4. A paraneoplastic case of dermatomyositis

INTRODUCTION: Dermatomyositis is a rare idiopathic autoimmune condition predominantly affecting women in their fifth or sixth decades. Both cutaneous manifestations and the symptoms of proximal muscle weakness are well described in the literature, and these can often be found in the context of specific autoantibodies to aid diagnosis. The paraneoplastic subtype has been recognised for some time, notably in the absence of antisynthetase autoantibodies. More frequently, malignancies such as breast, ovarian and lung cancers as well as Hodgkin’s lymphoma are implicated, though we present a rare case of metastatic melanoma recurrence associated with the known phenotype. CASE DESCRIPTION: A 35-year-old lady of British origin presented to the acute medical take with a 4-week history of progressive, symmetrical proximal weakness predominantly affecting her neck, shoulders, deltoids and hip flexors. She had textbook Gottron’s papules overlying her metacarpophalangeal joints as well as a heliotrope rash, V-sign and shawl sign consistent with dermatomyositis. Her past medical history comprised superficial spreading melanoma, excised from skin over her right scapula 5 years previously with no evidence of metastatic disease on sentinel or axillary node biopsies. She also had well-controlled ulcerative colitis and eczema. She took no regular medications and there was no relevant family history of note. Initial biochemistry revealed a significantly elevated creatine kinase just north of 7000, a correspondingly raised alanine aminotransferase, but normal acute phase reactants. Interestingly, all autoimmune serology, including a dedicated myositis immunoblot, was negative. This finding, in addition to her past medical history, raised the suspicion of a paraneoplastic phenomenon. Indeed, FDG-PET/CT demonstrated an intensely avid splenic lesion (maximum standardized uptake value, max-SUV 10.7) concerning for metastasis. A faintly avid left apical lung nodule and lower density lesions within the liver were also visualised and further elucidated on ensuing cross-sectional staging imaging and a dedicated MRI of the liver. The FDG-PET/CT also highlighted moderate muscular uptake within the neck and upper limbs, whilst patchy high signal involving almost all muscle groups in both legs was seen on MRI in keeping with active inflammation. Subsequently, a right vastus lateralis muscle biopsy and an ultrasound-guided splenic biopsy were urgently performed without complication prior to initiation of intravenous methylprednisolone followed by a tapering course of oral prednisolone. Splenic histology revealed metastatic melanoma. After in-depth discussions with oncology the patient commenced encorafenib & binimetinib with marked symptomatic benefit. She continues to exhibit radiological and biochemical improvement to this day. DISCUSSION: This is an interesting and rare case. Our review of the existing literature found only 10 reports of melanoma presenting as paraneoplastic dermatomyositis. Melanoma is known to metastasise to the spleen, though it is extremely rare for it to be the first implicated site of spread. Rather, it is often a sign of multi-visceral involvement, and only found at post-mortem in the majority of cases. Evidently, therefore, stage IV malignant melanoma (distant metastases beyond regional lymph nodes) involving the spleen confers grave prognosis. This case demonstrates efficient use of the MDT leading to an accurate diagnosis and the swift initiation of effective treatment. Though it was initially felt the patient would require a splenectomy, the Oncologists and patient came to the shared decision that the use of BRAF and MEK inhibitors was preferable given the additional involved sites and the need to interrupt or delay dosing in the peri-operative period. Both agents selectively target key enzymes in the tumour-promoting MAPK pathway and initial signs are encouraging, with a repeat FDG-PET/CT a week into treatment demonstrating a significantly reduced metabolic activity in the spleen (SUV-max 3.5). The left apical lung nodule also appeared smaller on the CT component and will continue to be monitored. The muscle biopsy, largely academic in this context, should still garner interest. Perivascular lymphocytes were seen in both perimysium and endomysium leading to scattered atrophic fibres, though the perifascicular predilection that is highly characteristic of dermatomyositis was not observed in this case. However, immunohistochemistry in the paraffin sections demonstrated CD4 positive perivascular cells in the endomysium with no significant CD8 cells. This favourable ratio of CD4 is a hallmark of this subtype of idiopathic inflammatory myositis, in contrast with polymyositis where a CD8 infiltrate dominates. The lack of necrosis contrasts with another subtype, necrotising autoimmune myopathy. KEY LEARNING POINTS: This case highlights a rare subtype of idiopathic inflammatory myositis with a characteristic phenotype. Negative autoantibodies should raise suspicion of paraneoplastic pathology and a comprehensive history and examination of the patient should be undertaken followed by appropriate diagnostic tests. It is important to note treatment of the underlying neoplasm led to a much greater degree of improvement in clinical symptoms, compared to conventional corticosteroid therapy. This is a common theme described in the paraneoplastic subtype. As aforementioned, it is rare for the spleen to be the first site of melanomatous metastatic spread. Splenic involvement is more commonly seen in the context of advanced disseminated disease which confers a poor prognosis. The estimated 5-year survival rate for stage IV disease is approximately 20%, though the use of novel targeted treatments and a relatively young age at diagnosis are just a couple of factors in this case that could lead to a conclusion that defies the odds. Obtaining histology in a swift manner is another key factor that can lead to improved outcomes, though the spleen has a rich vascular supply and thus biopsy carries a significant complication risk. Therefore, it should only be performed by highly experienced radiologists or surgeons. The case also places emphasis on the role of FDG-PET/CT as a diagnostic and prognostic tool. SUV-max figures aid interpretation but should always be compared with a physiological baseline as patient-related factors can vary. A SUV-max greater than 2.5 is generally indicative of malignancy though this level can also be seen in the context of infection or active inflammation so clinical correlation is always advised. Values in excess of 10, as in this case, bear a high likelihood of aggressive disease. CONFLICT OF INTEREST: The authors declare no conflicts of interest.