A forty-three-year-old premenopausal caucasian woman with no relevant medical history presented with intermittent fever, fatigue, myalgia, dysphagia, and erythematous rash lasting over 1 month. The nonpruritic macular rash was initially localized on the back of patient’s hands and was followed by eruption of erythema over patient’s face after 1 week. The onset of pruritic macular rash on lateral sites of patient’s thighs and upper part of back followed. The patient presented first to her dermatologist who treated her with topical steroids for 2 weeks. However, no clinical effect was observed. Considering the skin manifestation and other symptoms suspicious of a systemic rheumatic disease, the patient was referred to a rheumatologist. She was later admitted to a hospital to establish a diagnosis and commence treatment.
The skin examination revealed a slight periorbital edema (Heliotrope rash) and erythematous rash localized over her cheeks and nasal bridge omitting the nasolabial sulcus. It was therefore resembling a typical malar rash in lupus erythematosus (Fig. 1). Erythematous hyperpigmented papules were found over the proximal and distal interphalangeal joints (Gottron’s sign). The pruritic maculopapular rash was also present on lateral sites of patient’s thighs and back (Figs. 2 and 3). V-sign, a typical distribution of macular exanthema on the front site of patient’s chest, was found (Fig. 4). The physical examination also revealed enlarged lymph nodes in her left axilla and supraclavicular region, which was further confirmed by ultrasound (Fig. 5), and painful swelling and enlargement of the whole left mammary gland.
Blood investigations revealed raised erythrocyte sedimentation rate (ESR, 34 mm/h). C-reactive protein (CRP) was slightly elevated (12.4 mg/L). Serum muscle enzyme concentrations were also elevated - alanine aminotransferase (0.71 μkat/L), aspartate aminotransferase (1.38 μkat/L), creatine kinase (CK, 26.24 μkat/L), and myoglobin (267 μg/L). Electromyography revealed no pathological findings. Skin biopsy from the affected area was performed with negative lupus band test (direct immunofluorescence test for lupus erythematosus). The whole panel of autoantibodies was examined using immunoblot technique (Euroimmun, Euroline Autoimmune Inflammatory Myopathies 16 Ag) with only anti-TIF-1γ antibodies being positive. The probability of DM was evaluated > 90 % using the IMCCP (The International Myositis Classification Criteria Project) criteria [13]. Muscle biopsy is not mandatory in the presence of typical skin manifestations according to these criteria. Considering the high probability of DM, further supported by the presence of anti-TIF-1γ, a muscle biopsy was omitted. Because of the patient’s complains of dysphagia gastro-duodenoscopy was performed to exclude the upper gastrointestinal tract involvement. The finding was consistent with erosive antral gastritis with negative rapid urease test (rapid diagnostic test for Helicobacter pylori infection). Series of investigations were performed to exclude an extra-muscular involvement - ophthalmologic, otorhinolaryngologic, neurologic, cardiac and renal - all with negative findings. Tumor markers including CEA, CA 15–3, CA 125, and CA 19–9 were negative. Mammography was performed to exclude breast cancer as an underlying condition. The result, however, was equivocal (sporadic microcalcifications without any obvious tumor mass). Neither ultrasound of the abdomen nor chest x-ray showed any abnormality. Since the conventional investigations were not conclusive, a whole body PET/CT scan was performed to exclude malignancy. The scan showed FDG-avid lesion 19 × 14 mm in the left mammary gland, and multiple FDG-avid lymph nodes in the left axilla and under the pectoralis major muscle (Figs. 6 and 7).
Direct core cut biopsy was not feasible since there was no evident mass within the breast according to mammography. Extirpation of the left supraclavicular lymph node was therefore performed to obtain the histopathological specimen and confirm the diagnosis. Metastasis of poorly differentiated adenocarcinoma was reported (Fig. 8). Immunohistochemical assessment of steroid hormone status was performed. The expression of the estrogen and progesteron receptors, and HER-2/neu protein were all negative. Additional in situ hybridization (ISH) found no HER-2/neu amplification, thus confirming the diagnosis of the triple-negative breast cancer. The disease was staged as cT1c N3c M0. Genetic testing to exclude BRCA 1/2 mutation was advised, considering the patient’s age and histological type of breast cancer (triple-negative).
The treatment of DM was initiated with intravenous pulse corticosteroid therapy (methylprednisolone 5 × 1000 mg alternate days), followed by oral corticosteroids. Initial daily dose of 32 mg of methylprednisolone was reduced by 8 mg every week to the maintenance dose of 8 mg/day. The muscle strength tended to deteriorate during the deescalation phase. This prompted the contemporary discontinuation of dose reduction, until muscle weakness improved (CK 1.03 μkat/L, myoglobin 25.5 μg/L). The symptoms of dysphagia and skin manifestation were promptly managed, enabling the anti-cancer therapy to be commenced. Considering both disease burden and histologic features, neoadjuvant chemotherapy was decided to be the option. The regimen containing 4 courses of doxorubicin 60 mg/m2 + cyclophosphamide 600 mg/m2 q3w followed by 4 courses paclitaxel 175 mg/m2 + carboplatin AUC 5 q3w was chosen. The patient continued with a maintenance dose of corticosteroids during the chemotherapy, which was well tolerated. However, the investigations following the last dose of chemotherapy (mammography, ultrasound of the breast and regional lymph nodes), did not show any signs of tumor regression. Surgery was still not feasible because of the supraclavicular and axillary lymph node persistence. Radiotherapy was therefore decided to be the option by the multidisciplinary board (including oncologist, breast surgeon and radiologist) in order to achieve local control. Primary chemoresistance of the tumor was an additional reason to support this approach.