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|Year : 2013 | Volume
| Issue : 2 | Page : 152-155
Incidence of malignancies in biopsy-proven inflammatory myopathy
Meena A Kannan1, C Sundaram2, Megha Uppin2, Rukmini Mridula1, Sheik Afshan Jabeen1, Rupam Borgohain1
1 Department of Neurology, Nizam's Institute of Medical Sciences, Punjagutta, Hyderabad, India
2 Department of Pathology, Nizam's Institute of Medical Sciences, Punjagutta, Hyderabad, India
|Date of Submission||24-Nov-2012|
|Date of Decision||14-Dec-2012|
|Date of Acceptance||08-Mar-2013|
|Date of Web Publication||29-Apr-2013|
Meena A Kannan
Department of Neurology, Nizam's Institute of Medical Sciences, Hyderabad - 500 044
Source of Support: None, Conflict of Interest: None
Background: Inflammatory myopathy (IM) as a manifestation of paraneoplastic syndrome has been well-documented. However, the prevalence of malignancies reported varies across the studies. There are very few studies reported from Asia, only one from India. Aim: The aim of this analysis was to study the prevalence of malignancy in biopsy-proven cases of IM in India and to study the difference between malignant and non-malignant groups. Materials and Methods: The study was a retrospective review of case records of patients with a biopsy-proven IM attending Tertiary Care University Hospital. Results: Of the total 86 patients with biopsy-proven IM, 22 patients were polymyositis, 63 patients had dermatomyositis (DM) and one was with an inclusion body myositis, not included for further analysis. Associated malignancy was diagnosed in 6 (7%) patients, and five of them were females. Diagnosis of associated malignancy was identified at the time of diagnosis of IM in four (66.7%) patients. All the six patients with an associated malignancy had DM. Only one patient died within 1 year of diagnosis. Creatinine kinase was much lower in patients with malignancy associated IM than in patients with no malignancy (P < 0.0001). Conclusion: The prevalence of malignancy was very low in our cohort as compared to the studies from other countries. Breast cancer was the most common malignancy associated with DM. The type of associated malignancy was quite variable.
Keywords: Creatinine kinase, inflammatory myopathy, paraneoplastic syndrome
|How to cite this article:|
Kannan MA, Sundaram C, Uppin M, Mridula R, Jabeen SA, Borgohain R. Incidence of malignancies in biopsy-proven inflammatory myopathy. Neurol India 2013;61:152-5
| » Introduction|| |
An association between malignancy and inflammatory myopathy (IM) was suspected as early as 1916  and a number of case series have been reported since then. Malignancy in inflammatory myopathies could be caused in part due to the clinical course of IM itself or due to paraneoplastic syndrome.  Most population-based studies suggest that the risk of cancer is greater in patients with dermatomyositis (DM), 27-40%, than in those with polymyositis (PM), 15-18%. ,,, One study documented a cancer risk of 23% in patients with inclusion body myositis (IBM).  A review of the literature shows data highlighting the prevalence and types of malignancies reported in Asian ethnic groups. ,, Porkodi et al. reported a single case of DM associated with breast cancer in a series of 87 patients with IM over a period of 10 years from India.  Therefore, we sought to study the prevalence of malignancies in our patient population who were diagnosed with IM and to study the clinical differences between the groups with and without malignancies.
| » Materials and Methods|| |
This was a retrospective review of case records of all patients with biopsy-proven IM attending the Nizam's Institute of Medical Sciences, a tertiary Care University Hospital in Hyderabad, South India from May 2000 to April 2009. All patients fulfilled Bohan and Peter's criteria for a definite diagnosis of PM and DM.  The diagnosis of malignancy with IM was limited to cases with confirmed malignancy on pathology. The demographic and clinical data of all patients were obtained from the medical records and the neuromuscular disorders registry. All the 86 patients were followed-up for a minimum period of 5 years and maximum 10 years after the diagnosis of IM. Patients with malignancies were analyzed according to primary organs of cancer, time period between the diagnosis of IM and malignancy. Laboratory findings at the time of the diagnosis included creatinine kinase (CK), erythrocyte sedimentation rate, and anti-nuclear antibodies.
| » Results|| |
Of the 86 patients with IM, in 22 patients (12 female and 10 male) the diagnosis was PM, in 63 (23 male and 40 female) the diagnosis was DM, and one patient had IBM, which was not included for further analysis. The mean age of the total cohort at the time of diagnosis was 38.7 ± 16.5 years (33 males, 38.6 ± 18.3 years and 53 females, 39.1 ± 15.4 years) [Table 1].
|Table 1: Characteristic features of patients with polymyositis and dermatomyositis|
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Malignancy and IM
Of the 85 patients included in the analysis, 6 (7%) patients were diagnosed to have malignancy and in all patients had DM and five of them were females. The mean age at the time of diagnosis was 50.8 ± 15.6 (range 37-75 years). Of these patients, in four patients the diagnosis of IM and an associated malignancy was established at the same time. In one patient malignancy (endometrial carcinome) was diagnosed after the diagnosis of IM and in another patient breast cancer was diagnosed before the diagnosis of IM. Malignancies associated with DM were breast (2), ovarian (1), endometrial cancer (1), non-Hodgkins lymphoma (NHL) (1) and lung cancer (1) [Figure 1]a and b. Follow-up period was 1-3 years. One male patient with the lung cancer and diabetes died due to sepsis [Table 2].
|Table 2: Clinical and CK value in 6 patients with DM at diagnosis of malignancy|
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Clinical picture and lab findings between malignancy and IM
All patients had subacute onset of weakness involving proximal muscles. Five patients had erythematous hyperpigmented patches involving the face and upper extremities and two had Grottrons papules on the hands. Two patients had dysphagia at presentation. At the time of diagnosis of IM, the mean serum CK level was significantly lower (1001.5 ± 282.3 IU/L) in the malignancy group than in the non-malignancy group (3075.6 ± 3595.7), which was statistically significant (P < 0.0001).
| » Discussion|| |
The peak incidence of malignancy diagnosis occurs within 2 years on either side of the diagnosis of IM. DM and PM are inflammatory myopathies that are an associated with virtually any type of cancer irrespective of location and race. High prevalence of cancers in the ovary, lung, and gastrointestinal tract have been reported from Europe in IM. , In addition, patients with PM had NHL most frequently followed by lung and bladder cancer.  Chow et al. reported ovarian cancer as the most common malignancy in DM and lymphoma and hematopoietic cancers in PM.  The incidence of ovarian cancer developing in the setting of DM was reported to be as high as 13.3% in one series.  In contrast, studies from Asian countries reported a high incidence of nasopharynx cancer in DM patients. , However, a study from Korea reported breast cancer as the most frequent tumor associated with DM. , In our experience of DM the malignancy spectrum was quite varied. Endometrial cancer has been reported very rarely. ,
Cancer can be diagnosed before, simultaneously with, or after the diagnosis of IM. Malignancy was diagnosed simultaneously or later in 74-81.8% of patients with IM and diagnosed before the onset of IM in 18.2-26% of patients.  In the present study, one patient had malignancy before and one after the diagnosis of IM. In four patients, malignancy was diagnosed simultaneously. The risk of cancer following PM and DM is highest in the first 3 years after the diagnosis of IM. Although, there is a trend toward decreased excess risk with increasing time, the risk is still higher 5 years after the diagnosis.  The mean age of patients with IM at the diagnosis of malignancy was more than 40 years in different studies. ,, In our series, the mean age at the time of malignancy was 50.8 years. Three patients were below 40 years and all were females. While the risk is elevated in both sexes, it is more significant for females in the age group of 45-74 years at the time of diagnosis. In some studies, male patients with DM have been identified as being at risk of developing malignancy. In our study, malignancy was diagnosed in five females out of six patients. Independent predictive factors associated with malignancies in patients with DM/PM were older age, presence of dysphagia, and absence of interstitial lung disease. ,,
The clinical picture was similar in patients with or without an associated malignancy, except that the CK levels, not significantly elevated in patients with malignancies as reported in other studies. , Muscle biopsy is the definitive diagnostic procedure and shows perivascular inflammatory infiltrates with perifascicular atrophy. Necrotizing myopathy with perifascicular atrophy has been seen in malignancy in one of our cases.
The close relationship between IM and cancer are consistent with the idea that paraneoplastic processes linked to oncogenesis and autoimmunity contribute to the disease in a subset of DM and PM. Myositis specific antibodies are occasionally detected in serum of patients with IM and they are less likely in cancer an associated myopathy.  As a result, the exact antibody/antigen in paraneoplastic myositis remains to be identified. Antip 155 was recently reported in 75% of cancer-associated DM cases in a small study which may be clinically relevant. , Treatment of paraneoplastic DM is generally the same for patients without a tumor. Nearly all patients respond to corticosteroids. Refractory patients can be treated with azathioprine. Methotrexate and cyclophosphamide can also be considered. In this study, all patients responded to steroids and were given azothiaprine as a steroid sparing drug.
| » Conclusion|| |
The prevalence of malignancy in Indian patients with IM was 7%. The spectrum of the malignancy was quite variable. However, our cohort size is small. The clinical and laboratory findings were not significantly different, except for CK between patients with malignancy and without malignancy.
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[Table 1], [Table 2]
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