Good prognosis for follicular lymphoma with estrogen receptor α-positive follicular dendritic cells.

Follicular lymphoma (FL) has a meshwork of follicular dendritic cells (FDCs). We previously demonstrated the presence of estrogen receptor alpha (ERα)+ CD23+ FDCs in grades 1-2 FL. The significance of FDCs as a prognostic factor in FL remains unknown. The current study aimed to compare clinicopathological features, including prognosis, between FL with and without ERα+ FDCs. This study evaluated the clinicopathological significance of ERα expression in 70 FL patients by immunostaining. The presence of ERα mRNA on FDCs from 5 FL patients was confirmed by CD21/ERα double staining (immunohistochemistry and in situ hybridization). We defined patients with frequent ERα expression as the ERαhigh group and those with infrequent ERα expression as the ERαlow group. Thirty-two patients were assigned to the ERαhigh group (45.7%), and 38 patients were assigned to the ERαlow group (54.3%). Both overall survival (OS) and progression-free survival (PFS) were significantly better in the ERαhigh group than in the ERαlow group (OS, log-rank, P = .0465; PFS, log-rank, P = .0336). Moreover, high ERα expression on FDCs was an independent prognostic factor for OS in both the univariate ([hazard ratio] HR, 0.163; P = .0260) and multivariate (HR, 0.050; P = .0188) analyses and for PFS in both the univariate (HR, 0.232; P = .0213) and multivariate (HR, 0.084; P = .0243) analyses. ERα mRNA expression was detected in CD21+ FDCs within the neoplastic follicles of FL patients. In conclusion, a neoplastic follicular microenvironment with ERα-positive FDCs might affect the grade and presence of the follicular pattern of FL and improve patient prognosis.

Differential expression of estrogen receptor-α on follicular dendritic cells from patients with grade 1-2 and grade 3 follicular lymphoma.

Hormone therapy has been used for patients with estrogen receptor alpha (ERα)-positive breast cancers. Recently, some studies reported the expression of ERα on neoplastic cells from B-cell lymphomas. However, there has been only one report of ERα expression on the follicular dendritic cells (FDCs) that structurally and functionally support the microenvironment of follicular lymphomas (FLs). The objective of this study was to investigate the frequency of ERα expression on FDCs in nonneoplastic reactive lymphoid tissues and to compare the frequency of ERα expression on FDCs in the axillary lymph nodes between patients with and without antiestrogen therapy and among patients with grades 1-3 of FL. Reverse transcription-polymerase chain reaction was performed to detect ERα mRNA in FL. In nonneoplastic germinal centers (GCs) from patients with tonsillitis or reactive lymphadenitis, ERα was expressed in the light zone. ERα-positive cells strongly correlated with the width of GCs (rs  = 0.81, P < 0.01) and the CD21-positive (rs  = 0.69, P < 0.01) and CD23-positive (rs  = 0.83, P < 0.01) FDC meshwork. The axillary lymph nodes had fewer ERα-positive cells, smaller GCs, and a looser CD21- and CD23-positive FDC meshwork with hormone therapy than without hormone therapy (P < 0.01). Neoplastic follicles of G1-2 FL had more ERα-positive cells and a larger CD23+ FDC meshwork than those of G3 FL (P < 0.01). ERα mRNA was detected in both G1-2 FL and G3 FL by reverse transcription-polymerase chain reaction. In conclusion, these results suggested that antiestrogen hormone therapy may decrease the number of ERα-positive FDCs and that the responses mediated by the estrogen-ERα interaction on FDCs may differ between G1-2 FL and G3 FL.

Potential role of M2 TAMs around lymphatic vessels during lymphatic invasion in papillary thyroid carcinoma.

The aim of this study was to examine whether lymphatic invasion in papillary thyroid carcinoma (PTC) occurs when tumour-associated macrophages (TAMs) injure lymphatic vessels together with cancer cells. While there was no difference in the lymphatic vessel density in PTC and follicular thyroid carcinoma (FTC), the number of TAMs around the lymphatic vessels was increased in PTC compared to that in FTC. In particular, TAMs were observed together with cancer cells in lymphatic invasive lesions, and the number of M2 cells inside and outside the lymphatic vessels showed a significant correlation. MMP-2 mRNA was expressed in nonneoplastic stromal cells as well as cancer cells, and double immunofluorescence staining confirmed M2 positivity. Consequently, this study reveals that M2 TAMs around lymphatic vessels within the tumour border of PTC may be associated with the lymphatic invasion of cancer cells. This study represents a step forward in elucidating the mechanism of lymphatic invasion.

Other Iatrogenic Immunodeficiency-Associated Lymphoproliferative Disorders, Diffuse Large B-Cell Lymphoma Type, in a Patient with Behçet's Disease Treated with Cyclosporine A.

A 40-year-old man had been treated for Behçet's disease (BD) with cyclosporine A (CsA) for 14 years. He presented multiple lymphadenopathies with fever. Histological examination of surgical biopsy showed other iatrogenic immunodeficiency-associated lymphoproliferative disorders, diffuse large B-cell lymphoma type with positivity for Epstein-Barr virus encoding RNA-1 (EBER-1). BCL2-IgH, BCL6-IgH, and MYC-IgH translocations were not detected. CsA was stopped, and R-CHOP therapy was initiated. However, his lymphoma was chemotherapy resistant and rapidly progressed. To the best of our knowledge, this is the first case of diffuse large B-cell lymphoma that occurred in a BD patient treated with CsA reported in English. Both BD and CsA are associated with the pathogenesis of lymphoma. We also describe extremely rare cases in the form of a literature review.

Diagnostic utility of CD205 in breast cancer: Simultaneous detection of myoepithelial cells and dendritic cells in breast tissue by CD205.

BACKGROUND: CD205 can be used to detect myoepithelial cells (MECs) and dendritic cells (DCs) in breast tissue. However, the usefulness of CD205 immunostaining in the pathological diagnosis of breast tumors is not fully understood. The objective of this study was to re-evaluate CD205 co-expression with other MEC markers, such as p63 and CD10, in nonneoplastic and neoplastic breast tissue and to evaluate its pathological diagnostic utility in these types of breast cancer. MATERIAL AND METHODS: Nonneoplastic breast tissue samples with a terminal duct lobular unit and duct were obtained from fibroadenoma and mastopathy patients. Neoplastic breast tissue samples included ductal carcinoma in situ (DCIS) (n=43) and invasive ductal carcinoma (IDC) (n=60), including the tubule-forming type (n=20). These specimens were investigated by CD205, p63, and CD10 immunostaining. RESULTS: In addition to p63 and CD10, CD205 was expressed on MECs in nonneoplastic breast and DCIS tissue samples; CD205 was simultaneously detected on DCs that had infiltrated DCIS and IDC tumor nests. CD205 was expressed on cancer cells themselves in only 7.3% of the breast cancer samples. The number of intratumoral CD205⁺ DCs in tubular IDC was significantly higher than that in DCIS (P<0.01). CONCLUSION: Because CD205 was simultaneously detected on MECs and DCs in the same breast tissue sections, it may be useful for distinguishing tubular IDC from DCIS.

Immunoglobulin G Subclass 4-Related Lymphoplasmacytic Thoracic Aortitis in a Patient with Acute Type A Aortic Dissection.

Immunoglobulin G subclass 4-related disease (IgG4-RD) is a recently recognized systemic inflammatory disease characterized by an elevated serum IgG4 level and an IgG4-positive lymphocyte infiltrate mainly in exocrine tissues. Previous reports documented IgG4-RD in several cardiovascular disorders. We present a case of type A aortic dissection associated with IgG4-RD. A 52-year-old man diagnosed with a type A aortic dissection was referred for surgical treatment. He underwent emergency hemiarch reconstruction with a prosthetic graft. His postoperative recovery was uncomplicated. Histopathologic examination of his aortic tissue showed marked adventitial thickening with fibrosis and an IgG4-positive plasma cell infiltrate. He was diagnosed with type A aortic dissection incidentally complicated by IgG4-RD. The relationship between IgG4-RD and the pathogenesis of aortic dissection remains unknown and requires further investigation.

Detection of Minimal Bone Marrow involvement of Blastic Plasmacytoid Dendritic Cell Neoplastic Cells - CD303 immunostaining as a diagnostic tool.

Blastic plasmacytoid dendritic cell (pDC) neoplasm (BPDCN) is a relatively rare hematological malignancy with significantly complex clinicopathological features that are still unclear. This study aimed to analyze the clinicopathological data of BPDCN and evaluate immunohistochemical detection of minimal bone marrow (BM) involvement. In this study, we examined skin and BM lesions from 6 patients with BPDCN. Neoplastic cells tested positive for CD303 (polyclonal, 100%; monoclonal, 40%) in the skin lesions and for CD303 (polyclonal, 100%; monoclonal, 67%) in the BM clots. Although immunostaining of CD4, CD56, CD123, CD303, and TCLl detected minimal BM involvement in 3 patients, morphological identification was challenging in the BM clots stained with hematoxylin-eosin. In conclusion, our results demonstrate the significance of observing BM smears to detect neoplastic cells and that immunohistochemical examination, including CD303 antibodies, is useful to detect minimal BM involvement. This study is the first to report the expression of thymic stromal lymphopoietin (TSLP) and its receptor in BPDCN cells. Therefore, the TSLP/TSLP receptor axis may be associated with the proliferation of BPDCN, and consequently, the survival of patients.

Localization of collagen modifying enzymes on fibroblastic reticular cells and follicular dendritic cells in non-neoplastic and neoplastic lymphoid tissues.

The aim of this study was to evaluate the localization of collagen modifying enzymes (CMEs) on fibroblastic reticular cells (FRCs) and follicular dendritic cells (FDCs) in non-neoplastic lymphoid tissues and various malignant lymphomas. The expression of prolyl 4-hydroxylase 1 (P4H1), lysyl hydroxylase 3 (LH3), and protein disulfide isomerase (PDI) was frequently observed on FRCs and FDCs in the germinal center (GC), except for the mantle zone. The expression of CMEs was lower in most lymphomas than in their respective postulated normal counterparts. The ratio of transglutaminase II(+) FRCs/CD35(+) FDCs was also lower in follicular lymphomas (FL) than in other lymphomas. The mRNAs of some CMEs (P4H1, prolyl 4-hydroxylase 3, LH3, and heat shock protein 47) were confirmed in almost all lymphomas. These results indicate that lymphoma cell proliferation suppresses/decreases the number of CMEs expressing FRCs and FDCs in most lymphomas.