Journal of Pathology and Translational Medicine

Original Articles

Prognostic role of ALK-1 and h-TERT expression in glioblastoma multiforme: correlation with ALK gene alterations: Dalia Elsers, Doaa F. Temerik, Alia M. Attia, A. Hadia, Marwa T. Hussien; J Pathol Transl Med. 2021;55(3):212-224. Published online May 11, 2021; DOI: https://doi.org/10.4132/jptm.2021.03.15

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Background
Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase that is expressed in the developing central and peripheral nervous systems during embryogenesis. Human telomerase reverse transcriptase (h-TERT) protein resumption is the main process of preservation of telomeres that maintains DNA integrity. The present study aims to evaluate the prognostic role of ALK-1 and h-TERT protein expression and their correlation with ALK gene alterations in glioblastoma multiforme (GBM).
Methods
The current study is a retrospective study on a cohort of patients with GBM (n = 53) that attempted to detect ALK gene alterations using fluorescence in situ hybridization. ALK-1 and h-TERT proteins were evaluated using immunohistochemistry.
Results
Score 3 ALK-1 expression was significantly associated with male sex, tumor multiplicity, Ki labeling index (Ki LI), and type of therapeutic modality. Score 3 h-TERT expression exhibited a significant association with Ki LI. ALK gene amplifications (ALK-A) were significantly associated with increased Ki LI and therapeutic modalities. Score 3 ALK-1 protein expression, score 3 h-TERT protein expression, and ALK-A were associated with poor overall survival (OS) and progression-free survival (PFS). Multivariate analysis for OS revealed that ALK gene alterations were an independent prognostic factor for OS and PFS.
Conclusions
High protein expression of both ALK-1 and h-TERT, as well as ALK-A had a poor impact on the prognosis of GBM. Further studies are needed to establish the underlying mechanisms.

Citations

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TERT Gene Mutation in Gliomas Cross‐Linked With (NTRK, PDL1, ALK, IDH, P53, EGFR, HER2): A Integrative Review TERT Gene Mutation in Gliomas
Gunter Gerson Santos, Guilherme Nobre Nogueira, Iasmin Maria Rodrigues Saldanha, Ana Gabriela Ponte Farias, Cauan Miranda Mateus, Osvaldo Mariano Viana Neto, Maria Jânia Teixeira
Journal of Surgical Oncology.2024;[Epub] CrossRef
Association of human telomerase reverse transcriptase promoter mutation with unfavorable prognosis in glioma: A systematic review and meta-analysis
Rongxuan Hua, Qiuxuan Li, Han Gao, Boya Wang, Chengwei He, Ying Wang, Sitian Zhang, Lei Gao, Hongwei Shang, Wen Wang, Jingdong Xu
Journal of Research in Medical Sciences.2023;[Epub] CrossRef
Immunohistochemical surrogates for molecular alterations for the classification and grading of gliomas
Viharkumar Patel, Sanda Alexandrescu
Seminars in Diagnostic Pathology.2022; 39(1): 78. CrossRef
Meme Kanseri Hastalarında hTERT Gen Ekspresyonunun Klinikopatolojik Önemi
Ebubekir DİRİCAN, Burak KANKAYA, Zeynep TATAR
Sağlık Bilimlerinde Değer.2022; 12(1): 22. CrossRef
Prognostic and predictive markers in glioblastoma and ALK overexpression
Jang-Hee Kim
Journal of Pathology and Translational Medicine.2021; 55(3): 236. CrossRef

Clinicopathological Study of 18 Cases of Inflammatory Myofibroblastic Tumors with Reference to ALK-1 Expression: 5-Year Experience in a Tertiary Care Center: Ramesh Babu Telugu, Anne Jennifer Prabhu, Nobin Babu Kalappurayil, John Mathai, Birla Roy Gnanamuthu, Marie Therese Manipadam; J Pathol Transl Med. 2017;51(3):255-263. Published online April 17, 2017; DOI: https://doi.org/10.4132/jptm.2017.01.12

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Abstract PDF

Background
Inflammatory myofibroblastic tumor is a histopathologically distinctive neoplasm of children and young adults. According to World Health Organization (WHO) classification, inflammatory myofibroblastic tumor is an intermediate-grade tumor, with potential for recurrence and rare metastasis. There are no definite histopathologic, molecular, or cytogenetic features to predict malignant transformation, recurrence, or metastasis.
Methods
A 5-year retrospective study of histopathologically diagnosed inflammatory myofibroblastic tumors of various anatomic sites was conducted to correlate anaplastic lymphoma kinase-1 (ALK-1) expression with histological atypia, multicentric origin of tumor, recurrence, and metastasis. Clinical details of all the cases were noted from the clinical work station. Immunohistochemical stains for ALK-1 and other antibodies were performed. Statistical analysis was done using Fisher exact test.
Results
A total of 18 cases of inflammatory myofibroblastic tumors were found during the study period, of which 14 were classical. The female-male ratio was 1:1 and the mean age was 23.8 years. Histologically atypical (four cases) and multifocal tumors (three cases, multicentric in origin) were noted. Recurrence was noted in 30% of ALK-1 positive and 37.5% of ALK-1 negative cases, whereas metastasis to the lung, liver, and pelvic bone was noted in the ALK-1 positive group only.
Conclusions
Overall, ALK-1 protein was expressed in 55.6% of inflammatory myofibroblastic tumors. There was no statistically significant correlation between ALK-1 expression, tumor type, recurrence and metastasis. However, ALK-1 immunohistochemistry is a useful diagnostic aid in the appropriate clinical and histomorphologic context.

Citations

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Treatment and outcomes in pediatric inflammatory myofibroblastic tumors – A systematic review of published studies
Arimatias Raitio, Paul D. Losty
European Journal of Surgical Oncology.2024; 50(7): 108388. CrossRef
Case report: Epithelioid inflammatory myofibroblastic sarcoma treated with an ALK TKI ensartinib
Mengmeng Li, Ruyue Xing, Jiuyan Huang, Chao Shi, Chunhua Wei, Huijuan Wang
Frontiers in Oncology.2023;[Epub] CrossRef
Inflammatory Myofibroblastic Tumour of the Sinonasal Tract with Orbital and Intracranial Extensions Simulating a Malignancy: A Case Report and Review of Literature
Gaveshani Mantri, Subhalaxmi Rautray, Rahul Mohanty, Vinushree Karakkandy
Indian Journal of Otolaryngology and Head & Neck Surgery.2022; 74(S2): 1668. CrossRef
Clinical, pathologic, and molecular features of inflammatory myofibroblastic tumors in children and adolescents
Aurore Pire, Daniel Orbach, Louise Galmiche, Dominique Berrebi, Sabine Irtan, Sabah Boudjemaa, Hervé J. Brisse, Laureline Berteloot, Salma Moalla, Charlotte Mussini, Pascale Philippe‐Chomette, Bogdana Tilea, Gaelle Pierron, Florent Guerin, Véronique Minar
Pediatric Blood & Cancer.2022;[Epub] CrossRef
Case Report: Early Distant Metastatic Inflammatory Myofibroblastic Tumor Harboring EML4-ALK Fusion Gene: Study of Two Typical Cases and Review of Literature
Qianqian Han, Xin He, Lijuan Cui, Yan Qiu, Yuli Li, Huijiao Chen, Hongying Zhang
Frontiers in Medicine.2022;[Epub] CrossRef
Inflammatory myofibroblastic tumor: Amulti‐institutionalstudy from the Pediatric Surgical Oncology Research Collaborative
Barrie S. Rich, Joanna Fishbein, Timothy Lautz, Nathan S. Rubalcava, Tanvi Kartal, Erika Newman, Pei En Wok, Rodrigo L. P. Romao, Richard Whitlock, Bindi Naik‐Mathuria, Stephanie F. Polites, Katrine Løfberg, Danny Lascano, Eugene Kim, Jacob Davidson, Andr
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Child inflammatory myofibroblastic tumor of the kidney misdiagnosed as Wilms' tumor: case report
Yu-Feng Bai, Jing-Zhong Liu, Li-Na Yue, Li Chen, Sui-Yi Liu, Rui Liu
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A Common Cell of Origin for Inflammatory Myofibroblastic Tumor and Lung Adenocarcinoma with ALK rearrangement
Vasyl Nesteryuk, Omar Hamdani, Raymond Gong, Nava Almog, Brian M. Alexander, Steffan Soosman, Ken Yoneda, Siraj M. Ali, Alexander D. Borowsky, Jonathan W. Riess
Clinical Lung Cancer.2022; 23(8): e550. CrossRef
An extremely rare case of malignant jejunal mesenteric inflammatory myofibroblastic tumor in a 61-year-old male patient: A case report and literature review
Hamdi Al Shenawi, Salamah A. Al-Shaibani, Suhair K. Al Saad, Fedaa Al-Sindi, Khalid Al-Sindi, Noor Al Shenawi, Yahya Naguib, Rami Yaghan
Frontiers in Medicine.2022;[Epub] CrossRef
Primary inflammatory myofibroblastic tumor of stomach—report of a very rare case
Ranendra Hajong, Kewithinwangbo Newme, Donkupar Khongwar
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Complicated course of biliary inflammatory myofibroblastic tumor mimicking hilar cholangiocarcinoma: A case report and literature review
Sandra Strainiene, Kotryna Sedleckaite, Juozas Jarasunas, Ilona Savlan, Juozas Stanaitis, Ieva Stundiene, Tomas Strainys, Valentina Liakina, Jonas Valantinas
World Journal of Clinical Cases.2021; 9(21): 6155. CrossRef
Epithelioid Inflammatory Myofibroblastic Sarcoma Presenting as Gastrointestinal Bleed: Case Report and Literature Review
Alexandra Giannaki, Dimitrios Doganis, Panagiota Giamarelou, Anastasia Konidari
JPGN Reports.2021; 2(1): e019. CrossRef
Complete response to alectinib following crizotinib in an ALK-positive inflammatory myofibroblastic tumor with CNS involvement
Camila B. Xavier, Felipe S.N.A. Canedo, Fabíola A.S. Lima, Raíssa R. Melo, Luiz Guilherme C.A. Lima, José Flávio G. Marin, Ciro E. Souza, Olavo Feher
Current Problems in Cancer: Case Reports.2021; 4: 100117. CrossRef
Urinary Bladder Inflammatory Myofibroblastic Tumor With Mutated TP53 and PPFIBP1-ALK Gene Fusion
Andreia N. Barbieri, Christopher T. Tallman, Raj Satkunasivam, Joseph Annunziata, Jessica S. Thomas, Randall J. Olsen, Steven S. Shen, Michael J. Thrall, Mary R. Schwartz
AJSP: Reviews and Reports.2021; 26(1): 45. CrossRef
Therapeutic options in inoperable ROS1-rearranged inflammatory myofibroblastic tumor of the tongue in a child: a case report and literature review
Malgorzata Styczewska, Agastya Patel, Joanna Jaskulowska, Jan Godzinski, Dominik Swieton, Bartosz Wasag, Juliea Dass, Ewa Bien, Malgorzata A. Krawczyk
Anti-Cancer Drugs.2021; 32(10): 1111. CrossRef
Non-squamous cell carcinoma diseases of the larynx: clinical and imaging findings
Serap Doğan, Alperen Vural, Güven Kahriman, Hakan İmamoğlu, Ümmühan Abdülrezzak, Mustafa Öztürk
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Xiaoyan Si, Hanping Wang, Xiaotong Zhang, Mengzhao Wang, Yan You, Li Zhang
Thoracic Cancer.2020; 11(8): 2339. CrossRef
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Hiba Abduljawad, Ahmet Aslan, Khalifa Aldoseri, Erdem Yilmaz, Wael Ibrahim
Radiology Case Reports.2020; 15(8): 1266. CrossRef
Histopathological landscape of rare oesophageal neoplasms
Gianluca Businello, Carlo Alberto Dal Pozzo, Marta Sbaraglia, Luca Mastracci, Massimo Milione, Luca Saragoni, Federica Grillo, Paola Parente, Andrea Remo, Elena Bellan, Rocco Cappellesso, Gianmaria Pennelli, Mauro Michelotto, Matteo Fassan
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Laryngeal Inflammatory Myofibroblastic Tumor : Case Series and Literature Review
Ki-Ik Park, Sung-hoon Kim, In-Suh Park, Ji Won Kim
Journal of The Korean Society of Laryngology, Phoniatrics and Logopedics.2019; 30(1): 57. CrossRef
Anaplastic lymphoma kinase-negative pulmonary inflammatory myofibroblastic tumor with multiple metastases and its treatment by Apatinib
Qiuxia Liu, Jianguo Wei, Xizhong Liu, Jianfang Wang
Medicine.2019; 98(52): e18414. CrossRef
Inflammatory myofibroblastic tumor
Veronika Marcináková, Hana Dittrichová, Karel Franěk, Pavel Hanek
Urologie pro praxi.2019; 20(1): 40. CrossRef
Ureteral inflammatory myofibroblastic tumor
Faping Li, Hui Guo, Heping Qiu, Yuchuan Hou
Medicine.2018; 97(46): e13177. CrossRef
Pulmonary inflammatory myofibroblastic tumour misdiagnosed as a round pneumonia
Samira Naime, Anjum Bandarkar, Gustavo Nino, Geovanny Perez
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ALK-Positive Renal Cell Carcinoma in a Large Series of Consecutively Resected Korean Renal Cell Carcinoma Patients: Cheol Lee, Jeong Whan Park, Ja Hee Suh, Kyung Han Nam, Kyung Chul Moon; Korean J Pathol. 2013;47(5):452-457. Published online October 25, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.5.452

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Abstract PDF

Background

Recently, there have been a few reports of renal cell carcinoma (RCC) cases with anaplastic lymphoma kinase (ALK) gene fusion. In this study, we screened consecutively resected RCCs from a single institution for ALK protein expression by immunohistochemistry, and then we performed fluorescence in situ hybridization to confirm the ALK gene alteration in ALK immunohistochemistry-positive cases.

Methods

We screened 829 RCCs by ALK immunohistochemistry, and performed fluorescence in situ hybridization analysis using ALK dual-color break-apart rearrangement probe. Histological review and additional immunohistochemistry analyses were done in positive cases.

Results

One ALK-positive case was found. Initial diagnosis of this case was papillary RCC type 2. This comprises 0.12% of all RCCs (1/829) and 1.9% of papillary RCCs (1/53). This patient was a 44-year-old male with RCC found during routine health check-up. He was alive without evidence of disease 12 years after surgery. The tumor showed a papillary and tubular pattern, and showed positivity for CD10 (focal), epithelial membrane antigen, cytokeratin 7, pan-cytokeratin, PAX-2, and vimentin.

Conclusions

We found the first RCC case with ALK gene rearrangement in Korean patients by ALK immunohistochemistry among 829 RCCs. This case showed similar histological and immunohistochemical features to those of previous adult cases with ALK rearrangement, and showed relatively good prognosis.

Citations

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ALK-Rearranged Renal Cell Carcinoma: A Multi-Institutional Study of 9 Cases With Expanding the Morphologic and Molecular Genetic Spectrum
Ming Zhao, Xiaona Yin, Xiaoqun Yang, Hualei Gan, Ni Chen, Guangjie Duan, Yanfeng Bai, Xiaodong Teng, Jiayun Xu, Rong Fang, Suying Wang, Shan Zhong, Xiaotong Wang, Lisong Teng
Modern Pathology.2024; 37(8): 100536. CrossRef
Activity of ALK Inhibitors in Renal Cancer with ALK Alterations: A Systematic Review
Giovanni Maria Iannantuono, Silvia Riondino, Stefano Sganga, Mario Roselli, Francesco Torino
International Journal of Molecular Sciences.2022; 23(7): 3995. CrossRef
Novel, emerging and provisional renal entities: The Genitourinary Pathology Society (GUPS) update on renal neoplasia
Kiril Trpkov, Sean R. Williamson, Anthony J. Gill, Adebowale J. Adeniran, Abbas Agaimy, Reza Alaghehbandan, Mahul B. Amin, Pedram Argani, Ying-Bei Chen, Liang Cheng, Jonathan I. Epstein, John C. Cheville, Eva Comperat, Isabela Werneck da Cunha, Jennifer B
Modern Pathology.2021; 34(6): 1167. CrossRef
ESC, ALK, HOT and LOT: Three Letter Acronyms of Emerging Renal Entities Knocking on the Door of the WHO Classification
Farshid Siadat, Kiril Trpkov
Cancers.2020; 12(1): 168. CrossRef
ALK-rearranged renal cell carcinoma with a novel PLEKHA7-ALK translocation and metanephric adenoma-like morphology
Jen-Fan Hang, Hsiao-Jen Chung, Chin-Chen Pan
Virchows Archiv.2020; 476(6): 921. CrossRef
Characteristics of Renal Cell Carcinoma Harboring TPM3-ALK Fusion
Chang Gok Woo, Seok Jung Yun, Seung-Myoung Son, Young Hyun Lim, Ok-Jun Lee
Yonsei Medical Journal.2020; 61(3): 262. CrossRef
Report From the International Society of Urological Pathology (ISUP) Consultation Conference on Molecular Pathology of Urogenital Cancers
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American Journal of Surgical Pathology.2020; 44(7): e47. CrossRef
ALK rearranged renal cell carcinoma (ALK-RCC): a multi-institutional study of twelve cases with identification of novel partner genes CLIP1, KIF5B and KIAA1217
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ALK rearrangement in TFE3-positive renal cell carcinoma: Alternative diagnostic option to exclude Xp11.2 translocation carcinoma
Yiqi Zhu, Ning Liu, Wei Guo, Xiaohong Pu, Hongqian Guo, Weidong Gan, Dongmei Li
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New and emerging renal entities: a perspective post‐WHO 2016 classification
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Lack of expression of ALK and CD30 in breast carcinoma by immunohistochemistry irrespective of tumor characteristics
Samer Nassif, Ziad M. El-Zaatari, Michel Attieh, Maya Hijazi, Najla Fakhreddin, Tarek Aridi, Fouad Boulos
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Targeted next-generation sequencing revealed distinct clinicopathologic and molecular features of VCL-ALK RCC: A unique case from an older patient without clinical evidence of sickle cell trait
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ALK-rearranged renal cell carcinomas in Polish population
Adam Gorczynski, Piotr Czapiewski, Aleksandra Korwat, Lukasz Budynko, Monika Prelowska, Krzysztof Okon, Wojciech Biernat
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ALK-TPM3 rearrangement in adult renal cell carcinoma: Report of a new case showing loss of chromosome 3 and literature review
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A case of anaplastic lymphoma kinase‐positive renal cell carcinoma coincident with Hodgkin lymphoma
Yuzo Oyama, Haruto Nishida, Takahiro Kusaba, Hiroko Kadowaki, Motoki Arakane, Tsutomu Daa, Dai Watanabe, Yasuyuki Akita, Fuminori Sato, Hiromitsu Mimata, Shigeo Yokoyama
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Clinicopathologic and Molecular Pathology of Collecting Duct Carcinoma and Related Renal Cell Carcinomas
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Naoto Kuroda, Ondřej Hess, Ming Zhou
Diagnostic Histopathology.2016; 22(2): 47. CrossRef
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Case Reports

Follicular Lymphoma with Monoclonal Plasma Cell Differentiation: A Case Report.: Hyun chul Kim, Young Seok Lee, Jung woo Choi, Ae ree Kim, Bom Woo Yeom, Han kyeom Kim, In sun Kim; Korean J Pathol. 2006;40(2):151-155.

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Abstract PDF: We present a case of recurrent follicular lymphoma with an extensive plasma cell component involving infra-auricular lymph nodes in a 64 year-old woman. Immunohistochemical staining showed a strongly positive reaction of the follicles with CD20, bcl-2, bcl-6, CD10 and CD21 on the first biopsy specimen. The intrafollicular and interfollicular plasma cells showed monoclonality for IgG heavy chain and lambda light chain. The histological and immunohistochemical findings in the recurrent tumor were identical with those of the original. Discussion is focused on the importance of the differential diagnosis between reactive lymphoid hyperplasia and other lymphomas having plasmacytic differentiation.

Inflammatory Myofibroblastic Tumor of the Stomach: A Case Report.: Joon Mee Kim, In Suh Park, Lucia Kim, Suk Jin Choi, Jee young Han, Young Chae Chu, Kyoung Rae Kim; Korean J Pathol. 2006;40(2):148-150.

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Abstract PDF: Inflammatory myofibroblastic tumor of the stomach is a rare tumor-like, benign disease with an uncertain pathogenesis. A 15-year-old male presented with epigastric pain. Endoscopic ultrasonography revealed a 2.3 cm sized ovoid intramuscular mass in the lower body of the stomach at the lesser curvature. Histologically, the tumor was composed of smooth muscle actin positive- and vimentin positive spindle cells and there were a large number of lymphocytes, plasma cells and histiocytes in the fibrotic background. The spindle cells were also positive for ALK1, but negative for EBV in situ hybridization.

Original Article

Body Stalk Anomaly: Analysis of 10 Autopsy Cases.: Seung Sook Lee, Je G Chi; Korean J Pathol. 1993;27(3):235-242.

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Abstract PDF: Body stalk anomaly represents an extreme maldevelopment of embryonic body folding and is characterized by absence of the umbilicus and umbilical cord. The failure of complete obliteration of the extraembryonic coelom is responsible for the absence of the umbilical cord formation and the wide-based insertio of the amnioperitoneal membrane onto the placental chorionic plate. We have analyzed 10 autopsy cases of various midline anomalies of the body that could best be classified into body stalk anomaly. All cases were either stillborns or dead immediately after birth. The pregnancy was interrupted due to this anomaly in 6 cases, and their gestational ages varied from 17 weeks to 37 weeks. The affected fetuses were characterized bt absent or vestigial umbilical cord, and ruptured amnion with direct amnioperitoneal connection without the mediation of the umbilical cord. Exomphalos with abdominal wall defect and serve scoliosis were characteristic components of this anomaly, that provided important clues in differentiating other similar anomalies. Other associated anomalies included neural tube defect, intestinal atresia, genitourinary and skeletal defects, pulmonary hypoplasia, single umbilical artery and narrow-spaced chest and abdomen, etc. These findings strongly suggest that anomaly of body stalk represents mechanical teratogenesis due to early amnion repture and subsequent effect, and should be categorized into amniotic band disruption syndrome.

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