Whole-exome sequencing reveals a combination of extremely rare single-nucleotide polymorphism of DNAH9 and RSPH1 genes in a Japanese fetus with situs viscerum inversus.

Randomization of left-right body asymmetry, situs viscerum inversus (heterotaxy), is commonly associated with primary ciliary dyskinesia (PCD) resulting from an abnormal ciliary structure, with approximately 50% of PCD patients exhibiting organ laterality defects. I herein report an intrauterine fetal death case, in which an autopsy revealed two lobes of the bilateral lungs as well as heterotaxy of abdominal organs (right-sided spleen and inversion of the alimentary and biliary organs). Whole-exome sequencing (WES) identified a heterozygous single-nucleotide change (c.12775T>C) in exon 68 of the DNAH9 gene, which is a rare single-nucleotide polymorphism (SNP) of rs746081639 and results in the amino acid change of p.C4259R. WES also identified a rare SNP of rs763089682 (c.121G>A) in the RSPH1 gene that causes a heterozygous amino acid alteration of p.G41R. The frequencies of both SNPs, C in rs746081639 and A in rs763089682, are 0.00000824, and a polyphen-2 analysis predicted these amino acid changes to be probably damaging, with a score of 1.000. The combination of extremely rare SNPs in DNAH9 and RSPH1 genes might have been the possible mechanism underlying the development of the laterality defect in the present case.

Three cases of histologically proven hepatic epithelioid hemangioendothelioma evaluated using a second-generation microbubble contrast medium in ultrasonography: case reports.

BACKGROUND: Hepatic epithelioid hemangioendothelioma (HEH) is rare; it is reported in < 1 person in 1,000,000 individuals. For accurate diagnosis, information regarding multiple graphic modalities in HEH is required. However, there is very little information concerning Sonazoid® contrast enhanced ultrasonography (CEUS) in HEH. CASE PRESENTATION: The present report describes the histologically proven three HEH cases evaluated using Sonazoid® CEUS. Case 1 was a 33-year-old female patient with no relevant past medical history, who experienced right upper quadrant pain. Conventional abdominal US revealed multiple low echoic liver nodules with vague borderlines. In CEUS, the vascularity of the nodules was similar to that seen in the neighboring normal liver. Later in the portal venous and late phases (PVLP) and post vascular phase, washout of Sonazoid® was detected in the nodules. Case 2 was a 93-year-old female patient with a previous medical history including operations for breast cancer and ovary cancer in her 50's. Conventional abdominal US revealed multiple low echoic nodules, some of which contained cystic lesions. In the early vascular phase of CEUS, nodules excluding the central anechoic regions were enhanced from peripheral sites. Although the enhancement inside the nodules persisted in both the PVLP and post vascular phase, anechoic areas in the center of some nodules were not enhanced at all. Case 3 was a 39-year-old male patient presented with right upper-quadrant pain, without any relevant past medical history. Conventional abdominal US revealed multiple low echoic liver nodules. In the early vascular phase of CEUS, nodules were gradually enhanced from the peripheral sites as ringed enhancement. Sonazoid®was washed out from the nodules in the PVLP and post vascular phase. CONCLUSIONS: The most important feature was peripheral enhancement in the early vascular phase. In case 2, the enhancement of the parenchyma of liver nodules persisted even in the PVLP; indicating the lower degree of malignant potential than others. Actually, the tumors did not extend without any treatment in case 2. Since case 2 is the first case report of HEH with cystic lesions, in patients with liver nodules including cystic lesions, HEH is a potential diagnosis.

Biallelic alterations of the large tumor suppressor 1 (LATS1) gene in infiltrative, but not superficial, basal cell carcinomas in a Japanese patient with nevoid basal cell carcinoma syndrome.

The present study was conducted to address the molecular pathogenesis underlying the progression of basal cell carcinoma (BCC) in a nevoid basal cell carcinoma syndrome (NBCCS) patient. We analyzed infiltrative BCCs that invaded the subcutaneous tissue of the scalp and penetrated the skull in a 61-year-old Japanese female. Whole-exome sequencing validated by Sanger sequencing was applied to assess the subcutaneously infiltrative BCCs. Differences in genetic alterations between the superficial and infiltrative BCCs were also examined. Of particular note, the infiltrative BCCs showed a nonsense mutation, c.943C>T, resulting in p.Q315X in the large tumor suppressor 1 (LATS1) gene, as well as the loss of the wild-type allele of LATS1 (6q25.1), thus indicating that the LATS1 gene was biallelically disrupted. In contrast, no alterations in the LATS1 gene were observed in the superficial BCCs. Additionally, a loss of heterozygosity analysis revealed that the distal region of chromosome 6q where LATS1 locates was deleted in a heterozygous manner. The present results imply that the biallelic disruption of LATS1 is a progressive factor of the infiltrative BCCs observed in this NBCCS patient and suggest that the Hippo pathway is a potential therapeutic target in cases of infiltrative BCC.

A novel mutation of the axonemal dynein heavy chain gene 5 (DNAH5) in a Japanese neonate with asplenia syndrome.

Asplenia syndrome (Ivemark syndrome) is a complex disorder composed of asplenia, malpositioning of the visceral organs and congenital heart defects. To elucidate the underlying molecular mechanism of asplenia syndrome, we herein analyzed the fatal case of a male neonate who exhibited three lobes of the left lung, asplenia and complex heart anomalies and died 6 hours after delivery. A whole-exome sequence (WES) analysis followed by Sanger sequence identified a heterozygous single nucleotide change (c.7829A>G) in exon 47 of the axonemal dynein heavy chain gene 5 (DNAH5), which results in the missense mutation of p.Glu2610Gly. This mutation was found only in the neonate, but not in his parents, implying de novo mutation of DNAH5 that codes dynein heavy chain, a component of outer dynein arm. The WES analysis also identified a heterozygous single nucleotide substitution (c.3697C>T) in the axonemal dynein heavy chain gene 7 (DNAH7), resulting in p.Arg1233Cys, and a rare SNP (c.2029G>A, p.Gly677Ser) of the axonemal dynein intermediate chain gene 1 (DNAI1) in the patient and his mother, but not in his father. The mutation of p.Glu2610Gly in DNAH5 is novel and we here present a first Japanese case of asplenia syndrome who exhibited a DNAH5 mutation.

Biallelic disruption of the PTCH1 gene in multiple basal cell carcinomas in Japanese patients with nevoid basal cell carcinoma syndrome.

The aim of the present study is to address whether the molecular pathogenesis is identical among multiple basal cell carcinomas (BCCs) present in the same nevoid basal cell carcinoma syndrome (NBCCS) patient. Patient 1 is a 61-year-old (yo) Japanese female whose clinical characteristics and findings of a genetic analysis of PTCH1 have been previously described. Patient 2 is patient 1's 64-yo sister who also suffered from NBCCS with a single base deletion at nucleotide 2613 in exon 16 (c.2613delC) in one PTCH1 allele. Thirteen and 3 independent specimens of BCC were applied for a molecular analysis of loss of heterozygosity (LOH) in PTCH1 in patients 1 and 2, respectively. Of particular note is that all BCC specimens examined showed a loss of the wild-type allele of exon 16 in PTCH1, thus indicating that LOH results in the biallelic disruption of PTCH1 in multiple BCCs that develop in an age- and location-independent manner in the same patient. These results indicate that the germline single base deletion of PTCH1 (c.2613 delC) is a first hit and the LOH of the wild-type allele is a second hit, implying that all 16 BCCs detected in these NBCCS sisters fit the standard two-hit model.

[A case of esophageal squamous cell carcinoma with an adenocarcinoma component that dedifferentiated after chemotherapy].

CASE: A 69-year-old man was diagnosed with advanced esophageal cancer(well-differentiated squamous cell carcinoma). Neoadjuvant chemotherapy consisting of nedaplatin and 5-fluorouracil(5-FU)was initiated. After two courses of chemotherapy, the patient was judged to have achieved a clinical complete response. The patient then decided against undergoing surgery and opted instead to continue with the chemotherapy, receiving five courses in total. However, the esophageal cancer recurred, and subtotal esophagectomy was performed in January 2011. Squamous cell carcinoma with an adenocarcinoma component, which consisted of poorly differentiated squamous cell carcinoma and tubular adenocarcinoma cells, was observed at the primary site. Metastasis of the cancer to the liver was detected 2 months after surgery. The subsequent administration of four courses of docetaxel to the patient did not result in any beneficial effects, and the patient developed carcinomatous pleurisy and died of this complication in November 2011. The patient survived for a total of 21 months after starting chemotherapy. In this case, the chemotherapy itself may have resulted in the dedifferentiation of a well differentiated squamous cell carcinoma to result in a poorly differentiated squamous cell carcinoma with an adenocarcinoma component.

Magnetic resonance imaging-based radiomics analysis of the differential diagnosis of ovarian clear cell carcinoma and endometrioid carcinoma: a retrospective study.

PURPOSE: To retrospectively evaluate the diagnostic potential of magnetic resonance imaging (MRI)-based features and radiomics analysis (RA)-based features for discriminating ovarian clear cell carcinoma (CCC) from endometrioid carcinoma (EC). MATERIALS AND METHODS: Thirty-five patients with 40 ECs and 42 patients with 43 CCCs who underwent pretherapeutic MRI examinations between 2011 and 2022 were enrolled. MRI-based features of the two groups were compared. RA-based features were extracted from the whole tumor volume on T2-weighted images (T2WI), contrast-enhanced T1-weighted images (cT1WI), and apparent diffusion coefficient (ADC) maps. The least absolute shrinkage and selection operator (LASSO) regression with tenfold cross-validation method was performed to select features. Logistic regression analysis was conducted to construct the discriminating models. Receiver operating characteristic curve (ROC) analyses were performed to predict CCC. RESULTS: Four features with the highest absolute value of the LASSO algorithm were selected for the MRI-based, RA-based, and combined models: the ADC value, absence of thickening of the uterine endometrium, absence of peritoneal dissemination, and growth pattern of the solid component for the MRI-based model; Gray-Level Run Length Matrix (GLRLM) Long Run Low Gray-Level Emphasis (LRLGLE) on T2WI, spherical disproportion and Gray-Level Size Zone Matrix (GLSZM), Large Zone High Gray-Level Emphasis (LZHGE) on cT1WI, and GLSZM Normalized Gray-Level Nonuniformity (NGLN) on ADC map for the RA-based model; and the ADC value, spherical disproportion and GLSZM_LZHGE on cT1WI, and GLSZM_NGLN on ADC map for the combined model. Area under the ROC curves of those models were 0.895, 0.910, and 0.956. The diagnostic performance of the combined model was significantly superior (p = 0.02) to that of the MRI-based model. No significant differences were observed between the combined and RA-based models. CONCLUSION: Conventional MRI-based analysis can effectively distinguish CCC from EC. The combination of RA-based features with MRI-based features may assist in differentiating between the two diseases.

SRY-box Transcription Factor 6 Is Expressed Not Only in the Dorsal but Also in the Ventral Zone of the Neural Tube and Is Highly Expressed in the Notochord and Chordoma.

In the course of SRY-box transcription factor 6 (SOX6) expression profiling in human embryonic tissue, SOX 6 was found to be highly expressed in the notochord, based on the findings of immunohistochemistry (IHC). Sox6 is also expressed in the neural tube and the distribution of SOX6 is located in the ventral and dorsal zones of the neural tube. In contrast to the findings that SOX6-positive cells were located on the floor plate of the neural tube, OLIG2- and NKX2.2-expressing cells were lacking on the floor plate of the neural tube, and their expression was restricted only to the ventral zone of the neural tube. The expression patterns of SOX9 were similar to those of OLIG2 and NKX2.2 in the neural tube. NKX2.2 and OLIG2 are not expressed in the notochord, but SOX9 and SOX6 are. Because Sox6 is highly expressed in the notochord, the present study investigated whether or not SOX6 is an immunohistochemical marker for the pathologic diagnosis of chordoma, a neoplasm derived from the notochord. IHC revealed that chordoma was strongly positive for SOX6 in two cases of chordoma, one of which occurred in the sacrococcygeal region and another that developed at the base of the skull, suggesting that SOX6 is a useful marker for the histopathologic diagnosis of chordoma.

Autopsy cases of fulminant bacterial infection in adults: clinical onset depends on the virulence of bacteria and patient immune status.

To assist physicians in recognizing the potentially fatal onset of symptoms in cases of fulminant bacterial infection, we analyzed 11 autopsy cases of such infection (four caused by Streptococcus pneumoniae, four by S. pyogenes, one by S. dysgalactiae subsp. equisimilis, one by Staphylococcus aureus, and one by Vibrio vulnificus). Clinicohistopathologic features were evaluated. All patients experienced sudden onset of hypotension and multiple organ failure, leading to unexpected death. Blood culture confirmed bacteremia. The main chief complaints were gastrointestinal symptoms (45%) and limb pain (36%). All had an underlying chronic illness (82%), e.g., a hematologic disorder (36.3%) or liver cirrhosis (27.2%). Necrotizing fasciitis occurred in only 55% of cases, with none involving pneumococcal infection. Laboratory tests typically showed C-reactive protein elevation but without leukocytosis, indicating a high-level inflammatory state. In ten cases, death was attributed to circulatory collapse due to sepsis; severe pulmonary congestion and hemorrhage were present in these cases. The onset of fulminant bacterial infection depends on both virulence of the bacterium and status of the host defense system.

Small intestinal bleeding and stricture caused by Meckel's diverticulum.

A 44-year-old man presented to our hospital with lower gastrointestinal bleeding. We performed balloon-assisted enteroscopy, which revealed diverticulum and stricture at the ileum. The patient underwent segmental small bowel resection and diagnosed with Meckel's diverticulum. We should keep in mind the possibility of intestinal stricture due to Meckel's diverticulum.

A case report on severe nivolumab-induced adverse events similar to primary sclerosing cholangitis refractory to immunosuppressive therapy.

INTRODUCTION: Immune checkpoint inhibitors (ICIs), particularly anti-PD-1 antibody, have dramatically changed cancer treatment; however, fatal immune-related adverse events (irAEs) can develop. Here, we describe a severe case of sclerosing cholangitis-like irAE. We report the use of 3 immunosuppressive agents that resulted in the death of the patient due to treatment inefficacy. According to a postmarketing study of nivolumab, the frequency of ICI-related sclerosing cholangitis is 0.27% and that of ICI-related cholangitis is 0.20%. There have been 4 case reports of sclerosing cholangitis-like irAE, with imaging findings, including typical intrahepatic bile duct beaded constriction in primary sclerosing cholangitis. Treatment starts with prednisolone and is combined with an immunosuppressant in refractory cases. There are no reports of severe cases that ultimately led to death. PATIENTS CONCERNS: The patient is a 64-year-old male with Stage IV squamous cell lung carcinoma; he was hospitalized with abdominal pain and elevation of aspartate transaminase and alanine transaminase, approximately 4 months after ICI administration was suspended. This occurred because the patient treated with nivolumab as the second-line chemotherapy and developed type 1 diabetes mellitus after 11 courses. DIAGNOSIS: A grade 3 increase in bilirubin was observed and he was diagnosed with sclerosing cholangitis, based on magnetic resonance cholangiopancreatography imaging and pathological findings of the liver and bile duct. INTERVENTIONS: Prednisolone, mycophenolate mofetil, and tacrolimus combination therapy was administered. OUTCOMES: The treatment was difficult and failed. He died from liver failure 8 months after diagnosis. In this case, hepatitis and cholangitis, mainly alanine transaminase-dominant liver disorder, developed in the early stages of irAEs. Although he showed some improvement after prednisolone administration, bilirubin levels began rising again, and sclerosing cholangitis did not improve even with the use of 3 immunosuppressive agents recommended by the ESMO Clinical Practice Guidelines for immune-related hepatotoxicity management. Although the antitumor effect showed a complete response, liver failure led to death. CONCLUSION: This is the first case report on the ineffectiveness of triple immunosuppressant combination therapy recommended by the guidelines for immune-related hepatotoxicity. It is necessary to develop more appropriate treatment for severe sclerosing cholangitis-like irAE based on the robust evidence.

Coordinate expression of cytokeratin 8 and cytokeratin 17 immunohistochemical staining in cervical intraepithelial neoplasia and cervical squamous cell carcinoma: an immunohistochemical analysis and review of the literature.

OBJECTIVE: Several Cytokeratin (CK) isoforms have been analyzed in cervical intraepithelial lesions. However, previously reported numbers of specimens have been too low to evaluate any correlation between CK and CIN. METHODS: We examined the immunohistochemical staining of p16, CK8, and CK17 in 134 cervical tissues obtained by punch biopsy and graded as follows: CIN I (n=39), CIN II (n=31), CIN III (n=43), SCC (n=21). RESULTS: p16 staining was identified in 74.4% of CIN I, 93.6% of CIN II, 97.7% of CIN III, and 100% of SCC cases. CK8 and CK17 staining were identified in 12.8% and 33.3% of CIN I, 22.6% and 58.1% of CIN II, 62.8% and 81.4% of CIN III, and 71.4% and 95.2% of SCC cases, respectively. Interestingly, positivity for CK8 and CK17 correlated with increasing lesion grade of the intraepithelial lesions and also correlated with p16 staining (p16, p=0.0008; CK8, p<0.0001, and CK17, p<0.0001), and a coordinate expression profile of CK8[+]/CK17[+] correlates with increasing CIN grade and carcinoma (likewise, a coordinate expression profile of CK8[-]/CK17[-] correlates with decreasing CIN grade and absence of carcinoma), but expression of just CK8 (CK8[+]/CK17[-]) or just CK17 (CK8[-]/CK17[+]) does not correlate with increasing CIN grade and carcinoma. CONCLUSIONS: Results of the present study showed that p16, CK8, and CK17 immunostaining differed according to the degree of cervical intraepithelial lesions and SCC, and surprisingly, that staining was significantly correlated with increasing lesion grade of CIN and SCC.

Autopsy cases of fulminant-type bacterial infection with necrotizing fasciitis: group A (beta) hemolytic Streptococcus pyogenes versus Vibrio vulnificus infection.

Two autopsy cases of fulminant-type infection associated with necrotizing fasciitis were analyzed clinicopathologically. Both cases involved 57-year-old alcohol abusers. The former was a woman with group A (beta) hemolytic Streptococcus pyogenes infection, and the latter was a man with Vibrio vulnificus infection. The sudden onset of shock with high fever resulted in sepsis, decreased clotting, and hepatorenal symptoms, followed by death within a few days. Post-mortem examination showed widespread congestion and bleeding, and alcoholic liver cirrhosis was observed. Necrotizing fasciitis was identified in both cases. Bacteria from the pharynx or intestinal tract invaded the blood, and marked bacterial proliferation produced sepsis, resulting in necrotizing fasciitis. Despite the presence of sepsis, bilateral pulmonary congestion and bleeding were observed without pneumonia. Due to the rapid progression of sepsis, there was no time for granulocyte migration from the bone marrow. It seems that almost all mature granulocytes which had already existed in the bone marrow accumulated at the focus of necrotizing fasciitis because the bone marrow had few mature granulocytes and lacked hypercellularity. The cause of death in each case was circulatory collapse due to septic shock. It was difficult to distinguish the type of infection on histopathology. Cultures were necessary to determine the bacterial agents involved.

Analysis of YAP1 and TAZ expression by immunohistochemical staining in malignant mesothelioma and reactive mesothelial cells.

[This retracts the article DOI: 10.3892/ol.2018.8225.].

Analysis of YAP1 and TAZ expression by immunohistochemical staining in malignant mesothelioma and reactive mesothelial cells.

Gene mutations are involved in the development of malignant mesothelioma. Important mutations have been identified in the genes for cyclin-dependent kinase inhibitor 2A (p16) alternative reading frame, breast cancer-associated protein 1 (BAP1) and neurofibromatosis type 2 (NF2). Previously, the utility of detecting the loss of BAP1 by immunohistochemistry (IHC) and p16-deletion by fluorescence in situ hybridization has been identified in several studies. However, NF2-associated examinations have not been performed. The present study aimed to evaluate the expression of yes-associated protein 1 (YAP1) and tafazzin (TAZ) protein, which are associated with NF2 gene mutations, in malignant mesothelioma (MM) and reactive mesothelial cells (RMCs). Formalin-fixed paraffin-embedded tissues from 31 MM and 33 RMC samples were analyzed. The expression of YAP1 and TAZ protein were examined by IHC. Positivity for YAP1 was identified 27/31 MM and 15/33 RMC samples. Positivity for TAZ was identified in 28/31 MM and 18/33 RMC samples. Using the optimal cutoff points determined by the receiver operating characteristic curve, a positive IHC result for YAP1 and TAZ was 74% sensitive and 94% specific for detecting MM. The results indicate that increased expression of YAP1 and TAZ may be associated with mesothelial tumorization, and aid in the diagnosis of MM.

Increased expression of interleukin-17 is associated with macrophages in chronic immune thrombocytopenia.

Objectives: Interleukin-(IL-)17-mediated cells contribute to the imbalance of cellular immunity in the pathogenesis of immune thrombocytopenia (ITP). We examined samples of bone marrow (BM) clots to determine if IL-17-mediated immunological changes involve the BM and to identify clinical predictors of treatment response. Methods: We enrolled 33 patients with chronic ITP. BM clots were obtained before treatment and stained with the following markers: CD3, CD4, CD8, CD20, CD25, CD68, CD163, and IL-17. Pathological findings and clinical information, including laboratory data, were compared between the patients and 11 control subjects and between IL-17-high and -low-expression groups. Results: Univariate analysis revealed increased cells expressing CD68, CD163, and IL-17 in the patients with ITP than in the control subjects (P = 0.02, 0.001, and 0.001, respectively). The expression of both CD68 and CD163 showed correlation with IL-17 expression (r = 0.60 and 0.48, respectively). Responses to Eltrombopag were better in the IL-17-low-expression group than in the IL-17-high-expression group (P = 0.056). Conclusions: Macrophages and monocytes were associated with IL-17 expression in patients with ITP. We demonstrated that ITP is associated with IL-17-expressing monocytes/macrophages and might be more difficult to treat.

Expression of matrix metalloproteinase-7 correlates with the invasion of T1 colorectal carcinoma.

T1 colorectal carcinomas (CRCs) are an initial site of metastatic spread. Various risk factors for lymph node metastasis have been investigated in T1 CRCs. However, the major step in the entire process of metastasis remains unclear. In terms of carcinoma invasion and metastasis, matrix metalloproteinases (MMPs) have recently gained increasing attention. Notably, MMP-7 is frequently overexpressed in CRCs, but its implication has not been determined in T1 CRCs yet. The present study aimed to clarify the associations between the pathological risk factors of T1 CRCs and MMP-7. In the current study, 211 lesions of T1 CRC that were resected endoscopically or surgically at Showa University Northern Yokohama Hospital (Yokohama, Japan) between April 2008 and December 2009 were retrospectively analyzed. MMP-7 was immunostained and evaluated by its frequency of expression. Pathological factors of T1 CRCs were analyzed in association with MMP-7 expression. Furthermore, the ultrastructural alterations of carcinoma invasion were examined using low vacuum-scanning electron microscopy (LV-SEM). MMP-7 expression was associated with venous invasion (P=0.005), and LV-SEM revealed the disappearance of the normal structure of collagen and elastic fibers of veins invaded by tumor cells expressing MMP-7. At the invasive front, MMP-7 has a vital role in carcinoma invasion, correlating with venous invasion of T1 CRCs.

Mutation of the PTEN gene in a human hepatic angiosarcoma.

The phosphatase and tensin homolog (mutated in multiple advanced cancers 1) gene, or PTEN, encodes a lipid phosphatase that contains a PTPase domain and a C2 domain and plays a role as a tumor suppressor that negatively regulates the cell-survival signaling pathway initiated by phosphatidylinositol 3-kinase (PI3K). The PTEN protein inhibits angiogenesis, and somatic mutations of the PTEN gene are involved in canine hemangiosarcoma. We screened for mutations of the PTEN gene in two patients with human hepatic angiosarcoma to determine whether PTEN is involved in the pathogenesis of human hepatic angiosarcoma. In one patient, who suffered from breast cancer, pharyngeal cancer, and hepatic angiosarcoma, we found a single base substitution in exon 7 (640C>T) of the PTEN gene in both the hepatic angiosarcoma and normal tissues. This transition results in a germline nonsense mutation (Q214X). These findings indicate that analysis of PTEN gene mutations may be useful for characterization of the molecular event in hepatic angiosarcoma and cancer predisposition.

Novel BLIMP1/PRDM1 gene mutations in B-cell lymphoma.

B lymphocyte-induced maturation protein 1 (BLIMP1)/PR domain containing 1 with zinc finger domain (PRDM1) is a transcriptional repressor with a SET domain and Kruppel-type zinc fingers. BLIMP1/PRDM1 is expressed in a subset of germinal center B cells and in all plasma cells, and it is required for terminal B-cell differentiation. Mutations of the BLIMP1 gene have been reported in patients with diffuse large B-cell lymphoma. Here, we describe novel mutations in the BLIMP1 gene in 2 of 15 (13%) cases of B-cell lymphoma (two cases of primary effusion lymphoma and 13 cases of diffuse large B-cell lymphoma). A tandem 10-base pair duplication (5'-GCTGAGTTTG-3') was found in exon 2 of the BLIMP1 gene in primary effusion B-cell lymphoma. We also found in diffuse large B-cell lymphoma a single base substitution in exon 6 (1747C-->T) that results in a somatic nonsense mutation (Q583X). These findings indicate that mutational analysis of the BLIMP1 gene may be useful for characterizing the molecular basis of B-cell lymphoma.