Identification of Glandular (Acinar)/Tubule Formation in Invasive Carcinoma of the Breast: A Study to Determine Concordance Using the World Health Organization Definition.

CONTEXT.­: 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.­: To investigate the ability of pathologists to identify individual structures that should be classified as glandular (acinar)/tubule formation. DESIGN.­: 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.­: 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.­: 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.

Apocrine Variant of Pleomorphic Lobular Carcinoma In Situ: Further Clinical, Histopathologic, Immunohistochemical, and Molecular Characterization of an Emerging Entity.

To date, the apocrine variant of lobular carcinoma in situ (AP-LCIS) has been cursorily described as a subtype of lobular carcinoma in situ (LCIS). We retrospectively reviewed 34 cases of AP-LCIS (including 23 associated with invasive lobular carcinoma) to fully characterize it. AP-LCIS typically presented with screen-detected calcifications in older women (mean age: 65 y) and was characterized by distended terminal duct lobular units with relatively large "pleomorphic" cells, central necrosis, and calcifications. AP-LCIS cells exhibited abundant eosinophilic occasionally granular cytoplasm, hyperchromatic nuclei, and prominent nucleoli. Synchronous classic and/or florid LCIS was identified in 24/34 (70%) AP-LCIS, and in 9/11 (82%) pure AP-LCIS. Most (68%) cases of AP-LCIS were estrogen receptor-positive (50% strongly), 35% were progesterone receptor-positive, 26% were human epidermal growth factor 2-positive, 18% demonstrated high-proliferation rate (Ki67: >15%), and 90% were androgen receptor-positive. Aurora kinase A, immunoreactive in 38% of AP-LCIS cases, was not significantly associated with recurrence, development of invasion, or nodal positivity (P>0.05). Compared with conventional (nonapocrine) pleomorphic lobular carcinoma in situ (P-LCIS), aurora kinase A was expressed in a significantly greater proportion of P-LCIS (100%). AP-LCIS and P-LCIS did not otherwise differ in clinicopathologic features. Next-generation sequencing utilizing the Oncomine Comprehensive Panel v2, performed on 27 AP-LCIS cases, showed no specific molecular findings. In a mean follow-up of 57 months, 2 (of 11, 18%) pure AP-LCIS cases recurred (2 both in situ and invasive) and none metastasized or proved fatal. AP-LCIS should be regarded as another high-grade LCIS similar to P-LCIS in many respects, and pending additional studies should be managed similarly.

Rabbit monoclonal E-cadherin antibody: A cost-effective alternative to mouse monoclonal antibody in distinguishing ductal carcinoma in situ from lobular carcinoma in situ.

Rabbit monoclonal antibody (RabMAb) demonstrates higher sensitivity without sacrificing specificity than mouse monoclonal antibody (MMAb). MMAb against E-cadherin stain is heavily utilized in distinguishing ductal carcinoma in situ (DCIS) from lobular carcinoma in situ (LCIS). We aimed to compare the E-cadherin stain using RabMAb vs MMAb in distinguishing DCIS from LCIS. One hundred and seventeen in situ breast carcinomas (55 DCIS, 58 LCIS, and 4 DCIS and LCIS) were studied. Sections from a representative block of each were stained with RabMAb [EP700Y] and MMAb [36B5]. Scanned images of stained slides were compared in tandem. All DCIS cases (59/59) showed comparable staining by RabMAb and MMAb. Comparable staining was also observed in all but one case of LCIS (61/62; 98%). One case of pleomorphic LCIS showed mostly complete, weak to moderately intense membranous staining with RabMAb and fragmented, weak membranous staining with MMAb. Consistently better staining quality was observed in slides stained by RabMAb vs MMAb. RabMAb and MMAb against E-cadherin were diagnostically equivalent with the exception of one case where RabMAb may have led to diagnostic misinterpretation. However, the not insignificant cost savings and easier interpretation using RabMAb may justify the risk of misinterpretation of increased staining in rare cases, largely avertable with proper training.

Cytological diagnosis of papillary thyroid carcinoma with tall cells on ThinPrep liquid-based cytology.

BACKGROUND: The tall cell variant of papillary thyroid carcinoma (PTC-TC) has been associated with aggressive features including extrathyroidal extension, higher rate of lymph node and distant metastases, and higher recurrence rate. We aimed to evaluate the cytomorphologic features of PTC-TC on ThinPrep (TP) along with its diagnostic efficacy to detect PTC-TC. METHODS: Preoperative cytology samples from 30 cases of histologically-proven PTC-TC and 30 classical PTC controls were selected for this study. TP preparations were evaluated for varying architectural and cytomorphologic features. RESULTS: Tall cells were present in the majority of PTC-TC cases and were located at the periphery of cell clusters and as single cells. Cytoplasmic cuff along the periphery of cell clusters and soap-bubble pseudoinclusions were very specific features of PTC-TC, when present. PTC-TC cases were more likely to show abundant oncocytic cytoplasm and distinct cell borders. Cytoplasmic tails were more likely to be present and more numerous in PTC-TC. The presence of nuclear grooves, papillary architecture, and giant cells were not reliable distinguishing features of PTC-TC vs controls. CONCLUSION: Our results indicate that tall cell cytomorphologic and architectural features in PTC are identifiable on TP.

Mammary Epithelial-Myoepithelial Carcinoma: Report of a Case With HRAS and PIK3CA Mutations by Next-Generation Sequencing.

We present the case of a 73-year-old woman with an epithelial-myoepithelial carcinoma of the left breast (ie, malignant adenomyoepithelioma). In both the initial needle core biopsy and in the subsequently performed lumpectomy, the tumor consisted of nests of neoplastic epithelium and myoepithelium with cytologic atypia, increased mitoses, and infiltrative growth into the surrounding tissue. Mutational analysis showed oncogenic driver mutations in HRAS and PIK3CA. In this article, we describe an epithelial-myoepithelial carcinoma of the breast with focal metaplastic differentiation, an extremely rare entity, and report the results of targeted next-generation sequencing. Our patient has not shown any evidence of recurrent or metastatic disease at 29 months follow-up.

Accuracy of next-generation sequencing for the identification of clinically relevant variants in cytology smears in lung adenocarcinoma.

BACKGROUND: Minimally invasive diagnostic procedures such as needle-core biopsy and fine-needle aspiration provide adequate material for molecular analyses. Advances in precision oncology are trending toward the interrogation of limited amounts of genomic material to guide clinical and therapeutic decisions. The aim of this study was to investigate the minimum cellularity needed on cytologic smears for the identification of clinically relevant variants with next-generation sequencing (NGS). METHODS: Thirty cases of cytologically diagnosed, resection-proven primary lung adenocarcinoma were identified. Nineteen of the 30 cases were known to harbor actionable variants. One Diff-Quik (DQ)-stained slide and 1 Papanicolaou (Pap)-stained slide were selected from each case. Cases were categorized as containing fewer than 100 tumor cells, 100 to 500 tumor cells, or more than 500 tumor cells. NGS was performed on the Ion Torrent platform. RESULTS: NGS was successfully performed on all cell blocks and on 90% of the smears. Paired DQ and Pap smears showed similar cellularity, and cases that differed in cellularity were within 1 category of each other. The cases with more than 100 tumor cells had a 93% success rate; this was significantly different from the situation for cases with fewer than 100 tumor cells, which were successfully sequenced only 67% of the time. Overall, NGS was able to provide clinically relevant information for 83% of DQ smears and for 90% of Pap smears tested. CONCLUSIONS: The data show a significantly higher likelihood of successful NGS with cytologic smears with more than 100 tumor cells. There was a trend for a higher NGS success rate with Pap smears versus DQ smears. Cancer Cytopathol 2017;125:398-406. © 2017 American Cancer Society.