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MBBS, MD (Pathology),
Sanjay Gandhi institute of trauma and orthopedics,
Bengaluru.
On Aug 2018




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Dr. Mamta Gupta
Consultant
(Ex HOD Obs &Gynae, Hindu Rao Hospital and associated NDMC Medical College, Delhi)
Aug 2018




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Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
E-mail: drrajendrak1@rediffmail.com
On May 11,2011




Dr. Shankar P.R.

"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
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Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
E-mail: ravi.dr.shankar@gmail.com
On April 2011
Anuradha

Dear team JCDR, I would like to thank you for the very professional and polite service provided by everyone at JCDR. While i have been in the field of writing and editing for sometime, this has been my first attempt in publishing a scientific paper.Thank you for hand-holding me through the process.


Dr. Anuradha
E-mail: anuradha2nittur@gmail.com
On Jan 2020

Important Notice

Case report
Year : 2022 | Month : April | Volume : 16 | Issue : 4 | Page : ED03 - ED05 Full Version

Intracholecystic Papillary Neoplasm with Low-grade Intraepithelial Neoplasia: A Rare Entity


Published: April 1, 2022 | DOI: https://doi.org/10.7860/JCDR/2022/52489.16147
Vertika Gupta, Sarita Devdhar, Rashmi Gautam, Arun Chaudhary, Bhuvan Adhlakha

1. Assistant Professor, Department of Pathology, Noida International Institute of Medical Sciences, Noida International University, Greater Noida, Uttar Pradesh, India. 2. Professor, Department of Pathology, Noida International Institute of Medical Sciences, Noida International University, Greater Noida, Uttar Pradesh, India. 3. Associate Professor, Department of Pathology, Noida International Institute of Medical Sciences, Noida International University, Greater Noida, Uttar Pradesh, India. 4. Professor, Department of Pathology, Noida International Institute of Medical Sciences, Noida International University, Greater Noida, Uttar Pradesh, India. 5. Assistant Professor, Department of Pathology, Noida International Institute of Medical Sciences, Noida International University, Greater Noida, Uttar Pradesh, India.

Correspondence Address :
Vertika Gupta,
Assistant Professor, Department of Pathology, Noida International Institute of Medical Sciences, Noida International University, Greater Noida, Uttar Pradesh, India.
E-mail: drvertikagupta@gmail.com

Abstract

Intracholecystic Papillary Neoplasm (ICPN) is a recently described, rare, mass forming, epithelial neoplasm originating in the mucosa of the gall bladder. It usually protrudes in the lumen and is generally non invasive, but may show dysplastic changes which may be low-grade or high-grade or may be associated with invasive carcinoma. Authors, hereby, describe a case of ICPN in a 57-year-old female patient who reported to Surgery Outpatient Department (OPD) with the chief complaint of pain in abdomen since last five days. On ultrasonography, gall stones were detected for which she underwent cholecystectomy. Histopathological Examination (HPE) revealed a papillary growth in the body of gall bladder measuring 1.0 cm in diameter. Sections from the growth showed back-to-back arranged glands exhibiting a papillary pattern. The glands were lined by columnar epithelium with basally located nuclei. Pyloric metaplasia was noted focally. No foci of invasion were seen. Papillary hyperplasia was noted in adjacent areas along with features consistent with chronic cholecystitis. Thus, a diagnosis of ICPN with low-grade intraepithelial neoplasia was made. The patient recovered well postsurgery and is on regular follow-up.

Keywords

Dysplasia, Gall bladder, Invasive carcinoma, Polypoidal

Case Report

The present case is of a 57-year-old female patient who was admitted in the Surgery Ward with the chief complaint of dull pain in abdomen since last five days. There was no other relevant present or past medical history. The patient was afebrile and on physical examination, mild tenderness was detected in right hypochondrium. Ultrasound findings included fatty change liver (grade 1) and gall stones. Complete blood count revealed mild anaemia (haemoglobin was 10.9 gm/dL). Her other routine investigations were within normal limits except for slightly raised serum alkaline phosphatase (154 U/L).

On the basis of clinical, laboratory and radiological findings, a provisional diagnosis of cholecystitis with cholelithiasis was made. Cholecystectomy was performed, which was uneventful. Operative findings included friable liver bed, thick-walled gall bladder with multiple adhesions with short cystic duct and a solitary stone impacted at the neck. Post surgery patient was administered intravenous fluids and prescribed injectable antibiotics and antacids. Cholecystectomy specimen was sent for Histopathological Examination (HPE). On gross examination, gall bladder measured 8.0×3.0×3.0 cm. On cut section, a papillary, pale yellow, sessile growth was seen in the body of the gall bladder measuring 1.0 cm in diameter. Adjacent mucosa was velvety and bile stained. Wall thickness measured 0.5 cm (Table/Fig 1). A cholesterol stone was received in the container. Haematoxylin and Eosin (H&E) stained sections from the papillary growth showed proliferating glands arranged in papillary pattern with thin fibrovascular core. The glands were lined by columnar epithelium with basally located nuclei and showed complex configuration with back-to-back arrangement with little intervening stroma consistent with intestinal morphology (Table/Fig 2)a,b. Pyloric metaplasia was also noted at places (Table/Fig 2)c. As pyloric metaplasia was focal, differential diagnosis of pyloric gland adenoma was ruled out. No foci of invasion were seen. Sections from the adjacent areas showed papillary hyperplasia with similar morphology. Few areas showed features consistent with chronic cholecystitis. Immunohistochemical analysis was not done due to lack of facility for the same.

As invasive carcinoma may not be detected grossly and may even occur away from Intracholecystic Papillary Neoplasm (ICPN), therefore, regrossing was done and entire gall bladder was submitted for histologic evaluation. HPE revealed similar findings and no foci of invasive carcinoma were detected. Based on gross features (papillary, intraluminal growth measuring 1 cm) and microscopic findings (compact back-to-back arrangement of glands with little intervening stroma, minimal cytologic atypia and maintained nuclear polarity), a diagnosis of ICPN with low-grade intraepithelial neoplasia was given. The postoperative course was uneventful and the patient was discharged and was under regular follow-up till the writing of the present report.

Discussion

The incidence of mucosal polypoid lesions of the gall bladder is 5-7% in the general population (1). ICPN is a polypoidal lesion that has been put under the category of ‘Benign epithelial tumours and precursors’ in the World Health Organisation (WHO) 2019 classification of the tumours of gall bladder and extrahepatic bile ducts (2). ICPN is a papillary, intraluminal growth that arises in the mucosa of gall bladder. It is usually non invasive, but may exhibit low-grade or high-grade dysplasia. If there is a component of invasive carcinoma, the lesion is referred to as ICPN with associated invasive carcinoma. As ICPN is a rare lesion that has been described recently, hence, the diagnostic criteria are not very well defined, thus making it difficult to differentiate it from other polypoidal lesions.

Adsay V et al., described the entity in detail in 2012 after analysing 123 cholecystectomy specimens that had a well-defined exophytic neoplasm measuring ≥1 cm, followed by some case reports and two case series by Isozaki M et al., describing 23 cases and Bennett S et al., which included seven cases (3),(4),(5). According to the study published by Adsay V et al., ICPN was found in 0.4% of cholecystectomies and in 6.4% cases, gall bladder carcinomas arise in association with ICPN (3). In their study, the average tumour size of 2.6 cm was observed with a median of 2.2 cm (range, 1.0 to 7.7 cm); 70% of the cases were found to be solitary while 30% were multifocal. In the present case, ICPN was found in 0.6% of cholecystectomies (similar to incidence noted by Adsay V et al.,)the tumour was solitary and measured 1.0 cm. The most common locations were fundus and body (88% of the cases), similar to the index case. Adsay V et al., further observed that ICPN occurred more commonly in females, between 20-94 years (mean age 61 years); half of the patients complained of upper outer quadrant pain, and in the other half, lesion was detected incidentally and gall stones were identified in 20% of the cases (3). In the present study, the patient did complain of upper quadrant pain but the diagnosis of ICPN was incidental upon HPE.

There are no known aetiological factors and unlike gall bladder carcinomas, ICPN has no association with gall stones (2). It is believed that these intraepithelial neoplasms represent an “adenoma-carcinoma” sequence (3),(6),(7),(8). Although 90% of the ICPNs showed a mixture of papillary and tubular areas, 43% were categorised as papillary, 26% as tubular, and 31% as tubulo-papillary (3). ICPN can have various cell lineages like biliary, gastric, intestinal and oncocytic as also seen in dysplastic lesions of bile duct and pancreas, the most common cell lineage being biliary, seen in 50% cases, followed by gastric pyloric in 20% cases, gastric foveolar in 16%, intestinal in 8% and oncocytic in 6% cases [3,9]. Immunohistochemical profile of these lineages reveal that 66% of biliary type were MUC1+, all cases of gastric foveolar type were MUC5AC+, 92% of gastric pyloric type were MUC6+, intestinal type were 100% CK20+; 75% CDX2+; 50%, MUC2+ while oncocytic type showed 17% positivity for HepPar and 17% for MUC6; however, in 90% cases, a secondary or unclassifiable pattern and hybrid immunophenotypes were detected (3),(7),(10). Based on highest degree of cytoarchitectural atypia in the epithelium, ICPNs are classified as low-grade or high-grade. Mild-moderate atypia is seen in low-grade ICPNs while high-grade lesions reveal architectural complexity, nuclear pleomorphism and loss of polarity (2).

It has been observed that the lesions which are less than 1.0 cm in size are less likely to be associated with invasive foci, but the larger lesions showed more propensity towards neoplastic transformation through the adenoma-dysplasia-carcinoma sequence (3),(6),(7),(8). Half of the lesions measuring ≥1 cm have foci of invasive carcinoma at diagnosis (3). Morphological features associated with the presence of invasive foci are the presence of a papillary pattern, high-grade dysplasia, and the predominance of a non pyloric cell line (8),(11). Most of the invasive carcinomas seen in ICPNs are pancreato-biliary-type gall bladder adenocarcinomas; however, other types such as mucinous, neuroendocrine, etc., are also seen (3). Because most lesions are diagnosed after surgery and are not suspected before surgery, no specific management strategy is described. In most cases, cholecystectomy or radical cholecystectomy was performed when the suspicion of adenocarcinoma of the gall bladder was raised on the basis of the imaging studies (12). Simple cholecystectomy without lymphadenectomy is done if ICPN is diagnosed preoperatively (8),(13). Patients with non invasive ICPNs had one, three and five years survival rates of 90%, 90%, and 78%, while those with associated invasive disease had survival rate of 69%, 60%, and 60%, respectively (3),(9).

Thus, histopathological study is essential and helpful in defining the main characteristics that impact management, survival and prognosis in these patients.

Conclusion

Intracholecystic papillary neoplasm in the gall bladder is similar to their pancreatic and biliary counterpart. They show variable morphological sub-types, a mixture of papillary or tubular growth patterns and low-grade or high-grade dysplasia, often with significant overlap. ICPNs have a relatively indolent course and better prognosis as compared to pancreato-biliary type gall bladder carcinomas. Further studies are required to define pathological features, that may help in diagnosis and determining prognosis in these cases.

References

1.
Myers RP, Shaffer EA, Beck PL. Gallbladder polyps: Epidemiology, natural history and management. Can J Gastroenterol. 2002;16:187-94. [crossref] [PubMed]
2.
WHO Classification of Tumours Editorial Board. Digestive system tumours. Lyon (France): International Agency for Research on Cancer: 2019. (WHO classification of tumours series, 5th ed; vol. 1).
3.
Adsay V, Jang KT, Roa JC, Dursun N, Ohike N, Bagci P, et al. Intracholecystic papillary-tubular neoplasms (ICPN) of the gallbladder (neoplastic polyps, adenomas, and papillary neoplasms that are ≥1.0 cm): Clinicopathologic and immunohistochemical analysis of 123 cases. Am J Surg Pathol. 2012;36(9):1279-301. [crossref] [PubMed]
4.
Isozaki M, Ohike N, Mitsuya T, Takimoto M. Clinicopathological study of intracystic papillary-tubular neoplasms (ICPN) of the gallbladder. Showa Univ J Med Sci. 2014;26:17-26. [crossref]
5.
Bennett S, Marginean EC, Paquin-Gobeil M, Wasserman J, Weaver J, Mimeault R, et al. Clinical and pathological features of intraductal papillary neoplasm of the biliary tract and gallbladder. HPB (Oxford). 2015;17:811-18. [crossref] [PubMed]
6.
Kozuka S, Tsubone N, Yasui A, Hachisuka K. Relation of adenoma to carcinoma in the gallbladder. Cancer. 1982;50:2226-34. 3.0.CO;2-3>[crossref]
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SaeiHamedani F, Garcia-Buitrago M. Intracholecystic Papillary-Tubular Neoplasms (ICPN) of the gallbladder: A short review of literature. Appl Immunohistochem Mol Morphol. 2020;28(1):57-61. [crossref] [PubMed]
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Logrado A, Constantino J, Daniel C, Pereira J, Carvalho MT, Casimiro C. Low-grade dysplastic intracholecystic papillary neoplasia: A case report. Am J Case Rep. 2021;22:e929788. Doi: 10.12659/ajcr.929788. [crossref] [PubMed]
9.
Furukawa T, Klöppel G, VolkanAdsay N, Albores-Saavedra J, Fukushima N, Horii A, et al. Classification of types of intraductal papillary-mucinous neoplasm of the pancreas: A consensus study. Virchows Arch. 2005;447(5):794-99. [crossref] [PubMed]
10.
Odze RD, Goldblum JR. Odze and Goldblum surgical pathology of the GI tract, liver, biliary tract, and pancreas. 3rd edn. Philadelphia:Elsevier Saunders. 2014.
11.
McClellan JM, Escobar MA Jr. Intracholecystic papillary-tubular neoplasm of the gallbladder. J Pediar Surg Case Rep. 2017;25:46-48. [crossref]
12.
Mizobuchi N, Munechika J, Takeyama N, Ohgiya Y, Ohike N, Abe R, et al. Three cases of intracystic papillary neoplasm of gallbladder. Abdom Radiol (NY) 2018;43(7):1535-39. [crossref] [PubMed]
13.
Muranushi R, Saito H, Matsumoto A, Kato T, Tanaka N, Nakazato K, et al. A case report of intracholecystic papillary neoplasm of the gallbladder resembling a submucosaltumor. Surgical Case Reports. 2018;4:124. [crossref] [PubMed]

DOI and Others

DOI: 10.7860/JCDR/2022/52489.16147

Date of Submission: Sep 21, 2021
Date of Peer Review: Nov 19, 2021
Date of Acceptance: Jan 12, 2022
Date of Publishing: Apr 01, 2022

AUTHOR DECLARATATION:
• Financial or Other Competing Interests: None
• Was informed consent obtained from the subjects involved in the study? Yes
• For any images presented appropriate consent has been obtained from the subjects. Yes

PLAGIARISM CHECKING METHODS:
• Plagiarism X-checker: Sep 22, 2021
• Manual Googling: Dec 07, 2021
• iThenticate Software: Jan 12, 2022 (16%)

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  • EBSCOhost
  • Google Scholar
  • HINARI Access to Research in Health Programme
  • Indian Science Abstracts (ISA)
  • Journal seek Database
  • Google
  • Popline (reproductive health literature)
  • www.omnimedicalsearch.com