A case of polymorphous light eruption with atypical lymphocytic infiltration in the dermis.

Object. The aim of this study was to analyze the cellular immune response and histopathological changes in secondary brain tumors after gamma knife surgery (GKS). Methods. Two hundred ten patients with cerebral metastases underwent GKS. Seven patients underwent subsequent craniotomy for tumor removal between 1 and 33 months after GKS. Four of these patients had one tumor, two patients had two tumors, and one patient had three. Histological and immunohistochemical investigations were performed. In addition to routine H & E and Mallory trichrome staining, immunohistochemical reactions were conducted to characterize the phenotypic nature of the cell population contributing to the tissue immune response to neoplastic deposits after radiosurgery. Light microscopy revealed an intensive lymphocytic infiltration in the parenchyma and stroma of tumor samples obtained in patients in whom surgery was performed over 6 months after GKS. Contrary to this, extensive areas of tissue necrosis with either an absent or scanty lymphoid population were observed in the poorly controlled neoplastic specimens obtained in cases in which surgery was undertaken in patients less than 6 months after GKS. Immunohistochemical characterization demonstrated the predominance of CD3-positive T cells in the lymphoid infiltration. Conclusions. Histopathological findings of the present study are consistent with a cellular immune response of natural killer cells against metastatic brain tumors, presumably stimulated by the ionizing energy of focused radiation.

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Is Immune Response Relevant in Interstitial Lung Disease?

Current Immunology Reviews ◽

10.2174/1573395516999200914143054 ◽

2020 ◽

Vol 16 (1) ◽

pp. 18-27

Author(s):

Manzoor M. Khan

Keyword(s):

Immune Response ◽

Interstitial Lung Disease ◽

Lung Disease ◽

Lung Fibrosis ◽

Lymphocytic Infiltration ◽

Therapeutic Strategies ◽

Mediators Of Inflammation ◽

Acquired Immune Responses ◽

Novel Therapeutic Strategies

Interstitial lung disease, a term for a group of disorders, causes lung fibrosis, is mostly refractory to treatments and has a high death rate. After diagnosis the survival is up to 3 years but in some cases the patients live much longer. It involves a heterogenous group of lung diseases that exhibit progressive and irreversible destruction of the lung due to the formation of scars. This results in lung malfunction, disruption of gas exchange, and eventual death because of respiratory failure. The etiology of lung fibrosis is mostly unknown with a few exceptions. The major characteristics of the disease are comprised of injury of epithelial type II cells, increased apoptosis, chronic inflammation, monocytic and lymphocytic infiltration, accumulation of myofibroblasts, and inability to repair damaged tissue properly. These events result in abnormal collagen deposition and scarring. The inflammation process is mild, and the disease is primarily fibrotic driven. Immunosuppressants do not treat the disease but the evidence is evolving that both innate and acquired immune responses a well as the cytokines contribute to at least early progression of the disease. Furthermore, mediators of inflammation including cytokines are involved throughout the process of lung fibrosis. The diverse clinical outcome of the disease is due to different pattern of inflammatory markers. Nonetheless, the development of novel therapeutic strategies requires better understanding of the role of the immune response. This review highlights the role of the immune response in interstitial lung disease and considers the therapeutic strategies based on these observations. For this review several literature data sources were used to assess the role of the immune response in interstitial lung disease and to evaluate the possible therapeutic strategies for the disease.

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Platelet Depletion is Effective in Ameliorating Anxiety-Like Behavior and Reducing the Pro-Inflammatory Environment in the Hippocampus in Murine Experimental Autoimmune Encephalomyelitis

Journal of Clinical Medicine ◽

10.3390/jcm8020162 ◽

2019 ◽

Vol 8 (2) ◽

pp. 162 ◽

Cited By ~ 4

Author(s):

Pece Kocovski ◽

Xiangrui Jiang ◽

Claretta D’Souza ◽

Zhenjiang Li ◽

Phuc Dang ◽

...

Keyword(s):

Experimental Autoimmune Encephalomyelitis ◽

Neuropsychiatric Symptoms ◽

Critical Role ◽

Clinical Manifestations ◽

Lymphocytic Infiltration ◽

Disease Stage ◽

Autoimmune Encephalomyelitis ◽

Significant Difference ◽

Platelet Depletion ◽

Experimental Autoimmune

The neuropsychiatric symptoms of multiple sclerosis (MS), such as anxiety and depression, can result from disease activity itself as well as psychological reaction to an unfavorable diagnosis. Accordingly, the literature reports evidence of increased anxiety-like behavior in experimental autoimmune encephalomyelitis (EAE), an accepted MS model. Due to the recently described critical role of platelets in inflammation and autoimmune disease, we examined the relationship between platelets, inflammation, and anxiety-like behavior in EAE. In the elevated plus maze, EAE-induced C57BL/6J mice showed decreased time spent in the open arms relative to vehicle-only controls, demonstrating an increase in anxiety-like behavior. This effect occurred in the presence of platelet–neuron association, but absence of lymphocytic infiltration, in the hippocampal parenchyma. Platelet depletion at the pre-clinical disease stage, using antibody-mediated lysis prevented the EAE-induced increase in anxiety-like behavior, while no significant difference in distance moved was recorded. Furthermore, platelet depletion was also associated with reduction of the pro-inflammatory environment to control levels in the hippocampus and prevention of EAE disease symptomology. These studies demonstrate the high efficacy of a platelet-targeting approach in preventing anxiety-like symptoms and clinical manifestations of EAE and have implications for the treatment of neuropsychiatric symptoms in MS.

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Presence and significance of NK cells in glioblastomas

Journal of Neurosurgery ◽

10.3171/jns.1989.70.5.0728 ◽

1989 ◽

Vol 70 (5) ◽

pp. 728-731 ◽

Cited By ~ 25

Author(s):

Jesús Vaquero ◽

Santiago Coca ◽

Santiago Oya ◽

Roberto Martínez ◽

Josefa Ramiro ◽

...

Keyword(s):

Monoclonal Antibody ◽

Nk Cells ◽

Survival Time ◽

Tumor Cells ◽

Lymphocytic Infiltration ◽

Surface Marker ◽

Content Type ◽

Hematoxylin And Eosin ◽

Hematoxylin And Eosin Staining ◽

Fine Print

✓ A monoclonal antibody against the surface marker IOT-10 of natural killer (NK) cells was used to investigate the presence of these cells in a series of 25 glioblastomas. In 40% of the tumors, IOT-10-positive NK cells were found in small numbers scattered among the tumor cells. The presence of IOT-10-positive NK cells was not related to the degree of lymphocytic infiltration in the tumor as demonstrated by hematoxylin and eosin staining, nor did it appear to influence the survival time of the patients studied.

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Complement C9 expression is associated with damaged myocardial cells in pediatric sudden death cases of fulminant myocarditis

Egyptian Journal of Forensic Sciences ◽

10.1186/s41935-020-00211-5 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Akari Takaya Uno ◽

Masahito Hitosugi ◽

Mami Nakamura ◽

Tomoyuki Nakanishi ◽

Takahiro Mima ◽

...

Keyword(s):

Sudden Death ◽

Acute Myocarditis ◽

Lymphocytic Infiltration ◽

Pericardial Fluid ◽

Sirtuin 1 ◽

Fulminant Myocarditis ◽

Myocardial Cells ◽

Hematoxylin And Eosin ◽

Hematoxylin And Eosin Staining ◽

Complement C9

Abstract Background Because disease progression is so fast in sudden death of acute fulminant myocarditis, damage of myocardial cells is not evident in routine hematoxylin and eosin staining. To understand damage to myocardial cells and the mechanism of sudden death, immunohistochemical staining was performed for two forensic autopsy cases. Case presentation The patients were a healthy 5-year-old girl and 8-year-old boy. They suddenly died within 2 days of appearance of flu-like symptoms. An autopsy showed accumulation of yellowish-clear pericardial fluid containing fibrin deposits, fluid blood in the heart, and congestion of visceral organs. Histologically, minor necrosis or degeneration of myocardial cells with mainly lymphocytic infiltration was observed sometimes in tissue sections. Immunohistochemically, positive complement C9 staining and negative sirtuin 1 staining were found. These findings suggested wide damage of myocardial cells, even in regions with no marked changes in myocardial cells with hematoxylin and eosin staining. These areas corresponded to those with strong accumulation of lymphocytes. Conclusions Immunohistochemistry for complement C9 and sirtuin 1 might become a new tool for evaluating damage of myocardial cells of fulminant acute myocarditis.

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296 Immune correlates of clinical response to Avelumab in patients with advanced thymic epithelial tumors

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-sitc2020.0296 ◽

2020 ◽

Vol 8 (Suppl 3) ◽

pp. A323-A323

Author(s):

Yo-Ting Tsai ◽

Arun Rajan ◽

James Gulley ◽

Jeffrey Schlom ◽

Renee Donahue

Keyword(s):

Clinical Response ◽

Mononuclear Cells ◽

Predictive Biomarkers ◽

Lymphocytic Infiltration ◽

Peripheral Blood Mononuclear ◽

Thymic Epithelial Tumors ◽

Link Type ◽

Epithelial Tumors ◽

Immune Correlates ◽

Tcr Diversity

BackgroundThymic epithelial tumors (TET), consisting of thymomas and thymic carcinomas, are PD-L1-expressing tumors characterized by varying degrees of lymphocytic infiltration and a predisposition towards the development of paraneoplastic autoimmunity. As part of a phase I study (NCT01772004), the anti-tumor activity of patients with relapsed, advanced TET to avelumab (anti-PD-L1), was demonstrated and was accompanied by a high frequency of immune related adverse events (irAE). The current study aimed to identify immune related signatures that associate with clinical response and/or the development of irAE.MethodsEight patients with recurrent TET were treated with avelumab at doses of 10 mg/kg to 20 mg/kg every 2 weeks until disease progression or development of intolerable side effects. Peripheral blood mononuclear cells (PBMC) were obtained before and during therapy, and interrogated by multicolor flow cytometry to evaluate 123 immune subsets, as well as by T-cell receptor (TCR) sequencing to evaluate TCR diversity.ResultsFour of 8 TET patients had partial responses and 3 had stable disease. All responders developed irAEs that resolved with immunosuppressive therapy, compared to only 1 of 4 non responders. Analyses of PBMC subsets prior to therapy showed that responders had higher absolute lymphocyte counts, and lower frequencies of B cells, Tregs, conventional dendritic cells (cDCs), and NK cells, compared to non-responders. There was also a trend towards a higher level of TCR diversity in those patients who subsequently had a radiological response and developed irAE.ConclusionsImmune profiling identified specific immune measures prior to therapy that differed between responders and non-responders, that may serve as predictive biomarkers to identify patients with relapsed TET most likely to benefit from avelumab and/or to develop irAE.Trial RegistrationNCT01772004Ethics ApprovalAll patients provided written informed consent for participation in a clinical trial that was approved by the Institutional Review Board at the National Cancer Institute (NCT01772004).

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Extra-nodal Rosai-Dorfman Disease Confined to Breast

American Journal of Clinical Pathology ◽

10.1093/ajcp/aqaa161.087 ◽

2020 ◽

Vol 154 (Supplement_1) ◽

pp. S41-S42

Author(s):

E Ozluk ◽

R Shackelford

Keyword(s):

Plasma Cells ◽

African American Woman ◽

American Woman ◽

Lymphocytic Infiltration ◽

Needle Aspiration ◽

Left Breast ◽

Unknown Etiology ◽

Diagnostic Challenge ◽

Ductal Cells ◽

Rosai Dorfman Disease

Abstract Introduction/Objective First described by Rosai and Dorfman in 1969, Rosai-Dorfman Disease (RDD) is an uncommon, idiopathic, reactive lymph node process with an unknown etiology. It may involve extra-nodal organs including the skin, bone, soft tissue, and eyes. However, breast involvement is rare and RDD confined to breast without nodal involvement is extremely uncommon. Methods Here we present a case of RDD confined to breast. The patient was a 51-year-old African American woman who was found to have an irregular, solid left breast mass on routine mammogram, which had speculated irregular margins and measured of 37.0 x 32.0 x 32.0 mm. She did not have any symptoms, nor any palpable lymph nodes. The clinician stated that the lesion was highly suspicious for a breast malignancy and requested a fine needle aspiration (FNA) of the mass, followed by total excision. Results An FNA was interpreted as atypical histiocytic cells in a mixed lymphoid background. Histopathologic examination revealed an ill-defined mass with sheets of histiocytes, plasma cells, and a mixed lymphocytic population, with occasional germinal centers. Some of the histiocytes were spindle shaped and associated with storiform collagen deposition. The histiocytes had single and multiple nuclei and exhibited occasional emperipolesis. Immunohistochemical staining with S100 diffusely highlighted the histiocytes, whereas CD1a was negative. CD3 and CD20 immunostains were positive for mixed-type lymphocytic infiltration. Cytokeratin staining was performed and reassuringly stained only the benign ductal cells. A diagnosis of RDD of the breast was made, based on these histopathologic findings. Conclusion We report an example of an extra-nodal RDD involving the mammary gland that was initially suspected to be breast carcinoma. RDD may still be a diagnostic challenge, especially in a patient with suspected carcinoma. It is the pathologist’s role to lead the clinician to the proper diagnosis and render a correct histopathologic diagnosis.

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Lymphocytic Infiltration in Pediatric Thyroid Carcinomas

Pediatric and Developmental Pathology ◽

10.1007/s10024-003-3028-3 ◽

2004 ◽

Vol 7 (5) ◽

pp. 487-492 ◽

Cited By ~ 10

Author(s):

Van H. Savell ◽

Stephen M. Hughes ◽

Charles Bower ◽

David M. Parham

Keyword(s):

Papillary Carcinoma ◽

Follicular Carcinoma ◽

Thyroid Neoplasms ◽

Lymphocytic Infiltration ◽

Lymphocytic Infiltrate ◽

Low Grade ◽

Lymphoid Infiltrate ◽

Thyroid Carcinomas ◽

Thyroid Papillary ◽

Adults And Children

Lymphocytic thyroiditis has been associated with an increase in the incidence of thyroid papillary carcinoma in some reports, mostly series of both adults and children. Relatively little is written about thyroiditis and follicular carcinomas. We have seen several cases of pediatric follicular thyroid carcinomas, that had an associated lymphocytic infiltrate, which led us to examine all primary malignant thyroid neoplasms in our surgical files from 1984 through 2000 to examine this relationship. We also investigated the nature of the lymphocytic infiltrate with routine immunohistochemistry. Ten patients (five male, five female, ages 4.5–21 years of age) had a thyroid carcinoma resection, six (three males and three females) with papillary carcinoma and four patients (two males and two females) with low-grade follicular carcinoma. Seven samples (one male had two cases with tumor) from patients who had a papillary carcinoma resection with tissue blocks available were identified (one patient had slides but no blocks), as were all four patients with a follicular carcinoma. The thyroid of all patients with a follicular carcinoma contained a lymphocytic infiltrate; only four of the seven papillary carcinoma samples had an associated lymphoid infiltrate. In all cases with a lymphoid infiltrate, the infiltrate was present in both lobes (both adjacent and separate from the tumor). B lymphocytes were present in the lymphoid infiltrate of three of four patients with follicular carcinomas and in 1 of 3 cases of papillary carcinomas. T cells were dispersed throughout all the tumors with lymphoid infiltrates. We conclude that pediatric follicular carcinomas have an associated lymphocytic infiltrate in the tumor and/or adjacent thyroid, more commonly than papillary carcinomas.

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