What is the etiology of myositis in a patient with biopsy-proven adenocarcinoma and markedly elevated tumor markers?

Etiology of Myositis in a Patient with Adenocarcinoma

The myositis in this case is most likely paraneoplastic myositis secondary to the patient's biopsy-proven adenocarcinoma. The clinical presentation, laboratory findings, and imaging results strongly support this diagnosis.

Clinical Evidence Supporting Paraneoplastic Myositis

The patient presents with several key features that point to a paraneoplastic etiology:

• Severe inflammation of trapezius, anterior deltoid, and supraspinatus muscles on MRI
• Markedly elevated tumor markers (CEA 233, CA 19-9 9,851)
• Biopsy-proven adenocarcinoma with hepatic metastatic lesions
• Temporal relationship between cancer diagnosis and myositis symptoms
• Normal CPK (52) and aldolase (9.1) levels, which is consistent with some forms of paraneoplastic myositis

Diagnostic Reasoning

Paraneoplastic myositis occurs as an immune-mediated response to underlying malignancy. According to the American College of Chest Physicians guidelines, dermatomyositis and inflammatory myopathies are well-established paraneoplastic syndromes associated with various cancers, including lung cancer 1. The diagnostic criteria typically include:

1. Progressive muscle weakness (present in this case)
2. Abnormal MRI findings showing muscle inflammation (present in this case)
3. Temporal association with cancer diagnosis (present in this case)

Differential Diagnosis

1. Immune Checkpoint Inhibitor-Induced Myositis

While immune checkpoint inhibitor (ICPi) therapy can cause myositis 1, there is no mention of the patient receiving such therapy, making this diagnosis unlikely.

2. Pyomyositis

Pyomyositis was considered due to:

• Neutrophilic leukocytosis
• Parotid swelling
• Sepsis physiology

However, the absence of abscess formation on imaging and the patient's partial response to antibiotics make this less likely than paraneoplastic syndrome. Additionally, pyomyositis typically presents with elevated CPK, which was normal in this case.

3. Other Autoimmune Conditions

IgG4-related disease, Sjögren's syndrome, and POEMS syndrome were considered but are less likely given the strong correlation with the patient's confirmed malignancy.

Diagnostic Approach for Paraneoplastic Myositis

The American College of Chest Physicians guidelines recommend the following diagnostic workup for suspected paraneoplastic myositis 1:

• Muscle and skin biopsy (though not always necessary when clinical picture is clear)
• Electromyography (EMG) to detect myopathic changes
• MRI showing increased signal intensity on T2-weighted images (present in this case)
• Laboratory tests including muscle enzymes (CPK, aldolase)

Treatment Implications

Recognition of paraneoplastic myositis is crucial as:

1. Treatment of the underlying malignancy often leads to improvement of the paraneoplastic syndrome 1, 2
2. Immunosuppressive therapy may be required for symptom control:
   • High-dose corticosteroids are first-line therapy 2
   • Second-line agents include methotrexate, azathioprine, cyclophosphamide, or mycophenolate 1

Clinical Pitfalls and Caveats

• Normal CPK levels do not rule out paraneoplastic myositis. While inflammatory myositis typically shows elevated muscle enzymes, some paraneoplastic forms may present with normal CPK levels 3.
• Muscle biopsy may not be necessary when clinical, laboratory, and imaging findings strongly suggest paraneoplastic myositis in a patient with confirmed malignancy 1.
• Paraneoplastic myositis can precede cancer diagnosis by months to years, highlighting the importance of thorough cancer screening in patients with new-onset myositis 4.

In this patient's case, the constellation of findings—biopsy-proven adenocarcinoma, markedly elevated tumor markers, MRI evidence of severe muscle inflammation, and absence of other clear etiologies—strongly supports paraneoplastic myositis as the most likely diagnosis.