- Preclinical, non-genetic models of lung adenocarcinoma: a comparative survey. [Journal Article]
- OOncotarget 2018 Jul 17; 9(55):30527-30538
- Lung cancer is the leading cause of cancer-related mortality worldwide. Animal models are key in analyzing cancer biology and therapy evaluation. We here compared relevant non-genetic lung cancer mod...
Lung cancer is the leading cause of cancer-related mortality worldwide. Animal models are key in analyzing cancer biology and therapy evaluation. We here compared relevant non-genetic lung cancer models with regard to tumor induction period, incidence, morbidity and mortality rate and the immunological composition of primary tumors and the occurrence of tertiary lymphoid organs (TLO): (I) intraperitoneal Urethane injection (1g/kg), (II) Lewis lung carcinoma (LLC) cell line model (intravenous or subcutaneous), and (III) ex vivo three-dimensional (3D) primary cell culture model established from subcutaneously developed LLC-induced tumors. The incidence of Urethane induced lung tumors was 100% in both, C57BL/6 and BALB/c strains without morbidity or mortality at twenty weeks after injection. The mean size of tumor nodules after Urethane injection was significantly larger in BALB/c mice vs. C57BL/6 (p<0.01). Three times of Urethane injection produced significantly more tumor nodules in both mouse strains compared to one injection (BALB/c: p<0.01; C57BL/6: p<0.05). TLOs were only found in the Urethane-induced model. Although the cell line models also showed 100% induction rate, morbidity was high due to skin ulceration on the inoculation site and the development of pleural effusions in the subcutaneous model and the intravenous model, respectively. Tendencies, but no significant differences (p>0.05) could be found in the count of CD4+, CD8+, F4/80+ and NKp46+ cells in a tumor nodule among investigated models. All discussed models provided a high tumor incidence rate. TLOs were exclusively found in the Urethane-induced model. No significant difference could be found regarding immune cells across models.
- Dermatophytic pseudomycetomas in two ferrets (Mustela putorius furo). [Case Reports]
- VDVet Dermatol 2018 Aug 09
- CONCLUSIONS: To the best of the authors' knowledge, this is the first description of dermatophytic pseudomycetoma in domestic ferrets. This disease should be included in the differential diagnosis of nodular dermatopathies in this species.
- Suture granulomas developing after the treatment of oral squamous cell carcinoma. [Journal Article]
- IJInt J Surg Case Rep 2018 Jul 27; 50:68-71
- CONCLUSIONS: Chemoradiation therapy may enhance the immunoreaction of macrophages in the radiation field and promote the formation of granulation tissue in a short period of time. In addition, cisplatin, which was concurrently administered with radiation in our case, could have influenced the development of the suture granuloma.In addition to tumor recurrence, suture granulomas should be considered a differential diagnosis for nodules occurring after surgery, even if they develop in the field of radiation.
- Hardness and Painful Lesion of the Breast. [Journal Article]
- ADActa Dermatovenerol Croat 2017; 25(4):305-306
- Dear Editor, Lupus panniculitis or lupus profundus is a rare inflammatory complication found in patients with systemic lupus erythematosus (SLE), or discoid lupus erythematosus (DLE) (1). When the br...
Dear Editor, Lupus panniculitis or lupus profundus is a rare inflammatory complication found in patients with systemic lupus erythematosus (SLE), or discoid lupus erythematosus (DLE) (1). When the breast is involved, the term lupus mastitis (LM) is used. This disease involving the breast is rare, and the lesions may precede, coincide with, or occur later than the onset of other lupus lesions. Tissue biopsy is required to confirm the suspected diagnoses of LM. We report a case of a patient with lupus mastitis due to the important differential diagnosis. A 60-year-old woman presented with a painful nodular lesion in her left breast that had appeared 15 days ago (Figure 1, a). She had been previously diagnosed with discoid lupus erythematosus 3 years ago. Physical examination revealed a deep and firm erythematous subcutaneous nodule without overlying skin involvement in the lower-central portion of the left breast. Laboratory findings were positive for antinuclear antibodies (1:80) and double-stranded deoxynucleic acid antibodies (1:10). Mammography and ultrasounds showed an area of increased density and irregular breast tissue along with an important thickening of the overlying skin (Figure 1, b). On suspicion of malignancy, a needle biopsy of the breast lesion was performed and showed vacuolar alteration and lymphocytic infiltrate in the basal layer. Subcutaneous fat showed a lobular panniculitis with a prominent lymphocytic infiltrate and hyalinization of the fat lobules (hyaline fat necrosis). Direct immunofluorescence of the face biopsy revealed IgA, IgG, IgM, and C3 granular deposition. Based on these results, a diagnosis of lupus mastitis associated with DLE was established. Antimalarial therapy resulted in complete resolution of the clinical features. Three years later, the patient presented with a disfiguring atrophy with retraction in the damaged areas of the breast (Figure 2). Lupus mastitis is a very unusual disease that most commonly affects middle-aged women. The first case of LM was described by Tuffanelli in 1971. The lesions usually present following the diagnosis of SLE/DLE; however, on rare occasions they may be observed earlier (2). The histophysiology of this disease remains unclear, but the predominant theory suggests an autoimmune-related etiology. Corroborating evidence for this theory includes the finding of immune complexes, both at the basement membrane of the dermal-epidermal junction and in the blood vessels in the areas of panniculitis (3). Lupus mastitis may be present in the breast as single or multiple subcutaneous nodules that may be tender or painful and can progress to chronic ulcers over time or resolve, leaving atrophic scars. The overlying skin can be normal, erythematous, poikilodermic or ulcerated. When skin changes are prominent, the lesion may clinically and radiologically mimic inflammatory breast carcinoma. Mammographic and ultrasounds findings include an ill-defined breast density with or without associated microcalcifications (4). Histologically, this disease is characterized by lobular lymphocytic panniculitis and predominantly involves the fat lobule and the presence of anucleated adipocytes in a background of a glassy-appearing collagenous stroma (hyaline fat necrosis). Fibrinoid necrosis of the vessel wall has also been reported, but is usually absent (5). Differential diagnosis of lupus mastitis includes inflammatory breast carcinoma, primary medullary carcinoma, and other immune-mediated inflammatory conditions such as diabetic mastopathy. The first line of treatment the use of antimalarial drugs such as hydroxychloroquine. Systemic steroids and cyclophosphamide have also been used. Surgical treatment should be considered only in patients who do not respond to management with medications. In summary, we reported a case of lupus mastitis in a patient with discoid lupus erythematosus. This dermatosis should be considered in the differential diagnosis of breast lesions in lupus patients, and a biopsy of the breast lesion is essential to reject suspected malignancy. If the disease is left untreated, unsightly atrophy will appear; it is thus important to diagnose early on. The course of the disease tends to be chronic with remission and flares, so patients should be followed-up regularly due to the risk of recurrences in the same area or in a different location.
- Subcutaneous Granuloma Annulare. [Journal Article]
- ADActa Dermatovenerol Croat 2017; 25(4):292-294
- Dear Editor, Subcutaneous granuloma annulare (SGA) is considered a rare clinical variant of granuloma annulare, a common self-healing chronic inflammatory disorder that may appear in childhood as wel...
Dear Editor, Subcutaneous granuloma annulare (SGA) is considered a rare clinical variant of granuloma annulare, a common self-healing chronic inflammatory disorder that may appear in childhood as well as in adult age (1-3). A 29-year-old female patient reported the onset of several small subcutaneous nodules on the dorsal aspect of the second interphalangeal joint of the left medius finger and the left elbow, accompanied by vague joint pain, had occurred 13 years ago. Specific markers for rheumatoid arthritis were negative, leading to a diagnosis of sero-negative rheumatoid arthritis, for which treatment with methotrexate was initiated. No clinical benefit was obtained and the treatment was abandoned. New nodules continued to appear on several distal joints of the fingers of both hands and, in the last 6 months, on the second right toe. The course of the disease included spontaneous remission of some of the nodules. Personal medical history was significant for a thyroid nodule, surgically removed at the age of 22. A general physical exam did not reveal pathological changes. A clinical dermatological exam at the time of presentation revealed several round to oval, deep subcutaneous, indurated, asymptomatic, discreetly pigmented lesions with a diameter of 4-6 mm, located on the dorsal aspect of the interphalangeal joints of the fingers of both hands (Figure 1) and the second right toe. Hematologic and biochemical tests were within normal limits, as well as the serological tests for rheumatoid factor, ANCA, ANA, and anti-CCP antibody. Hand radiographs did not show geodes, marginal erosions, or narrow joint spaces. A pathological exam of a subcutaneous nodule showed focally altered collagen surrounded by fibroblasts, phagocytes, rare lymphocytes, and neutrophils, as well as small capillaries (Figures 2-5), compatible with the diagnosis of a pseudorheumatoid nodule or benign rheumatoid nodule in the clinical and paraclinical context. SGA is considered a rare clinical and histological variant of granuloma annulare that predominantly affects children and occasionally young adults (1-6). In 1941, Ziegler first described a case of subcutaneous nodules that appeared concomitantly with classical cutaneous lesions of granuloma annulare, as well as the histological aspect of these nodules similar to that of rheumatoid nodules (RN) (7). Since then, several case reports in the literature refer to the subcutaneous lesions of GA as "pseudorheumatoid nodules", "deep granuloma annulare" or "palisading granuloma" (3,4,8). Most reported cases of SGA occur in the first three decades of life: 98% according to Muhlemann, 79% according to Andersen and Verdich, 62% according to Studer; most cases occur in children between 2 and 6 years of age (9). Lesions often regress spontaneously, but recurrences are common in 19%-75% of the patients, often on the same anatomical areas (9,10). Reported SGA cases in adult patients predominantly affected women, and typically involved multiple lesions located on the hands, feet, ankles, and inferior pretibial area (4-6). The etiology and pathogenesis of SGA are not completely understood. Precipitating factors such as insect bites, infections with Borellia spp., herpetic virus, EBV, Streptococcus spp., PUVA-therapy, several drugs, physical trauma, acute phlebitis, and post-surgery sepsis have been considered (8). There is evidence for the pathogenic involvement of an immunological mechanism, possibly a delayed type hypersensitivity reaction mediated by T-cells that triggers a panniculitis-type inflammatory response (8,10). Correlations between SGA and systemic diseases such as diabetes mellitus, sarcoidosis, HIV infection, or autoimmune diseases have not been found (8). A positive diagnosis of pseudorheumatoid nodules relies on clinical and anamnestic data. Differential diagnosis includes rheumatoid nodules, benign rheumatoid nodules, foreign body reactions, hematomas, abscesses, and infectious granulomas (3,5). Pseudorheumatoid nodules and SGA have a low risk of progression to a systemic connective tissue disorder. In the presence of subcutaneous nodular lesions with an uncertain clinical diagnosis, cutaneous biopsy, hematological and immunological tests, and imaging may be performed to establish a positive diagnosis. Skin biopsy is the most useful test for the diagnostic approach because, even though it is sometimes difficult to interpret, a pathological exam may offer important data to distinguish between rheumatoid and pseudorheumatoid nodules. Necrobiosis may be identified in the deep dermis and subcutaneous tissue, and rarely in the deep soft tissues. Necrobiosis is less important and less deep than in rheumatoid nodules, as well as less extensive and less diffuse than in lipoidic necrobiosis (6). Anomalies in the morphology of the deep cutaneous structures may coexist with typical changes in classical granuloma annulare. Immunohistochemical studies using specific histiocyte markers such as CD68/PGM1 proved to be occasionally useful in differentiating SGA from other granulomatous conditions (11). Several tests are necessary to exclude an association with a systemic disease: hemoleucogram (absence of leucocytosis), ESR (normal values), acute phase reactants (negative fibrinogen, RCP), autoantibodies (negative ANA), and rheumatoid factor (negative). SGA is a benign disorder with esthetic implications and sometimes functional impairment. Surgical excision is only required for juxta-articular nodules causing functional impairment. Partial therapeutic benefit was reported after the administration of dapsone, clorambucil, isotretinoin, potassium iodide, or intralesional/topical steroids. Even though the risk of systemic involvement is low, periodical follow-up of these patients is required given the reported cases of associated systemic connective tissue disorders (8,12).
- Multiple Subcutaneous Nodules as Initial Presentation of Diffuse Large B-cell Non-Hodgkin Lymphoma (DLBCL) Detected by PET/CT. [Journal Article]
- CNClin Nucl Med 2018 Jul 27
- Subcutaneous tissue as a manifestation of generalized disease is commonly involved in lymphomas. However, only skin involvement without other sites of extracutaneous disease was rarely presented, esp...
Subcutaneous tissue as a manifestation of generalized disease is commonly involved in lymphomas. However, only skin involvement without other sites of extracutaneous disease was rarely presented, especially in diffuse large B-cell lymphoma (DLBCL). Herein, we reported an unusual case of primary cutaneous DLBCL, solely presenting with multiple subcutaneous nodules in the abdomen and back, and these nodules showed increased FDG uptake on PET/CT images. PET/CT is very helpful for diagnosing primary cutaneous DLBCL.
- [18F]Fluorocholine and [18F]fluoroacetate PET as imaging biomarkers to assess phosphatidylcholine and mitochondrial metabolism in preclinical models of TSC and LAM. [Journal Article]
- CCClin Cancer Res 2018 Jul 27
- CONCLUSIONS: In summary, our findings provide mechanistic evidence for testing the potential of [18F]FCH and [18F]FACE as metabolic imaging biomarkers for TSC and LAM proliferative lesions, and novel insights into the metabolic reprogramming of TSC tumors.
- Urticarial vasculitis and subcutaneous nodules in the extremities seen in a patient with mucopolysaccharidosis II after hematopoietic stem cell therapy. [Letter]
- JDJ Dermatol 2018 Jul 26
- Acid ceramidase deficiency: Farber disease and SMA-PME. [Review]
- OJOrphanet J Rare Dis 2018 Jul 20; 13(1):121
- Acid ceramidase (ACDase) deficiency is a spectrum of disorders that includes a rare lysosomal storage disorder called Farber disease (FD) and a rare epileptic disorder called spinal muscular atrophy ...
Acid ceramidase (ACDase) deficiency is a spectrum of disorders that includes a rare lysosomal storage disorder called Farber disease (FD) and a rare epileptic disorder called spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME). Both disorders are caused by mutations in the ASAH1 gene that encodes the lysosomal hydrolase that breaks down the bioactive lipid ceramide. To date, there have been fewer than 200 reported cases of FD and SMA-PME in the literature. Typical textbook manifestations of classical FD include the formation of subcutaneous nodules, accumulation of joint contractures, and development of a hoarse voice. In reality, however, the clinical presentation is much broader. Patients may develop severe pathologies leading to death in infancy or may develop attenuated forms of the disorder wherein they are often misdiagnosed or not diagnosed until adulthood. A clinical variability also exists for SMA-PME, in which patients develop progressive muscle weakness and seizures. Currently, there is no known cure for FD or for SMA-PME. The main treatment is symptom management. In rare cases, treatment may include surgery or hematopoietic stem cell transplantation. Research using disease models has provided insights into the pathology as well as the role of ACDase in the development of these conditions. Recent studies have highlighted possible biomarkers for an effective diagnosis of ACDase deficiency. Ongoing work is being conducted to evaluate the use of recombinant human ACDase (rhACDase) for the treatment of FD. Finally, gene therapy strategies for the treatment of ACDase deficiency are actively being pursued. This review highlights the broad clinical definition and outlines key studies that have improved our understanding of inherited ACDase deficiency-related conditions.
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- Endobronchial benign nerve sheath tumour presenting with significant shortness of breath and haemoptysis. [Journal Article]
- OMOxf Med Case Reports 2018; 2018(7):omy033
- Peripheral nerve sheath tumours are rare within the thoracic cavity, with non-specific presentation. A 29-year-old patient presented with shortness of breath, cough, haemoptysis and recurrent chest i...
Peripheral nerve sheath tumours are rare within the thoracic cavity, with non-specific presentation. A 29-year-old patient presented with shortness of breath, cough, haemoptysis and recurrent chest infections. Suspicion of a primary lung carcinoma or a neuroendocrine tumour was raised following a CT and PET-CT. An endobronchial tumour suggested on histology a diagnosis of benign nerve sheath tumour, with positive staining for S100, CD56 and CD34. Following lung resection, the patient complained of fatigue and developed subcutaneous erythematous nodules on the anterior right chest, which raised the suspicion for a differential diagnosis of neurofibromatosis type I. The nodules resolved spontaneously within two weeks and the diagnosis of neurofibromatosis was ruled out on subsequent magnetic resonance imaging head and chest.