Influence of FOXP3 single-nucleotide polymorphism after allogeneic hematopoietic stem cell transplantation.

The impact of FOXP3 single-nucleotide polymorphisms (SNP) on clinical outcomes after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains poorly understood. We investigated the relationship between a FOXP3 SNP (rs3761548) and clinical outcomes in 91 patients with hematological malignancies after allo-HSCT. Multivariate analysis showed that risk of severe chronic graft-versus-host disease (cGVHD) was significantly higher in patients with the FOXP3-3279C/A or FOXP3-3279A/A genotype than those with the FOXP3-3279C/C genotype [hazard ratio (HR), 2.69; 95% confidence interval (CI) 1.14-6.31; p = 0.023]. Therefore, FOXP3 at SNP rs3761548 can be a useful marker for predicting the occurrence of severe cGVHD.

Characteristics and predictors of post-transplant-associated hemophagocytic lymphohistiocytosis in adults.

Hemophagocytic lymphohistiocytosis (HLH) is an uncontrolled hyperinflammatory disorder driven by an overactive immune system that results in high mortality. Post-transplant-associated hemophagocytic lymphohistiocytosis (PT-HLH) is a type of secondary HLH that occurs following allogeneic hematopoietic stem cell transplantation (allo-HSCT). The clinical features of PT-HLH remain unclear and diagnostic and prognostic tools have not yet been established. Here, we retrospectively evaluated the clinical manifestations and outcomes of PT-HLH in 94 patients who underwent allo-HSCT. According to our PT-HLH criteria (hyperferritinemia and increased macrophage count in bone marrow), PT-HLH occurred in 12 patients (12.8%). The PT-HLH patients showed splenomegaly (P = .001), a higher risk of engraftment failure (P = .013), and an increased percentage of macrophages and hemophagocytes in bone marrow aspirates (P = .0009 and P = .0006, respectively). Moreover, univariate and multivariate analyses revealed that the survival rate was lower in PT-HLH patients than non-PT-HLH patients (P = .0017 and P = .034, respectively). This study defines the clinical features of PT-HLH and PT-HLH criteria that could be useful tools for diagnosing PT-HLH.

Effusion cytomorphology and immunocytochemistry of malignant melanoma: five cases of melanotic melanoma and one case of amelanotic melanoma.

Effusion cytological analyses of amelanotic malignant melanoma (AMM) are very rare and no concise description of AMM related cytomorphologic features using effusion have been reported. Here, we report the cytomorphological, immunohistochemical, and immunocytochemical findings in the effusion cytology of six cases of malignant melanoma (MM), one case of AMM, and five cases of melanotic malignant melanoma. Papanicolaou-stained smears exhibited conspicuous nucleoli, multinucleation, and cytoplasmic vacuolization in all of the MM cases. In addition, the AMM case displayed numerous mitotic figures and intranuclear cytoplasmic inclusions. With regard to the immunohistochemistry findings, all six cases of melanoma were positive for Melan-A/MART-1, HBME-1, and S-100. In the immunohistochemistry analyses, five of six cases of melanoma were positive for WT-1, as was the AMM specimen. Furthermore, because the effusion analysis of malignant mesothelioma proved positive for WT-1, it should be noted that WT-1 effusion analysis is not an appropriate means to distinguish between MM and malignant mesothelioma. We suggest that it is important to recognize cytomorphologic characteristics, such as melanin pigment, conspicuous nucleoli, multinucleation, and cytoplasmic vacuolization, and to choose appropriate antibodies for the correct diagnosis of MM in effusion.

Combined small cell carcinoma with pulmonary blastoma and adenocarcinoma: case report and clonality analysis.

We describe a rare tumor occurring in the left pulmonary lobe of a 71-year-old Japanese man. The tumor, which was resected by left lower lobectomy, measured 65 x 50 x 50 mm. Histologic examination revealed papillary adenocarcinoma in small cell carcinoma, and chondrosarcoma. Also, the blastemal cells were located between the small cell carcinoma and the chondrosarcoma, and intermingled with both components. In blastemal cells, some glands resembled a well-differentiated fetal adenocarcinoma. The tumor was diagnosed as combined small cell carcinoma with pulmonary blastoma and papillary adenocarcinoma according to the 2004 WHO classification. Immunohistochemically, the small cell carcinoma expressed TTF-1, pancytokeratin, CD56, synaptophysin, and S100 protein, while blastemal cells expressed vimentin, desmin, smooth muscle actin, CD56, and S100 protein. To investigate whether the tumor was clonal or not, p53 gene mutation of each tumor component was analyzed by laser-captured microdissection, polymerase chain reaction-single-strand conformation polymorphism and direct sequencing. Despite the histologic complexity, all components showed the same mutation at exon5 of the p53 gene. These results indicate that the tumor was clonal and arose from a relatively primitive cell, and that p53 mutation occurred before histologic metamorphosis or differentiation.

Decreased nm23 expression, but not Ki-67 labeling index, is significantly correlated with lymph node metastasis of breast invasive ductal carcinoma.

The nm23 gene was originally identified by differential hybridization of metastatic murine melanoma cell lines. Some experimental studies demonstrated a significantly reduced metastatic potential of melanoma cell lines transfected with the nm23 gene. In this study, we clarified the relationship between lymph node status and nm23 immunoreactivity, as well as Ki-67 labeling index (LI), of human breast cancer. Of the 44 breast invasive ductal carcinomas, nm23-diffusely positive expression [nm23(+)] was detected in 17 (38.6%), and focally positive/negative expression [nm23(+/-/-)] in 27 (61.4%) cases. Lymph node metastasis was found at a significantly higher incidence in the nm23(+/-/-) cases (18/27, 66.7%) than in the nm23(+) cases (4/17, 23.5%) (p>0.001). In the lymph node metastasis-positive cases, mean LI of Ki-67 cells was 20.9% at the center of the tumors and 24.0% at the advanced margins. In the lymph node metastasis-negative cases, mean LI of Ki-67 cells was 12.4% at the center of the tumors and 27.2% at the advanced margins. Decrease of nm23 expression, but not Ki-67 LI, was significantly correlated with lymph node metastasis of breast invasive ductal carcinoma.