Concurrent Invasive Carcinoma Research Articles

Concurrent Invasive Carcinoma and Fibroadenoma Arising from Bilateral Ectopic Breast Tissue in the Chest Wall: A Case Report and Literature Review

Concurrent Invasive Carcinoma and Fibroadenoma Arising from Bilateral Ectopic Breast Tissue in the Chest Wall: A Case Report and Literature Review

Does Non-Classic Lobular Carcinoma In Situ at the Lumpectomy Margin Increase Local Recurrence?

The clinical significance of nonclassic, lobular carcinoma in situ (NC-LCIS) at the surgical margin of excisions for invasive cancer is unknown. We sought to determine whether NC-LCIS at or near the margin in the setting of a concurrent invasive carcinoma is associated with risk of ipsilateral breast tumor recurrence (IBTR) and locoregional recurrence (LRR). Patients with stage 0-III breast cancer and NC-LCIS who underwent lumpectomy between January 2010 and January 2022 at a single institution were retrospectively identified. NC-LCIS margins were stratified as <2 mm, ≥2 mm, or within shave margin. Rates of IBTR and LRR were examined. A total of 511 female patients (median age 60 years [interquartile range (IQR) 52-69]) with NC-LCIS and an associated ipsilateral breast cancer with a median follow-up of 3.4 years (IQR 2.0-5.9) were identified. Final margins for NC-LCIS were ≥2 mm in 348 patients (68%), <2 mm in 37 (7.2%), and within shave margin in 126 (24.6%). Crude incidence of IBTR was 3.3% (n = 17) and that of LRR was 4.9% (n = 25). There was no difference in the crude rate of IBTR by NC-LCIS margin status (IBTR rate: 3.7% ≥2 mm, 0% <2 mm, 3.2% within shave margin, p = 0.8) nor in LRR (LRR rate: 4.9% ≥2 mm, 2.7% <2 mm, 5.6% within shave margin, p = 0.9). For completely excised invasive breast cancers associated with NC-LCIS, extent of margin width for NC-LCIS was not associated with a difference in IBTR or LRR. These data suggest that the decision to perform reexcision of margin after lumpectomy should be driven by the invasive cancer, rather than the NC-LCIS margin.

In Search of Calcifications : Histologic Analysis and Diagnostic Yield of Stereotactic Core Needle Breast Biopsies.

Stereotactic core needle biopsy (SCNB) is used in the diagnostic assessment of suspicious mammographic calcifications to rule out breast ductal carcinoma in situ (DCIS). With advances in imaging technology and increased biopsy tissue volume, the detection rate of calcifications and DCIS in SCNB is unclear. This retrospective study included 916 consecutive SCNBs for calcifications performed on 893 patients in a 2-year period. We found the cancer detection rate was 27.1% (DCIS, 23.7%; invasive, 3.4%). The detection rate for calcifications was 74.8% with the standard 3 levels. Additional leveling of calcification-negative cases further increased the detection of both calcifications (to 99.4% of cases) and DCIS (to 32.9% of cases). Lobular neoplasia (LN) was diagnosed in 41 cases. Twenty-five (61.0%) cases of LN were incidental without associated calcification. Of 32 invasive carcinomas detected on SCNB, 87.5% were T1a or less, and calcifications were associated with atypical ductal hyperplasia/DCIS or LCIS. The common benign lesions associated with calcifications were fibrocystic change (32.5%), fibroadenomatous change (30.2%), and columnar cell change and hyperplasia (8.2%). We determined the up-to-date detection rates of calcification and DCIS in SCNB, as well as the common benign and malignant breast lesions associated with calcifications. Additional levels significantly increase the detection rate when standard levels show only stromal or scant/absent calcifications. Lobular neoplasia is often an incidental finding in SCNB for calcifications. When calcifications are present with LN, they are commonly florid, pleomorphic LCIS, or with concurrent invasive carcinoma.

Encapsulated papillary carcinoma of the breast: An institutional case series and literature review.

Encapsulated papillary carcinoma of the breast is rare, making difficult diagnosis and resulting in patients undergoing excision biopsy before definitive surgery. Evidence-based guidelines are sparse. We would like to further elucidate the clinicopathological, treatment and survival outcomes. 54 patients identified, with a median follow up duration of 48 months. Patients' demographics, radiological and clinicopathological characteristics, treatment, adjuvant therapies as well as survival data were analysed. 18 (33.3%) cases were pure EPC, 12 (22.2%) were EPC associated with ductal carcinoma in situ (DCIS) and 24 (44.4%) cases had concurrent invasive ductal carcinoma. EPCs were more likely to present as a solid-cystic mass on sonography (63.8%), regular-shaped (oval or round) (97.9%), lack spiculations (95.7%) and lack suspicious microcalcifications (95.6%). Median tumour size was largest in the EPC with IDC group (18.5 mm). 2 patients developed loco-regional recurrence. Overall survival is good for EPCs of all subtypes. EPC is a rare tumour with excellent prognosis.

Concurrent Invasive Ductal Carcinoma and Pancreatic Intraepithelial Neoplasia in Duodenal Heterotopic Pancreas: A Case Report

Concurrent Invasive Ductal Carcinoma and Pancreatic Intraepithelial Neoplasia in Duodenal Heterotopic Pancreas: A Case Report

Intraductal Adenocarcinoma of the Prostate With Cribriform or Papillary Ductal Morphology: Rare Biopsy Cases Lacking Associated Invasive High-grade Carcinoma.

Prostatic duct adenocarcinoma, characterized by pseudostratified columnar epithelium, has historically been considered invasive carcinoma, although it may commonly have an intraductal component. Usual (acinar) intraductal carcinoma of the prostate (IDC-P) is a noninvasive high-risk lesion typically associated with high-grade, high-stage prostate cancer. Whereas there have been rare biopsy studies of pure acinar IDC-P or IDC-P associated with only low-grade carcinoma, there have been no analogous series of IDC-P with cribriform or papillary ductal morphology on biopsy unassociated with invasive high-grade carcinoma. We identified 14 patients with biopsies showing IDC-P with ductal morphology, defined as prostatic duct adenocarcinoma confined to glands/ducts with immunohistochemically proven retention of basal cells. Our series includes 12 patients with pure IDC-P and 2 patients with concurrent low-volume Grade Group 1 invasive cancer in unassociated cores. Three patients underwent radical prostatectomy: 2/3 had high-grade cancer in their resection specimen (Grade Group 3, Grade Group 5), including 1 with advanced stage and nodal metastases; 1/3 had Grade Group 1 organ-confined carcinoma and spatially distinct IDC-P with ductal morphology. Five men had only follow-up biopsies: 2/5 had cancer (Grade Group 2, Grade Group 4); 1/5 had IDC-P (on 2 repeat biopsies); and 2/5 had benign transurethral resection of the prostate. In all 5 cases with invasive cancer, the invasive portion was comprised purely of acinar morphology; no invasive ductal component was identified. Five patients did not have follow-up biopsies and were treated with radiation therapy±androgen deprivation. One patient had no follow-up information. In an analogous situation to acinar IDC-P, we propose that rarely there is a precursor form of ductal adenocarcinoma that can exist without concurrent invasive high-grade carcinoma and propose the term "IDC-P with ductal morphology," consistent with the terminology for acinar prostate adenocarcinoma. Until more evidence is accumulated, we recommend reporting and treating patients with IDC-P with ductal morphology in a manner analogous to those with acinar IDC-P. As with pure IDC-P with acinar morphology, we would also recommend not grading pure IDC-P with ductal morphology. Finally, we propose a new addition to the diagnostic criteria of IDC-P to include intraductal lesions with ductal morphology consisting of papillary fronds or cribriform lesions lined by cytologically atypical pseudostratified epithelium.

Comprehensive genomic profiling reveals ubiquitous KRAS mutations and frequent PIK3CA mutations in ovarian seromucinous borderline tumor

The molecular underpinnings of seromucinous borderline tumor (SMBT) – an uncommon ovarian epithelial neoplasm characterized by association with endometriosis, frequent bilateral ovarian involvement, and occasional progression to invasive carcinoma – remain poorly understood. Here, we sought to comprehensively characterize the mutational landscape of SMBT and elucidate the clonal relationship between bilateral ovarian SMBTs. We also compared the mutational profiles between SMBTs and concurrent invasive carcinomas. Formalin-fixed, paraffin-embedded tissue specimens were retrieved from 28 patients diagnosed with SMBT. Massively parallel sequencing of 409 cancer-related genes was conducted to identify somatic mutations in 33 SMBT samples and four concurrent invasive carcinoma specimens. TERT promoter mutations were assessed by Sanger sequencing, whereas immunohistochemistry was used as a surrogate tool for detecting deletions or epigenetic silencing of relevant tumor suppressor genes. Twenty-six (92.9%) of the 28 patients were diagnosed with stage I SMBTs. Seven (25%) cases showed bilateral ovarian involvement and 13 (46%) had concomitant endometriosis. Concurrent ovarian carcinomas were identified in three patients, whereas one case had a synchronous endometrial carcinoma. Somatic mutations in the KRAS, PIK3CA, and ARID1A genes were identified in 100, 60.7, and 14.3% of SMBT samples, respectively. In contrast, TERT promoter mutations and DNA mismatch repair deficiencies were absent. Sequencing of paired specimens from patients with bilateral SMBT revealed the presence of at least two shared somatic mutations, suggestive of a clonal relationship. Similarly, we identified shared somatic mutations between SMBT samples and concurrent ovarian carcinoma specimens. Taken together, these findings demonstrated a distinct mutational landscape of SMBT in which (1) KRAS is invariably mutated, (2) PIK3CA is frequently mutated, and (3) TERT promoter mutations and DNA mismatch repair deficiencies are absent. Our findings represent the first extensive characterization of this rare ovarian neoplasm, with potential implications for disease classification and molecular diagnostics.

When to Worry about Cancer: Concurrent Carcinoma and Recurrence in Borderline Ovarian Tumors.

The objectives of this study were to identify and assess the factors associated with concurrent carcinoma and recurrence in women with epithelial borderline ovarian tumors. The cancer and pathology databases at a tertiary care academic cancer center were queried for all borderline ovarian tumors from 2005 to 2015. Cases with/without concurrent ovarian carcinoma and with/without recurrence were compared. A total of 123 women with borderline tumors were identified (mean age 51.3 years). Concurrent carcinoma was present in 31 (25.2%). Women with concurrent carcinoma were significantly more likely to be peri- or postmenopausal, have an elevated CA-125, and have a nonserous histology. Seven (5.7%) women's cancer recurred at a mean of 23.5 months (mean follow-up 30.0 months). Women with recurrence were more likely to be nonwhite, have concurrent invasive carcinoma, and have had residual disease at the time of surgery. Epithelial borderline ovarian tumors often co-exist with carcinoma and occur more frequently in postmenopausal women, in women with elevated CA-125, and in tumors with nonserous histology. The presence of any of these factors should alert clinicians to the potential need for comprehensive staging at the time of surgery. The recurrence of borderline tumors is associated with nonwhite race, concurrent carcinoma, and residual disease at initial surgery.

Prevalence of Germline Mutations Associated With Cancer Risk in Patients With Intraductal Papillary Mucinous Neoplasms

Many patients with pancreatic adenocarcinoma carry germline mutations associated with increased risk of cancer. It is not clear whether patients with intraductal papillary mucinous neoplasms (IPMNs), which are precursors to some pancreatic cancers, also carry these mutations. We assessed the prevalence of germline mutations associated with cancer risk in patients with histologically confirmed IPMN. We obtained nontumor tissue samples from 315 patients with surgically resected IPMNs from 1997 through 2017, and we sequenced 94 genes with variants associated with cancer risk. Mutations associated with increased risk of cancer were identified and compared with individuals from the Exome Aggregation Consortium. We identified 23 patients with a germline mutation associated with cancer risk (7.3%; 95% confidence interval, 4.9-10.8). Nine patients had a germline mutation associated with pancreatic cancer susceptibility (2.9%; 95% confidence interval, 1.4-5.4). More patients with IPMNs carried germline mutations in ATM (P < .0001), PTCH1 (P < .0001), and SUFU (P < .0001) compared with controls. Patients with IPMNs and germline mutations associated with pancreatic cancer were more like to have concurrent invasive pancreatic carcinoma compared with patients with IPMNs without these mutations (P < .0320). In sequence analyses of 315 patients with surgically resected IPMNs, we found that almost 3% to carry mutations associated with pancreatic cancer risk. More patients with IPMNs and germline mutations associated with pancreatic cancer had concurrent invasive pancreatic carcinoma compared with patients with IPMNs without these mutations. Genetic analysis of patients with IPMNs might identify those at greatest risk for cancer.

Characterization of Molecular Subtypes of Paget Disease of the Breast Using Immunohistochemistry and In Situ Hybridization.

Paget disease of the breast, in most cases, represents intraepidermal spread of ductal carcinoma in situ. Molecular subtypes of invasive carcinoma of the breast have prognostic and therapeutic significance and show characteristic distribution. Little is known about the distribution of molecular subtypes in Paget disease of the breast. To examine the distribution of molecular subtypes in Paget disease of the breast and to compare them to concurrent invasive carcinoma of the breast, if present. We examined 48 cases of Paget disease of the breast with immunohistochemistry and antibodies against estrogen and progesterone receptors, human epidermal growth factor receptor 2 (HER2), and Ki-67, as well as HER2 chromogenic in situ hybridization, to classify the cases into molecular subtypes. Then, we compared the results to the molecular subtypes of associated invasive carcinoma of the breast, if present. The HER2 subtype was the most common found in Paget disease of the breast, followed by the luminal B subtype and 2 cases of the triple-negative subtype. The associated invasive carcinoma cases were most often of the luminal B subtype, followed by the HER2 subtype and the triple-negative subtype. The molecular subtype of Paget disease and invasive carcinoma was congruent in most of the cases. Molecular subtypes of invasive carcinoma of the breast can already be detected in Paget disease. The distribution of molecular subtypes of Paget disease and of Paget disease-associated invasive carcinoma differs from invasive carcinoma without associated Paget disease, with the HER2 subtype overrepresented in Paget disease and associated invasive carcinoma and the luminal and triple-negative subtypes underrepresented.

Urothelial Carcinoma In Situ of the Bladder With Glandular Differentiation: Report of 92 Cases.

Urothelial carcinoma in situ (CIS) of the bladder with glandular differentiation (CIS-GL) is rare with some showing an association with small cell carcinoma. There is a paucity of data on whether CIS-GL diagnosed in the absence of invasive carcinoma is associated with an increased risk of developing small cell carcinoma of the bladder. Twenty-seven cases of CIS-GL were identified from the consult files of one of the authors from 2008 to 2015 without prior or coexisting invasive carcinoma at the time of diagnosis. Sixty-five additional cases were identified with concurrent CIS-GL and invasive carcinoma to assess the nature of the association. Of the 27 cases with only CIS-GL without invasive carcinoma at the time of diagnosis, follow-up time ranged from 11 to 91 months (mean, 41.1 mo). Of 24/27 cases with follow-up information: 13 (54.2%) had no evidence of disease at last follow-up, typically treated with induction and maintenance Bacillus Calmette-Guerin; 3 (12.5%) patients underwent radical cystectomy due to disease progression; 2 (8.3%) patients had recurrent CIS, and 1 (4.2%) had recurrent noninvasive low-grade papillary urothelial carcinoma (UC) (these patients underwent transurethral resection of the bladder and Bacillus Calmette-Guerin treatment); 2 (8.3%) patients died of metastatic UC; and 3 (12.5%) died of other or unknown causes. Of note, none of these 24 patients developed small cell carcinoma. Of the 65 cases with concurrent CIS-GL and invasive carcinoma, the invasive carcinoma was: pure UC in 29/65 (45%); invasive UC with GL in 13/65 (20%); coexisting small cell carcinoma and invasive UC in 8/65 (12%); plasmacytoid UC in 7/65 (11%); sarcomatoid UC in 3/65 (5%); micropapillary UC in 2/65 (3%); squamous in 2/65 (3%); and signet ring with colloid features in 1/65 (1%). Patients with CIS-GL without invasive carcinoma are at significant risk for cancer progression and in a minority of cases at risk for death from bladder carcinoma, similar to usual CIS. Typically, subsequent invasive carcinoma is UC rather than adenocarcinoma. Similarly, the largest fraction of concurrent invasive carcinoma and CIS-GL is UC. However, this study for the first time demonstrates the wide spectrum of other UC variants that coexist with CIS-GL, including a sizeable minority of cases with invasive UC with GL. Although there is a disproportionately high fraction of CIS-GL with coexisting small cell carcinoma, small cell carcinoma does not seem to develop at high frequency following the diagnosis and treatment of CIS-GL.

ERG and PTEN status of isolated high-grade PIN occurring in cystoprostatectomy specimens without invasive prostatic adenocarcinoma

High-grade prostatic intraepithelial neoplasia (HGPIN) is widely believed to represent a precursor to invasive prostatic adenocarcinoma. However, recent molecular studies have suggested that retrograde spread of invasive adenocarcinoma into pre-existing prostatic ducts can morphologically mimic HGPIN. Thus, previous molecular studies characterizing morphologically identified HGPIN occurring in radical prostatectomies or needle biopsies with concurrent invasive carcinoma may be partially confounded by intraductal spread of invasive tumor. To assess ERG and PTEN status in HGPIN foci likely to represent true precursor lesions in the prostate, we studied isolated HGPIN occurring without associated invasive adenocarcinoma in cystoprostatectomies performed at Johns Hopkins between 2009 and 2014. Of 344 cystoprostatectomies, 33% (115/344) contained invasive prostatic adenocarcinoma in the partially submitted prostate (10 blocks/case on average) and were excluded from the study. Of the remaining cases without sampled cancer, 32% (73/229) showed 133 separate foci of HGPIN and were immunostained for ERG and PTEN using genetically validated protocols. Of foci of HGPIN with evaluable staining, 7% (8/107) were positive for ERG. PTEN loss was not seen in any HGPIN lesion (0/88). Because these isolated HGPIN foci at cystoprostatectomy are unlikely to represent retrograde spread of invasive tumor, our study suggests that ERG rearrangement, but not PTEN loss, is present in a minority of potential neoplastic precursor lesions in the prostate.

Abstract P1-15-03: Long term outcomes in patients with phyllodes tumor of the breast: The UT MD Anderson experience

Abstract Purpose: Phyllodes tumor is a relatively rare disease of the breast, and the risk factors for local versus distant failure are unclear. The goal of this study was to identify factors influencing local, distant, and cause-specific survival outcomes in patients with phyllodes tumors, and to assess the impact of local radiotherapy (RT). Methods: We retrospectively reviewed the records of 387 patients recorded in the MD Anderson tumor registry as having "cystosarcoma phyllodes" or "phyllodes". After excluding patients with recurrent disease at presentation to the institution, concurrent invasive ductal carcinoma, absence of confirmation of phyllodes tumor, or inadequate follow up after surgery, 229 patients diagnosed from 1964-2011 were evaluable. The median tumor size was 4 cm (range, 0.7-28 cm); histology was benign in 29%, indeterminate in 7%, and malignant in 41% (23% unknown). Stromal overgrowth was present in 18% (n=40). Local therapy consisted of breast-conserving surgery (n=184) or mastectomy (n=43); 15% (n=34) also received local RT. Chemotherapy was administered in 9% (n=21). We used Kaplan-Meier analyses and Cox proportional hazards models to estimate the associations between patient/tumor characteristics and treatment on local control (LC), distant metastasis-free survival (DMFS), and cause specific survival (CSS). Results: At a median follow-up of 76 months (range, 1-485 months), the actuarial 5-yr LC for the entire cohort was 75%; 5-yr DMFS was 78%; and 5-yr CSS was 86%. Factors influencing LC included receipt of RT (5-yr LC 97% versus 72%, p=.005) and age over 50 (85% versus 72%, p=.044). Neither malignant histology nor stromal overgrowth increased the risk of local failure. Factors influencing DMFS included malignant histology (5-yr DMFS 65% versus 91%, p=.001) and stromal overgrowth (50% versus 84%, p&amp;lt;.001). Factors influencing CSS included malignant histology (5-yr CSS 77% versus 100%, p=.002) and stromal overgrowth (58% versus 92%, p&amp;lt;.001). Patients with stromal overgrowth or malignant histology were much more likely to receive RT (p&amp;lt;.001 for both factors). RT improved 5-yr LC for both breast conserved and mastectomy patients, but did not improve DMFS or CSS. In multivariable models, the following associations were noted (HR=hazard ratio; CI= 95% confidence interval): LC – RT (HR 0.13, CI .03-.55); DMFS – malignant histology (HR 2.99, CI 1.41-6.34); CSS – malignant histology (HR 4.18, CI 1.43-12.24). Conclusions: Adjuvant RT after surgery improves local control in phyllodes tumor; however, it does not improve DMFS or CSS. Stromal overgrowth and malignant histology are associated with worse DMFS and CSS, but do not impact local control. Therefore malignant histology and stromal overgrowth should not be deciding factors in the use of local RT, as escalated local therapy in patients with these tumor characteristics does not improve DMFS or CSS. Other strategies should be considered for patients with phyllodes tumor who are at high risk of distant failure, including systemic therapy. Citation Format: Bobbi A Porche, Pamela K Allen, Simona Shaitelman, B Ashleigh Guadagnolo, Wendy A Woodward, Constance Albarracin, Abenaa M Brewster, Kelly K Hunt, Welela Tereffe. Long term outcomes in patients with phyllodes tumor of the breast: The UT MD Anderson experience [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-15-03.

Intracystic papillary carcinoma of breast: interrelationship with in situ and invasive carcinoma and a proposal of pathogenesis: array comparative genomic hybridization study of 14 cases

Classifying intracystic papillary carcinoma under invasive or in situ ductal carcinoma is still a matter of debate. The purpose of this study was to explore the genomic relationship of this tumor to its concurrent invasive ductal carcinoma and ductal carcinoma in situ using array comparative genomic hybridization. Intracystic papillary carcinoma cases were classified into three categories: pure, with concurrent ductal carcinoma in situ or with concurrent invasive ductal carcinoma. Each component was dissected using laser capture microdissection. DNA was extracted and array comparative genomic hybridization was performed. The test of difference in copy number changes among the three tumors was carried out using CGHMultiArray. Intracystic papillary carcinoma clustered with four of five concurrent ductal carcinoma in situ cases and with two of two invasive ductal carcinoma cases. Intracystic papillary carcinoma showed the highest proportions of genome copy number aberration, followed by ductal carcinoma in situ, and then by invasive ductal carcinoma (P=0.06). Comparing intracystic papillary carcinoma with invasive ductal carcinoma vs without invasive ductal carcinoma, the former had 11q22.1–23.3 loss (P=0.031) and chr5 gain (P=0.085), and was enriched with matrix metalloproteinase genes. Comparing intracystic papillary carcinoma with ductal carcinoma in situ vs without ductal carcinoma in situ, the former had gain in 5q35.3 (P=0.041), 8q24.3 (P=0.041) and 21q13.2 to 21q13.31 (P=0.011). Comparing intracystic papillary carcinoma with ductal carcinoma in situ, the latter acquired a group of genes involved in cell adhesion and motility, whereas intracystic papillary carcinoma differentially expressed genes that are involved in papillary carcinomas of other organs (thyroid and kidney). We conclude that the overall molecular change in intracystic papillary carcinoma is closer to ductal carcinoma in situ than to invasive ductal carcinoma, which may explain the indolent behavior of this tumor. We offer herein a proposal of intracystic papillary carcinoma pathogenesis through its relation to invasive ductal carcinoma and ductal carcinoma in situ.

Florid lobular carcinoma in situ: molecular profiling and comparison to classic lobular carcinoma in situ and pleomorphic lobular carcinoma in situ

We evaluated genomic alterations and biomarker expression in 20 florid lobular carcinomas in situ using array-based comparative genomic hybridization and immunohistochemical analysis. The genetic characteristics of florid lobular carcinoma in situ were compared with 20 classic lobular carcinomas in situ and 21 pleomorphic lobular carcinomas in situ (which included 8 apocrine variants), from our previously published data performed on a similar array-based comparative genomic hybridization platform. All 20 florid lobular carcinoma in situ cases were E-cadherin negative, and 92% were positive for estrogen receptor. Cyclin D1 expression correlated significantly negatively with estrogen receptor expression and was higher in cases with cyclin D1 (CCND1) gene amplification. Compared with classic lobular carcinoma in situ, florid lobular carcinoma in situ displayed significantly more fraction genome alteration (mean, 0.109 versus 0.072; P=.007), fraction genome loss (mean, 0.06 versus 0.03; P=.007), numbers of breakpoints (mean, 11.55 versus 6.95; P=.002), numbers of chromosome with breakpoints (mean, 5.85 versus 3.8; P=.004), and higher numbers of amplifications (mean, 2.10 versus 0.25; P=.03). Interestingly, florid lobular carcinoma in situ had the same genetic complexity as apocrine pleomorphic lobular carcinoma in situ. Our study demonstrated that florid lobular carcinoma in situ shares the cytologic features, E-cadherin loss, and the lobular genetic signature of 1q gain and 16q loss found in classic lobular carcinoma in situ. However, this variant demonstrates more genomic alterations than classic lobular carcinoma in situ and shares the same genetic complexity as apocrine pleomorphic lobular carcinoma in situ. Our data support the conclusion that florid lobular carcinoma in situ is genetically more advanced compared with the indolent phenotype of classic lobular carcinoma in situ. This may explain the greater frequency of concurrent invasive carcinoma in florid lobular carcinoma in situ compared with classic lobular carcinoma in situ.

Cytoplasmic PTEN protein loss distinguishes intraductal carcinoma of the prostate from high-grade prostatic intraepithelial neoplasia

Intraductal carcinoma of the prostate is a marker of aggressive disease. However, intraductal carcinoma exists on a morphologic continuum with high-grade prostatic intraepithelial neoplasia (PIN) and distinguishing intraductal carcinoma from PIN is a common diagnostic dilemma with significant clinical implications. We evaluated whether immunostains for PTEN and ERG can sensitively identify intraductal carcinoma and accurately distinguish it from high-grade PIN. A combined immunostain for PTEN, ERG, p63 and CK903 was developed and validated. Radical prostatectomy specimens with lesions meeting criteria for intraductal carcinoma (n=45), intraductal cribriform proliferations falling short of intraductal carcinoma (n=15), and PIN lesions (n=39) were retrospectively identified and assessed for PTEN and ERG. Cytoplasmic PTEN loss was identified in 84% (38/45) of the intraductal carcinoma and 100% (15/15) of intraductal cribriform proliferation cases. In contrast, cytoplasmic PTEN loss was never observed in PIN (0/39; P<0.0001). Of the 53 cases of intraductal carcinoma or intraductal cribriform proliferation with cytoplasmic PTEN loss, it was homogeneously lost in 42 cases (79%). Weak, focal nuclear positivity for PTEN was retained in 31 of these 42 cases (74%). ERG expression was identified in 58% (26/45) of intraductal carcinoma and 67% (10/15) of intraductal cribriform proliferations compared with 13% (5/39) of PIN. Concordance between the PTEN/ERG status of the intraductal carcinoma lesions and the concurrent invasive carcinoma was high (>95% and P<0.0001 for each), and substantially less for PIN and the concurrent invasive tumor (83% for PTEN and 67% for ERG; P=NS for each). Cytoplasmic PTEN loss occurs in the majority of intraductal carcinoma and intraductal cribriform proliferation cases. Cytoplasmic PTEN loss was never observed in PIN (100% specificity). Our study identifies PTEN loss as a potentially useful marker to distinguish intraductal carcinoma from PIN and provides a plausible molecular explanation for why intraductal carcinoma is associated with poor prognosis.

Chronic Lymphocytic Leukemia Involving the Breast Parenchyma, Mimicker of Invasive Breast Cancer: Differentiation on Breast MRI

Leukemic involvement of the breast is rare, particularly involvement by chronic lymphocytic leukemia (CLL). While concurrent invasive ductal carcinoma and CLL manifesting as a collision tumor in the breast is extremely rare, this association (CLL and carcinoma) has been described in other organs. We report here a case of a 58-year-old woman with concurrent invasive ductal carcinoma and CLL and describe the imaging features of CLL, particularly the differentiation on MRI.

Biphasic Papillary and Lobular Breast Carcinoma With PIK3CA and IDH1 Mutations

Morphologic "special types" of breast carcinomas have been recognized for many years, and their molecular and genetic properties have not been specifically studied until recently. Lobular carcinoma lacks functional E-cadherin expression but shares molecular similarities with low-grade invasive ductal carcinomas. Papillary carcinoma is relatively rare, and molecular features are just being elucidated. We report a case of concurrent invasive lobular and papillary carcinoma, the latter with extensive nodal involvement. Multiplex screening for activating point mutations identified different point mutations in the distinct morphologic components: lobular PIK3CA H1047R, papillary; PIK3CA Q546P, and IDH1 R132H. These molecular data favor coincidental "collision tumors" over clonal evolution. The IDH1 R132H point mutation is common in gliomas and acute myelogenous leukemia, but this has not been previously reported in breast carcinoma. The characterization of activating point mutations in morphologic special types of breast carcinoma may suggest avenues amenable to targeted therapy.

Chronic lymphocytic leukemia mimicking recurrent carcinoma of the breast: Case report and review of the literature

Secondary localization of chronic lymphocytic leukemia (CLL) in breast is rare, while concurrent invasive ductal carcinoma and CLL manifesting as a collision tumor in breast is extremely rare. The observation of a CLL infiltration closely associated with a distinct breast neoplasm with the absence of any other localization for the leukemia is an indisputable argument for a relationship between the two diseases. The presence of both tumors is not simply due to chance. This association (CLL and carcinoma) has also been described in other organs. Hereafter, we report a second case of an 80 year-old woman in whom a leukemic infiltrate was confined to the region immediately surrounding poorly differentiated primary breast carcinoma, and we will discuss the association between CLL and carcinoma.

MicroRNA expression patterns in lobular neoplasia.

10551 Background: Lobular carcinoma in situ (LCIS) is a marker of increased risk for subsequent development of invasive breast cancer. Molecular studies have identified a clonal relationship between LCIS and concurrent invasive lobular carcinoma (ILC), suggesting that LCIS may be a precursor lesion of ILC. We hypothesized that differences in miRNA expression patterns might exist in LCIS lesions with concurrent ILC compared with LCIS lesions found alone. Methods: RNA was collected from matched frozen and archival formalin fixed paraffin embedded (FFPE) breast tissue using TRIZOL extractions. MiRNA expression profiling was performed using the Illumina miRNA DASL assay, in duplicate experiments, allowing simultaneous profiling of 735 miRNAs. MiRNAs of interest were further validated and analyzed by quantitative RT-PCR (qrt-PCR) in triplicate. To verify our data by localizing specific miRNA sequences of interest, in situ hybridization was performed on FFPE sections using a one-day protocol with locked nucleic acid (LNA) detection probes for miR-375 and miR-182, the U6 small nuclear RNA probe as a positive control and a scrambled miRNA probe as a negative control. Results: qrt-PCR analysis of the miR-183/182/96 cluster and miR-375 was performed using normal breast tissue, LCIS alone, and matched synchronous LCIS and ILC. A trend of increasing miRNA expression correlating with a model of histological progression toward invasive disease was observed. Results of in-situ hybridization confirmed this trend, showing the weakest signal intensity for both miR-375 and miR-182 in normal breast tissue, a stronger signal in LCIS alone, and the strongest signal in LCIS associated with synchronous ILC. Localization of signal to the nucleus was observed in normal breast tissue and LCIS alone, while a more diffuse cytoplasmic localization pattern was observed in LCIS associated with ILC, possibly suggesting nucleocytoplasmic transport for further processing of these miRNAs during progression to a more invasive phenotype. Conclusions: Upregulation of miR-375 and the miR-183/182/96 cluster in LCIS may correlate with risk for progression to ILC. These novel biomarkers may also be potential targets for treatment.