Kidney-limited intravascular large B cell lymphoma: a distinct variant of IVLBCL?

Intravascular large B cell lymphoma (IVLBCL) is a rare type of non-Hodgkin lymphoma characterized by a disseminated intravascular proliferation of tumor cells in the lumina of small vessels. Although the kidney is one of the target organs of IVLBCL, it is extremely rare that lymphoma cells are localized only in the kidney. We report here a Japanese patient with kidney-limited IVLBCL. The patient presented with mild proteinuria and a good performance status without B symptoms at presentation. A renal biopsy showed large B cell neoplastic lymphocytes in the glomerular capillary lumina. Extensive systemic examinations showed no other organ involvement. The patient responded well to rituximab and anthracycline-based chemotherapy. A follow-up renal biopsy showed the disappearance of intraglomerular lymphoma cells with restoration of glomerular architecture. Within 20 months past the discontinuation of chemotherapy, no evidence of recurrence was observed. Although IVLBCL is commonly a fatal disease, favorable clinical courses were reported in some cases of IVLBCL, such as the cutaneous variant. To our knowledge, there are 8 reported cases of kidney-limited IVLBCL in the English literature. All 4 patients treated with intensive chemotherapy responded well to the treatment as our patient. We suggest that kidney-limited IVLBCL might be a distinct variant of IVLBCL.

Four novel mutations in the thiazide-sensitive Na-Cl co-transporter gene in Japanese patients with Gitelman's syndrome.

BACKGROUND: Gitelman's syndrome (GS) is an autosomal recessive disorder resulting from inactivating mutations in the thiazide-sensitive Na-Cl co-transporter (NCCT) gene. To date, almost 90 mutations have been identified. It is possible that there is a population-specific distribution of mutations. In this study, we analysed mutations in the NCCT gene of seven Japanese patients with GS. METHODS: Peripheral blood mononuclear cells were isolated from patients with GS, their family members and healthy control subjects. A mutation analysis of the NCCT gene was performed completely by direct automated sequencing of polymerase chain reaction-amplified DNA products. In patients with a deletion or splice site mutation, we undertook cDNA sequence analysis. RESULTS: We identified nine mutations. Five of them [c.185C>T (Thr60Met), c.1712C>T (Ala569Val), c.1930C>T (Arg642Cys), c.2552T>A (Leu849His) and c.1932delC] have been reported in Japanese patients, but not in GS patients from other ethnic groups. The remaining four mutations [c.7A>T (Met1Leu), c.1181_1186+20del26, c.1811_1812delAT and IVS16+1G>A] were novel. In cDNA derived from a patient with c.1181_1186+20del26, a deletion of exon 9 and a frameshift at the start of exon 10 were observed. In cDNA derived from patients with IVS16+1G>A, an additional 96 bp insertion between exons 16 and 17 was observed. Six out of seven patients were compound heterozygotes, and the remaining one carried a single heterozygous mutation. CONCLUSIONS: We found four novel mutations in the NCCT gene in seven Japanese patients with GS. Moreover, our study suggests that the distribution of mutations in the NCCT gene in Japanese GS patients potentially differs from that in other populations.

Analysis of mutations in alpha-actinin 4 and podocin genes of patients with chronic renal failure due to sporadic focal segmental glomerulosclerosis.

Although the pathogenesis of idiopathic focal segmental glomerulosclerosis (FSGS) may be heterogeneous, autosomal dominant and recessive forms of FSGS are recognized. Recently, mutations in alpha-actinin 4 (ACTN4) and podocin genes were reported in patients with such familial FSGS. However, whether mutations in ACTN4 and podocin genes are associated with sporadic FSGS has not been determined. In the present study, we clarified the relation between mutations in ACTN4 and podocin genes and sporadic FSGS. We analyzed these reported mutations in ACTN4 and podocin in five patients with chronic renal failure due to therapy-resistant FSGS by direct sequencing of polymerase chain reaction products of ACTN4 and podocin. We found a C to T transition at nucleotide 465 in the ACTN4 gene in all of patients, and a T to C transition at nucleotide 954 in exon eight of podocin gene in two of five patients, resulting in no amino acid substitutions. Other mutations were not found in ACTN4 and podocin genes. Our findings suggest that sporadic FSGS is a heterogeneous disease, since ACTN4 and podocin genes are not found in our patients with sporadic FSGS.