ABSTRACT
A 59-year-old woman with history of metastatic melanoma, currently on nivolumab, presents for a restaging FDG PET/CT scan. New subcutaneous hypermetabolic foci are seen in bilateral lower extremities, suggestive of recurrent melanoma. She is referred for percutaneous image-guided biopsy for definitive diagnosis of progressive disease. Ultrasound shows the subcutaneous foci to be hyperechoic (fat density), and biopsy of the right thigh nodule shows fat necrosis with no evidence of tumor. Fat necrosis, an immune-related adverse event, can be FDG-avid and mimic malignancy on PET/CT scan.
Subject(s)
Fat Necrosis/chemically induced , Fat Necrosis/immunology , Fluorodeoxyglucose F18/metabolism , Nivolumab/adverse effects , Subcutaneous Fat/pathology , Fat Necrosis/diagnostic imaging , Fat Necrosis/pathology , Female , Humans , Image-Guided Biopsy , Melanoma/drug therapy , Middle Aged , Positron Emission Tomography Computed Tomography , Skin Neoplasms/drug therapy , Subcutaneous Fat/drug effects , Melanoma, Cutaneous MalignantABSTRACT
Lupus erythematosus panniculitis (LEP) is an inflammatory disorder of the subcutaneous fat in patients with lupus erythematosus (LE). It is a rare variant of the disease, which occurs approximately in 1%-3% of patients with cutaneous LE. The purpose of this study was to investigate the clinical, histopathologic, immunophenotypical, and molecular profiles of LEP. We performed a retrospective study of 19 biopsy specimens from 17 patients with LEP. We reviewed their clinical data and reexamined the histopathology. Immunophenotyping and molecular studies were done using sections from paraffin-embedded formalin-fixed tissue. The most common clinical manifestation was a depressed patch on upper arm. Patients showed good response to variable treatment modalities, but, generally, relapse of panniculitis was noted when treatment was discontinued. Histopathologically, most specimens revealed lymphoplasmacytic lobular panniculitis with epidermal and dermal changes of LE, hyaline fat necrosis, and lymphoid follicles. Immunohistochemistry showed a mixture of T and B cells in dermis and subcutis with a slight preponderance of T cell. Although the polymerase chain reaction analysis of the T-cell receptor-gamma gene rearrangement showed a polyclonal smear in 89.5% of cases, a small portion of specimens demonstrated monoclonality. LEP is a chronic recurrent disease with characteristic features. Its diagnosis is often challenging, and a precise diagnosis is achievable only upon elaborate clinicopathologic correlation and integrated interpretation of all diagnostic criteria.
Subject(s)
Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor/genetics , Panniculitis, Lupus Erythematosus , Adolescent , Adult , Aged , B-Lymphocytes/immunology , B-Lymphocytes/pathology , Biomarkers/metabolism , Child , Dapsone/therapeutic use , Drug Therapy, Combination , Fat Necrosis/immunology , Fat Necrosis/pathology , Female , Humans , Hydroxychloroquine/therapeutic use , Immunoenzyme Techniques , Immunophenotyping , Male , Methotrexate/therapeutic use , Middle Aged , Panniculitis, Lupus Erythematosus/genetics , Panniculitis, Lupus Erythematosus/immunology , Panniculitis, Lupus Erythematosus/pathology , Prednisolone/therapeutic use , Retrospective Studies , Skin/immunology , Skin/pathology , T-Lymphocytes/immunology , T-Lymphocytes/pathology , Young AdultABSTRACT
TLRs are thought to play a critical role in self/non-self discrimination by sensing microbial infections and initiating both innate and adaptive immunity. In this study, we demonstrate that in the absence of TLR11, a major TLR involved in recognition of Toxoplasma gondii, infection with this protozoan parasite induces an abnormal immunopathological response consisting of pancreatic tissue destruction, fat necrosis, and systemic elevations in inflammatory reactants. We further show that this immunopathology is the result of non-TLR dependent activation of IFN-gamma secretion by NK cells in response to the infection. These findings reveal that in addition to triggering host resistance to infection, TLR recognition can be critical for the prevention of pathogen-induced immune destruction of self tissue.
Subject(s)
Toll-Like Receptors/metabolism , Toxoplasma/immunology , Toxoplasmosis/pathology , Toxoplasmosis/prevention & control , Acute Disease , Animals , Fat Necrosis/genetics , Fat Necrosis/immunology , Fat Necrosis/pathology , Interferon-gamma/metabolism , Killer Cells, Natural/immunology , Killer Cells, Natural/metabolism , Killer Cells, Natural/pathology , Mice , Mice, Inbred C57BL , Mice, Knockout , Mice, Mutant Strains , Pancreatitis/genetics , Pancreatitis/immunology , Pancreatitis/pathology , Toll-Like Receptors/deficiency , Toll-Like Receptors/genetics , Toxoplasma/metabolism , Toxoplasmosis/genetics , Toxoplasmosis/immunologyABSTRACT
Ninety-three male breast specimens have been examined for the presence of pseudoangiomatous hyperplasia of the mammary stroma which has hitherto been described almost exclusively in females. Forty-four cases (47.4%) showed some degree of hyperplasia, varying from small microscopic foci to extensive change involving 90% of the mammary tissue. All but one were found in association with gynaecomastia, early and intermediate stage. The association between pseudoangiomatous hyperplasia and benign proliferative lesions mirrors that reported in the female breast, and our findings suggest that the change may represent a stage in the maturation of newly formed mammary stroma.
Subject(s)
Breast/pathology , Gynecomastia/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Antigens, CD/analysis , Antigens, Differentiation, Myelomonocytic/analysis , Cell Adhesion Molecules/analysis , Fat Necrosis/complications , Fat Necrosis/immunology , Fat Necrosis/pathology , Gynecomastia/complications , Gynecomastia/immunology , Humans , Hyperplasia/complications , Hyperplasia/immunology , Hyperplasia/pathology , Keratins/analysis , Male , Membrane Glycoproteins/analysis , Middle Aged , Mucin-1 , Mucins/analysis , Platelet Endothelial Cell Adhesion Molecule-1 , Vimentin/analysis , von Willebrand Factor/analysisABSTRACT
The antiphospholipid syndrome produces acute occlusions of arteries and veins. This syndrome can cause a multiple organ systems failure whose outcome is often fatal. The authors report a case of the primary, antiphospholipid syndrome characterized by this fatal outcome, a so-called "devastating" syndrome following pulse steroids. In this patient, the antiphospholipid antibodies had been found after presenting bone-marrow fat necrosis, which led to extensive lesions of knees, hips and shoulders. Damage to the cell membranes in necrotic lesions might have promoted the immune response against phospholipids. The potential risks of pulse doses of steroids in the antiphospholipid syndrome are documented by the present observation, which also suggests that antiphospholipid antibodies should be determined in cases of fat necrosis of all origins.
Subject(s)
Antiphospholipid Syndrome/etiology , Fat Necrosis/complications , Fat Necrosis/immunology , Fatal Outcome , Humans , Injections, Jet , Male , Middle Aged , Multiple Organ Failure , Prednisone/adverse effectsABSTRACT
Feeding a choline-deficient diet containing 0.5% DL-ethionine induces an acute hemorrhagic pancreatitis in 100% of young female mice. Evidence for deposition of the third component of complement (C3) on acinar cell plasma membranes was sought, during the inductive stages, by a sandwich immunofluorescence technique. Such a localization could not be demonstrated even though the method is capable of detecting less than 8 x 10(-5) microgram of protein/mm2 of cell membrane. Artifactual binding of immunoglobulin reagents was encountered when goat antisera, with high levels of circulating immune complexes, formed the middle layer in the sandwich technique. This was attributed to the appearance of Fc receptors on the plasma membrane of degenerating acinar cells, and could be avoided by ultracentrifuging acinar cells, and could be avoided by ultracentrifuging the goat antisera prior to sue. In view of the fact that C3 cleavage represents an amplification loop in both the calssical and alternate pathways of complement activation, the lack of demonstrable C3 staining in tbe present experiments strongly suggests that complement plays no role in acinar cell necrosis in this model of pancreatitis.