[Gastric type adenoma with submucosal invasive carcinoma:a case study].

A 75-year-old woman visited our hospital for the examination of esophagogastroduodenoscopy (EGD) without any major complaint. The patient's medical history included hypertension, but no carcinoma. EGD revealed a 30-mm elevated lesion located in the anterior wall of the upper region of the stomach. The lesion, which was a 0-IIa+I type lesion with fading-like and light flare-like domains, was surgically removed using endoscopic submucosal dissection (ESD) and then the patient was diagnosed with gastric type adenoma with submucosal invasive carcinoma. To the best of our knowledge, this is the first report of a gastric type adenoma with submucosal invasive carcinoma and may therefore provide significant insights into the malignant potential of gastric type adenoma lesions.

[A Case of Duodenal Invasive Advanced Gastric Cancer in Which the Primary Tumor Achieved pCR, but Viable Cancer Cells Remained in Lymph Node No.13 after Neoadjuvant Chemotherapy].

A woman approximately 70-years-old with duodenal invasive advanced gastric cancer was referred to our hospital. Meta- stasis to lymph node(LN)No.13 was suspected based on FDG/PET-CT. For better curability, we selected neoadjuvant chemotherapy( NAC)with S-1 plus oxaliplatin(SOX therapy). After 3 courses of SOX, distal gastrectomy with D2(+No.13) lymphadenectomy was performed. Upon pathological evaluation, no viable cancer cells were found in the primary tumor, but viable cancer cells were identified in LN No.6 and 13. LN No.13 was defined as M1 according to the current Japanese classification of gastric carcinoma. On the other hand, the 2014 Japanese gastric cancer treatment guidelines(ver. 4)mentioned that D2(+No.13)lymphadenectomy may be an option in potentially curative gastrectomy for tumors invading the duodenum. This case suggests that No.13 lymphadenectomy is necessary as a curative operation for duodenal invasive advanced gastric cancer, even if the primary tumor has achieved pCR after NAC.

[A Rare Case of Abdominal Malignant Triton Tumor].

A 60-year-old woman presented at our hospital with abdominal pain and vomiting.Three abdominal tumors were detected, and she was referred to our department for surgery.She underwent an enterectomy including 2 of the tumors.The third tumor could not be resected because it had invaded the superior mesenteric artery(SMA)and superior mesenteric vein(SMV). Based on positive immunohistochemistry results for S-100 protein and desmin, nerve sheath differentiation with rhabdomyoblastic differentiation was confirmed, and she was diagnosed with a malignant triton tumor(MTT).She received postoperative chemotherapy with adriamycin and dacarbazine.However, she died 7 months after surgery, with multiple peritoneal metastases.MTT is a subtype of malignant peripheral nerve sheath tumor and is very rare.MTT has a poor prognosis with a high tendency of local recurrence and early metastasis.The most common treatment strategy is radical resection followed by postoperative chemoradiotherapy.When preoperative diagnosis is possible, radical resection with clear margins should be performed.

Association between IgG4-related disease and progressively transformed germinal centers of lymph nodes.

Progressively transformed germinal centers is a benign condition of unknown pathogenesis characterized by a distinctive variant form of reactive follicular hyperplasia in lymph nodes. We recently reported Ig G4-related disease in progressively transformed germinal centers. However, no large case series has been reported and clinicopathologic findings remain unclear. Here, we report 40 Japanese patients (28 men, 12 women; median age, 56 years) with progressively transformed germinal centers of the lymph nodes who fulfilled the histological diagnostic criteria for IgG4-related disease (IgG4(+) progressively transformed germinal centers), with asymptomatic localized lymphadenopathy involving the submandibular nodes in 24, submandibular and cervical nodes in 14, cervical nodes only in 1, and cervical and supraclavicular nodes in 1. In all, 16 (52%) of 31 examined patients had allergic disease. Histologically, the lymph nodes demonstrated uniform histological findings, namely marked follicular hyperplasia with progressively transformed germinal centers, and localization of the majority of IgG4(+) plasma cells in the germinal centers. Serum IgG4, serum IgE and peripheral blood eosinophils were elevated in 87%, 92% and 53% of examined patients, respectively. Eighteen patients subsequently developed extranodal lesions (including five who developed systemic disease), which on histological examination were consistent with IgG4-related disease. IgG4(+) progressively transformed germinal centers presents with uniform clinicopathological features of asymptomatic localized submandibular lymphadenopathy, which persists and/or relapses, and sometimes progresses to extranodal lesions or systemic disease. Nine patients were administered steroid therapy when the lesions progressed, to which all responded well. We suggest that IgG4(+) progressively transformed germinal centers should be included in the IgG4-related disease spectrum.

Clinical features of biliary tract cancer in Japanese individuals with Lynch syndrome.

Background: Biliary tract cancer (BTC) is a Lynch syndrome (LS)-associated cancer with a high mortality rate. This study aimed to clarify the clinical features of BTC in individuals with LS and to discuss its management. Methods: We obtained data from genetically verified Japanese individuals with LS who were diagnosed at a single institution, between January 2003 and April 2021. Moreover, 21 individuals with sporadic BTC (n=15) and LS associated BTC (n=6) underwent microsatellite instability (MSI) testing. Results: Among 92 individuals with LS, 6 individuals with MLH1 variants developed BTCs (10 lesions, male/female, 2:1). The median age at diagnosis of initial BTC was 69 years (range, 34-78 years). Histological examination revealed a predominance of differentiated adenocarcinoma (89%). Then, 2 individuals had multiple BTCs. All available 7 BTC lesions showed high-frequency of microsatellite instability (MSI-H). MLH1 carriers showed a 7.2% cumulative risk of BTC development at an age of 70 years. Five of the six individuals died of BTC. Conclusions: MSI analysis could facilitate LS identification in individuals with BTC. Surveillance for BTC should be considered for MLH1 carriers in Japan.

Clinicopathologic Analysis of Sinonasal Inverted Papilloma, with Focus on Human Papillomavirus Infection Status.

Sinonasal inverted papilloma (SNIP) can recur; however, the factors related to tumor recurrence remain unclear. This study aimed to analyze risk factors, including human papillomavirus (HPV) infection, as well as other factors associated with SNIP recurrence. Thirty-two patients who were diagnosed with SNIP and underwent surgery between 2010 and 2019 were enrolled: 24 men and 8 women, with a mean age of 59.2 years. The mean follow-up was 57.3 months. Demographics and information about history of smoking, diabetes mellitus (DM), hypertension, allergic rhinitis, alcohol consumption, tumor stage, surgical approach, and recurrence were reviewed retrospectively. Specimens were investigated using polymerase chain reaction to detect HPV DNA (high-risk subtypes: 16, 18, 31, 33, 35, 52b, and 58; low-risk subtypes: 6 and 11). Seven patients (21.9%) experienced recurrence. HPV DNA was detected in five (15.6%) patients (high-risk subtypes, n = 2; low-risk subtypes, n = 3). Patients with recurrence of SNIP had a higher proportion of young adults and displayed higher rates of HPV infection, DM, and advanced tumor stage than those without recurrence. HPV infection, young adulthood, DM, and advanced tumor stage could be associated with a high recurrence rate, which suggests that patients with these risk factors could require close follow-up after surgery.

Small cell variant of mantle cell lymphoma is an indolent lymphoma characterized by bone marrow involvement, splenomegaly, and a low Ki-67 index.

Mantle cell lymphoma (MCL) is recognized as a well-defined B cell neoplasm characterized by overexpression of cyclin D1 (CCND1), with "classical" and "aggressive" variant subtypes. A small-cell variant of MCL (small-MCL), resembling small lymphocytic lymphoma/chronic lymphocytic lymphoma (CLL/SLL), has been added to the World Health Organization classification. However, to the best of our knowledge, there have been no studies focusing on this neoplasm. In the present study, we analyzed 15 cases of CCND1-positive small-MCL, including immunohistochemical analysis of Ki-67 and CCND1 expression, and compared our findings with those of 151 cases of classical MCL. Morphologically, most small-MCL showed a diffuse growth pattern (76.9%), whereas others featured a very thin mantle zone pattern resembling a reactive follicle (23.1%). Bone marrow involvement and splenomegaly occurred significantly more frequently in small-MCL than in classical MCL (P < 0.05). Ki-67 expression in small-MCL was lower than in classical MCL (mean [± 2 SD] 12.5 ± 17.3% and 25.2 ± 25.5%, respectively; P < 0.001), but there was no significant difference in CCND1 expression (P = 0.2445). The 5-year survival rate in small-MCL was 83.3%. Although there was no significant difference in outcome between small-MCL and classical MCL (P = 0.287), only one small-MCL patient died of the disease. Thus, small-MCL constitutes a specific subset of indolent lymphoma with distinguishing features, possibly making a major contribution to the accuracy of therapeutic decisions. In addition, clinicians should be aware of the possible presence of small-MCL to avoid making a misdiagnosis of follicular hyperplasia or CLL/SLL.

Primary gastrointestinal follicular lymphoma involving the duodenal second portion is a distinct entity: a multicenter, retrospective analysis in Japan.

We conducted a multicenter, retrospective study to determine the anatomical distribution and prognostic factors of gastrointestinal (GI) follicular lymphoma (FL). This study included 125 patients with stage I and II(1) GI-FL. Of the 125 patients, the small intestine was examined in 70 patients, with double-balloon endoscopy and/or capsule endoscopy. The most frequently involved GI-FL site was the duodenal second portion (DSP) (81%), followed by the jejunum (40%); 85% of patients with involvement of the DSP also had jejunal or ileal lesions. The absence of abdominal symptoms and macroscopic appearance of multiple nodules were significantly present in the DSP-positive group. During a median follow up of 40 months, six patients showed disease progression. Patients with involvement of the DSP had better progression-free survival (PFS) than those without such involvement (P = 0.001). A multivariate analysis revealed that male sex, the presence of abdominal symptoms, and negative involvement of the DSP were independently associated with poor PFS. In conclusion, most patients with GI-FL have duodenal lesions associated with multiple jejunal or ileal lesions. Gastrointestinal follicular lymphomas involving the DSP might be a distinct entity showing a favorable clinical course.

Multi-step aberrant CpG island hyper-methylation is associated with the progression of adult T-cell leukemia/lymphoma.

Aberrant CpG island methylation contributes to the pathogenesis of various malignancies. However, little is known about the association of epigenetic abnormalities with multistep tumorigenic events in adult T cell leukemia/lymphoma (ATLL). To determine whether epigenetic abnormalities induce the progression of ATLL, we analyzed the methylation profiles of the SHP1, p15, p16, p73, HCAD, DAPK, hMLH-1, and MGMT genes by methylation specific PCR assay in 65 cases with ATLL patients. The number of CpG island methylated genes increased with disease progression and aberrant hypermethylation in specific genes was detected even in HTLV-1 carriers and correlated with progression to ATLL. The CpG island methylator phenotype (CIMP) was observed most frequently in lymphoma type ATLL and was also closely associated with the progression and crisis of ATLL. The high number of methylated genes and increase of CIMP incidence were shown to be unfavorable prognostic factors and correlated with a shorter overall survival by Kaplan-Meyer analysis. The present findings strongly suggest that the multistep accumulation of aberrant CpG methylation in specific target genes and the presence of CIMP are deeply involved in the crisis, progression, and prognosis of ATLL, as well as indicate the value of CpG methylation and CIMP for new diagnostic and prognostic biomarkers.

Association between the expression pattern of p16, pRb and p53 and the response to intravesical bacillus Calmette-Guerin therapy in patients with urothelial carcinoma in situ of the urinary bladder.

There is limited data regarding the association between the expression of cell cycle-regulating molecules and the response of patients with urothelial carcinoma in situ (CIS) to bacillus Calmette-Guerin (BCG) therapy. To examine the relationship between p16, pRb and p53 expression in bladder CIS and patient response to initial BCG therapy, we performed immunohistochemical studies for 27 patients with bladder CIS. Overexpression of p16, pRb, and p53 was observed in 37%, 41%, and 48% of patients, respectively. Initial BCG therapy was effective in 21 patients (78%). Coexistence of papillary urothelial carcinoma, depth (pTa or pT1) and grade of coexisting papillary carcinoma did not affect the response to BCG therapy. pRb overexpression had a significant relationship to poor response to BCG therapy (P= 0.027). The results of this study indicate that overexpression of pRb in bladder CIS predicts poor response of intravesical BCG instillation and status of p16 and p53 may not be predictive of initial BCG failure.

Mantle cell lymphoma shows three morphological evolutions of classical, intermediate, and aggressive forms, which occur in parallel with increased labeling index of cyclin D1 and Ki-67.

Although the 2008 World Health Organization classification defines two subtypes of mantle cell lymphoma (MCL), classical and aggressive, we often encounter MCL with both features in the same site. We named this feature "MCL with focal aggressive form (intermediate MCL)". In the present study, we reclassified 237 patients with cyclin D1 (CCND1)-positive MCL on the basis of the concept of intermediate MCL, and analyzed the correlation of this reclassification with immunohistochemical detection of CCND1, Ki-67, p53, p27(Kip1), and p21(WAF/Cip1). The median overall survival was 77, 31, and 18 months for classical, intermediate, and aggressive MCL, respectively, showing a statistically significant difference (P < 0.0001). The expression levels of CCND1, Ki-67, p53, and p21(WAF/Cip1) in aggressive MCL (mean 80.1 +/- 27.8%, 73.7 +/- 28.9%, 31.0 +/- 69.0%, and 10.4 +/- 24.8%, respectively) were higher than those in classical MCL (mean 58.1 +/- 36.7%, 25.2 +/- 25.5%, 6.5 +/- 24.3%, and 2.5 +/- 13.0%, respectively) and intermediate MCL (mean 75.7 +/- 31.4%, 30.8 +/- 33.3%, 21.0 +/- 57.4%, and 4.8 +/- 16.5%, respectively). Significantly different levels of Ki-67 and p21(WAF/Cip1) were only recognized between intermediate and aggressive (P < 0.05 and P < 0.0001, respectively), whereas those of CCND1 and p53 were only between classical and intermediate (P < 0.0001 and P < 0.05, respectively). There were no significant differences in p27(Kip1) among the three groups. The subsequent discriminant analysis with independent prognostic factors clearly demonstrated that the morphological evolution of MCL occurs in parallel with increased labeling index of CCND1 and Ki-67. The diagnosis of intermediate MCL thus proved to be of major significance and should enable the design of more tailored therapies.

[A case of neurofibromatosis-1 in which severe bleeding was observed from a neurofibroma under the scalp].

Neurofibroma is a representative external abnormality observed along with café-au-lait spots in association with neurofibromatosis type 1 (NF-1). We encountered a case of NF-1 in which severe bleeding was observed from a neurofibroma under the scalp due to minor trauma. Only four similar cases have been reported in the past literature and we believed that it was a significantly rare case, and we herein report the case with bibliographical considerations. The subject was a 23-year-old male. He was gently hit on the right side of the head during work and the bruised site gradually became bloated. Even on the following day, the bloating continued and he also started feeling severe pain, and as a result, he visited our emergency department. A head CT scan revealed a subcutaneous high-density area from the right-frontal area of the head to the side of the head that appeared to be a hematoma. The pain was severe and we therefore performed emergency surgery to remove the subcutaneous hematoma, but due to severe bleeding during the operation, we ultimately removed only part of the hematoma. However, because the pain was relieved, he was discharged from the hospital and he subsequently stopped visiting the hospital regularly. Three years later, he visited our department again with similar head bloating due to a mild head bruise. When surgery was performed again, an obvious neoplastic lesion was observed along with the subcutaneous hematoma. The pathological findings suggested it was a neurofibroma but no malignant findings were observed.

Effectiveness of gallium scintigraphy in diagnosing a spontaneous giant chronic expanding hematoma of the adrenal gland: A case report.

INTRODUCTION: A chronic expanding hematoma in the retroperitoneal space is a rare disease with poorly understood pathology, and preoperative diagnosis of such hematomas using conventional methods is sometimes difficult. PRESENTATION OF CASE: A 68-year-old man with a history of slowly progressive abdominal distention was referred to our department for further evaluation. Contrast-enhanced CT revealed a large retroperitoneal tumor of the adrenal gland. MRI revealed that the tumor was iso-intense to hyperintense on T2-weighted imaging, with heterogeneous signal intensity on T1-weighted imaging without fat components. Angiography of the left adrenal artery confirmed many extravasations into the tumor. However, gallium scintigraphy showed no accumulation in the tumor. These findings were suggestive of a chronic expanding hematoma of left adrenal gland. This patient underwent complete tumor resection. Postoperative histopathological findings revealed a chronic expanding hematoma. DISCUSSION: Chronic expanding hematomas are slowly expanding, space-occupying masses as a result of trauma, surgery, or bleeding disorders. Chronic expanding hematomas mimic malignant tumors such as sarcomatous lesions. Although CT and MRI are used to obtain the diagnosis, the diagnosis is sometimes difficult. Gallium scintigraphs play a pivotal role in the differential diagnosis between them. CONCLUSION: Gallium scintigraphs, magnetic resonance imaging and computed tomography, are useful tools to differentiate chronic expanding hematomas from sarcomatous lesions.

Resected case of stage IV pleomorphic carcinoma of the lung with long-term survival.

BACKGROUND: No established treatments for pulmonary pleomorphic carcinoma exist because of its rarity, and the prognosis is poorer than that of other non-small cell lung cancers. CASE REPORT: We present a case of stage IV pleomorphic carcinoma; the patient was a 66-year-old male. He was referred to our hospital because of a right adrenal hemorrhage and a lung tumor. A systemic examination revealed that the lung tumor was a primary lung cancer and that the adrenal hemorrhage was due to a metastatic cancer. We performed an adrenalectomy and resection of the lung tumor and obtained a diagnosis of pleomorphic carcinoma with adrenal metastasis. The patient has remained recurrence-free for 6 years since the surgery. CONCLUSIONS: We report a patient with stage IV pleomorphic carcinoma of the lung and an oligometastasis in whom a complete resection enabled a good outcome. Additional reports are needed to clarify definite prognostic factors and the optimal treatment for pleomorphic carcinoma.

Triple-negative pleomorphic lobular carcinoma and expression of androgen receptor: Personal case series and review of the literature.

Pleomorphic lobular carcinoma (PLC) is a histological variant of invasive lobular carcinoma (ILC) and is associated with worse prognosis than classical ILC. It exhibits a greater degree of cellular atypia and pleomorphism and is occasionally accompanied with apocrine morphology. We investigated the immunohistochemical characteristics of samples from 31 Japanese patients with PLC to elucidate the clinicopathological characteristics of PLC including androgen receptor (AR) immunoreactivity. The surrogate molecular subtypes were luminal A-like, luminal B-like, luminal B-like/HER2, HER2-type, and triple-negative in 5, 4, 3, 5, and 14 cases, respectively. AR was positive in 92.8% (13/14) of the triple-negative PLC cases and 100% (10/10) of the non-triple-negative PLC cases. Disease-specific survival was worse in patients with histological grade 3 PLCs than in those with histological grade 2 PLCs (p = 0.007). However, there was no significant difference in the progression-free survival between the two groups (p = 0.152). No other clinicopathological characteristics were associated with prognosis. These results reveal that PLC exhibits various surrogate molecular subtypes and that the triple-negative subtype frequently expresses AR. The observed molecular apocrine differentiation implicates that triple-negative PLC can be categorized into the luminal AR subtype. Furthermore, AR-targeted therapy might be useful for patients with triple-negative PLC.

A rare case of enlarged gastric heterotopic pancreas with retention cysts: A case report and literature review.

INTRODUCTION: Gastric heterotopic pancreas (HP) is usually asymptomatic and benign; however, it may become evident when it is complicated by pathological changes such as inflammation, bleeding, and malignant transformation. PRESENTATION OF CASE: A 43-year old man was diagnosed with gastric HP 18 years prior suffered a haemorrhage from the enlarged gastric HP with multiple cystic lesions. Although endoscopic ultrasonography-guided fine needle aspiration showed no malignancy, he underwent a partial gastrectomy for diagnosis and treatment. Postoperative histological findings revealed ectopic pancreatic tissue with retained cysts that consisted of dilated pancreatic ducts without malignancy. DISCUSSION: This is a first report of enlarged gastric HP due to the expansion of retained cysts. Gastric HP is rarely enlarged by pathological changes including inflammation, retention cysts, or malignant neoplasms. CONCLUSION: Symptomatic enlarged gastric HP should be respected and further examined histologically to ensure diagnostic accuracy.

Patients with localized primary non-tonsillar oral diffuse large B-cell lymphoma exhibit favorable prognosis despite a non-germinal center B-cell-like phenotype.

Diffuse large B-cell lymphomas are detected frequently in the oral cavity. Although tonsillar lymphomas have been rather well characterized, lymphomas originating from non-tonsillar regions, such as the gingiva, palate, and tongue, have not been well studied. We examined the pathology of clinical samples obtained from 21 patients with localized primary non-tonsillar oral diffuse large B-cell lymphoma. Immunohistological examination of CD10, Bcl-6, and MUM1 determined that 17 of 21 (81%) samples exhibited non-germinal center B-cell type, an increased proportion of non-germinal center B-cell type compared with previous reports in samples of tonsillar origin (P<0.05). The four remaining samples exhibited germinal center B-cell type, although one sample expressed MUM1. Follow-up clinical survival data were obtained from the 17 patients over a range from 4 to 173 months (mean 52 months). All patients were treated with chemotherapies, irradiation, or surgical resection. Sixteen patients achieved complete remission and two patients relapsed, but no patient has died of disease. Extranodal diffuse large B-cell lymphomas of non-germinal center B-cell type are generally characterized by poor prognosis, regardless of localized disease. Interestingly, our results indicate that, unlike similar lymphomas of tonsillar origin, localized primary non-tonsillar oral diffuse large B-cell lymphomas exhibit favorable prognosis, suggesting that these lymphomas may be clinicopathologically distinct.

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.

Duodenal and nodal follicular lymphomas are distinct: the former lacks activation-induced cytidine deaminase and follicular dendritic cells despite ongoing somatic hypermutations.

Although most follicular lymphomas are believed to be of nodal origin, they sometimes originate from the duodenum. We have reported that the latter differ from nodal follicular lymphomas in having lower clinical stages and uniformly low histological grades, along with variable region of immunoglobulin heavy chain gene (VH) usage that is more similar to mucosa-associated lymphoid tissue (MALT) lymphomas. Little is known, however, about whether they possess other characteristics of nodal follicular lymphomas, particularly ongoing mutations with follicular dendritic cells. We examined 17 cases for which PCR identified the monoclonal bands of the immunoglobulin gene. The duodenal cases showed ongoing mutations, but they lacked activation-induced cytidine deaminase (AID) expression, a statistically significant difference from the nodal cases (P<0.001), and their follicular dendritic cell networks were disrupted. Moreover, not only were VH deviations observed but also they used very restricted VH genes. Although the mechanisms of ongoing mutation without AID and follicular dendritic cell were not clarified, restricted VH usage strongly suggested that antigen stimulation was involved, and that was similar to MALT lymphomas. In conclusion, duodenal follicular lymphomas were shown to be unique, in that they had ongoing hypermutations such as nodal cases, but the mechanisms involved in the hypermutation were quite different; furthermore, restricted VH usage suggested a strong similarity to the antigen-dependent origin of MALT lymphomas.