Epstein-Barr virus-positive inflammatory follicular dendritic cell sarcoma (EBV+ IFDCS), recently reclassified in the 5th edition of the WHO classification of lymphoid neoplasms, is a rare mesenchymal and dendritic cell tumor distinct from conventional follicular dendritic cell sarcoma (FDCS) in cellular origin and clinicopathological features. To address this, we present the largest sequencing cohort of EBV+ IFDCS to date, combining targeted next-generation sequencing (NGS) of 12 cases and whole-exome sequencing (WES) of 3 cases. This study aims to elucidate the molecular characteristics of EBV+ IFDCS to better understand its pathogenesis and identify potential therapeutic targets. 12 EBV+ IFDCS cases were analyzed using next-generation sequencing (NGS) with a 506-gene panel, and whole-exome sequencing (WES) was performed on 3 cases. The analysis focused on identifying copy number variations (CNVs), gene fusions, and pathogenic mutations. KEGG pathway analysis was conducted to explore enriched oncogenic pathways. CNV analysis via WES identified focal chromosomal deletions in 2 of 3 cases: 7p and 14q deletions in Case 1, and 17p deletion plus deep deletions in NPRL2 (chromosome 3) and STK11 (chromosome 19) in Case 6. While pathogenic/drug-sensitive SNVs varied across the 12 patients (Fig.2). Only Patient 3 (48-year-old female, splenic classical subtype EBV+ IFDCS) was TMB-H (11.2 mutations/Mb, ≥ 10 mutations/Mb as threshold), harboring NQO1 p.P187S (VAF = 32.6%) and a germline PKHD1 Class 3 VUS. This case had no unique somatic mutations vs. low-TMB cases, with histological features (fascicular spindle cells, moderate lymphoplasmacytic infiltration) consistent with the classical subtype (Fig.1A). KEGG pathway analysis revealed enrichment in PI3K-AKT, cell cycle, Notch, and EBV infection pathways. WES of Patients 1, 6, 10 showed TMB-L (1.8-3.5 mutations/Mb); Patient 3's TMB-H (11.2 mutations/Mb, ≥ 10 mutations/Mb as solid tumor threshold) was validated via targeted NGS (723× coverage). WES of TMB-L cases revealed predominant missense mutations/SNVs (C > T transitions: 50% of SNPs, Fig.5C), with 3-9 somatic mutations per case and no shared mutations-highlighting potential potential high tumor heterogeneity, further supported by Patient 3's unique TMB-H phenotype. This study reveals the unique molecular landscape of EBV+ IFDCS, characterized by frequent NQO1 mutations and activation of key oncogenic pathways. These findings provide critical insights into the tumor's pathogenesis and suggest potential molecular targets for future therapeutic strategies.

Amplification and Overexpression of Cyclin D1 in Epstein-Barr Virus-Positive Inflammatory Follicular Dendritic Cell Sarcoma: A Targeted Next-Generation Sequencing Study.

Intrahepatic neoplastic lesions with prominent inflammatory background (HNLwPIBs) constitute a heterogeneous group of entities that frequently pose substantial diagnostic challenges because of overlapping morphological features. To characterize their clinicopathological spectrum, diagnostic pitfalls, and key distinguishing clues, we retrospectively analyzed 60 cases of HNLwPIBs diagnosed at our institution over a 11-year period (2015-2025). The cohort comprised 8 distinct entities, including lymphoepithelioma-like cholangiocarcinoma (LEL-ICC), lymphocyte-rich hepatocellular carcinoma (LR-HCC), inflammatory angiomyolipoma (IAML), inflammatory pseudotumor (IPT) versus inflammatory myofibroblastic tumor (IMT), EBV-positive inflammatory follicular dendritic cell sarcoma (EBV+IFDCS), EBV-positive diffuse large B-cell lymphoma (EBV+DLBCL), pseudolymphoma (PL), and mucosa-associated lymphoid tissue extranodal marginal zone B-cell lymphoma (MALT lymphoma). Each entity showed characteristic morphologic and immunophenotypic features that supported accurate classification when systematically integrated. Several diagnostically challenging patterns were identified. One case of LEL-ICC showed well-differentiated glandular structures mimicking pseudolymphoma. Another case of EBV+IFDCS contained sparse inflammatory infiltrates and predominant spindle cell proliferation, resulting in potential misdiagnosis as a mesenchymal neoplasm. One IPT vs. IMT case demonstrated marked IgG4-positive plasma cell infiltration, raising the concern of IgG4-related disease. We also encountered a rare presentation of EBV+DLBCL with spindle cell morphology and focal follicular dendritic cell marker expression, closely simulating EBV+IFDCS. Our findings highlight critical morphologic and immunophenotypic distinctions among these diagnostically challenging lesions and provide practical strategies to avoid common pitfalls. These findings support a structured, morphology-driven diagnostic approach integrating EBER status, immunophenotype, and molecular testing to improve diagnostic precision in this challenging group of lesions.

Paraneoplastic pemphigus is a rare and fatal autoimmune mucocutaneous blistering disease associated with underlying tumors. We describe FDG PET/CT findings in a case of paraneoplastic pemphigus associated with pelvic follicular dendritic cell sarcoma transformed from Castleman disease. FDG PET/CT showed intense activity in the oral cavity, diffuse, heterogeneous activity in the skin, linear activity in the upper esophagus, focal activity in the anus, and heterogeneous activity in the pelvic tumor. This case indicates that paraneoplastic pemphigus should be considered as a differential diagnosis in patients with hypermetabolic mucocutaneous lesions.

ABSTRACTParaneoplastic pemphigus (PNP) is a life‐threatening autoimmune blistering disease with a mortality rate of 70%–90%, driven largely by respiratory complications such as bronchiolitis obliterans. Managing respiratory failure in these patients remains exceptionally difficult. We report a 33‐year‐old male with follicular dendritic cell sarcoma who developed severe PNP complicated by type II respiratory failure and obstructive bronchiolitis requiring veno‐venous extracorporeal membrane oxygenation (ECMO) support. The patient's PNP skin lesions improved during a treatment course that included ECMO support, intravenous immunoglobulin (IVIG), immunosuppressants, hemodialysis, and plasma exchange. Serial immune cell subset monitoring showed a rising CD4/CD8 ratio (+94.8%) and Helper T cells (+33.8%), alongside declining NK cells (−48.2%), T lymphocytes (−17.7%), and Suppressor T cells (−31.6%). This case illustrates successful short‐term management of severe PNP with respiratory failure through multidisciplinary care, including ECMO. Because multiple interventions were administered concurrently, improvement cannot be attributed to any single therapy. Serial immune‐cell monitoring may help track treatment response in this setting.

Primary colonic Epstein-Barr virus-positive inflammatory follicular dendritic cell sarcoma (EBV+ iFDCS) is a rare, poorly characterized neoplasm. This study aims to delineate its clinicopathological features and thereby facilitate accurate diagnosis. This study retrospectively analyzed 14 cases of primary colonic EBV+iFDCS and conducted a systematic review of 18 additional cases from the literature. The median age was 51 years (range, 35-68 years), with 10 females and 4 males. All cases were confined to the colon, with the transverse colon as the most common site (50%, 7/14), followed by the descending colon (28.6%, 4/14), sigmoid colon (14.3%, 2/14), and ascending colon (7.1%, 1/14). The vast majority of cases (85.7%, 12/14) were asymptomatic and were incidentally detected during routine physical examinations. Endoscopically, the tumors presented as either pedunculated polyps (9 cases) or sessile polypoid lesions (5 cases) with surface congestion. Their histology was characterized by mucosal erosion, prominent superficial perpendicular vessels, and secondary lymphoid follicular (SLF)hyperplasia. Neoplastic spindle cells were arranged in scattered and fascicular patterns within a background of plasma cells and small lymphocytes. Morphological subtypes comprised classic/lymphoma-like mixed type (64.3%, 9/14) and lymphoma-like type (35.7%, 5/14). Tumor cells expressed multiple FDC markers (CD21, CD23, CD35), co-expressed SMA (100%, 13/13) and CD56 (100%, 12/12), while SSTR2 was typically negative or only weakly expressed. The microenvironment was characterized by a B-cell predominance. EBV-encoded RNA was detected in perivascular and interfollicular tumor cells, with positivity also in germinal center FDCs. Clonality assays were negative in all but two cases (one case each with TCR rearrangement and IG rearrangement). All patients were underwent endoscopic submucosal resection, with no recurrence or major complications. Primary colonic EBV+iFDCS is a distinct, low-grade malignant neoplasm that typically presents as polyp or polypoid lesion. Its hallmark histologic features include a characteristic arrangement of vessels and SLFs in a prominent lymphocytic background. The tumor exhibits a dual immunophenotype, expressing markers of both FDCs and follicular reticular cells. Because the disease follows an indolent clinical course with a favorable prognosis, accurate diagnosis is essential to avoid overtreatment.

Follicular dendritic cell sarcoma (FDCS) is a rare neoplasm that usually occurs in the adult population. Since its first description, only 9 cases have been reported in children. Due to its rarity, there is no standardized treatment. We present a case of multiply-relapsed FDCS in an adolescent patient that responded favorably to chemotherapy. For many, wide local excision of FDCS may be curative. However, more research is required to determine the best course of treatment for patients requiring adjuvant chemotherapy or radiation. In addition, expanding genetic research has the potential to provide targeted therapy in the future.

Follicular dendritic cell sarcoma (FDCS) is a rare malignant neoplasm commonly found in extranodal sites with unclear pathogenesis. Tumor cells typically exhibit a spindled morphology, whereas epithelioid morphology is rarely reported. Here, we have presented a rare biphasic FDCS with distinct immunophenotypic and molecular characteristics. A 63-year-old female presented with constipation and rectal bleeding. Imaging revealed an 11.4cm lobulated enhancing soft tissue mass in the posterior pelvis. H&E sections revealed 2 sharply demarcated biphasic neoplastic populations: one population comprised spindled cells expressing CD21, CD23, CD35, clusterin, EMA, and D2-40; the other population consisted of epithelioid cells lacking CD21 and other FDC-associated markers except for focal weak clusterin expression. Both populations tested negative for CD163, CD68, S-100, langerin, CD1a, ALK-1, CD30, CD117, HMB45, Pan-CK, and EBER. The tumor was initially misdiagnosed as a collision (FDCS and perivascular epithelioid cell tumor) tumor. Molecular studies revealed a nearly identical mutational profile in both components confirming clonal identity and ruling out a composite tumor. In addition, low-level pathogenic mutations (variant allele frequency <10%) were found in GABRA6 , ICOSLG , and VEGFA , alongside altered transcript expression in PDGFRB in both populations. Although no RNA fusions were detected, we demonstrated a significant increase in PDGFRB expression using the RNA Salah Targeted Expression panel, with a log 2 ratio > 2, indicating a more than 4-fold increase compared with a pooled normal control. Here, we have provided molecular characterization of biphasic FDCS. Prior such characterization seems to be unavailable in the literature.

Follicular dendritic cell sarcoma (FDCS) is a rare neoplasm with morphologic and phenotypic features resembling those of normal follicular dendritic cells (FDCs). FDCS has been classified into two distinct entities based on their association with Epstein-Barr Virus (EBV): classic FDCS (cFDCS) and EBV-positive inflammatory FDCS (EBV + IFDCS). Diagnosis relies on characteristic histopathology and immunohistochemistry using FDC markers and EBV in situ hybridization (EBER). This study aimed to compare the clinical presentations, histologic features, and immunoprofiles between these two entities in a Taiwanese cohort. We retrospectively reviewed histological features of in-house and consultation cases of FDCS. Immunohistochemistry with novel markers including serglycin (SRGN), FDC-secreted protein (FDCSP) was applied, together with conventional FDC markers (CD21, CD23, CD35) and EBER. Programmed death ligand-1 (PD-L1), a potential therapeutic marker, was additionally evaluated and scored. Clinical and histological parameters, inflammatory cell infiltration, mitotic rate, and PD-L1 tumor proportion score (TPS) were compared statistically. We identified 30 patients including 16 cFDCS and 14 EBV + IFDCS. The median age was 56years old (range, 22-80), with a female preponderance in EBV + IFDCS. EBV + IFDCS occurred exclusively in extra-nodal sites, while cFDCS more commonly involved lymph nodes. EBV + IFDCS showed significantly higher PD-L1 TPS (p = 0.012), more prominent inflammatory cell infiltration (90.0% vs. 12.5%, p < 0.001) in the presence of germinal centers (50% vs. 6%, p = 0.012), and lower mitotic activity (0.5 vs. 2.5/10 HPFs, p = 0.002). We identified distinct clinical and histologic features, as well as differential PD-Ll expression between cFDCS and EBV + IFDCS, supporting their classification as separate entities. Further molecular studies are needed to investigate their pathogenesis.

Follicular dendritic cell sarcoma (FDCS) of the duodenum is extremely rare. We describe the contrast-enhanced CT and FDG PET/CT findings in a case of duodenal FDCS. Contrast-enhanced CT revealed a large, irregular mass originating from the horizontal portion of the duodenum. The mass demonstrated heterogeneous enhancement, with internal areas of low-attenuation necrosis and coarse calcifications. The mass showed significantly increased FDG uptake. The patient underwent surgical resection, and histopathologic examination revealed a spindle cell tumor positive for CD21 and CD35, confirming the diagnosis of FDCS.

Clinicopathological characteristics of intra-abdominal follicular dendritic cell sarcomas: a multicenter real-world study

Clinicopathological features of hepatic Langerhans cell histiocytosis: report of ten cases and review of the literature.

Hepatic Epstein-Barr virus-positive inflammatory follicular dendritic cell sarcoma (EBV+IFDCS) is an extremely rare low-grade malignant tumor. Due to its rarity and lack of specific symptoms, laboratory markers, or characteristic imaging features, this disease is frequently misdiagnosed. A 50-year-old woman was diagnosed with left hepatic mass and underwent laparoscopic left hemihepatectomy. The postoperative histopathology confirmed EBV+IFDCS. To our knowledge, we conducted the first-ever genetic testing for hepatic EBV+IFDCS. The analysis indicates that the patient has a low tumor mutational burden and low microsatellite instability, with no identifiable targetable gene mutations, but may have potential sensitivity to certain chemotherapy agents. Postoperatively, the patient was empirically treated with six cycles of S-1 chemotherapy (60 mg twice daily, 2 weeks on/1 week off), and the recovery process was uneventful. We hope that our findings may contribute to the understanding and clinical management of this disease. Not applicable.

1262 Genomic landscape of Follicular Dendritic Cell Neoplasms and molecular differences in Follicular Dendritic Cell Sarcoma with and without hyaline vascular Castleman Disease

1148 Epstein-Barr Virus-Positive Inflammatory Follicular Dendritic Cell Sarcoma: Case Series of Six Patients with Unique Clinicopathologic Profiles

Follicular dendritic cell sarcoma (FDCS) is a rare, aggressive malignant neoplasm usually arising in lymph nodes of the head and neck, but it can also occur at extranodal sites (ENFDCS). Due to its rarity, optimal management is not well defined, underscoring the need for further research. We conducted a retrospective analysis of patients with histologically confirmed ENFDCS treated in the gastrointestinal oncology unit of a tertiary cancer center. Clinical features, treatments, and outcomes were reviewed. Fourteen patients (10 males, 4 females; median age 41 years) were included. Primary sites were colon (n = 6), retroperitoneum (n = 3), rectum (n = 2), mesentery (n = 1), liver (n = 1), and pelvis (n = 1). Four tumors (28.6%) were initially misdiagnosed. Final diagnosis was based on morphology and immunohistochemistry for CD21, CD23, and CD35; Epstein-Barr virus testing was not performed. Five patients underwent primary surgery at our center; two patients with metastatic disease at presentation received systemic therapy alone. Among the five primary surgeries, three were preceded by perioperative chemotherapy (n = 1), neoadjuvant chemotherapy (n = 1), or neoadjuvant radiotherapy (n = 1). Seven patients presented with residual or recurrent disease after prior surgery elsewhere; three underwent re-resection following appropriate systemic therapy, and four received only systemic therapy. At a median follow-up of 26 months (range 7-153), median overall survival was not reached, and median disease-free survival was 24 months. Four of five patients primarily operated at our center remained disease free; one recurred at 39 months, was successfully treated with re-resection and systemic therapy, and was alive at 153 months. Of the three patients re-resected at our center, one remained disease free at 17 months, one developed systemic recurrence and eventually received best supportive care at 11 months, and one was disease free until 94 months before being lost to follow-up. Overall, 10 patients were alive, two died of disease progression, and two were lost to follow-up. ENFDCS is frequently misdiagnosed; surgery is the cornerstone of treatment, and multimodality therapy for recurrences can yield durable survival. Outcomes appear better when patients are managed at specialized oncologic centers, highlighting the importance of early recognition and timely referral.

A Rare Case of Follicular Dendritic Cell Sarcoma Masquerading as Ovarian Sex Cord Stromal Tumor

Follicular dendritic cell sarcoma (FDCS) is a rare mesenchymal neoplasm arising from the follicular dendritic cells (FDC) of lymphoid follicles. FDCS can be found in nodal and extranodal sites. In this report, we present an unusual case of pleura-based FDCS with epithelioid cytology and aberrant expression of cytokeratins, including discussion of differential diagnosis. A comprehensive panel of immunohistochemical (IHC) stains was performed. Additionally, fluorescence in situ hybridization, allele-specific quantitative polymerase chain reaction, and next-generation sequencing assays were utilized to detect somatic gene mutations and potential fusions. This case of FDCS reveals predominantly epithelioid cytology with a focal spindle cell component. Upon IHC staining, both the epithelioid and spindle cells are positive for FDC markers, including CD21, CD23, CD35, clusterin, CXCL13, and podoplanin. Particularly, both components show aberrant expression of cytokeratin (CK) AE1/3 and CAM5.2. Molecular genetic studies detected a splice site alteration of RB1 gene without other significant changes. FDCS is a rare neoplasm with variable morphologic and staining patterns. To the best of our knowledge, this is the first reported instance of pleura-based FDCS with epithelioid morphology and aberrant expression of cytokeratins. Diagnosis of such cases can be challenging, which has to be separated from the morphologic mimicries, particularly carcinoma and mesothelioma.

Epstein-Barr virus (EBV)-positive inflammatory follicular dendritic cell sarcoma (EBV+ IFDCS) is a rare, indolent malignant neoplasm. Due to its rarity, a comprehensive assessment of its immunophenotypic spectrum and molecular analysis is still lacking. This study aimed to characterize the immunophenotypic and genetic alterations of EBV+ IFDCS to improve understanding of its cell of origin and molecular pathogenesis and to identify potential therapeutic targets. Immunohistochemical staining for a panel of follicular dendritic cell (FDC) and fibroblastic reticular cell (FRC) lineage markers, along with targeted next-generation sequencing, was performed. Nineteen cases of EBV+ IFDCS were classified into four immunophenotypes: nine FDC, two FRC, three biphasic and five null phenotypes. Morphologically, cases with a null phenotype more frequently exhibited a lymphoma-like growth pattern (4/5, 80%) compared with those with a definite FDC and/or FRC phenotype (1/14, 7.1%, P = 0.006). Moreover, a scattered distribution of neoplastic cells was more commonly observed in null phenotype cases (4/5, 80%) than in FDC and/or FRC phenotype cases (3/14, 21.4%, P = 0.038). Targeted sequencing revealed somatic variants in chromatin modifier-related genes in 60.0% (9/15), homologous recombination repair (HRR)-related genes in 53.3% (8/15) and Hippo pathway-relatedgenes (FAT2 and FAT1) in 26.7% (4/15) of cases. These findings demonstrate the wide morphological and immunophenotypic spectrum of EBV+ IFDCS. Furthermore, variants in chromatin modifier and HRR-related genes may participate in its pathogenesis, and PARP inhibition may represent a potential therapeutic strategy for patients with unresectable disease.

Diseases caused by immune system disorders fall under the care of every medical specialty. In hematology, these are diseases caused by autoantibodies, several autoinflammatory diseases (Schnitzler syndrome and VEXAS syndrome), as well as immune disorder-induced diseases presenting with systemic inflammatory reactions and lymphadenopathy. In the 5th edition of the WHO classification, these diseases are categorized under the chapter "Tumour-like lesions with B-cell predominance", which includes Castleman disease (CD). This paper provides an overview of information on CD from the perspective of the years 2025 and 2026. In patients with unicentric CD (UCD), associations with paraneoplastic pemphigus or obliterative bronchiolitis have been described in rare cases. Prognostically unfavorable is the transformation of UCD into a follicular dendritic cell sarcoma. In cases of multicentric CD (MCD), the etiology is exceptionally identified as an infection with human herpesvirus 8. In rare cases of MCD combined with POEMS syndrome, the etiology is considered to be a monoclonal gammopathy. In most cases of MCD, none of the aforementioned etiologies are demonstrated, and these forms of MCD are referred to as idiopathic MCD (iMCD). The most aggressive form of iMCD is called iMCD-TAFRO, and its course resembles a cytokine storm. The form with the lowest aggressiveness was defined recently - idiopathic plasmacytic lymphadenopathy (iMCD-IPL) with a high concentration of polyclonal immunoglobulins and a higher concentration of the IgG4 subclass of immunoglobulins. Between these two extreme forms lies the majority of cases falling into the iMCD-NOS (not otherwise specified) category. Differences in the aggressiveness are caused by differences in etiopathogenesis. The text presents recent criteria for these diseases, information on symptoms, diagnosis, and prognosis. In MCD, suspicion must be raised in individuals with a systemic inflammatory response and lymphadenopathy after ruling out autoimmune, malignant, and infectious etiologies. Diagnosis of CD is clinico-pathological, meaning it arises based on the exchange of information between the clinician, who must suspect the disease, and the pathologist, who examines the histomorphological findings while taking into account the information provided by the clinicians.