Trametinib for a child with refractory Rosai-Dorfman-Destombes disease harboring a novel somatic mutation in MAP2K1.

Rosai-Dorfman-Destombes disease (RDD) is a rare histiocytosis characterized by accumulation of S100 + , CD68 + , and CD1a- histiocytes, with emperipolesis. It occurs predominantly in black adolescents and young adults, but rarely in Japanese children. Recently, oncogenic mutations in mitogen-activated protein kinase (MAPK) pathway genes were reported in 30-50% of patients with RDD, and several studies have described treatment of adult patients with MAPK inhibitors.

Elevation of serum fibroblast growth factor 23 level in a pediatric patient with lupus nephritis.

Fibroblast growth factor 23 (FGF-23), a hormone mainly secreted by osteocytes and osteoblasts, regulates phosphate and vitamin D levels. However, the in vivo significance of FGF-23 is not fully elucidated. This case report describes a 12-year-old girl with systemic lupus erythematosus (SLE), lupus nephritis, and an elevated serum FGF-23 level.

Topoisomerase IIβ immunoreactivity (IR) co-localizes with neuronal marker-IR but not glial fibrillary acidic protein-IR in GLI3-positive medulloblastomas: an immunohistochemical analysis of 124 medulloblastomas from the Japan Children's Cancer Group.

We previously reported observing GLI3 in medulloblastomas expressing neuronal markers (NM) and/or glial fibrillary acidic protein (GFAP). Furthermore, patients with medulloblastomas expressing NM or GFAP tended to show favorable or poor prognosis, respectively. In the present study, we focused on the role of topoisomerase IIβ (TOP2β) as a possible regulator for neuronal differentiation in medulloblastomas and examined the pathological roles of GLI3, NM, GFAP, and TOP2β expressions in a larger population.

Two cases of a non-progressive hepatic form of glycogen storage disease type IV with atypical liver pathology.

Glycogen storage disease type IV (GSD IV) is a rare inborn metabolic disorder characterized by the accumulation of amylopectin-like glycogen in the liver or other organs. The hepatic subtype may appear normal at birth but rapidly develops to liver cirrhosis in infancy. Liver pathological findings help diagnose the hepatic form of the disease, supported by analyses of enzyme activity and gene variants.

Capillary hemangioma involved in filar lipoma: A case report.

Filar lipomas are a subtype of spinal lipomas wherein adipose tissue accumulation is restricted to the filum terminale. Embryologically, filar lipomas are considered to occur because of the failure of secondary neurulation, although the precise mechanism is not yet completely understood. Involvement of ectopic mesodermal, ectodermal, and endodermal tissues in spinal lipomas has been occasionally reported, and the origin of these ectopic tissues has been supposed to be migration of pluripotent tissues, which exist during secondary neurulation.

An Acquired Form of Dandy-Walker Malformation with Enveloping Hemosiderin Deposits.

Dandy-Walker malformation (DWM) is a posterior fossa anomaly characterized by hypoplasia and upward rotation of the cerebellar vermis and cystic dilation of the fourth ventricle. The cyst of DWM rarely extends posteriorly to almost completely fill the entire posterior fossa, which mimics primary cerebellar agenesis, a cerebellar porencephalic cyst, and an arachnoid cyst due to the lack of clarity of the thin cystic wall. A 10-month-old female born at 23 weeks' gestation with cerebellar hemorrhage in the neonatal period was admitted to our hospital with dysphagia and side-to-side head bobbing.

Significance of p53-binding protein 1 (53BP1) expression in thyroid papillary microcarcinoma: association with BRAFV600E mutation status.

Aims: In a previous report, we proposed that analysis of 53BP1 expression by immunofluorescence could be a useful tool in estimating the level of genomic instability (GIN), as well as the malignant potential, of thyroid tumours. In an attempt to clarify the value of 53BP1 expression as a new molecular marker for the aggressiveness of thyroid papillary microcarcinoma (PMC), we assessed the association between the type of 53BP1 expression and clinicopathological features such as tumour size, extrathyroidal invasion, lymph node metastasis and BRAF(V) (600E) mutation of PMC.

Methods And Results: A total of 36 surgically resected thyroid tumours, including 13 PMC and 23 conventional papillary thyroid carcinomas (PTC), were available for this study.

Thyroid papillary carcinoma with solid sclerosing change in IgG4-related sclerosing disease.

IgG4-related sclerosing disease (IgG4-RSD) is an inflammatory and fibrosing disorder characterized by lymphoplasmacytic inflammation with infiltration of various organs, including the pancreas, bile ducts, lung, kidney, and retroperitoneum. As for malignancy in IgG4-RSD, only limited literature is available. We report here a case of thyroid papillary carcinoma showing unique morphology in IgG4-RSD.

Aberrant expression of interferon regulatory factor 3 in human lung cancer.

We analyzed the subcellular distributions and gene structures of interferon regulatory factor 3 (IRF3) transcription factor in 50 cases of human primary lung cancer. The immunohistochemical analyses revealed substantially aberrant IRF3 expression specific to the cancer lesions (2 and 6 tumors with nuclear staining, and 4 and 5 tumors with negative staining, in adenocarcinoma and squamous cell carcinoma, respectively), while the morphologically normal region around the tumors exhibited only cytoplasmic staining. In addition, we determined the sequence of the entire IRF3 coding region, and found two novel variants with the amino acid changes (S(175)(AGC)-->R(175)(CGC) and A(208)(GCC)-->D(208)(GAC)).

Genomic instability in the epidermis induced by atomic bomb (A-bomb) radiation: a long-lasting health effect in A-bomb survivors.

Background: Radiation etiology is suggested in the occurrence of basal cell carcinoma (BCC) of the skin among atomic bomb (A-bomb) survivors. Any genotoxicity, including ionizing radiation, can induce a DNA damage response (DDR), leading to genomic instability (GIN), which allows the accumulation of mutations during tumorigenesis. In this study, the authors evaluated the presence of GIN in the epidermis of survivors as a late effect of A-bomb radiation.

Immunohistochemical analyses of beta-catenin and cyclin D1 expression in giant cell tumor of bone (GCTB): a possible role of Wnt pathway in GCTB tumorigenesis.

Giant cell tumor of bone (GCTB) is a benign neoplasm but occasionally shows local recurrence, and histologically consists of osteoclast-like giant cells (GC) and stromal mononuclear cells (SC), which are capable of proliferation and osteoblastic differentiation. Activation of Wnt signaling can induce osteoblast differentiation and osteoclastgenesis during bone resorption process. This study analyzed the profiles of beta-catenin and cyclin D1 expression in GCTB to elucidate an involvement of Wnt pathway in tumorigenesis.

Alteration of p53-binding protein 1 expression during skin carcinogenesis: association with genomic instability.

Epidermal cells are the first cells to be exposed to environmental genotoxic agents such as ultraviolet and ionizing radiations, which induce DNA double strand breaks (DSB) and activate DNA damage response (DDR) to maintain genomic integrity. Defective DDR can result in genomic instability (GIN) which is considered to be a central aspect of any carcinogenic process. P53-binding protein 1 (53BP1) belongs to a family of evolutionarily conserved DDR proteins.

Foci formation of P53-binding protein 1 in thyroid tumors: activation of genomic instability during thyroid carcinogenesis.

Defective DNA damage response (DDR) can result in genomic instability (GIN) and lead to the transformation into cancer. P53-binding protein 1 (53BP1) belongs to a family of evolutionarily conserved DDR proteins. Because 53BP1 molecules localize at the sites of DNA double strand breaks (DSBs) and rapidly form nuclear foci, the presence of 53BP1 foci can be considered as a cytologic marker for endogenous DSBs reflecting GIN.

Cyclin D1 overexpression in thyroid tumours from a radio-contaminated area and its correlation with Pin1 and aberrant beta-catenin expression.

Cyclin D1 is a target molecule transcriptionally activated by aberrant beta-catenin in Wnt signalling, while prolyl isomerase Pin1 promotes cyclin D1 overexpression directly or through accumulation of beta-catenin in cancer cells. This study aimed to elucidate whether Pin1 was involved in cyclin D1 overexpression and aberrant beta-catenin in thyroid tumourigenesis by examining 14 follicular adenomas (FAa) and 14 papillary thyroid carcinomas (PTCs). All PTCs displayed cyclin D1 overexpression and strong cytoplasmic beta-catenin and/or decreased membrane beta-catenin expression by immunohistochemistry.