (91.9 %) cases with bilateral lymphadenopathies was established. These cases had benign (n=455) , and malignant (n=40) etiologies. Two hundred and four (12 %) of them underwent biopsies. On histological evaluation TB (n=6), Kawasakisyndrome (n=3), catscratch syndrome (n=4), toxoplasmosis (n=17), sarcoidosis (n=22), non-Hodgkinlymphoma (n=23),Hodgkin lymphoma (n=15), and Langerhans cell histiocytosis (n=2) were detected. Histological examination of the biopsy specimens of 110 cases revealed nonspecific histological changes. A total of 1205 (70.88%) patients without definitive diagnosis had undergone ultrasonographic assessments, and clinical evaluations performed before or within 4 weeks after antibiotic therapy and revealed regression of the lesions. CONCLUSIONS: The most widely encountered cause of lymphadenopathy is infection. Most of them are secondary to nonspecific viral, and bacterial infections. Most frequently diagnosed viral infections are caused by cytomegalovirus (CMV), and Ebstein-Barr virus (EBV). The most important issue in patients presenting with complaints of lymphadenopathy is the detection of the underlying malignant disease (if any), with the most frequent being non-Hodgkin lymphoma. Excisional biopsy is still the gold standard diagnostic method. Although our hospital was not an oncology center, our malignancy rate was higher than seen in some series. This might be possibly due to referral of monitored patients to our regional hospital for biopsy.

[A rare case of myeloproliferative disease with t(8;13)(p11;q12) associated with eosinophilia and lymphadenopathy]. / Redkii sluchai mieloproliferativnogo zabolevaniya s t(8;13)(p11;q12), protekayushchego s eozinofiliei i limfadenopatiei.

Myeloproliferative disease associated with FGFR1 rearrangement (8p11), which is included in the 2008 WHO Classification of Myeloid Neoplasms, is a rare and extremely aggressive abnormality. The paper describes a clinical case of a 39-year-old female patient who was detected to have leukocytosis (as high as 47.2·109/l), absolute eosinophilia (as high as 3.1·109/l), and enlarged peripheral lymph nodes during her visit to a doctor. The bone marrow (BM) showed the changes typically encountered in myeloproliferative disease with eosinophilia. The patient was found to have t(8;13)(p11;q12) translocation associated with the rearrangement of the FGFR1 gene located at the 8p11 locus. Molecular and cytogenetic examinations failed to reveal BCR-ABL chimeric transcript, Jak2 V617F mutation, and deletions and translocations involving PDGFRA (4q12) and PDGFRB (5q32-33). The similar changes in the karyotype were also found in the lymph node cells. The undertaken treatment with hydroxyurea and the tyrosine kinase inhibitor dasatinib turned out to be ineffective. The patient underwent allogeneic BM transplantation from a HLA-identical sibling. Graft rejection occurred 6 months later. Allogeneic BM transplantation from the same donor (100% donor chimerism; FGFR1/8р11 translocation was not detected), which was complicated by the development of chronic graft-versus-host reaction, was performed again in March 2015. The patient is being followed up and continues to receive immunosuppressive therapy.

Survival in esophageal cancer with nonregional lymphadenopathy: a propensity score-matched analysis.

BACKGROUND: Survival among patients with esophageal cancer with stage IV nonregional lymphadenopathy treated with neoadjuvant therapy and surgical resection is not well described. This study aimed to compare the survival outcomes of patients with nonregional lymphadenopathy with a propensity-matched cohort of patients with locoregional disease. METHODS: This was a retrospective cohort analysis of a prospectively maintained database from a regional upper gastrointestinal cancer network in Quebec, Canada. From January 2010 to December 2022, patients with radiologically suspicious nonregional retroperitoneal or supraclavicular lymphadenopathy were identified. Using 1:1 propensity score matching, a control group without nonregional disease was created. RESULTS: Of the 1235 patients identified, 39 met the inclusion criteria and were allocated to the study group of whom 35 of 39 (89%) had adenocarcinoma. Retroperitoneal and supraclavicular lymphadenopathy occurred in 26 of 39 patients (67%) and 13 of 39 patients (33%). Of the 39 patients, 34 (87%) received neoadjuvant chemotherapy, and 5 (13%) received chemoradiotherapy. After resection, ypN0 of nonregional lymph node stations occurred in 21 of 39 patients (54%). When comparing the study group with a matched non-stage IV control group, the median overall survival was similar in patients with retroperitoneal lymphadenopathy (21.0 months [95% CI, 8.0-21.0] vs 27.0 months [95% CI, 13.0-41.0]; P = .262) but not with supraclavicular disease (13.0 months; 95% CI, 8.0-18.0; P = .039). The median follow-up intervals were 40.1 months (95% CI, 1.0-83.0) for the study group and 70.0 (95% CI, 33.0-106.0) for the control groups. CONCLUSION: Compared with a matched cohort of patients with similar disease burden but not stage IV disease, retroperitoneal lymphadenopathy did not negatively affect survival outcomes. Multimodal curative intent therapy may be appropriate in select cases.

[Lymphadenopathy in general practice]. / Lymfadenopathie in de eerste lijn.

Lymphadenopathy (painfull or enlarged lymph nodes) is a common reason for consulting a physician working in primary or secondary health care. Lymphadenopathy can be the reason for consultation, but can also be observed in patients who present with other complaints. The differential diagnosis is very broad and varies from self-limiting benign disorders, where a wait-and-see policy is sufficient, to a more serious and life-threatening disease for which no further delay is warranted. In daily practice it can sometimes be challenging to determine which policy is indicated. In this article, we propose tools in order to assist the primary care physician to determine which policy is needed in patients presenting with lymphadenopathy.

Mediastinal lymphadenopathy: a practical approach.

Introduction: Mediastinal lymphadenopathy is secondary to various benign and malignant etiologies. There is a variation in the underlying cause in different demographic settings. The initial clue to the presence of enlarged mediastinal lymph nodes is through thoracic imaging modalities. Malignancy (Lung cancer, lymphoma, and extrathoracic cancer) and granulomatous conditions (sarcoidosis and tuberculosis) are the most common causes. For a confident diagnosis, the clinician must choose from several available options and integrate the clinical, radiological, and pathology findings. An accurate diagnosis is necessary for optimal management.Areas covered: We performed a search of the PUBMED database to identify relevant articles on the causes, imaging modalities, and interventional modalities to diagnose these conditions. We discuss a practical approach toward the evaluation of a patient with mediastinal lymphadenopathy.Expert opinion: Mediastinal lymphadenopathy is a commonly encountered clinical problem. Treating physicians need to be aware of the clinico-radiological manifestations of the common diagnostic entities. Selecting an appropriate tissue diagnosis modality is crucial, with an intent to use the least invasive technique with good diagnostic yield. Endosonographic modalities (EBUS-TBNA, EUS-FNA, and EUS-B-FNA) have emerged as the cornerstone to most patients' diagnosis. An accurate diagnosis translates into favorable treatment outcomes.