PD-L1 and Notch as novel biomarkers in pancreatic sarcomatoid carcinoma: a pilot study.

BACKGROUND: The improved immunological understanding revealed the tumor microenvironment as an appealing driver to restore the immune response against cancer cells resulting in a paradigm shift in the oncology field. However, the complexity of the tumor milieu suggests the role of several pathways linking in immunomodulation mechanisms. Pancreatic cancer represents a model of the intricate relationship between malignant cells and their surrounding neighborhood. RESEARCH DESIGN AND METHODS: In this study, we analyzed, retrospectively, six cases of rare pancreatic sarcomatoid carcinoma (PSC) and evaluated the expression of PD-L1 and Notch, aiming to explore new attributes in immunophenotype. RESULTS: PD-L1 CPS ≥ 1was common in PSCs (83%) with half samples expressing PD-L1 CPS ≥ 50. Notch1 and Notch3 demonstrated a high range of expression. A direct significant correlation between PD-L1 and Notch3 overexpression (r = 0.7; p = 0.036) has been observed. Immunofluorescence studies revealed a co-localization of Notch3 and PD-L1 when both proteins were over-expressed within cytoplasmic or membranous compartments of the same cells. CONCLUSIONS: Our data identify a unique biological characterization of this rare pancreatic histotype. These findings provide a rationale for future studies evaluating the potential crosstalk between PD-L1/PD-1 axis and Notch pathways and prompting the development of novel therapeutics strategy.

Metaplastic carcinoma of the breast with dominant squamous and sebaceous differentiation in the primary tumor and osteochondroid metaplasia in a distant metastasis: report of a case with review of sebaceous differentiation in breast tumors.

Metaplastic breast carcinoma is an uncommon tumor that develops from conventional ductal mammary carcinoma, usually consisting of squamous and/or spindle cell components and/or mesenchymal elements. Although several morphological subtypes of metaplastic breast carcinoma are known, sebaceous metaplasia has not yet been described in this context. The authors report a case of an 84-year-old woman with a huge, ulcerated primary tumor in her left breast that had already been present for 10 years. Pulmonary and bone metastases and a tumor nodule in the contralateral breast were also detected at the time of admission. Left simple mastectomy was performed. Histological examination of the tumor revealed metaplastic carcinoma consisting of ductal carcinoma, which immunohistochemically exhibited a triple-negative immunoprofile, along with dominant areas of squamous and sebaceous differentiation. Adjuvant chemotherapy was subsequently given with partial regression of the systemic metastases. Seven months after surgery and diagnosis, a new, rapidly growing, large soft tissue metastatic tumor appeared in the intramuscular compartment of the patient's right thigh, which was removed and histologically examined. Morphologically this metastatic tumor showed ductal adenocarcinoma along with areas of sebaceous differentiation and, in addition, osteochondroid metaplasia. Immunohistochemically, unlike the primary, this tumor expressed HER-2. The case is presented because of its rarity, and sebaceous differentiation is also proposed as a novel type of metaplasia in this context, expanding the spectrum of the histological patterns of metaplastic breast carcinoma. The literature concerning breast sebaceous lesions is reviewed, and the hypothetical biological mechanisms responsible for the tumor pathogenesis in this case are discussed.