Encapsulated Papillary Carcinoma Membrane Characteristics
Overview
This study focused on encapsulated papillary carcinoma (EPC), a type of breast carcinoma characterized by a thick fibrous capsule-like structure surrounding the tumor, often interpreted as a thickened basement membrane (BM). The primary objective was to investigate the geometric properties of the EPC capsule and determine whether it results from an expansion of the native BM or arises from stromal reactive processes.
To accomplish this, the study examined 100 cases categorized into four groups: EPC, ductal carcinoma in situ (DCIS), normal breast tissue, and invasive tumors. An additional control group included encapsulated papillary thyroid carcinoma (EPTC). The researchers utilized picrosirius red (PSR) staining and polarized microscopy to analyze representative tissue slides. Image analysis software, including ImageJ, CT-FIRE, and Curve align, aided in extracting quantitative data.
The findings indicated several distinctive characteristics of the EPC capsule compared to other groups. In the EPC group, collagen fiber width, straightness, and density were notably increased, while fiber length decreased significantly. The arrangement of collagen fibers within the EPC capsule displayed less alignment and a more perpendicular orientation. Furthermore, this capsule was enriched with disorganized collagen type I fibers (stromal collagen). In terms of thickness, distribution, and fiber organization, the EPC capsule exhibited substantial intracapsular heterogeneity.
Compared to BM-like material in the invasive tumor group, the EPC capsule had a higher density of collagen fibers that were longer, straighter, and better aligned. However, there were no differences in the distribution of collagen types I and III. Interestingly, when compared to EPTC, the EPC and EPTC capsules were largely similar, except that the fibers within the EPC capsule appeared straighter. Notably, both normal ducts and lobules and DCIS BM displayed differences in collagen fiber density, straightness, orientation, and alignment when compared to the EPC capsule.
The study’s findings suggest that the EPC capsule is a reactive process rather than a manifestation of a thickened native BM, as seen in normal and in situ lesions. These observations provide further evidence supporting the notion that EPC is an indolent invasive carcinoma, as implied by the characteristics of its capsule.
Introduction
This study focused on papillary lesions of the breast, particularly encapsulated papillary carcinoma (EPC). These lesions exhibit fibrovascular cores covered by epithelial cells, ranging from benign to malignant. EPC presents as well-circumscribed masses with a capsule-like structure, initially thought to be a thickened basement membrane (BM). This BM typically separates epithelial and myoepithelial cells from surrounding tissue. The study aimed to determine if the EPC capsule represents a reactive process similar to invasive tumors or an expansion of the native BM, resembling some cases of ductal carcinoma in situ (DCIS). The investigation utilized collagen staining techniques to analyze the capsule’s geometric characteristics.
Methods
Inclusion Criteria
- Cases of breast tissue, including normal and neoplastic samples.
- Patients who presented to Nottingham City Hospital, Nottingham, UK between 1999 and 2006.
- Four groups of cases, including encapsulated papillary carcinoma (EPC), ductal carcinoma in situ (DCIS), normal breast tissue, and invasive carcinoma (INV).
- Additional encapsulated papillary thyroid carcinoma (EPTC) cases for comparison.
- Freshly cut, 4-μm thick, full-face tissue sections for analysis.
- Tissue sections stained with picrosirius red (PSR) stain for collagen assessment.
Exclusion Criteria
- Cases not meeting the specified inclusion criteria.
- Tissue sections that were not properly stained with picrosirius red (PSR) for collagen analysis.
- Cases from outside the defined time frame (1999-2006) or location (Nottingham City Hospital, Nottingham, UK).
- Cases not falling into one of the four specified groups (EPC, DCIS, normal breast tissue, INV).
- Inadequate or damaged tissue sections that cannot be accurately analyzed.
- Cases with incomplete or missing clinical information.
Statistical Analysis
Statistical analyses were conducted with a significance threshold set at P<0.05. The analyses were performed using either SPSS version 26 (IBM, Armonk, NY, USA) or GraphPad Prism (Boston, MA, USA). Various statistical tests, including Kruskal–Wallis, one-way analysis of variance (ANOVA), chi-square test, paired T-test, and Wilcoxon signed ranks tests, were applied as appropriate based on the specific context of each analysis. Graphs and tables were generated using GraphPad Prism software. The results are presented as the mean ± standard deviation (SD) unless otherwise specified.
Results
The study found that encapsulated papillary carcinoma (EPC) exhibited a significantly thicker capsule (59.65 ± 18.50 µm) compared to basement membranes (BMs) in normal breast tissue (0.032 ± 0.009 µm) and ductal carcinomas in situ (DCIS) (0.058 ± 0.017 µm). However, there was no significant difference between the BM thickness of DCIS and normal breast tissue. EPC capsules also showed a significantly higher collagen density (53.47 ± 4.27 pixels) compared to both normal breast tissue (18.43 ± 5.06 pixels) and DCIS (25.94 ± 8.02 pixels). The majority of collagen in EPC capsules was collagen type I, whereas normal breast tissue and DCIS BMs contained less collagen type I. EPC capsules had wider, shorter, and straighter collagen fibers compared to normal and DCIS BMs. Moreover, EPC capsules displayed less fiber alignment than normal and DCIS BMs. When compared to invasive tumor BM-like material, EPC capsules had higher collagen density, longer and straighter fibers, but no difference in collagen type content. EPC capsules also showed less fiber alignment compared to invasive tumor BM-like material.
In addition, the study compared EPC capsules to encapsulated papillary thyroid carcinoma (EPTC) capsules and found no significant differences in capsule thickness or collagen density between the two. Both EPC and EPTC capsules were mainly composed of collagen type I and collagen type III. While EPC capsules had straighter fibers, the difference was not significant. Finally, within the EPC group, the outer part of the capsule had higher collagen density compared to the inner part. Both inner and outer parts of the EPC capsule displayed wider, longer, and straighter collagen fibers compared to other groups, and the outer part had a similar fiber width to the invasive group.
These findings suggest that EPC capsules exhibit distinct collagen characteristics, such as thickness, density, fiber composition, and alignment, which differentiate them from normal breast tissue and DCIS. However, they share similarities with EPTC capsules and exhibit variations in collagen characteristics between the inner and outer parts of the capsule.
Conclusion
Papillary lesions of the breast, especially encapsulated papillary carcinoma (EPC), have posed challenges in their categorization as either in situ or invasive disease. This categorization is critical for clinical management decisions. A study examined the characteristics of the basement membrane (BM) and capsule in EPC and compared them with normal breast tissue, ductal carcinoma in situ (DCIS), and invasive breast tumors.
The study found that normal breast tissue exhibited a BM with collagen type III fibers that were thinner, shorter, and more curved. DCIS had BMs similar to normal tissue but denser collagen fibers with less alignment. In contrast, the BM-like material surrounding invasive tumors had a high density of collagen fibers, primarily collagen type I, which were thicker, shorter, straighter, and less aligned.
EPCs presented with a thickened capsule with dense collagen fibers enriched in collagen type I, resembling the BM-like material around invasive tumors. There was marked heterogeneity within EPC capsules, with the outer part exhibiting features more similar to invasive tumors.
The study’s findings support the hypothesis that EPCs are invasive carcinomas with indolent behavior and an expansile growth pattern, rather than in situ lesions with a thickened BM. These characteristics align with other papillary tumors in various organs, which exhibit BM-like material and indolent behavior. The presence of collagen IV and laminin in EPCs was considered insufficient evidence for an in situ diagnosis, as these components can also be found in some invasive cancers.
In summary, EPCs display unique characteristics in their capsule and BM-like material, challenging their categorization as in situ or invasive. The study suggests that EPCs share more similarities with invasive carcinomas and highlights the importance of further investigation into the mechanisms underlying these phenomena in papillary tumors across different organs.
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