[Guidelines for the management of malignant colo-rectal polyps (pTis and pT1) treated by endoscopic resection]. / Protocole d'examen d'un polype colorectal pTis/pT1 traité par exérèse endoscopique.

The therapeutic management of malignant colorectal polyp with endoscopic resection is mainly based on specific histopathological criteria. The quality of these criteria is strongly linked to the management of the endoscopic specimen. The French Pathology Society drafted a standardized pathological report with guidelines for the macroscopic management of the endoscopic specimen and explanatory notes for each histopathological criteria. These guidelines are based on the TNM AJCC/UICC classification, 8th edition and the WHO 2010 classification of colorectal tumors, the recommendations of the French Society of Digestive Endoscopy, the synthesis of the literature and on international consensus for prognostic criteria. The pathological report of a malignant colorectal polyp must clearly mention: the histological type and the size of the polyp, the pT stage and the following five prognostic criteria: the value of the resection margins, the level of tumor invasion into the submucosa, the grade of the tumor, the absence or presence of vascular emboli and of tumor budding.

Identification of Feeder Vessels in Ocular Surface Neoplasia Using Indocyanine Green Angiography.

PURPOSE: To evaluate indocyanine green angiography (ICGA) for the identification and characterization of afferent (feeding) and efferent (draining) vessels in patients with ocular surface neoplasia. MATERIALS AND METHODS: Consecutive patients with biopsy-proven benign, pre-invasive, or invasive ocular surface tumors of the bulbar conjunctiva were included. Patients underwent anterior segment optical coherence tomography, ICGA, and color photography for the evaluation of the thickness, location, number, and diameter of afferent and efferent vessels of the lesions. RESULTS: Twenty-two eyes of 22 patients with papillomas (n = 4), intra-epithelial neoplasia lesion (n = 2) in situ or invasive carcinomas (n = 6), nevus (n = 5), conjunctival melanocytic intra-epithelial neoplasia lesion (n = 1), and in situ or invasive melanomas (n = 4) were investigated. Afferent (feeder) vessels were identified in all lesions. There were fewer afferent (3.1 ± 1.6) than efferent (7.5 ± 3.5) vessels per lesion (p < 0.001) and the mean diameter was smaller for afferent (101 ± 62 µm, 28-281) than efferent vessels (137 ± 51 µm, 31-652; p = 0.017). The number of afferent and efferent vessels was associated with the thickness of the lesion (p = 0.037, p < 0.01). Lesion filling times differed between benign and invasive or pre-invasive lesions (p = 0.018). CONCLUSIONS: ICGA is a useful adjunctive in vivo imaging method for the assessment of the vasculature in patients with suspected ocular surface neoplasia.

Topical Bevacizumab for the Treatment of Ocular Surface Squamous Neoplasia.

PURPOSE: To determine the efficacy and safety of topical bevacizumab treatment in patients with ocular surface squamous neoplasia (OSSN). METHODS: Six eyes of 6 patients with primary OSSN confirmed by impression cytology received topical 5 mg/mL bevacizumab 4 times daily for a period of 8 weeks. Patients were evaluated in 2-week intervals. Digital photography images were obtained at each visit and changes in the size of the lesions were analyzed by image analysis software. RESULTS: The mean age of the patients was 66 ± 13 (± SD) years. Four tumors were nasal in origin and 2 tumors were temporal. The mean reduction observed in the lesion area was 43% ± 24.2% (range, 20%-71%) in the first month and 68% ± 29.7% (range, 42%-100%) in the second month when compared with the baseline area. Four patients required tumor excision at the end of the treatment period. Surgical treatment was not necessary in 2 patients due to complete disappearance of the tumor, which was confirmed by impression cytology. The visual acuity was stable in all patients and no systemic or visual side effects were observed during the study period. CONCLUSIONS: Topical bevacizumab is effective as a neoadjuvant therapy combined with surgical excision for the treatment of OSSN. Topical bevacizumab may be used before surgery to decrease the size of the excision. Excision may be unnecessary in responsive patients.

Use of topical bevacizumab for conjunctival intraepithelial neoplasia.

PURPOSE: To report our experience in the treatment of intraepithelial neoplasia of the conjunctiva using topical bevacizumab. METHODS: Ten eyes of 10 patients with conjunctival neoplasia received 25 mg/mL bevacizumab topically. Changes in the lesions were documented weekly using digital photography. After topical treatment, excisional biopsy was performed. RESULTS: The mean age of the patients was 60.5 ± 12 (33-77) years. The mean duration of topical treatment was 7.8 ± 1.3 (5-14) weeks. The size and vascularity of the tumors reduced weekly. All patients underwent excisional biopsy, cryotherapy, and amnion membrane transplantation. The histopathologic diagnosis of the lesions was carcinoma in situ. No recurrence was observed during the follow-up of patients for 6 months. CONCLUSIONS: Topical bevacizumab is an effective treatment to reduce the tumor size before surgery and may be a good alternative for adjuvant therapy of conjunctival neoplasms.

Repression of miR-126 and upregulation of adrenomedullin in the stromal endothelium by cancer-stromal cross talks confers angiogenesis of cervical cancer.

miR-126 is an endothelial-specific microRNA essential for maintaining vessel integrity during development. Its role of tumor angiogenesis in cancer stroma is unclear. This study investigated the temporal and spatial expression and the role of miR-126 in the course of cervical carcinogenesis. miR-126 was found to be mainly expressed in the stromal endothelium of the uterine cervix. This downregulation was recapitulated in a cell coculture model, wherein cross talk of cervical cancer cells and fibroblasts induced a downregulation of miR-126 in human umbilical vein endothelial cells, with consequent increase of tube formation. Coinjection of cancer-associated fibroblasts of human cervix enhanced tumorigenesis of cervical cancer cells, with an increase of microvessel density and dye retention in the tumor vasculature. In association with angiogenesis, host-originated miR-126 in these xenograft tumors was progressively downregulated, whereas supplement of the miR-126 precursor in the coinjection suppressed angiogenesis and tumor growth. A proangiogenic gene adrenomedullin (ADM), which was found to be upregulated in the stroma of cervical cancer and which localized mainly in the blood and lymphatic vessels, was identified as a target of inhibition by miR-126 at the carcinoma in situ-to-invasion stage. The study suggests a cancer stroma cross talk induced repression of miR-126 and upregulation of ADM, and probably other proangiogenic factors, to facilitate angiogenesis and invasion growth of cervical cancer.

Subconjunctival bevacizumab injection for ocular surface squamous neoplasia.

PURPOSE: To determine the efficacy and safety of perilesional/subconjunctival bevacizumab injections in the management of ocular surface squamous neoplasia (OSSN). METHODS: Ten eyes of 10 patients with an OSSN diagnosis confirmed by impression cytology received 2 perilesional/subconjunctival injections of bevacizumab at a 2-week interval. Patients were evaluated for 3 months, during which time, changes in the lesions were documented using digital photography. After this period, excisional biopsy of the remaining tumor and cryotherapy of the conjunctival borders were performed if deemed necessary. RESULTS: The mean age of the patients was 65 ± 12 years (± SD). All of the tumors were nasal in origin and had varying degrees of vascularization. The mean lesion area before treatment was 16 ± 6.9 mm2. Two weeks after the first injection, the mean reduction observed in the tumor area was 25% ± 5.65% and ranged from 17% to 33% (P = 0.001). Two weeks after the second injection, the mean tumor area was further decreased (42% ± 33%, ranging from 15% to 100%, P = 0.049). Corneal extension of the tumor was not affected significantly in 8 of the eyes with concomitant conjunctival and corneal involvement. Complete disappearance of the tumor was demonstrated by impression cytology and occurred in 2 cases involving lesions clinically confined to the conjunctiva. No systemic or ocular side effects occurred during the study period. CONCLUSIONS: Perilesional/subconjunctival injections of bevacizumab decrease the size and vascularity of OSSN and may be curative in lesions limited to the conjunctiva. However, this treatment has no significant effect on the corneal extension of OSSN.

Intraepithelially entrapped blood vessels in oral carcinoma in-situ.

It can be difficult to make a certain diagnosis in case of an oral borderline malignant lesion on hematoxylin-eosin-stained sections only. Furthermore, assessment of surgical margins of borderline lesions is difficult with the naked eye. We set out to determine the topographical distribution of capillary blood vessels within the epithelial zone and to assess its use as an aid for histopathological diagnosis and a framework for clinical assessment of lesional margins using optical techniques, such as narrow-band imaging (NBI) endoscopy. Capillary blood vessels entrapped in the epithelial compartment, which we have designated as intraepithelially entrapped blood vessels (IEBVs), were examined for their frequency, location, and shape in normal mucosa, dysplasia, and carcinoma in-situ (CIS) of the tongue using immunohistochemistry for CD31 and type IV collagen. When counted per unit length of epithelial surface, IEBVs increased in number significantly in CIS (5.6 ± 2.8), which was two times more than in normal (1.9 ± 1.6) and dysplastic (2.4 ± 1.5) epithelia. In addition, IEBVs in CIS had compressed shapes with occasional obstruction or collapse with hemorrhage and were arranged perpendicular to and extending up to the epithelial surface. These characteristic IEBVs in CIS were considered to be generated by complex expansion of rete ridges due to carcinoma cell proliferation within the limited epithelial space determined by the basement membrane. The recognition of IEBVs was helpful in the differential diagnosis of oral CIS, and the present data provide a valuable frame of reference for detecting oral CIS areas using such NBI-based optical devices.

Predictors of disease progression in ductal carcinoma in situ of the breast and vascular patterns.

Breast carcinoma-induced angiogenesis helps meet growing metabolic needs of tumors and progressively increases with malignant transformation of benign ducts to ductal carcinoma in situ (DCIS) and ductal carcinoma in situ to invasive carcinoma. There are conflicting data regarding the difference in angiogenesis in low-, intermediate-, and high-grade ductal carcinoma in situ. If angiogenesis is related to ductal carcinoma in situ progression, the types of ductal carcinoma in situ with more aggressive biologic potential would have different vascular patterns than the less aggressive ones. In this study, we classified 51 cases of ductal carcinoma in situ as low (10-20 years to progression to invasive carcinoma), moderate, or high aggressive (2-5 years to progression to invasive carcinoma), based on criteria outlined by Tsikitis and Chung (Am J Clin Oncol 2006; 29:305), which takes into account nuclear grade, mitotic rate, Ki-67, Her2Neu, P53, estrogen, and progesterone receptor expression. We correlated these 3 groups of ductal carcinoma in situ with the extent of periductal and stromal vascularity and the presence and type of vascular breaks. No association of aggressive biologic behavior of ductal carcinoma in situ with any vascular pattern was found. Moreover, no correlation was found between vascular patterns and classifiers of aggressiveness, microvascular density, or outcome (local recurrence, invasive carcinoma, or metastatic disease). To validate our cohort, we confirmed expected correlations of all measured parameters of aggressiveness by correlating them with each other. In summary, vascular patterns in ductal carcinoma in situ do not correlate with the predictors of aggressive behavior, suggesting that the biologic potential of ductal carcinoma in situ is independent of angiogenesis.

Different expression patterns of CEACAM1 and its impacts on angiogenesis in gastric nonneoplastic and neoplastic lesions.

OBJECTIVE: This study was designed to investigate the expression patterns of CEACAM1 and its relationship with angiogenesis in nonneoplastic and neoplastic gastric lesions. METHODS: CEACAM1 and TGF-ß expression was detected by immunohistochemical staining and dual-labeling immunohistochemical staining in neoplastic and nonneoplastic lesions. MVD-CD31 and MVD-CD105 were counted in CEACAM1-positive areas by dual-labeling immunohistochemistry. RESULTS: There was no expression of CEACAM1 in normal gastric mucosa. In IM and GIN, CEACAM1 was mainly expressed with membranous pattern. CEACAM1 was expressed with membranous pattern in well-differentiated adenocarcinoma, with cytoplasmic pattern in poorly differentiated adenocarcinoma, and with cytoplasmic and membranous pattern mixed together in intermediately adenocarcinoma. The expression patterns of CEACAM1 showed a significant difference (P < 0.05) in nonneoplastic and neoplastic lesions. Coexpression of CEACAM1 and TGF-ß was elevated and significantly different from nonneoplastic to neoplastic lesions (P < 0.05). Moreover, CEACAM1 and TGF-ß coexpression were related to carcinoma progression (r = 0.35; P < 0.05). MVD-CD31 and MVD-CD105 showed significant differences from nonneoplastic to neoplastic lesions (P < 0.05). CONCLUSIONS: CEACAM1 has different expression patterns in nonneoplastic and neoplastic lesions. The coexpression of CEACAM1 and TGF-ß increased from nonneoplastic to neoplastic lesions and may be related with tumor progression via promoting tumorous angiogenesis.

Comparison of magnifying chromoendoscopy and narrow-band imaging in estimation of early colorectal cancer invasion depth: a pilot study.

BACKGROUND: Several previous studies have identified narrow-band imaging (NBI) with magnification as being useful in evaluating early colorectal cancer invasion depth, but comparative diagnostic accuracy of invasion depth between pit pattern analysis using magnifying chromoendoscopy and NBI remains unclear. The aim of this retrospective study was to compare NBI and pit pattern analysis using magnifying chromoendoscopy in estimating early colorectal cancer invasion depth and to assess interobserver agreement. PATIENTS AND METHODS: We analyzed a total of 72 early colorectal cancers in 72 patients fulfilling the inclusion criteria. Each lesion image was subsequently reviewed by two experienced colonoscopists (A, B) and then classified clinically based on invasive/non-invasive pattern and Sano's capillary pattern classification with a five-point scale of confidence. RESULTS: In terms of diagnostic accuracy with confidence for A and B, the areas under the receiver operating characteristics curve were 0.84 and 0.81 for pit pattern analysis and 0.82 and 0.79 for NBI, respectively. Interobserver agreement for the diagnosis of submucosal deep (>1000 µm) invasion was evaluated for both modalities and indicated substantial agreement with pit pattern analysis (κ = 0.63) and moderate agreement with NBI (κ = 0.44). CONCLUSION: Estimating invasion depth of early colorectal cancer using NBI appeared to have been comparable to pit pattern analysis, but there was greater interobserver variability using NBI.

Longitudinal investigation of permeability and distribution of macromolecules in mouse malignant transformation using PET.

PURPOSE: We apply positron emission tomography (PET) to elucidate changes in nanocarrier extravasation during the transition from premalignant to malignant cancer, providing insight into the use of imaging to characterize early cancerous lesions and the utility of nanoparticles in early disease. EXPERIMENTAL DESIGN: Albumin and liposomes were labeled with (64)Cu (half-life 12.7 hours), and longitudinal PET and CT imaging studies were conducted in a mouse model of ductal carcinoma in situ. A pharmacokinetic model was applied to estimate the tumor vascular volume and permeability. RESULTS: From early time points characterized by disseminated hyperproliferation, the enhanced vascular permeability facilitated lesion detection. During disease progression, the vascular volume fraction increased 1.6-fold and the apparent vascular permeability to albumin and liposomes increased ∼2.5-fold to 6.6 × 10(-8) and 1.3 × 10(-8) cm/s, respectively, with the accumulation of albumin increasing earlier in the disease process. In the malignant tumor, both tracers reached similar mean intratumoral concentrations of ∼6% ID/cc but the distribution of liposomes was more heterogeneous, ranging from 1% to 18% ID/cc compared with 1% to 9% ID/cc for albumin. The tumor-to-muscle ratio was 17.9 ± 8.1 and 7.1 ± 0.5 for liposomes and albumin, respectively, indicating a more specific delivery of liposomes than with albumin. CONCLUSIONS: PET imaging of radiolabeled particles, validated by confocal imaging and histology, detected the transition from premalignant to malignant lesions and effectively quantified the associated changes in vascular permeability.

Use of narrow band imaging guidance in the management of oral erythroplakia.

Erythroplakia is an epithelial lesion that holds the highest risk of showing severe dysplasia or microinvasive carcinoma. The gold standard treatment is total excision to obtain a complete histopathological diagnosis. Traditionally this has been done by illumination of the lesion with white light, and resection with adequate margins. The difficulty with erythroplakia is that margins can be hard to delineate precisely, and even severe dysplasia can be seen with only subtle changes in the surface mucosa. Narrow band imaging is a novel technique that enhances the diagnostic potential of endoscopy. It highlights abnormalities in the superficial vasculature, which means that lesions such as oral erythroplakia can be identified more easily. We report its use in the identification of the full extent of lesions, and show its intraoperative advantages in obtaining resection margins free from disease.

Microvascular irregularities are associated with composition of squamous epithelial lesions and correlate with subepithelial invasion of superficial-type pharyngeal squamous cell carcinoma.

AIMS: Superficial squamous epithelial lesions of the pharynx are increasingly recognized by architectural changes in the intraepithelial papillary capillary loop (IPCL) assessed by narrow-band imaging (NBI). The aim was to explore the histology of squamous epithelial precursor lesions and superficial-type pharyngeal squamous cell carcinoma (STPSCC), including squamous cell carcinoma (SCC) in situ and early invasive SCC, by focusing on microvascular irregularities to investigate the composition of those lesions and to explore the pathological characteristics of STPSCCs. METHODS AND RESULTS: Several pathological factors including thickness of intraepithelial squamous cell carcinoma (IESCC) and tumour thickness and microvascular density (MVD) were examined in 104 STPSCCs from 69 patients. The results show that architectural change of IPCL was recognized in precursor lesions in parallel with architectural disturbance and cytological atypia for criteria of diagnosing dysplasia. In 104 STPSCCs, the MVD of IESCC was correlated with the thickness of IESCC (P = 0.0115). Moreover, invasive SCC showed significantly higher MVD of IESCC (P = 0.0078) and there was significant correlation between the thickness of IESCC and subepithelial invasion (P < 0.0001). CONCLUSIONS: Microvascular irregularities are an important pathological factor in carcinogenesis and early invasiveness of SCC of the pharynx.

[Heterogeneity of angioarchitecture and their hemodynamic changes in benign and malignant breast tumors].

OBJECTIVE: To explore the differences between the angioarchitecture, hemodynamics, ultrastructure of neovasculr endothelial cells, and vascular distribution in different perfusion regions in benign and malignant breast tumors. METHODS: 30 cases of breast carcinoma (33 lesions) and 30 cases of breast fibroadenoma (34 lesions) were examined by contrast enhanced microvascular imaging (MVI), and perfusion indexes were collected both inside and at the margin of each focus according to time-intensity quantitative analysis, including peak intensity (PI), area under the curve (AUC), time to peak (TTP) and wash-out time (WOT). The ultrastructure of neovascular endothelial cells was examined by transmission electron microscopy. The expression of CD34, VEGF, Flk-1/KDR in both two groups were detected by immuhistochemistry. RESULTS: Significant differences were found between the two groups characterized with filling defect, vascular distortion, dilatation and uneven enhancement. Most of the curves of malignant group (87.9%, 29/33) ascended rapidly and dropped slowly while those of the benign group (79.4%, 27/34) ascended slowly and dropped rapidly. The AUC and WOT of malignant tumor group were significantly higher than those of benign group, while the PI and TTP had statistically no significant difference. In the malignant tumor group, PI, AUC and WOT collected from the margin of foci were significantly different from those collected inside the foci, however, there was no significant difference in the benign group. The margin of foci was characterized with dilated and distorted vessels, and the center of the foci was occupied by narrow or occluded blood vessels, sometimes with contracted endothelial cells and pericytes. Abundant microvascular areas located at the margin of foci. The ultrastructure of endothelial cells in the newly formed blood vessels of malignant group showed strong ability to divide, which was different from normal endothelium cells. CONCLUSION: The perfusion pattern, mode of time-intensity curve, mean perfusion parameter and variation of regional perfusion parameters provide a valuable diagnostic basis in distinguishing benign and malignant breast tumors. The density, morphology, distribution, structure and function of newly formed microvessels in tumor foci are also crucial factors when tumors are assessed by imaging examination.

Narrow band imaging in the diagnosis of intra-epithelial and invasive laryngeal squamous cell carcinoma: a preliminary report of two cases.

Narrow band imaging (NBI) is a novel optical technique that enhances the diagnostic capability of the gastrointestinal endoscope (GIE) by illuminating the intraepithelial papillary capillary loop (IPCL) using narrow bandwidth filters in a red-green-blue sequential illumination system (CV-260SL processor and CLV-260SL light source, Olympus Optical Co. Ltd, Tokyo, Japan). The NBI filter sets (415 nm and 540 nm) are selected to obtain fine images of the microvascular structure. Because 415 nm is the hemoglobin absorption band, capillaries on the mucosal surface can be seen most clearly at this wavelength. NBI is able to represent more clearly both capillary patterns and the boundary between different types of tissue, which are necessary for diagnosing a tumor in its early stage (Gono K, Yamazaki K, Doguchi N, Nonami T, Obi T, Yamaguchi M, et al. Endoscopic observation of tissue by narrow band illumination. Opt Rev 2003;10:211-215, Gono K, Obi T, Yamaguchi M, Ohyama N, Machida H, Sano Y, et al. Appearance of enhanced tissue feature in narrow-band endoscopic imaging. J Biomed Opt 2004;9:568-577). We present two patients with laryngeal squamous cell carcinoma in whom the spread and the depth of invasion was evaluated with transnasal GIE equipped with NBI. Based on our results, the vascular neoplastic changes of carcinoma in situ of the larynx could be similar to carcinoma in situ of the esophagus.

Whole-breast volume perfusion images using 256-row multislice computed tomography: visualization of lesions with ductal spread.

BACKGROUND: The aim of this study was to apply perfusion techniques to breast tumors using a prototype 256-row multislice computed tomography (CT) scanner (which allows a wide range of 128 mm to be scanned and can provide whole-breast perfusion maps without any dead angles) to improve contrast and assess the possibility of precisely depicting the extent of breast cancer. PATIENTS AND METHODS: The study group included seven patients with breast cancer who were scheduled to undergo radical surgery and radiotherapy. Dynamic scanning was performed using a 256-row multislice CT scanner during normal respiration. Volume perfusion images of the entire breast were obtained using the maximum slope method. Perfusion map images and early-phase breast CT images at 54 s were compared by means of pathological examination. RESULTS: All breast cancers could be distinguished from normal mammary glands based on the perfusion value. The extent of cancer depicted in perfusion images showed excellent agreement with the pathology findings for invasive ductal carcinoma and ductal carcinoma in situ. In three patients, all ductal spread, parts of which were not visualized by early-phase CT, were depicted in volume perfusion images. Simulation analysis suggested that perfusion maps could be generated with fewer scanning points. CONCLUSION: The results of the present study suggest that volume perfusion imaging may be useful for depicting the extent of breast cancer, with excellent sensitivity. Further research is needed to determine the clinical relevance of these findings.

Angiogenesis in preinvasive, early invasive bronchial lesions and micropapillomatosis and correlation with EGFR expression.

AIMS: To study the association between morphological changes of the bronchial epithelium and its angiogenic status evaluated by microvessel count (MVC), in order to gain a better understanding of bronchial carcinogenesis. Also, to correlate MVC with epidermal growth factor receptor (EGFR) expression. METHODS AND RESULTS: Eighty-three biopsy specimens were assessed for MVC: four normal bronchial epithelia, 23 hyperplasias, 26 metaplasias, two mild dysplasias, five moderate dysplasias, nine severe dysplasias, three carcinomas in situ, six early invasive squamous cell carcinomas (EIC) and five cases of micropapillomatosis. We observed a statistically significant difference in terms of MVC between EIC and all other subgroups and between micropapillomatosis and all other subgroups. There was also a statistically significant difference between micropapillomatosis and EIC. We did not observe any difference in MVC between normal mucosa, metaplasias, hyperplasias, dysplasias or carcinoma in situ. EGFR expression was higher in severe dysplasia, carcinoma in situ and EIC, whereas it was very low in micropapillomatosis. A statistically significant difference was observed in the expression profile of EGFR vs. MVC. EGFR expression was increased in severe dysplasia, whereas an increase in MVC occurred only in EIC. CONCLUSION: During bronchial carcinogenesis, except for micropapillomatosis, EGFR expression appears to be a prerequisite for neoangiogenesis in bronchial carcinogenesis.

Intraductal low papillary histological pattern of carcinoma component shows intraductal spread in invasive carcinoma of the pancreas.

BACKGROUND/PURPOSE: We attempted to discriminate between carcinoma in situ (CIS) and the intraductal invasion/cancerization of invasive ductal carcinoma (IDC) of the pancreas, by comparing the histological patterns of the intraductal components and those of venous invasion. METHODS: Specimens from 30 patients with IDC were examined histopathologically. Intraductal components and blood vessel invasion in IDC were assessed in specimens stained with hematoxylin & eosin and elastica van Gieson (EVG). RESULTS: Intraductal components of IDC were found in 28 of the 30 cases of IDC, in 261 ducts, and in 2.3 ducts per one section of one case, on average. The intraductal components of IDC were classified into three histological patterns, as follows: low papillary (including flat), tubular (including solid and cribriform), and mixed (low papillary plus tubular). The incidences of the low papillary, tubular, and mixed patterns in the 261 ducts, were 39% (102 ducts), 56% (145 ducts), and 5% (14 ducts), respectively. The histological pattern of venous invasion was tubular in all but 1 of the 26 cases, and this 1 case showed low papillary patterns as well as a tubular pattern. CONCLUSIONS: A tubular pattern of intraductal components in IDC of the pancreas indicates intraductal invasion, while a low papillary pattern indicates CIS or carcinoma in another location to which it has spread.