Imiquimod (IMQ), a synthetic agonist to Toll-like receptor (TLR) 7, is being successfully used for the treatment of certain skin neoplasms, but the exact mechanisms by which this compound induces tumor regression are not yet understood. While treating basal cell carcinoma (BCC) patients with topical IMQ, we detected, by immunohistochemistry, sizable numbers of both myeloid dendritic cells (mDCs) and plasmacytoid DCs (pDCs) within the inflammatory infiltrate. Surprisingly, peritumoral mDCs stained positive for perforin and granzyme B, whereas infiltrating pDCs expressed tumor necrosis factor–related apoptosis-inducing ligand (TRAIL). The biological relevance of this observation can be deduced from our further findings that peripheral blood–derived CD11c+ mDCs acquired antiperforin and anti–granzyme B reactivity upon TLR7/8 stimulation and could use these molecules to effectively lyse major histocompatibility complex (MHC) class Ilo cancer cell lines. The same activation protocol led pDCs to kill MHC class I–bearing Jurkat cells in a TRAIL-dependent fashion. While suggesting that mDCs and pDCs are directly involved in the IMQ-induced destruction of BCC lesions, our data also add a new facet to the functional spectrum of DCs, ascribing to them a major role not only in the initiation but also in the effector phase of the immune response.
Gallbladder adenomyomatosis (GA) is a benign alteration of the gallbladder wall that can be found in up to 9% of patients. GA is characterized by a gallbladder wall thickening containing small bile-filled cystic spaces (i.e., the Rokitansky–Aschoff sinuses, RAS). The bile contained in RAS may undergo a progressive concentration process leading to crystal precipitation and calcification development. A correct characterization of GA is fundamental in order to avoid unnecessary cholecystectomies. Ultrasound (US) is the imaging modality of choice for diagnosing GA; the use of high-frequency probes and a precise focal depth adjustment enable correct identification and characterization of GA in the majority of cases. Contrast-enhanced ultrasound (CEUS) can be performed if RAS cannot be clearly identified at baseline US: RAS appear avascular at CEUS, independently from their content. Magnetic resonance imaging (MRI) should be reserved for cases that are unclear on US and CEUS. At MRI, RAS can be identified with extremely high sensitivity, but their signal intensity varies widely according to their content. Positron emission tomography (PET) may be helpful for excluding malignancy in selected cases. Computed tomography (CT) and cholangiography are not routinely indicated in the suspicion of GA.Teaching points1. Gallbladder adenomyomatosis is a common benign lesion (1–9% of the patients).2. Identification of Rokitansky–Aschoff sinuses is crucial for diagnosing gallbladder adenomyomatosis.3. Sonography is the imaging modality of choice for diagnosing gallbladder adenomyomatosis.4. Intravenous contrast material administration increases ultrasound accuracy in diagnosing gallbladder adenomyomatosis.5. Magnetic resonance is a problem-solving technique for unclear cases.
Pap smears after BMT show a high incidence of dysplastic lesions. Moreover, conditioning including busulfan is often associated with therapy-related cytologic atypia, which may lead to unnecessary colposcopies and biopsies. Knowledge of the patient's history and a careful evaluation of the smears are mandatory in these cases.
BackgroundSilicone implants have been successfully used for breast augmentation and reconstruction in millions of women worldwide. The reaction to the silicone implant is highly variable; it can lead to local inflammatory symptoms, and sometimes to systemic symptoms and disease. Over 80 cases of anaplastic lymphoma kinase-negative anaplastic large cell lymphoma have been reported in patients with silicone breast implants and have been accepted as a new clinical entity. To the best of our knowledge, an intravascular large B-cell lymphoma associated with a silicone breast implant has not been reported previously.Case presentationA 48-year-old Caucasian woman who presented with high fever was found to have splenomegaly on physical examination. A laboratory diagnosis revealed pancytopenia, hypertriglyceridemia, and hyperferritinemia. She developed signs of altered sensorium, hemiparesis, aphasia, and cauda equina syndrome. On further evaluation, she fulfilled the necessary five out of eight criteria for diagnosis of macrophage activation syndrome/hemophagocytic lymphohistiocytosis. Dexamethasone administration was followed by prompt improvement; however, 3 days later she again manifested high fever, which persisted despite administration of immunoglobulin and cyclosporine A. Her silicone breast implant was considered a possible contributor to her macrophage activation syndrome and was therefore removed. A histological examination of the capsule tissue showed an extensive lymphohistiocytic/giant cell foreign body reaction suggestive of autoimmune/inflammatory syndrome induced by adjuvants. However, the histological examination unexpectedly also revealed an intravascular large B-cell lymphoma.ConclusionsThe genetic background of our patient with silicone breast implants might have predisposed her to three rare and difficult to diagnose syndromes/diseases: macrophage activation syndrome/hemophagocytic lymphohistiocytosis, autoimmune/inflammatory syndrome induced by adjuvants, and intravascular large B-cell lymphoma. The simultaneous manifestation of all three syndromes suggests causal interrelationships. Human leukocyte antigen testing in all women who undergo silicon breast implantation could in the future enable us to better evaluate the risk of potential side effects.Electronic supplementary materialThe online version of this article (doi:10.1186/s13256-016-0993-5) contains supplementary material, which is available to authorized users.
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