Gastric CD30-positive anaplastic large-cell lymphoma is a very rare disease. It is sometimes difficult to distinguish it from undifferentiated carcinoma, sarcoma and so on. We report here on a case of primary gastric anaplastic large-cell lymphoma. A 50-yr-old woman complained of epigastric pain and severe chest pain for 1 week. The gastroendoscopic examination revealed geographic mucosal irregularities with shallow ulceration at the antrum. She underwent a total gastrectomy. The gross finding of the resected stomach was an 8×4.5 cm sized ulceroinfiltrative lesion at the pyloric antrum along the lesser curvature. The microscopic examination revealed diffuse and solid proliferations of large atypical cells with pleomorphic nuclei. Immunohistochemically, the tumor cells were positive for CD30, vimentin and CD3, and this was a finding compatible with anaplastic large-cell lymphoma. To the best of our knowledge, this is the first such reported case in Korea.
Antigens, CD30; Lymphoma Large-Cell, Ki-1; Stomach Neoplasms; Immunohistochemistry
Mantle cell lymphoma represents 2.5–7% all of non Hodgkin's lymphomas. Stomach is the most common site of extranodal lymphoma. However, that is not the case with mantle cell lymphoma, which is extremely rare. We present a case of 71-year-old woman admitted to the Internal Clinic of the University Clinical Hospital Center Rijeka, because of stomach discomfort and melena. Endoscopy and computed tomography revealed a polyp in gastric antrum. Histopathologic, immunohistochemic and genetic methods were also performed and the results were consistent with primary gastric mantle cell lymphoma without periepigastric and/or local or distant abdominal lymph node involvement.
primary gastric mantle cell lymphoma; diagnosis; therapy.
Primary or idiopathic hypertrophy of the pyloric muscle in adult, so called torus hyperplasia, is an infrequent but an established entity. It is caused by a circular muscle hypertrophy affecting the lesser curvature near the pylorus. Since most of the lesions are difficult to differentiate from tumor, distal gastrectomy is usually preformed to rule out most causes of pyloric lesions including neoplastic ones through a pathological study. A 56-yr-old man with a family history of gastric cancer presented with abdominal discomfort of 1 month duration. Upper gastrointestinal endoscopy showed a 1.0 cm sized irregular submucosal lesion proximal to the pylorus to the distal antrum on the lesser curvature. On colonoscopy examination, a 1.5 cm sized protruding mass was noticed on the appendiceal orifice. Gastrectomy and cecectomy were done, and histological section revealed marked hypertrophy of the distal circular pyloric musculature and an appendiceal mucocele. To the best of our knowledge, this is the first case of torus hyperplasia with appendiceal mucocele which is found incidentally.
Hyperplasia; Antrum, Pyloric; Appendix; Mucocele
Cell lineage is the major criterion by which lymphomas are classified. Immunohistochemistry has greatly facilitated lymphoma diagnosis by detecting expression of lineage-associated antigens. However, loss or aberrant expression of these antigens may present diagnostic challenges. Anaplastic large cell lymphoma is a T-cell lymphoma that shows morphologic and phenotypic overlap with classical Hodgkin lymphoma, a tumor of B-cell derivation. Staining for the B-cell transcription factor, PAX5, has been suggested to be helpful in this differential, as it is positive in most classical Hodgkin lymphomas, but absent in anaplastic large cell lymphomas. Herein, we report four systemic T-cell anaplastic large cell lymphomas positive for PAX5 by immunohistochemistry, with weak staining intensity similar to that seen in classical Hodgkin lymphoma. All diagnoses were confirmed by a combination of morphologic, phenotypic, and molecular criteria. Three cases were ALK-negative and one was ALK-positive. PAX5 immunohistochemistry was negative in 198 additional peripheral T-cell lymphomas, including 66 anaplastic large cell lymphomas. Unexpectedly, though PAX5 translocations were absent, all evaluable PAX5-positive anaplastic large cell lymphomas showed extra copies of the PAX5 gene locus by fluorescence in situ hybridization. In contrast, only 4% of PAX5-negative peripheral T-cell lymphomas had extra copies of PAX5. We conclude that aberrant expression of PAX5 occurs rarely in T-cell anaplastic large cell lymphomas, and may be associated with extra copies of the PAX5 gene. PAX5-positive lymphomas with morphologic features overlapping different lymphoma types should be evaluated with an extensive immunohistochemical panel and/or molecular studies to avoid diagnostic errors that could lead to inappropriate treatment. Since PAX5 overexpression causes T-cell neoplasms in experimental models, PAX5 may have contributed to lymphomagenesis in our cases.
Anaplastic large cell lymphoma; Hodgkin lymphoma; PAX5; CD30; T-cell receptor gene rearrangement; Immunohistochemistry; FISH
Epithelial ovarian carcinoma rarely metastasizes to the parenchyma of the stomach. A 55-years-old woman presented with epigastric pain and a feeling of fullness for one month. A subsequent contrast-enhanced CT scan demonstrated a 4.5×4 cm submucosal mass with focal ulceration in the gastric antrum, and this finding was suggestive of GIST. After gastric antrectomy, the final pathology showed metastatic gastric tumor from a primary ovarian serous carcinoma. Because epithelial ovarian carcinoma is usually spread along the peritoneal surface, stomach involvement is rare. Furthermore, transmural gastric metastasis is very rare in a patient with primary ovarian carcinoma. Until now, there has been no reported case of stomach involvement at presentation in a patient with primary ovarian carcinoma. We present here a case of ovarian carcinoma with gastric metastasis that mimicked GIST.
Gastric metastasis; Gastrointestinal stromal tumors; Ovarian carcinoma
A debate is currently ongoing about whether a large gastrointestinal stromal tumor (GIST) should be treated by the laparoscopic approach because of the increased risk of tumor rupture during manipulation of the tumor with laparoscopic instruments and the resultant peritoneal tumor dissemination. Herein, we report a case of a large GIST of the stomach which was successfully treated by the laparoscopic approach. A 57 year old female patient visited our institution complaining of postprandial epigastric discomfort. An esophagogastroduodenoscopy and an abdominal computed tomography scan revealed a 10×8 cm sized submucosal tumor at the greater curvature side of the gastric antrum. The patient underwent laparoscopic distal gastrectomy with intracorporeal Billroth-II reconstruction without any breakage of the tumor. Her postoperative course was uneventful and she was discharged on the 7th postoperative day. Even a large GIST of the stomach can safely be treated by the laparoscopic approach when it is performed with proper techniques by an experienced surgeon.
Gastrointestinal stromal tumor; Stomach; Laparoscopy
Ewing's sarcoma is a neoplasm of the undifferenciated small round cells, which generally affects the bone and deep soft tissues of children and adolescents. We present a case of gastric Ewing's sarcoma; a 35-year-old female who had no symptoms. While she was at a routine medical checkup, a protruding mass in her gastric antrum was incidentally found on esophagogastroduodenoscopy. Endoscopic ultrasonogram showed a submucosal mass on the same lesion and a laparosopic wedge resection was done. Pathologic gross findings showed a granular grape appearance tissue and histoloigc examination revealed a small round cell tumor with CD 99 immunoexpression positive. In general, a combined modality therapy for Ewing's sarcoma such as surgical resection with chemotherapy, is accepted as an effective method. However, this patient had no adjuvant chemotherapy after surgery and she has no recurrence for eleven months.
Ewing's sarcoma; Combined modality therapy; Chemotherapy
We report the case of a 65 year-old man who presented with epigastric pain and guaic-positive stool. Upper and lower endoscopy revealed abnormalities in the gastric antrum and terminal ileum. Biopsy of these sites revealed histologically and immunophenotypically distinct lymphomas: gastric extranodal marginal zone lymphoma in the background of Helicobacter pylori infection and follicular lymphoma of the terminal ileum. After treatment with an H. pylori eradication regimen, repeat endoscopy showed resolution of the gastric extranodal marginal zone lymphoma and persistence of the ileal follicular lymphoma. Interestingly, molecular studies performed on the biopsy specimens revealed a common IgH rearrangement, suggesting a common precursor cell responsible for these two malignant processes. We present this unique case with a review of the literature, highlighting treatment principles for these two subtypes of indolent gastrointestinal non-Hodgkin lymphoma.
follicular lymphoma; extranodal marginal zone lymphoma; MALT; Helicobacter pylori
Identification of tumor suppressor genes (TSGs) silenced by CpG methylation uncovers the molecular mechanism of tumorigenesis and potential tumor biomarkers. Loss of heterozygosity at 11q25 is common in multiple tumors including nasopharyngeal carcinoma (NPC). OPCML, located at 11q25, is one of the downregulated genes we identified through digital expression subtraction.
Semi-quantitative RT-PCR showed frequent OPCML silencing in NPC and other common tumors, with no homozygous deletion detected by multiplex differential DNA-PCR. Instead, promoter methylation of OPCML was frequently detected in multiple carcinoma cell lines (nasopharyngeal, esophageal, lung, gastric, colon, liver, breast, cervix, prostate), lymphoma cell lines (non-Hodgkin and Hodgkin lymphoma, nasal NK/T-cell lymphoma) and primary tumors, but not in any non-tumor cell line and seldom weakly methylated in normal epithelial tissues. Pharmacological and genetic demethylation restored OPCML expression, indicating a direct epigenetic silencing. We further found that OPCML is stress-responsive, but this response is epigenetically impaired when its promoter becomes methylated. Ecotopic expression of OPCML led to significant inhibition of both anchorage-dependent and -independent growth of carcinoma cells with endogenous silencing.
Thus, through functional epigenetics, we identified OPCML as a broad tumor suppressor, which is frequently inactivated by methylation in multiple malignancies.
Primary non-Hodgkin’s lymphoma of the ovary is a rare occurrence. An ovarian involvement by non-Hodgkin lymphoma (NHL) may include one of the four subtypes of lymphoma: diffuse large B-cell lymphoma, Burkitt’s lymphoma (BL), lymphoblastic lymphoma or anaplastic large cell lymphoma. Burkitt’s lymphoma is a rare entity with a specific poorly differentiated pattern.
Most women experience an ovarian BL with abdominal pelvic pain, abnormal vaginal bleeding, bowel obstruction, urinary frequency, incontinence and abdominal mass. Sometimes these warning signs may be absent, causing a late and more difficult diagnosis.
Here we report a case of a primary ovarian Burkitt’s lymphoma with bilateral involvement in a 57 year old patient. She firstly presented neurological symptoms in the upper limbs and she was treated with surgery and combined chemotherapy. The diagnosis of malignant lymphoma was established after bilateral adnexectomy and histological study of the excised tissue.
Burkitt; Ovarian lymphoma; Hypoaesthesia; Oophorectomy; Chemotherapy
We describe here a case of 51-year-old woman with a symptomatic hepatic cyst that was misdiagnosed as a gastric submucosal tumor (SMT) with endoscopic ultrasound (EUS) and CT scan. The patient presented with an epigastric pain for two months. On endoscopy, a submucosal tumor was found on the cardia of the stomach. Based on EUS and abdominal CT scan, the lesion was diagnosed as a gastric duplication cyst or a gastrointestinal stromal tumor (GIST). The operative plan was laparoscopic wedge resection for the GIST of the gastric cardia. A cystic mass arising from the left lateral segment of the liver was found at the laparoscopic examination. There was no abnormal finding at the gastric cardia. She was treated by laparoscopic hepatic wedge resection including the hepatic cyst using an endoscopic linear stapler.
Hepatic cyst; Submucosal tumor; Stomach
Gastric ulcer secondary to direct invasion from pancreatic adenocarcinoma is rare. Metastases to the stomach have been commonly reported with melanoma and with primary tumors of the breast, lung, ovary, liver, colon and testis. We report a patient who presented with epigastric pain and in whom subsequently upper endoscopy showed a malignant gastric ulcer secondary to direct invasion from pancreatic adenocarcinoma of the body. An 81-year-old female presented to our hospital with epigastric pain and subsequently underwent endoscopy with endoscopic ultrasound for evaluation of a pancreatic body mass. She had a large gastric ulcer in the fundus which was in direct continuity with the pancreatic mass. Pathology from biopsy of the ulcer revealed invasive well-to-moderately-differentiated adenocarcinoma, and immunohistochemical stains were strongly positive for CA19-9, CK7, CK19 and carcinoembryonic antigen. These findings were consistent with a histopathological diagnosis of metastatic carcinoma of the pancreas. Patients with gastrointestinal metastases usually have advanced malignancy with poor prognosis. Endoscopic evaluation with adequate biopsies should be performed for symptomatic patients.
Pancreatic adenocarcinoma; Gastric ulcer; Gastrointestinal metastasis; Endoscopic evaluation
An isolated parenchymal gastric metastasis from ovarian carcinoma without any other sites of recurrence is extremely rare. Only two cases have been reported, both of which were symptomatic. We herein report such a case without any symptoms. A 61-year-old woman presented with a high cancer antigen-125 level without any other clinical manifestation. A subsequent 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography scan revealed a submucosal mass with hypermetabolism of 18F-FDG (standardized uptake value: 5.36) in the gastric antrum. The final pathology after gastric antrectomy showed a metastatic gastric tumor from a primary ovarian carcinoma. We also performed an extensive literature review about gastric metastasis from ovarian carcinoma published until recently, and this is the first case of an isolated parenchymal gastric metastasis from ovarian carcinoma without any symptoms.
Ovarian carcinoma; Gastric antrum; Metastasis; Submucosal tumor; Parenchymal tumor
A retrospective histological study of 540 malignant lymphomas diagnosed at the Department of Pathology of the Seoul National University from 1976 through 1986 is presented. Malignant lymphoma is the 10th most common malignant tumor in Korea, comprising 3.07% of all malignancy during period of study. Among malignant lymphomas non-Hodgkin's lymphoma accounted for 82% and accordingly the Hodgkin's disease was for 18%. The most common type of non-Hodgkin's lymphoma was diffuse histiocytic lymphoma of Rappaport. Follicular lymphoma was very rare, comprising only 2.3%. T-cell lymphoma accounted for 9.6% of non-Hodgkin's lymphomas, the most frequent type being lymphoblastic lymphoma. Immunoblastic sarcoma and mycosis fungoides were occasionally seen but there was no case of pleomorphic adult T-cell lymphoma. Among Hodgkin's diseases, mixed cellularity type was the most common type, and nodular sclerosis type was relatively rare.
We report the rare case of a 72-year-old man with double cancers (gastric adenocarcinoma and Hodgkin's lymphoma) with collision between gastric adenocarcinoma and Hodgkin's lymphoma. Abdominal computed tomography showed increased wall thickness in the fundus region of the stomach and multiple lymph node swellings in the lesser curvature, periceliac and left cardial regions. Upper gastrointestinal endoscopy showed an ulcer approximately 5 cm in diameter with a malignant appearance in the fundus region of the stomach. On histopathologic examination, two completely different tumors were recognized in the stomach. One tumor was a poorly differentiated adenocarcinoma characterized by poorly developed tubular structures associated with prominent lymphoid infiltration of the stroma. The other tumor was found to have proliferated in the wall of the stomach, with diffuse granulomatous lesions and bordering the adenocarcinoma. Large atypical lymphoid cells with prominent nucleoli and enlarged mononuclei or multinuclei were seen in the latter tumor. Hodgkin's lymphoma was also found in the swollen lesser curvature lymph nodes. As a result, gastric adenocarcinoma and metastasis of Hodgkin's lymphoma were collided in the stomach. In conclusion, this case might be helpful in exploring the occurrence mechanism of tumor collision between lymphoma and carcinoma.
Synchronous; Gastric adenocarcinoma; Hodgkin's lymphoma; Collision
Lipomatous hemangiopericytomas (LHPCs) are rare soft-tissue tumors that are histologically characterized by hemangiopericytomatous vasculature and the presence of mature adipocytes. We present the clinicopathological features of a case of gastric LHPC in a 56-year-old female, along with a literature review. Endoscopy and endoscopic ultrasound showed a submucosal tumor 0.8 cm across in the greatest dimension in the lesser curvature side of the gastric antrum. Grossly, the well-defined mass had a solid and tan-white cut surface admixed with myxoid regions and yellowish areas. Histological examination revealed a submucosal well-circumscribed lesion composed of cellular nodules with the classic appearance of an hemangiopericytoma admixed with clusters and lobules of mature adipocytes. The ill-defined tumor cells had weakly eosinophilic cytoplasm and contained spindled nuclei with occasional small nucleoli. Nuclei atypia and mitoses were absent, and no cellular atypia, necrosis or vascular invasion was observed. Immunohistochemistry showed that the tumor cells were diffusely positive for CD34, CD99, and vimentin and were focally reactive for bcl-2. This is the first known report of an LHPC in the stomach. The patient was followed for 12 mo without any evidence of metastasis or recurrence.
Lipomatous hemangiopericytoma; Hemangiopericytoma; Solitary fibrous tumor; Stomach; Immunohistochemistry
Primary orbital non-Hodgkin’s lymphoma is a mucosa-associated lymphoid tissue (MALT)-type extranodal marginal zone lymphoma. Chronic antigen stimulation is implicated as a causative agent in the development of some mature B-cell proliferations; for example, there are associations involving Helicobacter pylori with gastric or conjunctival MALT lymphoma and Chlamydia psittaci with ocular adnexal lymphoma. We examined the molecular signatures of H pylori and Chlamydia in eight orbital lymphomas.
Polymerase chain reaction (PCR) was performed on DNA extracted from microdissected lymphoma cells. H pylori was detected with the urease B and vac/m2 primers. A multiplex touchdown enzyme time-release PCR assay designed to simultaneously detect Chlamydia trachomatis, Chlamydia pneumoniae, and C psittaci was performed. Authenticity of the PCR-amplified products was verified by Southern blot hybridization.
H pylori DNA was detected in an orbital lymphoma of a French patient who had positive serum H pylori titer. C pneumoniae, but neither C psittaci nor C trachomatis, DNA was detected in another orbital lymphoma of a Chinese patient from Hong Kong. H pylori, C pneumoniae, and C psittaci genes were not found in the other six orbital lymphomas.
H pylori or C pneumoniae genomic fingerprints were detected in two of seven primary orbital MALT lymphomas. These findings provide evidence for a possible involvement of particular infectious microorganisms such as H pylori and Chlamydia in primary orbital lymphoma. These different microorganisms may play similar roles in the etiology of orbital MALT lymphomas from different geographic regions. Antibiotic therapy could be considered for orbital MALT lymphomas associated with positive infection.
Gastric cavernous hemangioma is a relatively rare benign gastric disease. Here we report the case of a 25-year-old male patient who had been admitted complaining of epigastric pain and hematemesis. Preoperative imaging indicated that the mass lesion palpated in the epigastric region was a probable mesenchymal tumor of gastric origin. Due to the hypervascular nature and submucosal localization of the mass, we did not obtain definitive preoperative diagnosis by endoscopic biopsy. The histologic diagnosis of cavernous hemangioma was confirmed by post-resection histopathologial evaluation of the mass.
Hemangioma; Vascular disease; Gastric Hemangiomas
Epigenetic inactivation of tumor suppressor genes (TSG) by promoter CpG island hypermethylation is a hallmark of cancer. To assay its extent in human lymphoma, methylation of 24 TSG was analyzed in lymphoma-derived cell lines as well as in patient samples.
We screened for TSG methylation using methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) in 40 lymphoma-derived cell lines representing anaplastic large cell lymphoma, Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), Hodgkin lymphoma and mantle cell lymphoma (MCL) as well as in 50 primary lymphoma samples. The methylation status of differentially methylated CD44 was verified by methylation-specific PCR and bisulfite sequencing. Gene expression of CD44 and its reactivation by DNA demethylation was determined by quantitative real-time PCR and on the protein level by flow cytometry. Induction of apoptosis by anti-CD44 antibody was analyzed by annexin-V/PI staining and flow cytometry.
On average 8 ± 2.8 of 24 TSG were methylated per lymphoma cell line and 2.4 ± 2 of 24 TSG in primary lymphomas, whereas 0/24 TSG were methylated in tonsils and blood mononuclear cells from healthy donors. Notably, we identified that CD44 was hypermethylated and transcriptionally silenced in all BL and most FL and DLBCL cell lines, but was usually unmethylated and expressed in MCL cell lines. Concordant results were obtained from primary lymphoma material: CD44 was not methylated in MCL patients (0/11) whereas CD44 was frequently hypermethylated in BL patients (18/29). In cell lines with CD44 hypermethylation, expression was re-inducible at mRNA and protein levels by treatment with the DNA demethylating agent 5-Aza-2'-deoxycytidine, confirming epigenetic regulation of CD44. CD44 ligation assays with a monoclonal anti-CD44 antibody showed that CD44 can mediate apoptosis in CD44+ lymphoma cells. CD44 hypermethylated, CD44- lymphoma cell lines were consistently resistant towards anti-CD44 induced apoptosis.
Our data show that CD44 is epigenetically regulated in lymphoma and undergoes de novo methylation in distinct lymphoma subtypes like BL. Thus CD44 may be a promising new epigenetic marker for diagnosis and a potential therapeutic target for the treatment of specific lymphoma subtypes.
A 70-year-old woman was admitted to our department with epigastric discomfort and nausea over the duration of 1 month. An esophagogastroduodenoscopy showed the presence of a 1.0×1.0 cm-sized flat lesion with central ulceration at the greater curvature side of the antrum. A biopsy demonstrated the presence of an adenocarcinoma of well differentiated, intestinal type in the stomach. Endoscopic submucosal dissection was done and the diagnosis of a composite neuroendocrine carcinoma with an adenocarcinoma of the stomach was confirmed. We report a case of a gastric composite tumor with an adenocarcinoma and neuroendocrine carcinoma confirmed by endoscopic submucosal dissection with a review of the literature.
Composite tumor; Adenocarcinoma; Carcinoma, neuroendocrine
Immunocytochemical stains for three epithelial cell markers--keratin, epithelial membrane antigen (EMA) and carcinoembryonic antigen (CEA)--have been examined on paraffin-embedded material from 14 patients with nasopharyngeal carcinoma (NPC). Tumour cells staining positively for keratin were found in all cases and for EMA in eight; two tumours contained CEA-positive cells. Seven cases of Hodgkin's disease and 24 non-Hodgkin's lymphomas were uniformly negative. Keratin is the most reliable epithelial marker for identifying NPC and excluding lymphoma. The regular finding of stainable keratin in non-keratinising and anaplastic NPC supports the view that NPC is a homogeneous group exhibiting variable degrees of squamous differentiation.
Primary bone lymphoma (PBL) is a relatively uncommon entity. However, involvement of the cranial vault is an unusual manifestation of aggressive non-Hodgkin’s lymphoma. We report the case of a 42-year old immunocompetent woman who presented with an enlarging mass involving the right parietal bone. Magnetic resonance imaging (MRI) of the brain revealed an expansive tumor that affects the right parietal bone. Computed tomographic (CT) scans of the abdomen, chest and pelvis were negative for lymphadenopathy or organomegaly. Biopsy of the mass showed diffuse large B-cell non-Hodgkin’s lymphoma confirmed by immunohistochemical study. The patient had a complete response after 4 cycles of chemotherapy followed by external beam radiotherapy. After a follow-up of more than 9 months the patient is still in good local control without distant metastasis. The aim of our work is to report a case of Primary bone lymphoma of the cranial vault with good response to treatment combining sequential chemotherapy and radiotherapy.
B-Cell lymphoma; primary bone lymphoma; extranodal lymphoma; cranial vault
Epstein-Barr virus (EBV), a human gammaherpesvirus, is associated with a series of malignant tumors. These include lymphomas (Burkitt’s lymphoma, Hodgkin’s disease, T/NK-cell lymphoma, post-transplant lymphoproliferative disease, AIDS-associated lymphoma, X-linked lymphoproliferative syndrome), carcinomas (nasopharyngeal carcinoma, gastric carcinoma, carcinomas of major salivary glands, thymic carcinoma, mammary carcinoma) and a sarcoma (leiomyosarcoma). The latent EBV genomes persist in the tumor cells as circular episomes, co-replicating with the cellular DNA once per cell cycle. The expression of latent EBV genes is cell type specific due to the strict epigenetic control of their promoters. DNA methylation, histone modifications and binding of key cellular regulatory proteins contribute to the regulation of alternative promoters for transcripts encoding the nuclear antigens EBNA1 to 6 and affect the activity of promoters for transcripts encoding transmembrane proteins (LMP1, LMP2A, LMP2B). In addition to genes transcribed by RNA polymerase II, there are also two RNA polymerase III transcribed genes in the EBV genome (EBER 1 and 2). The 5′ and internal regulatory sequences of EBER 1 and 2 transcription units are invariably unmethylated. The highly abundant EBER 1 and 2 RNAs are not translated to protein. Based on the cell type specific epigenetic marks associated with latent EBV genomes one can distinguish between viral epigenotypes that differ in transcriptional activity in spite of having an identical (or nearly identical) DNA sequence. Whereas latent EBV genomes are regularly targeted by epigenetic control mechanisms in different cell types, EBV encoded proteins may, in turn, affect the activity of a set of cellular promoters by interacting with the very same epigenetic regulatory machinery. There are EBNA1 binding sites in the human genome. Because high affinity binding of EBNA1 to its recognition sites is known to specify sites of DNA demethylation, we suggest that binding of EBNA1 to its cellular target sites may elicit local demethylation and contribute thereby to the activation of silent cellular promoters. EBNA2 interacts with histone acetyltransferases, and EBNALP (EBNA5) coactivates transcription by displacing histone deacetylase 4 from EBNA2-bound promoter sites. EBNA3C (EBNA6) seems to be associated both with histone acetylases and deacetylases, although in separate complexes. LMP1, a transmembrane protein involved in malignant transformation, can affect both alternative systems of epigenetic memory, DNA methylation and the Polycomb-trithorax group of protein complexes. In epithelial cells LMP1 can up-regulate DNA methyltransferases and, in Hodgkin lymphoma cells, induce the Polycomb group protein Bmi-1. In addition, LMP1 can also modulate cellular gene expression programs by affecting, via the NF-κB pathway, levels of cellular microRNAs miR-146a and miR-155. These interactions may result in epigenetic dysregulation and subsequent cellular dysfunctions that may manifest in or contribute to the development of pathological changes (e.g. initiation and progression of malignant neoplasms, autoimmune phenomena, immunodeficiency). Thus, Epstein-Barr virus, similarly to other viruses and certain bacteria, may induce pathological changes by epigenetic reprogramming of host cells. Elucidation of the epigenetic consequences of EBV-host interactions (within the framework of the emerging new field of patho-epigenetics) may have important implications for therapy and disease prevention, because epigenetic processes are reversible and continuous silencing of EBV genes contributing to patho-epigenetic changes may prevent disease development.
Gastric lipomatosis is an extremely rare condition. We present a case of a 69-year-old woman admitted with epigastric soreness. Computerized tomography (CT) revealed extrinsically compressing, fat-containing mass lesions on the entire gastric wall of the antrum and body except for the lesser curvature. A subtotal gastrectomy was performed. Pathology findings confirmed a gastric lipomatosis with multiple gastric ulcerations and extensive disruptions of the muscular layers. This case and reports of other gastric lipomatosis cases indicate that CT should be used to characterize large submucosal masses because CT can show the specific nature and extent of the disease. We believe that surgical treatment is the most appropriate treatment for symptomatic gastric lipomatosis that shows extensive gastric involvement, or when there are multiple gastric lipomas.
Stomach neoplasms; Lipomatosis; Gastrectomy
A heterotopic pancreas in the gastrointestinal tract is mostly found incidentally and its malignant transformation is extremely rare. We describe the second case of adenocarcinoma arising in a gastric heterotopic pancreas of an asymptomatic 35-yr-old man in Korea. Esophagogastroduodenoscopy revealed a submucosal tumor with an irregular central umbilication in the gastric antrum. A wedge resection specimen demonstrated a submucosal oligolocular cystic mass (1.7×1.4×1.2 cm) with a solid portion. Microscopically, the cystic portion was composed of dilated pancreaticobiliary type ducts with adjacent small foci of periductal glandular structures. The adenocarcinoma components in the solid area infiltrated the proper muscle and the overlying mucosa of the stomach. The transitional area between the benign ductal structures and the adenocarcinoma component was found. The follow-up course was uneventful 5 months postoperatively.
Adenomyoma; Stomach Neoplasms; Adenocarcinoma