Immunohistochemical Staining Characteristics of Low-Grade Invasive Ductal Carcinoma Using the ADH5 Cocktail (CK5/14, P63, and CK7/18): A Potential Interpretative Pitfall.

Background: In our practice, the antibody cocktail ADH5 (CK5/14, p63, and CK7/18) helps with diagnostic challenges, such as identifying microinvasion and foci of invasive carcinoma, differentiating atypical ductal hyperplasia from hyperplasia of the usual type, and distinguishing basal phenotypes in triple-negative carcinomas. However, the ADH5 cocktail does have pitfalls and caveats. Methods: We describe our experience with the ADH5 cocktail of antibodies in breast pathology. Institutional knowledge and a literature search form our data sources. Results: We analyzed 44 cases. Four out of a total of 44 cases (9.1%)-two tubular carcinomas and two low-grade invasive breast carcinomas of no special type (ductal) with tubular features-showed an expected pattern of staining for ADH5 with a loss of brown (P63, CK5/14) staining around invasive glands and diffuse red (CK7/18) expression. Forty out of 44 (90.9%) cases showed an unexpected staining pattern (mixture of cytoplasmic brown and red). All 44 cases (100%) showed negative myoepithelial staining around invasive foci when separately stained for P63 and SMMH (Smooth Muscle Myosin Heavy). Conclusions: The unexpected staining pattern of ADH5 in low-grade invasive ductal carcinomas can be challenging to interpret in these lesions with low-grade cytology. The occurrence can cause confusion among users who employ multiplex stains, and it is important for users to be aware of this potential pitfall.

Two major chromosome evolution events with unrivaled conserved gene content in pomegranate.

Pomegranate has a unique evolutionary history given that different cultivars have eight or nine bivalent chromosomes with possible crossability between the two classes. Therefore, it is important to study chromosome evolution in pomegranate to understand the dynamics of its population. Here, we de novo assembled the Azerbaijani cultivar "Azerbaijan guloyshasi" (AG2017; 2n = 16) and re-sequenced six cultivars to track the evolution of pomegranate and to compare it with previously published de novo assembled and re-sequenced cultivars. High synteny was observed between AG2017, Bhagawa (2n = 16), Tunisia (2n = 16), and Dabenzi (2n = 18), but these four cultivars diverged from the cultivar Taishanhong (2n = 18) with several rearrangements indicating the presence of two major chromosome evolution events. Major presence/absence variations were not observed as >99% of the five genomes aligned across the cultivars, while >99% of the pan-genic content was represented by Tunisia and Taishanhong only. We also revisited the divergence between soft- and hard-seeded cultivars with less structured population genomic data, compared to previous studies, to refine the selected genomic regions and detect global migration routes for pomegranate. We reported a unique admixture between soft- and hard-seeded cultivars that can be exploited to improve the diversity, quality, and adaptability of local pomegranate varieties around the world. Our study adds body knowledge to understanding the evolution of the pomegranate genome and its implications for the population structure of global pomegranate diversity, as well as planning breeding programs aiming to develop improved cultivars.

Cough and Progressive Pleuritic Chest Pain With an Enlarging Cavity on Imaging.

CASE PRESENTATION: A 49-year-old woman sought treatment at the hospital for evaluation of an enlarging cavitary mass of the right lung associated with worsening ipsilateral pleuritic chest pain and cough. She had recent hospitalizations for complications relating to recurrent lung abscesses, including one in which she underwent wedge resection of the right lung. She had been treated with several courses of antibiotics, which only temporarily relieved her symptoms. She did not report any fevers, chills, skin changes, diarrhea, or changes to her bowel habits. Her long-term medications included albuterol, dapsone, and prednisone 15 mg or 20 mg doses alternating daily. Her only past medical history was asthma and primary cutaneous pyoderma gangrenosum. The patient never smoked and did not report any recent sick contacts.

The significance of enhancer of zeste homolog 2 (EZH2) expression in spindle cell lesions of the breast.

Spindle cell lesions of the breast are rare entities and pose a diagnostic challenge for pathologists due to overlapping morphologic and immunohistochemical features. We evaluated EZH2 expression in various benign (fibromatosis (n = 8), myofibroblastoma (n = 7), neurofibroma (n = 1), nodular fasciitis (n = 5), benign phyllodes tumor (n = 18)) and malignant (malignant phyllodes tumor (n = 8), metaplastic breast carcinoma (n = 16) and angiosarcoma (n = 8)) spindle cell lesions as a potential diagnostic and therapeutic marker. The EZH2 expression was evaluated semi-quantitatively to categorize the cases as 'low' and 'high' expression. All benign lesions showed low EZH2 expression, whereas high EZH2 expression was observed in the majority (28/32; 88%) of malignant lesions. The study results suggest that EZH2 may be used both as an additional diagnostic tool to reach an accurate diagnosis of the spindle cell lesions of the breast and as a therapeutic target for the malignant lesions.

Lymphoma of the breast: A clinicopathologic analysis of 51 cases with a specific emphasis on patients with a history of breast carcinoma.

We herein report our experience with 51 breast lymphoma (BL) cases from 46 patients with a specific focus on patients with a history of breast carcinoma. The overall most common subtype was diffuse large B-cell lymphoma, followed by MALT lymphoma and follicular lymphoma. Eleven of 46 (24%) patients had either previous history of or concurrent breast carcinoma. There was no significant difference in clinicopathologic characteristics between patients with primary and secondary BL. On follow-up, patients with secondary BL had a worse disease-free survival with no difference in overall survival between the two groups.

Benign and borderline phyllodes tumors of the breast: Clinicopathologic analysis of 205 cases with emphasis on the surgical margin status and local recurrence rate.

BACKGROUND: The management of benign and borderline phyllodes tumors of the breast with a positive surgical margin is still controversial. Our aim in this study was to evaluate the impact of surgical margin status on the local recurrence rate of benign and borderline phyllodes tumors. METHODS: We reviewed 205 phyllodes tumors (191 benign, 14 borderline) that were surgically excised at our hospital between 2005 and 2019. Follow-up information extending to at least 6 months after surgery was retrieved from the clinical, radiology, and pathology records. RESULTS: The initial surgical margin was negative in 54 (26%) cases, close (≤ 1 mm) in 29 (14%) cases, and positive in 122 (60%) cases. Approximately half of the cases with a close margin and two-third of the cases with a positive margin underwent re-excision to obtain negative margins. Three (2.3%) local recurrences were observed among 131 cases with follow-up information, all three with benign phyllodes tumor. Of these three patients, one had a positive final margin, and two had negative final margins. There was no significant difference in the rate of local recurrence between PT with a positive surgical margin versus a close and negative margin. CONCLUSION: The study results suggest that close clinical and radiologic follow-up may provide a better course of management rather than re-excision when managing positive margins in benign and borderline phyllodes tumors.

High EZH2 expression in ductal carcinoma in situ diagnosed on breast core needle biopsy is an independent predictive factor for upgrade on surgical excision.

PURPOSE: Approximately 25 % of DCIS diagnosed on breast core needle biopsy (CNB) is upgraded to invasive carcinoma on surgical excision. Risk factors to predict the upgrade on excision are not well established, leading many patients to be over or under-treated. EZH2 was shown to be associated with aggressive behavior of cancer from many sites, including breast cancer. We aimed to analyze EZH2 expression and tumor infiltrating lymphocytes (TILs) in DCIS as predictive factors for an upgrade on excision. METHODS: We assessed EZH2 expression in 34 DCIS cases diagnosed on CNB and upgraded to invasive carcinoma on excision. Then, we compared these cases with 60 control cases that were not upgraded on excision. A staining score for DCIS (0-12) was obtained by multiplying the staining intensity (0-3) and the percentage of positive cells (1-4). The nuclear staining score ≥6 was considered as 'high' expression. RESULTS: 46 of 94 (49 %) DCIS on CNB showed high EZH2 expression. EZH2 expression was directly correlated with TILs density, nuclear grade, HER2 expression, Ki-67 index and negative ER status. On univariate analysis, upgrade on excision was associated with high EZH2 expression, high TILs density, negative ER status and high Ki-67 index. Multivariate analysis revealed the high EZH2 expression as the only independent predictive factor for upgrade on excision. CONCLUSIONS: Our study revealed the high EZH2 expression as the only independent predictive factor for an upgrade on excision. Future studies should focus on the evaluation of EZH2 expression in tumor-microenvironment interaction in terms of diagnostic, treatment and prognostic purposes.

The rate of incidental atypical and malignant breast lesions in reduction mammoplasty specimens.

AIMS: Reduction mammoplasty (RM) is one of the most common plastic surgeries in the United States. We aimed to demonstrate the rate of incidental atypical and malignant breast lesions (AMBL) found in RM specimens and the impact of the number of submitted tissue sections on the rate of AMBL. METHODS AND RESULTS: We analysed our database for patients who had undergone reduction mammoplasty between 2000 and 2018. Patients with a history of breast cancer were excluded from the study. All pathology reports were analysed for AMBL (ALH, LCIS, FEA, ADH, DCIS, invasive carcinoma). The grossing protocol was to submit 10 sections from each breast between 2000 and 2013 and six sections between 2014 and 2018. One hundred and sixty-nine of 5208 patients (3.3%) and 216 of 10 340 RM specimens (2.1%) showed at least one AMBL. Nineteen (0.36%) patients had incidental cancer. The median age of patients with AMBL was significantly higher than patients without ABL (aged 59 years versus 45 years). There was no cancer in patients aged <30 years. The age-controlled rate of overall AMBL as well as atypia and cancer only did not decrease by submitting fewer sections during the 2014-18 period compared to the 2010-13 period. CONCLUSIONS: Decreasing the number of tissue sections from 10 to six did not lead to a significant decrease in the rate of overall AMBL or cancer. Our data suggest that submitting six tissue sections from each breast for patients aged >30 years and two sections from each breast for patients aged <30 years would be sufficient.

Correction to: Is Low-Volume Disease in the Sentinel Node After Neoadjuvant Chemotherapy an Indication for Axillary Dissection?

The following are corrections to the original article.

Upgrade rate of intraductal papilloma without atypia on breast core needle biopsy: A clinical, radiological and pathological correlation study.

BACKGROUND: The aim of the study was to determine the upgrade rate on excision of intraductal papilloma (IDP) without atypia diagnosed on breast core needle biopsy (CNB). METHODS: We searched our pathology department database for breast CNB with a diagnosis of IDP from 2013 to 2018. The exclusion criteria included radiologic-pathologic discordance, atypia on the same CNB, absence of histologic slides to review or absence of excision information. Upgrade was defined as ductal carcinoma in situ (DCIS) or invasive cancer identified on excision. RESULTS: 126 IDP without atypia cases from 94 patients were identified. The upgrade rate was 1.58% (2/126). Both upgrade cases showed DCIS with low and intermediate nuclear grade. Histologic size of IDP ≥1 cm was the only statistically significant predictor factor for an upgrade on excision. CONCLUSION: The results suggest that non-surgical management of patients with radiologic-pathologic concordant IDP without atypia diagnosed on CNB may be appropriate in routine practice.

Outcomes of classic lobular neoplasia diagnosed on breast core needle biopsy: a retrospective multi-center study.

Management of classic lobular neoplasia (cLN) diagnosed on core needle biopsy (CNB) is controversial. Our aim in this study was to review cases of cLN diagnosed on CNB to determine the rate and risk factors of an upgrade to ductal carcinoma in situ (DCIS) or invasive carcinoma on excision. All breast CNBs with a diagnosis of atypical lobular hyperplasia (ALH) or classic lobular carcinoma in situ (cLCIS) from three different institutions within a single health care system between 2013 and 2018 were retrieved. Cases with any additional high-risk lesions in the same CNB or discordant radiological-pathological correlation were excluded. Information about age, personal history of prior or concurrent breast cancer (P/CBC), and radiological and histological findings were recorded. A total of 287 cLN cases underwent surgical excision. Analysis of these 287 cLN cases showed 11 (3.8%) upgrade lesions on excision. Among the 172 ALH cases, there were 3 (1.7%) upgrades, which were all invasive lobular carcinomas (ILCs). On the other hand, 8 of 115 (7%) cLCIS cases revealed upgrade on excision (2 ILC, 5 DCIS. and 1 ILC + DCIS). Statistical analysis revealed that cLN cases with P/CBC, radiological asymmetry, or architectural distortion had a statistically significant higher upgrade rate on excision. Our findings revealed a low upgrade rate (3.8%) on the excision of classic lobular neoplasia diagnosed on breast core needle biopsy. Clinicoradiological surveillance can be appropriate when lobular neoplasia is identified on core biopsy with pathological radiological concordance in patients without a history of breast cancer, with the caveat that radiological asymmetry and architectural distortion are associated with a significant increase in an upgrade on excision.

Accuracy of Intraoperative Frozen Section of Sentinel Lymph Nodes After Neoadjuvant Chemotherapy for Breast Carcinoma.

False-negative (FN) intraoperative frozen section (FS) results of sentinel lymph nodes (SLN) have been reported to be more common after neoadjuvant chemotherapy (NAC) in the primary surgical setting. We evaluated SLN FS assessment in breast cancer patients treated with NAC to determine the FN rate and the histomorphologic factors associated with FN results. Patients who had FS SLN assessment following NAC from July 2008 to July 2017 were identified. Of the 711 SLN FS cases, 522 were negative, 181 positive, and 8 deferred. The FN rate was 5.4% (28/522). There were no false-positive results. Of the 8 deferred cases, 5 were positive on permanent section and 3 were negative. There was a higher frequency of micrometastasis and isolated tumor cells in FN cases (P<0.001). There was a significant increase in tissue surface area present on permanent section slides compared with FS slides (P<0.001), highlighting the inherent technical limitations of FS and histologic under-sampling of tissue which leads to most FN results. The majority (25/28, 89%) of FN cases had metastatic foci identified exclusively on permanent sections and were not due to a true diagnostic interpretation error. FN cases were more frequently estrogen receptor positive (P<0.001), progesterone receptor positive (P=0.001), human epidermal growth factor receptor-2 negative (P=0.009) and histologic grade 1 (P=0.015), which most likely reflects the lower rates of pathologic complete response in these tumors. Despite its limitations, FS is a reliable modality to assess the presence of SLN metastases in NAC treated patients.

Is Low-Volume Disease in the Sentinel Node After Neoadjuvant Chemotherapy an Indication for Axillary Dissection?

BACKGROUND/OBJECTIVE: Intraoperative evaluation of sentinel lymph nodes (SLNs) after neoadjuvant chemotherapy (NAC) has a higher false-negative rate than in the primary surgical setting, particularly for small tumor deposits. Additional tumor burden seen with isolated tumor cells (ITCs) and micrometastases following primary surgery is low; however, it is unknown whether the same is true after NAC. We examined the false-negative rate of intraoperative frozen section (FS) after NAC, and the association between SLN metastasis size and residual disease at axillary lymph node dissection (ALND). METHODS: Patients undergoing SLN biopsy after NAC were identified. The association between SLN metastasis size and residual axillary disease was examined. RESULTS: From July 2008 to July 2017, 702 patients (711 cancers) had SLN biopsy after NAC. On FS, 181 had metastases, 530 were negative; 33 negative cases were positive on final pathology (false-negative rate 6.2%). Among patients with a positive FS, 3 (2%) had ITCs and no further disease on ALND; 41 (23%) had micrometastases and 125 (69%) had macrometastases. Fifty-nine percent of patients with micrometastases and 63% with macrometastases had one or more additional positive nodes at ALND. Among those with a false-negative result, 10 (30%) had ITCs, 15 (46%) had micrometastases, and 8 (24%) had macrometastases; 17 had ALND and 59% had one or more additional positive lymph nodes. Overall, 1/6 (17%) patients with ITCs and 28/44 (64%) patients with micrometastases had additional nodal metastases at ALND. CONCLUSION: Low-volume SLN disease after NAC is not an indicator of a low risk of additional positive axillary nodes and remains an indication for ALND, even when not detected on intraoperative FS.