Follicular dendritic cell tumor: review of the entity.
Perez-Ordoñez B,Rosai J
Seminars in diagnostic pathology
Malignant neoplasms showing follicular dendritic cell differentiation are uncommon. Most reported cases have involved lymph nodes of the neck, mediastinum, and axilla. Approximately 30% of the cases were located in extranodal sites, such as liver, tonsil, and intra-abdominal soft tissue. Microscopically, follicular dendritic cell tumor is composed of oval to spindle cells with eosinophilic cytoplasm arranged in sheets, fascicles, and whorls, sometimes admixed with foci showing a storiform pattern of growth. The tumor cells are characteristically admixed with small lymphocytes. The tumor nuclei are oval to spindle, with thin nuclear membranes, small basophilic nucleoli, and clear or dispersed chromatin. Scattered multinucleated tumor cells are frequently seen. Necrosis, marked cellular atypia, high mitotic rate, and abnormal mitoses may occur and are harbingers of an aggressive behavior. The tumor cells typically express CD21, CD35, Ki-M4p, Ki-FDRC1p, and vimentin, with occasional positivity for S-100 protein, muscle-specific actin, and epithelial membrane antigen. Ultrastructural examination shows complex interdigitating cytoplasmic processes joined by desmosomes. The behavior of these tumors is more akin to that of a low-grade soft tissue sarcoma than a malignant lymphoma and is characterized by local recurrences in 36% of cases and metastases in 28%. A small proportion of cases have arisen against a background of Castleman disease of the hyaline-vascular type and others in association with Epstein-Barr virus infection. Complete surgical resection is the treatment of choice whenever feasible. Adjuvant radiotherapy or chemotherapy appears indicated in cases having adverse pathological features and in recurrent or incompletely resected lesions. Much still needs to be learned about the most effective adjuvant therapy and the molecular biology of these tumors.
Inflammatory pseudotumor-like follicular dendritic cell sarcoma of the spleen: a report of six cases with increased IgG4-positive plasma cells.
Choe Ji-Young,Go Heounjeong,Jeon Yoon Kyung,Yun Ji Yun,Kim Young A,Kim Hyun-Jung,Huh Jooryung,Lee Hojung,Shin Dong Hoon,Kim Ji Eun
Pathology international
Inflammatory pseudotumor (IPT)-like follicular dendritic cell (FDC) sarcoma is a rare neoplasm typically occurring in the spleen or liver. We present six cases of EBV(+) IPT-like FDC sarcoma of the spleen among Koreans along with their clinicopathologic features and IHC results. Most patients presented with an asymptomatic, incidentally detected single splenic mass and were successfully managed by splenectomy alone. Concomitant disease was found in one case, showing EBV(+) gastric carcinoma with lymphoid-rich stroma. Histologic features showed fibro-inflammatory lesions that were often accompanied by necrosis and epithelioid histiocytic collection, which are barely distinguishable from IPT. Tumor cells did not frequently express conventional FDC markers, including CD21 (3/6 positive cases), clusterin (4/6), and D2-40 (2/6), but showed uniform positivity for smooth muscle actin (SMA). Noticeably, significant numbers of IgG4(+) plasma cells were found within all six tumors. We suggest that the diagnosis of IPT-like FDC sarcoma should be made by the application of a panel of FDC markers, and CD21 negativity or SMA positivity cannot be the criterion for exclusion of IPT-like FDC sarcoma. Relationship of IPT-like FDC sarcoma of the spleen and IgG4-related sclerosing disease should be investigated in further studies.
10.1111/pin.12057
Follicular dendritic cell sarcoma of gastrointestinal tract with two emerging distinct subtypes: a case report and systemic review.
Diagnostic pathology
BACKGROUND:Follicular dendritic cell sarcoma (FDCS) is a rare neoplasm of mesenchymal origin. FDCS of gastrointestinal tract (GI) are exceedingly uncommon. CASE PRESENTATION:We report the first case of classic type FDCS in a 34-year-old male with Birt-Hogg-Dubé syndrome, which presented as a mass at the ileo-cecal junction. He received no further treatment after resection and remained disease free for 3.5 years. We further analyze and review the clinical and pathologic findings of 33 cases of GI tract FDCS reported in the literature. CONCLUSIONS:There are two distinct subtypes of FDCS in the GI tract: the classic type occurs in relatively younger patients (mean = 45.3 years) without Epstein-Barr virus (EBV) association, and behaves more aggressively; the inflammatory subtype presents as colonic polypoid tumor in older patients (mean = 60.7 years) and is EBV positive. The clinical outcome in the latter group appears favorable although mortality rate is not necessarily low.
10.1186/s13000-022-01246-z
Challenges in the Diagnosis of Epstein-Barr Virus-positive Inflammatory Follicular Dendritic Cell Sarcoma: Extremely Wide Morphologic Spectrum and Immunophenotype.
The American journal of surgical pathology
Epstein-Barr virus (EBV)-positive inflammatory follicular dendritic cell (FDC) sarcoma (EBV + IFDCS) is a rare entity, and its histopathological characteristics have not been fully described. Here, we investigated the wide morphologic spectrum and immunophenotype of this tumor with the aim to help avoid misdiagnosis. Thirteen cases of EBV + IFDCS were retrospectively analyzed, combined with a review of 70 cases reported in the literature. The median age of patients was 49 (range, 29 to 67 y). Six patients were male and 7 were female. Most cases (92.3%, 12/13) occurred in the liver or spleen, and only 1 case affected an extra-hepatosplenic site (lung, 7.7%, 1/13). Tumors were assessed for a variety of histologic features and assigned to the following morphologic groups: classic type (53.8%, 7/13), lymphoma-like subtype (38.5%, 5/13), and hemangioma-like subtype (7.7%, 1/13). The classic type had distinct EBV-positive neoplastic cells with a fascicular or storiform growth pattern, variable lymphoplasmacytic infiltrates, and blood vessels. The lymphoma-like subtype had extremely prominent lymphoplasmacytic infiltrates (resembling marginal zone lymphoma with plasmacytoid differentiation) with singly dispersed distinct EBV-positive neoplastic cells, highlighted by in situ hybridization for EBV-encoded small RNA. The hemangioma-like subtype had extremely prominent blood vessels with hyaline and/or fibrinoid degeneration, singly dispersed distinct EBV-positive neoplastic cells, and limited lymphoplasmacytic infiltrates. Immunohistochemically, the neoplastic cells showed variable staining for FDC markers (CD21, CD35, CD23, and SSTR2) and the fibroblastic marker SMA, with the staining ranging from very focal to extensive. The number of EBV-positive neoplastic cells ranged from 80 to 400/HPF. All cases showed variable expression of PD-ligand 1 (PD-L1) (CPS: 5-90). IgG4-positive cells ranged from rare up to 100/HPF. Interestingly, 2 cases satisfied the criteria proposed in a previous study, mimicking IgG4-related disease. EBV + IFDCS is an entity with an extremely wide morphologic spectrum and immunophenotype. Awareness of the spectrum of morphologic presentations of this rare tumor, specifically the lymphoma-like subtype and hemangioma-like subtype, is important for accurate diagnosis.
10.1097/PAS.0000000000002011
EBV-Positive Inflammatory Follicular Dendritic Cell Sarcoma of the Spleen: Report of an Aggressive Form With Molecular Characterization.
International journal of surgical pathology
EBV-positive inflammatory follicular dendritic cell sarcoma (EBV+ inflammatory FDCS) is a rare neoplasm almost exclusively located in the spleen or liver. It is characterized by a proliferation of EBV-positive spindle-shaped cells bearing follicular dendritic cell markers, associated with an abundant lymphoplasmacytic infiltrate. EBV+ inflammatory FDCS is often asymptomatic or responsible for mild symptoms. It usually displays an indolent course and its prognosis is excellent after tumor removal, although relapsing and metastatic forms exist. Herein, we describe an aggressive form of splenic EBV+ inflammatory FDCS in a 79-year-old woman presenting with abdominal pain, deterioration of general health status, major inflammatory syndrome, and symptomatic hypercalcemia. A splenectomy was performed leading to a rapid improvement in her clinical condition and normalization of laboratory abnormalities. Unfortunately, her symptoms and laboratory abnormalities reappeared 4 months later. Computed tomography showed a mass in the splenectomy site and multiple liver and peritoneal nodules. Further analyses were performed on tumor tissue and showed positive phospho-ERK staining of tumoral cells indicating activation of MAPK pathway. Inactivating mutations were found on and genes. Subsequently, the patient's condition deteriorated rapidly. Since interleukin-6 levels were dramatically increased, tocilizumab was used but only had a transient effect on the patient's symptoms and inflammatory syndrome. Antitumor agent gemcitabine was initiated but her clinical condition continued to deteriorate and the patient died 2 weeks later. The management of aggressive forms of EBV+ inflammatory FDCS remains challenging. However, since these tumors seem to display genetic alterations, better characterization could lead to molecular targeted therapies.
10.1177/10668969231168345
Case Report: Identification of a novel mutation in EBV-positive inflammatory follicular dendritic cell sarcoma.
Frontiers in oncology
EBV-positive inflammatory follicular dendritic cell sarcoma (EBV+ IFDCS) is an uncommon disease primarily observed in Asia. It is characterized by the development of tumors believed to originate from follicular dendritic cells (FDC). The consistent association between this condition and clonal EBV infection suggests EBV's involvement as an etiological factor. However, diagnosing EBV+ IFDCS can be challenging due to its morphological variability and diverse immunohistochemical staining patterns. The genetic characteristics of EBV+ IFDCS remain insufficiently understood. To address this knowledge gap, we present a case study of a 47-year-old male patient diagnosed with EBV+ IFDCS. We utilized a Next-generation sequencing (NGS) platform to investigate the genetic profile of the tumor cells. We identified a single pathogenic mutation (G618R) in the gene. This finding provides valuable insights into the genetic alterations associated with EBV+ IFDCS and potentially contributes to our understanding of the disease's pathogenesis.
10.3389/fonc.2023.1266897
Angioimmunoblastic T-cell lymphoma and Kaposi sarcoma: A fortuitous collision?
Histopathology
AIMS:Follicular helper T-cell (TFH) lymphoma of the angioimmunoblastic-type (AITL), one of the most prevalent T-cell lymphomas, typically encompasses proliferation of high endothelial venules and Epstein-Barr virus-positive immunoblasts, but neither infection with HHV8 nor association with Kaposi's sarcoma (KS) have been described. The aims of this study are to characterise the association between AITL and HHV8 infection or KS. METHODS AND RESULTS:Three male patients aged 49-76 years, HIV-negative, with concurrent nodal involvement by AITL and KS, were identified from our files and carefully studied. Two patients originated from countries where endemic KS occurs, including one with cutaneous KS. The lymphomas featured abundant vessels, expanded follicular dendritic cells and neoplastic TFH cells [PD1+ (three of three), ICOS+ (three of three), CXCL13+ (three of three), CD10 (two of three), BCL6 (two of three)] but lacked EBV+ immunoblasts. The foci of KS consisted of subcapsular proliferations of ERG+, CD31 and/or CD34 , HHV8+ spindle cells. High-throughput sequencing showed AITL-associated mutations in TET2 (three of three), RHOA (G17V) (three of three) and IDH2 (R172) (two of three), which were absent in the microdissected KS component in two cases. Relapses in two patients consisted of AITL, without evidence of KS. No evidence of HHV8 infection was found in a control group of 23 AITL cases. CONCLUSION:Concurrent nodal involvement by AITL and KS is rare and identification of both neoplastic components may pose diagnostic challenges. The question of whether the association between AITL and KS may be fortuitous or could reflect the underlying immune dysfunction in AITL remains open.
10.1111/his.15083
EBER-negative inflammatory pseudotumor-like follicular dendritic cell sarcoma of liver: A case report.
Medicine
RATIONALE:Inflammatory pseudotumor-like follicular dendritic cell sarcoma (IPT-like FDCS) of the liver is rare. It was previously believed that Epstein-Barr virus (EBV) positivity was a necessary criterion for pathological diagnosis. However, we found that there were also cases of EBV negativity. Therefore, clinicians and pathologists are reminded that EBV positivity is not a necessary condition for diagnosis. PATIENT CONCERNS:A 70-year-old female underwent computed tomography (CT) examination for upper abdominal discomfort, which revealed the presence of a liver tumor. Follow-up revealed that the tumor had progressively increased in size. DIAGNOSIS:The final diagnosis was an IPT-like follicular cell sarcoma, based on CT, MRI, HE staining, and immunohistochemical staining. INTERVENTIONS:The patient underwent a laparoscopic left hemihepatectomy. OUTCOMES:The patient has not undergone any special treatment, such as radiotherapy and chemotherapy, and has been followed up for over 3 years without experiencing any recurrence. LESSONS:IPT-like FDCS is a rare tumor that lacks definitive criteria, and its diagnosis mainly relies on pathological findings. Previously, it was believed that being EBV-positive was an important condition for diagnosis. Primary IPT-like FDCS in the liver is even rarer, and the patient in this case tested negative for EBV. It may be necessary for pathologists to consider the role of EBV in the diagnosis of IPT-like FDCS.
10.1097/MD.0000000000037651
EBV-positive inflammatory follicular dendritic cell sarcoma of the colon with clonal immunoglobulin gene rearrangement: A case report and literature review.
Heliyon
Introduction:Epstein-Barr virus-positive (EBV+) inflammatory follicular dendritic cell (FDC) sarcoma is a rare neoplasm characterized by spindle-shaped follicular dendritic cells, marked lymphoplasmacytic infiltration, and a consistent link to EBV. While it typically affects the liver and spleen, it is exceptionally rare in the digestive tract. We present a special case of EBV + inflammatory FDC sarcoma arising in the colon with clonal immunoglobulin (IG) gene rearrangement. Case presentation:A 70-year-old man presented with a one-month history of abdominal distension. Colonoscopy revealed a pedunculated polyp in the ascending colon, which was subsequently removed via endoscopic polypectomy. Histological examination of the colonic polyp demonstrated a pronounced lymphoplasmacytic infiltrate with scattered EBV + neoplastic cells, as evidenced by EBV-encoded small RNA in situ hybridization (EBER ISH). The neoplastic cells were positive for FDC-specific markers, including CD21, CD35, and CD23. Additionally, the tumor exhibited clonal rearrangement of the immunoglobulin heavy chain (IGH) gene. The diagnosis was confirmed as EBV + inflammatory follicular dendritic cell sarcoma. Conclusions:We described an exceptional case of EBV + inflammatory FDC sarcoma presenting as a colonic polyp, featuring a clonal IGH gene rearrangement not previously documented in this colonic tumor type. Heightened awareness of this rare neoplasm within the gastrointestinal tract is essential for both accurate diagnosis and effective patient management.
10.1016/j.heliyon.2024.e31947
Stroma-derived neoplasms and pseudoneoplastic lesions of the spleen: a select review of pathologic and CT/MRI findings.
Abdominal radiology (New York)
A wide spectrum of benign and malignant primary mesenchymal tumors and tumor-like lesions of the spleen has been recently included under the umbrella term 'stroma-derived' neoplasms and tumor-like lesions. These include dendritic cell neoplasms such as follicular dendritic cell sarcoma, EBV-positive inflammatory follicular dendritic cell sarcoma, and fibroblastic reticular cell tumor; smooth muscle and myofibroblastic lesions such as inflammatory pseudotumor, EBV-associated smooth muscle tumor and undifferentiated pleomorphic sarcoma as well as a diverse spectrum of vascular and vascular-stromal tumors and tumor-like lesions. While some tumor and tumor-like lesions are unique to the spleen, others may also occur in diverse extra-splenic viscera. These tumors and tumor-like lesions demonstrate characteristic histopathology, immunocytochemistry and biological behavior. While cross-sectional imaging studies allow detection, staging and limited characterization of these splenic lesions, histopathological confirmation permits optimal management and surveillance strategies.
10.1007/s00261-024-04461-y
A rare case of an EBV-positive inflammatory follicular dendritic cell tumor of the spleen.
Journal of surgical case reports
Epstein-Barr virus positive inflammatory pseudotumor follicular dendritic cell sarcoma (EBV+ FDCS) is a rare indolent neoplasm that presents primarily in the spleen and liver. We display a case of EBV+ FDCS in the spleen, its clinic-pathologic properties, and treatment. Our patient was evaluated following an incidental finding of a splenic mass on imaging after a traumatic injury. Computed tomography and magnetic resonance imaging both confirmed a well-circumscribed lesion in the spleen. Consequently, the patient underwent a robotic-assisted diagnostic splenectomy. Histologic examination revealed portions of spleen with partial effacement of tissue architecture by a well-circumscribed nonencapsulated mass displaying atypical, spindled cells-positive for EBER (CISH), EBV LMP1, smooth muscle actin, and clusterin-mixed inflammatory elements, and interspersed small lymphocytes.
10.1093/jscr/rjae600
Uncommon granulomatous manifestation in Epstein-Barr virus-positive follicular dendritic cell sarcoma: a case report.
Journal of pathology and translational medicine
Hepatic Epstein-Barr virus-positive inflammatory follicular dendritic cell sarcoma (EBV+ IFDCS) represents a rare form of liver malignancy. The absence of distinct clinical and radiological characteristics, compounded by its rare occurrence, contributes to a challenging diagnosis. Here, we report a case of a 54-year-old Chinese female with a background of chronic hepatitis B virus treated with entecavir and complicated by advanced fibrosis presenting with a liver mass found on her annual surveillance ultrasound. Hepatectomy was performed under clinical suspicion of hepatocellular carcinoma. Immunomorphologic characteristics of the tumor were consistent with EBV+ IFDCS with distinct non-caseating granulomatous inflammation. Our case illustrates the importance of considering EBV+ IFDCS in the differential diagnosis of hepatic inflammatory lesions. Awareness of this entity and its characteristic features is essential for accurately diagnosing and managing this rare neoplasm.
10.4132/jptm.2024.09.27
Clinicopathological and molecular genetic insights into EBV-positive inflammatory follicular dendritic cell sarcoma.
Human pathology
Epstein-Barr virus (EBV)-positive inflammatory follicular dendritic cell (FDC) sarcoma (EBV + IFDCS) is a rare entity, and its histopathological characteristics have not been fully described. This study aimed to investigate the clinical characteristics, pathological features, and molecular genetic profiles of EBV + IFDCS to improve our understanding of these lesions. A total of 12 EBV + IFDCS specimens were obtained from patients in our pathology diagnostic center. The clinical data, morphology, immunohistochemistry, in situ hybridization, and high-throughput DNA-targeted sequencing data were collected, and follow-up data were analyzed. These data were compared with those of 6 patients with traditional FDCS. The patients with EBV + IFDCS ranged from 21 to 84 years old, with a mean age of 52.3 years and a male-to-female ratio of 1:5. At the last follow-up, all patients were alive, with 2 experiencing recurrence and metastasis. In these cases, four were classified as the classical subtype, four as the angiomatoid/sclerosing subtype, and four as the lymphoma-like subtype, with two cases also exhibiting epithelioid granulomas. All patients exhibited heterogeneous expression of follicular dendritic cell markers (CD21, CD23, CD35, and CXCL13) alongside the fibroblast marker SMA, with significantly higher expressions of IgG4, EBER, and SMA in EBV + IFDCS patients compared to FDCS patients (P < 0.05). Conversely, SSTR2, EGFR, and STAT3 expression were significantly lower in the EBV + IFDCS group (P < 0.05). The average value of EBER was significantly higher in the classical subtype group (P = 0.022). Among the four cases of EBV + IFDCS analyzed for molecular genetic features, one patient exhibited germline mutations in the CDKN1C, PDGFRA, MSH2, FANCG, MLH1, ALK, and RUNX1 genes; three exhibited simultaneous SNP variations in the MTHFR gene; and two exhibited simultaneous SNP variations in the NQO1 gene. We conducted KEGG pathway analysis on the mutant genes, revealing significant enrichment in the cAMP signaling pathway, which plays a crucial role in tumor development. Survival analysis demonstrated that the median PFS rates were not reached (NR) for EBV + IFDCS patients, compared to 5 months (HR = 7.76) for FDCS patients. The 3-year PFS rates were 66.67% and 16.67%, respectively. Compared with the FDCS group, EBV + IFDCS patients had a significantly longer median PFS time (p < 0.05). In conclusion, EBV + IFDCS represents a group of tumors with unique clinical, morphological, immunological, prognostic, and molecular cytogenetic characteristics.
10.1016/j.humpath.2024.105668