Anti-Mi-2 antibody-positive lung cancer-associated polymyositis.

After a 75-year-old man was diagnosed with lung cancer, proximal weakness and myalgia in the bilateral lower extremities developed, and the creatinine kinase (CK) level was elevated. The anti-Mi-2 antibody test was positive, muscle T2-weighted/fat-suppressed magnetic resonance imaging showed high intensity, and there were no skin lesions. Therefore, he was diagnosed with lung cancer-associated polymyositis (PM). The lung tumour shrank after chemotherapy, accompanied by gradual improvement of his PM-derived symptoms and CK level. Although positive anti-Mi-2 antibody tests rarely indicate PM and cancer, examining myositis-specific autoantibodies, including anti-Mi-2, should be considered if the CK level increases after a cancer diagnosis.

Paraneoplastic Necrotizing Myopathy Associated With Metastatic Colon Cancer: A Case Report.

Necrotizing myopathy (NM) as a paraneoplastic process in malignancies is a rare phenomenon. An association of inflammatory myositis with malignancy and chemotherapies has been reported in several case reports. Here, we present an unusual case of paraneoplastic NM associated with metastatic colon cancer.

Paraneoplastic musculoskeletal disorders: review and update for radiologists.

Rheumatic paraneoplastic syndromes are rare syndromes that occur at distant sites from the underlying tumor and may involve the bones, joints, fasciae, muscles, or vessels. In the absence of a known tumor, early recognition of a rheumatic syndrome as paraneoplastic permits dedicated work-up for, and potentially early treatment of an occult malignancy. Although there is a continuously growing list of paraneoplastic rheumatic disorders, not all of these disorders have a well-established association with a neoplastic process. The goals of this article are to review the clinical characteristics, diagnostic work-up, and imaging findings of well-documented rheumatic paraneoplastic disorders.

Management of Cancer-Associated Myositis.

Purpose of the Review: Cancer-associated myositis (CAM) is defined as when cancer appears within 3 years of myositis onset. Dermatomyositis and seronegative immune-mediated necrotizing myopathy are the phenotypes mostly related to cancer. In general, treatment principles in myositis patients with and without CAM are similar. However, some aspects of myositis management are particular to CAM, including (a) the need for a multidisciplinary approach and a close relationship with the oncologist, (b) the presence of immunosuppressive and antineoplastic drug interactions, and (c) the role of the long-term immunosuppressive therapy as a risk factor for cancer relapse or development of a second neoplasm. In this review, we will also discuss immunotherapy in patients treated with checkpoint inhibitors as a treatment for their cancer. Recent Findings: Studies on cancer risk in patients treated with long-term immunosuppressive drugs, in autoimmune diseases such as systemic lupus erythematosus or rheumatoid arthritis, and in solid organ transplant recipients have shed some light on this topic. Immunotherapy, which has been a great advance for the treatment of some types of malignancy, may be also of interest in CAM, given the special relationship between both disorders. Summary: Management of CAM is a challenge. In this complex scenario, therapeutic decisions must consider both diseases simultaneously. Supplementary Information: The online version contains supplementary material available at 10.1007/s40674-022-00197-2.

Not a Statin-Induced Myopathy: Metastatic Pancreatic Adenocarcinoma Presenting As Paraneoplastic Myositis.

Polymyositis is an inflammatory disease that causes bilateral proximal muscle weakness; unlike dermatomyositis, it is not usually associated with malignancy. However, there are a handful of case reports documenting polymyositis in patients with lymphoma, breast, lung, and bladder cancer. Here we report a case of metastatic pancreatic adenocarcinoma disguised by presenting as polymyositis. Clinical presentation, laboratory values, muscle biopsy, and imaging were all diagnostic of paraneoplastic polymyositis. The patient has significantly improved in symptoms are receiving systemic steroids and pancreaticoduodenectomy.

Development of dermatomyositis after anti-transcriptional intermediary factor 1-γ antibody seroconversion during treatment for small cell lung cancer.

BACKGROUND: Inflammatory myositis, such as dermatomyositis, is sometimes complicated by cancer and is recognized as cancer-associated myositis. Although some autoimmune antibodies are considered to be involved in the development of myositis in cancer patients, the precise mechanism has not been clarified. The findings of the present case shed light on the mechanism by which anti-transcriptional intermediary factor 1 (TIF1)-γ Ab was produced and the pathogenesis of cancer-associated myositis. CASE PRESENTATION: We describe a case of dermatomyositis that developed in a 67-year-old man who had been diagnosed with small cell lung cancer of clinical T4N3M0 stage IIIB/limited disease during treatment. He received systemic chemotherapy and radiation therapy, and dermatomyositis developed along with a significant decrease in tumor size. TIF1-γ Ab, which is one of the myositis-specific antibodies, was found to be seroconverted. In addition, immunohistochemical analysis showed that cancer cells were positive for the TIF1-γ antigen. CONCLUSION: The findings of the present case suggest that transcriptional intermediary factor 1-γ, which is released from tumor cells, induces the production of TIF1-γ Ab, leading to the development of dermatomyositis.

Anti-nuclear Matrix Protein 2 Antibody-positive Dermatomyositis Associated with Cervical Cancer Recurrence after 6 Years of Stable Disease.

A 79-year-old woman was evaluated for weakness, dysphagia, and elevated levels of creatinine kinase. Her medical history included stage IIIB cervical cancer eight years previously, which improved after undergoing radiotherapy. Two years later, cancer recurred in the right hilar and mediastinal lymph nodes, and the patient was successfully treated with chemotherapy. Physical examinations showed Gottron's sign, the V sign, the Holster sign, and nailfold erythema. Computed tomography revealed left supraclavicular lymphadenopathy, compatible with cancer recurrence. Anti-nuclear matrix protein 2 (NXP2) antibody was found in her sera and a diagnosis of cancer-associated dermatomyositis was thus made. This case suggests that cancer progression over a period of years may have triggered the onset of autoimmunity against NXP2.

Clinical value of cancer-associated myositis-specific antibodies, anti-transcriptional intermediary factor 1-γ, and anti-nuclear matrix protein 2 antibodies in a retrospective cohort of dermatomyositis/polymyositis in a Japanese community hospital.

Among the myositis-specific antibodies (MSA), anti-transcriptional intermediary factor 1 (TIF1)-γ and anti-nuclear matrix protein 2 (NXP2) antibodies are reportedly associated with cancer-associated myositis (CAM). We aimed to investigate patient characteristics of CAM and the clinical role of cancer-associated MSA (caMSA) in a retrospective cohort from a city hospital. All patients visiting our department between April 2014 and October 2021 with newly diagnosed dermatomyositis, polymyositis, and clinically amyopathic dermatomyositis were included. Anti-TIF1-γ and anti-NXP2 antibodies were collectively considered as caMSA. First, we compared clinical characteristics in CAM, defined as cases showing onset or recurrence of malignancy within 5 years, versus non-CAM. Second, we investigated independent risk factors for CAM. Third, we compared clinical characteristics with and without caMSA within CAM. Finally, we investigated whether caMSA was predictive of poor prognosis. The cohort of 39 patients included 12 (30.7%) CAM cases. Compared with non-CAM, CAM had significantly more dermatomyositis and higher frequencies of dysphagia, anti-TIF1-γ antibody, and caMSA. Using logistic regression analysis, caMSA was an independent risk factor for CAM. In a comparison between caMSA and non-caMSA within CAM, caMSA was associated with higher frequencies of stage ≥ II. However, caMSA did not necessarily indicate a poor prognosis. Only caMSA represented an independent risk factor for CAM and showed a significant association with advanced cancer. Key Points • Cancer-associated MSA was an independent risk factor for cancer-associated myositis. • Cancer-associated MSA was associated with advanced cancer.

Serum levels of anti-transcriptional intermediary factor 1-γ autoantibody associated with the clinical, pathological characteristics and outcomes of patients with dermatomyositis.

OBJECTIVE: To investigate the association of the serum levels of anti-transcriptional intermediary factor 1 (TIF1)-γ autoantibodies with the clinical and pathological characteristics, as well as the prognosis of adult patients with dermatomyositis (DM). METHODS: Eighty-seven adult DM patients with anti-TIF1-γ autoantibodies positive screened by immunoblotting assay were enrolled in the study. The presence and levels of anti-TIF1-γ autoantibodies were examined through enzyme-linked immunosorbent assay (ELISA). Muscle biopsy specimens were obtained from 52 patients, and immunohistochemistry was performed to visualize major histocompatibility complex (MHC)-I, CD3, CD20 and C5b-9. Muscle biopsy scores and disease activity were evaluated. RESULTS: A total of 80 patients were positive for anti-TIF1-γ autoantibodies confirmed by ELISA assay, including 30 cancer-associated myositis (CAM) and 50 non-CAM. Serum levels of anti-TIF1-γ autoantibodies did not significantly differ between the CAM and non-CAM groups. The levels of anti-TIF1-γ were associated with disease activity scores. A total of 63.9% of non-CAM patients displayed a classical DM pathological phenotype. Conversely, CAM patients presented with classical DM (25%), immune-mediated necrotizing myopathy (25%), non-specific myositis (32.3%), and normal (18%) phenotypes of muscle biopsy. Anti-TIF1-γ autoantibody levels were positively associated with muscle biopsy total scores, muscle fiber scores and inflammatory infiltration scores in the non-CAM patients but not in the CAM patients. The survival rate of CAM patients presenting with high anti-TIF1-γ autoantibody levels was lower than that of patients with low levels. However, no difference in survival rate was observed in the non-CAM group between high and low autoantibody levels. CONCLUSION: The distinct associations of anti-TIF1-γ autoantibody levels with disease activity, muscle histopathology damage and outcome indicated that different pathogenesis might be involved in DM with or without cancer.

Update on Malignancy in Myositis-Well-Established Association with Unmet Needs.

Idiopathic inflammatory myopathies are a group of rare connective tissue diseases with a well-documented association with malignancy. The mechanisms underlying the increased risk of neoplasms in the course of myositis are not fully understood. The Pubmed database has been thoroughly screened for articles concerning cancer-associated myositis (CAM). The article summarizes the current state of knowledge on the epidemiology and pathogenesis of CAM. Furthermore, it analyses potential risk and protective factors for developing CAM, with particular emphasis on the association with distinct serological profiles. The review summarizes recommendations proposed so far for the management of CAM and presents a novel scheme for cancer screening proposed by the authors. Moreover, promising areas requiring further research were indicated.

Cancer screening in idiopathic inflammatory myopathies: Ten years experience from a single center.

OBJECTIVE: There is a well-recognized association between cancer and myositis, so cancer screening at diagnosis is recommended. We aim to report the results of our cancer screening strategy and to ascertain the reliability of using PET/CT to identify cancer-associated myositis (CAM) in a large cohort of patients with myositis from a single center over 10 years. METHODS: This retrospective observational study included all patients diagnosed with any type of myositis except for inclusion body myositis. Cancer screening strategy was individualized according to clinical and serological data, including PET/CT as the main test to detect occult cancer (OC). Procedures derived from a positive PET/CT were registered. Qualitative data expressed as percentages, and quantitative data as the median with the interquartile range were analyzed. A ROC curve was used to estimate the reliability of PET/CT for CAM diagnosis. RESULTS: Seventy-seven out of 131 patients underwent a PET/CT for OC screening. The performance of the PET/CT in patients with myositis at disease onset yielded an area under the curve ROC of 0.87 (0.73-0.97) for CAM diagnosis. Invasive procedures in 7 (9%) patients without a final diagnosis of cancer did not cause derived complications. Patients not evaluated for OC did not develop cancer after a median follow-up of 3.3 years (1.7-6.7). CONCLUSION: Cancer screening strategy should be individualized. PET/CT at myositis onset seems to be an efficient approach to rule out CAM. This practice does not seem to significantly increase harm to patients related to the additional tests needed to clarify inconclusive results.

Case report: Rare intrapulmonary malignant mesothelioma complicated with myositis.

Malignant pleural mesothelioma is an uncommon aggressive tumor. Its incidence is even lower when the lung parenchyma is the primary site. Myositis is a common paraneoplastic syndrome, but it rarely presents with malignant pleural mesothelioma. This report presents a rare intrapulmonary malignant mesothelioma complicated by cancer-associated myositis. The patient presented with limb muscle weakness as the first symptom and was diagnosed with intrapulmonary malignant mesothelioma complicated by cancer-associated myositis on the basis of clinical, histological, immunohistochemical, and radiological findings. The patient responded poorly to conventional hormone therapy and died of respiratory failure within 2 months after the first presence of limb muscle weakness.

Transcriptional intermediary factor 1 (TIF1) and anti-TIF1γ antibody-positive dermatomyositis.

Recently, great advancements have been made towards understanding the mechanisms underlying dermatomyositis (DM). Many novel autoantibodies, such as anti-MDA5, anti-TIF1γ, anti-NXP2, and anti-SAE, have been reported to be involved in DM. DM is now classified based on these myositis-specific autoantibodies. Anti-TIF1γ antibodies are closely associated with juvenile DM and adult cancer-associated DM. Anti-TIF1γ antibody-positive DM tends to present severe cutaneous manifestations, mild myositis, and dysphagia. TIF1γ (also known as TRIM33) plays a role in transcriptional elongation, DNA repair, differentiation of cells, embryonic development, and mitosis. Moreover, TIF1γ has been shown to suppress various tumors via the TGF-ß/Smad and the Wnt/ß-Catenin signaling pathways. In this review, we explore the relationship between TIF1γ, cancer, and DM. We also discuss the pathogenesis of anti-TIF1γ antibody-positive DM.

Follicular lymphoma associated paraneoplastic myositis.

This case illustrates an unusual presentation of paraneoplastic myositis in stage IV follicular lymphoma managed with high-dose steroids, a previously unreported entity in the literature.

Analysis of myositis autoantibodies in Chinese patients with cancer-associated myositis.

BACKGROUND: Cancer-associated myositis (CAM) has poor prognosis and causes higher mortality. In general, myositis-specific autoantibodies (MSAs) and myositis-associated autoantibodies (MAAs) have been shown to be useful biomarkers for its diagnosis. METHODS: In the present study, focus was given in assessing the presence, prevalence, and diagnostic values of myositis autoantibodies in Chinese patients diagnosed with CAM. The sera collected from 49 CAM patients, 108 dermatomyositis/polymyositis (DM/PM) patients without cancer, 105 disease controls, and 60 healthy controls were detected for the presence of 16 autoantigens (Jo-1, OJ, EJ, PL-7, PL-12, MDA5, TIF1γ, Mi-2α, Mi-2ß, SAE1, NXP2, SRP, Ku, PM-Scl75, PM-Scl100, and Ro-52) using a commercial Euroline assay. RESULTS: The frequency of anti-TIF1γ was significantly higher in CAM patients than in DM/PM patients without cancer (46.9% vs 14.8%, P < .001). Importantly, the sensitivity and specificity for this MSA were 46.9% and 85.2%, respectively. These helped to differentiate CAM patients from DM/PM patients without cancer. However, there was no difference in other MSAs and MAAs between CAM and DM/PM patients without cancer. CONCLUSION: The present study indicates that anti-TIF1γ levels can serve as important biomarkers for CAM diagnosis and help in distinguishing between CAM and DM/PM patients without cancer.

Retrospective Analysis of Cancer-Associated Myositis Patients over the Past 3 Decades in a Hungarian Myositis Cohort.

Association between cancer and myositis has been extensively reported and malignancy is a potentially life-threating complication in myositis. In this retrospective study authors give an overview of Hungarian cancer-associated myositis (CAM) patients treated at a single centre managing 450 myositis patients. All patients were diagnosed according to Bohan and Peter. Statistical analysis of disease onset, age, sex, muscle, skin and extramuscular symptoms, muscle enzymes, presence of antibodies, treatment and prognosis was performed. 43 patients could be considered as having CAM. 83.72% had cancer within one year of diagnosis of myositis. Most common localizations were ductal carcinoma of breast and adenocarcinoma of lung. Significant differences were observed between CAM and the non-CAM control patients: DM:PM ratio was 2.31:1 vs. 0.87:1, respectively (p = 0.029), age at diagnosis was 56.60 ± 12.79 vs. 38.88 ± 10.88 years, respectively (p < 0.001). Tumour-treatment was the following: surgical removal in 55.81%, chemotherapy in 51.1%, radiotherapy in 39.53%, hormone treatment in 18.6%, combination therapy in 51.16% of patients. Muscle enzyme levels of patients undergoing surgery were significantly reduced after intervention. 36 patients died (83.72%); 25 DM (83.33%) and 11 PM patients (84.62%); 5 years survival was 15.4% for PM and 27.5% for DM. This study demonstrates that DM, distal muscle weakness, asymmetric Raynaud's phenomenon, older age, ANA-negativity are risk factors for developing malignancy and polymyositis patients have less chance of long-lasting survival. It is very important to think about cancer and follow every single myositis patient in the clinical routine because survival rate of CAM is very poor.

[Paraneoplastic rheumatologic syndromes in the elderly].

Risk of development of malignant tumors increases in elderly people. There are numerous clinical symptoms mimicking primary rheumatic diseases in the course of cancers, referred to as paraneoplastic rheumatologic syndromes. They are not caused directly by the tumor or its metastases, but result from the action of biologically active substances released by cancer cells and abnormal immunological reactions. Paraneoplastic rheumatologic syndromes may precede the diagnosis of cancer, occur simultaneously or occur after the diagnosis of malignancy. In clinical practice, it is very difficult to distinguish paraneoplastic syndromes from idiopathic rheumatic diseases. However, some clinical features may suggest the paraneoplastic nature of rheumatic diseases, including the onset of symptoms in old age, atypical and rapidly progressive course or poor response to conventional treatment. Early and well-targeted diagnostics allow the diagnosis of often latent neoplasm, and its effective treatment may lead to resolution of paraneoplastic rheumatic symptoms. This paper discusses selected paraneoplastic rheumatologic syndromes that often occur in older people, including carcinomatous polyarthritis, remitting seronegative symmetrical synovitis with pitting edema (RS3PE), palmar fasciitis-polyarthritis syndrome, hypertrophic osteoarthropathy, tumor-induced osteomalacia, cancerassociated myositis, paraneoplastic scleroderma like syndrome, paraneoplastic vasculitis and paraneoplastic Raynaud's syndrome.