Search

We investigated whether a unique immune response was instigated with the development of oral tongue squamous cell carcinomas (OTSCC), with/without nodal involvement, with/without recurrent metastatic disease, or within tumor involved nodes. One hundred and ten formalin‐fixed paraffin‐embedded samples were collected from a retrospective cohort of 67 OTSCC patients and 10 non‐cancerous tongue samples. Targets including CD4, CD8, FOXP3, PD‐L1, and PD‐1 were analyzed by immunohistochemistry. The Nanostring PanCancer Immune Profiling Panel was used for gene expression profiling. Data were externally validated in the The Cancer Genome Atlas (TCGA) head and neck (HNSCC), melanoma and lung squamous cell carcinoma (LSCC) cohorts. A 24‐immune gene signature was identified that discriminated more aggressive OTSCC cases, and although not prognostic in HNSCC was associated with survival in other TCGA cohorts (improved survival for melanoma, P <.001 and worse survival for LSCC, P =.038). OTSCC exhibited concordant gene and immunohistochemical (IHC) features characterized by a TH‐2 biased, proinflammatory profile with upregulated B cell and neutrophil gene activity and increased CD4, FOXP3, and PD‐L1 expression (P <.001 for all by IHC). Compared to less advanced disease, nodal involvement and recurrent OTSCC did not induce a different immune response although recurrent disease was characterized by significantly higher PD‐L1 expression (P =.004 by SP263, P =.013 by 22C3, P =.004 for gene expression). Identification of a gene signature associated with different prognostic effects in other cancers highlights common pathways of immune dysregulation that are impacted by the tumor origin. The significant immunosuppressive signaling in OTSCC indicates primary failure of immune system to control carcinogenesis emphasizing the need for early, combination therapeutic approaches. [ABSTRACT FROM AUTHOR]

Objectives: To describe three further cases of anaplastic large cell lymphoma (ALCL) occurring in patients with preexisting chronic lymphocytic leukemia (CLL). We also reviewed the literature of previously published cases.Methods: We discuss the clinical features, histopathology, and outcomes for three patients with ALCL and CLL from Perth, Australia. The cases were also included in a literature review of existing cases and comparisons were made with our cohort.Results: The three patients included two men (aged 77 and 74 years) and one woman (aged 66 years). All had a history of untreated CLL with diagnosis established 4 to 16 years before. They had lymphadenopathy and/or cutaneous/soft tissue lesions that proved to be ALCL, ALK+ (one case) or ALCL, ALK- (two cases).Conclusions: Further research is required in this area to establish prognostic and management recommendations. Increasing numbers of cases are being described. Positron emission tomography with computed tomography was not useful in our cohort for diagnosing progression. [ABSTRACT FROM AUTHOR]

Spot the differences between tumors: Immune checkpoint inhibitors, a form of cancer immunotherapy, have revolutionized cancer treatment in recent years, but unfortunately, not all tumors respond to these drugs. To gain insight into why some tumors might not respond, Zemek et al. compared gene expression patterns and cellular makeup of murine tumors that did or did not respond to immune checkpoint targeting. The authors then identified an immunotherapeutic combination that could be used to convert the microenvironment to a more favorable configuration in mice, suggesting that it may be possible to sensitize patients' tumors to immunotherapy by a similar approach. Cancer immunotherapy using antibodies that target immune checkpoints has delivered outstanding results. However, responses only occur in a subset of patients, and it is not fully understood what biological processes determine an effective outcome. This lack of understanding hinders the development of rational combination treatments. We set out to define the pretreatment microenvironment associated with an effective outcome by using the fact that inbred mouse strains bearing monoclonal cancer cell line–derived tumors respond in a dichotomous manner to immune checkpoint blockade (ICB). We compared the cellular composition and gene expression profiles of responsive and nonresponsive tumors from mice before ICB and validated the findings in cohorts of patients with cancer treated with ICB antibodies. We found that responsive tumors were characterized by an inflammatory gene expression signature consistent with up-regulation of signal transducer and activator of transcription 1 (STAT1) and Toll-like receptor 3 (TLR3) signaling and down-regulation of interleukin-10 (IL-10) signaling. In addition, responsive tumors had more infiltrating-activated natural killer (NK) cells, which were necessary for response. Pretreatment of mice with large established tumors using the STAT1-activating cytokine interferon-γ (IFNγ), the TLR3 ligand poly(I:C), and an anti–IL-10 antibody sensitized tumors to ICB by attracting IFNγ-producing NK cells into the tumor, resulting in increased cure rates. Our results identify a pretreatment tumor microenvironment that predicts response to ICB, which can be therapeutically attained. These data suggest a biomarker-driven approach to patient management to establish whether a patient would benefit from treatment with sensitizing therapeutics before ICB. [ABSTRACT FROM AUTHOR]

Poorly differentiated thyroid carcinoma (PDTC) is rare and is usually widely invasive at presentation. Here we present an unusual case with a component meeting diagnostic criteria for PDTC by Turin consensus proposal arising within a follicular adenoma. A 44-year-old female was found to have an incidental right thyroid nodule that was suggestive of follicular neoplasm on FNA. Histological examination of hemithyroidectomy revealed an 11 mm focus with insular growth pattern, alteration in cell morphology, and high mitotic count meeting criteria for PDTC. In addition there were several regions showing trabecular architecture with increased mitotic activity but not meeting criteria for PDTC. The literature for such cases is sparse but suggests much better prognosis than conventional invasive PDTC, although a biological potential for aggressive behaviour may be possible. [ABSTRACT FROM AUTHOR]

Hyaline-vascular Castleman disease (HVCD) often presents as unicentric disease which is usually cured by surgical resection. Here, we report a case of a 23-year-old man with HVCD in the mediastinum, in which an apparently indolent T-lymphoblastic proliferation and extensive organoid proliferation of follicular dendritic cells were also present. The patient had no systemic involvement and no further disease at follow-up. In addition, there is a possible unique family history of HVCD. This case highlights an interesting combination of elements, mostly likely benign in nature. [ABSTRACT FROM AUTHOR]