Adrenal Cortical Neoplasm with Uncertain Malignant Potential Arising in the Heterotopic Adrenal Cortex in the Liver of a Patient with Beckwith-Wiedemann Syndrome

Patients with Beckwith-Wiedemann syndrome (BWS) are predisposed to developing embryonal tumors, with hepatoblastoma being the most common type. Our patient showed hemihypertrophy, macroglossia, and paternal uniparental disomy in chromosome 11 and was diagnosed with BWS. When the patient was 9 months old, a 2.5×1.5 cm oval hypoechoic exophytic mass was detected in the inferior tip of his right liver. Preoperative imaging identified it as hepatoblastoma; however, histologic, immunohistochemistry, and electron microscopic findings were compatible with adrenal cortical neoplasm with uncertain malignant potential. The origin of the adrenal tissue seemed to be heterotopic. Here, we describe for the first time an adrenal cortical neoplasm with uncertain malignant potential arising in the heterotopic adrenal cortex located in the liver of a patient with BWS.

Wharton Jelly Hair in a Case of Umbilical Cord Stricture and Fetal Death

No abstract available.

Chronic Placental Inflammation as a Risk Factor of Severe Retinopathy of Prematurity

BACKGROUND: Chronic placental inflammation (CPI) has been implicated in the pathogenesis of diseases in premature infants, whereas retinopathy of prematurity (ROP) is a major complication primarily affecting preterm and very low-birth-weight (VLBW) infants. This study aims to investigate the association between CPI and ROP in VLBW infants. METHODS: We performed a retrospective review of clinical records of VLBW infants born between 2013 and 2016. Placental pathology findings including CPI cases were analyzed using logistic regression to study infants’ morbidities and other clinical characteristics. RESULTS: A total of 402 infants with a mean (standard deviation) gestational age of 28.5 (2.8) weeks and birth weight of 1,027.2 (304.4) g were included. The incidence of ROP was 24.1%. CPI was found in 90 infants (22.4%), among which 28.9% (26 of 90) developed ROP, and 21.1% (19 of 90) underwent laser photocoagulation. Lower gestational age, lower birth weight, longer duration of oxygen supply, and presence of CPI were associated with the development of ROP. After adjustment for gestational age, birth weight, sex, duration of oxygen supply, and other overlapping placental pathology, CPI was associated with the odds for type 1 ROP that required laser photocoagulation (adjusted odds ratio, 2.739; 95% confidence interval, 1.112 to 6.749; p = .029). CONCLUSIONS: CPI was associated with severe ROP requiring treatment with laser photocoagulation in VLBW infants.

Characteristic Changes in Decidual Gene Expression Signature in Spontaneous Term Parturition

BACKGROUND: The decidua has been implicated in the “terminal pathway” of human term parturition, which is characterized by the activation of pro-inflammatory pathways in gestational tissues. However, the transcriptomic changes in the decidua leading to terminal pathway activation have not been systematically explored. This study aimed to compare the decidual expression of developmental signaling and inflammation-related genes before and after spontaneous term labor in order to reveal their involvement in this process. METHODS: Chorioamniotic membranes were obtained from normal pregnant women who delivered at term with spontaneous labor (TIL, n = 14) or without labor (TNL, n = 15). Decidual cells were isolated from snap-frozen chorioamniotic membranes with laser microdissection. The expression of 46 genes involved in decidual development, sex steroid and prostaglandin signaling, as well as pro- and anti-inflammatory pathways, was analyzed using high-throughput quantitative real-time polymerase chain reaction (qRT-PCR). Chorioamniotic membrane sections were immunostained and then semi-quantified for five proteins, and immunoassays for three chemokines were performed on maternal plasma samples. RESULTS: The genes with the highest expression in the decidua at term gestation included insulin-like growth factor-binding protein 1 (IGFBP1), galectin-1 (LGALS1), and progestogen-associated endometrial protein (PAEP); the expression of estrogen receptor 1 (ESR1), homeobox A11 (HOXA11), interleukin 1β (IL1B), IL8, progesterone receptor membrane component 2 (PGRMC2), and prostaglandin E synthase (PTGES) was higher in TIL than in TNL cases; the expression of chemokine C-C motif ligand 2 (CCL2), CCL5, LGALS1, LGALS3, and PAEP was lower in TIL than in TNL cases; immunostaining confirmed qRT-PCR data for IL-8, CCL2, galectin-1, galectin-3, and PAEP; and no correlations between the decidual gene expression and the maternal plasma protein concentrations of CCL2, CCL5, and IL-8 were found. CONCLUSIONS: Our data suggests that with the initiation of parturition, the decidual expression of anti-inflammatory mediators decreases, while the expression of pro-inflammatory mediators and steroid receptors increases. This shift may affect downstream signaling pathways that can lead to parturition.

Identification of Epstein-Barr Virus in the Human Placenta and Its Pathologic Characteristics

Epstein-Barr virus (EBV), a common pathogen in humans, is suspected as the cause of multiple pregnancy-related pathologies including depression, preeclampsia, and stillbirth. Moreover, transmission of EBV through the placenta has been reported. However, the focus of EBV infection within the placenta has remained unknown to date. In this study, we proved the expression of latent EBV genes in the endometrial glandular epithelial cells of the placenta and investigated the cytological characteristics of these cells. Sixty-eight placentas were obtained from pregnant women. Tissue microarray was constructed. EBV latent genes including EBV-encoding RNA-1 (EBER1), Epstein-Barr virus nuclear antigen 1 (EBNA1), late membrane antigen (LMP1), and RPMS1 were detected with silver in situ hybridization and/or mRNA in situ hybridization. Nuclear features of EBV-positive cells in EBV-infected placenta were compared with those of EBV-negative cells via image analysis. Sixteen placentas (23.5%) showed positive expression of all 4 EBV latent genes; only the glandular epithelial cells of the decidua showed EBV gene expression. EBV infection status was not significantly correlated with maternal, fetal, or placental factors. The nuclei of EBV-positive cells were significantly larger, longer, and round-shaped than those of EBV-negative cells regardless of EBV-infection status of the placenta. For the first time, evidence of EBV gene expression has been shown in placental tissues. Furthermore, we have characterized its cytological features, allowing screening of EBV infection through microscopic examination.

History of the Official Journal Published by the Korean Society of Pathologists: From the Korean Journal of Pathology to the Journal of Pathology and Translational Medicine

No abstract available.

Diagnostic Significance of Cellular Neuroglial Tissue in Ovarian Immature Teratoma

BACKGROUND: Immature teratoma (IT) is a tumor containing immature neuroectodermal tissue, primarily in the form of neuroepithelial tubules. However, the diagnosis of tumors containing only cellular neuroglial tissue (CNT) without distinct neuroepithelial tubules is often difficult, since the histological characteristics of immature neuroectodermal tissues remain unclear. Here, we examined the significance of CNT and tried to define immature neuroectodermal tissues by comparing the histological features of neuroglial tissues between mature teratoma (MT) and IT. METHODS: The histological features of neuroglial tissue, including the cellularity, border between the neuroglial and adjacent tissues, cellular composition, mitotic index, Ki-67 proliferation rate, presence or absence of tissue necrosis, vascularity, and endothelial hyperplasia, were compared between 91 MT and 35 IT cases. RESULTS: CNTs with a cellularity grade of ≥ 2 were observed in 96% of IT cases and 4% of MT cases (p < .001); however, CNT with a cellularity grade of 3 in MT cases was confined to the histologically distinct granular layer of mature cerebellar tissue. Moreover, CNT in IT exhibited significantly higher rates of Ki-67 proliferation, mitoses, and necrosis than those in MT (p < .001). Furthermore, an infiltrative border of neuroglial tissue and glomeruloid endothelial hyperplasia were significantly more frequent in IT cases than in MT cases (p < .001). CONCLUSIONS: Our results suggest that if CNT with a cellularity grade of ≥ 2 is not a component of cerebellar tissue, such cases should be diagnosed as IT containing immature neuroectodermal tissue, particularly if they exhibit an infiltrative border, mitoses, necrosis, and increased Ki-67 proliferation.

SNP-Based Fetal DNA Detection in Maternal Serum Using the HID-Ion AmpliSeq™ Identity Panel / 대한법의학회지

Fetal DNA (fDNA) detection in maternal serum is a challenge due to low copy number and the smaller size of fDNA fragments compared to DNA fragments derived from the mother. Massively parallel sequencing (MPS) is a useful technique for fetal genetic analysis that is able to detect and quantify small amounts of DNA. In this study, seven clinical samples of maternal serum potentially containing fDNA were analyzed with a commercial single nucleotide polymorphism (SNP) panel, the HID-Ion AmpliSeq™ Identity Panel, and the results were compared to those from previous studies. Reference profiles for mothers and fetuses were not available, but multiple Y chromosomal SNPs were detected in two samples, indicating that fDNA was present in the serum and thereby validating observations of autosomal SNPs. This suggests that SNP-based MPS can be valuable for fDNA detection, thereby offering an insight into fetal genetic status. This technology could also be used to detect small amounts of DNA in mixed DNA samples for forensic applications.

A case of prenatally diagnosed extrapulmonary arteriovenous malformation associated with a complex heart defect

Pulmonary arteriovenous malformations are rare vascular anomalies of the lung, only a few cases of which have been diagnosed prenatally. The diagnostic clue for prenatal diagnosis was cardiomegaly with a particularly enlarged left atrium. All previous cases of pulmonary arteriovenous malformations diagnosed prenatally have been reported as an isolated anomaly or in association with simple heart defects. We here describe the first case of a pulmonary arteriovenous malformation with a complex heart defect that was diagnosed prenatally at 21.0 weeks of gestation and confirmed by postmortem autopsy.

In Memory of Professor Je Geun Chi, a Great Mentor and Pathologist

No abstract available.

Newly Detected PKHD1 Gene Mutation in a Newborn with Fatal Autosomal Recessive Polycystic Kidney Disease

Autosomal recessive polycystic kidney disease is among the most common inherited ciliopathies and is caused by mutations in the polycystic kidney and hepatic disease 1 (PKHD1) gene. Despite its great phenotypic variability, this condition is usually diagnosed during the neonatal and early infantile periods. We report a 37+3 -gestational-week neonate presenting with fatal autosomal recessive polycystic kidney disease who died at 28 hours of life from severe respiratory failure. The familial history is significant because a previous sibling died in utero at 24+2 weeks of gestational age and was diagnosed with polycystic kidney disease based on prenatal ultrasonography and autopsy. Our patient's autopsy revealed findings compatible with polycystic kidney disease. In addition, a PKHD1 gene study of peripheral blood leukocytes identified the compound heterozygote mutation c.274C>T(p.Arg92Trp), as well as the novel heterozygous nonsense mutation c.2770C>T(p.Gln924*).

Overexpression of C-reactive Protein as a Poor Prognostic Marker of Resectable Hepatocellular Carcinomas

BACKGROUND: C-reactive protein (CRP) is an acute phase reactant synthesized in the liver. CRP immunoreactivity is a feature of inflammatory hepatocellular adenomas with a higher risk of malignant transformation. A high serum CRP level denotes poor prognosis in hepatocellular carcinoma (HCC) patients. This study was conducted to determine whether CRP is produced in HCC and to assess the clinicopathologic significance of CRP expression in cancer cells. METHODS: CRP immunoreactivity was examined in treatment-naive HCCs (n=224) using tissue microarrays and was correlated with clinicopathologic parameters. The expression of CRP mRNA and protein was also assessed in 12 HCC cases by quantitative real-time polymerase chain reaction and immunoblotting. Hep3B and SNU-449 HCC cell lines were used for the analysis of CRP mRNA regulation by interleukin 6 (IL-6). RESULTS: CRP was expressed in 133 of 224 HCCs (59.4%) with a variable degree of immunoreactivity (grade 1 in 25.9%; grade 2 in 20.1%; grade 3 in 13.4%). There was an inverse relationship between grade 3 CRP immunoreactivity and cancer-specific survival (p=.0047), while no associations were found with other parameters, including recurrence-free survival. The CRP mRNA expression level was significantly higher in CRP immunopositive cases than in immunonegative cases (p<.05). CRP mRNA expression was increased in Hep3B cells, but was not detected in SNU-449 cells even after IL-6 treatment. CONCLUSIONS: We report the expression of CRP in HCC for the first time. CRP expression was associated with poor cancer-specific survival in patients with resectable HCC.

Galectins: Double Edged Swords in the Cross-roads of Pregnancy Complications and Female Reproductive Tract Inflammation and Neoplasia

Galectins are an evolutionarily ancient and widely expressed family of lectins that have unique glycan-binding characteristics. They are pleiotropic regulators of key biological processes, such as cell growth, proliferation, differentiation, apoptosis, signal transduction, and pre-mRNA splicing, as well as homo- and heterotypic cell-cell and cell-extracellular matrix interactions. Galectins are also pivotal in immune responses since they regulate host-pathogen interactions, innate and adaptive immune responses, acute and chronic inflammation, and immune tolerance. Some galectins are also central to the regulation of angiogenesis, cell migration and invasion. Expression and functional data provide convincing evidence that, due to these functions, galectins play key roles in shared and unique pathways of normal embryonic and placental development as well as oncodevelopmental processes in tumorigenesis. Therefore, galectins may sometimes act as double-edged swords since they have beneficial but also harmful effects for the organism. Recent advances facilitate the use of galectins as biomarkers in obstetrical syndromes and in various malignancies, and their therapeutic applications are also under investigation. This review provides a general overview of galectins and a focused review of this lectin subfamily in the context of inflammation, infection and tumors of the female reproductive tract as well as in normal pregnancies and those complicated by the great obstetrical syndromes.

A Role for Surgical Pathologists in 'Cytophenomics' and 'Histophenomics'

No abstract available.

A case of jejunal primitive neuroectodermal tumor in an adult female / 대한내과학회지

Primitive neuroectodermal tumor (PNET) is frequent in children and adolescents, but rare in adults. Most of the extraosseous Ewing's sarcoma or PNET occur in the soft tissues of the extremities, the paravertebral region, and the pelvic cavity. PNET in the gastrointestinal tract is uncommon. We report herein a case of PNET arising from the jejunum in a 38-year-old woman. She presented with anorexia, nausea, vomiting, and weight loss. Abdominal computed tomography revealed a mass in the small bowel with obstruction. She had a small bowel segmental resection, from which PNET was diagnosed. Multi-agent chemotherapy comprised of vincristine, adriamycin, cyclophophamide, ifosfamide, and etoposide (VAC/IE) was administered for 1 year. The treatment was well-tolerated. She remains alive and continues to be disease free 30 months postoperatively.

Metanephric Adenoma of the Kidney in an Infant: A Case Report

Metanephric adenoma is a rare tumor of the kidney that has been reported mostly in adults. Despite its rarity, metanephric adenoma should be included in any differential diagnosis of solid renal masses in children, especially because of its benign nature and benign clinical course allowing for nephron sparing surgery. We report a case of metanephric adenoma, presented as a solid renal mass in a 14-month-old boy, and discuss the histologic basis of the imaging features of this entity.

The Effect of Histologic Chorioamnionitis on the Development of Respiratory Distress Syndrome and Chronic Lung Disease in Preterm Infants / 소아과

PURPOSE: Histologic chorioamnionitis may play a role in the development of respiratory distress syndrome(RDS) and chronic lung disease(CLD) independently or through its association with preterm birth. We investigated the relationship between histologic chorioamnionitis and clinical complications including, RDS and CLD, of preterm infants. METHODS: Clinical data were collected retrospectively from 478 preterm infants(gestational period< or =34 weeks) who were admitted to the neonatal intensive care unit(NICU) in Seoul National University Children's Hospital from January 1993 to December 2000. RESULTS: Histologic chorioamnionitis(CA) was observed in 210 of 478 infants(44%). Lower gestational period was detected in CA(+) group(31+1 +/- 2+2 weeks vs. 30+1+/-2+3 weeks). CA(+) group had decreased incidence of RDS(38.4% vs. 28.1%)[odds ratio, OR 0.35(P=0.0004, 95% confidence intervals, CI 0.19-0.63)], and increased incidence of CLD(7.5% vs. 13.3%)[OR 1.95(P=0.047, 95% CI 1.01-3.79)] combined much more "atypical CLD"(10.5% vs. 55.6%). CA(+) group had decreased incidence of patent ductus arteriosus(33.3% vs. 25.4%)[OR 0.37(P=0.003, 95% CI 0.19-0.71)]. There was no difference between the two groups in birth weight. CONCLUSION: It is suggested that intrauterine infections and fetal inflammatory responses might play a role in the outcome of preterm infants, and histologic chorioamnionitis is an isolated risk factor in the development of RDS and CLD of the preterm infants.

A Case of Desmoplastic Small Round Cell Tumor / 대한소아혈액종양학회지

Desmoplastic small round cell tumor (DSRCT) is a distinct clinicopathologic entity that has only recently been described. This aggressive malignant small cell neoplasm tends to occur in adolescents and young adults, who may present with vague abdominal discomfort or distention. We report a case of DSRCT in a 13 year-old girl who presented with intermittent abdominal pain and bulky intra-abdominal mass, accompanied by an increased serum level of a tumor marker CA125. Clinical, pathological, immunohistochemical and radiologic features were compatible with DSRCT. She is under aggressive combination chemotherapy after surgical resection.

Differential Expression of Promyelocytic Leukemia Protein in Autoimmune Liver Diseases

BACKGROUND: Promyelocytic leukemia protein (PML) is a primary biliary cirrhosis (PBC)-specific autoantigen. Anti-PML antibody is analyzed using cultured cells with patient sera, however, PML expression has rarely been examined in liver tissues. METHODS: In the present study, PML expression was examined immunohistochemically in paraffin embedded liver needle biopsy specimens obtained from 20 cases of PBC, 10 cases of autoimmune cholangitis, 36 cases of autoimmune hepatitis and from 5 cases of noninflammatory livers. RESULTS: Variable PML immunopositivity was detected in the bile duct epithelial cells of 18 (90.0%) of 20 PBC cases and in all 10 cases (100.0%) of autoimmune cholangitis, whereas it was only present in 6 (16.7%) of 36 cases of autoimmune hepatitis (p<0.001). In contrast, hepatocyte PML immunopositivity was higher in autoimmune hepatitis (33/36 cases, 90.8%), than in PBC (10/20 cases, 50.0%) or autoimmune cholangitis (3/10 cases, 30.0%) (p<0.05). CONCLUSION: Our data indicate that the differential expression of PML is closely related to autoimmune liver diseases type, and suggest that the overexpression of PML protein in bile duct cells is associated with the development of autoantibodies in patients with PBC or autoimmune cholangitis. Furthermore, PML immunoreactivity may be useful for the diagnosis of autoimmune cholangitis and overlap syndrome.

Dedifferentiated Chondrosarcoma with Giant Cell-rich Sarcomatous Component Resembling Giant Cell Tumor: A Case Report

Dedifferentiated chondrosarcoma is an uncommon bone tumor, defined as a tumor in which two components -a low-grade chondrosarcoma and a high-grade non-cartilaginous sarcoma-coexist with abrupt interface. We report a rare case of giant-cell rich dedifferentiated chondrosarcoma occurred in the right distal femur shaft of a 60 year-old female. The plain X-ray film showed an irregular radiolucent mass. The T2-weighted MRI revealed a heterogeneous high signal intensity. It was an irregular mass composed of bluish-white, translucent chondroid elements and yellowish solid components with extraosseous invasion. Microscopically, a low-grade chondrosarcoma and a giant-cell rich spindle cell sarcoma with areas resembling giant cell tumor were recognized with abrupt transition. Immunohistochemical staining revealed a S100 protein positivity in chondroid cells and a few spindle cells. CD68 was strongly positive in giant cells. Vimentin was positive in both components and smooth muscle actin was positive in some spindle cells. There was no cytokeratin, desmin and myogenin immunopositivity. It is important to be aware of this rare variant of dedifferentiated chondrosarcoma to avoid the misdiagnosis of more common bone tumors including giant cell tumors.