Granulomatous gastritis induced by chronic peanut ingestion.

Granulomatous gastritis (GG) is a rare condition, with incidence between 0.08 and 0.35% in gastric biopsies. Various infectious and non-infectious aetiologies can be considered to cause granulomatous gastritis. Foreign bodies are a rare aetiology of GG and may result from foods, suture materials, or medications. We report a 59-year-old woman who had eaten large amounts of peanuts for more than 10 years and presented with epigastric discomfort. Esophagogastroduodenoscopy revealed multiple nodular lesions with ulcer scars at the stomach, which was diagnosed as GG probably caused by chronic peanut ingestion on endoscopic mucosal resection.

Lack of Association between Chlamydophila psittaci and Ocular Adnexal MALT Lymphoma in Korean Patients-Is the Geographic or Genetic Difference Significant?

Clamydophila psittaci (C. psittaci) has been proposed to be an etiologic factor in extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) in the ocular adnexa. However, the pathogenetical significance of the infection has not been fully elucidated. Many previous studies have shown controversial results regarding C. psittaci detection rates in said patients, ranging from 0 to 87%. We investigated the presence of C. psittaci in a single institutional cohort (n = 150) of ocular adnexal MALT lymphoma (OAML) patients in Korea. We tried to exclude the methodological biases derived from the different primer sets in polymerase chain reaction-based studies. For that reason, we applied five sets of primers, including four previously reported and one newly designed primer set. There was no case of C. psittaci-positive OAML in repeated trials validated with appropriate positive and negative controls. All 150 cases showed negative results with five primer sets. These results suggest that the pathogenetic role of C. psittaci in ocular adnexal MALT lymphoma might have been overestimated to date, at least in the Korean population. Therefore, the molecular diagnosis of C. psittaci is considered a very low priority.

Comparison of Ki-67 Labeling Index Patterns of Diffuse Large B-Cell Lymphomas and Burkitt Lymphomas Using Image Analysis: A Multicenter Study.

Diffuse large B-cell lymphoma (DLBCL) is the most common high-grade B-cell lymphoma found in Korea; it manifests with a variety of cellular morphologies and a high proliferation index. It is difficult to differentiate between DLBCL and Burkitt lymphoma (BL) based on immunohistochemistry, histology, and Epstein-Barr virus infection status owing to the overlap in findings. In this study, we performed comparative morphometric analysis to understand the proportional difference in Ki-67 staining between DLBCL and BL. We analyzed Ki-67-stained slides of 103 DLBCLs and 29 BLs that were pathologically confirmed using a three-tier classification system (negative, 1+, 2+, and 3+) to compare Ki-67 expression between BL and activated B-cell and germinal center B-cell subtypes of DLBCL and DLBCL with high proliferation indices (>90% of 2+ and 3+ cells). Patients with DLBCL were older than those with BL (62.1 versus 51.0 years). The number and proportion of negative cells (passenger and true negative cells) were significantly lower in BLs than those in DLBCLs (337.4, 5.9% versus 690.3, 12.4%). The number and proportion of 3+ cells were significantly higher in BLs than those in DLBCLs (5213.6, 96.3% versus 3132.4, 62.0%). BLs and DLBCLs with a high proliferation index showed similar results as those between BLs and overall DLBCLs. We were able to differentiate BLs and DLBCLs with 98.1% sensitivity and 100.0% specificity using an optimal cut-off of 97.9% of 2+/3+ Ki-67-positive cells. Thus, the Ki-67 labeling index may be a good differential biomarker for DLBCLs and BLs.

Central Nervous System Solitary Fibrous Tumor/Hemangiopericytoma Penetrating the Skull Bone: An Unusual Presentation.

BACKGROUND: Central nervous system (CNS) solitary fibrous tumor/hemangiopericytoma (SFT/HPC) is a soft tissue neoplasm that accounts for <1% of all intracranial tumors. Its growth will be mostly intracranial, usually along the sinuses. We have reported a rare case of direct extracranial extension of CNS SFT/HPC penetrating the frontal bone. CASE DESCRIPTION: A 64-year-old woman had visited our institution for treatment of a forehead mass. With the impression that it was a subcutaneous mass, we had planned a simple excision with the patient under local anesthesia. However, the intraoperative findings showed extension of the mass into the skull and attachment to the dura mater. Brain magnetic resonance imaging showed a 1.8-cm solid mass with an adjacent skull defect, and examination of the biopsy specimen confirmed the diagnosis as grade II CNS SFT/HPC. Definitive excision was performed by en bloc tumor resection with a 2-cm safety margin. Adjuvant radiotherapy was performed with 60 Gy in 30 fractions. The patient showed no signs of recurrence or metastasis during 2 years of follow-up. CONCLUSIONS: The present case has shown that CNS SFT/HPC can infiltrate the full thickness of the skull bone and grow extracranially, even if low grade. However, the unusual presentation of the present made early exploration and total resection possible.

Comparison of the Lymph2Cx Assay and Hans Algorithm in Determining the Cell-of-Origin of Diffuse Large B-Cell Lymphomas, Not Otherwise Specified.

In the era of precision medicine, accurate and reproducible assignment of cell-of-origin (COO) in diffuse large B-cell lymphoma patients has become important. The Lymph2Cx assay is accurately determining COO by analyzing RNA expression of 20 selected genes while the Hans algorithm based on immunohistochemistry is the most popular method for routine daily diagnosis. However, there are discrepancies between the 2 methods, which need to be evaluated for better correlation. We prospectively analyzed 156 cases of diffuse large B-cell lymphoma, not otherwise specified to analyze the characteristics of discrepancy groups of COO determined by Lymph2Cx and Hans algorithm. We investigated the pattern and cause of discrepancy of COO assigned by the 2 methods. Hans algorithm classified 50 cases (32%) as germinal-center B-cell-like (GCB) type and 106 cases (68%) as non-GCB type. Lymph2Cx assay assigned 43 cases (28%) as GCB type, 94 cases (60%) as activated B-cell-like type, and 19 cases (12%) as intermediate/unclassified type. The agreement rate was 86% after exclusion of unclassified type. With regard to the clinicopathologic factors related with discrepancy between Hans algorithm and Lymph2Cx assay, endoscopic biopsy of the gastrointestinal tract (4/11, 36%) showed higher discrepancy rate (P=0.052). Immunophenotypically, CD10/BCL6/MUM1 GCB type and CD10/BCL6//MUM1 (=30%, low level expression) non-GCB type exhibited a significantly higher discrepancy rate (6/13, 46%; 4/13, 31%) (P=0.0001). Activated B-cell-like subgroup via Lymph2Cx assay predicted poor progression-free survival (mean survival duration 28.6 mo, P=0.049) compared with the GCB and unclassified type. Hans algorithm revealed no significant difference in progression-free survival and overall survival (P=0.122 and 0.121). These results suggest that when assigning COO via Hans algorithm, CD10/BCL6/MUM1 GCB type and CD10/BCL6/MUM1 (=30%, low level) non-GCB type require careful interpretation, especially if the MUM1 staining is weak and heterogeneous in the biopsied specimen.

Serum levels of soluble programmed death-ligand 1 (sPD-L1) in patients with primary central nervous system diffuse large B-cell lymphoma.

BACKGROUND: The interaction of programmed death-1 protein (PD-1) and programmed death-1 ligand (PD-L1) produces immunosuppressive activity, protecting tumor cells from anti-tumor immunity and possibly releasing soluble PD-L1 (sPD-L1) from PD-L1 expressing tumor cells. Therefore, we measured serum levels of sPD-L1 in patients with primary central nervous system lymphoma (PCNSL) and explored its clinical implications. METHODS: Sixty-eight patients with newly diagnosed PCNSL had diffuse large B-cell lymphoma and were treated with high-dose methotrexate-containing chemotherapy. The measurement of sPD-L1 and cytokines was performed using serum samples archived at diagnosis, and the tissue expression of PD-L1 was also analyzed from archived paraffin-embedded tissue blocks. Disease relapse, progression-free survival (PFS), and overall survival (OS) were analyzed according to the extent of sPD-L1 in serum and PD-L1 in tissue. RESULTS: The median level of serum sPD-L1 (0.429 ng/mL) was higher than in healthy control patients (0.364 ng/mL). The occurrence of relapse was more frequent in the high sPD-L1 (78%) than the low sPD-L1 group (50%), though the groups did not have different clinical or pathological characteristics at diagnosis. As a result, the OS and PFS for the high sPD-L1 group were significantly lower than those in the low group. PD-L1-positive tumor cells were found in 35 patients (67%), and the extent of PD-L1-postive tumor cells was positively associated with serum sPD-L1 levels (r = 0.299, P = 0.031). Among the 34 cytokines analyzed, only the serum level of IL-7 correlated with the serum level of sPD-L1 (r = 0.521, P < 0.001). CONCLUSIONS: Serum levels of sPD-L1 could reflect the expression of PD-L1 in PCNSL tumor cells and predict patient survival outcomes. Therefore, sPD-L1 in serum could be a feasible biomarker for determining a risk-adapted treatment strategy for PCNSL patients. TRIAL REGISTRATION: The study population was patients who were diagnosed with PCNSL between January 2009 and February 2017 and registered for our prospective cohort studies after providing written informed consent (ClinicalTrials.gov: NCT00822731 [date of registration - January 14, 2009] and NCT01877109 [date of registration - June 13, 2013]).

Paired genomic analysis of squamous cell carcinoma transformed from EGFR-mutated lung adenocarcinoma.

OBJECTIVES: Adenocarcinoma (ADC) to squamous cell carcinoma (SCC) transformation (AST) is reported in epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer after tyrosine kinase inhibitor (TKI) failure. However, little is known about the underlying genomic changes during the AST process. MATERIALS AND METHODS: We retrospectively reviewed our tissue database collected after first- or second- generation EGFR TKI resistance (n = 263) and identified 3 cases of AST. The additional case was acquired from the osimertinib resistance sample. Deep target sequencing (381 genes) using paired samples from 4 patients with AST after EGFR TKI treatment was performed. The histology of each sample was confirmed by TTF-1 and p63 immunohistochemistry. The patients received first- or second-generation EGFR TKI as an initial treatment. RESULTS: Overall incidence of AST was 1.1% (3/263). Transformed SCC acquired genomic alterations related to the PI3K/AKT/mTOR pathway, in addition to the initial EGFR mutation. In a representative case, two separate sub-clones, with a PTEN nonsense mutation and EGFR p.T790 M mutation, were observed without histologic transformation at the time of gefitinib resistance. After subsequent treatment with osimertinib, SCC transformation was observed with the disappearance of the EGFR p.T790 M mutation and acquired copy number loss in PTEN. Adopting the sub-clonal fraction model elucidates the sub-clonal evolution process of the PTEN mutant sub-clone toward AST under the background of EGFR mutation. The rest of the transformed samples also had acquired genomic alterations in PTEN, LKB1, PIK3CA, or RICTOR, which are related to the PI3K/AKT/mTOR pathway. CONCLUSIONS: Paired genomic analysis from our sample provides early clinical evidence of the ADC to SCC lineage transition that might be provoked by an alteration in the PI3K/AKT/mTOR pathway during EGFR TKI treatment. This finding could potentially broaden the known spectrum of EGFR TKI resistance mechanisms.

Comparison of Efficacy of Pembrolizumab between Epstein-Barr Virus‒Positive and ‒Negative Relapsed or Refractory Non-Hodgkin Lymphomas.

PURPOSE: Pembrolizumab, a programmed cell death protein 1 (PD1) inhibitor inhibits the interplay between PD1 of T-cell and programmed cell death ligand 1 (PDL1) on tumor cells. Although pembrolizumab has been tried to various subtypes of non-Hodgkin lymphoma (NHL), realworld data about the efficacy of pembrolizumab in NHL patients are limited. MATERIALS AND METHODS: We analyzed the outcome of 30 relapsed or refractory NHL patients treated with pembrolizumab, and compared the outcome between Epstein-Barr virus (EBV)‒positive and negative subtypes because EBV infection of tumor cells can upregulate PDL1 expression. RESULTS: Seven patients with EBV-positive NHL showed a response including NK/T-cell lymphoma (6/14, 44%) and primary mediastinal B-cell lymphoma (1/4, 25%) whereas EBV-negative subtypes did not respond such as diffuse large B-cell lymphoma and T-lymphoblastic lymphoma. We also evaluated PDL1 expression using tumor tissue of 76 patients. High PDL1 expression (positive staining of > 50% of tumor cells) was more frequent in NK/T-cell lymphoma and primary mediastinal B-cell lymphoma than other subtypes. Thus, PDL1 expression was significantly higher in EBV-positive (18/32, 56%) than EBV-negative NHL (4/38, 11%, p < 0.001). Furthermore, NK/T-cell lymphoma patients with high PDL1 expression showed a higher response (4/6, 67%) than those with low PDL1 expression (1/5, 20%). CONCLUSION: Pembrolizumab could be useful as a salvage treatment for relapsed or refractory EBV-positive NHL, especially NK/T-cell lymphoma. However, its efficacy in EBV-negative NHL with low or absent PDL1 expression is still not clear although pembrolizumab could be a potential treatment option for relapsed or refractory NHL.

Synchronous Primary Anorectal Melanoma and Sigmoid Adenocarcinoma.

A primary anorectal malignant melanoma is a rare tumor. Moreover, cases involving a synchronous anorectal melanoma and colon adenocarcinoma are extremely rare. The authors report a case of a synchronous anorectal melanoma and sigmoid adenocarcinoma in an 84-year-old man. The regions of the anorectal melanoma showed melanocytic nevi in the adjacent mucosa of the anal canal and rectum. A dysplastic nevus was also identified in the anal mucosa. This case demonstrates that an anorectal melanoma can arise from pre-existing anorectal melanocytic lesions.

Significance of Parafibromin Expression in Laryngeal Squamous Cell Carcinomas.

BACKGROUND: Parafibromin is a product of the tumor suppressor gene that has been studied as a potential indicator of tumor aggressiveness in the parathyroid, breast, colorectum, and stomach. However, the clinical significance and potential function of parafibromin expression in head and neck squamous cell carcinomas remain largely unknown. The aim of this study was to evaluate the expression of parafibromin in laryngeal squamous cell carcinoma (LSCC) and to verify its potential as a biomarker of tumor behavior. METHODS: Parafibromin expression was evaluated in 30 cases of LSCC using immunohistochemistry. The correlations between parafibromin expression and clinicopathologic parameters were investigated. RESULTS: Parafibromin expression was positive in 15 cases (50%) and negative in 15 cases (50%). Tumor size and T stage showed a statistically significant inverse relationship with parafibromin expression (p=.028 and p<.001, respectively). Parafibromin expression was not associated with age, sex, lymph node metastasis, tumor differentiation, or tumor location. There was no statistically significant relationship between parafibromin expression and progression-free survival in the patients (p>.05). CONCLUSIONS: Our results indicate that the downregulation or loss of parafibromin expression can be employed as a novel marker of tumor progression or aggressiveness in LSCC.

Efficacy of p16 and Ki-67 immunostaining in the detection of squamous intraepithelial lesions in a high-risk HPV group.

p16 and Ki-67 immunohistochemistry can be used as an ancillary method for the diagnosis of squamous intraepithelial lesion (SIL) versus atrophic change and atypical squamous metaplasia. The aim of the present study was to evaluate the efficacy of these two immunohistochemical markers in the accurate interpretation of cervical biopsies and correlate this data with human papilloma virus (HPV) infection status. The study included 103 formalin-fixed cervical punch and cone biopsy samples, with corresponding HPV DNA test data. Histopathological staining with hematoxylin and eosin, and immunohistochemical staining for p16 and Ki-67 were reviewed by two pathologists. The positivity of p16 and Ki-67 increased significantly with the severity of the cervical lesion in patients with a high-risk-HPV (HR-HPV) infection status (P<0.001). However, there was discordance in the HPV-negative group. Furthermore, concomitant diffuse, strong and block positive staining of p16, and a high Ki-67 index were implicated in high-grade SIL in the HR-HPV group. Thus, the two markers were efficient in advancing the diagnostic accuracy of cervical biopsies in the HR-HPV group; however, application of immunohistochemical results should be carefully considered in the HPV-negative group.

Clear Cell Adenocarcinoma Arising from Adenofibroma in a Patient with Endometriosis of the Ovary.

Ovarian clear cell adenocarcinomas (CCACs) are frequently associated with endometriosis and, less often with clear cell adenofibromas (CCAFs). We encountered a case of ovarian CCAC arising from benign and borderline adenofibromas of the clear cell and endometrioid types with endometriosis in a 53-year-old woman. Regions of the adenofibromas showed transformation to CCAC and regions of the endometriosis showed atypical endometriotic cysts. This case demonstrates that CCAC can arise from CCAF or endometriosis.

Poorly differentiated cecal adenocarcinoma showing prominent rhabdoid feature combined with appendiceal mucinous cystadenoma: A case report and review of the literature.

Extrarenal rhabdoid tumors (ERRTs) are extremely rare neoplasms; of these, colorectal ERRTs are the most rare, and only nine cases have been previously described in the English language literature. The current study reports the pathological features of a case of poorly differentiated cecal adenocarcinoma with prominent rhabdoid feature, which was combined with mucinous cystadenoma of the appendix in a 73-year-old male, and additionally reviews the previously reported cases. Microscopically, the majority of tumor cells were non-cohesive or loosely cohesive, with a polygonal morphology and prominent rhabdoid feature, showing eccentric vesicular nuclei, prominent nucleoli and abundant eosinophilic cytoplasm. Immunohistochemically, the tumor cells were positive for cytokeratin (CK) and vimentin, but negative for CK20, CK7, desmin and smooth muscle actin. This indicated a diagnosis of poorly differentiated adenocarcinoma with prominent rhabdoid features, combined with appendiceal mucinous cystadenoma. At two months following surgery the patient succumbed to peritoneal seeding and metastasis of liver and bone The emergence of the rhabdoid phenotype is invariably associated with an aggressive and almost always fatal clinical course. The present case is the 10th example of such a tumor in the colon, and to the best of our knowledge, this is the first case of colonic rhabdoid tumor coinciding with appendiceal benign mucinous neoplasm.

Double primary hepatic cancer (sarcomatoid carcinoma and hepatocellular carcinoma): A case report.

Primary liver sarcomatoid carcinoma (SC) is a rare and aggressive tumor exhibiting rapid growth and a high recurrence rate following resection. To date, there have been no reports of primary liver SC occurring simultaneously with hepatocellular carcinoma (HCC). This is the case report of a 54-year-old man with liver cirrhosis due to hepatitis B virus (HBV) infection and alcoholic hepatitis. The abdominal computed tomography and magnetic resonance imaging revealed two distinct hepatic masses in a background of hepatic cirrhosis and esophageal varices. Following a clinical diagnosis of two HCCs, a right hepatic lobectomy was performed. Grossly, two distinct lesions were identified: the larger mass was gray to white and well-demarcated, sized 2.5×2.0 cm, located in S5-6, whereas the other was a gray to whitish nodule, sized 1.3×1.0 cm, located in S8. The microscopic analysis revealed that the larger mass was a primary liver SC, which was immunoreactive for cytokeratin (CK) and vimentin (VMT) and negative for hepatocyte-specific antigen (HSA). The other nodule was histologically diagnosed as HCC, which was positive for HSA and CK and negative for HSA, VMT, CK7 and CK19. There was no transition or intermingling lesion between the two tumors. To the best of our knowledge, this is the first case report of double primary liver cancer comprising an SC and a HCC.