Pure Invasive Micropapillary Carcinoma Research Articles

The differences between pure and mixed invasive micropapillary breast cancer: the epithelial-mesenchymal transition molecules and prognosis.

Invasive micropapillary carcinoma (IMPC) of the breast is known for its high metastatic potential, but the definition of pure and mixed IMPC remains unclear. This retrospective cohort study aims to investigate the prognostic significance of the micropapillary component ratio and the expression of critical molecules of epithelial-mesenchymal transition (EMT), including E-cadherin (E-cad), N-cadherin (N-cad), CD44s, and β-catenin (β-cat), in distinguishing between pure and mixed IMPCs. We analyzed 100 cases of locally advanced IMPC between 2000 and 2018 and excluded patients who received neoadjuvant chemotherapy. Pure IMPC was defined as having a micropapillary component of over 90%. A comprehensive recording of prognostic parameters was conducted. The IMPC areas were analyzed using the immunohistochemical (IHC) staining method on the microarray set for pure and mixed IMPC patients. Pearson's chi-square, Fisher's exact tests, Kaplan-Meier analysis, and Cox proportional hazards analysis were employed. The comparative survival analysis of the entire group, based on overall survival (OS) and disease-free survival (DFS), revealed no significant difference between the pure and mixed groups (P = 0.480, HR = 1.474 [0.502-4.325] and P = 0.390, HR = 1.587 [0.550-4.640], respectively). However, in the pure IMPC group, certain factors were found to be associated with a higher risk of short survival. These factors included skin involvement (P = 0.050), pT3&4 category (P = 0.006), a ratio of intraductal component (> 5%) (P = 0.032), and high-level expression of N-cad (P = 0.020). Notably, none of the risk factors identified for short OS in pure IMPC cases were observed as significant risks in mixed cases and vice versa. Furthermore, N-cad was identified as a poor prognostic marker for OS in pure IMPCs (P = 0.002). The selection of a 90% ratio for classifying pure IMPCs revealed significant differences in certain molecular and prognostic parameters between pure and mixed groups. Notably, the involvement of N-cadherin in the epithelial-mesenchymal transition (EMT) process provided crucial insights for predicting OS and DFS while also distinguishing between the two groups. These findings strongly support the notion that the pure IMPC subgroup represents a distinct entity characterized by unique molecular characteristics and behavioral patterns.

Correlation Analysis of Digital Mammography, Ultrasonography, and Pathologic Features in Pure Invasive Micropapillary Carcinoma of the Breast (PIMPC).

This study determined the digital mammography and ultrasonography imaging features of pure invasive micropapillary carcinoma of the breast (PIMPC) and the correlation with pathologic features. Nineteen patients diagnosed with PIMPC at Yantaishan Hospital from October 2015 to February 2022 were included in the study group. Forty patients with breast masses diagnosed as nonspecific invasive ductal carcinoma of the breast (NIDC) from July to December 2021 were included in the control group. Digital mammography and ultrasonography features were compared between the two groups. Patients with PIMPC had a younger age profile compared to patients with NIDC (P=0.017). Moreover, PIMPC masses were smaller than NIDC masses (P=0.040). Imaging features analysis revealed significant differences in age groups (<45 years: χ²=5.971, P=0.044) and the presence of spiculations or the crab claw sign (χ²=8.583, P=0.004) between patients with PIMPC and NIDC. However, there were no statistically significant differences in the presence of calcifications, blood flow grading, pathologic molecular subtypes between the study and control groups. The Ki-67 proliferative index (χ²=1.052, P=0.389), vascular invasion (χ²=2.263, P=0.197), and lymph node metastasis (χ²=1.968, P=0.386) showed no significant differences between PIMPC and NIDC patients. PIMPC imaging features show specificity, such as tiny breast masses, spiculated edges, or crab claw-like patterns, and malignant signs appeared when the lesion was <2 cm in diameter. PIMPC mainly occurs in middle-aged women 45-59 y of age. Patients with PIMPC and NIDC of the breast are frequently associated with lymph node metastases and greater than one-half of the cases (74%) were shown to have a Ki-67 index >30%, suggesting a significant risk of recurrence and metastasis. Early therapeutic care for these patients is crucial. These results warrant further validation with additional samples from several centers due to the limited single-center sample size in the current study.

The Clinicopathological Characteristics of Pure and Mixed Invasive Micropapillary Breast Carcinomas: A Single Center Experience.

Background:Invasive micropapillary carcinoma (IMPC) is a rare tumor of the breast. IMPC can be classified as a pure or mixed type based on the extent of micropapillary differentiation.Aims:To evaluate the prognostic importance of the IMPC component in breast cancer through retrospective comparison of the clinicopathological characteristics and clinical outcomes of pure and mixed IMPC patients.Study Design:The data of 147 (2.2%) patients with IMPC among 6648 patients histopathologically diagnosed with invasive breast cancer between January 2000-2022 were retrospectively reviewed. The patients were assigned to two groups: pure IMPC and mixed IMPC.Methods:The clinicopathological features such as age at diagnosis, histological type, grade, size, and components of mixed carcinoma, the numbers of metastatic lymph nodes, presence of lymph vascular invasion, hormone receptor, and the Her-2 status of the tumor, T, N, M stages, and the survival rates were reviewed. The clinicopathologic features, patterns of failures, and survival rates were coded and compared between pure and mixed IMPC patients.Results:A total of 45 patients (30.6%) had pure and 102 patients (69.4%) had mixed IMPC. The median follow-up time was 46 months (3-178). The progesterone receptor positivity rate was significantly lower in the pure group than in the mixed group (66.7% vs. 83.3%, p: 0.024). In the pure and mixed groups, respectively, the 5-year overall survival was 90% and 91% (p: 0.839); progression-free survival was 70% and 77% (p: 0.537); locoregional recurrence-free survival was 86% and 95% (p: 0.043); 5-year distant metastasis-free survival was 88% and 83% (p: 0.066), and the locoregional recurrence rate was 10.3% and 2% (p: 0.052).Conclusion:Compared to the mixed IMPC, pure IMPC appears to have a more aggressive behavior with lower locoregional recurrence-free survival and more locoregional recurrences. This may be due to the low progesterone receptor positivity rate.

Assessment of stromal tumor infiltrating lymphocytes and immunohistochemical featuresin invasive micropapillary breast carcinoma with long-term outcomes.

We studied the long-term outcomes of invasive micropapillary carcinoma (IMPCs) of the breast in relation to stromal tumor infiltrating lymphocytes (sTILs), prognostic biomarkers and clinicopathological features. Stage I-III IMPCs treated with upfront surgery at our institution (January 2000 and December 2016) were included. Central pathology review was performed and sTILs (including zonal distribution and hot spot analysis) and tumor-associated plasma cells (TAPC) were evaluated. Expression of P53, BCL2, FOXP3, and WT1, which are variably linked to breast cancer prognosis, was measured by immunohistochemistry using tissue microarrays. Time-to-event endpoints were distant recurrence free interval (DRFI) and breast cancer-specific survival (BCSS). We included 111 patients of whom 59% were pure IMPCs. Standard clinicopathological features were comparable between pure and non-pure IMPCs. Overall, the mean sTILs level was 20% with higher proportion of sTILs present at the invasive front. There were no significant differences between pure- and non-pure IMPCs in sTILs levels, nor in the spatial distribution of the hot spot regions or in the distribution of TAPC. Higher sTILs correlated with worse DRFI (HR = 1.55; p = 0.0172) and BCSS (HR = 2.10; p < 0.001). Clinicopathological features, geographical distribution of sTILs and TAPC are similar between pure and non-pure IMPCs. Despite a high proportion of grade 3 tumors and lymph node involvement, we observed a low rate of distant recurrences and breast cancer-related death in this cohort of stage I-III IMPCs treated with primary surgery. Caution in interpretation of the observed prognostic correlations is required given the very low number of events, warranting validation in other cohorts.

Abstract P3-08-31: Clinical and pathological features of invasive micropapillary carcinoma of the breast and correlation with prognosis

Abstract Background and objective: Invasive micropapillary carcinoma (IMPC) of the breast is a special variant of breast carcinoma with a unique morphology. Data about long-term outcome are conflicting and reports on stromal tumor infiltrating lymphocytes (sTILs) and their correlation with prognosis are scarce. In this retrospective cohort study we aimed to describe clinical and pathological features of IMPC, including sTILs assessment and immunohistochemistry studies, and their correlation with long-term outcome. Materials and methods: Patients with stage I-III IMPC (pure and mixed forms) who underwent upfront surgery at our institution between 2000 and 2016 were included. All patients signed informed consent. Standard clinico-pathological features and follow-up data to calculate distant relapse-free interval and breast cancer-specific survival were obtained from clinical records. Pathologic review of representative H&amp;E-slides of the resection specimens included evaluation of sTILs and assessment of the micropapillary component. Surrogate molecular subtypes were based on receptor-status and histological grade. Using tissue microarrays we assessed by immunohistochemistry the pattern of staining of P53, and scored semi-qualitatively the expression of Bcl2, PAX8 and WT1. The association between predictors and outcome is analyzed using the Fine and Gray model, accounting for other-cause death as competing event. All tests are two-sided, assuming a 5% significance level. The sample size did not allow multivariate analysis. Results: We included 111 patients (median age 61,5 years; range 33-88). Luminal surrogate subtypes were most prevalent with 51 luminal A-like, 41 luminal B-like, 12 luminal HER2+, 5 HER2+ and 2 triple negative IMPC. 89% of patients had a T1 or T2 tumor and 50% of IMPC were poorly differentiated. Lymph node involvement was present in 59% and lymphovascular invasion in 44% of cases. Adjuvant chemotherapy, radiotherapy and endocrine therapy was administered in 47%, 87% and 90% of patients, respectively. Of all cases 59% were pure IMPC. Standard clinico-pathological features were comparable between pure and non-pure IMPC. sTILs were classified as low (&amp;lt;30%), intermediate (30-50%) and high (&amp;gt;50%) in 78%, 14% and 8% of specimens respectively. Comparison between surrogate subtypes showed higher sTILs (p=0.025) and a higher likelihood of aberrant P53 expression (p&amp;lt;0.001) in HER2+ compared to luminal A-like subtype. Immunohistochemistry studies performed on 105 samples with enough material showed aberrant P53 expression in 10% and WT1 nuclear expression in 7% of cases. Pax8-staining was negative in all IMPC in this cohort. Bcl-2 expression was strongly related to all luminal subtypes (p&amp;lt;0.03). After a median follow-up of 100 months, we observed 8 distant relapses (7,2%) and 3 breast cancer-related deaths (2,7%). All events occurred in non-pure IMPC. Surrogate subtypes for patients with distant relapses where luminal A-like in 4 patients while the other subtypes where each observed in 1 patient. Five out of eight patients with distant relapse had received prior adjuvant chemotherapy. Six had lymph node involvement. Higher median sTILs was correlated with worse distant relapse-free interval (HR=1.55; p=0.0172) and breast cancer-specific survival (HR=2.10; p&amp;lt;0.001). Conclusions: Standard clinico-pathological features were similar in pure and non-pure IMPC. Despite high proportion of grade 3 differentiation and lymph node involvement, we observed a low rate of distant metastasis and within the pure IMPC (59% of patients), no distant relapses occurred. These findings could be explained by the high proportion of luminal-A like tumors in our cohort and need confirmation. Higher sTILs was associated with worse outcome in this IMPC cohort, confirming previously published observations. Citation Format: Kevin Punie, Frederik Deman, Annouschka Laenen, Timothy Faes, Hans Wildiers, Ann Smeets, Ines Nevelsteen, Chantal Van Ongeval, Adinda Baten, Melissa Christiaens, Eva Oldenburger, Hilde Janssen, Caroline Weltens, Tatjana Geukens, Nynke Willers, Jan Ardui, Hava Izci, Laurence Slembrouck, Patrick Neven, Christine Desmedt, Giuseppe Floris. Clinical and pathological features of invasive micropapillary carcinoma of the breast and correlation with prognosis [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-31.

Loss of ARID1A expression is associated with poor prognosis in invasive micropapillary carcinomas of the breast: A clinicopathologic and immunohistochemical study with long-term survival analysis.

Invasive micropapillary carcinoma (IMPC) of the breast is a highly aggressive and a rare subtype of breast cancer. In this study, we aimed to investigate differences between pure and mixed IMPCs of the breast in terms of clinicopathologic features, and also to analyze the significance of expressions of ARID1A and bcl-2 regarding prognosis. Sixty-nine of IMPCs consisting of 21 pure and 48 mixed type diagnosed at Pathology Department of Istanbul Medical Faculty between 2000 and 2011, who had complete follow-up data, were collected to analyze ARID1A and bcl-2 expressions immunohistochemically with prognosis. The median follow-up period was 94months. No significant difference was found between pure and mixed type IMPC, as well as in luminal subgroups in terms of prognostic and clinicopatologic features. ARID1A and human epidermal growth factor receptor-2 (Her-2) status were found to be independent prognostic factors of both overall survival (OS) (HR=6.1, 95% CI 1.4-26.6, P=.02; HR=15.9, 95% CI 3.5-71.5, P<.0001, respectively) and disease free survival (DFS) (HR=4, 95% CI 1.1-14.9, P=.04; HR=7.2, 95% CI 2-25.4, P=.002, respectively) in multivariate analysis using Cox regression. The loss of ARID1A expression was significantly related with 10year-OS (P=.001) and 10year-DFS (P=.05). Statistically significant effect of ARID1A expression was also stated on DFS and OS in Luminal B group (P=.05 and P=.001 respectively). Pure and mixed type IMPCs are similar in terms of clinicopathologic and prognostic features. The loss of ARID1A expression and Her-2 positivity have significant adverse effect clinical outcomes of IMPC patients.

Invasive Micropapillary Carcinoma of the Breast: An Update.

-Invasive micropapillary carcinoma (IMPC) is a distinct variant of mammary carcinoma in which tumor cells are arranged in morulelike clusters devoid of fibrovascular cores and situated within empty stromal spaces. Identification of IMPC can be achieved by the assessment of morphologic features in conjunction with the characteristic "inside-out" staining pattern of epithelial membrane antigen and sialyl Lewis X highlighted by immunohistochemical analysis. Although recognizing micropapillary architecture is often not challenging, the criteria for distinguishing between mixed and pure IMPC remain imprecise. Some mucin-producing carcinomas can also have micropapillary histology, but there is no consensus on whether these tumors are variants of IMPC or mucinous carcinomas. The molecular genetic studies demonstrate that IMPCs have distinct molecular genetic profiles, supporting the theory that they constitute distinct pathologic entities. However, genomic analyses have not identified any specific genomic aberration that may explain the distinctive morphology and clinical behavior of IMPC. -To provide an overview on the current concepts in the diagnosis and pathogenesis of IMPC of the breast, incorporating recent molecular genetic advances and prognosis-based reclassification. -PubMed search and the cited references were reviewed. -The recent evolution of prognosis-based reclassification and molecular genetic advances has enhanced our knowledge of the pathogenesis of IMPC of the breast. Additional studies might reveal consistent molecular alterations that underlie the formation of the inside-out growth pattern, and they might elucidate the molecular mechanisms responsible for the unfavorable clinical behavior of IMPC.

Invasive Micropapillary Carcinoma of the Breast: Immunophenotypic Analysis and Role of Cell Adhesion Molecules (CD44 and E-Cadherin) in Nodal Metastasis.

Invasive micropapillary carcinoma is a morphologically distinct subtype of breast carcinoma with high frequency of lymph node metastasis. In this study, we analyzed clinicopathologic features, immunophenotype, and expression of adhesion molecules [CD44 and E-cadherin (E-Cad)] in pure invasive micropapillary carcinoma of the breast. All cases had diffuse micropapillary pattern and were grade II tumors. Lymphovascular emboli were present in 80% and lymph node tumor deposits were seen in 69.2% cases. The cases were classified as; luminal A (11 cases), luminal B (8 cases), Her-2-neu overexpressing (4 cases), and triple negative (2 cases). All cases were positive for luminal cytokeratin (CK)CK8/18, and 2 cases showed <10% positivity for CK5/6. Eighteen cases showed loss of CD44 expression and 7 cases showed only weak positivity. Seven cases with lymph node metastasis showed reexpression of CD44 at metastatic site. Strong to moderate expression of E-Cad was observed in all cases and the corresponding nodal metastasis. To conclude, the loss of the CD44 expression plays role in lymphovascular permeation and metastasis and it can be hypothesized that its reexpression at metastatic site may play a role in homing of tumor cells. However, intact E-Cad expression could be because of the fact that tumour cells travel as clusters and retain their expression of E-Cad.

Pure invasive micropapillary carcinoma of the male breast: Report of a rare case with C-MYC amplification

Male breast cancer is rare. The most common histological subtypes include invasive carcinoma “of no special type” and papillary carcinoma. Other variants, including pure micropapillary carcinoma, have been described as well but are extremely rare. Pure micropapillary carcinoma has been recently characterized by a C-MYC gene amplification in women.We report here, occurring in a 73-year-old man, the first case of pure micropapillary carcinoma with amplification of the C-MYC gene.

Polarity gene alterations in pure invasive micropapillary carcinomas of the breast.

IntroductionPure invasive micropapillary carcinoma (IMPC) is a special type of breast carcinoma characterised by clusters of cells presenting polarity abnormalities. The biological alterations underlying this pattern remain unknown.MethodsPangenomic analysis (n = 39), TP53 (n = 43) and PIK3CA (n = 41) sequencing in a series of IMPCs were performed. A subset of cases was also analysed with whole-exome sequencing (n = 4) and RNA sequencing (n = 6). Copy number variation profiles were compared with those of oestrogen receptors and grade-matched invasive ductal carcinomas (IDCs) of no special type.ResultsUnsupervised analysis of genomic data distinguished two IMPC subsets: one (Sawtooth/8/16) exhibited a significant increase in 16p gains (71%), and the other (Firestorm/Amplifier) was characterised by a high frequency of 8q (35%), 17q (20% to 46%) and 20q (23% to 30%) amplifications and 17p loss (74%). TP53 mutations (10%) were more frequently identified in the amplifier subset, and PIK3CA mutations (4%) were detected in both subsets. Compared to IDC, IMPC exhibited specific loss of the 6q16-q22 region (45%), which is associated with downregulation of FOXO3 and SEC63 gene expression. SEC63 and FOXO3 missense mutations were identified in one case each (2%). Whole-exome sequencing combined with RNA sequencing of IMPC allowed us to identify somatic mutations in genes involved in polarity, DNAH9 and FMN2 (8% and 2%, respectively) or ciliogenesis, BBS12 and BBS9 (2% each) or genes coding for endoplasmic reticulum protein, HSP90B1 and SPTLC3 (2% each) and cytoskeleton, UBR4 and PTPN21 (2% each), regardless of the genomic subset. The intracellular biological function of the mutated genes identified by gene ontology analysis suggests a driving role in the clinicopathological characteristics of IMPC.ConclusionIn our comprehensive molecular analysis of IMPC, we identified numerous genomic alterations without any recurrent fusion genes. Recurrent somatic mutations of genes participating in cellular polarity and shape suggest that they, together with other biological alterations (such as epigenetic modifications and stromal alterations), could contribute to the morphological pattern of IMPC. Though none of the individual abnormalities demonstrated specificity for IMPC, whether their combination in IMPC may have a cumulative effect that drives the abnormal polarity of IMPC needs to be examined further with in vitro experiments.

Invasive Micropapillary Carcinoma of the Breast: A Clinicopathologic Study of 103 Cases of an Unusual and Highly Aggressive Variant of Breast Carcinoma

Invasive micropapillary carcinoma (IMPC) of the breast is an uncommon, highly aggressive breast cancer that may occur in pure and mixed forms. Our aim in this study is to investigate the relationship between clinical, histopathologic, and immunohistochemical features of pure and mixed IMPC cases diagnosed and treated at our institution. One hundred and three IMPC cases diagnosed at our institution over a period of 19 years have been selected. Clinical, histopathologic features, as well as hormone status and c-erb-B2 overexpression of tumors were re-evaluated. Mann-Whitney U, chi-squared, Kaplan-Meier, and Fisher's exact tests were used for statistical analyses. Results were considered to be significant at p < 0.05. Twenty cases (19.4%) were pure, and 83 cases (80.6%) were mixed IMPC. The most common nonmicropapillary invasive carcinoma component in mixed cases was invasive ductal carcinoma (IDC; 78.3%). Progesterone receptor was significantly less positive in pure IMPC cases (p = 0.031). There was no statistically significant difference between the two groups, in terms of mean age of the patients (53.0 versus 52.8), mean tumor size (26.6 mm versus 27.7 mm), presence of high-grade tumor (p = 0.631), presence of sentinel lymph node (SN) metastasis (p = 1.000), axillary lymph node metastasis (p = 1.000), lymphatic invasion (p = 1.000) and blood vessel invasion (p = 0.475), c-erbB-2 overexpression of tumor cells (p = 0.616), distant metastasis (p = 0.549), or overall survival (p = 0.759). The local recurrence rate of the two groups was not statistically significant either (16.7% versus 4.3%). However, local recurrence was detected 12% more commonly (p = 0.100), and ~8 months earlier (p = 0.967) in pure IMPC cases, compared to mixed cases. In addition, presence of local recurrence was found to be statistically significantly associated with estrogen receptor (ER) status (p = 0.004), progesterone receptor (PR) status (p = 0.001), and c-erb-B2 overexpression (p = 0.016) in all patients. Overall survival rate was significantly associated with ER staining of the tumor (log-rank = 0.028). Our findings suggest that hormone receptor negativity may explain the more aggressive behavior of pure IMPC compared to mixed cases. Besides, longer survival period of patients with ER positivity, and the relationship of hormone status and c-erb-B2 overexpression and local recurrence further support favorable prognostic value of hormone receptors in invasive breast cancer.

Inverted Apical CD24 and Weak EZH2 Expressions Are Phenotypic Characteristics of Pure Invasive Micropapillary Carcinoma of the Breast

Invasive micropapillary carcinomas (IMPC) of the breast account for less than 2% of all breast cancers and have been recently described as luminal B carcinomas. CD24, CD44, ALDH1 and EZH2 are commonly used as stem-cell markers that display differential expression as a function of stage and molecular type, but their pattern of expression according to this rare histological type remains poorly defined and unknown for EZH2. We assessed expression of these markers in a series of 28 micropapillary breast carcinomas and compared the results with those obtained in a series of luminal A (27 cases) and B (34 cases) invasive carcinomas not otherwise specified (IC-NST). CD24 and CD44 were expressed in most cases. However, CD24 was expressed at the inverted apical membrane in 85% of invasive micropapillary carcinoma and at the apical pole of gland-forming cells in 45% of luminal A (p-val = 6.8 × 10－4) and 13% of luminal B cases (p-val = 1.1 × 10－7). ALDH1 was expressed in the stroma in most tumors, but in only 25%, 11% and 15% in epithelial cells of IMPC, luminal A and B IC-NST, respectively. Nuclear expression of EZH2 was not observed in luminal A tumors, and was detected in 35% (12/34) of luminal B carcinomas (p-val = 6.1 × 10－3) and only 4% (1/28) of invasive micropapillary carcinomas. This series shows that invasive micropapillary carcinomas harbor a CD24-positive inverted apical pole associated with weak EZH2 expression, phenotypical characteristics that distinguish this entity from other luminal carcinomas.

Deep sequencing reveals small RNA characterization of invasive micropapillary carcinomas of the breast

Invasive micropapillary carcinoma (IMPC) is an uncommon histological type of breast cancer. IMPC has a special growth pattern and a more aggressive behavior than invasive ductal carcinomas of no special types (IDC-NSTs). microRNAs are a large class of non-coding RNAs involved in the regulation of various biological processes. Here, we analyzed the small RNA transcriptomes of five formalin-fixed paraffin-embedded (FFPE) pure IMPC samples and five FFPE IDC-NSTs samples by means of next-generation sequencing, generating a total of >170,000,000 clean reads. In an unsupervised cluster analysis, differently expressed miRNAs generated a tree with clear distinction between IMPC and IDC-NSTs classes. Paired fresh-frozen and FFPE specimens showed very similar miRNA expression profiles. By means of RT-qPCR, we further investigated miRNA expression in more IMPC (n=22) and IDC-NSTs (n=24) FFPE samples and found let-7b, miR-30c, miR-148a, miR-181a, miR-181a*, and miR-181b were significantly differently expressed between the two groups. We also elucidated several features of miRNA in these breast cancer tissues including 5' variability, miRNA editing, and 3' untemplated addition. Our findings will lead to further understanding of the invasive potency of IMPC and gain an insight into the diversity and complexity of small RNA molecules in breast cancer tissues.

Rapid Progression of Submucosal Invasive Micropapillary Carcinoma of the Colon in Progressive Systemic Sclerosis: Report of a Case

A 71-year-old woman presented with hematochezia and narrowing of the stool. She suffered from progressive systemic sclerosis for 12 years and underwent home oxygen therapy due to pulmonary fibrosis and moderate pulmonary hypertension. Colonoscopy revealed a pedunculated, cauliflower-like polyp with a depressed surface in the sigmoid colon. The polyp was regarded as early colon cancer with possible submucosal invasion, and subsequent computed tomographic (CT) scans showed no evidence of lymph node involvement or distant metastases. Because of perioperative risks due to moderate pulmonary hypertension, she underwent an endoscopic resection of the early colon cancer. Pathological examination of the resected specimen of 20 mm diameter revealed the peculiar morphology of an adenocarcinoma with moderate lymphatic invasion. Immunohistochemical analysis for epithelial membrane antigen showed the specific 'inside-out growth pattern' indicative of invasive micropapillary carcinoma (IMPC). Taking the perioperative risks into consideration, she opted to undergo close follow-ups without an additional sigmoidectomy. At 6 months after the resection, the follow-up colonoscopy revealed a local recurrence of the colon cancer, and subsequent CT scans revealed multiple distant metastases including the lung, liver, lymph nodes and spleen. This is a rare case of a pure, submucosal IMPC of the colon. Furthermore, pure IMPC of the colon may represent a reliable predictor of lymphogenous and/or hematogenous metastases. Therefore, one should recommend an additional colectomy after endoscopic mucosal resection treatment when pathological findings confirmed IMPC of the colon and should continue a close follow-up for IMPC patients even when curative resections were performed at an early stage.

Luminal group may give more benefit for invasive micropapillary carcinoma component breast cancer patients: experience from Cancer Hospital Fudan University.

Abstract Abstract #6152 Objective: Comparative studies on clinical features and outcomes of very rare invasive micropapillary carcinoma of breast cancer of 4 subtypes by immunohistochemistry staining.&amp;#x2028; Methods: From Aug 2005 to Mar 2008, a total of 52 breast cancer patients(BCPs) with an invasive micropapillary component (IMPC) among 1951 Chinese BCPs with complete of clinicopathologic data in our institution were enrolled into a retrospective analysis. We characterized all these 52 patients and analyzed using various parameters.&amp;#x2028; Results: The 52 cases of breast carcinoma with an IMPC all occurred in women. Mean age was 51 years (range from 26-82). All of these patients had breast masses; one also had metastasis to the supraclavicular lymph node at the time of diagnosis., mean tumor size was 2.83cm(T2), 23.08%(12/52) was pure invasive micropapillary carcinoma, and lymph node positive percentage was 75.59 %( 36/51).Fifty one patients received surgery, while one of them lost the chance of surgery. Forty of them received the modified mastectomy while one was performed lumpectomy due to old age. One was performed LAND alone and four were performed lumpectomy and sentinel lymph node biopsy.&amp;#x2028; By using IHC staining, when we regard HER2/neu 0 and +as negative. The Luminal A group, Luminal B, trip-negative, HER2+ /ER- were 76.92% (40/52), 11.54 %( 6/52), 7.69 %( 4/52), 3.85 %( 2/52), respectively. Compared to the database of 2005 breast cancer carcinoma in our institution, there was more Luminal A group patients than the whole group (P=0.01, chi-square test.), more Luminal B (P=0.028, Fisher exact possibility test), less trip-negative group (P=0.001, chi-square test). The positive lymph node among the Luminal A group, Luminal B, trip-negative, HER2+ /ER- were 65%,80%, 100%, 100%, respectively, while the lymphvascular invasion were 55%,33.33%,50%,50%,respectively, Mulifocality in Luminal A was 25% , 16.67% in Luminal B , while 50% in both trip-negative and HER2+/ER-.&amp;#x2028; Twenty-one of them received both anthracyclines and Taxane, while 27 only received anthracyclines, Four patients only were received only AIs due to old age. All the luminal group patients received endrocine therapy after chemo. After nearly 14 months (2∼34 months) follow up, thirty-six women were disease free, one had local recurrence, and 1 had lung metastasis, while 1 had ovary carcinoma when the diagnosis of breast malignant, one patient lost following up due to mental disorder. Among the luminal B, one had metastasis when diagnosis, others were disease free. One woman of the trip-negative died of non-breast cancer disease,the HER2+/ER- group was no recurrence or metastasis.&amp;#x2028; Discussion: The prelimary results showed that more luminal group in the IMPC may get benefit from the endocrine therapy. However the number of these cases is small and follow-up time is not very long, further studies are necessary to explain these rare and unique pattern of invasive carcinoma. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6152.

Genomic and immunophenotypical characterization of pure micropapillary carcinomas of the breast

Pure invasive micropapillary carcinoma (MPC) is a special histological type that accounts for 0.7-3% of all breast cancers. MPC has a distinctive growth pattern and a more aggressive clinical behaviour than invasive ductal carcinomas of no special type (IDC-NSTs). To define the molecular characteristics of MPCs, we profiled a series of 12 MPCs and 24 grade and oestrogen receptor (ER)-matched IDC-NSTs using high-resolution microarray comparative genomic hybridization (aCGH). In addition, we generated a tissue microarray containing a series of 24 MPCs and performed immunohistochemical analysis with ER, PR, Ki-67, HER2, CK5/6, CK14, CK17, EGFR, topoisomerase-IIalpha, cyclin D1, caveolin-1, E-cadherin, and beta-catenin antibodies. In situ hybridization probes were employed to evaluate the prevalence of amplification of HER2, TOP2A, EGFR, CCND1, MYC, ESR1, and FGFR1 genes. aCGH analysis demonstrated that MPCs significantly differed from IDC-NSTs at the genomic level. Gains of 1q, 2q, 4p, 6p, 6q23.2-q27, 7p, 7q, 8p, 8q, 9p, 10p, 11q, 12p, 12q, 16p, 17p, 17q, 19p, 20p, 20q, and 21q, and losses of 1p, 2p, 6q11.1-q16.3, 6q21-q22.1, 9p, 11p, 15q, and 19q were more prevalent in MPCs. High-level gains/amplifications of 8p12-p11, 8q12, 8q13, 8q21, 8q23, 8q24, 17q21, 17q23, and 20q13 were significantly associated with MPCs. A comparison between 24 MPCs and a series of 48 grade and ER-matched IDC-NSTs revealed that high cyclin D1 expression, high proliferation rates, and MYC (8q24) amplification were significantly associated with MPCs. Our results demonstrate that MPCs have distinct histological features and molecular genetic profiles supporting the contention that they constitute a distinct pathological entity.

A Pure Invasive Micropapillary Carcinoma of the Pancreatic Head

Kitagawa, Hirohisa MD, PhD*; Nakamura, Mari MD, PhD*; Tani, Takashi MD, PhD*; Tajima, Hidehiro MD, PhD*; Nakagawara, Hisatoshi MD, PhD*; Ohnishi, Ichiro MD, PhD*; Takamura, Hiroyuki MD, PhD*; Kayahara, Masato MD, PhD*; Ohta, Tetsuo MD, PhD*; Zen, Yoh MD†; Minato, Hiroshi MD†; Gabata, Toshifumi MD‡; Matsui, Osamu MD‡ Author Information