Gastric dysplastic lesions in Helicobacter pylori-naïve stomach: Foveolar-type adenoma and intestinal-type dysplasia.

Reports of Helicobacter pylori (Hp)-naïve gastric neoplasm (HpNGN) cases have been rapidly increasing due to the recent increase in the Hp-naïve population in Japan. Most HpNGNs exhibit the gastric immunophenotype and a low malignant potential regardless of histological type. Especially, foveolar-type gastric adenoma (FGA) and intestinal-type gastric dysplasia (IGD) rarely progress to invasive carcinoma. FGA is a foveolar epithelial neoplasm that occurs in the fundic gland (oxyntic gland) mucosa and is classified as the flat type or raspberry type (FGA-RA). The flat type is a large, whitish flatly elevated lesion while FGA-RA is a small reddish polyp. Genomically, the flat type is characterized by APC and KRAS gene mutations and FGA-RA by a common single nucleotide variant in the KLF4 gene. This KLF4 single-nucleotide variant reportedly induces gastric foveolar epithelial tumorigenesis and activates both cell proliferation and apoptosis, leading to its slow-growing nature. IGD consists of an intestinalized epithelial dysplasia that develops in the pyloric gland mucosa, characterized as a superficial depressed lesion surrounded by raised mucosa showing a gastritis-like appearance. Immunohistochemically, it exhibits an intestinal or gastrointestinal phenotype and, frequently, p53 overexpression. Thus, IGD shows unique characteristics in HpNGNs and a potential multistep tumorigenic process.

A Case Report of Carcinoid With Teratoma Arising From the Renal Hilum.

Teratoma is a germ cell tumor composed of 2 or 3 germ cell layers, and it can occur in various parts of the human body. However, teratomas of the renal hilum are particularly rare, and those complicated by carcinoids are even more uncommon. Herein, we report the example of an asymptomatic 49-year-old woman in whom a tumor in the right renal hilum was unexpectedly discovered on imaging. Histological examination revealed a carcinoid tumor arising from a simple cyst composed of teratomatous tissue. Although the tumor was located in the renal hilum and touched the renal parenchyma, it appeared independent of the kidney and urinary tract. This report highlights the rare occurrence of teratomas with carcinoids and provides insights into their origins.

Association of troponin I and macrophages in cardiac tamponade with Stanford type A aortic dissection.

Background: Acute aortic dissection has a high mortality rate, especially for Stanford type A with a dissected ascending aorta. Cardiac tamponade is one of the most common complications of acute type A aortic dissection (ATAAD) and can cause death. However, the pathogenesis is often unclear. We aimed to examine laboratory findings at the onset of disease and macrophage involvement. Methods: Hematological and biochemical parameters, and D-dimer, brain natriuretic peptide (BNP), and high-sensitivity troponin I (hs-cTnI) levels in 70 patients with ATAAD at our hospital were investigated. Additionally, the myocardium and aorta after autopsy of an ATAAD case with cardiac tamponade were pathologically examined. Results: Forty-four ATAAD cases were complicated by cardiac tamponade. The mean age of patients with cardiac tamponade and proportion of patients over 70 years of age were both significantly higher than for those without cardiac tamponade. Evaluable D-dimer values were higher than 0.5 µg/mL in all patients. Significantly elevated laboratory parameters in patients with cardiac tamponade included: lactate dehydrogenase, aspartate aminotransferase, C-reactive protein, lactate, BNP, and hs-cTnI. However, multivariate analysis showed only hs-cTnI was significantly associated with cardiac tamponade. Histological examination revealed numerous M2-like macrophages infiltrating the myocardium and dissecting aorta, expressing CC chemokine ligand (CCL)2 together with vascular endothelial growth factor-C and matrix metalloproteinase-9. The peripheral monocyte-to-neutrophil ratio (MNR) was also significantly higher in cardiac tamponade. Conclusions: In ATAAD patients with cardiac tamponade, hs-cTnI was significantly elevated and CCL2 expression was observed, which may be involved in the expression of M2-like macrophages via an increased MNR.

Treatment of new-onset primary central nervous system lymphoma in elderly patients using RMPV chemotherapy: a single-institution experience.

The prognosis of primary central nervous system lymphoma (PCNSL) in the elderly remains poor. We aimed to evaluate the outcome of rituximab, methotrexate, procarbazine, and vincristine (RMPV) chemotherapy in elderly patients with new-onset PCNSL. Twenty-eight patients aged ≥ 70 years treated for PCNSL between 2010 and 2020 were examined retrospectively. Nineteen patients received RMPV and nine did not qualify. Patients received five to seven cycles of RMPV plus response-adapted whole-brain radiotherapy (WBRT) and cytarabine. Ten of the 19 patients who received RMPV (52.6%) completed the induction, but only four patients (21.1%) completed RMPV chemotherapy, WBRT 23.4 Gy, and cytarabine. Median progression-free survival (PFS) and overall survival (OS) in the RMPV group was 54.4 and 85.0 months, respectively. Both PFS and OS were significantly longer in patients who received RMPV chemotherapy than in those who did not, and in patients who started but did not complete RMPV than in those who did not receive RMPV. Patients who received incomplete RMPV tended to have a favorable prognosis. Initial treatment with RMPV chemotherapy was effective in elderly patients with PCNSL. Adjusting the number of courses of RMPV may improve the prognosis of elderly patients with PCNSL, but further verification is necessary.

Mogamulizumab for post-transplant relapse of adult T-cell leukemia/lymphoma: a case study.

Mogamulizumab (MOG), a humanized monoclonal anti-CCR4 antibody, exerts strong antibody-dependent cellular cytotoxic effects on CCR4-positive adult T-cell leukemia/lymphoma (ATLL) cells. As CCR4 is highly expressed on regulatory T cells as well as ATLL cells, pre-transplant MOG induces severe graft-versus-host disease (GvHD). However, limited data are available on post-transplant use of MOG for relapsed ATLL. Here we describe the case of a patient with ATLL who experienced post-transplant relapse with involvement of peripheral blood, skin, lungs, and lymph nodes. Neither tacrolimus dose reduction nor cytotoxic chemotherapy was effective, but a single dose of MOG (1 mg/kg) induced complete remission. After treatment with MOG, leukemic cells in the peripheral blood rapidly disappeared, and the skin, lymph node, and lung lesions gradually regressed. Most notably, the long-term remission was accompanied by recurrence of moderate acute GvHD (grade II, skin stage 2, gut stage 1, liver stage 0). Our findings indicate that MOG can augment allogeneic immune-mediated anti-tumor reactions through graft-versus-ATLL (GvATLL) even during post-transplant relapse involving the lymph nodes and lungs, along with inducing GvHD.

Substantial improvement of histopathological diagnosis by whole-slide image-based remote consultation.

Consultation by subspecialty experts is the most common mode of rendering diagnosis in challenging cases in pathological practice. Our study aimed to highlight the diagnostic benefits of whole-slide image (WSI)-based remote consultation. We obtained diagnostically challenging cases from two institutions from the years 2010 and 2013, with histological diagnoses that contained keywords "probable," "suggestive," "suspicious," "inconclusive," and "uncertain." A total of 270 cases were selected for remote consultation using WSIs scanned at 40 × . The consultation process consisted of three rounds: the first and second rounds each with 12 subspecialty experts and the third round with six multi-expertise senior pathologists. The first consultation yielded 44% concordance, and a change in diagnosis occurred in 56% of cases. The most frequent change was from inconclusive to definite diagnosis (30%), followed by minor discordance (14%), and major discordance (12%). Out of the 70 cases which reached the second round, 31 cases showed discrepancy between the two consultants. For these 31 cases, a consensus diagnosis was provided by six multi-expertise senior pathologists. Combining all WSI-based consultation rounds, the original inconclusive diagnosis was changed in 140 (52%) out of 266 cases. Among these cases, 80 cases (30%) upgraded the inconclusive diagnosis to a definite diagnosis, and 60 cases (22%) changed the diagnosis with major or minor discordance, accounting for 28 cases (10%) and 32 cases (12%), respectively. We observed significant improvement in the pathological diagnosis of difficult cases by remote consultation using WSIs, which can further assist in patient healthcare. A post-study survey highlighted various benefits of WSI-based consults.

[Successful treatment of myelodysplastic syndromes complicated by myeloid sarcoma with haploidentical allogeneic hematopoietic stem cell transplantation using post-transplant cyclophosphamide].

Using post-transplant cyclophosphamide (PTCy-haplo), haploidentical allogeneic hematopoietic stem cell transplantation has shown a surge in popularity in recent years. There are, however, only a few reports of PTCy-haplo being used to treat myelodysplastic syndromes (MDS) that have been complicated by myeloid sarcoma (MS). An immuno-suppressive therapy was given to a 25-year-old man who was diagnosed with low-risk MDS in September 2007. After an ileocecal ulcer biopsy that revealed MS in July 2019, a chromosomal analysis of the bone marrow cells in August 2019 revealed loss of chromosome 7, which is associated with poor prognosis. Because the patient lacked an HLA-matched sibling donor, he underwent PTCy-haplo in December 2019. On day 33, complete remission and donor chimerism was achieved. Ileocecal ulcer scarring was discovered by a colonoscopy on day 54. Grade I cutaneous acute graft-versus-host disease was discovered approximately on day 30 and treated with topical steroids. PTCy-haplo may be an effective treatment for MS.

[Warm autoimmune hemolytic anemia accompanied by metachronous double primary cancer].

In about half of the cases, autoimmune hemolytic anemia (AIHA) is secondary to an underlying disease, often due to paraneoplastic syndromes. Recently, the number of patients developing metachronous multiple primary malignant tumors (MPMTs) has been increasing due to the aging of the population and the longer survival times of those with malignant tumors. A 78-year-old woman was diagnosed with sigmoid colon cancer in May 2017 and with warm AIHA in October 2017. She received prednisolone for her warm AIHA treatment, which relieved her anemia symptoms. In January 2020, she had a warm AIHA relapse and received PSL again. In May 2020, she was diagnosed with peritonitis due to a small intestinal perforation and underwent laparoscopic partial resection of the small intestine. Subsequently, she was diagnosed with diffuse large B-cell lymphoma. It is important to consider the possibility of MPMTs and perform the appropriate examinations to determine whether malignant tumors are present in patients with a history of malignant tumors and a long history of AIHA relapse.

Relationship of histamine expression with chemokine balance in the tumor microenvironment of squamous cell carcinoma of the tongue.

BACKGROUND: Tumor-associated macrophages in the tumor microenvironment (TME), as a factor affecting lymphocytes, have received much attention. Both lymphocytes and macrophages can switch the expression of histamine receptors. In this study, we investigated the role of histamine in the TME of tongue squamous cell carcinoma (SCC). METHODS: Sixty-seven patients with stage I tongue SCC were studied. Histamine was evaluated by the expression of L-histidine decarboxylase (HDC). Macrophages, T lymphocytes, and lymph vessel density, as well as the Ki-67 labeling index (LI) and depth of invasion (DOI), were compared with HDC expression. RESULTS: HDC expression was significantly affected by the TME. The DOI, worst pattern of invasion, and Ki-67 LI were associated with histamine expression. C-C motif chemokine ligand (CCL) 2 and CCL22 were co-expressed with histamine H1 and H2 receptors. Histamine expression was most affected by the DOI. CONCLUSIONS: Tongue SCC expressing histamine affected the TME via histamine receptors and chemokines.

Blocking cholesterol efflux mechanism is a potential target for antilymphoma therapy.

Cholesterol is an essential plasma membrane lipid for the maintenance of cellular homeostasis and cancer cell proliferation. Free cholesterol is harmful to cells; therefore, excessive free cholesterol must be quickly esterified by acetyl-coenzyme A:cholesterol acetyltransferase (ACAT) and exported by scavenger receptor class B member I (SR-BI) or ATP-binding cassette protein A1 from specific cells such as macrophage foam cells, which contain cholesteryl ester-derived vacuoles. Many vacuoles are present in the cytoplasm of Burkitt lymphoma cells. In this study, we observed that these vacuoles are often seen in high-grade lymphomas. Cell culture study using lymphoma cell lines found that esterified cholesterol is the main component of these vacuoles and the expression of cholesterol metabolism-related molecules was significantly upregulated in lymphoma cell lines, with SR-BI and ACAT inhibitors (BLT-1 and CI-976, respectively) impeding lymphoma cell proliferation. Cytoplasmic free cholesterol was increased by ACAT and SR-BI inhibitors, and the accumulation of free cholesterol induced lymphoma cell apoptosis by inducing endoplasmic reticulum stress. Furthermore, synergistic effects of SR-BI and ACAT inhibitors were observed in a preclinical study. Treatment with SR-BI inhibitor suppressed lymphoma progression in a tumor-bearing mouse model, whereas ACAT inhibitor did not. Therefore, SR-BI inhibitors are potential new antilymphoma therapeutics that target cholesterol metabolism.

Incidence Patterns of Sequential or Composite Lymphoma: A Population-Based Cancer Registry Study.

The development of multiple histologic types of lymphoma in a single patient has been sporadically reported as sequential or composite lymphoma. However, the incidence pattern of such patients has been rarely evaluated in a large population-based setting. We investigated the incidence of sequential or composite lymphoma based on 11,174 lymphoma records from a population-based cancer registry between 1985-2012 in Nagasaki Prefecture, Japan. We identified 99 lymphoma records were of 49 independent patients other than relapse. The prevalence of the sequential or composite lymphomas in a single patient was 0.44% (95% confidence interval [95% CI], 0.32-0.56%) without sex difference. Among the 49 patients, five (10.2%) were composite/discordant lymphoma. The most frequent "composite lymphoma" was a combination of diffuse large B-cell lymphomas (DLBCL) and adult T-cell leukemia (n = 3). A case of "discordant lymphoma" was a combination of follicular lymphoma on spleen and Waldenström macroglobulinemia on bone marrow. The rest of the patients (n = 44, 89.8% of all composite lymphoma) were "sequential lymphoma" with various combination of lymphoma subtypes on different dates. The major combination of the sequential lymphoma was DLBCL after marginal zone lymphomas (n = 4). In the era of improved survival of lymphoma patients, hematologists should be aware of the development of additional lymphomas.

FDG-PET vs. chemical shift MR imaging in differentiating intertrabecular metastasis from hematopoietic bone marrow hyperplasia.

PURPOSE: To evaluate the utility of SUVmax on FDG-PET and chemical shift imaging (CSI) on MRI in the differentiation of intertrabecular metastasis (ITM) from hematopoietic bone marrow hyperplasia (HBMH). PATIENTS AND METHODS: We retrospectively evaluated 54 indeterminate focal bone marrow lesions in 44 patients detected on FDG-PET. The lesions were assigned to the metastasis group (M group, 29 lesions of 24 patients) and the non-metastasis group (non-M group, 25 lesions of 20 patients) based on the follow-up or the histopathological studies. The lesions were assessed with the maximum standardized uptake value (SUVmax) on FDG-PET CT images and signal change ratio (SCR) on CSI. RESULTS: The median SUVmax were 5.62 and 2.91; the median SCR were - 0.08 and - 34.8 in M and non-M groups respectively, with significant difference (p < 0.001). With ROC curve analysis, the optimal cutoff value of SUVmax was 4.48 with a sensitivity of 72.4%, a specificity of 100%, and AUC of 0.905. The cutoff value of SCR was - 6.15 with a sensitivity of 82.8%, a specificity of 80%, and AUC of 0.818. CONCLUSION: FDG-PET and CSI on MRI are useful in distinguishing ITM from HBMH. Though their sensitivities are similar, the specificity of FDG-PET was higher than that of MRI.

Usefulness of 18F-fluorodeoxyglucose positron emission tomography for assessment of tumorviability after resection of granulocyte-colony-stimulating-factor -Producing cholangiocarcinoma-a case report.

INTRODUCTION AND IMPORTANCE: Granulocyte colony-stimulating factor (G-CSF)-producing intrahepatic cholangiocarcinoma is rare. Surgical cases with postoperative clinical course have rarely been reported. CASE PRESENTATION: A 63-year-old woman complained upper abdominal pain. Computed tomography (CT) showed intrahepatic mass measuring 9 × 9 × 9 cm in the left lateral segment. 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) showed high uptake by the tumor, with diffuse uptake in the bone marrow. An extended left lobectomy was performed to achieve complete resection. Histopathological examination showed poorly differentiated adenocarcinoma with no lymph node metastasis. Immunohistochemical analysis revealed that tumor cells produced G-CSF. After chemotherapy with S-1 regimen at 10 months after the operation, CT and FDG-PET detected lymph node metastasis in the peri-duodenal area and left kidney metastasis, with no FDG uptake in the bone marrow. Serum G-CSF was normal. Combination chemotherapy with gemcitabine plus cisplatin was administered, and, 12 months after liver resection, metastases were enlarged and FDG uptake in the bone marrow was detected again. Serum G-CSF was elevated at 71.6 pg/mL. The patient was enrolled in a clinical trial of chemotherapy with another regimen and was alive at 19 months after liver resection. CLINICAL DISCUSSION: Because of rapid progression, rapid diagnosis and resection are important. FDG uptake in the bone marrow is characteristic in G-CSF producing tumor. In this case, FDG uptake in the bone marrow reappeared after the enlargement of recurrent lesions, followed by tumor enlargement. CONCLUSION: FDG-PET was useful for differential diagnosis and to assess tumor viability and determine the surgical indication.

Significance of abnormal 53BP1 expression as a novel molecular pathologic parameter of follicular-shaped B-cell lymphoid lesions in human digestive tract.

The digestive tract is a common site of extranodal malignant lymphomas (MLs) and benign lymphoid lesions (BLs). TP53-binding protein 1 (53BP1) expression has been widely investigated in class switch recombination but rarely in human lymphoid tissues with respect to tumorigenesis. We previously reported that immunofluorescence (IF) analysis of 53BP1 nuclear foci (NF), reflecting DNA double strand breaks, is useful for estimating genomic instability in different tumor types. In this study, we evaluated the potential of IF-based analysis of 53BP1 expression in differentiating MLs from BLs. We examined 231 biopsied tissue samples of primary MLs and BLs in the digestive tract. The 53BP1 immunoreactivity pattern was determined by multicolor IF. Compared to BLs, MLs showed a high frequency of abnormal 53BP1 expression (p < 0.0001). Statistically, abnormal 53BP1 expression is an effective test for distinguishing follicular lymphomas from BLs (specificity 98.6%, sensitivity 86.8%) and for distinguishing small B-cell lymphomas from BLs (specificity 98.3%, sensitivity 77.6%). Furthermore, a high frequency of abnormal 53BP1 expression was associated with "high-risk" MALT lymphomas, which exhibited t(11;18)(q21;21) (p = 0.0145). Collectively, these results suggest that IF-based analysis of 53BP1 expression in biopsy samples is a promising technique for diagnosing MLs in the digestive system.

Ruptured aneurysm-induced pituitary apoplexy: illustrative case.

BACKGROUND: Pituitary apoplexy associated with aneurysmal rupture is extremely rare and may be misdiagnosed as primary pituitary adenoma apoplexy. The authors present a case of a patient with pituitary apoplexy caused by rupture of an anterior cerebral artery aneurysm embedded within a giant pituitary adenoma, and they review the relevant literature. OBSERVATIONS: A 78-year-old man experienced sudden headache with progressive vision loss. Magnetic resonance imaging (MRI) revealed a giant pituitary tumor with abnormal signal intensity. Magnetic resonance angiography immediately before surgery showed a right A1 segment aneurysm, suggesting coexisting pituitary apoplexy and ruptured aneurysm. The patient underwent urgent transsphenoidal surgery for pituitary apoplexy. The tumor was partially removed, but the perianeurysmal component was left behind. Subsequent cerebral angiography showed a 5-mm right A1 aneurysm with a bleb that was successfully embolized with coils. Retrospective review of preoperative dynamic MRI showed extravasation of contrast medium from the ruptured aneurysm into the pituitary adenoma. Histopathologic examination showed gonadotroph adenoma with hemorrhagic necrosis. Postoperatively, the patient's visual function improved. LESSONS: MRI identification of pituitary apoplexy caused by aneurysmal rupture has not been reported previously. Aneurysmal rupture should be considered in the differential diagnosis of pituitary apoplexy. When a ruptured aneurysm is encountered, the authors recommend treating it before addressing pituitary apoplexy.

Acute perforating appendicitis caused by metastatic squamous cell carcinoma from the lung: A case report.

INTRODUCTION: Lung cancer is one of the most common cancers. On the other hand, lung cancer metastasis to the appendix is extremely rare, and in many cases it has been diagnosed with the onset of acute perforating appendicitis. PRESENTATION OF CASE: An 85-year-old man with fever and abdominal pain visited our hospital. He had a history of squamous cell carcinoma of the left upper and lower lobes, metastasis to the ipsilateral lung and femur. CT showed that a finding of acute perforating appendicitis, emergency cecal resection was performed. Examination of the resected specimen showed that the appendix was thickened overall, with a white nodular structure at the root and a perforation in the middle. The final diagnosis was acute perforating appendicitis caused by metastatic squamous cell carcinoma from the lung. The patient had no particular problems during the postoperative course. DISCUSSION: A PubMed search was performed, this appears to be the first reported case of appendiceal metastasis of squamous cell carcinoma of the lung. Since squamous cell carcinoma of the lung has a stronger tendency for local extension than other histological types, perforating appendicitis due to distant metastasis to the abdominal organs and metastasis to the appendix was reported as a very valuable case. CONCLUSION: Because the progression of concomitant or secondary appendicitis is rapid, we recommend frequent imaging modalities, prophylactic appendectomy be considered for patients who also have lung cancer and imaging findings show suspected metastasis to the appendix.

Correction to: Programmed death 1 ligand (PD-L1) in solid cancers after allogeneic hematopoietic stem cell transplantation: a retrospective analysis by the Nagasaki Transplant Group.

In the original publication of the article, the authors would like to alter the color of characters in the Supplemental Table 1 and 2.

Programmed death 1 ligand (PD-L1) in solid cancers after allogeneic hematopoietic stem cell transplantation: a retrospective analysis by the Nagasaki Transplant Group.

Programmed death 1 ligand (PD-L1) is an immunomodulatory molecule expressed by cancer cells, and it has been widely demonstrated to inhibit host antitumor responses. The aim of the present study was to identify clinicopathological features associated with PD-L1 expression in the secondary solid cancers of patients after allogeneic hematopoietic stem cell transplantation. In this database of 530 patients who received allo-HSCT between 1990 and 2017, 15 developed solid cancers with a median interval of 3487 days after transplantation. Three patients had 2 different solid cancers. Eighteen solid cancer cases were identified. A multivariate analysis showed that chronic graft-versus-host disease (GVHD) was associated with an increased risk of solid cancer. The presence of chronic GVHD was observed in 8 out of 18 cases at the diagnosis of secondary malignancies. PD-L1 expression levels in cancers were significantly higher in patients with active chronic GVHD than in those without chronic GVHD (P = 0.020). Five cases of cancer that developed in the involved organs of chronic GVHD showed 30% or higher PD-L1 positivity. The present results revealed distinct PD-L1 expression in the secondary solid cancers of post-transplant patients with chronic GVHD.