Prenatal to peripubertal exposure to Di(2-ethylhexyl) phthalate induced endometrial atrophy and fibrosis in female mice.

Di(2-ethylhexy) phthalate (DEHP) is a widely used plasticizer that is ubiquitously found in the environment. Using a mouse model, we investigated the impact of early life DEHP exposure ranging from the prenatal to peripubertal developmental period of the female reproductive system. Pregnant female mice were allocated to three groups as follows: control, 100 mg/kg/day, and 500 mg/kg/day DEHP treatment. DEHP exposure was introduced through feeding during pregnancy (3 weeks) and lactation (3 weeks). After weaning, the offspring were also exposed to DEHP through feeding for another 2 weeks. Observations were conducted on female offspring at 10 and 24 weeks. The number of live offspring per dam was significantly lower in the high-DEHP-exposed group (500 mg/kg/day) compared to the control group (7.67 ± 1.24 vs. 14.17 ± 0.31; p < 0.05) despite no difference in pregnancy rates across the groups. Low-DEHP exposure (100 mg/kg/day) resulted to a decreased body weight (36.07 ± 3.78 vs. 50.11 ± 2.11 g; p < 0.05) and decreased left uterine length (10.60 ± 1.34 vs. 14.77 ± 0.82 mm; p < 0.05) in 24-week- old female mice. As early as 10 weeks, endometrial atrophy and fibrosis were observed, and endometrial cystic hyperplasia was noted in female mice at 24 weeks. Our study is the first to demonstrate that female mice exposed to DEHP in the early life developed endometrial fibrosis in the female offspring. Further studies on the consequences of these observations in fecundity and other reproductive functions are warranted.

A Rare Occurrence of Primarily Extranodal Spinal Epidural Lymphoma With Spinal Cord Compression and Invasion to the Thoracic Cavity.

A 41-year-old man suffered from progressive radiculomyelopathy caused by spinal epidural mass primarily encasing the spinal cord at the cervicothoracic vertebrae that extended into the thoracic cavity through the neural foramen. An urgent decompressive laminectomy and epidural tumor resection were performed to prevent neurological deterioration and effective spinal cord decompression. The histopathologic diagnosis was diffuse large B-cell lymphoma. As first-line treatment for stage II extranodal lymphoma, he received 6 cycles of R-CHOP (rituximab/cyclophosphamide, hydroxydaunorubicin, Oncovin, and prednisone) chemotherapy. Consequently, follow-up positron-emission tomography CT and MR images demonstrated a complete metabolic response (Deauville score 1). This rare occurrence of primarily extranodal spinal epidural lymphoma with limited disease will be presented in a literature review.

Gastric Inverted Polyps-Distinctive Subepithelial Lesions of the Stomach: Clinicopathologic Analysis of 12 Cases With an Emphasis on Neoplastic Potential.

Gastric inverted polyps (GIPs) are rare gastric polyps characterized by a submucosal inverted growth of mucosal components. Because of their rarity, they are not well characterized and are diagnostically challenging. We examined 12 cases of GIPs arising in 8 male and 4 female patients (mean age: 56 y). Most GIPs (11/12, 92%) occurred as a single, rounded subepithelial lesion in the body or fundus (mean size: 14.9 mm). Histologically, GIPs consisted of gastric-type glandular epithelium and smooth muscle component, growing in an endophytic manner; however, they displayed significant morphologic variations. We classified GIPs into 3 subtypes by the following features: communication with the mucosal surface, smooth muscle boundary, and tissue organization. The defining characteristics of type 1 were a mucosal communicating structure at the center and a well-defined smooth muscle boundary, resulting in a characteristic low-magnification morphology of a round vase. Type 2 had an organized glandular proliferation with smooth muscle boundary and no central communicating structure. Type 3 GIPs had no mucosal communicating structure or smooth muscle boundary; its key histologic feature was the lobular organization pattern produced by proliferations of cystic or hyperplastic glands and smooth muscle. All type 1 GIPs exhibited coexisting adenocarcinoma (3 cases) or stromal proliferation (3 cases). Three patients with type 2 GIP had separate adenocarcinoma. None of the type 3 GIPs had accompanying carcinoma. In conclusion, GIPs are a heterogenous group showing different morphology and clinical behavior. Notably, type 1 GIP could be considered a precancerous lesion with the potential to develop adenocarcinoma.

Proposed Modification of Staging for Distal Cholangiocarcinoma Based on the Lymph Node Ratio Using Korean Multicenter Database.

The 8th American Joint Committee on Cancer (AJCC) staging system for distal cholangiocarcinoma (DCC) included a positive lymph node count (PLNC), but a comparison of the prognostic predictive power of PLNC and lymph node ratio (LNR) is still under debate. This study aimed to compare various staging models made by combining the abovementioned factors, identify the model with the best predictive power, and propose a modified staging system. We retrospectively reviewed 251 patients who underwent surgery for DCC at four centers. To determine the superiority of various staging models for predicting overall OSR, Akaike information criterion (AIC), Bayesian information criterion (BIC), AIC correction (AICc), and Harrell's C-statistic were calculated. In multivariate analysis, age (p = 0.003), total lymph node count (p = 0.033), and revised T(LNR)M staging (p < 0.001) were identified as independent factors for overall survival rate. The predictive performance of revised T (LNR) M staging (AIC: 1288.925, BIC: 1303.377, AICc: 1291.52, and Harrell's C statics: 0.667) was superior to other staging system. A modified staging system consisting of revised T category and LNR predicted better overall survival of DCC than AJCC 7th and AJCC 8th editions. In the future, external validation of the proposed new system using a larger cohort will be required.

Diffuse Involvement of Primary Colorectal Lymphoma Simulating Ulcerative Colitis.

Diffuse involvement of colorectal lymphoma masquerading as colitis is a very rare presentation of primary colorectal lymphoma. Detecting occult lymphoma is difficult in the setting of diffuse colonic involvement with no definite mass and inflammatory mucosal changes. We encountered a case of diffuse-type primary colorectal lymphoma simulating ulcerative colitis in a previously healthy 31-year-old woman. Despite multiple mucosal biopsies, the biopsy diagnosis was not made due to unawareness of atypical lymphocytes admixed with dense lymphoplasmacytic infiltration. The present case emphasizes the importance of being aware of this rare presentation of primary colorectal lymphoma in order to avoid misdiagnosis.

Provisional Guideline Recommendation for EGFR Gene Mutation Testing in Liquid Samples of Lung Cancer Patients: A Proposal by the Korean Cardiopulmonary Pathology Study Group.

Liquid biopsy for detection of mutation from circulating tumor DNA is a new technology which is attractive in that it is non-invasive. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) is an effective first line drug for advanced non-small cell lung cancer patients who harbor activating EGFR mutation. During the course of treatment, resistance against TKI arises which can be contributed to EGFR T790M mutation in about 50-60% of patients. Third generation TKI may overcome the resistance. In patients who cannot undergo tissue biopsy due to variable reasons, liquid biopsy is an excellent alternative for the detection of EGFR T790M mutation. However, this relatively novel method requires standardization and vigorous quality insurance. Thus, a standard set of guideline recommendations for liquid biopsy for EGFR mutation testing suitable for the Korean medical community is necessary. In this article, we propose a set of provisional guideline recommendations that was discussed and approved by the Cardiopulmonary Pathology Study Group of the Korean Society of Pathologists.

Metaplastic Meningioma Overspreading the Cerebral Convexity.

Meningioma is relatively common, benign, and extra-axial tumor accounting for about 20% of primary brain and spinal cord tumors. The World Health Organization (WHO) classified these tumors into Grade I (benign), Grade II (atypical), and Grade III (anaplastic) meningioma. Grade I meningioma which is slowly growing tumor and have some rare subtypes. Among them, metaplastic subtype is defined as a tumor containing focal or widespread mesenchymal components including osseous, cartilaginous, lipomatous, myxoid or xanthomatous tissue, singly or in combinations. We report a rare metaplastic meningioma overspreading nearly whole cerebral convexity from main extra-axial tumor bulk in the parietal lobe.

Pulmonary Leukocytoclastic Vasculitis as an Initial Presentation of Myelodysplastic Syndrome.

Systemic vasculitis involving the lung is a rare manifestation of myelodysplastic syndrome (MDS), and secondary vasculitis is considered to have poor prognosis. A 44-year-old man presented with fever and dyspnea of 1 month duration. A chest radiograph revealed bilateral multiple wedge shaped consolidations. In addition, the results of a percutaneous needle biopsy for non-resolving pneumonia were compatible with pulmonary vasculitis. Bone marrow biopsy was performed due to the persistence of unexplained anemia and the patient was diagnosed with MDS. We reported a case of secondary vasculitis presenting as non-resolving pneumonia, later diagnosed as paraneoplastic syndrome of undiagnosed MDS. The cytopenia and vasculitis improved after a short course of glucocorticoid treatment, and there was no recurrence despite the progression of underlying MDS.

Analysis of Mutations in Epidermal Growth Factor Receptor Gene in Korean Patients with Non-small Cell Lung Cancer: Summary of a Nationwide Survey.

BACKGROUND: Analysis of mutations in the epidermal growth factor receptor gene (EGFR) is important for predicting response to EGFR tyrosine kinase inhibitors. The overall rate of EGFR mutations in Korean patients is variable. To obtain comprehensive data on the status of EGFR mutations in Korean patients with lung cancer, the Cardiopulmonary Pathology Study Group of the Korean Society of Pathologists initiated a nationwide survey. METHODS: We obtained 1,753 reports on EGFR mutations in patients with lung cancer from 15 hospitals between January and December 2009. We compared EGFR mutations with patient age, sex, history of smoking, histologic diagnosis, specimen type, procurement site, tumor cell dissection, and laboratory status. RESULTS: The overall EGFR mutation rate was 34.3% in patients with non-small cell lung cancer (NSCLC) and 43.3% in patients with adenocarcinoma. EGFR mutation rate was significantly higher in women, never smokers, patients with adenocarcinoma, and patients who had undergone excisional biopsy. EGFR mutation rates did not differ with respect to patient age or procurement site among patients with NSCLC. CONCLUSIONS: EGFR mutation rates and statuses were similar to those in published data from other East Asian countries.

Innervation in women with uterine myoma and adenomyosis.

OBJECTIVE: To determine if neurofilament (NF) is expressed in the endometrium and the lesions of myomas and adenomyosis, and to determine their correlation. METHODS: Histologic sections were prepared from hysterectomies performed on women with adenomyosis (n=21), uterine myoma (n=31), and carcinoma in situ of the uterine cervix. Full-thickness uterine paraffin blocks, which included the endometrium and myometrium histologic sections, were stained immunohistochemically using the antibodies for monoclonal mouse antihuman NF protein. RESULTS: NF-positive cells were found in the endometrium and myometrium in 11 women with myoma and in 7 with adenomyosis, but not in patients with carcinoma in situ of uterine cervix, although the difference was statistically not significant. There was no significant difference between the existence of NF-positive cells and menstrual pain or phases. The NF-positive nerve fibers were in direct contact with the lesions in nine cases (29.0%) of myoma and in five cases (23.8%) of adenomyosis. It was analyzed if there was a statistical significance between the existence of NF positive cells in the endometrium and the expression of NF-positive cells in the uterine myoma/adenomyosis lesions. When NF-positive cell were detected in the myoma lesions, the incidence of NF-positive nerve cells in the eutopic endometrium was significantly high. When NF-positive cell were detected in the basal layer, the incidence of NF-positive nerve cells in the myoma lesions and adenomyosis lesions was significantly high. CONCLUSION: We assume that NF-positive cells in the endometrium and the myoma and adenomyosis lesions might play a role in pathogenesis. Therefore, more studies may be needed on the mechanisms of nerve fiber growth in estrogen-dependent diseases.

Peripheral T Cell Non-Hodgkin's Lymphoma following Treatment of Hodgkin's Lymphoma.

Previous reports have suggested that non-Hodgkin's lymphoma (NHL) is more likely to develop in patients with Hodgkin lymphoma (HL) compared to the general population. These two can occur synchronously or metachronously. We report here on a case of nodular sclerosis classical HL and T cell NHL that occurred in a patient metachronously. Peripheral T cell lymphoma (PTCL) of the patient was found about 2 years after treatment of classical HL. When the patient was diagnosed with HL, biopsy revealed typical RS cells, presenting positive for CD30 and CD15 and negative for CD79a and CD3 in immunohistochemistry. And PCR analysis showed IgH gene rearrangement; however, T cell receptor gene rearrangement and Epstein-Barr virus (EBV) were not detected on PCR analysis. After 2 years of treatment of HL, colonoscopic biopsy and lymph node biopsy showed CD3 positive atypical cells intermixed with small reactive lymphoid cells and plasma cells, indicating T cell lymphoma. PCR analysis demonstrated T cell receptor gene rearrangement and did not detect EBV. Although it is rare, synchronous or metachronous HL and NHL may occur. Therefore, we may need to ensure pathological confirmation, especially in case of lymphoma that did not respond to chemotherapy.

Progesterone reduces neurofilament (NF)--positive nerve fibers in eutopic endometrium of patients with endometriosis and myomata.

OBJECTIVE: To evaluate whether there are neurofilament (NF)-positive nerve fibers in the eutopic endometrium of patients with myoma and endometriosis by using stromal cell culture and to verify whether progesterone has an effect on the NF-positive nerve fiber by using stromal cell culture. STUDY DESIGN: Patients with uterine myoma (N = 11), ovarian and pelvic endometriosis (N = 10), and without myoma and endometriosis (N = 10) were included in the study. Human endometrial tissues were obtained from hysterectomy and curettage. The stromal cells were cultured and immunostaining was performed before and after treatment with progesterone by using NF. RESULTS: Before progesterone treatment the percentage of NF-positive nerve fibers between the uterine myoma group (4.91 +/- 2.05) and the endometriosis group (2.22 +/- 0.92) was statistically significant, and there was a significantly different percentage of NF-positive nerve fibers between the uterine myoma group (4.91 +/- 2.05) and the levonorgestrel intrauterine device-inserted group (1.50 +/- 0.25). After progesterone treatment the percentage of NF-positive nerve fibers was significantly decreased in the uterine myoma (2.09 +/- 1.73) and the endometriosis (1.48 +/- 0.80) groups. CONCLUSION: We showed that the NF-positive nerve fibers were reduced after progesterone treatment by using stromal cell culture and suggest that progesterone could have a role in the decrease of endometriosis/myoma-associated pain.

Cytogenetic and molecular genetic study on granular cell glioblastoma: a case report.

Granular cell astrocytoma is a rare infiltrative malignant glioma with prominent granular cell change. Granular cell astrocytomas are biologically aggressive compared with conventional infiltrating astrocytomas of similar grades, but their genetic alterations are poorly known. We report a case of granular cell glioblastoma and its genetic and molecular features. Histologically, the tumor not only showed features typical of granular cell astrocytoma but also demonstrated frequent mitoses, pseudopalisading necrosis, and vascular endothelial hyperplasia, compatible with glioblastoma. Array-based comparative genomic hybridization and focused molecular genetic analyses demonstrated gain of chromosome 7; losses of chromosome 1p, 8p, 9p, 10, 13q, and 22q; amplification of epidermal growth factor receptor; and homozygous deletion of CDKN2A as well as MGMT promoter methylation. However, neither isocitrate dehydrogenase 1 mutation nor codeletion of 1p/19q was found. Our results indicate that granular cell glioblastomas, despite having its peculiar granular cell changes, share common molecular genetic features with conventional glioblastoma, especially the classical subtype.

WITHDRAWN: Cytogenetic and molecular genetic study on glioblastoma arising in granular cell astrocytoma: a case report.

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Xanthogranulomatous pancreatitis presents as a solid tumor mass: a case report.

Xanthogranulomatous inflammation (XGI) is a rare, idiopathic process in which lipid-laden histiocytes are deposited at various locations in the body. Although XGI has been reported to occur in various organs such as the gallbladder, kidney, bone, stomach, colon, appendix, lymph nodes, urachus, and urinary bladder and in soft tissues, xanthogranulomatous pancreatitis (XGP) is extremely rare. Herein, we report a case of XGP occurring in a 70-yr-old woman, who presented with abdominal pain for several months. On physical examination, mild epigastric tenderness was noted. Abdomen CT scan revealed a low attenuated mass in uncinate process of pancreas, suggesting malignant lesion. Whipple's operation was performed and the final pathologic diagnosis was XGP. The patient's post-operative course was uneventful, and no recurrence was found within 7 months of the operation. When a pancreatic mass does not show clinico-radiological features typical of common pancreatic neoplasms, XGP should be considered for a differential diagnosis.

Duodenal somatostatinoma: a case report and review.

Somatostatinomas are rare functioning carcinoid tumors that usually arise in the pancreas and duodenum. They are seldom associated with typical clinical symptoms; their diagnosis is confirmed only by histological and immunohistochemical studies and the presence of specific hormones. Two distinct clinicopathological forms of somatostatinoma exist: duodenal and pancreatic somatostatinomas. Clinically, compared to pancreatic somatostatinomas, duodenal somatostatinomas are more often associated with nonspecific symptoms and neurofibromatosis, but less often with somatostatinoma syndrome or metastasis. Histologically, duodenal somatostatinomas frequently have psammoma bodies in the tumor cells. We report a case of duodenal somatostatinoma in 58-year-old man with vague epigastric pain and nausea. He did not have diabetes, steatorrhea, or cholelithiasis. Abdominal computed tomography showed a 25-mm mass in the duodenum and 25-mm nodule in the liver. Endoscopic retrograde cholangiopancreatography showed a duodenal submucosal tumor. Although the endoscopic biopsies were free of malignancy, the patient subsequently underwent Whipple's operation for the duodenal mass. Examination revealed as a somatostatinoma using a special stain for somatostatin.

Splenic infarction in a patient with autoimmune hemolytic anemia and protein C deficiency.

Splenic infarction is most commonly caused by cardiovascular thromboembolism; however, splenic infarction can also occur in hematologic diseases, including sickle cell disease, hereditary spherocytosis, chronic myeloproliferative disease, leukemia, and lymphoma. Although 10% of splenic infarction is caused by hematologic diseases, it seldom accompanies autoimmune hemolytic anemia (AIHA). We report a case of a 47-year-old woman with iron deficiency anemia who presented with pain in the left upper abdominal quadrant, and was diagnosed with AIHA and splenic infarction. Protein C activity and antigen decreased to 44.0% (60-140%) and 42.0% (65-140%), respectively. Laboratory testing confirmed no clinical cause for protein C deficiency, such as disseminated intravascular coagulation, sepsis, hepatic dysfunction, or acute respiratory distress syndrome. Protein C deficiency with splenic infarction has been reported in patients with viral infection, hereditary spherocytosis, and leukemia. This is a rare case of splenic infarction and transient protein C deficiency in a patient with AIHA.

Tricuspid valvular myxoma: unusual case of tricuspid valve myxoma mimicking thrombus after pulmonary artery embolectomy and tricuspid annuloplasty in pulmonary thromboembolism patient.

A 55-year-old man with massive pulmonary thromboembolism underwent thrombolysis, pulmonary artery embolectomy and tricuspid annuloplasty. Nine months later, a mobile echogenic intra-cardiac mass was found in the tricuspid valve. Because the patient had undergone annuloplasty, thrombosis was suspected as the most likely diagnosis and thrombolytic therapy was instituted. However, the size of the cardiac mass did not change and after surgical excision the mass was found to be a myxoma. Cardiac valvular tumors are uncommon and when they occur they are usually slow growing fibroelastomas. In this case, the rapid growing cardiac myxoma on the tricuspid valve was found after the occurrence of pulmonary thromboembolism. To our knowledge, this is first reported case of tricuspid valve myxoma in Korea.