Foci Of Microinvasion Research Articles

Intratesticular Mullerian Serous Borderline Tumor With Microinvasion: A Rare Tumor and Review of the Literature.

Ovarian-type (ie, Mullerian) epithelial tumors occurring in the testicular and paratesticular regions are exceptionally rare, with only a handful reported worldwide. Serous tumors are the most frequently encountered subtype among these rare tumors. The pathogenesis of these tumors within the testicular and paratesticular regions remains a subject of intrigue and debate, with various hypotheses attempting to explain their presence in the paratestis region, where most tumors occur. However, our understanding of the pathogenesis of intratesticular tumors is limited. To date, 11 known examples of intratesticular serous Mullerian tumors have been reported globally. In this report, we present an extraordinary tumor, an intratesticular Mullerian serous borderline tumor with foci of microinvasion, in a 38-year-old male patient. This tumor exhibits histological features similar to their ovarian counterparts and is confirmed through an immunohistochemical panel. Our report underscores the extreme rarity of these tumors, emphasizes the importance of heightened awareness among clinicians and pathologists, and provides valuable insights into their complex development and histogenesis. This contribution aims to enhance diagnostic precision and optimize therapeutic strategies for similar tumors.

Beta-Catenin Nuclear Expression in Squamoid Morules in Colorectal Adenomas: Clinicopathologic Study of Fifteen Cases

Abstract Introduction/Objective Squamoid morules are an intriguing finding rarely seen in colorectal adenomas, mimicking foci of microinvasion or neuroendocrine differentiation. Previous observations include mostly case reports and small series, with few examining the squamoid morules in detail. Methods/Case Report We identified fifteen colorectal adenomas with squamoid morules and collected clinicopathological data including age, sex, procedure, location, pathologic diagnosis, and size. A representative block was chosen for immunohistochemistry in each case. The expression of p40, p63, CK5/6, beta-catenin, synaptophysin, chromogranin, and Ki-67 in squamoid morules were examined immunohistochemically. Results (if a Case Study enter NA) The fifteen patients comprised thirteen males and two females ranging in age from 45 to 85 years (average: 60.6 years old). The adenomas were removed by endoscopic resection (n = 7) or surgical resection (n = 8). Nine adenomas were found in the rectosigmoid colon, one in the descending colon, and five in the right colon. Eleven adenomas were tubulovillous adenomas (average: 3.8 cm, ranging 1.0 to 6.0 cm) and four were tubular adenomas (average: 2.6 cm, ranging 1.6 to 3.0 cm). Seven adenomas contained invasive adenocarcinoma. Squamoid morules were randomly distributed in adenomas. All foci of squamoid morules showed beta-catenin nuclear positivity and most (more than 90 %) showed CK5/6 expression. Squamoid morules were focally positive for p63 in three adenomas and focally positive for p40 in one adenoma. In one adenoma squamoid morules are positive for both synaptophysin and chromogranin. In all fifteen adenomas squamoid morules were negative for Ki- 67. Conclusion Squamoid morules are characterized by strong male predominance, association with large adenoma size, beta-catenin nuclear positivity, CK5/6 expression, and no Ki-67 expression. Beta-catenin nuclear expression is helpful in distinguishing squamoid morules from foci of microinvasion.

More microinvasive foci in larger tumours of breast ductal carcinoma in situ.

Microinvasion (Mi) is often thought to be an interim stage between ductal carcinoma in situ (DCIS) and invasive ductal carcinoma. This study aimed to investigate the potential influence of Mi on survival and assess its correlations with clinicopathological parameters, prognosis and molecular markers. The number of Mi foci in a cohort of 66 DCIS-Mi cases was assessed from haematoxylin and eosin-stained sections. Disease-free survival, clinicopathological parameters and biomarker expression were correlated with the number of Mi foci. Higher numbers of Mi foci were found in larger tumours (P = 0.031). Greater extent of DCIS is associated with multifocal Mi.

Subtype-Specific Tumour Immune Microenvironment in Risk of Recurrence of Ductal Carcinoma In Situ: Prognostic Value of HER2.

Increasing evidence suggests that the significance of the tumour immune microenvironment (TIME) for disease prognostication in invasive breast carcinoma is subtype-specific but equivalent studies in ductal carcinoma in situ (DCIS) are limited. The purpose of this paper is to review the existing data on immune cell composition in DCIS in relation to the clinicopathological features and molecular subtype of the lesion. We discuss the value of infiltration by various types of immune cells and the PD-1/PD-L1 axis as potential markers of the risk of recurrence. Analysis of the literature available in PubMed and Medline databases overwhelmingly supports an association between densities of infiltrating immune cells, traits of immune exhaustion, the foci of microinvasion, and overexpression of HER2. Moreover, in several studies, the density of immune infiltration was found to be predictive of local recurrence as either in situ or invasive cancer in HER2-positive or ER-negative DCIS. In light of the recently reported first randomized DCIS trial, relating recurrence risk with overexpression of HER2, we also include a closing paragraph compiling the latest mechanistic data on a functional link between HER2 and the density/composition of TIME in relation to its potential value in the prognostication of the risk of recurrence.

Abstract P3-12-36: The diagnosis and prognosis of ductal carcinoma in situ (DCIS) with microinvasion - Results from the United Kingdom Sloane project

Abstract Background/objectives The natural history of microinvasive carcinoma of the breast (one or more foci of invasion of 1mm or less) and its optimal management remain controversial. We analysed the frequency and outcome of patients with DCIS plus microinvasion within a large prospective cohort of screen-detected DCIS. Methods Patients with screen-detected DCIS diagnosed between 2003 and 2012 with or without microinvasion in the final surgical specimen were identified from the UK Sloane Project database. Comprehensive imaging, surgical, pathology, oncology and subsequent outcome data were collected with a median follow-up of 9 years. Results Among 11285 DCIS patients diagnosed in the UK, microinvasion was reported in 521 (4.6%). The frequency of reported microinvasion varied considerably among screening units (0-25%) but overall decreased from 7% in 2003/04 to 3% in 2011/12.As reported elsewhere, microinvasion was significantly associated with high grade DCIS (5.9% of 7182 cases) compared to 2.9% of intermediate grade and <1% of low grade DCIS (p<0.001, Chi square test). Microinvasion was associated with larger DCIS size (p<0.001) 2.2% of DCIS <10mm, 3.9% of DCIS 10-20mm, 5.8% of DCIS 20-30mm, 5.2% of DCIS 30-40mm and 8.0% of DCIS >40mm had microinvasive foci reported. Microinvasion was also associated with the presence of comedo necrosis (p<0.001), and solid (p<0.001), cribriform (p<0.001) or flat (p=0.03) DCIS architecture.Microinvasion was identified more frequently in patients who underwent mastectomy (6.9%) than in those who had breast conserving surgery (BCS) (3.6%; p<0.001). Axillary nodal surgery was more commonly performed for microinvasion (60.4% compared to 30.3%) including for patients undergoing BCS (43.4% vs 8.5% of all patients with BCS; p<0.001). The rate of nodal metastasis was, however, low and not statistically significantly different between those with and without microinvasion (0.4% and 0.1% respectively, p=0.27).Patients with microinvasion who underwent BCS were also more likely to receive radiotherapy (p<0.001). There was no significant association between the presence or absence of microinvasion with margin status or width. Subsequent events data for England showed that microinvasion was associated with a low rate of ipsilateral subsequent events, with 2.3% of patients having recurrent DCIS and 4.2% developing invasive carcinoma. This was not statistically significantly different from DCIS without microinvasion. All subsequent ipsilateral DCIS events in patients with microinvasion were of high grade. The majority (71.4%) of subsequent ipsilateral invasive carcinomas were of grade 3 compared with only 30.4% of grade 3 carcinomas in patients with DCIS without microinvasion (p=0.02). Breast cancer mortality was significantly higher in women whose tumours showed microinvasion (2.1%) compared with those without it (0.8%; p=0.005). Conclusions Microinvasion was most commonly identified within high-grade DCIS and in larger DCIS lesions, and was associated with comedo necrosis. Its pathological reporting decreased over a 10-year period, but there was significant variation between departments, which requires further evaluation. Patients with DCIS plus microinvasion were more likely to have undergone mastectomy, axillary node surgery and to receive radiotherapy after BCS. Microinvasive breast carcinoma was associated with a low rate of subsequent in situ/invasive events and had a good prognosis but, nevertheless, a higher breast cancer mortality than DCIS without microinvasion. Citation Format: Abeer M Shaaban, Bridget Hilton, Karen Clements, David Dodwell, Nisha Sharma, Cliona Kirwan, Elinor Sawyer, Anthony Maxwell, Matthew Wallis, Hilary Stobart, Senthurun Mylvaganam, Janet.Litherland Litherland, Samantha Brace-Mcdonnell, Joanne Dulson-Cox, Olive Kearins, Elena Provenzano, Sarah Pinder, Alastair Thompson. The diagnosis and prognosis of ductal carcinoma in situ (DCIS) with microinvasion - Results from the United Kingdom Sloane project [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-12-36.

Multiple Microinvasion Foci in Ductal Carcinoma In Situ Is Associated With an Increased Risk of Recurrence and Worse Survival Outcome.

BackgroundDuctal carcinoma in situ with microinvasion (DCISM) was defined as one or more foci of invasion beyond the basement membrane within 1 mm. The size of primary lesion is associated with axillary status and prognosis in patients with invasive breast cancer; thus, it is of interest to determine whether multiple foci of microinvasion are associated with a higher risk of positive axillary status or worse long-term outcomes in patients with DCISM.MethodsThis study identified 359 patients with DCISM who had undergone axillary evaluation at our institute from January 2006 to December 2015. Patients were categorized as one focus or multiple foci (≥2 foci) according to the pathological results. Clinicopathological features, axillary status, and disease-free survival rate were obtained and analyzed.ResultsOf 359 patients, 233 (64.90%) had one focus of microinvasion and 126 (35.10%) had multiple foci. Overall, 242 (67.41%) and 117 (32.59%) patients underwent sentinel lymph nodes biopsy (SLNB) and axillary lymph nodes dissection (ALND), respectively. Isolated tumor cells were found in four (1.11%) patients and axillary metastasis rate was 2.51%. Neither axillary evaluation methods (P = 0.244) nor axillary metastasis rate (P = 0.559) was significantly different between patients with one focus and multiple foci. In univariate analysis, patients with multiple foci tended to have larger tumor size (P < 0.001), higher nuclear grade (P = 0.001), and higher rate of lymphatic vascular invasion (P = 0.034). Also, the proportion of positive HER2 (P = 0.027) and Ki67 level (P = 0.004) increased in patients with multiple foci, while in multivariate analysis, only tumor size showed significant difference (P = 0.009). Patients with multiple foci were more likely to receive chemotherapy (56.35 vs 40.77%; P = 0.028). At median 5.11 years follow-up, overall survival rate was 99.36%. Patients with multiple microinvasive foci had worse disease-free survival rate compared with one-focus patients (98.29 vs 93.01%, P = 0.032).ConclusionEven though the numbers of microinvasion were different and patients with multiple foci of microinvasion tended to have larger tumor size, there was no higher risk of axillary involvement compared with patients with one focus of microinvasion, while patients with multiple microinvasive foci had worse DFS rate. Thus, DCISM patients with multiple foci of microinvasion may be the criterion for more aggressive local–regional treatment. Optimization of adjuvant therapy in DCISM patients is required.

Multiple foci of microinvasion is associated with an increased risk of invasive local recurrence in women with ductal carcinoma in situ treated with breast-conserving surgery.

The impact of Ductal Carcinoma in Situ (DCIS) with multiple foci of microinvasion (MI) (≤ 1mm) on the risks of local recurrence (LR) and invasive LR is unknown, leading to uncertainty if DCIS with multiple foci of MI requires more aggressive treatment. We report a population-based analysis of the impact of multiple foci of MI, confirmed by pathology review, on the 15-year risks of LR and invasive LR treated with breast-conserving surgery (BCS) ± radiotherapy (RT). Cohort includes all women diagnosed with DCIS ± MI from 1994 to 2003 treated with BCS ± RT. Cox proportional hazards model was used to evaluate the impact of multiple foci of MI on the risks of LR and invasive LR, adjusting for covariates. The 15-year local and invasive local recurrence-free survival rates were calculated using the Kaplan-Meier method with differences compared by log-rank test. The cohort includes 2988 women treated by BCS; 2721 had pure DCIS (51% received RT), 267 had DCIS with one or more foci of MI (58% had RT). Median follow-up was 13years. Median age at diagnosis was 58years. On multivariable analyses, the presence of multiple foci of MI was associated with an increased risk of invasive LR (HR = 1.59, 95% CI 1.01-2.49, p = 0.04) but not DCIS LR (HR = 0.89, 95% CI 0.46, 1.76, p = 0.7). The 15-year invasive LRFS risks for cases with pure DCIS, with 1 focus or multiple foci of MI were 85.7%, 85.6%, 74.7% following treatment by BCS alone, 87.2%, 89.9%, and 77% for those treated with BCS + RT without boost and 89.2%, 91.3%, and 95% for women treated with BCS + RT and boost. The presence of multiple foci of MI in DCIS is associated with higher 15-year risks of invasive LR after breast-conserving therapy compared to women with pure DCIS but treatment with whole breast and boost RT can mitigate this risk.

Abstract P2-08-03: Multiple foci of microinvasion is associated with an increased risk of invasive local recurrence and an increased risk of breast cancer mortality in women with ductal carcinoma in situ treated with breast-conserving therapy

Abstract Purpose: Ductal Carcinoma in Situ (DCIS) with microinvasion (MI) (&amp;lt; 1mm) includes a spectrum of cases with a single focus of MI and those with multiple foci (2 or more) of MI. The impact of multiple foci of MI on the risks of local recurrence (LR), invasive LR and breast cancer-specific survival (BCSS) is unknown, leading to uncertainty if DCIS with multiple foci of MI requires more aggressive treatment than those with a single focus of MI or pure DCIS. We examined the impact of multiple foci of MI, confirmed by expert pathology review, on the 15-yr risks of LR, invasive LR and breast-cancer specific survival (BCSS) in a population cohort of DCIS (+/-MI) treated with breast-conserving surgery (BCS) +/- radiotherapy (RT). Methods: The cohort includes all women diagnosed with DCIS +/- MI in Ontario from 1994-2003 treated with BCS+/-RT. Cases with prior malignancy were excluded. Treatment and outcomes were ascertained by deterministic linkage with chart validation. Cause of death was determined from the provincial cancer registry or terminal hospital admission records. Cox proportional hazards model was used to evaluate the impact of multiple foci of MI on the risks of ipsilateral invasive LR and ipsilateral DCIS LR, adjusting for significant co-variates. The 15-yr invasive local recurrence-free survival (LRFS), DCIS LRFS and 15-yr BCSS risks were calculated using the Kaplan-Meier method with differences compared using the log-rank test. Results: The cohort includes 3529 women; 2988 (85%) with pathology review are included in this analysis. 2,721 had pure DCIS (51% received RT), 267 had DCIS with MI (1 focus, N=156; multiple foci, N=111 (58% had RT)). Median follow-up was 13 years. Median age at diagnosis was 58 years. LR developed in 571 cases (21%) of pure DCIS, 33 cases (21%) with 1 focus of MI and 23 cases (27%) with multiple foci of MI. On multivariable analyses, the presence of multiple foci of MI was associated with an increased risk of invasive LR (HR=1.59, 95%CI: 1.01-2.49, p=0.04) but not DCIS LR (HR=0.89, 95%CI: 0.46, 1.76, p=0.7). Women with multiple foci of MI had higher risks of invasive LR and lower BCSS at 15 years compared to those with pure DCIS. The 15-year invasive LRFS risks for cases with pure DCIS, with 1 focus or multiple foci of MI were 85.7%, 85.6%, 74.7% for cases treated by BCS alone and 87.2%, 89.9% and 77% following BCS+RT without boost; however, women treated with boost RT had substantially higher 15-yr invasive LRFS risks than those who did not receive boost RT. The 15-yr invasive LRFS risks for those with pure DCIS, 1 or multiple foci of MI, were 89.2%, 91.3% and 95% (all p values&amp;gt;.05, limited by low event rate). The 15-yr BCSS risks for cases with 1 focus, multiple foci of MI or pure DCIS were 92.1%, 93.1%, 96.4% (p=.006). Conclusions: The presence of multiple foci of MI in DCIS is associated with higher 15-year risks of invasive LR and lower breast-cancer specific survival after breast-conserving therapy compared to women with pure DCIS but treatment with whole breast and boost RT can mitigate this risk. Citation Format: Rakovitch E, Sutradhar R, Lalani N, Gu S, Nofech-Mozes S, Hanna W, Fong C, Paszat L. Multiple foci of microinvasion is associated with an increased risk of invasive local recurrence and an increased risk of breast cancer mortality in women with ductal carcinoma in situ treated with breast-conserving therapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-08-03.

Processing the entire capsule in thyroid follicular lesions improves diagnostic accuracy

BackgroundThere is contradictory evidence in literature with respect to diagnosis and management of follicular lesions of the thyroid gland. From surgical pathology stand point, pathologists require submission and processing of entire capsule for microscopic evaluation. This can be extremely challenging especially in larger lesions. MethodWe studied the impact of submitting entire capsule on final pathologic diagnosis in cases on which only representative sections were submitted initially and entire capsule was submitted subsequently. ResultsA total of 80 specimens were identified. Mean size of the nodule in these cases was 4.4 ± 1.9 cm. Mean initial tissue sections submitted were 11.6 ± 3.6. Entire capsule was submitted subsequently in an additional 12.6 ± 13.3 sections. Submission of entire capsule contributed to final diagnosis in 3 (3.8%) cases whereby foci of capsular microinvasion were identified. There was no significant difference in the requirement of subsequent sections in specimens grossed by residents compared to those grossed by pathologist assistants (10.4 ± 10.8 vs. 14.4 ± 14.9, p = 0.18). The processing cost of additional sections of capsule was $ 4143 in these cases. ConclusionProcessing of entire capsule in thyroid follicular lesions has a definitive yield that comes at a high cost. Thin slicing and looking for areas of gross abnormality such as mushrooming may be more practical especially in larger lesions.

Well-differentiated papillary mesothelioma: A 17-year single institution experience with a series of 75 cases

We present our experience with 75 cases of well-differentiated papillary mesothelioma (WDPM) that were diagnosed at our institution between 2000 and 2017. The patients included 58 females and 17 males with age ranging from 18 to 69 years (mean, 42 years). Clinically, the vast majority of WDPMs were incidental findings during laparotomy or laparoscopic surgery for a variety of benign or malignant disease. The lesion manifested as either a small solitary nodule or multiple miliary nodules on the peritoneum or serosal surfaces of internal organs. Histologically, 67 cases were consistent with a classical WDPM, of which 6 cases contained microinvasive foci and 1 case had malignant transformation. Eight cases were hybrid tumors with variable combined component of adenomatoid tumor (n = 4), multicystic mesothelioma (n = 2), and both (n = 2). By immunohistochemistry, besides calretinin, D2-40, CK5/6 and WT1, 94% (29/31) of cases also showed immunostaining for PAX8. In comparison, PAX8 staining was only present in 12% (6/50) of epithelioid malignant mesothelioma selected as control cases. Follow-up information available in 46 cases revealed no signs of tumor progression or local recurrence except for the case that showed transformation to a fully malignant mesothelioma after a period of 15 years. Our comprehensive study further expanded the clinical and histopathological spectrum of WDPM. Compared with epithelioid malignant mesothelioma, PAX8 staining is highly sensitive and specific for WDPM (P < 0.001).

Abstract P4-15-05: The presence of one or multiple foci of microinvasion is not associated with an increased risk of local recurrence in women with ductal carcinoma in situ treated with breast conserving therapy

Abstract Background: Ductal Carcinoma in Situ (DCIS) is a non-invasive breast cancer often treated with breast-conserving surgery (BCS) with or without radiotherapy (RT). It is unclear if the presence of microinvasion (MI) (invasion ≤1mm) is associated with an increased risk of LR (DCIS or invasive) or invasive LR compared to women with pure DCIS. In addition, the impact of multiple foci (&amp;gt;2) of MI compared to pure DCIS is also unknown; therefore, it is unclear if some women with MI require more aggressive treatment. We evaluated the impact of the presence of MI and the number of foci of MI on the risks of any LR and invasive LR in a population of women with DCIS with and without MI treated with BCS. Methods: The cohort includes all women diagnosed with pure DCIS or DCIS with MI in Ontario from 1994-2003 treated with BCS +/- RT. All cases had systematic pathology review to confirm the presence and number of foci of MI. Treatment and outcomes were ascertained through administrative databases and validated by chart review. Cox proportional hazards model was used to evaluate the impact of MI and the number of foci of MI (1 vs &amp;gt;2 foci) on the development of any LR and invasive LR compared to cases with pure DCIS. The 10-yr local recurrence-free survival (LRFS) and invasive LRFS rates were calculated using the Kaplan-Meier approach with differences compared using the log-rank test. Results: The population cohort includes 2,988 women with DCIS treated by BCS (N=2,721 pure DCIS, N= 267 DCIS with MI). Median follow-up (12 years; p=.23) and median age at diagnosis (58 years; p=.17) were similar in both groups. RT was given in 58% of cases with MI and 51% of cases with pure DCIS (p=.03). Hormonal therapy was utilized in 7.1% of women with MI and 5.3% of women with pure DCIS (p=.22). LR developed in 59 (22.1%) cases with MI and 530 (19.6%) cases of pure DCIS. Women with MI were more likely to have high nuclear grade (p&amp;lt;.001), and larger tumor size (p&amp;lt;.001) compared to those without MI. On multivariable analyses adjusted for age, the presence of 1 focus of MI(HR=.92, 95% CI: .64-1.33) or ≥2 foci of MI (HR=1.26, 95% CI: .85-1.85) was not associated with an increased risk of any LR compared to cases with pure DCIS. Factors associated with any LR were age &amp;lt;50 years at diagnosis, RT, multifocality and high nuclear grade. The presence of 1 focus of MI (HR=.86, 95% CI: .52-1.40) or &amp;gt; 2 foci of MI (HR=1.45, 95% CI: .90-2.32) was also not associated with an increased risk of invasive LR compared to cases of pure DCIS. Among women treated with BCS alone, the 10 year LRFS rates were 80%, 75% and 73% for women with pure DCIS, 1 focus, &amp;gt;2 foci of MI (p=.10). The invasive LRFS rates were 89%, 91% and 85% (p=.26). Among women treated with BCS+RT, the 10 year LRFS rates were 87%, 88% and 80% (p=0.32) for women with pure DCIS, 1 focus or ≥2 foci of MI. The invasive LRFS rates were 93%, 90% and 86% (p=.44). There was no interaction between the presence of MI and RT. Conclusions: Women with DCIS with one or multiple foci of microinvasion (&amp;lt;1mm) treated by breast conserving therapy do not have an increased risk of LR or invasive LR compared to women with pure DCIS. Citation Format: Lalani N, Paszat L, Sutradhar R, Gu S, Fong C, Nofech-Mozes S, Hanna W, Tuck A, Youngson B, Miller N, Done SJ, Chang MC, Sengupta S, Elavathil L, Jani PA, Bonin M, Rakovitch E. The presence of one or multiple foci of microinvasion is not associated with an increased risk of local recurrence in women with ductal carcinoma in situ treated with breast conserving therapy [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-15-05.

Impact of Microinvasion as a Predictor of Local Recurrence in Ductal Carcinoma In Situ Treated With Breast Conserving Therapy

The significance of microinvasion (MI) (invasive cancer ≤1mm) on the risk of local recurrence (LR) in women with ductal carcinoma in situ (DCIS) is unclear. We report a population-based analysis of women with DCIS with and without MI treated with breast-conserving surgery (BCS) alone or with radiotherapy (RT), and evaluated the impact of MI on the risks of any LR (DCIS or invasive) and invasive LR Cohort includes all women diagnosed with pure DCIS or DCIS with MI in Ontario from 1994-2003 that were treated with BCS +/- RT and had undergone expert pathology review. Treatments and outcomes were assessed through administrative databases and validated by chart review. Local recurrence-free survival (LRFS) was calculated using the Kaplan-Meier approach with differences compared using the log-rank test. The impact of MI on the development of LR was assessed using Cox proportional hazards model adjusted for propensity score to account for systematic differences in women treated with and without RT. Population cohort includes 2,988 women with DCIS treated by BCS (N=2,721 with pure DCIS, N= 267 DCIS with MI). Median follow-up was 13 years. Median age at diagnosis was 58 years. RT was given in 58% of cases with MI and 51% of cases with pure DCIS (p=.03). RT boost was given in 16.6% of women with MI and 14.4% of those with pure DCIS (p=.21). Women with MI were more likely to have high nuclear grade (p<.001), and larger tumour size (p<.001) versus pure DCIS. LR developed in 59 (22.1%) cases with MI and 530 (19.6%) cases of pure DCIS. Among women treated with BCS alone, the 15 year LRFS rate for DCIS with MI versus pure DCIS was 66% v 75% (p=.03) for any LR and 83% v 86% (p=.30) for invasive LR. Among women treated with BCS and RT, the 15 year LRFS rate for DCIS with MI versus pure DCIS was 82% v 82% (p=.74) for any LR and 88% v 88% (p=.84) for invasive LR. However, on multivariable analyses adjusted for age, propensity score and year of diagnosis, the presence of MI was not associated with an increased risk of any LR (HR=1.05, 95% CI: .80-1.38) or invasive LR (HR=1.08, 95% CI: .76-1.54). There was no significant interaction between the presence of MI and provision of RT for any LR (p=.15) or invasive LR (p=.67). Factors associated with any LR include RT (HR=.60, 95% CI: .51–.71), high nuclear grade (HR=1.21, 95% CI 1–1.45) and multifocality (HR=1.35, 95% CI: 1.12-1.64). Factors associated with invasive LR include RT (HR=.76, 95% CI: .61–.94) and multifocality (HR=1.40, 95% CI: 1.09-1.79). The presence of MI with DCIS is not associated with an increased risk of any LR or invasive LR after BCS with or without RT. The impact of number of foci of microinvasion on the risk of LR is in progress.

P16-negative warty carcinoma of the uterine cervix with superficial invasion to the endometrium: A case report focusing on diagnostic pitfalls

Warty carcinoma of the uterine cervix is a very rare and specific variant of invasive squamous cell carcinoma, usually described as a hybrid of the features of both condyloma acuminatum and invasive squamous cell carcinoma. The diagnostic pitfalls of this lesion are: 1) the bland appearance of cytomorphology, 2) distinct koilocytotic atypia, and 3) p16 negativity. A case of warty carcinoma with a fungating mass on the uterine cervix of a 75-year-old woman is presented. The original diagnosis by punch biopsy was atypical squamous cells, undetermined for malignancy, adjunct with p16 negativity. The subsequent radical hysterectomy showed a protruding mass (5.7 cm in horizontal dimension) of the uterine cervix. Light microscopy revealed a protruding mass composed of exophytic papillae and inverted nests along the endocervical glands. There were multiple micro-invasive foci (&lt; 1 mm) of tongue like projections at the nest base and slight involvement of the upper vagina and endometrial surface. The p16 immunohistochemical staining yielded negative results. The results of the HPV DNA chip test from paraffin-embedded tissue were 6 (low risk, +++) and 42 (low risk, +). The Ki-67 proliferation index was approximately 20%. The invasive foci and patient’s age were the determining differential factors for malignancy rather than benign condylomatous lesion.

Extent of microinvasion in ductal carcinoma in situ is not associated with sentinel lymph node metastases.

Ductal carcinoma in situ with microinvasion (DCISM) is a rare diagnosis with a good prognosis. Although nodal metastases are uncommon, sentinel lymph node biopsy (SLNB) remains standard care. Volume of disease in invasive breast cancer is associated with SLNB positivity, and, thus we hypothesized that in a large cohort of patients with DCISM, multiple foci of microinvasion might be associated with a higher risk of positive SLNB. Records from a prospective institutional database were reviewed to identify patients with DCISM who underwent SLNB between June 1997 and December 2010. Pathology reports were reviewed for number of microinvasive foci and categorized as 1 focus or ≥2 foci. Demographic, pathologic, treatment, and outcome data were obtained and analyzed. Of 414 patients, 235 (57 %) had 1 focus of microinvasion and 179 (43 %) had ≥2 foci. SLNB macrometastases were found in 1.4 %, and micrometastases were found in 6.3 %; neither were significantly different between patients with 1 focus versus ≥2 foci (p = 1.0). Patients with positive SLNB or ≥2 foci of microinvasion were more likely to receive chemotherapy. At median 4.9 years (range 0-16.2 years) follow-up, 18 patients, all in the SLNB negative group, had recurred for an overall 5-year recurrence-free proportion of 95.9 %. Even with large numbers, there was no higher risk of nodal involvement with ≥2 foci of microinvasion compared with 1 focus. Number of microinvasive foci and results of SLNB appear to be used in decision making for systemic therapy. Prognosis is excellent.

Human epidermal growth factor receptor 2-positive microinvasive breast carcinoma with a highly aggressive course: a case report

BackgroundMicroinvasive ductal carcinoma in situ of the breast is a rare entity defined as ductal carcinoma in situ with invasive foci measuring no more than 1 mm. In general, the outcome is excellent, similar to ductal carcinoma in situ. We report a patient with breast ductal carcinoma in situ with microinvasion who died eight months after diagnosis due to progression of the disease – liver metastases. This is the first report in the literature of such an aggressive course.Case presentationA 47-year-old Caucasian woman presented with mammographic-detected suspicious microcalcinations in an area of 8.6 x 6 cm. A radical mastectomy with a sentinel lymph node biopsy and immediate breast reconstruction with implant was performed. A histopathological report showed a massive high grade ductal carcinoma in situ, of the solid and comedo type. In one quadrant, some foci of microinvasions of less than 1 mm were present. Tumour margins were free. Isolated tumour cells were found in the sentinel lymph node. Hormone receptors were negative and human epidermal growth factor receptor-2 status was not performed. The patient received no adjuvant systemic therapy. Eight months after the surgery, she died from hepatic failure without known breast cancer progression before. An autopsy revealed diffuse liver metastases with human epidermal growth factor receptor 2-positive, hormone receptor negative breast cancer. Dissemination to other organs was not proven.ConclusionOur patient is a rare case of ductal carcinoma in situ with microinvasion that developed distant metastases very early. In case of multiple foci of microinvasion, besides radical local treatment we suggest considering adjuvant systemic treatment based on biological characteristics since tumour size alone does not predict the prognosis well.

Microinvasive breast carcinoma carries an excellent prognosis regardless of the tumor characteristics

The clinical implication of microinvasive breast carcinoma (MIBC), especially when multiple foci are identified, is still not clearly defined. This study is designed to collect clinicopathologic and follow up data on patients with MIBC. Histologic data including invasive breast cancer type, nuclear grade, number of microinvasive foci and lymph node status, as well as associated in situ component histologic and biomarkers parameters were recorded. Clinical follow-up data, such as local recurrence, distant metastasis and survival was also noted. Forty MIBC cases were identified among 1180 invasive breast cancer cases between 1998 and 2012, representing 3.4% of the overall invasive cases. The majority of the cases (28/40) had three or less foci of microinvasion and had high nuclear grade (26/40). The associated carcinoma in situ was also mostly high grade. The biomarker expression for estrogen receptor/human epidermal growth factor receptor 2 (ER/HER2) of the in situ component was heterogeneous. Of the 35 cases with known nodal status, 1 had macrometastasis, 1 had micrometastasis, 3 had isolated tumor cells, and the remaining had negative nodes. In the follow-up period (mean 30 months, median 15 months) none of the patients had recurrence, distant metastasis or died of disease. In conclusion, MIBC represents a small portion of invasive carcinomas. The majority of cases have high nuclear grade and are associated with high grade ductal carcinoma in situ. The latter doesn't show consistent ER/HER2 expression. Overall, the number of microinvasive foci, the extent and biomarker expression of the in situ component do not appear to impact the overall excellent outcome.

Impact of Multifocality and Lymph Node Metastasis on the Prognosis and Management of Microinvasive Breast Cancer

There are few data on the long-term outcome of patients with microinvasive (T1mi) breast cancer. Moreover, predictors of lymph node involvement and the impact of multifocal microinvasion are not well understood. Patients with T1mi cancer, defined as tumors ≤1mm, surgically managed at our institute and who underwent axillary lymph node evaluation were identified. Specimen slides were independently reviewed. Multivariate analysis was used to identify factors predictive of lymph node involvement. Forty-five patients with T1mi cancer were identified. Median patient age was 52years, and median size of in situ disease was 4cm. Nine tumors (20.0%) had more than one focus of microinvasion. Lymph nodes metastasis were identified in 9 patients: 1 macrometastasis (2.2%), 4 micrometastases (8.9%), and 4 isolated tumor cells (8.9%). Seven of 9 patients with lymph node involvement underwent adjuvant chemotherapy. Estrogen receptor-negative invasive disease was a significant predictor of lymph node metastasis by multivariable analysis (p<0.02). There was also a trend toward lymph node involvement in patients with multifocal microinvasion compared to unifocal disease (33.3 vs. 16.7%, respectively). At a median follow-up of 83months, 3 patients (6.3%) had disease recurrence (1 local, 1 distant, 1 local and distant). All patients with recurrence initially had tumor-free lymph nodes and only one focus of microinvasion. Microinvasive breast cancer clearly has the ability to metastasize and recur, but in this series, only 2% of patients with nodal macrometastasis. Only two patients experienced local recurrence, neither of whom had lymph node metastasis. The importance of identifying nodal micrometastasis in T1mi disease needs to be further explored.

Is there a need for sentinel lymph node biopsy in microinvasive breast cancer?

1105 Background: There is limited data on the long-term outcome of patients with microinvasive breast cancer. Moreover, predictors of lymph node involvement and the impact of multifocal microinvasion are not well understood. We examined the occurrence of nodal metastasis and the significance of multifocality on disease recurrence. Methods: Patients with T1mic breast cancer, defined as tumors ≤1mm, surgically managed at our institute between 1995-2010 were identified. Specimen slides were independently reviewed. Multivariable analysis (MVA) was used to predict lymph node involvement and disease recurrence. Results: Fifty-two patients with T1mic breast cancers were identified. Median patient age was 53 (range 30-92), median size of in-situ disease was 3cm (range 0.1-12cm). Ten patients (19.2%) had multiple foci of microinvasion (range 2-7). The majority of tumors were high-grade (76.9%). When the invasive tumor component was evaluated, 31 of 41 (73.8%) were ER positive, 40.5% were HER2+(15/37), and only one was ER-/PR-/HER2-. Twenty-nine patients (55.8%) had breast conserving surgery and 23 had mastectomies. Lymph nodes were assessed in 48 patients; there was 1 macrometastasis (2.1%), 4 micrometastases (8.3%) and 4 (8.3%) with isolated tumor cells. Seven of 9 patients with lymph node involvement underwent adjuvant chemotherapy. Univariable analysis showed that ER(-) invasive disease and high-grade DCIS tumors were more likely to have involved lymph nodes. On MVA, only negative ER status was a significant predictor of lymph node metastasis (p&lt;0.02). At median follow-up of 83 months (range 6-172 months), 3 patients (6.3%) had disease recurrence (1 local, 1 distant, 1 local and distant) at 8, 17, and 130 months from presentation. All patients with recurrence had negative lymph nodes and only one focus of microinvasion. No factors predicted disease recurrence. Conclusions: Microinvasive breast cancer clearly has the ability to metastasize and recur, but in this series only 2% of patients presented with nodal macrometastasis. The evaluation of lymph nodes in T1mic cancer is unnecessary in the majority of patients. In our cohort, neither lymph node status nor multifocal microinvasion predicts recurrence.

Should palpable DCIS be treated as IDC? A retrospective audit.

146 Background: Ductal carcinoma in situ (DCIS) identified by screening mammography accounts for 20% of breast cancer diagnoses, and microinvasion (DCIS-M) is found in 5%-10%. There are no defined treatment guidelines for palpable DCIS or DCIS-M. In the developing world wherein screening mammography is controversial due to a predominantly premenopausal population, most women with DCIS present with a palpable lump in the breast. The objective of this study was to evaluate whether disease in these patients with palpable DCIS have been treated differently from screen detected DCIS. Methods: Annually we register 3,000 new cases of breast cancer of which DCIS constitute a small fraction. Over a period of 12 years (1998-2010) we registered 71 cases of DCIS for treatment. A retrospective analysis of these was performed. Results: Of the 71 patients reviewed, 35 (49.2%) had foci of microinvasion. The median age of presentation was 49 years and mean tumor size was 2.3 cm; all presented with palpable breast lumps. Of the 36 women with DCIS alone Tsize was &gt; 2 cm in 26 (72.2%), 14 (38.9%) had presence of comedo necrosis and 1 (2.7%) had positive lymph nodes on histopathology. Adjuvant chemotherapy was given to 4 (11.11%). Of the 35 women with DCIS-M Tsize was &gt; 2 cm in 23 (66%), 10 (29%) had comedo necrosis (compared to 38.9% in pure DCIS p=0.45), 3 (8.5%) had positive lymph nodes, and 17 (48.6%) received chemotherapy. We compared this data to that of women treated for invasive ductal carcinoma with pTsize &lt;2cm, at a median follow-up of 60 months, DFS for the women with DCIS was 82% (95% CI 0. 67- 0.98), for DCIS-M was 78% (95% CI 0. 59 -0.98), and that for IDC &lt; 2cm was 83% (95% CI 0.70-0.95). Conclusions: DCIS presenting in these palpable lesions poses a clinical dilemma for the use of adjuvant therapy. Over 49.2% of the palpable DCIS showed evidence of microinvasion. We thus need to consider the role of adjuvant chemotherapy when treating women with palpable DCIS.

Microinvasive (T1mic) Lobular Carcinoma of the Breast

The entity of microinvasive lobular carcinoma (MILC,<0.1 cm) of the breast remains hitherto poorly characterized. Clinical and pathologic material of cases in which MILC was either suspected or diagnosed over an 18-year period (1991 to 2009) was studied. Only cases in which MILC could be indisputably established, by immunohistochemical stains in equivocal cases, were included. Sixteen (0.02%) cases were confirmed to be MILC among 75,250 breast cases during the study period. Mean age of patients was 52 years (range, 41 to 65 y). Patients presented with either radiographic (13 cases) or palpable (3 cases) abnormality. MILC was unilateral in all cases (right: 8, left: 8). Mean number of microinvasive foci was 1.5 (range, 1 to 5). MILCs were associated with lobular carcinoma in situ (LCIS) predominantly of the classical type in 11 cases, of the florid type in 4 cases, and of the pleomorphic type (with high-grade nuclei) in 1 case. Slight enhancement of stromal cellularity was the only histologic hint of MILC at low-power microscopy. Six MILC cases, in which results could be obtained, were positive for both estrogen receptor and progesterone receptor, and all 6 were negative for HER2/neu. The final surgical procedure was excisional biopsy (8 cases), ipsilateral mastectomy (6 cases), and bilateral mastectomy (2 cases). Synchronous invasive ductal carcinoma (2 cases, 1 of which was contralateral), intraductal carcinoma (2 cases), and LCIS (16 cases) were identified therein. Axillary lymph node biopsies (including 9 sentinel lymph node samplings) were performed in 13 cases, with negative results in each. All patients were alive without evidence of recurrence or of metastases in a mean follow-up of 24 months (range, 1 to 72 mo). On the basis of this study, MILC is a rare disease that is typically associated with classical, florid, or pleomorphic forms of LCIS. MILC cases in this series showed low morbidity and no metastatic potential, at least in the short term.