Collagenous gastritis, a counterpart of collagenous colitis, is an extremely rare disorder. The first case of collagenous gastritis in a Korean boy in his pre-teens who had been receiving treatment for refractory iron deficiency anemia has been reported. The patient had been suffering from intermittent abdominal pain, recurrent blood-tinged vomiting and poor oral intake. The gastric endoscopy revealed diffuse cobble-stone appearance of the mucosa with easy touch bleeding throughout the stomach but no abnormalities in the esophagus, duodenum, and colon. Pathologic examination of the gastric biopsies from the antrum, body and cardia showed a subepithelial collagen deposition with entrapped dilated capillaries, moderate infiltrates of lymphoplasma cells and eosinophils of the lamina propria, and marked hypertrophy of the muscularis mucosa. The collagen deposition appeared as discontinuous bands with focally irregular extension into the deeper part of the antral mucosa. It measured up to 150 µm. Helicobacter pylori infection was not detected. The biopsies from the duodenum, esophagus and colon revealed no pathologic abnormalities.

We report a rare case of cerebellar liponeurocytoma with an unusually aggressive histopathology. A 49-year-old man presented with a four-month history of headache, vertigo, and progressive swaying gait. Magnetic resonance imaging showed a 3×3.5 cm sized relatively well-demarcated round mass lesion in the fourth ventricle, characterized by high signal intensity on T2-weighted images. Postcontrast images revealed strong enhancement of the solid portion and the cyst wall. The patient underwent suboccipital craniectomy and tumor removal. The pathologic diagnosis was cerebellar liponeurocytoma. Adjuvant radiotherapy was offered due to concerns related to the high proliferative index (Ki-67, 13.68%) of the tumor. At the last routine postoperative follow-up visit (12 months), the patient complained of no specific symptom and there was no evidence of tumor recurrence. However, long-term follow-up and the analysis of similar cases are necessary because of the low number of reports and the short follow-up of cases.

A set of proteins reflecting the prognosis of patients have clinical significance since they could be utilized as predictive biomarkers and/or potential therapeutic targets. With the aim of finding novel diagnostic and prognostic markers for glioblastoma (GBM), a tissue microarray (TMA) library consisting of 62 GBMs and 28 GBM-associated normal spots was constructed. Immunohistochemistry against 78 GBM-associated proteins was performed. Expression levels of each protein for each patient were analyzed using an image analysis program and converted to H-score [summation of the intensity grade of staining (0–3) multiplied by the percentage of positive cells corresponding to each grade]. Based on H-score and hierarchical clustering methods, we divided the GBMs into two groups (n=19 and 37) that had significantly different survival lengths (p<0.05). In the two groups, expression of nine proteins (survivin, cyclin E, DCC, TGF-β, CDC25B, histone H1, p-EGFR, p-VEGFR2/3, p16) was significantly changed (q<0.05). Prognosis-predicting potential of these proteins were validated with another independent library of 82 GBM TMAs and a public GBM DNA microarray dataset. In addition, we determined 32 aberrant or mislocalized subcellular protein expression patterns in GBMs compared with relatively normal brain tissues, which could be useful for diagnostic biomarkers of GBM. We therefore suggest that these proteins can be used as predictive biomarkers and/or potential therapeutic targets for GBM.

Purpose

Fibrous hamartoma (FH) of infancy is a distinctive fibrous growth that most frequently occurs at birth and during the postnatal period. It is important for clinicians and pathologists to recognize this entity to avoid an aggressive approach.

Methods

We herein describe the clinicopathologic features of 9 FHs diagnosed at a single institution between 1997 and 2010.

Results

There were 7 boys and 2 girls, and the mean age of presentation was 14.7 months. The common locations were the lower back and gluteal region (n = 3) and scrotum (n = 2). They were solitary lesions, and measured 1.0 to 7.0 cm in maximum diameter (mean, 4.9 cm). The excised masses tended to be poorly circumscribed, and consisted of an intimate mixture of firm, gray-white tissue with fat. Histologically, these lesions were composed of 3 components forming a vague, irregular, organoid pattern: well-defined intersecting trabeculae of fibrocollagenous tissue; loosely textured areas of small, rounded, primitive mesenchymal cells; and mature fat. Over a median follow-up of 72 months, no patient showed recurrence.

Conclusion

FH should be distinguished from other forms of fibromatosis and malignant tumors because it is benign and usually cured by local excision.

The mechanism of mouse parturition is thought to involve myometrial infiltration by amniotic fluid (AF) macrophages, activated by surfactant protein-A (SP-A). In humans, the concentration of AF SP-A decreases during labor, and no fetal macrophages are found in the myometrium after labor. Therefore, it appears that the mechanisms of labor in mice and humans are different. We investigated a potential role for SP-A in human pregnancy and parturition by examining SP-A expression patterns in AF and amnion. High molecular weight (HMW; >250 kD) oligomeric SP-A was increased in AF with advancing gestation. Interestingly, these oligomers were more abundant in placental amnion before labor at term, while they increased primarily in reflected amnion during labor (p<0.05). Immunoblotting showed a binding of HMW SP-A in AF to amnion. In C57BL/6 mice, oligomeric SP-A was also readily detected in AF from E15 onwards, but not in amnion. Macrophage density in mice myometrium did not change with advancing gestational age. Microarray analysis of human amnion explants incubated with SP-A revealed a molecular signature of inhibited cytokine-cytokine receptor interaction with down-regulation of IL-1β, CXCL2, and CXCL5 mRNA expression. The findings herein strongly suggest that SP-A signals amniotic anti-inflammatory response via amniotic fluid during pregnancy. We propose that a SP-A interaction among amniotic fluid, placental amnion, and reflected amnion is a unique mechanism for immunoregulation in human pregnancy akin to that established in lung biology. However, amniotic fluid SP-A and fetal macrophages by themselves do not seem to be exclusive effectors of parturition in humans.

This is an author-produced version of a manuscript accepted for publication in The Journal of Immunology (The JI). The American Association of Immunologists, Inc. (AAI), publisher of The JI, holds the copyright to this manuscript. This version of the manuscript has not yet been copyedited or subjected to editorial proofreading by The JI; hence, it may differ from the final version published in The JI (online and in print). AAI (The JI) is not liable for errors or omissions in this author-produced version of the manuscript or in any version derived from it by the U.S. National Institutes of Health or any other third party. The final, citable version of record can be found at www.jimmunol.org.

Intra-abdominal desmoplastic small round cell tumor (DSRCT) is a highly malignant tumor of uncertain histogenesis. Here we report a case of DSRCT involving the stomach, initially misdiagnosed as gastric cancer. A 12-year-old boy presented with upper abdominal pain developed 1 month prior. On gastroscopy, a 7-cm mass was noted involving the esophago-gastric junction to the fundus, and positron emission tomography showed multiple hot uptakes suggesting distant metastasis. Gastroscopic biopsy showed poorly differentiated malignant cells. We diagnosed as stage IV gastric cancer and treated with 6 cycles of chemotherapy. Laparotomy revealed a huge gastric mass along with peritoneal disseminations. Palliative proximal gastrectomy was performed. Pathological examination revealed transmural involvement of DSRCT, and t(11;22)(p12;q12) was demonstrated on fluorescence in situ hybridization test. The chemotherapeutic regimen was changed and the patient underwent 8 additional cycles of post-operative chemotherapy. The patient is now alive and the residual tumor shows no significant changes after chemotherapy.

The prognosis for patients with recurrent glioblastomas (GBMs) is dismal, with a median survival of 3–6 months. We performed a phase II trial of low-dose continuous (metronomic) treatment using temozolomide (TMZ) for recurrent GBMs. TMZ-refractory patients with GBM who experienced disease recurrence or progression during or after the cyclic treatment schedule of TMZ after surgery and standard radiotherapy were eligible. This phase II trial included 2 cohorts of patients. The initial cohort, comprising 10 patients, received TMZ at 40 mg/m2 everyday. After this regimen seemed safe and effective, the metronomic schedule was changed to 50 mg/m2 everyday. The second cohort, comprising 28 patients, received TMZ at 50 mg/m2 everyday. The 6-month progression-free survival in all 38 patients was 32.5% (95% CI: 29.3%–35.8%) and the 6-month overall survival was 56.0% (95% CI: 36.2%–75.8%). One patient developed a grade III neutropenia, grade II thrombocytopenia in 3 patients, and grade II increase of liver enzyme (GOT/GPT) in 3 patients. Of all patients included in this study, 4 patients were withdrawn from this study because of side effects including sustained hematological disorders, cryptococcal infection, and cellulitis. In a response group, quality of life measured with short form-36 was well preserved, when compared with the pretreatment status. Metronomic treatment of TMZ is an effective treatment for recurrent GBM that is even refractory to conventional treatment of TMZ and has acceptable toxicity.

We report a rare case of cavernous hemangioma (CH) which developed in adjacent location to a preexisting CH after gamma knife radiosurgery (GKRS). A 36-year-old woman underwent GKRS for a CH in the left lentiform nucleus. Three-and-half years after radiosurgery, MRI revealed a new CH in the left caudate nucleus. Surgical excision of the new lesion was performed. The pathological examination confirmed the diagnosis of CH. In radiosurgery for CH, it should be noted that a new CH may develop, which is likely to result from the interaction between radiation and predisposing factors of the patient.

Background

Gliomatosis cerebri (GC) is characterized by a diffuse infiltration of tumor cells throughout CNS, however, few details are available about the chemotherapeutic effect on GC. The aim of this study was to investigate its clinical course and to determine the efficacy of chemotherapy for GC.

Methods

Between Jan. 1999 and Dec. 2004, 37 GC patients were diagnosed by biopsy and treated with radiotherapy in a single institution. To determine the efficacy of chemotherapy for GC, we retrospectively reviewed their clinical courses. The study cohort was divided into 2 groups, those with and without receiving post-radiotherapy adjuvant chemotherapy such as temozolomide or nitrosourea-based chemotherapy.

Results

Nineteen patients with adjuvant chemotherapy were assigned to the chemotreatment group and 18 with radiotherapy alone were assigned to the control group. Mean survival for chemotreatment group and control group were 24.2 and 13.1 months, respectively (p = 0.045). Time to progression for these groups were 16.0 and 6.0 months, respectively (p = 0.007). Overall review of the clinical course of patients with GC provided that early appearance of new contrast-enhancing lesions within 6 months from the initial diagnosis and higher histological grade were closely associated with poor survival (p < 0.001 and p = 0.008).

Conclusion

Adjuvant chemotherapy following radiotherapy could prolong the survival in patients with GC. In addition, newly developed contrast-enhanced lesions on the follow-up MR images indicate the progression of GC.

There is a difference in the susceptibility to inflammation between the umbilical vein (UV) and the umbilical arteries (UAs). This led us to hypothesize that there is an intrinsic difference in the pro-inflammatory response between the UA and UV. Real-time quantitative RT-PCR and microarray analysis revealed higher expression of interleukin (IL)-1β and IL-8 mRNA in the UV and differential expression of 567 genes between the UA and UV associated with distinct biological processes, including the immune response. Differential expression of human leukocyte antigen (HLA)-DRA mRNA between the UA and UV was due to unexpected HLA-DR+ cells migrating via the umbilical vessels into Wharton’s jelly, more frequently in the UV. A significant proportion of these cells co-expressed CD45 and type I pro-collagen, and acquired CD163 or α-smooth muscle actin immunoreactivity in Wharton’s jelly. Migrating cells were also found in the chorionic and stem villous vessels. Furthermore, the extent of migration increased with progression of gestation, but diminished in intrauterine growth restriction (IUGR). The observations herein strongly suggest that circulating foetal fibrocytes, routing via umbilical and placental vessels, are a reservoir for key cellular subsets in the placenta. This study reports fibrocytes in the human umbilical cord and placenta for the first time, and a novel role for both circulating foetal cells and the umbilical vessels in placental development, which is deranged in IUGR.

We report a very rare case of hemangioblastomatosis that developed after surgical removal of a solitary cerebellar hemangioblastoma (HB). A 51-yr-old man presented with back pain 10 yr after undergoing surgery for cerebellar HB. Magnetic resonance imaging showed numerous mass lesions along the entire neuraxis accompanied by prominent leptomeningeal enhancement. Genomic DNA analysis showed no mutation in the von Hippel-Lindau (VHL) genes. A surgical specimen obtained from a lesion in the cauda equina showed pathological findings identical to those of the cerebellar HB that had been resected 10 yr earlier. External beam radiation therapy and radiosurgery were subsequently performed; however, the patient succumbed one year after receiving the diagnosis of hemangioblastomatosis. The reduction of tumor cell spillage during surgery and regular long-term follow-up are recommended for patients with HBs.

High-dose chemotherapy and autologous stem cell rescue (HDCT/ASCR) was applied to improve the prognosis of patients with high-risk stage 3 neuroblastoma. From January 1997 to December 2006, 28 patients were newly diagnosed as stage 3 neuroblastoma. Nine of 11 patients with N-myc amplification and 5 of 17 patients without N-myc amplification (poor response in 2 patients, persistent residual tumor in 2 and relapse in 1) underwent single or tandem HDCT/ASCR. Patients without high-risk features received conventional treatment modalities only. While 8 of 9 patients underwent single HDCT/ASCR and the remaining one patient underwent tandem HDCT/ASCR during the early study period, all 5 patients underwent tandem HDCT/ASCR during the late period. Toxicities associated with HDCT/ASCR were tolerable and there was no treatment-related mortality. While the tumor relapsed in two of eight patients in single HDCT/ASCR group, all six patients in tandem HDCT/ASCR group remained relapse free. The 5-yr event-free survival (EFS) from diagnosis, in patients with N-myc amplification, was 71.6±14.0%. In addition, 12 of 14 patients who underwent HDCT/ASCR remained event free resulting in an 85.1±9.7% 5-yr EFS after the first HDCT/ASCR. The present study demonstrates that HDCT/ASCR may improve the survival of patients with high-risk stage 3 neuroblastoma.

We report here on a neonate with congenital cerebellar mixed germ cell tumor, and this initially presented as cerebellar hemorrhage. Postnatal cranial ultrasonography revealed an echogenic cerebellar mass that exhibited the signal characteristics of hemorrhage rather than tumor on MR images. The short-term follow-up images also suggested a resolving cerebellar hemorrhage. One month later, the neonate developed vomiting. A second set of MR images demonstrated an enlarged mass that exhibited changed signal intensity at the same site, which suggested a neoplasm. Histological examination after the surgical resection revealed a mixed germ cell tumor.

Study Design

A retrospective study.

Purpose

To categorize the MR appearance of ischemic vertebral collapse and to correlate surgical and histologic findings.

Overview of Literature

X-ray and MRI findings of delayed posttraumatic vertebral collapse shows several patterns. Histopathologic signs of osteonecrosis were present only in minor portion of cases sampled for biopsy of delayed post-traumatic vertebral collapse in the literature.

Methods

Twenty-one patients (22 vertebral bodies), with surgically and histopathologically proven ischemic vertebral collapse were included. The patients were examined with a 1.5 T MR imager. Spin echo T1- and T2-weighted images were obtained in axial and sagittal planes. Two experienced musculoskeletal radiologists, who reached consensus, evaluated the MR images. Then, MR-pathology correlations were made.

Results

Four different MR patterns were identified. Fluid patterns, were seen in 14% (3/22) of the affected vertebral bodies, and were characterized by hypo-intense signals on T1-weighted images, and hyper-intense signals, similar to water, on T2-weighted images. Extensive bone necrosis was predominant. Compression pattern, the most common pattern, found in 41% (9/22 vertebral bodies), was characterized by a marked decrease of anterior column height. Bone necrosis, granulation tissue, marrow fibrosis, and reactive new bone formation were found in relatively equal proportion. Granulation pattern, seen in 27% (6/22 vertebral bodies), was characterized by hypo-intense signals on T1-weighted images, and intermediate signals on T2-weighted images. Extensive granulation tissue was predominant. Mixed patterns were present in 18% (4/22), of the vertebral bodies.

Conclusions

Awareness of histopathologic correlation of MR patterns in patients with delayed post-traumatic vertebral collapse may facilitate effective interpretation of clinical MR images of the spine.

Mesenchymal hamartoma (MH) of the liver is an uncommon benign lesion related to ductal plate malformation. It is usually cystic and mainly composed of myxoid mesenchymal tissue with tortuous or cystic bile ducts. In order to characterize the clinicopathological features of MH, the Korean Gastrointestinal Pathology Study Group collected a total of 17 MH cases diagnosed in 7 hospitals from 1992 to 2002 and compared the clinicopathologic findings of cystic MH with those of solid variant. Among the 17 cases, 7 (41%) were solid. The solid form showed a higher serum level of α-fetoprotein (AFP), the smaller bile ducts, and more frequent proliferation of vessels. Serum AFP level was related to the amount of hepatocytes. Two of seven solid cases harbored a larger amount of evenly distributed hepatocytes and proliferation of small duct with focal hepatocyte-bile duct transition. These histologic findings are similar to those of mixed hamartoma. Therefore, the mixed hamartoma and the MH of both solid and cystic types could be the variants of one disease spectrum. And hepatocytes within MH might be rather a genuine tumor component than entrapped into the tumor. In conclusion, MH can show various clinicopathological features and recognition of these features will facilitate accurate diagnosis of MH.

Emery-Dreifuss muscular dystrophy (EDMD) and limb-girdle muscular dystrophy type 1B (LGMD1B) are characterized by cardiac dysrhythmias, late-onset cardiomyopathy, slowly progressive skeletal myopathy and contractures of the neck, elbows and ankles. The causative mutation is either in the emerin gene (X-linked recessive EDMD) or lamin A/C gene (autosomal dominant EDMD2 or LGMD1B). We report three cases of EDMD, EDMD2 and LGMD1B. A 14-yr-old boy showed limitation of cervical flexion and contractures of both elbows and ankles. Sinus arrest with junctional escape beats was noted. He was diagnosed as X-linked recessive EDMD (MIM 310300). A 28-yr-old female showed severe wasting and weakness of humeroperoneal muscles. Marked limitation of cervical flexion and contractures of both elbows and ankles were noted. Varying degrees of AV block were noted. She was diagnosed as autosomal dominant EDMD2 (MIM 181350). A 41-yr-old female had contractures of both ankles and limb-girdle type muscular dystrophy. ECG revealed atrial tachycardia with high grade AV block. She was diagnosed as autosomal dominant LGMD1B (MIM 159001). Cardiac dysrhythmias in EDMD and LGMD1B include AV block, bradycardia, atrial tachycardia, atrial fibrillation, and atrial standstill, causing sudden death necessitating pacemaker implantation. Cardiologists should know about these unusual genetic diseases with conduction defects, especially in young adults.

A case of telangiectatic focal nodular hyperplasia (FNH) was detected at birth and was surgically removed. Grossly, the lesion was a solitary nodule and showed vague nodularity, appearing as an adenoma-like mass with fine fibrous septa, but having no macroscopic scar. On microscopic scale, the mass typically had neither fibrous central scar nor hyperplastic nodules different from the usual FNHs. The hepatic plates were separated by sinusoidal dilatation, sometimes alternating with areas of marked ectasia. Instead of large fibrous scar, thin fibrous septa were often found, and contained abnormal tortuous large arteries. These high-pressure vessels were connected directly into the adjacent sinusoids and made marked dilation of sinusoids. Bile ductular proliferation was also noted in the thin fibrous septa. To our knowledge, this is considered to be the first reported case of telangiectatic FNH detected at birth.

The term "chordoid meningioma" means meningioma, which is pathologically similar to chordoma, and previously reported that rarely associated with microcytic anemia and/or dysgammaglobulinemia especially in pediatric population. We present a case of this rare variant, which comprises less than 0.5% of all meningiomas. A 33-yr-old man visited our hospital, complaining visual field defect worsening over 7 yr. Neurological examination showed left homonymous hemianopsia. The brain magnetic resonance imaging revealed well enhancing right temporo-occipital mass with cystic portion. Histopathologic findings of resected tumor were compatible with chordoid meningioma which included trabeculae of eosinophilic, vacuolated cells in a myxoid matrix with prominent lymphoplasmacellular infiltration. The neoplastic cells were positive for vimentin and epithelial membrane antigen and negative for glial fibrillary acidic protein and cytokeratin. This is an adult case of chordoid meningioma without anemia or dysgammaglobulinemia.

Gliofibroma is a rare astrocytic tumor, composed of a glial component ranging from benign to high grade of malignancy and a consistently benign mesenchymal component. Its exact biological behavior is not fully known. In addition, histogenesis and prognostic factors are also still debatable. We herein present a rare case of gliofibroma in a 25-yr-old male with seizure. A computed tomographic scan of the brain showed a 1.5 cm-sized, enhancing mass with calcification. Histologically, the tumor consisted of glial fibrillary acidic protein (GFAP)-positive glial cells admixed with a mesenchymal component and extensive collagen lay down. The glial cells displayed variable cellularity, but without mitosis or necrosis. Since the MIB-1 labeling index was up to 35.8% in the cellular areas of the glial component, it could be considered to be a predictor of worse prognosis.

We report a first Korean case of presumably dominantly inherited primary tubular aggregate myopathy in a 19-yr-old man, who presented with slowly progressive proximal muscle stiffness and weakness. In hematoxylin and eosin stain, it showed subsarcolemmal, or central pale basophilic granular vacuoles, which stained red with modified Gomori's trichrome and intensive blue with nicotinamide adenonine dinucleotide-tetrazolium reductase, respectively. Ultrastructurally, aggregates of 60 nm-sized hexagonal tubules were found in both type 1 and type 2 fibers. We briefly review the pathologic findings of the previously reported cases of tubular aggregate myopathy and discuss the possible pathogenesis of this disease. We briefly discuss the possible pathogenesis of sarcoplasmic reticulum and review the ultrastructural characteristics.

We report a 52-yr-old Korean woman with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) whose diagnosis was confirmed by skin biopsy and the presence of a novel mutation in the NOTCH3 gene. The patient's clinical features were rather unusual in that 1) clinical presentations were only two episodes of stroke and mild dementia unaccompanied by mood disturbances or migraine, and 2) there was no family history. Brain MRI showed T2 hyperintensities in both temporal pole areas in line with the recent suggestion by O'Sullivan et al. that the abnormality could be a radiologic marker of CADASIL. FDG-PET also showed a hypometabolism in the temporal pole areas with an abnormal finding on MRI in addition to the hypometabolism in cortical and subcortical regions. We could learn from this case that CADASIL may be included in the differential diagnoses in patients with vascular dementia associated with a small vessel disease, even in the absence of a family history, especially when there are no known stroke risk factors and when the MRI shows T2 hyperintensity in the temporal pole regions.

Trilateral retinoblastoma is a rare, but well recognized syndrome. These tumors usually occur in the pineal, parasellar, or suprasellar regions several years after successful management of ocular retinoblastomas without evidence of direct extension or distant metastasis. Here we report a case of trilateral retinoblastoma presenting initially with a sellar tumor and with concurrent unilateral retinoblastoma. The patient was a 5-month-old baby girl showing poor eye contact and nystagmus for several days. She had no family history of retinoblastoma. Brain MRI revealed a midline suprasellar tumor without evidence of cerebrospinal fluid seeding or extracranial metastasis. A pathologic diagnosis of retinoblastoma was made for her brain tumor, and a small, intraocular retinoblastoma was detected in the left eye by thorough examination of the fundus. If a retinoblastoma occurs in the midline of the brain, including the pineal and sellar regions, a careful screening to detect any additional retinal tumors should be performed. Moreover, since these tumors are often hereditary and harbor a worse prognosis, the diagnosis has implications for genetic counseling. This is the first report on a case of trilateral retinoblastoma in Korea presented with a sellar mass.