Epithelial Misplacement Research Articles

Epithelial misplacement in Peutz-Jeghers polyps-the efficacy of the distribution of immunohistochemical markers in its diagnosis.

Epithelial misplacement in Peutz-Jeghers polyps-the efficacy of the distribution of immunohistochemical markers in its diagnosis.

Imaging of colorectal adenomas with pseudoinvasion and malignant polyps using two-photon excitation microscopy.

Although the incidence and mortality rates of colorectal cancer exhibit significant variability, it remains one of the most prevalent cancers worldwide. Endeavors to prevent colorectal cancer development focus on detecting precursor lesions during colonoscopy. The diagnosis of endoscopically resected polyps relies on hematoxylin and eosin staining examination. For challenging cases like adenomatous polyps with epithelial misplacement, additional diagnostic methods could prove beneficial. This paper aims to underscore stromal changes observed in malignant polyps and polyps with pseudoinvasion, leveraging two-photon excitation microscopy (TPEM), a technique extensively employed in the medical field in recent years. Both the subjective and quantitative analysis of TPEM images revealed distinct distributions and densities of collagen at the invasion front in malignant polyps compared to areas of pseudoinvasion. TPEM holds potential in discerning true invasion in malignant polyps from pseudoinvasion, offering enhanced visualization of local stromal changes.

Consideration of diagnosing extremely well differentiated adenocarcinoma of gastrointestinal tract

For gastrointestinal adenocarcinoma with excellent differentiation, some diagnostic names have emerged in recent years, which have overlapping and different meanings. Low-grade well differentiated adenocarcinoma and very well differentiated adenocarcinoma are terms for a group of adenocarcinomas with good differentiation and little cellular atypia, including a variety of histological types. It is suggested that specific histological types should be listed as far as possible in diagnosis, instead of using "low-grade well differentiated adenocarcinoma" or "very well differentiated adenocarcinoma" as a complete diagnosis. This kind of adenocarcinomas may lack cellular pleomorphism, so it is necessary to observe the structural atypia for diagnosis. At the same time, attention should be paid to the differentiation of reactive changes, low grade dysplasia, epithelial misplacement and other lesions.

Infrared Spectroscopic Analysis in the Differentiation of Epithelial Misplacement From Adenocarcinoma in Sigmoid Colonic Adenomatous Polyps

Purpose:The differential diagnosis of epithelial misplacement from invasive cancer in the colon is a challenging endeavour, augmented by the introduction of bowel cancer population screening. The main aim of the work is to test, as a proof-of concept study, the ability of the infrared spectroscopic imaging approach to differentiate epithelial misplacement from adenocarcinoma in sigmoid colonic adenomatous polyps.Methods:Ten samples from each of the four diagnostic groups, normal colonic mucosa, adenomatous polyps with low grade dysplasia, epithelial misplacement in adenomatous polyps and adenocarcinoma, were analysed using IR spectroscopic imaging and data processing methods. IR spectral images were subjected to data pre-processing and cluster analysis based segmentation to identify epithelial, connective tissue and stromal regions. Statistical analysis was carried out using principal component analysis and linear discriminant analysis based cross validation, to classify spectral features according to the pathology, and the diagnostic attributes were compared.Results:The combined 4-group classification model on an average showed a sensitivity of 64%, a specificity of 88% and an accuracy of 76% for prediction based on a ‘single spectrum’, whilst a ‘majority-vote’ prediction on an average showed a sensitivity of 73%, a specificity of 90% and an accuracy of 82%. The 2-group model, for the differential diagnosis of epithelial misplacement versus adenocarcinoma, showed an average sensitivity and specificity of 82.5% for prediction based on a ‘single spectrum’ whilst a ‘majority-vote’ classification showed an average sensitivity and specificity of 90%. A 92% area under the curve (AUC) value was obtained when evaluating the classifier using the Receiver Operating Characteristics (ROC) curves.Conclusions:IR spectroscopy shows promise in its ability to differentiate epithelial misplacement from adenocarcinoma in tissue sections, considered as one of the most challenging endeavours in population-wide diagnostic histopathology. Further studies with larger series, including cases with challenging diagnostic features are required to ascertain the capability of this modern digital pathology approach. In the long-term, IR spectroscopy based pathology which is relatively low-cost and rapid, could be a promising endeavour to consider for integration into the existing histopathology pathway, in particular for population based screening programmes where large number of samples are scrutinised.

The Bowel Cancer Screening Programme Expert Board: an analysis of activity during 2017-2020.

The inception of the National Health Service Bowel Cancer Screening Programme in England in 2006 highlighted the fact that the differential diagnosis between the presence of epithelial misplacement and adenocarcinoma occurring in colorectal adenomas is problematic. The pathology Expert Board (EB) was created to facilitate the review of difficult cases by a panel of three experienced gastrointestinal pathologists. This article describes a review of the work of the EB over a 4-year period (2017-2020). Four hundred and thirty polyps were referred to the EB from 193 pathologists and 76 hospitals during this time. The EB diagnosis was benign for 67%, malignant for 28%, and equivocal for 2% (with no consensus in the remainder). The most common diagnosis change made by the EB was from malignant to benign-made in 50% of polyps referred with an initially malignant diagnosis. The level of agreement between the individual EB members was 'good' (kappa score of 0.619) but that between the EB and the referring diagnosis was 'poor' (kappa score of 0.149). Data from one EB member indicated that the presence of lamina propria, features of torsion and cytological similarity between the superficial and deep glands were predictors of a benign diagnosis, whereas the presence of irregular neoplastic glands, a desmoplastic reaction and lymphovascular invasion were commonly observed features in polyps with a malignant diagnosis. Diagnostic agreement between EB members is better than that between the EB and referring pathologists. There was a consistent trend for the EB to change diagnoses from malignant to benign.

Invasive carcinoma versus pseudoinvasion: interobserver variability in the assessment of left-sided colorectal polypectomies

ObjectivesMisplaced epithelium in adenomas can occasionally be difficult to distinguish from invasive adenocarcinoma. We evaluated interobserver variability in the assessment of left-sided colon polypectomies for pseudoinvasion versus invasive adenocarcinoma and...

Expression of Extracellular Matrix-Related Genes and Their Regulatory microRNAs in Problematic Colorectal Polyps.

Simple SummaryDuring bowel cancer screening programs, many diagnostically problematic polyps are removed. The greatest challenge is to distinguish between adenomas with epithelial misplacement and adenomas with early carcinoma, considering the diagnosis affects prognosis and treatment. Our aim was to analyze the expression of extracellular matrix related genes and proteins DCN, EPHA4, FN1, SPARC, SPON2, and SPP1, in 44 biopsies. Differences were observed in most of the analyzed genes and proteins in adenoma with epithelial misplacement in comparison to adenoma with early carcinoma, reflecting inflammatory stromal reaction to traumatisation and misplacement of dysplastic glands in the submucosa in the former, and desmoplastic stromal reaction to true invasion of dysplastic glands in the submucosa in the latter. The observed expression patterns are too complex to be used in diagnostic work, but might contribute to better understanding extracellular matrix changes in colorectal cancerogenesis and help to find new diagnostic markers in the future.Colorectal carcinoma usually evolves gradually, forming a spectrum of lesions, due to accumulation of genetic mutations and epigenetic alterations. Many early lesions are detected since the introduction of screening programs. The greatest challenge is to distinguish between adenomas with epithelial misplacement (AEM) and adenomas with early carcinoma (AEC), considering the diagnosis affects prognosis and treatment. We analyzed the expression of selected extracellular matrix (ECM)-related genes and proteins, and their regulatory microRNAs using RT-qPCR and immunohistochemistry in biopsies from 44 patients. Differences were observed in AEM in comparison to AEC for DCN, EPHA4, FN1, SPON2, and SPP1, reflecting inflammatory stromal reaction to traumatisation and misplacement of dysplastic glands in the submucosa in the former, and desmoplastic stromal reaction to true invasion of dysplastic glands in the submucosa in the latter. Expression of regulatory microRNAs hsa-miR-200c and hsa-miR-146a significantly negatively correlated with the expression of their regulated genes, while significant difference between AEM and AEC was observed only for hsa-miR-29c. The described expression patterns are too complex to be used in diagnostic work, but might contribute to better understanding ECM changes in colorectal carcinoma development, helping to find new markers in the future.

Bioinformatics Analysis Reveals Most Prominent Gene Candidates to Distinguish Colorectal Adenoma from Adenocarcinoma.

Colorectal cancer (CRC) is one of the leading causes of death by cancer worldwide. Bowel cancer screening programs enable us to detect early lesions and improve the prognosis of patients with CRC. However, they also generate a significant number of problematic polyps, e.g., adenomas with epithelial misplacement (pseudoinvasion) which can mimic early adenocarcinoma. Therefore, biomarkers that would enable us to distinguish between adenoma with epithelial misplacement (pseudoinvasion) and adenoma with early adenocarcinomas (true invasion) are needed. We hypothesized that the former are genetically similar to adenoma and the latter to adenocarcinoma and we used bioinformatics approach to search for candidate genes that might be potentially used to distinguish between the two lesions. We used publicly available data from Gene Expression Omnibus database and we analyzed gene expression profiles of 252 samples of normal mucosa, colorectal adenoma, and carcinoma. In total, we analyzed 122 colorectal adenomas, 59 colorectal carcinomas, and 62 normal mucosa samples. We have identified 16 genes with differential expression in carcinoma compared to adenoma: COL12A1, COL1A2, COL3A1, DCN, PLAU, SPARC, SPON2, SPP1, SULF1, FADS1, G0S2, EPHA4, KIAA1324, L1TD1, PCKS1, and C11orf96. In conclusion, our in silico analysis revealed 16 candidate genes with different expression patterns in adenoma compared to carcinoma, which might be used to discriminate between these two lesions.

Colonic Tubulovillous Adenoma With High-Grade Dysplasia and Pseudoinvasion: A Diagnostic Pitfall

Introduction: interpretation of histopathologic features of resected colonic polyps is critical to subsequent management. We are a presenting a case of colonic villous adenoma with pseudoinvasion /misplacement of epithelium (PEM) into the stalk mimicking invasive carcinoma. Such phenomenon can be unfamiliar to the gastroenterologist. Case: 56 y/o male, h/o diabetes and hypertension, referred for colon cancer screening. Patient has been asymptomatic. His physical examination was unremarkable. Colonoscopy revealed 1.5 cm polyp with short stalk polyp at the splenic flexure (figure 1), which was removed wit hot snare. Pathology was consistent with tubulovillous adenoma with focal high grade dysplasia and pseudoinvasion involving the cauterized margin, with misplaced epithelium, and rounded, displaced glands surrounded by lamina propria (Figure 1).Figure: MUCOSA WITH RELATED MUSCULARIS MUCOSA. THE MUCOSA IS HERNIATING INTO THE SUBMUCOSA PSEUDOINVASION LOW POWER VIEW.Discussion: Colon cancer is the second leading cause of cancer-related deaths in the United States (when men and women are combined). It is established that removing precancerous adenomas not only reduce the risk of colorectal cancer but also significantly reduce the deaths from the disease. The histopathological features of resected polyps impact on subsequent management. In this case, there was high grade dysplasia, and the adenomatous epithelium appeared misplaced into the stalk and as such mimicking invasive carcinoma (pseuodinvasion). There are no definite endoscopic or clinical features to differentiate between the two lesions, and diagnosis depends solely on pathologic findings. In pseudoinvasion, the displaced glands are cytologically similar to the overlying adenoma and are rounded, often admixed with nonadenomatous glands, and surrounded by normal lamina propria, and often hemosiderin is seen in lamina propria. These features are in contrast with those of an invasive mucinous carcinoma. Additional histological scrutiny along with histochemical staining was necessary to exclude invasive cancer. Pseud invasion may be the result of repeated twisting of the stalk causing hemorrhage and this facilitates the prolapse of non-malignant adenomatous epithelium through the muscularis mucosa. Conclusion: There is difficulty inherent in distinguishing between pseudoinvasion and invasive carcinoma. Awareness and recognition of pseudo-carcinomatous invasion in adenomatous polyps and its distinction from invasive cancer is critical for both subsequent treatment and appropriate reporting.

Challenging diagnostic issues in adenomatous polyps with epithelial misplacement in bowel cancer screening: 5 years' experience of the Bowel Cancer Screening Programme Expert Board.

The diagnostic difficulties of differentiating epithelial misplacement from invasive cancer in colorectal adenomatous polyps have been recognised for many years. Nevertheless, the introduction of population screening in the UK has resulted in extraordinary diagnostic problems. Larger sigmoid colonic adenomatous polyps, which are those most likely to show epithelial misplacement, are specifically selected into such screening programmes, because these polyps are likely to bleed and screening is based on the detection of occult blood. The diagnostic challenges associated with this particular phenomenon have necessitated the institution of an 'Expert Board': this is a review of the first five years of its practice, during which time 256 polyps from 249 patients have been assessed. Indeed, the Expert Board contains three pathologists, because those pathologists do not necessarily agree, and a consensus diagnosis is required to drive appropriate patient management. However, this study has shown substantial levels of agreement between the three Expert Board pathologists, whereby the ultimate diagnosis has been changed, from that of the original referral diagnosis, by the Expert Board for half of all the polyps, in the substantial majority from malignant to benign. In 3% of polyp cases, the Expert Board consensus has been the dual diagnosis of both epithelial misplacement and adenocarcinoma, further illustrating the diagnostic difficulties. The Expert Board of the Bowel Cancer Screening Programme in the UK represents a unique and successful development in response to an extraordinary diagnostic conundrum created by the particular characteristics of bowel cancer screening.

Diagnostic Challenges Caused by Endoscopic Biopsy of Colonic Polyps: A Systematic Evaluation of Epithelial Misplacement With Review of Problematic Polyps From the Bowel Cancer Screening Program, United Kingdom.

Endoscopic mucosal biopsy may misplace mucosal elements into the submucosa of colonic adenomas, mimicking invasive adenocarcinoma. Biopsy-related misplacement can be more challenging to recognize than typical misplaced epithelium (pseudoinvasion) in pedunculated polyps. We compared the features of 16 polyps with biopsy-related misplaced epithelium with those of 10 adenomas with pseudoinvasion and 10 adenomas with invasive adenocarcinoma and performed Ki67 and p53 immunostaining on all cases. Features of misplaced epithelium in polyps referred to the Bowel Cancer Screening Program Expert Board in the United Kingdom were also evaluated for the same morphologic features. Biopsy-related epithelial misplacement occurred in adenomas throughout the colon and often appeared infiltrative (69%), including epithelial cells singly dispersed within reactive fibroinflammatory stroma or granulation tissue (44%). Misplaced epithelium displayed only low-grade cytologic features and was associated with extruded mucin (75%), tattoo pigment (63%), and misplaced normal glands (38%); scant lamina propria and muscularis mucosae were often present (88% and 44%, respectively). Cases referred to the Bowel Cancer Screening Program Expert Board also contained infiltrative-appearing misplaced epithelium (91%) that was cytologically low grade (72%), contained nondysplastic glands (11%), and showed other signs of injury. In contrast, misplaced epithelium in pedunculated polyps always had a lobular contour with a rim of lamina propria, hemorrhage, and/or hemosiderin. Invasive carcinomas showed malignant cytology and desmoplasia; most (70%) lacked features of trauma. Ki67 and p53 staining was patchy and weak in the misplaced epithelium, whereas invasive carcinomas showed increased staining for one or both markers. Pathologists should be aware that endoscopically manipulated adenomas may contain misplaced epithelium that simulates malignancy.

PTH-327 Epithelial misplacement versus polyp cancer: shedding new light on the diagnostic conundrum

<h3>Introduction</h3> Colorectal cancer is the second most common cause of cancer death in the UK.¹Colonic adenomas are often removed during colonoscopy as part of the Bowel Cancer Screening Programme to identify early cancers and improve patient survival rates.²Sigmoid adenomas may show features of benign epithelial misplacement in the submucosal stalk which in some cases may resemble an early infiltrating adenocarcinoma or polyp cancer³causing substantial diagnostic conundrum for pathologists. The aim of this study was to investigate and demonstrate the use of novel high resolution infrared spectroscopy to differentiate colonic epithelial misplacement (EM) from polyp cancer. <h3>Method</h3> 28 cases in total for the EM and cancer pathology groups were identified from 2011–2014. Tissue samples were formalin fixed and paraffin embedded, routinely processed and thin sections mounted onto calcium fluoride slides. Rapid mapping using a novel high resolution infrared spectrometer with a spatial resolution of 1.1 microns was performed on the tissue sections and the absorption spectra measured for each case. Accepted methods of multivariate spectral analysis were undertaken to elucidate the differences between the two pathologies across the dataset and classify the tissue based on the spectra. <h3>Results</h3> High resolution infrared spectral imaging was successfully performed on the colonic tissue. Analysis of 28 cases in two pathology groups generated over 500,000 spectra representative of the molecular biology of EM and cancer cases. Spectral differences between the two groups were analysed using principal component and linear discriminant analysis and a classification model built. Leave one sample out cross validation (LOSOCV) resulted in a sensitivity of 74.6% and a specificity of 82.3% for the technique to successfully discriminate EM from cancer. <h3>Conclusion</h3> Analysis of spectral data generated from novel high resolution infrared spectral imaging of colonic tissue has been proven to be successful in differentiating EM from cancer cases. The diagnostic difficultly of differentiating these cases is well documented, especially as one disease state approaches that of the other. However, novel high resolution spectroscopy may offer a new tool to aid the accurate diagnosis of early cancers. This technique has the potential to be used as an automated adjunct to traditional pathological diagnostics, may increase diagnostic speed in difficult cases and improve the efficiency of the patient management pathway. <h3>Disclosure of interest</h3> None Declared. <h3>References</h3> www.cancerresearchuk.org Mandel JS, Church TR, Bond JH, <i>et al</i>. N Engl J Med. 2000;343:1603–1607 Muto T, Bussey HRJ, Morson BC. J Clin Pathol. 1973;<b>26</b>:25–31

PWE-366 The bowel cancer screening programme (bcsp) pathology expert board: five years’ experience of an extraordinary pathological diagnostic conundrum

<h3>Introduction</h3> Adenomatous polyps of the colon, especially of the sigmoid colon, can show epithelial misplacement into the submucosa.¹Also termed pseudo-invasion, this feature can strongly mimic invasive adenocarcinoma. Recently described as the “diagnostic conundrum of the century”,²it is recognised that the differential diagnosis of polyp cancer versus epithelial misplacement poses particular difficulty for pathologists.³A national Expert Board (EB) was established in 2009 to provide a consensus histopathological diagnosis for challenging cases. The aim of this study was to review the first five years of the BCSP EB and to assess its effectiveness in a very difficult diagnostic area. <h3>Method</h3> A retrospective review was performed of all cases referred to the Expert Board in a five year period from its inception, in 2009, to 2013. Records were extracted from a prospectively maintained database, which included the opinion of the originating pathologist (s) and the results from each Board member. Levels of agreement between the originating pathologist (s) and between the three EB pathologists were then assessed using kappa statistics. <h3>Results</h3> A total of 249 cases were analysed. In this period, the EB had an increase in referrals of 260%, from 20 in 2009 to 72 in 2013. Of the 249 cases, 200 (80.3%) demonstrated a EB three-way agreement, with a kappa score of 0.67, defined as substantial agreement. There were marked differences between the diagnoses of the originating pathologist (s) and the Board consensus; for instance a benign diagnosis was made in 30.6% of cases by the originating pathologist (s) compared with 80.3% by the EB. The overall local to EB kappa consensus score was 0.09, only just better than chance. Of the 131 submissions submitted with a definite diagnosis, 47% had their grading revised by the EB consensus. <h3>Conclusion</h3> This study demonstrates a dramatic increase in referrals to the BCSP EB in its first five years. The diagnosis of the originating pathologist (s) was often at odds with the EB consensus and yet the Board demonstrated very good levels of agreement. The establishment of the Board is one of many successful developments in pathology associated with the introduction of cancer screening programmes and demonstrates the importance of expert opinion in difficult pathological diagnostic areas. <h3>Disclosure of interest</h3> None Declared. <h3>References</h3> Muto T, Bussey HJR, Morson BC. J Clin Pathol 1973; 26: 25–31 Shepherd NA, Griggs RKL. Mod Pathol2015; in press Loughrey MB, Shepherd NA. Histopathology 2015; 66: 66-77

The pathology of bowel cancer screening.

Colorectal cancer screening is widely promulgated in many parts of the world and population screening is occurring in many countries, especially in western Europe. Although, intuitively, it might be thought that the pathology resulting from screening should be straightforward, being mainly that of polyp diagnosis and the biopsy diagnosis and staging of established adenocarcinoma, in fact experience has shown that there are several areas of considerable difficulty and controversy. In the UK somewhat different programmes, all based on faecal occult blood (FOB) screening, have been developed and each has generated similar pathological conundra. These include the biopsy diagnosis of adenocarcinoma, colorectal serrated pathology, the diagnosis and management of polyp cancers and last, but certainly not least, the phenomenon of the large sigmoid colonic adenomatous polyp with epithelial misplacement/pseudo-invasion. Polyp cancers provide especially difficult management conundra and discussion of that management within a multidisciplinary team-based management meeting is regarded as essential in the UK. Large adenomatous polyps of the sigmoid colon with epithelial misplacement are selected into FOB-based screening programmes and have provided extraordinary diagnostic challenges. Finally, the quality assurance procedures introduced for screening can ensure a considerable overall improvement in the quality of lower gastrointestinal tract pathological reporting.

Colitis cystica profunda indefinite for dysplasia in Crohn disease: A potential diagnostic pitfall

Colitis cystica profunda (CCP) is a nonneoplastic condition characterized by misplaced glands deep to the muscularis mucosae of the colon and may be difficult to differentiate from well-differentiated mucinous adenocarcinoma. Absence of dysplasia in CCP usually aids in this distinction. We present a challenging case of CCP in the setting of Crohn disease (CD) containing foci of atypical epithelium. A right hemicolectomy from a 46-year-old woman contained a stricture associated with a proximal multilocular cystic lesion containing mucin-filled glands dissecting through the colonic wall. These glands had lobulated architecture with smooth contours surrounded by lamina propria and lacking desmoplastic stroma. The epithelium had focal nuclear crowding, enlargement, and hyperchromasia, with increased nucleus to cytoplasm ratio, but overall preserved polarity. Atypical cells were focally positive for CK7 and p53, with increased MIB-1 staining. These findings were interpreted as indefinite for dysplasia. Chronic transmural inflammation and mucosal regeneration probably facilitated epithelial misplacement, which secondarily developed cytologic atypia. However, the overall architecture and lack of dysplasia in the overlying mucosa argue against a diagnosis of adenocarcinoma. Our case illustrates the difficult diagnosis of this uncommon but problematic phenomenon, awareness of which is paramount for pathologists and clinicians participating in the management of CD patients.

Interobserver agreement in the reporting of colorectal polyp pathology among bowel cancer screening pathologists in Wales

To assess the interobserver agreement in the reporting of colorectal polyps among histopathologists participating in the Welsh Bowel Cancer Screening (BCS) programme. Twelve benign polyps representative of BCS cases were identified from pathology files and reported by 28 BCS histopathologists using proforma sheets. The level of agreement between the participants and a gold standard was determined using kappa (κ) statistics. A moderate level of agreement was achieved in the reporting of polyp type [κ = 0.45; 95% confidence interval (CI) 0.34-0.59] and adenomatous lesions were distinguished from non-adenomatous lesions in 96% of cases. Substantial agreement was obtained in distinguishing low- and high-grade dysplasias (κ = 0.67; 95% CI 0.50-0.86), but there was only fair agreement in reporting excision margin status (κ = 0.24; 95% CI 0.07-0.43) with frequent use of the 'uncertain' category. Significant issues included categorizing serrated lesions, recognizing focal high-grade dysplasia and epithelial misplacement, and apparent overdiagnosis of villous change in adenomas. Interobserver variability in some aspects of reporting colorectal polyps by BCS pathologists is suboptimal, with a potential impact upon patient management and the efficient running of the screening service. Approaches to addressing this are discussed.

Vascular pseudoinvasion in a solitary Peutz‐Jeghers polyp in the ileum

A Peutz-Jeghers polyp (PJP) is a hamartomatous lesion characterized by arborescent smooth muscle bundles covered with mucosa native to the site of involvement. PJPs in the small intestine may represent misplacement of non-neoplastic epithelium into the submucosa, muscularis propria and subserosa. Although epithelial misplacement in PJPs is a well-documented phenomenon, pseudoinvasion even into the vascular space in PJPs has not previously been reported. We report a case of a 22-year-old Japanese woman with a solitary PJP in the ileum. The ileal PJP in this patient showed epithelial herniation even into the vascular space. All the herniated epithelium, including the epithelial components invaginated into the vascular space, demonstrated features of pseudoinvasion, that is, presence of normal small intestinal type mucosa accompanied by the lamina propria, absence of any stromal desmoplastic reaction, and retention of the basal-luminal gradient. Pathologists must be aware of the possibility of vascular pseudoinvasion in small intestinal PJPs to avoid overdiagnosis of carcinoma and resulting unnecessary major surgery.

Tumor im Dünndarm bei Peutz-Jeghers-Syndrom

Epithelial misplacement can be present in small bowel polyps of patients with Peutz-Jeghers syndrome and can mimic invasive malignancy. For recognizing epithelial misplacement, which can also have dysplastic changes, it is helpful to demonstrate the associated lamina propria and the lack of desmoplastic response. Intramural mucinous cysts are frequently seen in the setting of epithelial misplacement.

Epithelial misplacement in the gastrointestinal tract: a diagnostic pitfall revisited in a patient with peutz jegher’s syndrome

Epithelial misplacement or ‘pseudoinvasion' is a known phenomenon occurring in the gastrointestinal tract that may potentially result in the misdiagnosis of a malignancy, particularly to the uninitiated. Recent papers indicated that similar diagnostic dilemmas occur in the breast and thyroid tissues, usually following a biopsy procedure. In the gastrointestinal tract, the epithelial displacement is thought to result from herniation of the mucosa through defects of the muscularis mucosae and propria secondary to trauma from medical procedures or due to the inherent peristaltic action. We detail an instance where epithelial misplacement in a hamar-tomatous polyp in the ileum affecting a 17-year-old Malay man with Peutz-Jeghers syndrome raised the concern for malignancy. The patient had undergone a subtotal colectomy with extended ileal resection following intussusception. The resected specimen revealed multiple hamartomatous polyps in the small bowel and caecum. On histology, one polyp disclosed the presence of mucosa and mucinous pools in the adipose tissue of the serosal layer which abut the peritoneal surface, mimicking an adenocarcinoma with mucinous features. The criteria and immunohistochemical stains acting as adjuncts for separating ‘pseudoinvasion' occurring in the various types of gastrointestinal polyp including those with dys-plasia from an adenocarcinoma are presented.

Entertis Cystica Profunda in Puetz-Jeghers Syndrome (PJS): A Case of Pseudo-Invasion

Purpose: 20-year-old Caucasian female with PJS with documented STK 11 mosaic mutation, underwent a wireless capsule study to evaluate abdominal pain. The capsule showed a large ileal polyp (Figure 1), biopsy of which showed a hamartoma without dysplasia, consistent with PJS. Attempts to remove the polyp endoscopically was unsuccessful due to its broad base. Patient later underwent a small bowel resection removal of 10 cm of her ileum along with the indurated broad based polyp which measured 1.5 x 1.0 cm. The pathology report determined the polyp to be a benign mucin filled cysts in the bowel wall penetrating through the mucosal layer consistent with enteritis cystica profunda (ECF). ECF are thought to arise after mucosal ulceration or inflammatory damage to the submucosa which allows outgrowth of epithelial element into other layers of the bowel wall. The histological findings of these mucin filled cysts leading the “ pseudoinvasion” (Figure 2) of the epithelial glands extending into the muscularis propia and serosa have been confused for mucin producing adenocarcinomas. Although there is an increased risk of malignant transformation in PJS, when surgical resection is required, a limited resection is recommend to minimize bowel loss. PJS polyps with epithelial misplacement can be confused with invasive cancer but the lack of nuclear atypia, normal appearing small bowel cells and lack of lymphatic invasion all serve to support the hamartomatous origin of a benign PJS polyp. Recognition of pseudo-invasion or enteritis cystica profunda of PJS polyps will prevent unnecessary surgical bowel resections.Figure: Endoscopic view of polyp.Figure: Pseudo-invasion of a Puetz-Jeghers polyp.