Follicular Dendritic Cell Tumor Research Articles

HPB P52 Castleman Disease in Hepato-pancreaticobiliary Surgery: Friend or Foe?

Abstract Background Castleman disease is a rare lymphoproliferative disorder with low malignant potential. It is associated with risk of lymphoma & follicular dendritic cell tumours. The disease is poorly understood and is well noted in literature, the difficulty in reaching to a diagnosis. While the systemic form of the disease is a subject of Hematological work up, the unifocal disease usually consists of radiologically detected retro-peritoneal or mesenteric masses posing diagnostic challenge to hepato-pancreatico-biliary surgeons. Methods Over a period of 12 years, from 2011 till 2023, in our institution we have identified 4 cases of Castleman disease. Median age of is 60 yo with equal incidence in both sexes. In our series, in all four cases, the diagnosis was incidental while they were being worked up for other conditions. In fact, in 1 case the diagnosis was unexpected after surgery for other reason. Extensive work up including cross-sectional imaging studies failed to reach a diagnosis, therefore, the latter was established by excision. Results All four patients underwent resection that accomplished diagnosis.Three patients underwent surgery for primary excision of the tumour located in various sites of upper abdomen; one para-duodenal, one retro-hepatic and one aorto-caval. In one case, the nodule was a FDG-PET avid mesenteric mass resected in the context of planned Whipple’s procedure for cancer. The Histopathological examination confirmed diagnosis in all cases. Haematology follow-up was recommended in two cases one of which progressed to follicular dendritic cell tumor. All patients were HIV negative and HHV-8 negative. The longest follow-up is 12 years with no evidence of recurrence. Conclusions Castleman’s disease is a rare entity with very low malignant potential. Cases with unifocal disease in upper abdomen are referred to Hepato-pancreato-biliary surgeons and resection is the treatment of choice. The latter allows histopathological analysis establishing the diagnosis. This case series is useful to all HPB surgeons who may come across this diagnostic challenge for this poorly understood pathology.

Extranodal Mesenteric Follicular Dendritic Cell Sarcoma Expressing Keratin Antigens: What Pitfalls Initiate Diagnostic Clues.

Extranodal follicular dendritic cell sarcomas are infrequent diagnostically challenging tumors. Because of their rarity, heterogeneous histomorphologic features and variable histologic grades a significant number of extranodal lesions are prone to be misdiagnosed. Even though they have a characteristic immunoprofile, expression of a range of nonspecific markers is well documented. Even though they are typically negative for keratins, few authors have reported lesions expressing keratin. Keratin expressing tumors are more likely to be misinterpreted by pathologists further deterring their inclusion in the differential diagnosis. We report an intraabdominal mesenteric follicular dendritic cell sarcoma in a 44-year-old male that immunophenotypically expressed keratin antigens. The lesion showed a high-grade pleomorphic epithelioid appearance and the initial differential diagnosis included lymphoma, sarcomas, melanoma, and carcinomas. Follicular dendritic cell sarcoma was not considered. Expression of epithelial membrane antigen and keratin further deterred the diagnosis which was reached only after extensive use of immunomarkers. The tumor cells expressed CD21, CD23, and D2-40. Morphologically, the tumor showed some thymoma-like features with occasional TDT-expressing background T-lymphocytes. These features were hints to reconsider our differential diagnosis to include follicular dendritic cell tumors. Awareness of this aberrant staining of epithelial immunomarkers and attention to certain clues should encourage pathologists to consider this entity. Speculative assumptions may explain this unusual keratin expression in some lesions. The histomorphologic and immunohistochemical heterogeneity may suggest different variants and grades of follicular dendritic cell sarcomas. The prevalence, importance, and histogenesis of keratin expression in follicular dendritic cell sarcomas warrant further studies.

Follicular dendritic cell sarcoma.

SummaryFollicular dendritic cells (FDC) are mesenchymal-derived dendritic cells located in B-follicles where they play a pivotal role in triggering and maintaining B-cell adaptive immune response. In 1986 Dr. Juan Rosai first reported a series of neoplasms showing features of FDC and defined it as Follicular Dendritic Cell Tumor, subsequently renamed as “sarcoma” (FDCS). In its seminal and subsequent articles Rosai and colleagues highlighted the heterogeneous microscopic appearance of FDCS and its immunohistochemical and ultrastructural features.FDCS mostly occurs in extranodal sites (79.4% of cases) and lymph nodes (15.1%); in about 7%-10% of cases it is associated with hyaline-vascular Castleman disease. Given its significant growth pattern and cytological variability, FDCS can be confused with various neoplasms and even inflammatory processes. The diagnosis requires the use of a broad spectrum of FDC markers (e.g. CD21, CD23, CD35, clusterin, CXCL13, podoplanin), particularly considering that tumor antigen-loss is frequent. The inflammatory-pseudotumor-like (IPT-like) variant of FDCS, in addition to its peculiar histopathological and clinical features, is characterized by positivity of tumor cells for Epstein-Barr virus, representing a diagnostic requisite.No distinctive genetic and molecular anomalies have been identified in FDCS. It often carries an aberrant clonal karyotype and chromosomal structural alterations, frequently involving onco-suppressor genes. Direct or next generation sequencing showed alterations on genes belonging to the NF-κB regulatory pathway and cell-cycle regulators. In contrast to hematopoietic-derived histiocytic and dendritic cells tumors, FDCS typically lacks mutations in genes related to the MAPK pathway.FDCS recurs locally in 28% and metastasizes in 27% of cases. Extent of the disease, surgical resectability and histopathological features are significantly associated with the outcome. IPT-like FDCS behaves as an indolent tumor, even if it often recurs locally over years.Complete surgical excision is the gold standard of treatment. Data on targeted therapies (e.g.: tyrosine kinase inhibitors) or immune checkpoint inhibitors are very limited and responses are variable. A better understanding of the molecular drivers of this tumor may lead to potential new therapeutic strategies.

Follicular dendritic cell tumor in the context of a Castleman disease in a patient with Diffuse Large B Cell Lymphoma: Diagnosis and follow-up with 18F-FDG PET/CT

Follicular dendritic cell tumor in the context of a Castleman disease in a patient with Diffuse Large B Cell Lymphoma: Diagnosis and follow-up with 18F-FDG PET/CT

Radiological features of follicular dendritic cell tumor of spleen

Objective To summarize the radiological features of follicular dendritic cell tumor of spleen (FDCS). Methods The clinical, radiological and pathological data of 8 patients from November 2011 to November 2017 in 5 hospitals with FDCS confirmed by pathology were retrospectively analyzed. All patients underwent CT examinations including plan and enhanced CT. Three patients underwent additional MRI and two patients underwent PET-CT examinations simultaneously. The imaging features such as location, number, shape, boundary, size, internal structure, density (or signal, 18F-fluorodeoxyglucose uptake), enhancement model and the relationship with surrounding structures were observed and compared with pathological results. Results Of the 8 patients with FDCS, 7 were located in the spleen and 1 was located in the spleen of the ectopic spleen of the pancreas. Seven patients with splenic FDCS underwent splenectomy and 1 patient with pancreatic ectopic spleen FDCS underwent resection of the pancreas. Multiple lesions were detected in 1 case, while single in the others. Tumor was round or oval. The tumors were well-circumscribed and presented as expansive growth. On unenhanced CT, the tumors showed a slightly lower density, and hemorrhage and necrosis could be detected in 6 lesions. Calcification was seen in 1 case, significant necrosis, and cystic change was presented in the pancreatic ectopic spleen FDCS. The solid part presented isointensity or slightly hypointensity on T1WI, and hyperointensity on T2WI. Cystic necrosis areas were hypointensitive on T1WI, and hyperointensitive on T2WI. Spoke-like areas with hypointensity on T1WI and hyperointensity on T2WI were detected in the center of the solid part with the distribution among the substantial degenerative and necrotic regions. PET-CT showed that the 18F-fluorodeoxyglucose was uptaked obviously. The enhancement CT showed that at the arterial phase, the tumors were markedly enhanced and continuously enhanced at portal vein phase and balance phase. Multiple liver metastases were detected in 1 case with huge FDCS. One patient was followed up for 6 years, and gastric lymphoma was detected. The others were followed up for 6 to 53 months, there remained no transfer or recurrence. Conclusions The features of FDCS of spleen mainly manifest as solid or cystic mass with clear solitary sphenoma accompanied by scarring, calcification and hemorrhage. The enhancement mode is persistent enhancement. MRI and PET-CT help to further reflect the tumor pathological basis and biological characteristics. Key words: Splenic neoplasms; Follicular dendritic cell sarcoma; Tomography, X-ray computed; Magnetic resonance imaging

Clinicopathologic features and prognosis of mantle cell lymphoma: an analysis of 349 cases

Objective: To investigate clinicopathologic features and prognostic factors of mantle cell lymphoma(MCL). Methods: The clinical data of 349 MCL patients diagnosed at Beijing Friendship Hospital from January 2004 to January 2016 were retrospectively collected. Corresponding histological sections were reviewed. Additional studies included immunohistochemical staining using the MaxVision two-step method, IgH/CCND1 fusion gene detection by fluorescent in situ hybridization (FISH), and correlative statistical analysis. Results: Of 349 patients with MCL, the median patient age was 61 years (range: 25-83 years, M∶F=2.7∶1.0) and the age of 243 patients ranged from 51 to 70 years (69.6%). Those with B symptoms accounted for 22.4% (70/313). Most of the patients presented with superficial lymphadenopathy and the clinical stage Ⅲ-Ⅳ accounted for 76.1% (235/309). Extranodal involvement was seen in 47.9% (148/309), among which the gastrointestinal tract accounted for 31.8% (47/148) and splenic involvement accounted for 15.4% (47/305). Three hundred and nine (88.5%) cases were of classical type and 40 (11.5%) cases were of aggressive variant type, and all were composed of proliferating lymphoid cells. All the tumors were positive for CD20 and cyclin D1, and 98.6% (344/349) tumors were weakly positive or positive for CD5. FISH test was positive in 12 cases that were CD5 negative and with cyclin D1 partial expression.Two hundred and forty-three (69.6%) patients had a median follow-up of 26 months (range: 3-108 months). The 3- and 5-year overall survival rates for patients were 63.0% and 34.8%, respectively. Single factor analysis showed that age of >60 years, splenic involvement, aggressive variant type, incompletely overlapping type [Based on the degree of overlap ≥90% and <90% between the follicular dendritic cell (FDC) meshwork and tumor cells, the tumors were divided into the completely overlapped type and incompletely overlapped type] and Ki-67 index >40% had poor prognosis (P<0.05). Multiple factor Cox proportional risk regression analysis after removing the aggressive variant type showed that age, splenic involvement, the degree of overlap between the FDC meshwork and tumor cells and Ki-67 index were independent prognostic factors for overall survival rate of MCL patients (P<0.05). Conclusions: MCL is more commonly found among middle-aged and elderly men. Patient age, splenic involvement, degree of overlap between FDC meshwork and tumor cells and Ki-67 index are the independent prognostic indicators for MCL.

Inflammatory Pseudotumor of the Spleen in a Patient with Idiopathic Thrombocytopenic Purpura

Inflammatory pseudotumor tumors (IPTs) of the spleen are uncommon lesions of uncertain pathogenesis. A definitive clinical diagnosis is challenging because radiological, as well as gross pathologic features may suggest a lymphoma, an inflammatory myofibroblastic tumor (IMT), or an IPT-like follicular dendritic cell tumor (IPT-FDC). Herein, we report a case of an IPT of the spleen in a 48-year-old woman who presented with idiopathic thrombocytopenic purpura (ITP) symptoms. The results of abdominal ultrasonography revealed the presence of a splenic mass that continued to enlarge after the recovery from ITP, leading to the suspicion of lymphoma. A splenectomy was performed for diagnostic and curative purposes. The lesion was a non-encapsulated yellowish mass (largest diameter: 4,4 cm). The presence of spindle cells expressing smooth muscle actin, vimentin, and focal CD68 admixed with polymorphous lymphoid infiltrate supported the IPT diagnosis. The negative expression of CD21, CD23, CD35, and ALK excluded inflammatory myofibroblastic and follicular dendritic cell tumors. Any evidence of the recurrence of either ITP or IPTs was not noted 60 months after the operation. The present case and the review revealed that splenic IPT tends to occur in middle-aged females and diagnosis is challenging due to the absence of specific symptoms or the characteristic hematological or radiological findings. Surgery is the most frequently performed treatment. Although multiple factors have been suggested in the etiology and pathogenesis, previous bleeding may also play a role in the presence of IPTs in patients with ITP. The rare occurrence of splenic IPT and the lack of diagnostic clinical signs and symptoms do not exclude their consideration in the differential diagnosis of spleen tumors, especially in patients with imaging features that cannot rule out malignancy.

Inflammatory pseudotumor-like follicular dendritic cell tumors misdiagnosed as liver cancer: a case report

Inflammatory pseudotumor-like follicular dendritic cell tumors misdiagnosed as liver cancer: a case report

The degree of overlap between the follicular dendritic cell meshwork and tumor cells in mantle cell lymphoma is associated with prognosis

This study concerning mantle cell lymphoma (MCL) investigated retrospectively an association between patient prognosis and the percentage of the total number of lymphoma cells found in the follicular dendritic cell (FDC) meshwork, that is, the degree of overlap of lymphoma cells. Two hundred and nine MCL patients were apportioned to grades I–III, in which the CD21-positive FDC meshwork covered ≤50%, 51%–89%, and ≥90% of the tumor area, respectively. Significant differences among the grades (all, P < 0.01) were found in the following: duration of disease (from onset of clinical manifestation to diagnosis); clinical staging; extranodal involvement (non-lymphoid organs); histological subtype; and Ki-67 proliferation index (PI). After removing the aggressive variants, the overall survival rates of grade I (n = 92) and II (n = 57) patients were similar. The overall survival rates of grade III (n = 46) patients differed from that of grade I + II patients (P < 0.01). The grades negatively correlated with the Ki-67 PI value (r = −0.234, P = 0.001). At each grade the OSR of patients with Ki-67 PI ≤30% was similar to that of patients with Ki-67 >30%. In the Ki-67 PI ≤30% group, the OSRs of the patients differed significantly among the grades. In the Ki-67 >30% group the OSRs of the grades were similar. The results of multivariate Cox regression analysis showed that the degree of overlap, age and Ki-67 PI was the independent prognostic factors of the OSRs of MCL patients. Our data suggests that MCL patients in whom there was a high degree of overlap between the FDC meshwork and tumor area have a better clinical prognosis. The degree of overlap correlates well with the Ki-67 PI, which can be used to predict the prognosis of patients.

A Tumor in Tumor Growing Pattern of Intra-abdominal Castleman's Disease Associated with a Follicular Dendritic Cell Tumor

A Tumor in Tumor Growing Pattern of Intra-abdominal Castleman's Disease Associated with a Follicular Dendritic Cell Tumor

Splenic Epstein-Barr Virus-Associated Inflammatory Pseudotumor.

Splenic inflammatory pseudotumor (IPT) is an uncommon lesion with an inflammatory morphologic aspect that often poses a diagnostic challenge. The etiology of IPT can be infectious, autoimmune, reactive, or neoplastic. Splenic Epstein-Barr virus (EBV)-associated IPTs form a subset of splenic IPTs in which there is a spindle cell component infected by EBV. The best characterized and most frequent subgroup of splenic EBV-associated IPT is IPT-like follicular dendritic cell tumor. This review also focusses on EBV-associated splenic IPTs without follicular dendritic cell marker expression. These lesions are less well characterized, making the differential diagnosis with other splenic lesions even more difficult. Recently, increased numbers of immunoglobulin G4-positive plasma cells and the presence of numerous granulomas have been reported in EBV-associated IPTs, and this can add to the difficulties in recognizing the neoplastic nature of these lesions. Herein, we also review the epidemiology, clinical features, histologic morphology, immunohistochemistry, electron microscopy, and pathogenesis of EBV-associated IPTs.

Hepatic inflammatory pseudotumour-like follicular dendritic cell tumor: A case report.

Hepatic inflammatory pseudotumor (IPT)-like follicular dendritic cell (FDC) tumor is a rare neoplasm. We herein report the case of 19-year-old female patient with an IPT-like FDC tumor and summarize 24 cases of hepatic FDC tumors previously reported in the English literature. The patient presented with complaints of abdominal discomfort, without significant laboratory abnormalities, and underwent surgical removal of a hepatic tumor. The resected tumor was 6 cm in the longest diameter and the tumor cells were positive for CD21, CD35 and Epstein-Barr virus (EBV). The postoperative course was uneventful and there have been no metastases or recurrence during 1 year of follow-up. The majority of the cases of hepatic IPT-like FDC tumors have a female predominance and exhibit an association with EBV infection. Their clinical manifestations and image findings are usually non-specific and the diagnosis of this disease mainly relies on pathology.

Identification of novel follicular dendritic cell sarcoma markers, FDCSP and SRGN, by whole transcriptome sequencing.

Follicular dendritic cell (FDC)-sarcoma is a rare neoplasm with morphologic and phenotypic features of FDCs. It shows an extremely heterogeneous morphology, therefore, its diagnosis relys on the phenotype of tumor cells. Aim of the present study was the identification of new specific markers for FDC-sarcoma by whole transcriptome sequencing (WTS). Candidate markers were selected based on gene expression level and biological function. Immunohistochemistry was performed on reactive tonsils, on 22 cases of FDC-sarcomas and 214 control cases including 114 carcinomas, 87 soft tissue tumors, 5 melanomas, 5 thymomas and 3 interdigitating dendritic cell sarcomas. FDC secreted protein (FDCSP) and Serglycin (SRGN) proved to be specific markers of FDC and related tumor. They showed better specificity and sensitivity values than some well known markers used in FDC sarcoma diagnosis (specificity: 98.6%, and 100%, respectively; sensitivity: 72.73% and 68.18%, respectively). In our cohorts CXCL13, CD21, CD35, FDCSP and SRGN were the best markers for FDC-sarcoma diagnosis and could discriminate 21/22 FDC sarcomas from other mesenchymal tumors by linear discriminant analysis. In summary, by WTS we identified two novel FDC markers and by the analysis of a wide cohort of cases and controls we propose an efficient marker panel for the diagnosis of this rare and enigmatic tumor.

Mulberry cells in the thyroid: warthin–finkeldey‐like cells in hashimoto thyroiditis‐associated lymphoma

Warthin-Finkeldey type giant cells were first described in autopsies performed on young children who died during the highly lethal measles epidemic in Palermo during the winter of 1908. The cells had 8-15 nuclei without identifiable cytoplasm within the germinal centers of lymphoid organs resembling megakaryocytes. We describe a case of Hashimoto thyroiditis with an enlarging substernal throid mass. The resection specimen contained many Warthin-Finkeldey-Like Cells (WFLC) in an extranodal marginal zone lymphoma (MALT type) with focal transformation to diffuse large B-cell lymphoma. The WFLC showed nuclear features similar to those of neighboring follicular dendritic cells (FDCs), favoring the hypothesis that these cells might be the product of fusion of FDCs. This is supported by immunostaining results and the occurrence of similar cells in follicular dendritic cell sarcomas and in "dysplastic" FDCs in hyaline vascular type Castleman disease, a possible precursor of follicular dendritic cell tumors. Diagn. Cytopathol. 2017;45:212-216. © 2016 Wiley Periodicals, Inc.

Paraneoplastic Pemphigus Associated with Follicular Dendritic Cell Tumor in the Mediastinum.

Paraneoplastic Pemphigus (PNP) is an autoimmune bullous disease characterized by severe stomatitis, polymorphous skin eruptions, and underlying neoplasms. Diagnosis of cutaneous paraneoplastic disorders requires high index of suspicion. We describe a patient with PNP associated with follicular dendritic cell (FDC) tumor in the mediastinum, a rare neoplasm originating from follicular dendritic cells. Its management requires identification of underlying malignancy and treatment of the same. Our patient showed remission of PNP upon excision of the tumor and remained disease-free for 8 years.

Clinicopathological features of inflammatory pseudotumour-like follicular dendritic cell tumour of the abdomen.

Inflammatory pseudotumour-like follicular dendritic cell (FDC) tumour is an extremely rare neoplasm. Herein, we report 10 cases of inflammatory pseudotumour-like FDC tumours in the abdomen and analyse their clinicopathological features. Seven patients were male, and three patients were female. The patients' age ranged from 28 years to 68 years (mean age, 52.9 years; median age, 51.5 years). Grossly, the tumour was usually solitary, well circumscribed, and solid, ranging from 23 mm to 233 mm in greatest diameter. Microscopically, the tumour was composed of variable amounts of spindle tumour cells with intense lymphoplasmacytic infiltrate. Unusual morphological findings, including eosinophils focally aggregated in one tumour admixed with multinucleated histiocytes in small clusters, fibrinoid deposits in the walls of ectatic blood vessel with occasional perivascular cuffs of lymphocytes, hyalinized fibrosis, and epithelioid granuloma, were identified. The tumour cells were immunoreactive for CD21, CD23, CD35, smooth muscle actin, and Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (7/10, 70%). EBV-encoded small RNA was positive in all cases by in situ hybridization. The recurrence rate was 10% with a median follow-up of 19 months. Inflammatory pseudotumour-like FDC tumour should be differentiated from inflammatory myofibroblastic tumour, Hodgkin lymphoma, interdigitating dendritic cell sarcoma, and gastrointestinal stromal tumour.

Inflammatory pseudotumor-like follicular dendritic cell tumor of liver: a report of one case

Inflammatory pseudotumor-like follicular dendritic cell tumor of liver: a report of one case

TdT+ T-Lymphoblastic Proliferation in Castleman Disease.

TdT+ T-Lymphoblastic Proliferation in Castleman Disease.

Inflammatory Pseudotumor-like Follicular Dendritic Cell Tumor of Liver and Spleen

Inflammatory pseudotumor-like follicular dendritic cell (FDC) tumor is an uncommon, Epstein-Barr virus-associated neoplasm of the liver or spleen, characterized by spindly tumor cells dispersed in a background of small lymphocytes and plasma cells. We report 6 diagnostically challenging cases in which the neoplastic component is further overshadowed by granulomas or eosinophils. The patients included 2 men and 4 women with a median age of 45.5 years, and 1 of them showed concurrent involvement of the liver and spleen. The presence of extensive coalescent epithelioid granulomas in 3 splenic tumors and 3 liver tumors raised the possibilities of an infective process or sarcoidosis. In another liver tumor, the massive infiltrate of eosinophils, accompanied by geographic eosinophilic abscesses, suggested parasitic infestation or so-called eosinophilic granuloma of the liver. However, scrutiny of the tissue between the granulomas or among the eosinophils revealed scattered atypical spindly cells with indistinct cell borders, large vesicular nuclei, and distinct nucleoli. The atypical cells were positive for FDC markers on immunostaining (CD21, CD35) and Epstein-Barr virus on in situ hybridization. Thus, a diagnosis of inflammatory pseudotumor-like FDC tumor could be confirmed. Awareness of the granulomatous and eosinophil-rich variants of this tumor type will facilitate the correct diagnosis to be made.

Imaging Findings of Inflammatory Pseudotumor-Like Follicular Dendritic Cell Tumor of Spleen

Inflammatory pseudotumor-like follicular dendritic cell tumor (IPT-like FDCT) histology is similar to that of the classical follicular dendritic cell (FDC) tumor, but, in addition, the inflammatory component is quite prominent. We report a case of IPT-like FDCT of the spleen by abdominal CT and 18F-FDG PET/CT. Abdominal CT showed a low-density, round, well-circumscribed defined mass in spleen, and the mass showed a high metabolism rate on 18F-FDG PET/CT.