浸潤性発育を示した後腹膜孤立線維性腫瘍の1例

56歳女.悪性後腹膜孤立性線維性腫瘍であり, 主訴は腹部腫瘤触知で, 腹部CT及びMRI検査にて左腎下方に接して, Gerota筋膜に沿うように発育する境界不明瞭な腫瘤を認めた.手術所見では後腹膜腔にゼラチン状の腫瘍を認め, 下行結腸周囲の脂肪組織やGerota筋膜周囲の脂肪組織に浸潤していた.Gerota筋膜内への浸潤は認めなかったので左腎は温存した.病理組織像では間質の膠原線維は著明に増殖し, hemangiopericytoma様のくちばし状を呈する血管も豊富に認められた.腫瘍組織内に腫瘍細胞密度の増加しているところや核異型度が強く分裂像を認める組織が混在しており, また周囲脂肪組織内に浸潤している所見を認めた.以上より, 悪性後腹膜孤立性線維性腫瘍と診断した.治療は外科的切除のみを行い, 2年4ヵ月を経過しても再発無く生存中であるSolitary fibrous retroperitoneal tumor is rare. We present a case with infiltrative growth in a 56-year-old female patient whose initial symptom was palpable tumor in the lower abdomen. Computed tomography and magnetic resonance imaging indicated a mass in the retroperitoneum under the left kidney with a poorly demarcated infiltrative growth. Surgical findings revealed a gelatinous tumor in the retroperitoneum, which had invaded up to the fatty tissue surrounding the Gerota's fascia and to the fatty tissue surrounding the descending colon. However, as there was no invasion into the Gerota's fascia, it was possible to preserve the left kidney. Pathohistological examination revealed increased cellularity in the tumor tissues as well as tissues with atypical nuclei of the tumor cells with some cell division. Due to these findings, it was diagnosed as malignant solitary fibrous tumor. Only surgical treatment was performed and the patient is alive without recurrence 2 years and 4 months after surgery

Vulvar microinvasive squamous cell carcinoma arising in vulvar intraepithelial neoplasia 3 complicated by genital warts and systemic lupus erythematosus: a case report

A patient suffering from long-term systemic lupus erythematosus attended with a complaint of recurrent genital warts. Perineal white-colored skin and a peri-anal papillary protrusion adjacent to the genital warts were biopsied and determined to be vulvar intraepithelial neoplasia (VIN) 3 and microinvasive squamous cell carcinoma (SCC), respectively. These lesions were locally excised. Human papillomavirus (HPV)-6 was detected in these lesions, including in the genital warts, while HPV-56 was detected only in the perineal VIN3 and peri-anal microinvasive SCC.

Collaborative Action of Brca1 and CtIP in Elimination of Covalent Modifications from Double-Strand Breaks to Facilitate Subsequent Break Repair

Topoisomerase inhibitors such as camptothecin and etoposide are used as anti-cancer drugs and induce double-strand breaks (DSBs) in genomic DNA in cycling cells. These DSBs are often covalently bound with polypeptides at the 3′ and 5′ ends. Such modifications must be eliminated before DSB repair can take place, but it remains elusive which nucleases are involved in this process. Previous studies show that CtIP plays a critical role in the generation of 3′ single-strand overhang at “clean” DSBs, thus initiating homologous recombination (HR)–dependent DSB repair. To analyze the function of CtIP in detail, we conditionally disrupted the CtIP gene in the chicken DT40 cell line. We found that CtIP is essential for cellular proliferation as well as for the formation of 3′ single-strand overhang, similar to what is observed in DT40 cells deficient in the Mre11/Rad50/Nbs1 complex. We also generated DT40 cell line harboring CtIP with an alanine substitution at residue Ser332, which is required for interaction with BRCA1. Although the resulting CtIPS332A/−/− cells exhibited accumulation of RPA and Rad51 upon DNA damage, and were proficient in HR, they showed a marked hypersensitivity to camptothecin and etoposide in comparison with CtIP+/−/− cells. Finally, CtIPS332A/−/−BRCA1−/− and CtIP+/−/−BRCA1−/− showed similar sensitivities to these reagents. Taken together, our data indicate that, in addition to its function in HR, CtIP plays a role in cellular tolerance to topoisomerase inhibitors. We propose that the BRCA1-CtIP complex plays a role in the nuclease-mediated elimination of oligonucleotides covalently bound to polypeptides from DSBs, thereby facilitating subsequent DSB repair

低蛋白血症で発見された骨髄腫関連疾患の一症例

広義の骨髄腫関連疾患には,古典的なmyelomaを始めとして,plasmacytic leukemia,plasmacytomaさらにmacroglobulinemia,lymphoplasmacytic lymphomaなどが含まれる.一般的には特徴的検査所見の一つに,血清総蛋白の高値がある.ところが,今回我々は血清総蛋白がむしろ低値であった骨髄腫関連疾患を経験した.症例は85歳女性.貧血軽度,黄疸(-),肝脾腫(-),リンパ節腫大(-),骨病変は軽微であった.検査所見:末梢血WBC4370/μl,RBC242万/μl,Hgb8.1g/dl,Hct25.6%,PLT6.2万/μl,Neut70.7%,Lym23.6%,Mono5.0%,Eos0.2%,Bas0.5%.生化学:TP5.3g/dl,Alb2.0g/dl,Glob3.3g/dlそのうちIgG532mg/dl,IgA79mg/dl,IgM2,035mg/dlで,免疫電気泳動にて明らかなM-bowを認め,IgM-_K型と判明した.骨髄:採取した標本では低形成で,Mgk10/μl,赤芽球15.6%,顆粒球系60.3%,リンパ球系23.8%,そのうち形質細胞1.9%であった.形態学的には,マクログロブリン血症の際にみられるリンパ・形質細胞様の所見であった.細胞表面マーカーの検索では,リンパ球全体ではCD7 33.5%,CD138 0.7%,CD19 7.0%,CD20 32.8%,形質細胞ではCD7 21.8%,CD138 57.7%,CD19 21.1%,CD20 39.7%であった.病理検査では,N/C比が高く異型性のある核を持つ細胞のシート状の集簇が認められた.腫瘍細胞の透過型電顕所見では,核は偏在し,大型のゴルジ野を有し,粗面小胞体はよく発達し,蛋白合成の盛んなことが推測された.細胞によっては,分化度が低く核クロマチンは繊細で明らかに芽球様の細胞も認められた.染色体分析:46,XX.末梢血生化学所見では総蛋白量の明らかな減少が認められたが,その病因は腫瘍細胞によるIgMの過剰産生にあり,その腫瘍性性質のため正常免疫グロブリン特にIgGおよびIgAの著しい産生抑制を生じたものと考えられる.細胞学的にはマクログロブリン血症と多発性骨髄腫とにまたがる境界領域に位置付けられるBリンパ球系悪性疾患と推定される.It is known that myeloma-related disorders include classical myeloma, plasmacytic leukemia, plasmacytoma, macroglobulinemia, lymphoplasmacytic lymphoma and others. Increased serum protein is one of the characteristic features in these disorders. We have recently experienced a case of myeloma-related disorder with hypoproteinemia. The patient (a 85 year-old female) demonstrated hypoproteinemia (total protein 5.3g/dl, Alb2.0g/dl, Glob3.3g/dl) with increased IgM 2,035mg/dl contrary to decreased IgG(532mg/dl) and IgA(79mg/dl). The presence of IgM-_K monoclonality was detected by immunoelectrophoresis. Peripheral blood showed slight anemia(RBC 2.42×10^6/μl) and thrombocytopenia(62×10^3/μl). Peripheral lymphocytes were 23.6% with lymphoplasmacytic appearance. Bone marrow examination revealed that lymphocytes were 23.8% with 1.9% of plasma cells: CD79a(+), CD138(+/-), CD20(+/-), CD5(-), cyclin D1(-), IgM(+), IgA(-), IgG(+-), and IgM_K -monoclonality(+) by immune staining method. Surface makers of all lymphoid cells indicated CD138 57.7%, CD19 21.1%, and CD20 39.7%. Clusters of malignant lymphoid cells were present in bone marrow specimen. Transmission electron microscopy (TEM) on the lymphoid cells indicated the dislocated nucleus and profound rough-surfaced ribosomes with large Golgi apparatus suggesting the markedly enhanced protein production. In some cells, the blastic appearance with fine nuclear chromatin structure was observed. The pathogenesis of hypoproteinemia appears to be due to suppression of IgG and IgA by increased IgM monoclonality, in addition to decreased level of serum albumin. The disorder is considered to be localized at the border area between classical myeloma and macroglobulinemia

Genetic Evidence for Single-Strand Lesions Initiating Nbs1-Dependent Homologous Recombination in Diversification of Ig V in Chicken B Lymphocytes

Homologous recombination (HR) is initiated by DNA double-strand breaks (DSB). However, it remains unclear whether single-strand lesions also initiate HR in genomic DNA. Chicken B lymphocytes diversify their Immunoglobulin (Ig) V genes through HR (Ig gene conversion) and non-templated hypermutation. Both types of Ig V diversification are initiated by AID-dependent abasic-site formation. Abasic sites stall replication, resulting in the formation of single-stranded gaps. These gaps can be filled by error-prone DNA polymerases, resulting in hypermutation. However, it is unclear whether these single-strand gaps can also initiate Ig gene conversion without being first converted to DSBs. The Mre11-Rad50-Nbs1 (MRN) complex, which produces 3′ single-strand overhangs, promotes the initiation of DSB-induced HR in yeast. We show that a DT40 line expressing only a truncated form of Nbs1 (Nbs1p70) exhibits defective HR-dependent DSB repair, and a significant reduction in the rate—though not the fidelity—of Ig gene conversion. Interestingly, this defective gene conversion was restored to wild type levels by overproduction of Escherichia coli SbcB, a 3′ to 5′ single-strand–specific exonuclease, without affecting DSB repair. Conversely, overexpression of chicken Exo1 increased the efficiency of DSB-induced gene-targeting more than 10-fold, with no effect on Ig gene conversion. These results suggest that Ig gene conversion may be initiated by single-strand gaps rather than by DSBs, and, like SbcB, the MRN complex in DT40 may convert AID-induced lesions into single-strand gaps suitable for triggering HR. In summary, Ig gene conversion and hypermutation may share a common substrate—single-stranded gaps. Genetic analysis of the two types of Ig V diversification in DT40 provides a unique opportunity to gain insight into the molecular mechanisms underlying the filling of gaps that arise as a consequence of replication blocks at abasic sites, by HR and error-prone polymerases