Diminutive and Small Colorectal Polyps: The Pathologist s Perspective

Transcription

1 Session IV Diminutive and Small Colorectal Polyps: The Pathologist s Perspective Yun Kyung Kang, M.D., Ph.D. Department of Pathology, Inje University Seoul Paik Hospital, Seoul, Korea Introduction Colonoscopy has become the primary method for colorectal cancer screening effective in detection and removal of adenomatous polyps 1,2 and is increasingly and widely used. 3,4 Accordingly, biopsy and final confirmative diagnosis of endoscopic procedures including polypectomy, mucosal resection and submucosal dissection are growing practices in surgical pathology work areas. 5 Histopathologic diagnosis of colorectal lesions plays a crucial role in patient management 6,7 therefore accurate pathologic examination of colorectal lesions is of paramount importance. The current standard guideline of colonoscopic management of polyps is to retrieve all resected tissue for pathologic assessment. 8 Recently the American Society for Gastrointestinal Endoscopy (ASGE) introduced a resect and discard strategy applied to diminutive colorectal polyps. 9 The 2014 guideline of the European Society of Gastrointestinal Endosdopy (ESGE) suggests that virtual and conventional chromoendoscopy can be used, under strictly controlled conditions, for real time optical diagnosis of diminutive colorectal polyps to replace histopathological diagnosis. 10 These documents were developed from evidence based methodology and expected to have substantial cost saving, however they have a number of limitations. 11,12 They should incorporate the multi society based consensus, most importantly the pathologist s perspective about the diminutive and small colorectal polyps. Classification of colorectal polyps: Histologic type and measurement Recent progress in advanced endoscopic imaging and electronic chromoendoscopy (EC) allows real time endoscopic estimation of the histology of polyps and its main performance is in the differentiation of adenomas from hyperplastic polyps. 11 Pathologically colorectal polyps may arise from mucosal glands, lamina propria or from connective tissue and encompass a wide range of histogenetic origins. They can be neoplastic, hamartomatous, inflammatory or various reactive conditions (Table 1). 13,14 The majority of these are adenomas and hyperplastic polyps, but other polypoid lesions of the mucosa and submucosa are readily detected at the time of colonoscopy. Though the endoscopic diagnosis of all these polyps can be either adenoma or nonadenoma it cannot reliably assess the infrequent but sometimes significant polyp and may distort the occurrence rate of 176 IDEN 2014

2 Table 1. Classification of colorectal polyps 13,14 Epithelial Conventional adenoma Tubular adenoma Tubulovillous adenoma Villous adenoma Flat adenoma Serrated polyp Hyperplastic polyp Sessile serrated adenoma/polyp Mixed polyp Traditional serrated adenoma Polypoid adenocarcinoma Inflammatory Mucosal prolapse associated polyp Inflammatory pseudopolyp Polypoid granulation tissue Infection associated polyp Hamartomatous Peutz Jehgers polyp Juvenile polyp Cowden syndrome Cronkite Canada syndrome Endocrine Well differentiated endocrine tumor/carcinoid Stromal Inflammatory fibroid polyp Fibroblastic polyp/perineurinoma Schwann cell hamartoma Nerve sheath tumor Ganglioneuroma Leiomyoma of muscularis mucosae Lipoma Lipohyperplasia of ileo caecal valve Gastrointestinal stromal tumor Neurofibroma Granular cell tumor Lymphoid Benign lymphoid polyp Prominent lymphoid follicle/rectal tonsil Lymphomatous polyposis Other Prominent mucosal fold Everted diverticulum Elastotic (elastofibromatous) polyp Heterotopic gastric mucosa Endometriosis Mucosal xanthoma Melanoma/Clear cell sarcoma Metastasis Table 2. Molecular features of serrated polyps 13 Molecular changes (%) BRAF mutation KRAS mutation CIMP high MSI high Hyperplastic polyp Goblet cell type 20 ~ ~ ~ 15 Microvesicular type 29 ~ ~ Sessile serrated adenoma/polyp 78 ~ 90 7 ~ 8 75 ~ 76 Mixed polyp 40 ~ ~ 50 Traditional serrated adenoma 36 ~ 77 8 ~ ~ 51 CIMP, DNA CpG island mathylation phenotype; MSI, microsatellite instability. each polyp with diverse histologic feature. Serrated polyps (SPs) have emerged as precursor lesions in CpG island methylation phenotype (CIMP) colorectal carcinogenesis known as a serrated neoplasia pathway. 15,16 This group of polyps comprises hyperplastic polyp (HP), sessile serrated adenoma/polyp (SSA/SSP), mixed polyp (MP) and traditional serrated adenoma (TSA). SPs including HPs frequently have clonal genetic aberrations including BRAF mutation, KRAS mutation and CIMP, and are in fact neoplastic (Table 2). 13 Classification of SPs is complicated by morphologic subtypes and overlapping features such as lack or presence of varying degrees of dysplasia. 17 The clinical sig- IDEN

3 IDEN 2014 nificance and histologic criteria of these polyps as with searching for the diagnostic biomarkers are currently under investigation It is more important to make standardized diagnostic criteria and understand the behavior of SPs through communication between clinicians and pathologists rather than discard small sized SPs. The size of the colorectal polyp (especially the adenoma) is important in terms of their relation to the likelihood of malignant transformation, and to the risk of synchronous and metachronous adenomas and carcinomas. 13 It is one of the major factors determining the risk groups of adenomas by 10mm criteria. 6,7 Small (< 10 mm) polyps were further divided into diminutive and small polyps by 5mm dimensions. 13 The resect and discard strategy is based on the data showing very low prevalence (< 2%) of advanced histology in diminutive polyps. 21 However endoscopic measurement of polyp size has been found to be inconsistent in a substantial cases and differ depending on the modality used to make the measurement. 22,23 Measurement by pathologists would be a preferable alternative however the same problem does exist. 24,25 Accurate polyp size measurement is important as it is the major judgment criteria determining the resect and discard policy but it could be one of the challenging problems in developing official adoption and legal standards of the strategy. Pathologic diagnosis and information: Practical and academic aspect Surgical pathology has long been the basis of medical practice by providing critical and definite diagnosis. Recent medical advances have broadened the diagnostic technologies and management options the most effective of which are prevention, early detection and complete cure of cancer. This brought about a need of a more elaborate tissue diagnosis and an additional consensus for the diagnostic terminology and histopathologic grading of precancerous lesions in almost every human organs, such as colorectal adenoma. 26 Pathologists should be aware of these facts clearly and constantly strive to develop more applicable consensus criteria, increase the inter observer agreement by consensus meeting and multicenter study and communicate with clinicians constantly, both informally and through interdepartmental conferences. 5,27,28 In terms of the public health system, pathology reports are essential supporting confirmatory information about the relevant performance of the medical procedure done on the patient and determining disease code for the national and private health insurance registration. 29,30 Pathologic examination, diagnosis and storage of all resected human tissue can provide legal authentication of the patient managemet. Even a small Human tissue, like a diminutive colorectal polyp, harbors vast amount of molecular information that may be crucial in the future medical issue nonetheless looks trivial at the present time. Pathologists can integrate both information from the traditional morphologic examination and the newer techniques increasingly applicable to the routinely processed tissue specimens. 31 The discard policy of diminutive colorectal polyps may interfere with next generation research more beneficial in the field of medicine. Resect and discard: Cost effectivness The major potential advantage of the resect and discard paradigm for diminutive polyps is a reduction in costs for histopathologic examination. 9,32 This may be quite real in the United States however such benefit cannot be estimated in other countries having different medical reimbursement system. For example in Korea, we have a generally undervalued reimbursement system for routine histopathology services and there has been no 178 IDEN 2014

4 Table 3. Current classification of the pathology services by the National Health Insurance system in Korea 34 Categories Codes RBRVS Cost (KRW/USD)* Biopsy C pieces ,426/18.71 C pieces ,179/25.22 C pieces ,932/31.73 C pieces ,529/39.05 C pieces or more ,283/45.55 Resected C5916 No of blocks ,676/29.55 Specimen** C5917 No of blocks ,815/42.21 Malignant tumor C5500 No of blocks ,914/51.94 without LN C5504 No of blocks 16 1, ,468/72.70 Malignant tumor C5918 No of blocks 20 1, ,767/71.07 with LN C5919 No of blocks 21 1, ,241/ Histopathologic C5505 with LN 1, ,121/ Mapping tumor C5508 without LN 1, ,647/74.80 RBRVS, resource based relative value score; No, number; LN, lymph node; KRW, Korean Won; USD, United States Dollar *Cost by health insurance reimbursement in year 2014 **Category for histopathologic examination of colorectal polypectomy specimen cost effectiveness analysis of the strategy. The classification of pathology services by the National Health Insurance system in Korea consists of 13 categories and the polypectomy is coded as C5916 or C5917 based on the number of resection or paraffin blocks (Table 3). 33,34 Following the definition, resected polyps (from single organ) of 6 or less in number are considered a single unit of code C5916 and polyps of 7 or more (unlimitedly) are considered a single unit of code C5917, without any overlap. It is completely different from the principles of anatomic pathology coding by American Medical Association that defines individual specimen as a unit of code and the actual fee is determined by multiplying the number of polyps and the price of the corresponding code. 35 Moreover the resource based relative value score (RBRVS) of pathology services in Korea is undervalued compared to that of the United States. 34 It is less likely that forgoing the pathologic examination of diminutive polyps has much economic benefit in Korea. Instead we cannot preclude the resect and discard strategy may bring about increasing medical cost caused by incorrect determination of the surveillance intervals. Conclusions Like many other paradigms in human activity the medical technology and strategy are continuously and rapidly evolving. Recently the histology of colorectal polyp is assessed by advanced colonoscopic imaging with a highly confident prediction rate, particularly done by expert endoscopist. However this new technique cannot provide information and responsibility beyond that provided by the histopathologic examination. In fact the highly confident endoscopic estimation of polyp type is a valuable one which can provide symbiosis of gastroenterologists and pathologists to make a more evident diagnosis and management of patient with colorectal polyp. In the pathologist s point of view the power of microscopic analysis and the amount of information that can be obtained even from a colorectal diminutive polyp represent a real acquisition and there is no available IDEN

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