Diagnostic Pathology
A case report of infantile cystic nephroblastoma--Manuscript Draft-Manuscript Number:

DPAT-D-18-00128R2

Full Title:

A case report of infantile cystic nephroblastoma

Article Type:

Case Report

Funding Information:
Abstract:

Background: Nephroblastoma (NB) is a malignant embryonal neoplasm derived fromnephrogenic blastemal cells. NB usually forms a solid mass, but in extremely rarecases, it may show cystic changes. Case Presentation: A six-month-old girl with apersistent high fever was found to have pyuria and bacteriuria. Ultrasonography
revealed multilocular cysts in the right kidney. Right nephrectomy was performed, but
the cystic wall was ruptured during surgery. An intraoperative rapid diagnosis based on
peritoneal fluid cytology confirmed three components of blastemal, stromal andepithelial cells. The blastemal cells were dyshesive, with naked nuclei with scant to nocytoplasm and were the most predominantly observed cell type. The spindle-shaped
stromal cells were arranged in fascicles. The epithelial cells demonstrated tubular
structures. Macroscopically, the resected cystic tumor measured 80 mm in maximum
diameter, and the cystic wall was thinned. Histologically, the tumor was diagnosed as
cystic NB (blastemal-predominant) displaying a triphasic pattern. Hyperchromatic
nuclei and apoptotic bodies were found. The clinical stage classification of Japan
Wilms Tumor Study group was 3. Chemotherapy and radiotherapy were performed,
and tumor recurrence and metastasis have not been observed in the eight months
since the surgery. Conclusion: This is an extremely rare case of infantile cystic NB. We
diagnosed the NB cells that appeared in the peritoneal fluid by intraoperative rapid
cytology. A cytological examination proved to be a very useful technique fordetermining the clinical stage of NB. Massive tumor degeneration and necrosis should
be considered as a pathogenic mechanism of cyst formation.

Corresponding Author:

Nozomu Kurose
Kanazawa Ika Daigaku Byoin
JAPAN

Corresponding Author Secondary
Information:
Corresponding Author's Institution:

Kanazawa Ika Daigaku Byoin

Corresponding Author's Secondary
Institution:
First Author:

Nozomu Kurose

First Author Secondary Information:
Order of Authors:

Nozomu Kurose
Michiho Takenaka
Manabu Yamashita
Chie Shimaguchi
Mariko Nakano
Bryant Britni
Xin Guo
Chizuru Futatsuya
Akihiro Shioya
Sohsuke Yamada

Order of Authors Secondary Information:
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Response to Reviewers:

Reviewer #1:-Page 6, lines 40-47: consider adding additional details to the cytopreparatory
techniques (fluid smear, cytospin, etc? staining method - DiffQuik, rapid Pap stain, fullPap stain, etc)
>We added "by rapid Papanicolaou stain".
-Page 6, line 50: this paragraph seems to be missing a topic sentence. I can assume
that this description is of the cytomorphology, but this is not clear from the text. Pleaserevise for clarity. Also, consider some re-wording/critical reading for quality oflanguage. For example, I'm not familiar with the term "reduced cell adhesion" - perhaps
you mean that the cells are dyshesive?
>We changed the this paragraph.
"Cytologically, the blastemal cells were dyshesive, with naked nuclei with scant to nocytoplasm and were the most predominantly observed cell type. "-Page 7: regarding the histomorphology - please describe the appearance of the cyst
wall. Any cyst lining cells? Please include a photomicrograph if possible.
>We described about cystic wall, and take a microphotograph of the cystic wall
(Fig4D).
The cystic wall was lined by blastemal cells (Fig. 4D). Some solid areas were present
within the cyst wall.
-Page 10, line 33: Please comment on if any of the previous cases of cystic Wilms
tumor also had tumor rupture (or if it is unknown, please include this information).
>We added about case report of ruptured cystic nephroblastoma. "However, there
were no case reports of ruptured Cystic NB."
Reviewer #2:-The case report needs to be better developed with expansion of the case presentationand discussion to show that this is a unique case. Cysts, hemorrhage and necrosis
are common in Wilms tumors. Sufficient description is needed to distinguish this casefrom a cystic partially differentiated Wilms tumor.
>We described cystic partially differentiated Wilms tumor.
The differential diagnosis of cystic NB is CPDNB. CPDNB is a multilocular lesion with
no apparent solid or nodular mass formation. CPDNB contains mature or immaturenephroblastic tissue, but conforms to the septum between cysts. Cystic NB is also amultilocular lesion but has obvious solid NB components expanding the cyst wall.

-In the case presentation, the macroscopic description can be improved by adescription of the cysts and solid components (expansive or within the walls of thecysts). The histology has limited detail and needs to be expanded (i.e. description of
the cystic regions, location of the solid Wilms tumors components, and any necrosis).
>We described about the cystic wall.
"The cystic wall was lined by blastemal cells (Fig. 4D). Some solid areas were present
within the cyst wall. "-In the discussion, the histologic differential diagnosis should be addressed. The
cytology is emphasized in the case presentation and conclusion but is not included in
the discussion. There needs to be clarification of the statement 'spontaneous
regression' (page 9, line 40). Degenerating tumor cells and apoptotic cells are notevidence of regression and are a relatively common finding in Wilms tumors. Thisfinding is not sufficient to argue that spontaneous regression occurs in Wilms tumors.
>We deleted supontaneous regression. And we changed conclusion. Massive tumor
degeneration and necrosis should be considered as a pathogenic mechanism of cyst
formation.
- Fig 1 and Fig 2 should be annotated for clarification of the important findings.
>We added figure legends (Fig 1 and Fig 2)-Fig 4 could be improved with a low-power image to show cystic areas. The quality of
the histology images could be improved - especially Fig 5.
>We added Fig4D (Cystic wall of the tumor). And we deleted Fig. 5 (Because
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degenerating tumor cells and apoptotic cells are a relatively common finding in Wilms
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Case Report
A case report of infantile cystic nephroblastoma

NozomuKurose(k-nozomu@kanazawa-med.ac.jp)1*,

MichihoTakenaka(michiho@kanazawa-med.ac.jp)2, Manabu Yamashita (yama-bu@kanazawa-med.ac.jp)2,
Chie

Shimaguchi(shima-c@kanazawa-med.ac.jp)2,

MarikoNakano(mariko-n@kanazawa-med.ac.jp)2, Bryant Britni (britni.bryant@uvmhealth.org)3, Xin Guo(xinguo@kanazawa-med.ac.jp)1,
Akihiro

ShioyaChizuru

Futatsuya(c-futats@kanazawa-med.ac.jp)1,(a-shioya@kanazawa-med.ac.jp)1,

Sohsuke

Yamada(sohsuke@kanazawa-med.ac.jp)1*

Short running head: Infantile cystic NB

1

Department of Pathology and Laboratory Medicine & 2Department of Pathology, Kanazawa

Medical University, Ishikawa, Japan. 3Department of Pathology and Laboratory Medicine,
University of Vermont College of Medicine, Burlington, Vermont, USA.

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*Corresponding author: Nozomu Kurose, M.D., Ph.D. & Sohsuke Yamada, M.D., Ph.D.,
Department of Pathology and Laboratory Medicine, Kanazawa Medical University, 1-1
Daigaku, Uchinada, Ishikawa, 920-0293, Japan. Tel: 81-76-218-8264; Fax: 81-76-286-1207;
and E-mail: k-nozomu@kanazawa-med.ac.jp
Word count: 2,420 words (Abstract 250 words); references: 13; figures: 4

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Abstract
Background: Nephroblastoma (NB) is a malignant embryonal neoplasm derived fromnephrogenic blastemal cells. NB usually forms a solid mass, but in extremely rare cases, it
may show cystic changes. Case Presentation: A six-month-old girl with persistent highfevers was found to have pyuria and bacteriuria. Ultrasonography revealed multilocular cysts
in the right kidney. Right nephrectomy was performed with cyst wall rupture during surgery.
An intraoperative rapid diagnosis, based on peritoneal fluid cytology, confirmed threecomponents of blastemal, stromal, and epithelial cells. The blastemal cells were dyshesive,with scant to no cytoplasm and were the predominant cell type. The spindle-shaped stromalcells were arranged in fascicles. The epithelial cells demonstrated tubular structures.
Macroscopically, the resected cystic tumor measured 80 mm in maximum diameter with aprominently thin cyst wall, but solid areas were also apparent. Histologically, the tumor wasdiagnosed as

cysticNB(blastemal-predominant) displaying a

triphasic pattern.

Hyperchromatic nuclei and apoptotic bodies were found. The clinical stage classification ofJapan Wilms Tumor Study group was 3. The patient was treated with chemotherapy andradiotherapy. Tumor recurrence and metastasis have not been observed in the eight months
since surgery. Conclusion: This is an extremely rare case of infantile cystic NB. We

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diagnosed the NB cells that appeared in the peritoneal fluid by intraoperative rapid cytology.
Cytological examination proved to be a very useful technique for determining the clinicalstage of NB. Additionally, we propose that massive tumor degeneration and necrosis beconsidered as a pathogenic mechanism of cyst formation in NB.

Key words: cyst, nephroblastoma (NB), infant, peritoneal fluid, cytology

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BackgroundWilms tumor, also known as nephroblastoma (NB) is a malignant embryonal neoplasm
derived from nephrogenic blastemal cells. NB is the most common malignant renal tumor inchildren and 98% of cases occur under the age of 10. The mean age at diagnosis is 37 months
and 43 months among males and females, respectively [1]. However, adult-onset cases havealso been reported [2]. Grossly, NB usually forms a solitary and rounded-solid mass.
Histologically, the three components of blastemal, epithelial, and stromal cells are mixed invarious proportions.
Renal cystic tumors in children can be benign, such as cystic nephroma (multilocularcyst), and malignant homologous tumors, such as cystic partially differentiated NB (CPDNB)[3]. Furthermore, very few case of cystic NBs in infants and adults have been reported [4-6].
We herein report an extremely rare case of cystic NB in an infant and discuss its
pathogenic mechanism. In addition, we also describe the cytological findings of NB thatappeared in peritoneal fluid.

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Case Presentation
A previously healthy six-month-old girl who was born full-term following an uncomplicatedpregnancy presented with persistent high fever and was found to have pyuria and bacteriuria.
Prior to this, she had no significant medical history. No obvious gross malformations wereobserved on physical examination nor was any pertinent family history noted.
Ultrasonography revealed multilocular cysts in the right kidney; of note, no abdominal
abnormalities had been observed at her four-month medical examination.
Abdominal contrast computed tomography (CT) revealed a multilocular cystic massaccompanied by septal wall formation pressing on the normal kidney parenchyma (Fig. 1).
The tumor had not directly infiltrated the renal pelvis and there was no coexistence ofhydronephrosis. Renal dysplasia was ruled out due to the presence of adjacent normal kidneyparenchyma. Because the cystic septa was thickened, cystic NB was deemed the most likely
entity, preoperatively. One month later, right nephrectomy was performed. Unfortunately, thecyst wall ruptured during surgery. An intraoperative cytological evaluation by rapid
Papanicolaou staining of peritoneal fluid confirmed three components of blastemal, stromal,and epithelial cells. The findings were interpreted on-site as NB (Fig. 2).

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Cytologically, the blastemal cells were dyshesive, exhibiting naked nuclei with scant toabsent cytoplasm and were the most predominant cell type. The spindle-shaped stromal cells
were arranged in fascicles, showing a fibroblast-like configuration. And epithelial cells
formed tubular structures. Macroscopically, the resected cystic tumor measured 80 mm in
maximum diameter involving the upper pole to middle portion of the right kidney (Fig. 3A)
and the cystic wall was predominantly thin. A portion of the cystic wall was ruptured by thesurgical procedure and was associated with hemorrhage in the surrounding tissues. On the cut
surface of the tumor, the cystic septum within the tumor had disappeared (Fig. 3B). Instead,hemorrhage and muddy, degenerative necrotic tumor tissue was found within the cystic space.
Solid areas were observed within the cyst walls.
Histologically, the tumor was diagnosed as cystic NB (blastemal-predominant)displaying a triphasic pattern. The blastemal cells showed a solid growth pattern, whereas theepithelial cells showed tubular structures (Fig. 4A and 4B). The spindle-shaped stromal cells
resembled embryonic mesenchyme, displaying differentiation into smooth muscles andfibroblasts (Fig. 4C). The cystic wall was lined by blastemal cells (Fig. 4D). Some solid areas
were present within the cyst wall. There were no anaplastic cells or atypical mitoses.
Degenerated hyperchromatic nuclei and apoptotic bodies were found in some areas.

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Immunohistochemically, the blastemal cells and epithelial cells were positive for WT1(WT49, Leica, diluted 1:1), but the stromal cells were negative. The Ki-67 (MIB-1,
BioGenex, diluted 1:30) labeling index of the tumor was as high as 90%, while thedegenerated necrotic tumor cells showed decreased staining properties. Nephrogenic rest, aprecursor lesion of NB, was not identified in the remaining renal parenchyma. The clinicalstage classification of the Japanese Wilms Tumor Study (JWiTS) group was 3. The patient
was treated with chemotherapy and radiotherapy and tumor recurrence and metastasis havenot been observed in the eight months since surgery.

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Discussion
This case report describes an extremely rare case of cystic NB that developed in an infant
with no family history or malformation. Furthermore, we describe the cytological findings ofthe tumor observed intraoperatively involving the peritoneal fluid.
The differential diagnosis of cystic NB includes CPDNB. CPDNB also exhibits
multiloculated cysts, as in this case, however these lesions should not have apparent solid or
nodular mass formation. CPDNB contains mature or immature nephroblastic tissue, butconforms to the septum between cysts. In contrast, cystic NB has solid NB components
expanding the cyst wall, which were easily identified in this case.
To our knowledge, only three cases of NB with cyst formation have been reported in the
English literature [4-6]. However, there were no case reports of ruptured cystic NB. One case
was an infantile case (9.5 months old) and the other 2 cases were in adults (36 and 30 yearsold). The mechanism underlying the cyst formation is not well understood. However, thefollowing two possible mechanisms have been proposed: 1) formation due to tumor
degeneration and necrosis and 2) formation due to the tumor infiltrating into the renal pelvis,
leading to urine inflow inside the tumor. In the present case, there was no extensive
coagulative necrosis or thrombus formation, nor any apparent perforation between the tumor

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and the renal pelvis. Although there have been no case reports of spontaneous regression of
NB, nephrogenic rest, which is a precursor lesion of NB, exhibits spontaneous regression andeventual scarring as obsolescent rest [7,8]. In our case, there was no nephrogenic rest or scartissue in the remaining renal parenchyma. Therefore, it was thought that cyst formation may
have been caused by massive tumor degeneration and necrosis of unknown etiology rather
than spontaneous regression, given the presence of degenerated tumor cells and apoptotic
bodies.
NB may be the cause of abdominal pain, anemia, and shock accompanying tumor
rupture. According to the staging system of the JWiTS and the National Wilms Tumor Study(NWTS), diffuse peritoneal contamination associated with spillage of NB cells before andduring surgery is classified as stage 3 [9-11]. The NWTS has also reported that spillage of
NB cells does not constitute a risk factor after three-drug chemotherapy and whole-abdomen
radiotherapy [12]. In addition, the Children's Oncology Group reported that the incidence of
intraoperative tumor spillage increased to 11.9%, and the odds ratio reached 2.183 in patientswith a maximum tumor diameter of ≥12 cm compared to those with <12 cm [13]. In thepresent case, the maximum tumor diameter was 8 cm, but there was intraoperative tumor
rupture associated with tumor cells in the peritoneal fluid. We propose that cystic changes in

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NB may be a risk factor for tumor rupture. After surgery, the patient received chemotherapy
and radiation therapy according to the protocol of the NWTS. Because of the patient’sfavorable histologic features (lack of anaplasia) and excellent response to therapy, this case is
expected to have a good prognosis.

Conclusions
We present an extremely rare case of infantile cystic NB. The diagnosis was able to be madeon-site by intraoperative rapid cytology of peritoneal fluid. This technique of cytologicalexamination proved to be very useful for determining the clinical stage of NB. Additionally,
massive tumor degeneration and necrosis should be considered as a possible mechanism ofcyst formation in NB.

Abbreviations
NB

Nephroblastoma

CPDNB

Cystic partially differentiated nephroblastomaCT

Computed tomography

JWiTS

Japanese Wilms Tumor Study

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NWTS

National Wilms Tumor Study

Declarations

Ethics approval and consent to participate.
Not applicable.

Consent for publication
Written informed consent was obtained from the patient’s parents for the publication of thiscase report and any accompanying images. A copy of the signed consent is available forreview by the editor of this journal.

Availability of Data and Materials
The dataset supporting the findings and conclusions of this case report is included within thearticle.

Funding

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None.

Competing Interests
The authors declare no conflicts of interest in association with this study.

Authors’ Contributions
NK and SY participated in the conception of the study and writing of the manuscript. MT,
MY, CS, MN, BB, XG, CF and AS performed the clinical imaging and/or
pathological/cytological/immunohistochemical interpretation of this lesion. All of the authors
have read and approved the final manuscript.

Authors’ Information
NK, XG, CF, AS and SY belong to the Department of Pathology and Laboratory Medicine,
Kanazawa Medical University, Ishikawa, Japan. MT, MY, CS and MN belong to the
Department of Pathology, Kanazawa Medical University, Ishikawa, Japan. BB belong to the
Department of Pathology and Laboratory Medicine, University of Vermont College ofMedicine, Burlington, Vermont, USA.

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Acknowledgments
We would like to thank Seiya Mizuguchi, Yumi Tsubata, Yoshiiku Ohkanemasa, Toshie
Terauchi and Satoko Nakada for their expert technical assistance and helpful comments.

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References
1. Moch H, Humphrey PA, Ulbright TM, Reuter VE. WHO Classification of Tumours of
the Urinary System and Male Genital Organs. Fourth Edition. Lyon: IARC Press,
2016, 49.
2. Huser J, Grignon DJ, Ro JY, Ayala AG, Shannon RL, Papadopoulos NJ. Adult Wilms'
tumor: a clinicopathologic study of 11 cases. Mod Pathol. 1990, 3: 321-326.
3. Babut JM, Bawab F, Jouan H, Coeurdacier P, Treguier C, Fremond B. Renal cystic
tumours in children-a diagnostic challenge. Eur J Pediatr Surg. 1993, 3:157-160.
4. Bindhu J, Imtiaz A, Kumar RV, Thejaswini MD. Cystic variant of favorable-histology
Wilms' tumor presenting with osteolytic metastasis to the ribs. J Postgrad Med. 2010,
56: 28-30.
5. Fujita K, Nishimura K, Yasunaga Y, Miyake O, Hirota S, Okuyama A. Adult Wilms'
tumor mimicking hemorrhagic renal cyst. Int J Urol. 2003, 10: 492-494.
6. Adjei ON, Tamura S, Sugimura H, Shimizu T, Kihara Y, Asato M, Qiang TX, Watanabe
K, Marutsuka K, Hasui Y. Adult cystic Wilms' tumor (nephroblastoma): radiologic
features with pathologic correlation. Radiat Med. 1996, 14: 287-291.

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7. Beckwith JB. Precursor lesions of Wilms tumor: clinical and biological implications.
Med Pediatr Oncol. 1993, 21: 158-168.
8. William MM, David JG, Elizabeth JP. Tumors of the Kidney, Bladder and Related
Urinary Structures (AFIP Atlas of Tumor Pathology 4th Series). Washington, DC:
AFIP Press, 2004, 38-47.
9. D'Angio GJ, Breslow N, Beckwith JB, Evans A, Baum H, deLorimier A, Fernbach D,
Hrabovsky E, Jones B, Kelalis P. Treatment of Wilms' tumor. Results of the Third
National Wilms' Tumor Study. Cancer. 1989, 64: 349-360.
10. Fukuzawa H, Shiima Y, Mishima Y, Sekine S, Miura S, Yabe K, Yamaki S,

Morita K, Okata Y, Hisamatsu C, Nakao M, Yokoi A, Maeda K, Kosaka Y.
Predictive factor for intraoperative tumor rupture of Wilms tumor. Pediatr
Surg Int. 2017, 33: 91-95.
11. Khanna G, Naranjo A, Hoffer F, Mullen E, Geller J, Gratias EJ, Ehrlich PF, Perlman EJ,
Rosen N, Grundy P, Dome JS. Detection of preoperative Wilms tumor rupture with
CT: a report from the Children's Oncology Group. Radiology. 2013, 266: 610-617.
12. Ehrlich PF, Anderson JR, Ritchey ML, Dome JS, Green DM, Grundy PE, Perlman EJ,
Kalapurakal JA, Breslow NE, Shamberger RC. Clinicopathologic findings predictive of

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relapse in children with stage III favorable-histology Wilms tumor. J Clin Oncol.
2013, 31: 1196-1201.
13. Gow KW, Barnhart DC, Hamilton TE, Kandel JJ, Chen MK, Ferrer FA, Price MR,
Mullen EA, Geller JI, Gratias EJ, Rosen N, Khanna G, Naranjo A, Ritchey ML, Grundy
PE, Dome JS, Ehrlich PF. Primary nephrectomy and intraoperative tumor spill:report from the Children's Oncology Group (COG) renal tumors committee. J
Pediatr Surg. 2013, 48: 34-38.

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FIGURE LEGENDS

Figure 1. Enhanced abdominal CT. Multilocular cystic mass located in the right kidney.
The septal wall of the tumor was thickened. Multiple solid areas were identified within thetumor.

Figure 2. Cytology of the peritoneal fluid. Three components of blastemal, stromal andepithelial cells were seen. The blastemal cells showed decreased cell adhesion (arrow), thestromal cells showed a fibroblast-like configuration (arrow head), and the epithelial cells
showed a tubular structure (inset) (Papanicolaou staining, x400).

Figure 3. Gross findings of the resected right kidney. A: The tumor was localized from theupper pole to the middle portion. B: The cystic septum within the tumor had disappeared.
Some solid areas were seen (arrow head).

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Figure 4. Histological findings of the tumor. A: Blastemal cells (H&E staining, x400). B: Epithelial

cells (H&E staining, x400). C: Stromal cells (H&E staining, x400). D: Low-powered view of cystic

wall of the tumor (H&E staining, x40).

19

Figure 1

Click here to access/download;Figure;E11804066
Kurose20180413 cystic NB Fig1.docx

Fig.1

Figure 2

Click here to access/download;Figure;E11804066 Kurose
20180413 cystic NB Fig2.docx

Fig. 2

Figure 3

Click here to access/download;Figure;E11804066
Kurose20180413 cystic NB Fig3.docx

Fig. 3A

B

Figure 4

Click here to access/download;Figure;E11804066 Kurose
20180413 cystic NB Fig4.docx

A

D

B

C

Personal Cover

Click here to access/download;Personal
Cover;renamed_c94b2.docx

Nozomu(k-nozomu@kanazawa-med.ac.jp)1*,

Kurose(michiho@kanazawa-med.ac.jp)2,

MichihoManabuTakenaka
Yamashita(yama-bu@kanazawa-med.ac.jp)2, Chie Shimaguchi (shima-c@kanazawa-med.ac.jp)2,
MarikoNakano(mariko-n@kanazawa-med.ac.jp)2,

BryantBritni(britni.bryant@uvmhealth.org)3, Xin Guo (xinguo@kanazawa-med.ac.jp)1, Chizuru
Futatsuya(c-futats@kanazawa-med.ac.jp)1,

Akihiro

Shioya(a-shioya@kanazawa-med.ac.jp)1, Sohsuke Yamada (sohsuke@kanazawa-med.ac.jp)1*

Short running head: Infantile cystic NB

1

Department of Pathology and Laboratory Medicine & 2Department of Pathology,

Kanazawa Medical University, Ishikawa, Japan.

3

Department of Pathology andLaboratory Medicine, University of Vermont College of Medicine, Burlington,
Vermont, USA.

*Corresponding author: Nozomu Kurose, M.D., Ph.D. & Sohsuke Yamada, M.D., Ph.D.,
Department of Pathology and Laboratory Medicine, Kanazawa Medical University, 1-1

Daigaku,

Uchinada,

Ishikawa,

920-0293,

Japan.

Tel:

81-76-218-8264;

81-76-286-1207; and E-mail: k-nozomu@kanazawa-med.ac.jp
Word count: 2,395 words (Abstract 250 words); references: 13; figures: 4

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