INTRODUCTION — Dermatomyositis (DM) and polymyositis (PM) are idiopathic inflammatory myopathies characterized by proximal skeletal muscle weakness and evidence of muscle inflammation. DM, unlike PM, is characterized by the presence of various cutaneous manifestations. DM and PM may also be associated with inflammatory arthritis, interstitial lung disease, Raynaud phenomenon, and the presence of autoantibodies.
An association between inflammatory myopathy and cancer has been recognized since the report of two cases of PM and gastric cancer in 1916 [1]. The association is stronger for patients with DM than PM. The evidence for an association between cancer and inflammatory myopathy includes:
●Epidemiologic evidence from large population studies
●Temporal relationship between the diagnosis of cancer and myopathy
●The improvement or resolution of myopathy after treatment of the cancer
●Relapse or development of myopathy associated with relapse of the cancer
The increased frequency of cancer in patients with inflammatory myopathy is consistent with the concept that paraneoplastic processes linked to oncogenesis and autoimmunity contribute to the disease in a subset of DM and PM cases.
Issues related to malignancy in patients with DM and PM will be reviewed here. The clinical manifestations, diagnosis, and management of both the adult and juvenile forms of these disorders are discussed separately. (See "Clinical manifestations of dermatomyositis and polymyositis in adults" and "Initial treatment of dermatomyositis and polymyositis in adults" and "Juvenile dermatomyositis and polymyositis: Epidemiology, pathogenesis, and clinical manifestations" and "Juvenile dermatomyositis and polymyositis: Treatment, complications, and prognosis".)
PATHOPHYSIOLOGY — The precise links between malignancy and inflammatory myopathy remain incompletely understood [2,3]. However, the temporal relationship in some patients between the development of cancer and diagnosis of inflammatory myopathy is reminiscent of that seen in neurologic paraneoplastic disorders in which the antigens targeted for an immune response are expressed at high levels in both the inciting tumor and the affected neuronal tissue [4,5]. (See "Overview of paraneoplastic syndromes of the nervous system".)
Regenerating cells in myositis muscle but not in normal muscle express high levels of myositis-specific autoantigens [2]. These same antigens are expressed at high levels in several cancers known to be associated with the development of inflammatory myopathy, but not in corresponding normal tissue. These observations suggest that the link between malignancy and inflammatory myopathy relates to the expression of common autoantigens between cancer tissue and muscle tissue in some patients with dermatomyositis (DM) or polymyositis (PM), and that the immune response directed at tumor cells may also target similar autoantigens in muscle tissue resulting in muscle damage.
EPIDEMIOLOGY — The association between malignancy and inflammatory myopathy has been supported by numerous epidemiologic studies, with the strongest association occurring in those with dermatomyositis (DM) [6-14].
Incidence — A review of 258 cases of DM and cancer reported in the literature from 1916 through the mid-1970s estimated that the incidence of cancer for patients with DM was increased five- to seven-fold compared with the general population [6]. The increased risk has subsequently been confirmed in population-based studies from a variety of countries. Standardized incidence ratios from population-based studies from Denmark [9], Australia [10], and Taiwan [11] range from approximately 3.0 to 6.0. The largest population study from Taiwan included 1,012 DM and 643 patients with polymyositis (PM) from the National Health Insurance Database from 1997-2007. Among the patients with DM, the frequency of cancer was 9.4 percent and the standardized incidence ratio (SIR) 5.11 (95% CI 5.01-5.22). In the PM group, the frequency of cancer was 4.4 percent with an SIR of 2.15 (95% CI 2.08-2.22) [11].
The cancer rates reported with PM are consistently lower than that of DM. Some investigators have questioned whether the modestly increased incidence in PM indicates a true increase in cancer risk or may reflect increased surveillance in patients with PM compared with the general population [8,13].
Types of malignancies — The types of cancer associated with inflammatory myopathy appear to mirror the incidence of cancer in the general population. As an example, a population-based study including patients from Sweden, Denmark, and Finland found an increased risk of ovarian, lung, breast, pancreatic, and colorectal cancers [15]. In another study including patients from Taiwan, nasopharyngeal carcinoma was the most common type of malignancy in patients with DM, followed by lung and breast cancer [11,16]. Ovarian, pancreatic, and gastric cancers appear to occur more frequently in patients with inflammatory myopathy than in the general population [15]. There is a strong association between ovarian cancer and the presence of the anti-transcription intermediary factor 1 (TIF1) antibody [17].
Temporal relationship — Cancer can be diagnosed before, simultaneously with, or after the diagnosis of inflammatory myopathy [11]. The peak incidence of a cancer diagnosis in DM and PM occurs simultaneously with and during the first year after the diagnosis of the muscle disease, and falls off gradually over the subsequent five years of follow-up [8,11,17-19], although there may still be some increased risk beyond five years [11,19].
In some patients, the inflammatory myopathy is diagnosed at the time of recurrence of previously diagnosed cancer. In others, previously diagnosed muscle disease becomes reactivated when the cancer appears [20,21].
RISK FACTORS — As noted above, most studies have concluded that the risk of cancer is greater in patients with dermatomyositis (DM) than in those with polymyositis (PM).
Clinical risk factors — Other factors associated with an increased risk of malignancy include:
●Evidence of capillary damage on muscle biopsy [22]
●Cutaneous necrosis
●Cutaneous leukocytoclastic vasculitis [23]
●Older age at disease onset [24]
●Dysphagia [24]
Patients with interstitial lung disease appear to have a lower frequency of malignancies [18,24,25].
Serum autoantibodies — Some serum antibodies in DM and PM confer a positive risk of malignancy, whereas others are associated with a negative risk.
●Positive risk – "Cancer-associated myositis" (CAM) in adults has been associated in several studies with antibodies to transcription intermediary factor (TIF)-1gamma (anti-p155, anti-p155/140) and with antibodies to nuclear matrix protein (NXP)-2 (anti-MJ or anti-p140) [19,26-29].
●Negative risk – Conversely, the presence of myositis-specific (anti-synthetase antibodies, anti-Mi-2, anti-SRP, and anti-MDA5) and myositis-associated antibodies (anti-RNP, anti-PM-Scl, anti-Ku) appears to be associated with a decreased risk of malignancy but an increased risk of interstitial lung disease in DM [26]. More study is required to determine the utility of these autoantibodies for cancer screening in patients with myositis.
APPROACH TO SCREENING — In the absence of definitive data suggesting one approach over another, screening practices vary among clinicians. The approach described below is based upon clinical experience and available observational data.
Initial screening for malignancy — All patients newly diagnosed with polymyositis (PM) or dermatomyositis (DM) should be evaluated for the possibility of an underlying malignancy. Most cancers will be found with a comprehensive history and physical examination, including a pelvic exam, along with the following investigations:
●Complete blood count, liver function tests, urinalysis
●Fecal occult blood test, if screening colonoscopy not indicated
●Chest radiograph
●Age- and sex-appropriate Pap test, testicular self-examination, mammography, and colonoscopy
Further investigation, including computed tomography (CT) scanning of the chest/abdomen/pelvis, is directed by abnormal results found on the above evaluation or should be performed in those patients assessed to be at high risk for an underlying malignancy. The presence of more than one risk factor should further increase suspicion for an underlying malignancy [30]. The following features are associated with an increased risk of malignancy:
●Older age at disease onset
●Severe cutaneous disease, especially patients with the shawl sign or skin necrosis
●Resistance to treatment
●Prior history of malignancy with the risk of relapse
●Absence of interstitial lung disease
●Absence of myositis-specific and myositis-associated antibodies and the presence of the p155/140 and/or anti-NXP2 antibodies
While there is no consensus regarding the utility of screening for ovarian cancer in patients with DM, our authors obtain serial measurements of CA 125 levels and a transvaginal ultrasound in women considered to be at high risk for ovarian cancer (table 1). A single CA 125 test is not recommended for screening, although increasing CA 125 levels on serial screening may be of value. (See "Screening for ovarian cancer", section on 'Screening approach'.)
Positron emission tomography (PET) using [18F] fluorodeoxyglucose (FDG) and combined with CT (FDG-PET/CT) is a highly sensitive imaging technique that has been used increasingly for the detection of malignancy, but few studies have examined its role in screening for malignancy in patients with DM and PM [31-33]. Further study is needed to determine whether FDG-PET/CT has a role is screening practices among patients with DM or PM. We do not perform routine PET scanning to screen patients with DM or PM for malignancy. Commercial insurances would not cover this indication in most cases. At this point, we employ the screening approach as outlined above. If a very high index of suspicion remained after extensive standard investigation, PET scanning could be considered in a patient with myositis at very high risk for an underlying malignancy in the same way that it would be considered in a patient without inflammatory myopathy.
Post-treatment surveillance — The value of repeat cancer screening in patients with established PM and DM is not well-established. Most studies have shown an increased risk of cancer for at least five years in patients with DM (but not PM), although the risk declines annually (see 'Temporal relationship' above). Therefore, the diagnostic yield of continued surveillance for cancer after the initial screening is low, unless specific signs suggestive of an underlying malignancy appear, or a relapse of the inflammatory myopathy occurs after a period of remission [9]. Patients should continue to have routine, age-appropriate screening (eg, mammogram, pelvic exam) as in the general population. (See "Overview of preventive care in adults", section on 'Cancer screening'.)
IMPACT OF MALIGNANCY ON DISEASE SEVERITY — The presence of a tumor does not appear to affect the severity or distribution of weakness, the duration of weakness prior to diagnosis, or the height of creatine kinase elevation. Myositis associated with cancer, however, responds more poorly to treatment than myositis in the absence of cancer, and survival rates are worse for patients with malignancy [34,35]. Poor response to myositis treatment therefore should raise the possibility of an underlying malignancy.
SUMMARY AND RECOMMENDATIONS
●Both dermatomyositis (DM) and polymyositis (PM) are idiopathic inflammatory myopathies associated with malignancies in a significant minority of cases. The close relationship between inflammatory myopathy and cancer is consistent with the concept that paraneoplastic processes linked to oncogenesis and autoimmunity contribute to the disease in a subset of DM and PM cases. (See 'Introduction' above and 'Pathophysiology' above.)
●Population-based cohort studies from a number of countries have confirmed the increased risk of malignancy among patients with inflammatory myopathies. The cancer rates reported with PM are consistently lower than that of DM. (See 'Epidemiology' above and 'Incidence' above.)
●Adenocarcinomas of the cervix, lung, ovaries, pancreas, bladder, and stomach account for approximately 70 percent of the cancers associated with inflammatory myopathies. (See 'Types of malignancies' above.)
●Cancer can be diagnosed before, simultaneously with, or after the diagnosis of inflammatory myopathy. (See 'Temporal relationship' above.)
●Clinical factors associated with an increased risk of malignancy include older age at disease onset, dysphagia, evidence of capillary damage on muscle biopsy, cutaneous necrosis, cutaneous leukocytoclastic vasculitis. Patients with interstitial lung disease appear to have a lower frequency of malignancy. (See 'Clinical risk factors' above.)
●Some serum autoantibodies in DM and PM confer a positive risk of malignancy, whereas others are associated with a negative risk. "Cancer-associated myositis" (CAM) in adults has been associated in several studies with antibodies to transcription intermediary factor (TIF)-1gamma (anti-p155, anti-p155/140) and with antibodies to nuclear matrix protein (NXP)-2 (anti-MJ or anti-p140). Conversely, the presence of myositis-specific (anti-synthetase antibodies, anti-Mi-2, anti-SRP) and myositis-associated antibodies (anti-RNP, anti-PM-Scl, anti-Ku) appears to be associated with a decreased risk of malignancy but an increased risk of interstitial lung disease in DM. (See 'Serum autoantibodies' above.)
●All patients newly diagnosed with PM or DM should be evaluated for the possibility of an underlying malignancy. Most cancers will be found with a comprehensive history and physical examination, including a pelvic exam, along with the following investigations (see 'Initial screening for malignancy' above):
•Complete blood count, liver function tests, urinalysis
•Fecal occult blood test, if screening colonoscopy not indicated
•Chest radiograph
•Age- and sex-appropriate Pap test, testicular self-examination, mammography, and colonoscopy
●Further investigation, including computed tomography (CT) scanning of the chest/abdomen/pelvis, is directed by abnormal results found on the above evaluation or should be undertaken in those patients assessed to be at high risk for an underlying malignancy. While there is no consensus regarding the utility of screening for ovarian cancer in patients with DM, our authors obtain serial measurements of CA 125 levels and a transvaginal ultrasound in women considered to be at high risk for ovarian cancer. (See 'Initial screening for malignancy' above.)
●The value of repeat cancer screening in patients with established PM and DM is not well-established. Most studies have shown an increased risk of cancer for at least five years in patients with DM (but not PM), although the risk declines annually. Patients should continue to have routine, age-appropriate screening (eg, mammogram, pelvic exam) as in the general population. (See 'Post-treatment surveillance' above.)
●The presence of a tumor or does not appear to affect the severity or distribution of weakness, the duration of weakness prior to diagnosis, or the height of creatine kinase elevation. Myositis associated with cancer, however, responds more poorly to treatment than myositis in the absence of cancer. (See 'Impact of malignancy on disease severity' above.)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Marc L Miller, MD, who contributed to an earlier version of this topic review.