Magnification endoscopy in esophageal squamous cell carcinoma: a review of the intrapapillary capillary loop classification

Abstract

Recent developments in image-enhancement technology have enabled clear visualization of the microvascular structure of the esophageal mucosa. In particular, intrapapillary capillary loops (IPCLs) are observed as brown loops on magnification endoscopy with narrow-band imaging (NBI). IPCLs demonstrate characteristic morphological changes according to the structural irregularity of esophageal epithelium and cancer infiltration, summarized in the IPCL classification. In this review, the process from the first endoscopic description of IPCLs to the eventual development of the IPCL classification is described and discussed, particularly focusing on early stage squamous cell carcinoma of the esophagus.

Keywords: Keywords intrapapillary capillary loop classification; endoscopic mucosal resection; endoscopic submucosal dissection; magnification endoscopy; narrow-band imaging.

Figure 1

(A) Squamous cell carcinoma developed on esophageal mucosa with multiple Lugol-voiding area. T1-EP (cancer confined with epithelium) (B) With narrow-band imaging, the cancerous area indicated in “A” appears shiny silver. This phenomenon is called “metallic silver sign” Lugol spraying on esophageal mucosa revealed mixture of stained and unstained area. This is called “leopard-print” pattern, often observed in patients with heavy alcohol use. Between the white arrows a “pink” lesion of squamous cell carcinoma was observed. Pink color sign is a valuable indicator to identify high-from low-grade dysplasia on squamous epithelium

Figure 2

Schematic drawing of magnification endoscopic findings for superficial vascular structure in the squamous esophagus. (Copied from reference 31) Superficial blood vessels in the esophageal mucosa consist of branching vessels which extend in the horizontal plane and exist immediately above the muscularis mucosae. The intra-epithelial papillary capillary loop (IPCL) originates from a branching vessel, and runs perpendicularly in the lamina propria finally reaching the intra-epithelial papilla. The blood vessel, observed under regular non-magnification endoscopy, is the branching vessel. When esophageal squamous mucosa is magnified up to around 100 times, looping vessels (IPCLs) are observed, as shown in Fig. 2, demonstrated as brown loops under narrow-band imaging-enhanced observation

Figure 3

Schematic drawing of typical intrapapillary capillary loop (IPCL) changes from normal to cancerous pattern. (Copied from reference 32) In normal epithelium, IPCL is observed as a smooth running, small-diameter capillary vessel (IPCL Type I). In carcinoma in situ IPCL demonstrates characteristic morphological changes. The abnormal IPCL pattern for m1 lesion (carcinoma in situ) is IPCL Type V-1, exhibiting the following four pattern changes: dilatation, meandering, irregular caliber, and form variation

Figure 4

Narrow-band imaging magnification endoscopic view of normal esophageal mucosa Intrapapillary capillary loop (IPCL) type I Brown loops are observed at the most superficial layer of the image: IPCLs. Behind them a large green vessel network is observed, the branching vessels. Branching vessel spread on horizontal plane just above the musclaris mucosae, and IPCLs runs perpendicularly from branching vessel network.

Figure 5

Original intrapapillary capillary loop (IPCL) pattern classification. (Modified from references 35,36) The IPCL pattern classification includes two sets of diagnostic criteria. IPCL pattern classification from IPCL type I to type V-1 is used for the tissue characterization of flat lesions (red outline). IPCL pattern classification from IPCL type V-1 to type VN reflects cancer infiltration depth (blue outline). IPCL type III corresponds to borderline lesions which potentially include esophagitis or low-grade intraepithelial neoplasia. IPCL type III should be considered for endoscopic follow up. In IPCL type IV, high-grade intraepithelial neoplasia appears, and then further treatment with endoscopic mucosal resection (EMR) / endoscopic submucosal dissection (ESD) is recommended. EMR/ESD for IPCL types V-1 and V-2 should be also considered as they are definite M1 or M2 lesion with no risk of lymph node metastasis. IPCL type V3 corresponds to an M3 lesion, and diagnostic EMR/ESD should be applied as a “complete biopsy” to decide on a final treatment strategy. IPCL type VN corresponds to a “new tumor vessel”, often associated with sm2 invasion with significantly increased risk of lymph node metastasis. Surgical treatment should be recommended.

Figure 6

Intrapapillary capillary loop (IPCL) changes followed by cancer infiltration Vessels involved in cancer tissue demonstrate significant morphological changes according to cancer invasion depth. This illustration is a cross-sectional view of vessels described by the blue outlined box of Fig. 5 (“non-neoplastic” changes are not shown).

Figure 7

Magnification endoscopy in conjunction with narrow-band imaging enhancement of carcinoma in situ Dilated and irregular shape of intrapapillary capillary loops (IPCLs) is observed at top two thirds of image. This pattern is called IPCL-V1. IPCL-V1 includes four major characteristic morphological changes of IPCL: dilation, meandering, irregular caliber, and figure variation.

Figure 8

Narrow-band imaging magnification endoscopy image of intramucosal cancer (M3) Loop-like vessels have already been destroyed in its figure and abnormal vessels are starting to interconnect. Those interconnected vessels spread in horizontal plane. This is typical image of intrapapillary capillary loop (IPCL)-V3. Cancer invasion depth was M3 (muscularis mucosae).

Figure 9

Narrow-band imaging magnification image of “intrapapillary capillary loop (IPCL)-VN” vessel Large white arrows point to large tumor vessel (IPCL-VN). The striking morphological feature is its extra-large diameter. Note the difference of vessel caliber between IPCL-V3 (small white arrow) and VN (large white arrow).