Lymph node involvement by enteropathy-like indolent NK-cell proliferation.

Natural killer (NK)-cell enteropathy (NKCE) and lymphomatoid gastropathy (LG) are closely related lymphoproliferative disorders (LPDs) composed of mature and Epstein-Barr virus (EBV)-negative NK-cells. Although these uncommon and indolent lymphoid proliferations mostly arise within the gastrointestinal (GI) tract as their designations implies, a few cases have been reported outside the GI tract. We hereby describe a unique case of lymph node infiltration by such EBV-negative NK-cell proliferation fortuitously found during routine examination of a gallbladder resected for biliary lithiasis. The histologic, phenotypic, and molecular features of this NK-cell proliferation, which were very similar if not identical to those previously reported in NKCE or LG, suggest that similar indolent EBV-negative NK-cell LPDs may also occasionally involve lymph nodes

Continuous quantification of HER2 expression by microfluidic precision immunofluorescence estimates HER2 gene amplification in breast cancer.

Chromogenic immunohistochemistry (IHC) is omnipresent in cancer diagnosis, but has also been criticized for its technical limit in quantifying the level of protein expression on tissue sections, thus potentially masking clinically relevant data. Shifting from qualitative to quantitative, immunofluorescence (IF) has recently gained attention, yet the question of how precisely IF can quantify antigen expression remains unanswered, regarding in particular its technical limitations and applicability to multiple markers. Here we introduce microfluidic precision IF, which accurately quantifies the target expression level in a continuous scale based on microfluidic IF staining of standard tissue sections and low-complexity automated image analysis. We show that the level of HER2 protein expression, as continuously quantified using microfluidic precision IF in 25 breast cancer cases, including several cases with equivocal IHC result, can predict the number of HER2 gene copies as assessed by fluorescence in situ hybridization (FISH). Finally, we demonstrate that the working principle of this technology is not restricted to HER2 but can be extended to other biomarkers. We anticipate that our method has the potential of providing automated, fast and high-quality quantitative in situ biomarker data using low-cost immunofluorescence assays, as increasingly required in the era of individually tailored cancer therapy

Dual JAK1 and STAT3 mutations in a breast implant-associated anaplastic large cell lymphoma.

SCOPUS: ar.jDecretOANoAutActifinfo:eu-repo/semantics/publishe

A CD64/FcγRI-mediated mechanism hijacks PD-1 from PD-L1/2 interaction and enhances anti-PD-1 functional recovery of exhausted T cells.

Therapeutic monoclonal antibodies (mAb) targeting the immune checkpoint inhibitor programmed cell death protein 1 (PD-1) have achieved considerable clinical success in anti-cancer therapy through relieving T cell exhaustion. Blockade of PD-1 interaction with its ligands PD-L1 and PD-L2 is an important determinant in promoting the functional recovery of exhausted T cells. Here, we show that anti-PD-1 mAbs act through an alternative mechanism leading to the downregulation of PD-1 surface expression on memory CD4 <sup>+</sup> and CD8 <sup>+</sup> T cells. PD-1 receptor downregulation is a distinct process from receptor endocytosis and occurs in a CD14 <sup>+</sup> monocyte dependent manner with the CD64/Fcγ receptor I acting as the primary factor for this T cell extrinsic process. Importantly, downregulation of surface PD-1 strongly enhances antigen-specific functional recovery of exhausted PD-1 <sup>+</sup> CD8 <sup>+</sup> T cells. Our study demonstrates a novel mechanism for reducing cell surface levels of PD-1 and limiting the inhibitory targeting by PD-L1/2 and thereby enhancing the efficacy of anti-PD-1 Ab in restoring T cell functionality

EBV-positive large B-cell lymphoma with an unusual intravascular presentation and associated haemophagocytic syndrome in an HIV-positive patient: report of a case expanding the spectrum of EBV-positive immunodeficiency-associated lymphoproliferative disorders.

Intravascular large B-cell lymphoma is a rare and aggressive EBV-negative large B-cell lymphoma with a dismal outcome. Here, we describe the case of a 76-year-old HIV-positive patient with an acute presentation of systemic symptoms and rapidly fatal outcome. Autopsy revealed a disseminated large B-cell lymphoma with an intravascular distribution involving the liver, lymph nodes, spleen, and bone marrow and associated to fibrin thrombi in hepatic capillary haemangiomas. The neoplastic B cells (CD79a + / - , CD20 + / - , CD30 + , MUM1 + , PD-L1 +) showed a Hodgkin and Reed-Sternberg-like morphology and were EBV-positive with a latency type II (LMP1 + , EBNA2-). Haemophagocytosis was documented in the bone marrow and lymph nodes. This case illustrates the diagnostic challenges of large B-cell lymphoma with intravascular presentation. We found only five other cases of EBV-positive large B-cell lymphoma with an intravascular presentation in the literature, three of which had an underlying immunodeficiency adding to the broad spectrum of EBV-associated lymphoma in the setting of immunosuppression

Advancing synoptic cancer reports beyond English: the University of Bern/PathoLink approach.

Synoptic reporting (SR) increases completeness and improves the understanding of pathology reports for tumours as compared to the more traditional “narrative” style. Furthermore, it is an important step towards higher levels of structured data capture [1]. SR is defined by a set of required data elements (RDE) specific for each tumour type and a characteristic paired format of RDE and response. The College of American Pathologists (CAP) requires accredited pathology laboratories to report many cancer types in a synoptic format and for this purpose publishes a comprehensive set of protocols [2]. More recently, the International Collaboration for Cancer Reporting (ICCR)—sponsored amongst others by the European Society of Pathology—has started to publish synoptic protocols with the aim to “produce internationally standardised and evidence-based datasets for the pathology reporting of cance

Case Report: Spontaneous Remission of an Infraorbital Follicular B-Cell Lymphoma: Case Report and Review of the Literature.

Non-Hodgkin lymphomas comprise a heterogeneous group of malignancies, with a wide scope of clinical, radiological and histological presentations. In this paper, a case is presented of a 59-year-old white male with an infraorbital follicular B-cell lymphoma, which appeared as a painless mass in the left cheek. The lymphoma achieved spontaneous remission five and a half months after his diagnostic incision biopsy. The literature is reviewed, focusing on this rare site of presentation and spontaneous remission. In literature, only four cases have been reported with a follicular B-cell lymphoma of the cheek or infraorbital region, and only 26 cases of spontaneous remission of an extracranial non-Hodgkin lymphoma in the head and neck region have been described. To the authors' best knowledge, this is the first time spontaneous remission of an infraorbital follicular lymphoma could be observed. The nature of the processes inducing spontaneous remission remains obscure. It is important to recognize this phenomenon as this might prevent unnecessary treatment

CD73 expression and clinical significance in human metastatic melanoma.

CD73 is an ectoenzyme involved in the production of adenosine. It exerts immunosuppressive and protumoral roles and has emerged as a potential immuno-oncology target. CD73 expression was detected in TC in 54% of melanoma metastases, involving < 50% TC in the majority of the cases, with variable intensity. CD73 expression was significantly associated with a lower Breslow's depth of the primary lesion and was more frequent in patients having received prior non-surgical therapies. In an adjusted analysis, CD73 expression in TC (H-score > 37.5 or intensity > 1) significantly correlated to decreased overall survival (OS) from biopsy. Of the samples containing TIMC, 35% presented CD73+ TIMC. Highly infiltrated tumors were more likely to contain CD73+ TIMC. CD73 expression in TIMC (percentage ≥1%) significantly correlated with improved OS from biopsy. Immunohistochemistry detected CD73 expression in more than half of metastatic melanomas. While CD73 expression in TC significantly correlated with decreased OS, CD73 expression in TIMC significantly associated with improved OS. These results encourage the study of anti-CD73 therapies for metastatic melanoma patients. CD73 expression was assessed by immunohistochemistry in metastatic melanomas from 114 patients. Immunostainings were evaluated in tumor cells (TC) (percentage, intensity (1-3) and H-score) and in tumor-infiltrating mononuclear cells (TIMC) (percentage)

Microfluidic-based immunohistochemistry for breast cancer diagnosis: a comparative clinical study.

Breast cancer is a highly heterogeneous disease. The efficacy of tailored therapeutic strategies relies on the precise detection of diagnostic biomarkers by immunohistochemistry (IHC). Therefore, considering the increasing incidence of breast cancer cases, a concomitantly time-efficient and accurate diagnosis is clinically highly relevant. Microfluidics is a promising innovative technology in the field of tissue diagnostic, enabling for rapid, reliable, and automated immunostaining. We previously reported the microfluidic-based HER2 (human epidermal growth factor receptor 2) detection in breast carcinomas to greatly correlate with the HER2 gene amplification level. Here, we aimed to develop a panel of microfluidic-based IHC protocols for prognostic and therapeutic markers routinely assessed for breast cancer diagnosis, namely HER2, estrogen/progesterone receptor (ER/PR), and Ki67 proliferation factor. The microfluidic IHC protocol for each marker was optimized to reach high staining quality comparable to the standard procedure, while concomitantly shortening the staining time to 16 min-excluding deparaffinization and antigen retrieval step-with a turnaround time reduction up to 7 folds. Comparison of the diagnostic score on 50 formaldehyde-fixed paraffin-embedded breast tumor resections by microfluidic versus standard staining showed high concordance (overall agreement: HER2 94%, ER 95.9%, PR 93.6%, Ki67 93.7%) and strong correlation (ρ coefficient: ER 0.89, PR 0.88, Ki67 0.87; p < 0.0001) for all the analyzed markers. Importantly, HER2 genetic reflex test for all discordant cases confirmed the scores obtained by the microfluidic technique. Overall, the microfluidic-based IHC represents a clinically validated equivalent approach to the standard chromogenic staining for rapid, accurate, and automated breast cancer diagnosis

Conjunctival MALT lymphoma: utility of FDG PET/CT for diagnosis, staging, and evaluation of treatment response.

A 67-year-old woman was referred for staging of a mucosa-associated lymphoid tumor lymphoma involving the left conjunctiva. CT scan had shown paravertebral and pelvic masses, and a breast nodule. FDG PET/CT demonstrated moderately increased uptake in the left ocular conjunctiva and confirmed the paravertebral and pelvic masses and the breast nodule. Moreover, abnormal FDG uptake was shown in 2 breast nodules, the flank, the gluteus maximus, and the gastric cardia. The patient received 6 cycles of rituximab-bendamustine chemotherapy with a complete clinical and metabolic response at the 6-month follow-up PET/CT and remained relapse-free without visual acuity problem after a 36-month follow-up