Tissue Selection for PD-L1 Testing in Triple Negative Breast Cancer (TNBC).

Atezolizumab in combination with nab-paclitaxel has been introduced for the treatment of locally advanced or recurrent triple negative breast cancer (TNBC). Patient selection relies on the use of immunohistochemistry using a specific monoclonal PD-L1 antibody (clone SP142) in a tightly controlled companion diagnostic test (CDx) with a defined interpretative algorithm. Currently there are no standardized recommendations for selecting the optimal tissue to be tested and there is limited data to support decision making, raising the possibility that tissue selection may bias test results. We compared PD-L1 SP142 assessment in a collection of 73 TNBC cases with matched core biopsies and excision samples. There was good correlation between PD-L1-positive core biopsy and subsequent excision, but we found considerable discrepancy between PD-L1 negative core biopsy and matched excision, with a third of cases found negative on core biopsies converting to positive upon examination of the excision tissue. In view of these findings, we developed a workflow for the clinical testing of TNBC for PD-L1 and implemented it in a central referral laboratory. We present audit data from the clinical PD-L1 testing relating to 2 years of activities, indicating that implementation of this workflow results in positivity rates in our population of TNBC similar to those of IMpassion130 clinical trial. We also developed an online atlas with a precise numerical annotation to aid pathologists in the interpretation of PD-L1 scoring in TNBC.

Breast Tumours Resembling the Tall Cell Variant of Thyroid Papillary Carcinoma: Are They Part of the Papillary Carcinoma Spectrum or a Distinct Entity?

BACKGROUND: Papillary tumours of the breast are diagnostically challenging lesions and represent a wide spectrum of diseases from papilloma to invasive papillary carcinoma. A rare subtype of breast papillary tumour resembling the tall cell variant of thyroid papillary carcinoma (BTRTPC) has been described. The nomenclature of this entity, its relationship to other papillary tumours, and its nature, whether in situ or invasive, remain unclear. METHODS: Seventy-five papillary carcinomas (PCs) of the breast previously diagnosed in routine practice were reviewed and the presence of features (n = 10) characteristic of BTRTPC were assessed to determine whether BTRTPC comprises a distinct entity or is part of the spectrum of the previously defined PC variants. RESULTS: Nuclear overlapping and eosinophilic granular cytoplasm were seen in 81 and 75% of the cases, whereas nuclear grooves, nuclear clearing, and tall cells were noticed in 51, 42, and 38% of the cases, respectively; 27% of the cases showed macro- and micro-follicular architecture filled with colloid-like material. Five cases (7%) lacked oestrogen receptor (ER) expression. Co-existing invasive carcinoma was seen in 25 cases (33%). Two cases displayed several features characteristic of BTRTPC, and both were ER-negative. CONCLUSION: Features characteristic of BTRTPC overlap with other PCs of the breast. Molecular and immunohistochemical biomarkers are needed to provide objective diagnostic criteria for the characterisation of such lesions in routine practice.

Osseous metaplasia of the colon in a diversion proctocolitis.

Osseous metaplasia within the gastrointestinal tract is a rare phenomenon, seen most frequently in mucinproducing left-sided colonic adenocarcinomas. It has also been documented in a variety of benign conditions, occurring in polyps and lesions associated with inflammation and ulceration. This is the first case report, to the authors' knowledge, of osseous metaplasia associated with a diversion proctocolitis. The diversion was performed following stricture formation, secondary to complicated diverticular disease with diverticular phlegmon formation. In common with other cases, in which osseous metaplasia arises within a background of inflammation, the present case demonstrated stromal fibroblastic proliferation. The underlying pathogenesis of osseous metaplasia has not yet been elucidated, but secretion of various bone morphogenic proteins (belonging to the transforming growth factor-beta superfamily) and increased alkaline phosphatase activity by both epithelial and stromal cells have been documented.