Incidence of lymphoid neoplasms among atomic bomb survivors by histological subtype, 1950 to 1994.

Epidemiological data have provided limited and inconsistent evidence on the relationship between radiation exposure and lymphoid neoplasms. We classified 553 lymphoid neoplasm cases diagnosed between 1950 and 1994 in the Life Span Study cohort of atomic bomb survivors into World Health Organization subtypes. Mature B-cell neoplasms represented 58%, mature T-cell and natural killer (NK)-cell neoplasms 20%, precursor cell neoplasms 5%, and Hodgkin lymphoma (HL) 3%, with the remaining 15% classified as non-Hodgkin lymphoid (NHL) neoplasms or lymphoid neoplasms not otherwise specified. We used Poisson regression methods to assess the relationship between radiation exposure and the more common subtypes. As in earlier reports, a significant dose response for NHL neoplasms as a group was seen for males but not females. However, subtype analyses showed that radiation dose was strongly associated with increased precursor cell neoplasms rates, with an estimated excess relative risk per Gy of 16 (95% Confidence interval: 7.0, >533) at age 50. The current data based primarily of tissue-based diagnoses suggest that the association between radiation dose and lymphoid neoplasms as a group is largely driven by the radiation effect on precursor cell neoplasms while presenting no evidence of a radiation dose response for major categories of mature cell neoplasms, either B- or T-/NK-cell, or more specific disease entities (diffuse large B-cell lymphoma, plasma cell myeloma, adult T-cell leukemia/lymphoma) or HL.

Non-sebaceous lymphadenoma-like mucoepidermoid carcinoma: A case report.

Non-sebaceous lymphadenoma is a rare benign salivary gland tumor comprised of non-sebaceous epithelial cells and lymphoid tissue. Although its clinicopathological features have been described, its histogenesis and genetic background have not yet been elucidated. MAML2 rearrangement and the resultant CRTC1/3-MAML2 fusion gene are well-known specific genetic changes in mucoepidermoid carcinoma. Here, we present a case of lymphoepithelial tumor characterized by histomorphology of the non-sebaceous lymphadenoma and CRTC1-MAML2 fusion gene. The patient was an 83-year-old woman with an 8-year history of a solid, well-circumscribed tumor in the parotid gland. Histologically, the tumor was surrounded by thin fibrous connective tissue and was composed of tubular-cystic and solid nests of epithelial cells equally distributed in the lymphoid tissue. The histological features were suggestive of non-sebaceous lymphadenoma. Although the histomorphology was not consistent with mucoepidermoid carcinoma, a diagnosis of non-sebaceous lymphadenoma-like mucoepidermoid carcinoma was made based on the presence of the CRTC1-MAML2 fusion gene. The histological features alone could not establish the diagnosis, and ancillary molecular analysis was required.

Increased risk of skin cancer in Japanese heterozygotes of xeroderma pigmentosum group A.

This study was designed to learn if asymptomatic heterozygotes with mutations in a DNA repair gene are at an increased risk for cancer. To examine this, we focused on carriers of an XPA founder mutation because the frequency of xeroderma pigmentosum (XP) patients is much greater among Japanese than Caucasians, more than half of Japanese XP patients are affected at the XPA gene, and the majority of XP-A patients carry the same founder mutation in the XPA gene. Here we show that the frequency of XPA heterozygote was 14/1698 (0.8%) in cancer-free controls, and the corresponding frequency in patients with nonmelanocytic skin cancer that developed in sun-exposed areas was 11/440 (2.5%, OR = 3.08, p = 0.0097) for basal cell carcinoma, and 3/272 (1.1%, OR = 1.34, p = 0.72) for squamous cell carcinoma. These results suggest a moderately elevated risk for skin cancer among XPA heterozygotes.

Watch-and-wait policy versus rituximab-combined chemotherapy in Japanese patients with intestinal follicular lymphoma.

BACKGROUND AND AIM: Few reports have demonstrated the effectiveness of treatments for intestinal follicular lymphoma (FL) because of the limited number of patients who undergo comprehensive small intestinal examinations. This study compared the efficacy of rituximab-combined chemotherapy in patients with asymptomatic and low tumor burden (LTB) intestinal FL, according to the criteria of the Groupe d'Etude des Lymphomes Folliculaires, with that of a "watch and wait" (W&W) approach. METHODS: The endoscopic examination for entire gastrointestinal tracts was performed in 29 Japanese patients with intestinal FL. These patients had CD21-positive follicular dendritic cells arranged in a duodenal pattern. In a prospective, two-center, open-label trial, this study evaluated the efficacy of rituximab-combined chemotherapy ([cyclophosphamide, doxorubicin, vincristine, and prednisone] or [cyclophosphamide, vincristine, and prednisone]) and prolonged treatment with rituximab (R-Chemo+prolongedR) in 14 patients and compared their outcomes with those of 15 patients managed with a W&W approach. RESULTS: Four patients managed with the W&W plan showed worsening macroscopic findings, lesion area enlargement, or clinical stage progression but stayed on this plan because they had LTB and experienced no changes in bowel function. In the R-Chemo+prolongedR group, all patients achieved complete remission; recurrence occurred in one patient, who was subsequently managed with the W&W plan because of LTB. There were no significant differences in progression-free survival between the two groups (P = 0.1045). Overall survival was 100% in both groups. CONCLUSIONS: The prognoses of patients with asymptomatic intestinal FL and LTB who were managed with a W&W strategy were comparable with those of patients receiving R-Chemo+prolongedR.

The role of "watch and wait" in intestinal follicular lymphoma in rituximab era.

OBJECTIVE: There is no consensus regarding the best treatment for intestinal follicular lymphoma (FL). We used "watch and wait" for patients with intestinal FL with low-tumor-burden (LTB) criteria and without mass formation causing bowel obstruction. We investigated the overall survival (OS) and time to treatment required (TTR). METHODS: Thirty-three intestinal FL patients [clinical stage (CS) I:16, II1:0, II2:7, IV:10; median observation period: 45.5 months, range: 13-110 months] were diagnosed via endoscopy. Detailed clinical and pathological examinations were performed, and neoplastic process behavior was monitored. RESULTS: All of the 33 patients were WHO grade 1. FL lesions in the digestive tract were found frequently in the second-fourth portion of the duodenum in 91% of the patients; 87% of those patients had lesions in a broader area including the small intestine. Two patients had an enlargement of the area of the lesions and a worsening of the macroscopic findings. Three patients had CS progression; however, these remained within the indication for "watch and wait." Two patients with transformation into diffuse large B-cell lymphoma received rituximab and chemotherapy, which led to complete remission. The OS was 100%. The time to treatment required (TTR) was 49 months in one patient and 37 months in one patient. CONCLUSION: Intestinal FL in CS I-IV with broad infiltration of the digestive tract meeting the criteria for LTB had a remarkably slow course. This study suggests that "watch and wait" is appropriate for the treatment of LTB intestinal FL even in the era of rituximab.

Characteristic miR-24 Expression in Gastric Cancers among Atomic Bomb Survivors.

OBJECTIVE: To elucidate the mechanism of radiation-induced cancers, we analyzed the expression profiles of microRNAs extracted from formalin-fixed paraffin-embedded (FFPE) gastric cancer (GC) tissue samples from atomic bomb survivors. METHODS: The expression levels of miR-21, miR-24, miR-34a, miR-106a, miR-143, and miR-145 were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR). RESULTS: The expression of microRNAs was measured by qRT-PCR in a Hiroshima University Hospital cohort comprising 32 patients in the high-dose-exposed group and 18 patients in the low-dose-exposed group who developed GC after the bombing. The GC cases showing high expression of miR-24, miR-143, and miR-145 were more frequently found in the high-dose-exposed group than in the low-dose-exposed group. We next performed qRT-PCR of miR-24, miR-143, and miR-145 in a cohort from the Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital comprising 122 patients in the high-dose-exposed group and 48 patients in the low-dose-exposed group who developed GC after the bombing. High expressions of miR-24 and miR-143 were more frequently found in the high-dose-exposed group than in the low-dose-exposed group. Multivariate analysis demonstrated that only high expression of miR-24 was an independent predictor for the exposure status. CONCLUSION: These results suggest that the measurement of miR-24 expression from FFPE samples is useful to identify radiation-associated GC.

[An epidermoid cyst derived from an intrapancreatic accessory spleen].

A 43-year-old female patient had high levels of CA19-9 marker; an abdominal ultrasound revealed a cyst. Further investigations with computed tomography (CT), magnetic resonance imaging, and endoscopic ultrasound CT identified a multilocular cystic lesion on the pancreatic tail. An abnormal wall was noted, and different signal strengths were measured in each cyst. Thus, a mucinous cystic tumor was diagnosed, and distal pancreatectomy combined with splenectomy was performed. During the surgery, we identified a multilocular pancreatic cyst with internal bleeding at its distal end. The lesion was ultimately diagnosed as an epidermoid cyst of an intrapancreatic accessory spleen. This diagnosis was based on the histological observation that the vascular construction of the cystic wall was equivalent to that of the spleen, and that its internal tissue was covered by squamous epithelium.

Case of early adenosquamous carcinoma of the stomach.

Adenosquamous carcinoma of the stomach is very rare; at present, there are only seven published reports. We report here an eighth case involving a 77-year-old Japanese man who was diagnosed with gastric cancer by upper endoscopy and computed tomography (CT). He underwent laparoscopic-assisted distal gastrectomy for early gastric cancer and the resected specimen was diagnosed as adenosquamous carcinoma limited to the submucosal layer. Only one lymph node metastasis was noted. Seven months later, liver metastasis (3 tumors, 15 mm maximum in diameter) was detected by abdominal CT. He was started on chemotherapy with S-1 and cisplatin (CDDP) and is alive 14 months after surgery. Almost all cases of adenosquamous carcinoma of the stomach are diagnosed in advanced stages and carry a very poor prognosis. Most patients with early adenosquamous carcinoma of the stomach survive for 2 or more years without recurrence, however our patient experienced recurrence 7 months after surgery. Therefore, future treatment for recurrent adenosquamous carcinoma of the stomach should be considered.

Orbital metastasis of invasive lobular carcinoma of the breast.

We herein report a case of orbital metastasis from the breast cancer in a 58-year-old woman presenting with visual disturbance and bilateral periorbital swelling. She had undergone radical mastectomy for right breast cancer 9 years previously and been receiving hormone therapy for bone metastasis of breast cancer for the past 4 years. Computed tomography and magnetic resonance imaging revealed an ill-defined mass in the bilateral orbits, whereas an excisional biopsy confirmed metastasis of invasive lobular carcinoma (ILC) of the breast. The appearance of eye symptoms in patients who have a history of breast cancer, especially ILC should be investigated, with a consideration of orbital metastasis.

Clinical features of gastrointestinal follicular lymphoma: comparison with nodal follicular lymphoma and gastrointestinal MALT lymphoma.

We retrospectively compared the clinicopathological features of primary intestinal follicular lymphomas (FL-GIs), nodal follicular lymphomas (FL-LNs) and gastrointestinal MALT lymphomas (MALT-GIs), and investigated the distribution and the endoscopic appearances of FL-GI to evaluate the effectiveness of treatment modality. The subjects were 28 FL-GI patients, 135 FL-LN patients and 70 MALT-GI patients. In FL-LNs the clinical stage III-IV was 83%, while in FL-GIs clinical stage I-II was 68%. In MALT-GIs clinical stage I-II was 87%. The overall survival was significantly better in MALT-GI patients than in FL-LN patients. All FL-GI patients were alive at the time of evaluation. Regarding the histological grade (WHO), grade 1 was 81% in FL-GI, whereas in FL-LN grade 2 was 28% and grade 3 was 11%. The Follicular Lymphoma International Prognostic Index was low in 61% of FL-GIs, while in FL-LNs it was equally distributed to low, intermediate and high, suggesting that the prognosis is better in FL-GIs than in FL-LNs. The clinicopathological studies revealed the FL-GI has intermediate characteristics between FL-LN and MALT-GI. We recommend a 'watch-and-wait' policy or chemotherapy with rituximab for the therapy of FL-GIs because the lesions are often located in broader areas from the lower duodenum to the small intestine.

Laparoscopy-assisted resection for Mesenteric Castleman's disease: Report of a case.

A 65-year-old female patient was diagnosed with breast cancer in 1995. An abdominal mass was detected by computed tomography and the patient was preoperatively diagnosed with a gastrointestinal stromal tumor. Laparoscopy-assisted surgical resection revealed a mesenteric Castleman's tumor of the hyaline vascular type. Mesenteric Castleman's disease is rare, and there have been only 42 cases reported in the English literature. We herein discuss the clinical findings of these cases.

A duodenal follicular lymphoma associated with the lesion mimicking MALT lymphoma in terminal ileum and Bauhin valve.

This is a case report of a 66-year-old woman who consulted us with a 1-week history of postprandial epigastric discomfort and dyspepsia. Upper and lower gastrointestinal endoscopy and double-balloon enteroscopy revealed lesions in three parts: a swelling with a shallow depression in the ampulla of Vater, flat and rough nodules in the jejunum, and a mixture of lymphoid polyposis and rough surface of follicular lymphoma of the terminal ileum and Bauhin valve. The histological, immunophenotypic, and molecular findings of the duodenal lesion confirmed the diagnosis of follicular lymphoma. We initially diagnosed the ileal lesion as MALT lymphoma immunohistochemically. However, Southern blot hybridization analysis for immunoglobulin heavy chain gene rearrangement showed identical monoclonal bands in both the duodenal and ileal lesions. The molecular cytogenetic studies were also positive for the 14;18 translocation in both lesions. Therefore, the true diagnosis of this ileal lesion should be a follicular lymphoma with marginal zone differentiation. Primary follicular lymphomas of gastrointestinal tract were suggested to have intermediate features between nodal follicular lymphoma and MALT lymphoma. This case is an important clue to prove the similarity of follicular lymphoma of gastrointestinal tract to MALT lymphoma and will be crucial in considering the therapeutic strategy.

Clinicopathological significance of CD79a expression in classic Hodgkin lymphoma.

Classic Hodgkin lymphoma (CHL) is a lymphoid neoplasia characterized by the presence of large tumor cells, referred to as Hodgkin and Reed-Sternberg (HRS) cells, originating from B-cells in an inflammatory background. As the clinical significance of B-cell markers has yet to be fully elucidated, this study aimed to clarify the clinicopathological significance of CD79a in 55 patients with CHL. They were immunohistochemically divided into two groups, comprising of 20 CD79a-positive and 35 CD79a-negative patients. There was no significant correlation between CD79a and CD20 expression (rs = 0.125, P = 0.362). CD79a-positive patients were significantly older at onset (P = 0.011). There was no significant correlation between CD79a-positivity and clinical stage (P = 0.203), mediastinal involvement (P = 0.399), extranodal involvement (P = 0.749), or laboratory findings, including serum levels of lactate dehydrogenase (P = 1) and soluble interleukin-2 receptor (P = 0.251). There were significant differences in overall survival (OS) (P = 0.005) and progression-free survival (PFS) (P = 0.007) between CD79a-positive and CD79a-negative patients (5-year OS: 64.6% and 90.5%; 5-year PFS: 44.0% and 76.6%, respectively). Five patients in whom the majority (> 80%) of HRS cells expressed CD79a consisted of 4 males and 1 female aged between 52 and 81 years; 4 of them were in a limited clinical stage. We concluded that CD79a-positive CHL may have unique clinicopathological features.

Serum soluble interleukin-2 receptor level and immunophenotype are prognostic factors for patients with diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma is the most common form of non-Hodgkin lymphoma. Although many studies have attempted to identify prognostic factors, most have focused on conventionally treated patients. The influence of anti-CD20 antibody (rituximab) should be considered now. We evaluated the prognostic significance of serum soluble interleukin-2 receptor levels and germinal center B-cell-like or non-germinal center B-cell like subgroups in 80 patients with diffuse large B-cell lymphoma, who had been treated with rituximab. Serum soluble interleukin-2 receptor levels ranged from 322 to 39900 U/mL (median 1365 U/mL). Sixteen (20%) were germinal center B-cell-like subgroups, and the remainder (80%) non-germinal center B-cell-like. Survival analysis associated lower serum soluble interleukin-2 receptor level and germinal center B-cell-like phenotype with better overall survival (P = 0.015), whereas multivariate analysis, including International Prognostic Index factors, revealed that only higher performance status score and higher serum lactate dehydrogenase levels significantly affected survival. However, serum soluble interleukin-2 receptor levels were elevated in patients with higher International Prognostic Index scores as well as in the non-germinal center B-cell-like subgroup. Serum soluble interleukin-2 receptor levels, International Prognostic Index, and subphenotypes were strongly correlated with each other. Our study showed that soluble interleukin-2 receptor is quite useful and may serve as a substitute for the International Prognostic Index, especially for patients undergoing treatment. Moreover, the differentiation between the germinal center B-cell-like and non-germinal center B-cell-like phenotypes is also useful for predicting patients with diffuse large B-cell lymphoma, even among those treated with rituximab.

Systemic IgG4-related lymphadenopathy: a clinical and pathologic comparison to multicentric Castleman's disease.

IgG4-related disease sometimes involves regional and/or systemic lymph nodes, and often clinically and/or histologically mimics multicentric Castleman's disease or malignant lymphoma. In this study, we examined clinical and pathologic findings of nine patients with systemic IgG4-related lymphadenopathy. None of these cases were associated with human herpes virus-8 or human immunodeficiency virus infection, and there was no T-cell receptor or immunoglobulin gene rearrangement. Histologically, systemic IgG4-related lymphadenopathy was classified into two types by the infiltration pattern of IgG4-positive cells: interfollicular plasmacytosis type and intra-germinal center plasmacytosis type. The interfollicular plasmacytosis type showed either Castleman's disease-like features or atypical lymphoplasmacytic and immunoblastic proliferation-like features. By contrast, the intra-germinal center plasmacytosis type showed marked follicular hyperplasia, and infiltration of IgG4-positive cells mainly into the germinal centers, and some cases exhibited features of progressively transformed germinal centers. Interestingly, eight of our nine (89%) cases showed eosinophil infiltration in the affected lymph nodes, and examined patients showed high elevation of serum IgE. Laboratory examinations revealed elevation of serum IgG4 and soluble interleukin-2 receptors. However, the levels of interleukin-6, C-reactive protein, and lactate dehydrogenase were within normal limits or only slightly elevated in almost all patients. One patient showed a high interleukin-6 level whereas C-reactive protein was within the normal limit. Autoantibodies were examined in five patients and detected in four. Compared with the previously reported cases of multicentric Castleman's disease, our patients with systemic IgG4-related lymphadenopathy were significantly older and had significantly lower C-reactive protein and interleukin-6 levels. In conclusion, in our systemic IgG4-related lymphadenopathy showed pathologic features only partially overlapping those of multicentric Castleman's disease, and serum data (especially C-reactive protein and interleukin-6) are useful for differentiating the two. Our findings of eosinophil infiltration in the affected tissue and elevation of serum IgE may suggest an allergic mechanism in the pathogenesis of systemic IgG4-related lymphadenopathy.

Hepatocellular carcinoma infiltrated with non-Hodgkin's lymphoma: report of a case.

A 70-year-old woman diagnosed to have a hepatitis C virus (HCV) infection was referred to our hospital because of a solitary liver tumor. because of a solitary liver tumor. She underwent a partial hepatectomy, and the tumor was histologically diagnosed as a hepatocellular carcinoma (HCC). diagnosed as a hepatocellular carcinoma (HCC). In addition, a focal follicle consisting of atypical lymphoid cells was seen within the HCC. cells was seen within the HCC. Two months later, she was readmitted because of weakness and rapidly developing abdominal fullness. developing abdominal fullness. An abdominal computed tomography scan showed widespread tumors with ascites. with ascites. A cytological examination of the ascites showed large-sized atypical lymphoid cells. showed large-sized atypical lymphoid cells. An immunohistochemical stain confirmed that the atypical lymphoid cells within the HCC were positive for the CD 20 antigen. antigen. Taking these findings into account, the hepatic tumor was determined to be a HCC infiltrated with diffuse large B-cell lymphoma. diffuse large B-cell lymphoma. The coexistence of HCC and non-Hodgkin's lymphoma (NHL) is extremely rare. and non-Hodgkin's lymphoma (NHL) is extremely rare. We herein report a case of HCC infiltrated with NHL. We herein report a case of HCC infiltrated with NHL.

Predictive value of endoscopy and endoscopic ultrasonography for regression of gastric diffuse large B-cell lymphomas after Helicobacter pylori eradication.

BACKGROUND: Some gastric diffuse large B-cell lymphomas have been reported to regress completely after the successful eradication of Helicobacter pylori. The aim of this study was to investigate the clinical characteristics of gastric diffuse large B-cell lymphomas without any detectable mucosa-associated lymphoid tissue (MALT) lymphoma that went into complete remission after successful H. pylori eradication. PATIENTS AND METHODS: We examined the effect of H. pylori eradication in 15 H. pylori-positive gastric diffuse large B-cell lymphoma patients without any evidence of an associated MALT lymphoma (clinical stage I by the Lugano classification) by endoscopic examination including biopsies, endoscopic ultrasonography, computed tomography, and bone marrow aspiration. RESULTS: H. pylori eradication was successful in all the patients and complete remission was achieved in four patients whose clinical stage was I. By endoscopic examination, these gastric lesions appeared to be superficial. The depth by endoscopic ultrasonography was restricted to the mucosa in two patients and to the shallow portion of the submucosa in the other two patients. All four patients remained in complete remission for 7-100 months. CONCLUSION: In gastric diffuse large B-cell lymphomas without a concomitant MALT lymphoma but associated with H. pylori infection, only superficial cases and lesions limited to the shallow portion of the submucosa regressed completely after successful H. pylori eradication. The endoscopic appearance and the rating of the depth of invasion by endosonography are both valuable for predicting the efficacy of H. pylori eradication in treating gastric diffuse large B-cell lymphomas.

Leiomyosarcoma originating from the superior mesenteric vein: a case report and review of the literature.

We describe a rare case of leiomyosarcoma originating from the superior mesenteric vein with concomitant liver metastases in a 62-year-old woman. She underwent a tumor resection and venous reconstruction, right hemicolectomy, and right hepatic lobectomy. Since the tumor was weakly positive for c-kit, she was treated with imatinib mesylate for the recurrent liver tumors. She has survived for about 3 years after undergoing the surgical procedures.

Putative lung adenocarcinoma with epidermal growth factor receptor mutation presenting as carcinoma of unknown primary site: A case report.

RATIONALE: Only a few cases of putative lung adenocarcinoma presenting as carcinoma of unknown primary site (CUP) with epidermal growth factor receptor (EGFR) mutation have been reported, and the efficacy of EGFR-tyrosine kinase inhibitors (TKIs) for these cases is unclear. PATIENT CONCERNS AND DIAGNOSES: A 67-year-old man complained of paresis of the right lower extremity, dysarthria, and memory disturbance. Computed tomography and magnetic resonance imaging showed multiple brain tumors with brain edema and swelling of the left supraclavicular, mediastinal, and upper abdominal lymph nodes. Moreover, a metastatic duodenal tumor was detected via upper gastrointestinal endoscopy examination. The biopsy specimen of the lesion was examined and was diagnosed as adenocarcinoma with CK7 and TTF-1 positivity. Finally, the case was diagnosed as EGFR mutation-positive putative lung adenocarcinoma presenting as CUP. INTERVENTIONS AND OUTCOMES: Oral erlotinib, an EGFR-TKI, was administered at 150 mg daily. Five weeks later, the brain lesions and several swollen lymph nodes showed marked improvement, and the symptoms of the patient also improved. Three months later, the duodenal lesion was undetected on upper gastrointestinal endoscopy. After an 8-month follow-up, the patient was well with no disease progression. LESSONS: Putative lung adenocarcinoma presenting as CUP may have EGFR mutation, and EGFR-TKI therapy may be effective for such malignancy.