Faculty Bibliography

CONTEXT.—/UNASSIGNED:The Nottingham Grading System (NGS) developed by Elston and Ellis is used to grade invasive breast cancer (IBC). Glandular (acinar)/tubule formation is a component of NGS. OBJECTIVE.—/UNASSIGNED:To investigate the ability of pathologists to identify individual structures that should be classified as glandular (acinar)/tubule formation. DESIGN.—/UNASSIGNED:A total of 58 hematoxylin-eosin photographic images of IBC with 1 structure circled were classified as tubules (41 cases) or nontubules (17 cases) by Professor Ellis. Images were sent as a PowerPoint (Microsoft) file to breast pathologists, who were provided with the World Health Organization definition of a tubule and asked to determine if a circled structure represented a tubule. RESULTS.—/UNASSIGNED:Among 35 pathologists, the κ statistic for assessing agreement in evaluating the 58 images was 0.324 (95% CI, 0.314-0.335). The median concordance rate between a participating pathologist and Professor Ellis was 94.1% for evaluating 17 nontubule cases and 53.7% for 41 tubule cases. A total of 41% of the tubule cases were classified correctly by less than 50% of pathologists. Structures classified as tubules by Professor Ellis but often not recognized as tubules by pathologists included glands with complex architecture, mucinous carcinoma, and the "inverted tubule" pattern of micropapillary carcinoma. A total of 80% of participants reported that they did not have clarity on what represented a tubule. CONCLUSIONS.—/UNASSIGNED:We identified structures that should be included as tubules but that were not readily identified by pathologists. Greater concordance for identification of tubules might be obtained by providing more detailed images and descriptions of the types of structures included as tubules.

Poly (ADP-ribose) polymerase inhibitors (PARPi) are used for patients with BRCA1/2 mutations, but patients with other mutations may benefit from PARPi treatment. Another mutation that is present in more cancers than BRCA1/2 is mutation to the TP53 gene. In 2D breast cancer cell lines, mutant p53 (mtp53) proteins tightly associate with replicating DNA and Poly (ADP-ribose) polymerase (PARP) protein. Combination drug treatment with the alkylating agent temozolomide and the PARPi talazoparib kills mtp53 expressing 2D grown breast cancer cell lines. We evaluated the sensitivity to the combination of temozolomide plus PARPi talazoparib treatment to breast and lung cancer patient-derived tumor organoids (PDTOs). The combination of the two drugs was synergistic for a cytotoxic response in PDTOs with mtp53 but not for PDTOs with wtp53. The combination of talazoparib and temozolomide induced more DNA double-strand breaks in mtp53 expressing organoids than in wild-type p53 expressing organoids as shown by increased γ-H2AX protein expression. Moreover, breast cancer tissue microarrays (TMAs) showed a positive correlation between stable p53 and high PARP1 expression in sub-groups of breast cancers, which may indicate sub-classes of breast cancers sensitive to PARPi therapy. These results suggest that mtp53 could be a biomarker to predict response to the combination of PARPi talazoparib-temozolomide treatment.

OBJECTIVES/OBJECTIVE:Recognition awards build physician reputation and facilitate career advancement. We hypothesize women physicians are underrepresented as award recipients by pathology medical societies compared with representation in the specialty. METHODS:We analyzed publicly available online information about physician recipients (January 2015 to December 2021) from three general pathology society websites. Recipient gender was determined by pronoun use, first name, and photograph. Representation was compared with Association of American Medical Colleges (AAMC) specialty data from 2015 and 2019, which showed a minimum of 36.7% women pathologists in 2015 and up to 43.4% in 2019. RESULTS:Twenty-six awards and 230 physician recipients were included in the analysis. A total of 159 (69.1%) men physicians and 71 (30.9%) women physicians received awards. Overall, women physicians were underrepresented in recognition awards compared with AAMC benchmarks. Prestigious awards (defined as those that recognize a person's body of work over time) showed a similar disparity with 22 (30.1%) of 73 recipients being women. Men physicians were more likely to receive multiple awards. CONCLUSIONS:Women physicians are underrepresented overall for recognition awards by pathology medical societies. Disparities are greater for prestigious awards. Further research is needed to better understand the reasons for these findings and how they affect women physicians' careers.

PURPOSE/OBJECTIVE:scores and determine if a combination of these biomarkers improves the ability to predict development of distant metastasis over and above that of either biomarker alone. METHODS:scores were evaluated and compared to identify the best performing combined marker by using the restricted mean survival time (RMST) difference method. RESULTS:analysis. CONCLUSIONS:Score alone in this cohort of 86 patients.

OBJECTIVES/OBJECTIVE:Subareolar tissue is examined during nipple-sparing mastectomy (NSM) to minimize the risk of occult malignancy within the preserved nipple. A positive subareolar tissue biopsy typically warrants subsequent nipple excision. We study the factors associated with a positive subareolar tissue biopsy, the rate of residual malignancy in subsequent nipple excisions, and the value of subareolar tissue biopsy intraoperative frozen section (IOF). METHODS:We identified 1,026 consecutive NSMs with separately submitted subareolar tissue biopsies over a 5.5-year period. Clinicopathologic data were reviewed. We examined concordance rates between subareolar tissue biopsy and subsequent nipple excisions as well as IOF diagnosis and permanent control diagnosis. RESULTS:Among cases of therapeutic NSM, the rate of a positive subareolar tissue biopsy was 7.2%. Multifocal/multicentric disease (P = .0005), presence of lymphovascular invasion (P = .033), and nodal involvement (P = .006) were significantly associated with a positive subareolar tissue biopsy. Thirty-nine of 41 cases with positive subareolar biopsies underwent subsequent nipple excision, with 20 (51%) showing residual carcinoma. Among all IOF samples, 9 (3.3%) showed a discrepancy between the IOF and permanent diagnoses, mostly because of false-negatives. CONCLUSIONS:A positive subareolar tissue biopsy predicts residual carcinoma in the excised nipples in 51% of cases. IOF is accurate and reliable.

CONTEXT.—/UNASSIGNED:Mucocele-like lesion of the breast (MLL) is an uncommon entity, and recent studies show low rates of upgrade from core needle biopsy (CNB) to excision. OBJECTIVE.—/UNASSIGNED:To evaluate features associated with upgrade of MLLs diagnosed on CNB. DESIGN.—/UNASSIGNED:Seventy-eight MLLs diagnosed on CNB from 1998-2019 and subsequent excisions were reviewed. Histologic parameters evaluated included the presence of atypia, presence and morphology of calcifications, and morphologic variant (classic [C-MLL], duct ectasia-like [DEL-MLL], or cystic mastopathy-like [CML-MLL]). RESULTS.—/UNASSIGNED:Overall, 45 MLLs lacked atypia and 33 were associated with atypia (atypical ductal hyperplasia, 32; atypical lobular hyperplasia, 1). Most were C-MLLs (61) with fewer DEL-MLLs (14) and CML-MLLs (3). Half showed both coarse and fine calcifications, with fewer showing only coarse or fine calcifications, and some showing none. Subsequent excision or clinical follow-up was available for 25 MLLs without atypia-of which 2 (8.0%) were upgraded to ductal carcinoma in situ (DCIS)-and 23 with atypia, of which 4 (17.4%) were upgraded to DCIS. No cases were upgraded to invasive carcinoma. All upgraded cases showed coarse calcifications on CNB, and all upgraded cases were associated with residual calcifications on post-CNB imaging. CONCLUSIONS.—/UNASSIGNED:Most MLLs present as calcifications and nearly half are associated with atypia. Upgrade to DCIS is twice as frequent in MLLs with atypia versus those without. A predominance of coarse calcifications and the presence of residual targeted calcifications following core biopsy may be associated with higher upgrade rates.

High-density foci within axillary lymph nodes are associated with a number of potential diagnoses. In this case series, we present four tattooed patients who had mammographic findings that demonstrated high-density material in axillary lymph nodes, indicative of tattoo pigment migration. The aim of presenting these cases is to highlight the importance of recognizing such pigment migration in order to help breast radiologists form an appropriate differential diagnosis that might include this entity.

BACKGROUND:When needle core biopsies (NCBs) of the breast reveal radial scar or complex sclerosing lesions (RSLs), excision is often recommended despite a low risk of malignancy in the modern era. The optimal management of NCBs revealing RSLs is controversial, and understanding of the natural history of unresected RSLs is limited. METHODS:We retrospectively analyzed pathology and imaging data from 148 patients with NCB revealing RSL without atypia from 2015 to 2019 to determine the prevalence of malignancy and the behavior of RSLs undergoing active surveillance (AS). RESULTS:The mean age of patients was 52 years, and most lesions were screen-detected (91%). The median lesion size was 6.0 mm (range 2-39). Most patients (66%, n = 98) underwent immediate surgery, while 34% (n = 50) of patients underwent AS, with a median follow-up of 16 months (range 6-51). Of the excised RSLs, 99% (n = 97) were benign and 1% (n = 1) revealed ductal carcinoma in situ (DCIS). In 17% (n = 17) of cases, additional high-risk lesions were discovered upon excision. Among the 50 patients undergoing AS, no lesions progressed on interval imaging. CONCLUSIONS:In this cohort, 99% of RSLs undergoing excision were benign, 1% revealed DCIS, and there were no invasive cancers. In the first study of patients with RSLs undergoing AS, we found that all lesions either remained stable or resolved. We propose that the vast majority of patients with RSL on NCB can be safely offered AS, and that routine excision is a low-value intervention.

Merkel cell carcinoma (MCC) of the breast is a very rare and aggressive type of neuroendocrine carcinoma of the breast (NECB) that typically occurs in older and immunocompromised individuals often presenting as a large palpable mass (Albright et al., 2018¹). Imaging features of MCC are similar to other NECBs, typically appearing as an oval circumscribed mass on mammography and as an irregular mass with increased vascularity on sonography (Jeon et al., 2014²). While both MCC and primary NECB demonstrate positive immunostaining for synaptophysin, obtaining immunohistochemical stains for specific markers, such as CK7 and CK20 is imperative to confirm the diagnosis of MCC (Albright et al., 2018¹). We present a case of a 57-year-old female patient with no personal or family history of breast cancer, who presented for evaluation of a palpable abnormality in her left breast. Initial diagnostic mammogram demonstrated a circumscribed mass in the upper outer quadrant of the left breast corresponding to the palpable area of concern, which correlated to an irregular mass with increased vascularity on targeted ultrasound, similar to other NECBs. Pathologic results after tissue sampling yielded poorly differentiated primary NECB. Following neoadjuvant chemotherapy, the patient underwent a lumpectomy and further immunohistochemical stains of the lumpectomy specimen demonstrated diffusely positive synaptophysin, negative CK7, and positive CK20, consistent with MCC of the breast.