Impact of NOTCH1 expression in primary breast adenoid cystic carcinoma.

AIMS: Adenoid cystic carcinoma (AdCC) originates from salivary-type like glands in the head and neck, lung, and breast. AdCC shows chromosomal translocation, resulting in MYB::NFIB fusion and overexpression of MYB. Recently, NOTCH1 pathway alteration has been recognised in a subset of patients with salivary gland AdCC and has been shown to be associated with poor survival. In this study, we investigated the correlation of NOTCH1 pathway alteration with the clinical outcome of patients with primary breast AdCC by examining NOTCH1 immunoreactivity in attempts to better predict clinical outcomes. METHODS: We identified 25 cases of breast AdCC, reviewed the clinical outcome and performed immunohistochemical (IHC) staining for NOTCH1 on FFPE sections. RESULTS: IHC evaluation of NOTCH1 expression in 25 cases of primary breast AdCCs revealed a positive correlation between NOTCH1 expression and primary tumour size. All cases with NOTCH1 expression were greater than 15 mm in size at presentation but only 50% of NOTCH1 negative tumours were greater than 15 mm. We demonstrated a positive correlation between NOTCH1 positive AdCCs and recurrence/metastases. 63.6% of NOTCH1 positive AdCCs had either metastases or recurrence. On the contrary, only 21.5% of NOTCH1 negative AdCCs had recurrence or metastases. AdCCs with NOTCH1 positivity correlated with inferior relapse free survival (median 33 vs 129 months). CONCLUSIONS: Our study demonstrates that in patients with breast AdCC, overexpression of NOTCH1 ≥20% is associated with larger tumour size and aggressive clinical outcomes. Importantly, NOTCH1 inhibitors may have potential therapeutic effect in patients with breast AdCC.

Immediate and delayed risk of breast cancer associated with classic lobular carcinoma in situ and its variants.

OBJECTIVE: To determine the risk of breast cancer due to lobular carcinoma in situ (LCIS). METHODS: This retrospective IRB-approved study identified cases of LCIS after percutaneous breast biopsy from 7/2005 to 7/2022. Excluded were cases with less than 2 years of imaging surveillance or a concurrent ipsilateral breast cancer diagnosis within 6 months of the LCIS diagnosis. Final outcomes of cancer versus no cancer were determined by pathology at surgical excision or the absence of cancer on imaging surveillance. RESULTS: A total of 116 LCIS lesions were identified. The primary imaging findings targeted for percutaneous biopsy included calcifications (50.0%, 58/116), MR enhancing lesions (25.0%, 29/116), noncalcified mammographic architectural distortions (10.3%, 12/116), or masses (14.7%, 17/116). Surgical excision was performed in 49.1% (57/116) and imaging surveillance was performed in 50.9% (59/116) of LCIS cases. There were 22 cancers of which 11 cancers were discovered at immediate excision [19.3% (11/57) immediate upgrade] and 11 cancers developed later while on imaging surveillance [18.6% (11/59) delayed risk for cancer]. Among all 22 cancers, 63.6% (14/22) occurred at the site of LCIS (11 at immediate excision and 3 at surveillance) and 36.4% (8/22) occurred at a location away from the site of LCIS (6 in a different quadrant and 2 in the contralateral breast). CONCLUSION: LCIS has both an immediate risk (19.3%) and a delayed risk (18.6%) for cancer with 90.9% occurring in the ipsilateral breast (63.6% at and 27.3% away from the site of LCIS) and 9.1% occurring in the contralateral breast.

A Comparative Evaluation of TRPS1 and GATA3 in adenoid cystic, secretory, and acinic cell carcinomas of the breast and salivary gland.

GATA3 is the most used marker to determine tumors' breast origin, but its diagnostic value in triple-negative breast cancer (TNBC) is limited. The newly identified TRPS1 is highly sensitive and specific for breast carcinoma, especially TNBC. Here, we compared the utility of TRPS1 and GATA3 expression in a subset of salivary gland-type breast tumors (including adenoid cystic, acinic cell, and secretory carcinomas [AdCC, ACC, and SC, respectively]), and we compared TRPS1 and GATA3 expression of such tumors with head and neck (H&N) and AdCC of upper respiratory tumors. TRPS1 was strongly expressed in basaloid TNBC and AdCCs with solid components, including 100 % of mixed and solid breast AdCCs. However, TRPS1 was positive in only 50 % cribriform AdCCs. Expression patterns of TRPS1 in H&N and upper respiratory AdCC were similar. TRPS1 was positive in 30 % of H&N cribriform AdCCs but was strongly expressed in mixed AdCC (67 %) and solid AdCC (100 %). In the upper respiratory AdCCs, TRPS1 was positive in 58.4 % of cribriform AdCCs and positive in 100 % of AdCCs with solid components. On the contrary, GATA3 was negative in predominant AdCCs of the breast, H&N, and upper respiratory tract. These data show that GATA3 and TRPS1 expression varies AdCCs. In addition, TRPS1 and GATA3 expression patterns were similar SC and ACC of breast and H&N. Both markers were positive in SC and negative in ACC. Therefore, TRPS1 and GATA3 cannot be used to differentiate salivary gland-type carcinomas of breast origin from those of upper respiratory or H&N origin.

Isolated Flat Epithelial Atypia: Upgrade Outcomes After Multidisciplinary Review-Based Management Using Excision or Imaging Surveillance.

Objective: To compare flat epithelial atypia (FEA) upgrade rates after excision versus surveillance and to identify variables associated with upgrade. Methods: This single-institution retrospective study identified isolated FEA cases determined by percutaneous biopsy from April 2005 through July 2022 with excision or ≥2 years surveillance. All cases were recommended for excision or surveillance based on multidisciplinary discussion of clinical, imaging, and pathologic variables with emphasis on sampling adequacy and significant atypia. Truth was determined by pathology at excision or the absence of cancer on surveillance. Upgrade was defined as cancer occurring ≤2 cm from the biopsy site. Demographic, imaging, and biopsy variables were compared between those that did and did not upgrade. Results: Among 112 cases of isolated FEA, imaging findings included calcifications in 81.3% (91/112), MRI lesions in 11.6% (13/112), and distortions or masses in 7.1% (8/112). Excision was recommended in 12.5% (14/112) and surveillance in 87.5% (98/112) of cases. Among those recommended for excision, 28.6% (4/14) of cases were upgraded, all to ductal carcinoma in situ. In those recommended for surveillance, 1.0% (1/98) were upgraded to invasive cancer. Overall, FEA had a 4.5% (5/112) upgrade rate, and 2.7% (3/112) also developed cancer >2 cm from the FEA. There were no significant differences in demographic, imaging, and biopsy variables between those that did and did not upgrade to cancer. Conclusion: Multidisciplinary management of isolated FEA distinguishes those at higher risk of upgrade to cancer (28.6%) in whom surgery is warranted from those at low risk of upgrade (1.0%) who can be managed non-operatively.

Absence of lobular carcinoma in situ is a poor prognostic marker in invasive lobular carcinoma.

AIM: To determine if the outcomes of patients with ILC co-occurring with LCIS are similar to pure ILC and if the presence of LCIS is a prognostic factor for ILC. METHODS: In an observational, population-based investigation using data from the MD Anderson breast cancer prospectively collected electronic database, we analysed patients with a diagnosis of stage I-III ILC. Patients were divided into two groups: those with ILC with co-occurring ipsilateral LCIS (ILC + LCIS) and those with pure ILC without a histologically detected co-occurring ipsilateral LCIS (ILC alone). We obtained data on demographics, pathologic tumour size (pT), pathologic lymph node (pN) involvement, estrogen (ER), progesterone (PR) receptor status, HER2 status, Ki67, treatment received, distant recurrence-free and overall survival (DRFS, OS). RESULTS: We identified 4217 patients with stage I-III ILC treated at MD Anderson between 1966 and 2021. 45% of cases (n = 1881) had co-existing LCIS. Statistically and numerically, ILC alone tended to associate with pT4 and pN3 stage (P < 0.001), ER/PR negativity (P = 0.0002), HER2 positivity (P = 0.010), higher Ki67 (P = 0.005), non-classical ILC subtype (P = 0.04) and more exposure to neoadjuvant chemotherapy (P = 0.0002) compared to the ILC + LCIS group. The median follow-up time was 6.5 years. Patients with ILC + LCIS had better median DRFS (16.8 versus 10.1 years, Hazard ratio [HR] 0.55, 95% confidence interval [CI] 0.50-0.60, P < 0.0001) and better median OS (18.9 versus 13.7 years, HR 0.62, 95% CI 0.56-0.69; P < 0.0001). Multivariate analysis showed the absence of LCIS to be an independent poor prognostic factor along with a higher pT stage and higher pN stage for DRFS and OS. CONCLUSION: The findings of this study suggests that the absence of ipsilateral LCIS with ILC is an independent poor prognostic factor and that further studies are warranted to understand this phenomenon.

Nuclear staining for pan-Trk by immunohistochemistry is highly specific for secretory carcinoma of breast: pan-Trk in various subtypes of breast carcinoma.

AIMS: Secretory carcinoma of breast (SCB) typically harbours ETV6-NTRK3 gene fusion. Pan-Trk immunohistochemistry analysis (IHC) has been shown to be sensitive for SCB diagnosis. However, weak focal pan-Trk nuclear staining was previously found in 10% of non-secretory breast carcinomas. To further examine pan-Trk IHC specificity, we evaluated pan-Trk staining in various breast carcinoma subtypes. METHODS: The study cohort consisted of 346 invasive breast carcinomas (IBCs), including 8 SCBs and 48 triple-negative histological mimickers (36 metaplastic carcinomas, including 12 matrix-producing carcinomas; 5 adenoid cystic carcinomas; 5 apocrine carcinomas; 2 acinic cell carcinomas), 101 triple-negative IBCs of no special type, 101 estrogen receptor (ER)-positive/HER2-negative IBCs and 88 HER2-positive IBCs. Six salivary gland secretory carcinomas were also included. Pan-Trk IHC was performed on tumours using a rabbit monoclonal pan-Trk antibody. Any nuclear staining in the invasive carcinoma cells was considered positive. RESULTS: All 14 secretory carcinomas from breast and salivary gland exhibited moderate to strong pan-Trk nuclear staining. In contrast, no pan-Trk nuclear staining was identified in any of the 338 non-secretory IBCs. Focal cytoplasmic pan-Trk staining was observed in nine non-secretory IBCs (2.7%), and was considered nonspecific and negative. CONCLUSIONS: Our results indicate that pan-Trk nuclear staining is highly specific for SCB. In low-grade to intermediate-grade IBCs that share histological features with SCB, adding pan-Trk to a routing panel of estrogen receptor/progesterone receptor/HER2 is highly diagnostic. Our results also support using pan-Trk IHC to differentiate SCB from its triple-negative histological mimickers, such as adenoid cystic carcinoma, matrix-producing carcinoma, apocrine carcinoma and acinic cell carcinoma.

Invasive Carcinoma With Skin Adnexal Trichilemmal Hair Follicular Differentiation Occurring in the Breast: A Case Report With Detailed Immunohistochemical and Molecular Analysis.

Cutaneous-type adnexal tumors involving the breast are rare and create a diagnostic dilemma as they are often indistinguishable from primary mammary neoplasms. Tumors showing hair follicular differentiation are particularly challenging due to their rarity and the subtle appreciation of the intricate microanatomy of the hair follicle. We report a triple negative cutaneous-type adnexal carcinoma with follicular differentiation involving the breast to bring attention to the existence of these specialized group of tumors which should be managed differently from conventional triple negative carcinomas of the breast.

TRPS1, GATA3, and SOX10 expression in triple-negative breast carcinoma.

A diagnostic dilemma can be encountered when primary triple-negative breast carcinoma (TNBC) without an in situ component or metastatic TNBCs lose the currently used organ-specific marker such as GATA3, raising concerns about metastatic carcinoma from other sites. In the current study, we compared the newly identified breast marker TRPS1 with currently used breast markers GATA3 and SOX10 in whole-tissue sections from 315 cases of various subtypes of TNBC. TRPS1 was highly expressed in 100% of triple-negative primary and metastatic invasive lobular carcinomas, 99% of triple-negative primary and metastatic invasive breast carcinoma of no special type (IBC-NST), and 95% of metaplastic breast carcinomas. In contrast, GATA3 and SOX10 were expressed in 94% and 0% of invasive lobular carcinomas, 63% and 74% of IBC-NST, and 50% and 49% of metaplastic breast carcinomas, respectively. For special-type TNBCs, both TRPS1 and GATA3 were negative in acinic cell carcinomas, most cribriform adenoid cystic carcinomas, and neuroendocrine carcinomas, but positive in secretory carcinomas. Triple-negative apocrine carcinoma was the only subtype of TNBC with positive GATA3 but negative TRPS1. These data indicate that TRPS1 is a highly sensitive marker for TNBCs with positivity not only in GATA3/SOX10-positive TNBCs but also in almost all GATA3/SOX10-negative TNBCs.

Metastatic nonhematopoietic neoplasms to the breast: a study of 238 cases.

The aim of this study was to review the clinicopathologic characteristics of metastatic nonhematopoietic malignancies to the breast, in order to identify salient features for practicing pathologists that are useful in distinguishing metastatic lesions from primary breast neoplasms. A total of 238 cases were identified during the period from January 2005 to January 2015. Clinicopathologic features of these cases were retrospectively reviewed. Primary tumors included melanoma (99, 42%), serous carcinoma (35, 15%), neuroendocrine neoplasm (32, 13%), sarcoma (23, 10%), and adenocarcinoma from various organs (47, 20%), and 2 others. Most metastases were unilateral (223, 94%) and unifocal (206, 87%) and were detected radiographically (167, 70%). Concurrent ipsilateral axillary metastasis occurred in 33 (14%) patients. Among 238 cases, 41 had metastatic disease to the breast concurrently or preceding the primary cancer diagnosis. Notably, in 39 (16%) cases, breast metastasis was the first clinical presentation of disease, and 16 (41%) of these cases were initially misdiagnosed as breast primaries. In contrast, with a known history of nonmammary primary tumors, only 4 of 197 (2%) cases were misdiagnosed (p < 0.0001). Metastatic tumors share many overlapping features with breast primary carcinomas. However, cases with a well-circumscribed tumor, lack of in situ component, estrogen receptor/progesterone receptor negativity, and unusual morphologic features should raise the consideration of metastatic disease. While clinical history is paramount for correct diagnosis, metastasis to the breast as the first clinical presentation is not uncommon.

Expression of TRPS1 in phyllodes tumor and sarcoma of the breast.

When a sarcomatous neoplasm is identified in the breast, distinguishing metaplastic carcinoma, malignant phyllodes tumor (MPT), and primary sarcoma is a diagnostic challenge, especially on small biopsies, as all these tumors may have overlapping morphological features, thoroughly grossing with histological examination and immunohistochemical staining being the standard approach to aid in classifying these lesions. Recently, we identified a highly sensitive and specific breast carcinoma marker TRPS1 with high expression in metaplastic breast carcinoma. In the current study, we tested TRPS1 in MPTs and primary sarcoma of the breast. We found TRPS1 was highly expressed (95%) within spindle cell, chondro-osseous, and/or liposarcomatous components of MPTs, in all breast primary chondrosarcomas and extraskeletal osteosarcomas, but not in other sarcomas of the breast. In extramammary sarcomas, TRPS1 was expressed in 28% of conventional chondrosarcomas and 56% of osteosarcomas of bone, but rarely in undifferentiated pleomorphic sarcomas (UPSs), liposarcomas, and angiosarcomas. In summary, MPTs may share similar genetic background with metaplastic carcinoma exhibiting TRPS1 expression, and TRPS1 may play a role in chondro-osseous differentiation because of its expression in chondro-osseous sarcomas from both breast and extramammary sites. Our findings suggest TRPS1 may be clinically useful in distinguishing MPT and metaplastic carcinoma from primary breast sarcoma except for tumors with chondro-osseous differentiation.

Axillary Nodal Metastases in Invasive Lobular Carcinoma Versus Invasive Ductal Carcinoma: Comparison of Node Detection and Morphology by Ultrasound.

BACKGROUND. Invasive lobular carcinoma is more subtle on imaging compared with invasive ductal carcinoma; nodal metastases may also differ on imaging between these two. OBJECTIVE. The purpose of this study was to determine whether invasive lobular carcinoma and invasive ductal carcinoma differ in the detection rate by ultrasound (US) of metastatic axillary nodes and in the metastatic nodes' US characteristics. METHODS. This retrospective study included 695 women (median age, 53 years) who had breast cancer in a total of 723 breasts (76 lobular, 586 ductal, 61 mixed ductal and lobular histology) with biopsy-proven axillary nodal metastases and who underwent pretreatment US. A single breast radiologist reviewed US images in patients with suspicious nodes on US and classified number of nodes, size, and morphology. Morphologic assessment used a previously described classification according to the relationship between node cortex and hilum. Nodal findings were compared between lobular and ductal carcinoma. A second radiologist independently classified node morphology in 241 cancers to assess interreader agreement. RESULTS. A total of 99 metastatic axillary nodes (15 lobular, 66 ductal, 18 mixed histology) were not visualized on US and were diagnosed by surgical biopsy. The remaining 624 metastatic nodes (61 lobular, 520 ductal, 43 mixed ductal and lobular histology) were visualized on US and diagnosed by US-guided fine-needle aspiration. US detected the metastatic nodes in 80.3% for lobular carcinoma versus 88.7% for ductal carcinoma (p = .04). Among metastatic nodes detected by US, retrospective review identified three or more abnormal nodes in 50.8% of lobular carcinoma versus 69.2% of ductal carcinoma (p = .003); node size was 2.0 cm or smaller in 65.6% for lobular carcinoma versus 47.3% for ductal carcinoma (p = .03); morphology was type III or IV (diffuse cortical thickening without hilar mass effect) rather than type V or VI (marked cortical thickening with hilar mass effect) in 68.9% for lobular carcinoma versus 28.8% for ductal carcinoma (p < .001). Interreader agreement assessment for morphology exhibited a kappa coefficient of 0.63 (95% CI, 0.54-0.73). CONCLUSION. US detects a lower percentage of nodal metastases in lobular than in ductal carcinoma. Nodal metastases in lobular carcinoma more commonly show diffuse cortical thickening and with less hilar mass effect. CLINICAL IMPACT. A lower threshold may be warranted to recommend biopsy of suspicious axillary nodes detected on US in patients with lobular carcinoma.

Primary Signet Ring Cell/Histiocytoid Carcinoma of the Eyelid: Clinicopathologic Analysis with Evaluation of the E-Cadherin/ß-Catenin Complex and Associated Genetic Alterations.

Signet Ring Cell (SRC)/Histiocytoid carcinoma of the eyelid is a rare neoplasm that shares histological and immunohistochemical similarities with diffuse gastric cancer and breast lobular carcinoma. The CDH1 gene, which encodes the E-cadherin protein, is the best known gene associated with these tumors. The structural and functional integrity of E-cadherin is regulated by interconnecting molecular pathways which might participate in the development of this disease. Hence, we analyzed the protein expression in key genes in E-cadherin-related pathways associated with primary SRC/Histiocytoid carcinoma of the eyelid. SRC/Histiocytoid carcinoma diagnosed in the eyelid/orbit at MD Anderson Cancer Center from 1990 to 2016 were evaluated. Clinicopathologic findings were studied to confirm the primary site of origin. Immunohistochemical studies for the expression of E-cadherin, ß-catenin, c-Myc, Cyclin D1, Src, and p53 were analyzed. Next generation sequencing for the detection of somatic mutations was performed on each tumor with matched normal tissue, examining 50 cancer-related genes. Four primary SRC/Histiocytoid carcinomas of the eyelid were diagnosed in four male patients aged 40-82 years. Immunohistochemically, two tumors with loss of E-cadherin expression had weak ß-catenin and low cytoplasmic staining for Src while the other two cases with intact E-cadherin showed strong ß-catenin expression and high cytoplasmic expression for Src. Cyclin D1 was focally positive in three cases. Somatic mutations in CDH1, PIK3CA, and TP53 genes were detected in two cases. Our results suggest an abnormality in the convergence of E-cadherin/ß-catenin pathways which may promote tumorigenesis by inducing expression of oncogenes such as Cyclin D1 and C-Myc. Mutations in CDH1, PIK3CA, and TP53 genes could induce E-cadherin dysfunction which takes part in the development and progression of this malignancy.

Evaluation of multiple transcriptomic gene risk signatures in male breast cancer.

Male breast cancer (BCa) is a rare disease accounting for less than 1% of all breast cancers and 1% of all cancers in males. The clinical management is largely extrapolated from female BCa. Several multigene assays are increasingly used to guide clinical treatment decisions in female BCa, however, there are limited data on the utility of these tests in male BCa. Here we present the gene expression results of 381 M0, ER+ve, HER2-ve male BCa patients enrolled in the Part 1 (retrospective analysis) of the International Male Breast Cancer Program. Using a custom NanoString™ panel comprised of the genes from the commercial risk tests Prosigna®, OncotypeDX®, and MammaPrint®, risk scores and intrinsic subtyping data were generated to recapitulate the commercial tests as described by us previously. We also examined the prognostic value of other risk scores such as the Genomic Grade Index (GGI), IHC4-mRNA and our prognostic 95-gene signature. In this sample set of male BCa, we demonstrated prognostic utility on univariate analysis. Across all signatures, patients whose samples were identified as low-risk experienced better outcomes than intermediate-risk, with those classed as high risk experiencing the poorest outcomes. As seen with female BCa, the concordance between tests was poor, with C-index values ranging from 40.3% to 78.2% and Kappa values ranging from 0.17 to 0.58. To our knowledge, this is the largest study of male breast cancers assayed to generate risk scores of the current commercial and academic risk tests demonstrating comparable clinical utility to female BCa.

Discordance in Diagnosis of Melanocytic Lesions and Its Impact on Clinical Management.

CONTEXT.­: Accurate diagnosis of melanocytic lesions is fundamental for appropriate clinical management. OBJECTIVE.­: To evaluate the degree of discordance, if any, between histopathologic diagnoses of melanocytic lesions at referring institutions and at a tertiary referral cancer center and the potential impact of such discordance on clinical management. DESIGN.­: We retrospectively identified all patients referred to our comprehensive cancer center for evaluation of a melanocytic lesion from January 2010 to January 2011. For each patient, the histopathologic diagnosis from the referring institution was compared with the histopathologic diagnosis from a dermatopathologist at our center. Discordances were classified as major if they resulted in a change in clinical management and minor if they did not. RESULTS.­: A total of 1521 cases were included. The concordance rates were 72.2% (52 of 72) for dysplastic nevus, 75.0% (15 of 20) for all other types of nevi, 91.1% (143 of 157) for melanoma in situ, 96.1% (758 of 789) for invasive melanoma, and 99.6% (478 of 480) for metastatic melanoma. Major discordances were found in 20.2% of cases (307 of 1521), and minor discordances were found in 48.8% of cases (742 of 1521). Compared with the guideline-based treatment recommendation based on the referring-institution diagnosis, the guideline-based treatment recommendation based on the cancer center diagnosis was more extensive in 5.9% (89 of 1521) of patients and less extensive in 5.0% (76 of 1521) of patients. CONCLUSIONS.­: Our findings underscore the importance of secondary histopathologic review of melanocytic lesions by expert dermatopathologists because significant changes in the diagnosis, tumor classification, and/or staging may be identified, thus, resulting in critical changes in recommendations for clinical management.

MYC and NOTCH1-positive postradiation cutaneous angiosarcoma of the breast.

Postradiation cutaneous angiosarcoma of the breast is a rare, delayed complication of adjuvant radiation treatment for breast carcinoma and is associated with a worse prognosis than the original primary cancer. Recent studies have characterized the diagnostic utility of MYC and NOTCH1 receptor expression as markers for secondary radiation-associated angiosarcomas. Herein, we report an exophytic secondary breast angiosarcoma with MYC and NOTCH1 immunoreactivity. This case illustrates the utility of these markers for the identification of radiation-associated angiosarcoma with MYC and NOTCH1 expression, potential for targeted therapy and need to identify patients for further studies of the clinicopathologic and prognostic significance.

Sinonasal analogue HPV related breast multiphenotypic carcinoma, a report of a case with the first description in the breast.

BACKGROUND: High grade basal-like breast carcinomas are triple negative, express basal cytokeratins, and are known for the overall poor prognosis and aggressive behavior. HPV related multiphenotypic sino-nasal carcinoma has overlapping histology with basal-like breast carcinomas, but carry the defining feature of association with high risk HPV. CASE PRESENTATION: We present a case of a perimenopausal woman with a non-healing ulcerated lesion involving the nipple and breast following a trauma. Biopsy performed showed an HPV-positive basal-like carcinoma with squamous differentiation involving the breast, analogous to multiphenotypic carcinoma previously described in the sinonasal tract. CONCLUSION: This is the first report of a case of a high- risk HPV related basal-like carcinoma with squamous differentiation, described in the literature. We highlight the morphology and immunophenotype of this lesion and its recognition when compared to other multiphenotypic lesions of the breast, and suggest that pathologists should consider HPV evaluation when encountering similar basal-like tumors involving the breast.

Value Added Impact of Both Point-of-Care and Laboratory Lactic Acid Analysis When Emergently Evaluating Cancer Patients.

INTRODUCTION: Cancer patients are immunosuppressed and may present to an emergency department with atypical symptoms. In the emergency setting, it is important ascertain rapidly if lactic acid levels are high, either due to sepsis or tumor lysis syndrome, to effectively manage symptoms. Therefore, it is critical to determine the blood lactic acid level to timely identify who is at risk of sepsis and provide early intervention. We have compared blood lactic acid concentrations (BLAC) in cancer patients obtained by point-of-care testing (POCT) and those measured by laboratory analysis in blood samples drawn within a short time of each other. METHODS: This was a retrospective study in cancer patients whose BLAC had been determined by POCT and laboratory analysis. Only those patients who had blood withdrawn for both testing methods within a 2-h timeframe were included in the study. Regressions were performed together with an analysis categorizing the BLAC from both testing methods. RESULTS: A total of 274 patients met the criteria for the study. The BLAC from POCT correlated well with the values from laboratory testing (R = 0.925). Categorization of BLAC showed that 88.32% of the patients had BLAC that directly matched between the two tests; 28 (10.22%) patients had a normal BLAC according to laboratory analysis but a high BLAC on POCT; and four (1.46%) patients had a high BLAC according laboratory analysis but normal BLAC on POCT. CONCLUSIONS: There was a high correlation between POCT and laboratory analysis values of BLAC in cancer patients, with the results from both testing methods agreeing 96% of the time. This finding suggests that POCT would suffice in most cases. Importantly, in 2% of the cancer patients who presented emergently, BLAC determined by POCT and laboratory analysis did not agree. Therefore, in subsequent decision-making, we recommend that if sepsis is suspected and BLAC determined by POCT is normal, nucleic acids, proteins, circulating cells, and interleukin-3 levels should also be obtained by POCT to confirm sepsis and/or rule out tumor lysis syndrome in patients with cancer.

Carcinoma In Situ Involving Sclerosing Adenosis on Core Biopsy: Diagnostic Pearls to Aid the Practicing Clinician and Avoid Overtreatment.

INTRODUCTION: Involvement of pre-existing benign lesions by ductal carcinoma in situ (DCIS) or lobular neoplasia (LN) can present difficult diagnostic challenges, and can easily cause misdiagnosis of invasive carcinoma and over-management of localized disease. Our objective was to gather the largest case series of DCIS and LN involving sclerosing adenosis (SA), and to report the characteristic features of these lesions, in order to provide histologic criteria for the diagnostician. METHODS: Our database was searched for core biopsy material diagnosed as carcinoma in situ involving adenosis. Glass slides and pathology reports were reviewed. The cases were studied for salient features, and clinical follow-up was also obtained. RESULTS: Thirty-one cases of DCIS or LN involving SA were obtained (12 cases of DCIS, 19 cases of LN including LCIS and ALH). Histomorphologic features commonly seen with DCIS or LN involving SA included lobulocentric architecture (31/31, 100%), myoepithelial cells visible by H&E at least focally (31/31, 100%), and separate areas of SA not involved by neoplasia (29/31, 93.5%). Features that were sometimes seen included hyaline basement membranes surrounding the lesion (14/31, 45.2%), DCIS/LN apart from the area of involvement by SA (16/31, 51.6%), and calcifications associated with DCIS/LN/SA (12/31, 38.7%). Features that were not commonly seen included desmoplasia (6/31, 19.4%), dense inflammation (4/31, 12.9%), and single epithelial cells enveloped by flattened myoepithelial cells (6/31, 19.4%). Of the ten cases of DCIS with known follow-up, four showed DCIS involving either SA or a complex SA on excision (4/10, 40%), four had only DCIS (4/10, 40%), one had DCIS with a small 1.8-mm focus of predominantly tubular carcinoma (1/10, 10%), and one showed invasive ductal carcinoma on excision (1/10, 10%). The latter case of invasive ductal carcinoma occurred in a patient who had a delay of 3 years from diagnosis to surgical resection. Of the eight cases of LN with surgical follow-up, seven had LCIS (7/8, 87.5%), and one showed only fibroadenoma and SA with no residual LN in the excised specimen (1/8, 12.5%). Importantly, no invasive carcinoma was identified in any of the resections for LN involving SA. CONCLUSIONS: In our series of carcinoma in situ (CIS) involving sclerosing adenosis diagnosed on core biopsy, lobular lesions involving SA were more common than ductal lesions. Ductal and lobular carcinoma in situ involving adenosis were best diagnosed by the low-power appearance of a lobulocentric pattern of growth. The most helpful diagnostic feature was the observation of additional foci of carcinoma in situ away from the adenosis. Immunohistochemical stains for myoepithelial cells were useful in particularly difficult cases. The presence of stromal desmoplasia does not preclude the diagnosis of carcinoma in situ involving adenosis. Knowledge of these diagnostic pearls can reduce over-interpretation of CIS on core biopsy and subsequent overtreatment.

Improving Patient Experience of Wait Times and Courtesy Through Electronic Sign-in and Notification in the Phlebotomy Clinic.

CONTEXT.­: The phlebotomy clinic, which sees on average 900 patients a day, was faced with issues of congestion and noise due to inefficient workflow and processes. The staff called each patient name for his or her turn, and patients were unsure of wait time and position in line. These factors led to unfavorable patient satisfaction regarding wait times and courtesy of the staff. OBJECTIVE.­: To improve patients' experience of wait times and courtesy in the phlebotomy clinic through an electronic sign-in and notification system, redesign of the area, and training of employees. DESIGN.­: An electronic sign-in and notification system was implemented in the phlebotomy clinic. Several sign-in stations and whiteboard wall monitors were installed in the clinic, along with a redesign of the patient flow. A Press Ganey survey was given to patients after their visit which included 3 questions related to wait times, courtesy, and information about delays, respectively. The mean responses for each month between March 2016 and December 2018 were aggregated and compared for each measure. RESULTS.­: Overall, wait time saw a 7.7% increase in satisfaction score, and courtesy saw a 1.0% increase in satisfaction score during the course of the several interventions that were introduced. The operational efficiency of the clinic also saw a veritable increase because the percent of patients processed within 20 minutes increased by 27%, from 62% (8212 of 13 245 blood draws) to 89% (11 703 of 13 143 blood draws). CONCLUSIONS.­: The interventions implemented proved to increase the patient satisfaction in each of the measures. The electronic sign-in and whiteboards provided valuable information to both patients and staff.