Journal of Pathology and Translational Medicine

Case Study

Adrenal Cortical Neoplasm with Uncertain Malignant Potential Arising in the Heterotopic Adrenal Cortex in the Liver of a Patient with Beckwith-Wiedemann Syndrome: Eun Na Kim, Dong Eun Song, Hee Mang Yoon, Beom Hee Lee, Chong Jai Kim; J Pathol Transl Med. 2019;53(2):129-135. Published online November 26, 2018; DOI: https://doi.org/10.4132/jptm.2018.11.13

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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.

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Functional adrenocortical carcinoma with adrenohepatic fusion: A case report
Pastor Escárcega-Fujigaki, Guillermo Hernández-Peredo Rezk, José de Jesús Loeza- Oliva, Anallely Luna-Hernández, Bethsaida Natali Arreguín-Cortés, Rafael López-Cruz
Journal of Pediatric Surgery Case Reports.2024; 107: 102841. CrossRef
Beckwith–Wiedemann syndrome: Clinical, histopathological and molecular study of two Tunisian patients and review of literature
Hela Sassi, Yasmina Elaribi, Houweyda Jilani, Imen Rejeb, Syrine Hizem, Molka Sebai, Nadia Kasdallah, Habib Bouthour, Samia Hannachi, Jasmin Beygo, Ali Saad, Karin Buiting, Dorra H’mida Ben‐Brahim, Lamia BenJemaa
Molecular Genetics & Genomic Medicine.2021;[Epub] CrossRef
Adrenocortical Tumors in Children With Constitutive Chromosome 11p15 Paternal Uniparental Disomy: Implications for Diagnosis and Treatment
Emilia Modolo Pinto, Carlos Rodriguez-Galindo, Catherine G. Lam, Robert E. Ruiz, Gerard P. Zambetti, Raul C. Ribeiro
Frontiers in Endocrinology.2021;[Epub] CrossRef

Brief Case Report

Wharton Jelly Hair in a Case of Umbilical Cord Stricture and Fetal Death: Eun Na Kim, Jae-Yoon Shim, Chong Jai Kim; J Pathol Transl Med. 2019;53(2):145-147. Published online November 14, 2018; DOI: https://doi.org/10.4132/jptm.2018.10.24

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Histomorphometric analysis of Wharton's jelly size in pregnancies with normal and pre-eclamptic conditions, and its relation to baby weight
Ankit Jain, Rashmi Jain, Amarjyoti Chaturvedi
Indian Journal of Obstetrics and Gynecology Research.2024; 11(4): 647. CrossRef
Loss of Wharton's jelly and fibrosis in umbilical cord stricture area: A case report
Alžbeta Blichárová, Ľudmila Verbóová, Zuzana Benetinová, Tibor Mátyás, Richard Bašista, Vladimír Tancoš, Patrícia Kollárová
Journal of Forensic and Legal Medicine.2023; 96: 102512. CrossRef

Original Articles

C-reactive Protein Overexpression in the Background Liver of Hepatitis B Virus–Associated Hepatocellular Carcinoma Is a Prognostic Biomarker: Jin Ho Shin, Eunsil Yu, Eun Na Kim, Chong Jai Kim; J Pathol Transl Med. 2018;52(5):267-274. Published online July 27, 2018; DOI: https://doi.org/10.4132/jptm.2018.07.14

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Abstract PDF

Background
Chronic hepatitis B virus (HBV) infection is a leading cause of hepatocellular carcinoma (HCC). Peripheral blood C-reactive protein (CRP) concentration and CRP overexpression in HCC cells are proven to be prognostic markers for HCC, but the significance of CRP expression in non-neoplastic hepatocytes, which are the primary origin of CRP, has not been studied. This study was conducted to determine the clinicopathologic significance of CRP immunoreactivity in the background liver of HBV-associated HCC.
Methods
CRP immunostaining was done on tissue microarrays of non-neoplastic liver tissues obtained from surgically resected, treatment-naïve HBV-associated HCCs (n = 156). The relationship between CRP immunoreactivity and other clinicopathologic parameters including cancer-specific survival was analyzed. CRP immunoreactivity was determined using a 4-tier grading system: grades 0, 1, 2, and 3.
Results
CRP was positive in 139 of 156 cases (89.1%) of non-neoplastic liver in patients with HCCs: grade 1 in 83 cases (53.2%); grade 2 in 50 cases (32.1%); and grade 3 in six cases (3.8%). The patients with diffuse CRP immunoreactivity (grade 3) had decreased cancer-specific survival (p = .031) and a tendency for shorter interval before early recurrence (p = .050). The degree of CRP immunoreactivity correlated with serum CRP concentration (p < .001).
Conclusions
CRP immunoreactivity in non-neoplastic liver is a novel biomarker for poor cancer-specific survival of HBV-associated HCC and correlates with serum CRP concentration.

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Evaluation of Serum Ferritin, Procalcitonin, and C-Reactive Protein for the Prediction of Severity and Mortality in Hemorrhagic Fever With Renal Syndrome
Lihe Che, Zedong Wang, Na Du, Liang Li, Yinghua Zhao, Kaiyu Zhang, Quan Liu
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Haeryoung Kim, Young Nyun Park
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Sarah Tan Siyin, Tong Liu, Wenqiang Li, Nan Yao, Guoshuai Xu, Jun Qu, Yajun Chen
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Chronic Placental Inflammation as a Risk Factor of Severe Retinopathy of Prematurity: Chae Young Kim, Euiseok Jung, Eun Na Kim, Chong Jai Kim, Joo Yong Lee, Ji Hye Hwang, Woo Sun Song, Byong Sop Lee, Ellen Ai-Rhan Kim, Ki-Soo Kim; J Pathol Transl Med. 2018;52(5):290-297. Published online July 16, 2018; DOI: https://doi.org/10.4132/jptm.2018.07.09

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Abstract PDF

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.

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Retinopathy prematurity: a systematic review and meta-analysis study based on neonatal and maternal risk factors
Tahereh Bahmani, Arezoo Karimi, Nazanin Rezaei, Salman Daliri
The Journal of Maternal-Fetal & Neonatal Medicine.2024; 35(25): 8032. CrossRef
Histological Chorioamnionitis and Funisitis as New Risk Factors for Retinopathy of Prematurity: A Meta-analysis
Salma El Emrani, Esther J.S. Jansen, Jelle J. Goeman, Enrico Lopriore, Jacqueline U.M. Termote, Nicoline E. Schalij-Delfos, Lotte E. van der Meeren
American Journal of Perinatology.2024; 41(S 01): e3264. CrossRef
Retinopathy of prematurity and placental histopathology findings: A retrospective cohort study
Sam Ebenezer Athikarisamy, Geoffrey C. Lam, Matthew N. Cooper, Tobias Strunk
Frontiers in Pediatrics.2023;[Epub] CrossRef
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Jamee Schoephoerster, Sydney Roston, Scott Lunos, Sara E. Ramel, Jill Anderson, Michael K. Georgieff, Ellen C. Ingolfsland
Journal of Perinatology.2023; 43(6): 702. CrossRef
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Xudong Wang, Tianxi Wang, Enton Lam, David Alvarez, Ye Sun
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Miaomiao Wang, Zhaoyu Wang, Yueyue Miao, Hongkui Wei, Jian Peng, Yuanfei Zhou
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Characteristic Changes in Decidual Gene Expression Signature in Spontaneous Term Parturition: Haidy El-Azzamy, Andrea Balogh, Roberto Romero, Yi Xu, Christopher LaJeunesse, Olesya Plazyo, Zhonghui Xu, Theodore G. Price, Zhong Dong, Adi L. Tarca, Zoltan Papp, Sonia S. Hassan, Tinnakorn Chaiworapongsa, Chong Jai Kim, Nardhy Gomez-Lopez, Nandor Gabor Than; J Pathol Transl Med. 2017;51(3):264-283. Published online February 22, 2017; DOI: https://doi.org/10.4132/jptm.2016.12.20

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Abstract PDF Supplementary Material

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.

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Editorial

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: Se Hoon Kim, Chong Jai Kim, SoonWon Hong; J Pathol Transl Med. 2017;51(1):1-6. Published online January 13, 2017; DOI: https://doi.org/10.4132/jptm.2017.01.07

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Original Article

Diagnostic Significance of Cellular Neuroglial Tissue in Ovarian Immature Teratoma: Yun Chai, Chang Gok Woo, Joo-Young Kim, Chong Jai Kim, Shin Kwang Khang, Jiyoon Kim, In Ah Park, Eun Na Kim, Kyu-Rae Kim; J Pathol Transl Med. 2017;51(1):49-55. Published online October 14, 2016; DOI: https://doi.org/10.4132/jptm.2016.09.19

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Abstract PDF

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.

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Ovarian cystectomy in the treatment of apparent early-stage immature teratoma
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Journal of International Medical Research.2017; 45(2): 771. CrossRef

Editorial

In Memory of Professor Je Geun Chi, a Great Mentor and Pathologist: Chong Jai Kim; J Pathol Transl Med. 2015;49(6):425-426. Published online November 15, 2015; DOI: https://doi.org/10.4132/jptm.2015.10.06

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Review

Galectins: Double-edged Swords in the Cross-roads of Pregnancy Complications and Female Reproductive Tract Inflammation and Neoplasia: Nandor Gabor Than, Roberto Romero, Andrea Balogh, Eva Karpati, Salvatore Andrea Mastrolia, Orna Staretz-Chacham, Sinuhe Hahn, Offer Erez, Zoltan Papp, Chong Jai Kim; J Pathol Transl Med. 2015;49(3):181-208. Published online May 15, 2015; DOI: https://doi.org/10.4132/jptm.2015.02.25

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Abstract PDF

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.

Citations

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Original Article

Overexpression of C-reactive Protein as a Poor Prognostic Marker of Resectable Hepatocellular Carcinomas: Jin Ho Shin, Chong Jai Kim, Eun Jeong Jeon, Chang Ohk Sung, Hwa Jeong Shin, Jene Choi, Eunsil Yu; J Pathol Transl Med. 2015;49(2):105-111. Published online March 12, 2015; DOI: https://doi.org/10.4132/jptm.2015.01.19

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Abstract PDF

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-naïve 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.

Citations

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HNF-1β is a More Sensitive and Specific Marker Than C-Reactive Protein for Identifying Biliary Differentiation in Primary Hepatic Carcinomas
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Malignant transformation of hepatocellular adenoma
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Steatotic and Steatohepatitic Hepatocellular Carcinomas
Umut Aykutlu, Asuman Argon, Mehmet Orman, Sezgin Ulukaya, Murat Zeytunlu, Zeki Karasu, Fulya Günşar, Deniz Nart, Ulus Akarca, Funda Yilmaz
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Letter to the Editor

A Role for Surgical Pathologists in 'Cytophenomics' and 'Histophenomics'.: Chong Jai Kim, Je G Chi; Korean J Pathol. 2009;43(3):199-200.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.3.199

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Abstract PDF: No abstract available.

Original Articles

Application of the Revised Case Matrix Format to Tutorial in Pathology Teaching: An Interim Approach toward Problem-Based Learning under Traditional Curricular Structure.: Yong Il Kim, Chong Jai Kim, Gee Young Kim, Chul Woo Kim, Woo Ho Kim, Ja June Jang, Je Geun Chi, Gyeong Hoon Kang, Myeong Cherl Kook, Jung Sun Kim, Tae Sook Kim, Gee Young Kwon, So Dug Lim; Korean J Pathol. 1996;30(8):570-661.

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10 Download

Abstract: This paper describes a student-centered case study program concerning the tumor pathology course for first year students in medical school under the traditional curricular structure. A traditional, discipline-oriented, lecture-laboratory approach was partly modified by introducing a tutuorial session using a modified case matrix format during the laboratory hours without altering the general scheme of the existing system. Small group tutorial sessions were set with the development of learning objectives emphasizing clinicopathologic reasoning and early exposure to future practical presentation which was followed by the large class session; each tutorial was supplied with a short clinical history, gross kodachrome slides, and microslides. The session for problem identification was replaced by proving a series of instructor-designed questions for both pathology and interdisciplinary correlation during which pedagogical implication was stressed the most. Student's active participation, development of self learning skill and vigorous teaching-learning process among students, and motivation/relevance for forthcoming pathology study were among the benefits conferred by this modification. We conclude that this approach is an interim step to meet the advantages of problem-based learning even in a traditional curricular structure.

Incidence of Acute Placental Inflammation through Histopathological Analysis: One year experience in 1995 at Seoul National University Hospital.: Hyun Ju Yoo, Yun Kyung Kang, Chong Jai Kim, Jung Sun Kim, Tae Sook Kim, Kyung Cheun Jung, Kyo Hoon Park, Jong Kwan Jun, Bo Hyun Yoon; Korean J Pathol. 1996;30(12):1123-1128.

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Abstract PDF: The diagnosis of acute inflammation of the placenta, represented as acute chorioamnionitis, is important in that it is associated with a poor clinical outcome for both the mother and the fetus, including major perinatal morbidities such as sepsis, respiratory distress syndrome, and CNS damage. However, current medical trends in Korea seem to overlook the significance of a histopathological diagnosis of acute placental inflammation, mainly due to the indifferences of clinicians and pathologists. Since late 1993, histopathological examinations have been performed on preterm placentas at Seoul National University. These examinations have demonstrated acute placental inflammation in a significant number of cases. In the present study the incidence of acute placental inflammation was analyzed in 521 placentas which were submitted for pathological examinations in 1995. Examinations were performed to provide basic information on the incidence and profile of acute placental inflammation in this hospital and, thereby, to emphasize the significance of histopathological examinations of the placenta in the routine surgical pathology service. Among the 521 placentas, acute inflammation was found in 194 cases (37.2%). In preterm placentas acute inflammation was found in 39.6% of the cases (67/169), while 36.1% (127/352) of term placentas showed acute inflammation. Taking the delivery mode into account, 26.3% (49/186) of the placentas delivered by cesarean section showed acute inflammation, while 43.3% (145/335) of the transvaginally delivered placentas showed inflammation. The present analysis demonstrates the existence of acute inflammation in a significant proportion of placentas with different clinical settings. The importance of a histopathological examination in routine hospital practice should be emphasized.

Congenital Anomalies Observed by Autopsies at the Seoul National University Children's Hospital.: Jin Haeng Chung, Jeong Wook Seo, Chong Jai Kim, Chul Woo Kim, Je G Chi; Korean J Pathol. 1997;31(2):93-99.

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Abstract PDF: A retrospective analysis was performed on the 968 cases of fetal or pediatric autopsies over five year period (1990-1994), at the Seoul National University Children's Hospital. Age/mode distribution of cases were artificial abortus(30.6%), spontaneous abortus(12.0%), stillbirth(21.9%), neonates(29%), infants(2.8%) and children(0.9%). Male/female ratio was 1.21. Overall incidence of congenital anomalies was 60.8% and 34.0% of all cases had anomalies involving multiple organ systems. Percentage of cases with any anomaly was 71.6% in artificial abortus, 35.3% in spontaneous abortus, 59% in still births, 65.5% in neonates and 38.9% in infant and children. Common organ systems involved were the cardiovascular system (39.0%), musculoskeletal system (23.6%), nervous system (22.6%), gastrointestinal system (19.9%), and urinary system (14.6%). From these results, we found that the congenital anomalies were most significant diseases of the perinatal period and the cardiovascular anomalies were the most common anomalies of them.

Congenital Cystic Disease of the Kidney overview and a classification.: Mee Joo, Yeon Mee Kim, Chong Jai Kim, Yeon Lim Suh, Jeong Wook Seo, Je Geun Chi; Korean J Pathol. 1997;31(3):233-243.

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Abstract PDF: The congenital renal cystic disease encompasses a complex group of pathologic and clinical entities. We retrospectively reviewed 42 cases of congenital renal cystic lesions classified into four Potter types in a series of 2,063 consecutive autopsies from 1981 to 1996. According to our study based on morphologic, clinical, genetic features and associated anomalies, type I and III are relatively compatible with Potter's original definition. However, it was reasonable that type II and IV are classified to the same group because of: 1) very similar histologic findings representing dysplastic kidney, 2) many associated anomalies, 3) no evidence of inheritance, and 4) presence of a combined type. Syndrome associated cysts, such as Meckel-Gruber syndrome, were also separately classified. If the dysplastic evidence was insufficient for diagnosis to the dysplastic kidney in type II and IV, then these cases would be better classified into a cystic disease associated with congenital hydronephrosis. We propose a classification of the congenital cystic disease of the kidney to be: 1) dysplastic kidney, 2) cystic disease associated with congenital hydronephrosis, 3) polycystic kidney, and 4) syndromic cystic disease.

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