Da Ren Shi

Cutaneous Rosai-Dorfman disease: A clinical and histopathologic study of 25 cases in China

Cutaneous Rosai-Dorfman disease (CRDD) is a rare proliferative disorder of histiocytes with unknown etiology, broadly different from systemic Rosai-Dorfman disease. We present the largest series of CRDD, describing the clinical manifestation, histopathology, immunohistochemistry, and follow-up course of 25 cases in China. Clinically, 39 skin lesions in 25 patients were divided into 3 main types: papulonodular type (79.5%), indurated plaque type (12.8%), and tumor type (7.7%). Extremities were the most frequently involved, followed by trunk and face. None of the patients was found to have visceral organ involvement or lymphadenopathy. Microscopically, CRDD was characterized by scattering, clusters or sheets of large polygonal histiocytes intermingled with a florid, mixed inflammatory infiltrate. The most important feature was emperipolesis, which can be highlighted by S-100 protein stain. Patch and bandlike infiltrate of numerous mature plasma cells around glands and vessels was a constant finding in all lesions. Neutrophils existed in all cases to a variable degree with 2 cases forming microabscess. Four cases were remarkable for fibrosis, and xanthomatous change was observed in 2 cases. Coexistence of localized Langerhans cell histiocytosis and CRDD was interestingly found in case 7, which was evidenced by CD1a stain. Clinical follow-up in 22 patients, ranging from 2 to 55 months, indicated that surgical excision was the exclusive effective treatment for CRDD. Partial or complete spontaneous remission was achieved in 7 patients within 6 to 55 months. Owing to its favorable outcome, CRDD should be differentiated from a variety of benign and malignant lesions. Recognition of its wide clinical spectrum and histologic features combined with S-100 protein stain can help to establish the correct diagnosis.

Subcutaneous panniculitis-like T-cell lymphoma: a clinicopathologic, immunophenotypic, and molecular study of 22 Asian cases according to WHO-EORTC classification.

Subcutaneous panniculitis-like T-cell lymphoma (SPTL) is defined as a rare cytotoxic α/β T-cell lymphoma characterized by primary involvement of subcutaneous tissue mimicking panniculitis and a predominant CD3+/CD4−/CD8+ phenotype in 2005 World Health Organization-European Organization for Research and Treatment of Cancer (WHO-EORTC) classification for cutaneous lymphomas. We presented a detailed study of SPTL, describing clinicopathologic, immunophenotypic, and molecular features of 22 cases in China. Strict diagnostic criteria according to the WHO-EORTC definition were applied to the diagnosis of all SPTL cases. Besides the common features described before, unusual CD4+/CD8− and CD4−/CD8− T-cell phenotypes were noted in 2 of our cases, respectively. CD30 was negative in all cases and CD56 was focally positive in 2 cases. Mortality in cases with angioinvasion (75%) was significantly higher than that in cases without angioinvasion (14.3%). Epstein-Barr virus (EBV) infection was detected in 1 immunocompetent patient by in situ hybridization. The frequency of rearranged TCRB, TCRG, and TCRD genes detected by BIOMED-2 multiplex polymerase chain reaction tubes was 80%, 67%, and 13%, respectively, with a total clonality detection rate of 100%. Clinical follow-up was available in 18 patients, ranging from 6 to 80 months. Most patients obtained complete or partial remission after therapy including one accompanied with EBV infection; 5 patients died: 3 of disease progression, 1 of severe infection, and 1 of complications caused by diabetes and hypertension. We conclude that SPTL as a cytotoxic lymphoma derived from α/β T cell has a predominant CD4−/CD8+ phenotype, but unusual CD4+/CD8− and CD4−/CD8− phenotypes do exist. Owing to its indolent clinical course and relatively high survival rate, SPTL should be differentiated from cutaneous γ/δ T-cell lymphoma. EBV is generally absent in SPTL but can rarely be detected especially in Asian population. Angioinvasion is a poor prognostic factor in SPTL.

FOXP1 expression and its clinicopathologic significance in nodal and extranodal diffuse large B-cell lymphoma

The aims of this study were to investigate FOXP1 expression in nodal and extranodal diffuse large B-cell lymphoma (DLBCL) and its association with the subclassification and other clinicopathologic parameters of DLBCL. Expression of FOXP1, CD10, Bcl6, MUM1, and Bcl2 was detected by immunohistochemistry on tissue microarray sections. The Kaplan–Meier method was used to estimate the overall survival of patients, and the log-rank test was used to compare survival differences between groups with different FOXP1 protein expressions. Expression of FOXP1 was detected in 67.4% (95/141) of DLBCLs. FOXP1 expression in non-GCB (67/90, 74.4%) was significantly higher than that in GCB (28/51, 54.9%) (p < 0.05). FOXP1 expression in MUM1-positive cases (62/81, 76.5%) was significantly higher than that in MUM1-negative cases (33/60, 55%) (p < 0.01). FOXP1 expression was positively correlated with Bcl2 (p < 0.05) in non-GCB among nodal DLBCL cases. Among the extranodal group, patients with FOXP1 expression had a significantly inferior OS compared to those with negative FOXP1 expression (p < 0.05), which was not seen in nodal group. In conclusion, FOXP1 expression might be involved in the tumorigenesis of both nodal and extranodal DLBCL. The most striking finding of this study was that FOXP1 expression had an adverse effect on survival of patients with extranodal DLBCL, which indicated that FOXP1 function might be mediated by different mechanisms in nodal and extranodal DLBCLs. FOXP1 might play a role in the pathogenesis of nodal non-GCB DLBCL through the pathways in which Bcl2 was involved, and it might be a second important biomarker for non-GCB.

Intravascular large B-cell lymphoma with cutaneous manifestations: a clinicopathologic, immunophenotypic and molecular study of three cases

Background:  Intravascular large B‐cell lymphoma (IVLBCL) is an extremely rare type of malignant lymphoma characterized by exclusive or predominant growth of neoplastic cells within the lumen of blood vessels. Cases in the literature predominantly involve the skin and central nervous system, with special emphasis on the ‘cutaneous variant’.

Cytoplasmic FOXP1 expression is correlated with ER and calpain II expression and predicts a poor outcome in breast cancer

BackgroundNuclear forkhead box protein P1 (N-FOXP1) expression in invasive breast cancer has been documented in the literature. However, the FOXP1 expression patterns at different stages of breast cancer progression are largely unknown, and the significance of cytoplasmic FOXP1 (C-FOXP1) expression in breast cancer has not been well illustrated. The aims of this study were to investigate FOXP1 expression patterns in invasive ductal carcinoma (IDC), ductal carcinoma in situ (DCIS), atypical ductal hyperplasia (ADH) and usual ductal hyperplasia (UDH), and to analyze the clinicopathological relevance of C-FOXP1 and its prognostic value in IDC.MethodsN-FOXP1 and C-FOXP1 expression in cases of IDC, DCIS, ADH and UDH was determined using immunohistochemistry. The correlation between C-FOXP1 expression and clinicopathological parameters as well as the overall survival (OS) and disease-free survival (DFS) rates of patients with IDC were analyzed.ResultsExclusive N-FOXP1 expression was found in 85.0% (17/20), 40.0% (8/20), 12.2% (5/41) and 10.8% (9/83) of UDH, ADH, DCIS, and IDC cases, respectively, and exclusive C-FOXP1 expression was observed in 0% (0/20), 0% (0/20), 4.9% (2/41), and 31.3% (26/83) of the cases, respectively. Both N- and C-FOXP1 staining were observed in 15.0% (3/20), 60.0% (12/20), 82.9% (34/41) and 48.2% (40/83) of the above cases, respectively, while complete loss of FOXP1 expression was observed in only 9.6% (8/83) of IDC cases. Estrogen receptor (ER) expression in C-FOXP1-positive IDC cases (31/66, 47.0%) was significantly lower than that in C-FOXP1-negative cases (13/17, 76.5%) (p = 0.030). Calpain II expression was observed in 83.3% (55/66) of C-FOXP1-positive IDC cases, which was significantly higher than that in C-FOXP1-negative cases (9/17, 52.9%) (p = 0.007). Calpain II was significantly associated with pAKT (p = 0.029), pmTOR (p = 0.011), p4E-BP1 (p < 0.001) and p-p70S6K (p = 0.003) expression levels. The 10-year OS and DFS rates of the C-FOXP1-positive patients were 60.5% and 48.7%, respectively, both of which were lower than those of the C-FOXP1-negative patients (93.3, 75.3%). The OS curve showed a dramatic impact of C-FOXP1 status on OS (p = 0.045).ConclusionsCytoplasmic relocalization of FOXP1 protein was a frequent event in breast IDC. Calpain II might play an important role in nucleocytoplasmic trafficking of FOXP1 and the AKT pathway might be involved in this process. C-FOXP1 expression was inversely associated with ER expression and might be a predictor of poor OS in patients with IDC.