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A submandibular mass can be attributed to a variety of potential diagnoses. We report a case of a 71-year-old man presenting with left submandibular swelling associated with multiple lymph nodes.All investigations were negative except for a suspected malignant submandibular tumour.Unicentric Castleman's disease was diagnosed based on the final histological examination. [ABSTRACT FROM AUTHOR]

Objective: Characterize the CT findings of abdominopelvic Castleman disease, including a new observation involving the perinodal fat. Methods: Multi-centre search at 5 institutions yielded 76 adults (mean age, 42.1 ± 14.3 years; 38 women/38 men) meeting inclusion criteria of histopathologically proven Castleman disease with nodal involvement at abdominopelvic CT. Retrospective review of the dominant nodal mass was assessed for size, attenuation, and presence of calcification, and for prominence and soft-tissue infiltration of the perinodal fat. Hypervascular nodal enhancement was based on both subjective and objective comparison with aortic blood pool attenuation. Results: Abdominal involvement was unicentric in 48.7% (37/76) and multicentric in 51.3% (39/76), including 31 cases with extra-abdominal involvement. Histopathologic subtypes included hyaline vascular variant (HVV), plasma cell variant (PCV), mixed HVV/PCV, and HHV-8 variant in 39, 25, 3 and 9 cases, respectively. The dominant nodal mass measured 4.4 ± 1.9 cm and 3.2 ± 1.7 cm in mean long- and short-axis, respectively, and appeared hypervascular in 58.6% (41/70 with IV contrast). Internal calcification was seen in 22.4% (17/76). Infiltration of the perinodal fat, with or without hypertrophy, was present in 56.6% (43/76), more frequent with hypervascular vs non-hypervascular nodal masses (80.5% vs 20.7%; P < .001). Among HVV cases, 76.9% were unicentric, 71.1% appeared hypervascular, and 69.2% demonstrated perinodal fat infiltration. Conclusion: Hypervascular nodal masses demonstrating prominence and infiltration of perinodal fat at CT can suggest the specific diagnosis of Castleman disease, especially the HVV. Advances in knowledge: Abdominopelvic nodal masses that demonstrate hypervascular enhancement and prominent infiltration of the perinodal fat at CT can suggest the diagnosis of Castleman disease, but nonetheless requires tissue sampling. [ABSTRACT FROM AUTHOR]

Summary: Background: Castleman disease (CD) comprises a group of rare and heterogeneous haematological disorders, including unicentric (UCD) and multicentric (MCD) forms, the latter further subdivided into HHV8‐MCD, POEMS‐MCD and idiopathic‐MCD (iMCD). However, according to the Castleman Disease Collaborative Network guidelines, the diagnosis of CD can only be achieved through collaboration between clinicians and pathologists. Methods: We applied these clinical and pathological criteria and implement with clonality testing to a retrospective cohort of 48 adult and paediatric Italian patients diagnosed with reactive lymphadenitis with CD‐like histological features. Results: We confirmed the diagnosis of CD in 60% (29/48) of the cases, including 12 (41%) UCD and 17 (59%; five HHV8‐MCD, three POEMS‐MCD and nine iMCD) MCD. Of the remaining 19 cases (40%) with multiple lymphadenopathy, 5 (26%) were classified as autoimmune diseases, 1 (5%) as autoimmune lymphoproliferative disorder, 1 (5%) as IgG4‐related disease, 11 (83%) as reactive lymphadenitis and 1 (5%) as nodal marginal zone lymphoma. Conclusions: Our study emphasizes the importance of the multidisciplinary approach to reactive lymphadenitis with CD‐like features in order to achieve a definitive diagnosis and choose the appropriate treatment. [ABSTRACT FROM AUTHOR]

Castleman disease is a rare and benign disorder, characterized by enlarged lymph nodes and angiofollicular lymphoid hyperplasia. We report a case of a 57-year-old male, who was admitted to our surgical department because of a retroperitoneal nodular mass measuring about 4 cm in maximum diameter, incidentally discovered on a radiologic exam performed for the onset of vague abdominal pain with posterior irradiation. The patient was subdue to laparoscopic removal of the mass and no intra- and post-operative complications were recorded. Histologic diagnosis of hyaline-vascular variant of the Castleman disease was confirmed. Only two cases have been found in the literature reporting the paraduodenal unicentric Castleman disease localization like our case. Although rare, the Castleman disease must be considered in the differential diagnosis among all the lymph nodes diseases, for avoiding improper therapies. [ABSTRACT FROM AUTHOR]

Early identification, diagnosis and treatment of TAFRO syndrome are very importants. We retrospectively analysed 6 patients with TAFRO syndrome. Their clinical manifestations, treatment methods, survival and other aspects were summarized. All patients were pathologically diagnosed with Castleman's disease, with fever, an inflammatory storm state and varying degrees of anasarca. All patients received steroid therapy; four of them also received chemotherapy, and 1 received rituximab. Of the 3 patients with severe disease, only 1 patient who received the recommended dose of glucocorticoids survived. Early administration of glucocorticoids can improve the prognosis, especially in patients with severe disease, and adequate glucocorticoids are important. [ABSTRACT FROM AUTHOR]

Background: The literature describes a case of systemic lupus erythematosus (SLE) complicated with Castleman's disease (CD) and secondary paraneoplastic pemphigus (PNP). Case presentation: A 12-year-old female presented with a neck mass, rash, arthralgia, and skin and mouth ulceration for 5 years were admitted. All blood cells were low. Multiple autoantibodies associated with SLE were positive. The pathology of the neck mass revealed the classical manifestations of CD. She was treated with prednisone, hydroxychloroquine, leflunomide, thalidomide, and dressings. Pathological examination of the skin revealed PNP. The neck mass was removed and continued to take antirheumatic drugs. At subsequent follow-up, the patient's disease status was stable and the skin mucosal lesion did not recur. Conclusion: The case of simultaneous SLE, CD, and PNP in children was rarely reported, and the correct diagnosis of the disease will help to take timely treatment. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Idiopathic multicentric Castleman disease (iMCD) is challenging to diagnose due to clinical similarities with other conditions, such as Still's disease. Once diagnosed, iMCD may be effectively managed with the anti‐interleukin‐6 antibody siltuximab. Here, we present the case of a 19‐year‐old Polish woman with persistent fever and enlarged lymph nodes and whose diagnosis remained inconclusive following initial clinical assessments and extensive laboratory analyses. The patient had subsequent complaints of joint pain and erythema which were suspicious of Still's disease and resolved with treatment with tocilizumab. Later, the progression of symptoms, such as lymphadenopathy, and elevated interleukin‐6 levels were consistent with Castleman disease, leading to the diagnosis of idiopathic multicentric Castleman disease seven years after the patient first reported symptoms. Treatment with the anti‐interleukin‐6 antibody siltuximab resulted in complete symptom resolution and normalization of inflammatory parameters. No adverse events were reported due to treatment with siltuximab. [ABSTRACT FROM AUTHOR]

Castleman disease is an uncommon nonneoplastic, lymphoproliferative disorder of that is associated with lymphadenopathy and nonclonal lymph nodes hyperplasia. It is further subdivided into two types: Unicentric Castleman disease and Multicentric Castleman disease. Unicentric Castleman disease is rare to be reported in patients having AIDS, because HIV infected patients most commonly presented with Multicentric Castleman disease and they mostly coinfected with HHV-8. Herein we reported a rare presentation of Unicentric Castleman disease with hyaline vascular variety evident Histopathologically as a preoperative diagnosis. The patient was initially managed conservatively and surgical excision (excisional biopsy) of the left cervical lymph node was than performed and sent for histopathology. The Immunohistochemistry findings were also consistent with the diagnosis of Castleman disease Hyaline vascular type as evident from left cervical lymph node excisional biopsy. [ABSTRACT FROM AUTHOR]

Idiopathic multicentric Castleman disease (iMCD) is an infrequent and life-threatening disorder characterized by systemic inflammatory symptoms, generalized lymphadenopathy, polyclonal lymphocyte proliferation and organ dysfunction caused by a hyperinflammatory state. It accounts for one-third to one-half of all multicentric Castleman disease (MCD) cases. iMCD is often associated with autoimmune manifestations that may precede the iMCD diagnosis, be identified at the same time or follow it. In addition, iMCD may also coincide with a number of autoimmune diseases (such as psoriasis or myasthenia gravis) or autoinflammatory diseases (such as familial Mediterranean fever). Moreover, diverse inflammatory disorders, such as rheumatoid arthritis, systemic lupus erythematosus, adult-onset Still disease, systemic juvenile idiopathic arthritis, immunoglobulin (IgG4) related disease, or the recently described VEXAS syndrome, can present clinical features or lymphadenopathy with histopathological 'Castleman-like' findings compatible with those of iMCD. Given the iMCD clinical heterogeneity and the overlap with other autoimmune or autoinflammatory disorders, iMCD diagnosis can be challenging. In this review, we explore the overlap between iMCD and inflammatory diseases and provide practical guidance on iMCD diagnosis in order to avoid misdiagnosis and confusion with other autoimmune or autoinflammatory conditions. [ABSTRACT FROM AUTHOR]

Introduction: An abnormal mass in the head and neck involving the supraglottic and cervical region offers a wide range of differential diagnoses. The pathology is either benign or malignant in nature. Castleman disease (CD) is an uncommon lymphoproliferative disorder characterised by hypervascular lymphoid hyperplasia and is classified into unicentric or multicentric disease. Histopathologically it is divided into hyaline vascular (HV), plasma cell (PC), and mixed cellularity variants. The multicentric disease is linked with PC and has the propensity to progress to lymphoma or Kaposi Sarcoma. Case Report: We report a case of a 45-year-old gentleman who presented with a painless anterior neck swelling and left supraglottic mass for six months. Computed tomography (CT) contrast imaging demonstrated a homogenous enhancing lesion at the left supraglottic and the midline of the anterior neck with erosive changes of the thyroid cartilage. A surgical resection of the anterior neck mass was performed. The diagnosis of Castleman disease plasma cell variant was made by histopathologic evaluation. The patient remained well post-resection. Conclusion: Supraglottic multicentric Castleman disease is the least expected diagnosis in this case. Unicentric disease is treated with surgery. However, limited studies are available in determining the effectiveness of surgery in multicentric diseases. The plasma cell variant requires a multidisciplinary and multimodal approach due to an inclination towards malignancy. Research is needed to determine the role of surgery in multicentric disease and to develop optimum guidelines for managing cases. To date, there is unsubstantial literature describing supraglottic multicentric disease. [ABSTRACT FROM AUTHOR]

Background: Castleman's disease is an extremely rare heterogenous lymphoproliferative pathology with a mostly benign behavior. It is a localized or generalized lymph node enlargement of an unknown aetiology. Unicentric form is typically a slow-growing solitary mass occurring mostly in the mediastinum, abdominal cavity, retroperitoneum, pelvis and neck. Aetiology and pathogenesis of CD is probably diverse, varying in different types of this heterogeneous disease. Materials and Methods: Authors present a review of this issue based on their extensive experience. The aim is to summarize the crucial factors in the management of diagnostics and a surgical treatment of the unicentric form of Castleman's disease. One of the key issues in the unicentric form is precise preoperative diagnostics and thus choosing the right surgical treatment strategy. Authors highlight pitfalls of the diagnosis and surgical treatment. Results: All histological types such as a hyaline vascular type, plasmacytic type and a mixed type are presented as well as options of surgical and conservative treatment. Differential diagnosis and malignant potential is discussed. Conclusion: Patients with Castleman's disease should be treated in the highvolume centers, with a great experience in major surgical procedures as well as with preoperative imaging diagnostic techniques. Specialized pathologists and oncologists focusing on this issue are also absolutely necessary to avoid misdiagnosis. Only this complex approach can lead to excellent outcomes in patients with UCD. [ABSTRACT FROM AUTHOR]

Castleman disease is a rare benign lymphoproliferative disorder that includes a spectrum of distinct histopathological entities. The differential diagnosis of Castleman disease is broad and includes lymphomas, HIV-related lymphadenopathy, autoimmune disorders, and inflammatory liposarcoma. When Castleman disease occurs in the retroperitoneum, the distinction from the inflammatory variant of well-differentiated liposarcoma can be very challenging in small biopsies. Herein we report a case of Castleman disease that presented as a retroperitoneal mass and expressed MDM2 and CDK4 by immunohistochemistry. To our knowledge, this is the first report of Castleman disease staining positively for MDM2/CDK4, and it underscores how immunohistochemistry can potentially serve as a pitfall when differentiating this rare entity from retroperitoneal sarcomas. [ABSTRACT FROM AUTHOR]

Background: Castleman disease and lymphoma each have a distinct treatment plan; however, they share the same features on contrast-enhanced computed tomography. Methods: To assess the quantitative outcomes of Castleman disease versus lymphoma using contrast-enhanced computed tomography based on Hounsfield units (HU). We retrospectively reviewed eight patients with unicentric Castleman disease and 30 patients with lymphoma based on pathological diagnosis at China Medical University Hospital between 2015 and 2020. Preoperative computed tomography with contrast scans was reviewed, and the HU of each tumor were measured. Results: This study included eight patients with unicentric Castleman disease (four men and four women; mean age, 33 years) and 25 patients with lymphoma (11 men and 14 women; mean age, 53 years). There was no significant difference in heterogeneity between the two diseases (0.161 ± 0.052 vs 0.239 ± 0.063, p = 0.22); however, enhancement in Castleman disease was higher than that in lymphoma (126.40 ± 31.90 vs 74.19 ± 7.11, p < 0.001), providing a very good diagnostic tool (cutoff point at 88.5-91.3, sensitivity 0.86/specificity 0.88). Furthermore, we found a highly linear relationship in Castleman disease, which was not noted in lymphoma. Conclusion: The value of HU provides a good diagnostic tool for the differential diagnosis of Castleman disease versus lymphoma in the neck lymph nodes. Considering the linear relationship in Castleman disease, an increasingly accurate differential diagnosis can be made. [ABSTRACT FROM AUTHOR]

Introduction: A wide variety of viruses can cause rash diseases (RDs) or acute febrile illness (AFIs) in children, adolescents and adults; however, approximately 19% of RD cases and 40% of AFI cases remain without a defined etiology. Parvovirus B19 (B19V) and herpesvirus infection can also cause RD and/or AFI, and in some risk groups, these infections can become persistent (or latent) and may require hospital treatment. Since these infections do not have mandatory reporting, they can be hidden by other diseases, such as those caused by arboviruses (e.g., dengue virus). In this context, the aim of this study was to pursue the differential laboratory diagnoses of B19V and herpesvirus infections in patients with RD and AFI, without a defined etiology, seen in hospitals and/or reference centers for infectious diseases in Rio de Janeiro. Methods: A total of 114 participants were enrolled in the study, including 54 children and 60 adults. B19V infection was assessed by real-time PCR (qPCR) and ELISA (anti-B19V IgM and IgG). EBV was assessed through qPCR, and betaherpesviruses (HCMV, HHV-6 and HHV-7) were assessed through multiplex qPCR. Sociodemographic and clinical data were obtained from the medical record data of these participants. Results: The median age of children with RD was 2 years (interquartile range (IQR): 5), and 55.6% were male. Among adults with AFI, the median age was 38 years (IQR: 21), and 56.7% were female. Regarding RD patients, viral prevalence (and load) were 5.5%(104IU/mL), 3.4%(104IU/mL), 5.5%(104IU/mL) and 11.1%(105IU/mL) for B19V, EBV, HCMV and HHV-6 infection, respectively, and in AFI patients they were 6.6%(105IU/mL), 1.6%(103IU/mL), 3.3%(104IU/mL) for B19V, HCMV and HHV-6, respectively. HHV-7 was not detected in RD or AFI patients. Conclusion: These results suggest the importance of including B19V and herpesviruses in the differential laboratory diagnoses for patients with RD and AFI, not only for epidemiological purposes but also for the proper management of the patient. [ABSTRACT FROM AUTHOR]

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Background: X‐linked lymphoproliferative syndrome type 1 (XLP1) is a rare primary immunodeficiency disorder characterized by severe immune dysregulation often after viral infection. It is caused by hemizygous mutations in the X‐linked SH2D1A gene. People with XLP1 have complex and variable phenotype manifestations as EBV‐driven severe or fulminant mononucleosis, hemophagocytic lymphohistiocytosis (EBV‐HLH), dysgammaglobulinemia, and B‐cell lymphoma. Methods: Immunological analyses, clinical laboratory testing, and whole exome sequencing (WES) were performed to help the disease diagnosis for the patient with severe immune dysregulation. Routine and extended WES analysis pipelines were applied to explore candidates. A complex genomic structural variation in SH2D1A was detected and verified by Inverse‐PCR, Gap‐PCR, and RT‐PCR. Results: Here we reported that a five‐year‐old male patient manifested with EBV‐HLH, recurrent infection by severe immune dysregulation, and successfully managed with HSCT. He finally established precise disease diagnosis as XLP1 caused by a complex genomic structural variation in SH2D1A (NC_000023.11:g. [124,350,560_124365777del; 124,365,777_124365917inv; 124,365,911_124365916del]). The mother and grandmother of the proband were confirmed to be carriers. The complex variant resulted in the exon 2 skipping and was predicted to generate a prematurely truncated protein. Conclusion: The complex structural variant combined with paracentric inversion and large size deletions was first reported in XLP1 cases. It is considered to be pathogenic based on the truncation of the mRNA sequence and cosegregation with the disease in three‐generation pedigree analysis. This finding has expanded the known XLP‐related mutation spectrum in Chinese patients and indicated remarkable effects on the early diagnosis and therapeutic implication using proper molecular testing techniques. [ABSTRACT FROM AUTHOR]

Acquired angioedema due to C1‐inhibitor (C1‐INH) deficiency (AAE‐C1‐INH) is rare and is associated with underlying lymphoproliferative diseases. C1‐INH deficiency may be due to neoplastic over‐consumption of C1‐INH and the generation of anti‐C1‐INH autoantibodies. Uncovering an occult malignancy can lead to earlier oncology referral and improvement of angioedema after treatment of the underlying lymphoproliferative disorder. We characterized seven patients with C1‐INH‐AAE that highlights the importance of recognizing the association between C1‐INH‐AAE and underlying malignancy. In acute attacks, patients may be resistant to C1‐INH therapy due to the presence of anti‐C1‐INH autoantibodies or rapid complement consumption, and may respond better to icatibant or ecallantide, which directly affect bradykinin. Treatment of the underlying malignancy also improves AAE‐C1‐INH symptoms and supports the role of lymphoproliferative B cells in AAE‐C1‐INH pathophysiology. Monitoring levels of C4, C1‐INH function and level, and C1q may be predictive of AAE‐C1‐INH control and be used as surrogates for treatment efficacy. With close monitoring, low‐dose danazol can be effective for long‐term prophylaxis. Annual evaluation in AAE‐C1‐INH is recommended if an underlying malignancy is not found, as angioedema may precede the development of malignancy by several years. Our single‐center study has aided in standardization of comprehensive AAE‐C1‐INH diagnosis, treatment, and monitoring strategies towards future therapeutic clinical trials. [ABSTRACT FROM AUTHOR]

Multifocal micronodular pneumocyte hyperplasia (MMPH) is the lesser known pulmonary manifestation of tuberous sclerosis. It manifests radiologically as diffuse small ground‐glass and solid nodules. Accurate diagnosis is essential as it can be mistaken for miliary tuberculosis or malignant lesions which necessitates specific treatment. Constellation of radiological features such as multicentric disease at onset and stability over time can help to distinguish MMPH from its differentials. Histologically, MMPH is characterized by hamartomatous proliferation of type II pneumocytes with a lack of high nuclear to cytoplasmic ratio. MMPH confers a benign prognosis unlike its differentials. Therefore, accurate diagnosis is paramount in ensuring appropriate care is delivered. Here, we describe the radiological and histological features of MMPH in a patient with genetically proven tuberous sclerosis complex and co‐existing lymphangioleiomyomatosis. [ABSTRACT FROM AUTHOR]

Background: Castleman's disease (CD) is a rare lymphoproliferative disease of unknown origin which rarely affects the spine. Here, we present CD involving a lytic, destructive C3 lesion with extension into the spinal canal contributing to upper cervical cord compression. Notably, the lesion mimicked other primary bone lesions, metastatic tumors, and/or lymphoma. Case Description: A 52-year-old male presented with progressive quadriparesis (i.e. weakness, instability of gait) and loss of dexterity in both hands over 2 weeks. The MRI, X-ray, and CT scans revealed a destructive lytic lesion involving the C3 vertebral body (i.e. including both anterior and posterior elements). The patient underwent a C3 total and C4 partial laminectomy followed by a C2-C4/5 instrumented fusion (i.e. included C2 pedicle screws/laminar screws, and C4/C5 lateral mass fixation). Histopathology showed a lymphoproliferative disorder with follicles of different sizes, central abnormal germinal structures, and a Mantle zone (i.e. expanded germinal centre with concentric layering with an "onionskin" appearance). These findings were all consistent with the diagnosis of CD (i.e. hyaline-vascular type). Conclusion: CD, a rare lymphoproliferative disease of unknown origin rarely affects the spine. Here, we presented a 52-year-old male with a C3 lytic lesion resulting in C3/4 cord compression that favorably responded to a C3/4 laminectomy with posterior instrumented fusion. [ABSTRACT FROM AUTHOR]

One of the complications of common variable immunodeficiency (CVID) is the development of lymphoid malignancy. In this retrospective, single‐center study of 647 CVID subjects followed over 4 decades, we present immunologic and clinical phenotypes, pathology, treatment, and outcomes of 45 patients (15 males and 30 females, 7%) who developed 49 lymphoid malignancies. The mean age at CVID diagnosis was 42.6 years) and at lymphoma diagnosis was 48.8 years. Of the 41 with known follow up, 29 (70%) have died, 27 of these due to this diagnosis. Twelve are alive, in remission or have achieved cure; four others were alive at last encounter. Some patients had a history of only recurrent infections (36.3%); others had autoimmunity (33%), enteropathy (20%), and/or granulomatous disease (11%). Six had previously been treated for another cancer. This report also includes 6 additional living CVID patients who had been diagnosed with NHL; 4 were given treatment for this. However, on pathology review, the initial diagnosis was reversed, as the findings were more consistent with a benign lymphoproliferative process. This study outlines the high incidence of lymphoma in this single CVID cohort, and some of the diagnostic challenges presented due to immune dysregulation characteristic of this immune defect. [ABSTRACT FROM AUTHOR]

Castleman disease is a rare lymphoproliferative disease also known as angiofollicular lymph node hyperplasia. It is classified as hyaline vascular and plasmacytic variants histologically but characteristics of both types can coexist. Most unicentric cases of the disease are hyaline vascular while most multicentric cases are of the plasmacytic type. Although the pathogenesis is not completely understood, the role of interleukin (IL)-6 in unicentric disease and the roles of IL-6 and human herpes virus-8 in multicentric disease are well defined. Unicentric disease is typically localized and symptoms are minimal and treated locally. Multicentric disease is systemic and clinically characterized by generalized lymphadenopathy, splenomegaly, anemia, and systemic inflammatory symptoms. Systemic therapies are primarily given. Several malignant diseases including lymphomas, POEMS syndrome, follicular dendritic cell sarcomas, paraneoplastic pemphigus, Kaposi sarcoma, and amyloidosis can be associated with Castleman disease. In this paper, recent information about Castleman disease, which is a rare disease, is summarized. [ABSTRACT FROM AUTHOR]

Purpose: To clarify the incidence, demography and clinical features of orbital tumors diagnosed in a single institute in Japan. Study design: Retrospective, observational case series. Methods: Patients with primary orbital tumors including tumor-like lesions diagnosed clinically or histopathologically at Tokyo Medical University Hospital between 1995 and 2019 were analyzed. Incidence of all orbital tumors, demographic profile and clinical features of major benign and malignant tumors were reviewed retrospectively. Results: Totally 1000 cases of primary orbital tumor were diagnosed clinically or histopathologically during the study period. Benign tumors accounted for 72% and malignant tumors 28%. 55% of benign tumors and 99% of malignant tumors were proven histopathologically. The most common benign orbital tumor was idiopathic orbital inflammation (27%), followed by IgG4-related ophthalmic disease (17%), cavernous venous malformation (13%) and pleomorphic adenoma (9%). The most common malignant tumor was lymphoma (70%), followed by adenoid cystic carcinoma (7%) and solitary fibrous tumor (5%). Conclusions: Epidemiology of orbital tumors has changed by the improvement of imaging techniques, establishment of novel clinical and histopathological criteria, and changes in population age structure associated with the aging society. Currently, lymphoproliferative diseases including lymphoma and IgG4-related ophthalmic diseases form the major orbital tumors in Japan. [ABSTRACT FROM AUTHOR]

TAFRO syndrome is defined by the presence of thrombocytopenia (T), anasarca (A), fever (F), reticulin fibrosis/renal dysfunction (R), and organomegaly (O) and can be seen with idiopathic multicentric Castleman disease (iMCD) or as an isolated process without iMCD. Although the diagnosis of iMCD in patients with TAFRO can be challenging to make, iMCD should remain high on the differential diagnosis. Similar to iMCD, the pathophysiology of TAFRO is not well understood but is thought to be related to hypercytokinemia, with interleukin (IL)-6 playing a pivotal role. Anti-IL-6 monoclonal antibody therapy is an effective treatment modality for iMCD, but to date, there is no clear guidance on treatment of TAFRO in the absence of definitive diagnosis of iMCD, leading to suboptimal management and high morbidity. We report a case of TAFRO syndrome and demonstrate benefit with the empiric use of anti-IL-6 antibody therapy in the context of delayed diagnosis of iMCD. [ABSTRACT FROM AUTHOR]

Introduction: Chronic B-Cell Lymphoproliferative Disorders (B-CLPD) are malignant neoplasms of B lymphocytes characterised by accumulation of mature B lymphocytes in the Bone Marrow (BM), peripheral blood, and lymphoid tissues. Multiparameter flowcytometry has become a powerful tool in diagnosing B-CLPD that identifies a clonal light-chain restricted population expressing B-cell markers. Aim: To study the morphologic and immunophenotypic profile of B-CLPD by flowcytometry and to determine the incidence of various subtypes. Materials and Methods: All consecutively diagnosed cases of chronic B lymphoproliferative disorders at Regional Cancer Centre, Trivandrum, Kerala, India from 1st December 2016 to 30th November 2018 were retrospectively analysed and studied. Diagnosis of CLPD was made based on peripheral smear and BM aspiration and immunophenotyping by flowcytometry. Flowcytometry was performed using BD FACS Verse flowcytometer. The results of immunophenotyping by flowcytometry were reviewed and analysed. Results: During the study period, 231 cases were diagnosed as Chronic Lymphoproliferative Disorder (CPLD), of which 209 cases were B-CLPDs. Male to female ratio was 2:1. In the present study, incidence of Chronic Lymphocytic Leukaemia (CLL) was 138 cases (66.03%), Follicular Lymphoma (FL) was 14 cases (6.7%), Hairy Cell Leukaemia (HCL) was 11 cases 5.26% and Mantle Cell Lymphoma (MCL) was 9 cases, (4.31%). Prolymphocytic leukaemia and splenic Marginal Zone Lymphoma (MZL) constituted 4 cases (1.91%) each. Some cases of B-CLPDs had no definite diagnoses which were diagnosed as CD5 positive B-CLPD unclassified 13 cases (6.22%) and CD5 negative B-CLPD unclassified 16 cases (7.66%). Conclusion: Flowcytometry has helped in definite subtyping of B-CLPD in most cases. Most common subtype in the present study was CLL. CD5+/CD23+ is highly specific for diagnosing CLL. CD200 is revealed to be an excellent marker to distinguish CLL from MCL. [ABSTRACT FROM AUTHOR]

Background: With widespread clinical application of imaging techniques, renal space-occupying lesions have been identified at an increasing frequency. Here, we report two rare cases, Castleman disease (CD) and IgG4-related disease (IgG4-RD), presenting primarily with the symptoms and imaging findings of kidney malignancy. Case presentation: In case 1, an occupying lesion located in the right renal pelvis was detected using magnetic resonance imaging in a 32-year-old female who presented with hematuria and lumbago. First misdiagnosed as carcinoma of the renal pelvis, the patient underwent right radical nephroureterectomy. However, postoperative pathological and immunohistochemistry studies finally confirmed the diagnosis of CD. In case 2, a 45-year-old male presented with the chief complaint of anuria. Nephrostomy and renal biopsy indicated lymphoma, following which, antegrade urography and computed tomography urography were performed, which revealed bilateral hydronephrosis and mass lesions around the renal pelvis. Partial resection of the masses and frozen section examination indicated the diagnosis of CD. However, the results of postoperative histopathology and immunohistochemistry combined with serum IgG4 were consistent with IgG4-RD. Both the patients recovered well after drug treatment without recurrence of the diseases. Conclusions: Inflammatory pseudotumor of CD and IgG4-RD with kidney involvement are primarily diagnosed by postoperative histopathology and can pose a preoperative diagnostic challenge because these lesions can masquerade as kidney malignancy. Therefore, we recommend core biopsy as a nonnegligible procedure to evaluate renal masses and potentially prevent unnecessary surgical treatment. [ABSTRACT FROM AUTHOR]

Diffuse lymphadenopathy has a long differential diagnosis that includes both malignant and benign causes. As part of the lymphadenopathy work-up, many patients undergo [18F]FDG-PET/CT for purposes of ruling out malignancy. FDG-avid lymph nodes, however, are not specific for malignancy. This review will illustrate the spectrum of nodal findings on FDG-PET/CT with correlation to other cross-sectional imaging and clinical history in patients with representative infectious, inflammatory, and benign lymphoproliferative disorders. These findings are important for the nuclear medicine radiologist to understand, as they can represent common pitfalls in the work-up of lymphadenopathy. While FDG-PET/CT may be limited in ascertaining a definitive diagnosis in a disease process as the cause of lymphadenopathy, it can help to narrow this differential and rule out certain diseases in the correct clinical context. [ABSTRACT FROM AUTHOR]

Hemophagocytic lymphohistiocytosis (HLH) is a life‐threatening disease characterized by excessive inflammation and tissue destruction due to a dysregulated immune response. Its secondary form is most commonly triggered by viral infection or malignancy. There have previously been 11 cases of acquired HLH described following liver transplantation in adult transplant recipients, most occurring within the first year following transplantation. Herein, we describe two cases of HLH in liver transplant recipients that both occurred remotely following transplantation. In the first case, HLH was thought to be triggered by the development of a post‐transplant lymphoproliferative disorder in a patient who was initially diagnosed with recurrent autoimmune hepatitis. In the second, it was thought to be triggered by a newly acquired human herpesvirus‐8 infection. In both cases, the syndrome was not recognized until treatment for the initial putative diagnoses was unsuccessful. Despite treatment, both patients unfortunately died from multiorgan failure. HLH in the post‐liver transplant setting is likely under‐recognized and has a high mortality; early diagnosis and intervention may lead to improved outcomes. [ABSTRACT FROM AUTHOR]

Background: Paraneoplastic autoimmune multiorgan syndrome (PAMS), first described as paraneoplastic pemphigus (PNP) is a heterogeneous autoimmune syndrome with a diverse spectrum of clinical and immunopathological features associated with an internal neoplasm. Materials and Methods: The details of the patients diagnosed with PAMS/PNP from an Indian tertiary center between January 2010 to December 2019 were retrieved from the hospital database. The clinical manifestations, histopathological features, immunofluorescence findings, and other relevant clinical details were obtained. Results: There were eight patients (4 males, 4 females) with PAMS, age ranging from 8 to 46 years (mean 31 years), of whom two were 8-year-old children. The mucocutaneous manifestations were polymorphic and all had recalcitrant oral mucosal involvement. The most common mucosal presentation was pemphigus-like (5/8), and the cutaneous presentation was lichen planus-like (5/8). Castleman's disease (5/8) was the commonest neoplasm followed by thymoma (2/8). Interface dermatitis was seen in all biopsies and three different patterns of direct immunofluorescence were seen, which were intercellular "fish-net" fluorescence in the epidermis (2/8), granular/linear deposition along the basement membrane (4/8) and a combination of both patterns (1/8). Indirect immunofluorescence done on rat bladder in 3 patients showed intercellular "fish-net" fluorescence. Desmoglein levels were not elevated in any of our patients. The follow-up period ranged from 1 to 112.5 months (mean, 23.6 months) with a mortality rate of 12.5%. Conclusion: In our study, Castleman's disease was the most common associated malignancy, and the mucocutaneous and histopathological findings were heterogeneous. Timely diagnosis and early intervention improved the outcome in our patients. [ABSTRACT FROM AUTHOR]

Pulmonary lymphomatoid granulomatosis (PLG) is a rare multisystem Epstein–Barr virus (EBV)‐associated lymphoproliferative disorder. Exact incidence is unknown and, with its variable clinical presentation, making an accurate diagnosis of PLG can be difficult. We present two distinct cases at our tertiary centre that underline PLG's non‐specific clinical presentations. This resulted in the failure of recognizing PLG early with consequently progressive fatal outcomes. The rationale is to enlighten us concisely the knowledge surrounding PLG and consider it as a potential differential diagnosis, particularly in those immunosuppressed patients with radiological evidence of worsening pulmonary infiltrates not responding to customary treatment for common diagnoses. Having a high degree of suspicion for PLG in the right setting and pursuing lung biopsy early if appropriate for histopathology examination would be justified. This is essential to correctly diagnose PLG up‐front and subsequently utilize best management approach for a better survival and mortality risk outlook. [ABSTRACT FROM AUTHOR]

Coupled with the patient's oral ulcers, a diagnosis of paraneoplastic pemphigus (PNP) related to unicentric Castleman disease was established. A 14-year-old girl, without any remarkable past medical history, presented with scattered round ulcers on the buccal mucosa, dorsal and lateral tongue (Figure 1), and gingiva for 4 months. Subsequent IIF confirmed the diagnosis of PNP, and the discovery of the mediastinal tumor later led to a diagnosis of Castleman disease. [Extracted from the article]

Splenic marginal zone lymphoma (SMZL) is a rare lymphoma belonging to the marginal zone lymphoproliferative disorders. Usually, SMZL occurs with indolent presentation and, when required, the standard of care is represented by rituximab-based regimens. No direct comparison of different rituximab-based combinations and polychemotherapy regimens has been conducted to date. In a monocentric cohort of 68 SMLZ patients, we showed that rituximab in monotherapy or in combination with bendamustine, compared with rituximab associated with the polychemotherapy cycle cyclophosphamide, hydroxydaunorubicin, vincristine and prednisolone (CHOP), resulted in a higher 5-year progression-free survival (91.3 ± 9% and 75 ± 15.7% vs. 30.8 ± 12.1%, p < 0.001). Platelets at diagnosis <100 ×109/L (p = 0.034, HR = 4.3) and transformation into diffuse large B-cell lymphoma (p = 0.031, HR = 4.3) were associated with a lower overall survival. [ABSTRACT FROM AUTHOR]

In immunocompromised patients, EBV may elicit B-cell transformation and proliferation. A 5-year-old microcephalic boy was admitted with fever and non-malignant polymorphic T-cell lymphoproliferative disease associated with EBV. A presumptive diagnosis of primary immunodeficiency with inability to control EBV was made and next-generation sequencing led to the identification of a novel ZBTB24 mutation (ICF2-syndrome). This case shows that susceptibility to EBV seems to be particular of ICF-2 as it has not been described in the other types of ICF. It is mandatory to raise the hypothesis of an underlying PID in case of severe EBV infection. [ABSTRACT FROM AUTHOR]

Castleman disease is a rare lymphoproliferative disorder presenting with localized or disseminated lymphadenopathy and systemic symptoms. It can be categorized clinically as unicentric or multicentric, histopathologically as hyaline vascular, plasma cell, or mixed variant, and etiologically, considering the subtypes based on causative viral agents and associated syndromes. The multicentric type can mimic other haematological malignancies, ranging from asymptomatic to multiple organ involvement. Although its pathophysiology is not well known, the current approved treatments are directed towards interleukin-6, CD-20, and viral agents. The authors present an 82-year-old leucodermic man presented with a 2-week history of constitutional symptoms. Examination revealed pallor, hepatosplenomegaly, and palpable left axillary lymphadenopathy. Investigation showed anaemia, thrombocytopenia, polyclonal hypergammaglobulinemia, hypoalbuminemia, and high acute phase reactants, with image study revealing multiple axillary, mediastinal, inguinal, and pelvic lymphadenopathies. The lymph node biopsy was consistent with hyaline vascular-type Castleman disease without human herpersvirus-8 markers. He started prednisolone with initial improvement evolved poorly on a short term. Castleman disease has a broad spectrum of clinical manifestations, associations, and complications that bring a diagnostic challenge, requiring a multidisciplinary approach. Clinicians should be familiar with its features because proper diagnosis and aggressive targeted treatment are the pillars of proper management of these patients. [ABSTRACT FROM AUTHOR]

Solid organ recipients have increased risk of malignancy in comparison with general population. Although post-transplant lymphoproliferative disorders are the second most common cancer in transplanted patients, primary CNS lymphoma is a rare presentation of these disorders. Among the wide range of neurologic complications in post-transplant period, some characteristics could be helpful for diagnosing of this disorder. Rarity of CNS lymphoma may lead to late diagnosis of this disease while early detection has utmost importance for better management of it. Here, we describe a heart recipient young woman with focal neurologic symptoms 14 months after transplantation and some features that could be helpful for on-time diagnosis. [ABSTRACT FROM AUTHOR]

Linked Article: Kempf et al. Br J Dermatol 2022; 186:887–897. [ABSTRACT FROM AUTHOR]

Background: Immunoglobulin G4-related disease (IgG4-RD) is a multi-organ disorder predominantly occurring in middle-aged to elderly male patients characterized by multi-organ fibrosis, specific pathological findings of storiform fibrosis with IgG4-positive plasma cell infiltration, and elevated serum IgG4 level. We herein report a rare presentation of IgG4-RD forming an isolated mass in the middle mediastinum mimicking a mediastinal tumor and discuss the clinical significance of mediastinal IgG4-RD. Case presentation: An 82-year-old male patient without any symptom was referred due to left middle mediastinal mass (3.8 × 2.4 cm). Because of suspected lymphoma, Castleman's disease, and lymphangitis due to tuberculosis, we performed a thoracoscopic resection for diagnosis and treatment. The mass was yellowish white with well-encapsulated, and storiform fibrosis with plasma cell infiltration, and obliterative phlebitis were observed microscopically. Additional immunohistochemical stain revealed IgG4-RD. Other radiological findings and serological results did not show evidence of other organs being affected from IgG4-RD nor autoimmune diseases. He is now followed at outpatient clinic without additional treatment for over a year, and an enhanced computed tomography does not show any recurrence. Conclusion: It was a rare presentation of IgG4-RD forming isolated middle mediastinal mass, which suggests that we might suspect IgG4-RD for undetermined mediastinal mass in case of middle to elderly male patient. [ABSTRACT FROM AUTHOR]

Multicentric Castleman disease (MCD) is an uncommon systemic lymphoproliferative disease. The diagnosis of this disease is typically challenging and requires collaboration between clinicians and pathologists. Moreover, it is important to exclude other diseases (such as malignancies, autoimmune diseases, and infectious diseases) that have similar clinical manifestations and pathological findings. Patients with untreated severe MCD have high mortality due to devastating cytokine storms. Thus, early diagnosis and prompt treatment is a key imperative. The diagnosis of MCD is based on the clinical signs of systemic inflammation, serological tests, and typical pathological features. In this review article, we provide an overview of MCD with a focus on the emerging evidence pertaining to its diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Background: Castleman disease (CD) is a rare polyclonal lymphoproliferative disorder with unknown etiology. TAFRO syndrome is now regarded as a specific subtype of CD, and is still a huge challenge for clinicians. Methods: To clarify the clinical features and management of TAFRO syndrome in China, we retrospectively analyzed 96 patients with HIV-negative CD (52 with unicentric CD and 44 with multicentric CD), who were diagnosed and treated at our center between 2008 and 2017. Specially, we systematically reviewed the 7 TAFRO syndrome cases based on the 2015 criteria proposed by Masaki. Results: Among the 7 cases, there were 3 men and 4 women, and the median age was 53 years. The main symptoms included thrombocytopenia (7/7), anasarca (7/7), fever (4/7), renal dysfunction (7/7), and organomegaly (6/7). One patient was treated with corticosteroid monotherapy, one received RD (Rituximab, dexamethasone), and 5 received CHOP/COP like chemotherapy as first-line treatment, 2 of the 5 combined with Rituximab. Four patients needed hemodialysis or CRRT because of progressive renal failure. The outcome for TAFRO syndrome was significantly worse compared to other types of CD. Although 3 patients improved after early treatment, 4 patients died due to disease progression, and only one patient achieved complete resolution of all the symptoms after changing to lenalidomide based regimen. Conclusions: This study reveals that TAFRO syndrome is more severe and has more systemic symptoms than other iMCD, most cases need active treatment, and their prognoses are poor. Lenalidomide based regimen may be as a promising new therapy for TAFRO syndrome. [ABSTRACT FROM AUTHOR]

Castleman disease (CD) is a rare clinical entity characterized by enlarged lymph nodes. It may affect a single lymph node (unicentric) or multiple lymph nodes in the body (multicentric). However, it is exceptionally uncommon for unicentric Castleman disease (UCD) to present in the mesentery. Herein, we report a case of 38-year-old female complaining of polymenorrhea and abdominal discomfort for 4 months. Her past medical history was unremarkable; however, she has started smoking recently. The physical examination and radiography indicated a large, well-defined mass in the right hypochondrium. Eventually, the patient underwent laparotomy and the mass was excised totally. The Pathologic study confirmed the diagnosis as mesenteric CD, hyaline-vascular type. After 5 months of follow-up, the patient showed no evidence of recurrence. In conclusion, this case underscores the importance of taking mesenteric CD into consideration in each patient who presents with solid abdominal mass or ambiguous abdominal discomfort. [ABSTRACT FROM AUTHOR]

Castleman's disease (CD) is an uncommon type of lymphoproliferative disorder. Its etiology and prevalence are unclear. The retroperitoneum is a very rare site for presentation of the unicentric variant, where it mimics malignant tumors. A 59-year-old man is referred to the urology outpatient clinic for the study of microhematuria found in a routine analysis. CT scan of the abdomen identified a solid, circumscribed mass, measuring 28 × 30 × 31 mm in the left para-aortic zone, with homogeneous contrast enhancement. Excisional surgery and regional lymphadenectomy were performed via laparoscopy. Postoperative course concurred without incidences. Histological diagnosis confirmed unicentric CD, hyaline-vascular type. CD is a rare entity, and the unicentric type presents as an asymptomatic mass. Retroperitoneum is a rare localization, where initial imaging diagnosis is unclear and surgical resection is the preferred treatment. [ABSTRACT FROM AUTHOR]

In this case, the core biopsy disclosed a diffuse proliferation of CD20-positive mature B cells, leading to a putative diagnosis of indolent non-Hodgkin B-cell lymphoma. Randomized comparison of power Doppler ultrasonography-guided core-needle biopsy with open surgical biopsy for the characterization of lymphadenopathies in patients with suspected lymphoma. Excisional biopsy of the same lymph node disclosed scattered Hodgkin/Reed-Sternberg (HRS) cells (insert), which were not evident on first biopsy. [Extracted from the article]

Multicentric Castleman disease (MCD) is a rare entity that, unlike unicentric Castleman disease, involves generalized polyclonal lymphoproliferation, systemic inflammation, and multiple-organ system failure resulting from proinflammatory hypercytokinemia, including, in particular, interleukin- A subset of MCD is caused by human herpesvirus-8 (HHV-8), although the etiology for HHV-8--negative, idiopathic MCD (iMCD) cases is unknown at present. Recently, a consensus was reached on the diagnostic criteria for iMCD to aid in diagnosis, recognize mimics, and initiate prompt treatment. Pediatric iMCD remains particularly rare, and differentiation from MCD mimics in children presenting with systemic inflammation and lymphoproliferation is a challenge. We report on a young boy who presented with a HHV-8--negative, iMCD-like phenotype and was found to suffer from the monogenic disorder deficiency of adenosine deaminase 2 (DADA2), which is caused by loss-of-function mutations in CECR1. DADA2 prototypic features include early-onset ischemic and hemorrhagic strokes, livedoid rash, systemic inflammation, and polyarteritis nodosa vasculopathy, but marked clinical heterogeneity has been observed. Our patient's presentation remains unique, with predominant systemic inflammation, lymphoproliferation, and polyclonal hypergammaglobulinemia but without apparent immunodeficiency. On the basis of the iMCD-like phenotype with elevated interleukin-6 expression, treatment with tocilizumab was initiated, resulting in immediate normalization of clinical and biochemical parameters. In conclusion, iMCD and DADA2 should be considered in the differential diagnosis of children presenting with systemic inflammation and lymphoproliferation. We describe the first case of DADA2 that mimics the clinicopathologic features of iMCD, and our report extends the clinical spectrum of DADA2 to include predominant immune activation and lymphoproliferation. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Unicentric Castleman's disease (CD) may rarely present as an isolated retroperitoneal tumor. Even experienced surgeons may misdiagnose CD because of its rarity. Surgeons should consider this disease when faced with an isolated retroperitoneal tumor. Unicentric CD is usually cured with surgical resection. In contrast, multicentric CD need numerous systemic therapies. [ABSTRACT FROM AUTHOR]

IgG4-related disease (IgG4-RD) is a multisystemic mass forming immune-mediated disease entity, commonly creating confusion and diagnostic challenges. We present a case of a 25-year-old female who presented with bilateral orbital masses, lymphadenopathy, paraspinal and renal masses, which clinicoradiologically simulated lymphoma. The lymph node biopsy revealed interfollicular sheets of plasma cells creating confusion with Castleman's disease and marginal zone lymphoma. The orbital biopsy revealed ductular destruction, periductular plasma cells, and fibrosis, mimicking Sjogren's syndrome and Castleman's disease. However, the correlation of the clinical features with histopathological findings, IgG4 immunopositivity, and serum studies helped in clinching the diagnosis. This case presents an uncommon combination of clinical features infrequently reported in literature. Furthermore, and more importantly, it highlights the need to keep a differential of IgG4-RD in mind, to aid early and correct treatment of the disease. [ABSTRACT FROM AUTHOR]

Castleman's disease (CD) is a rare benign lymphoproliferative disorder with unknown etiology and pathogenesis. It presents in two identified clinical forms of unicentric or multicentric. The disease is usually found incidentally in the mediastinal or hilar region in asymptomatic patients. In unicentric CD, constitutional symptoms are uncommon, and they can be misdiagnosed as lung infections or malignancy. Although imaging studies are helpful, but definitive diagnosis can be made with pathologic examination. Complete surgical resection is the method of choice for treatment of localized CD, and the prognosis is excellent. In this study, we elucidate clinical features and therapeutic consequences of four cases of unicentric CD referred to our department and review the literature on the diagnosis and management of this relatively rare disorder. Because of the rarity of the disease and nonspecific signs and symptoms of CD it must be considered in differential diagnosis of pulmonary and mediastinal masses. [ABSTRACT FROM AUTHOR]