Methotrexate

Abstract

Lymphoproliferative disorder and primary spinal lymphoma: case report A 54-year-old woman developed lymphoproliferative disorder of the thoracic spine and primary spinal lymphoma during treatment with methotrexate for rheumatoid arthritis (RA). The woman with RA presented with 3 months history of back pain and numbness in the bilateral lower limbs. She had been receiving methotrexate 10 mg/week for approximately 7 years [route not stated], followed by adalimumab and iguratimod for approximately 3 years. A X-ray examination by her previous physician revealed a spinal tumor. Therefore, she was presented to the hospital for further investigation and treatment (current presentation). Initial examination showed enhanced bilateral patellar and Achilles reflexes, muscle weakness in the bilateral iliopsoas, a manual muscle testing score of 4 and sensory deficit in the bilateral posterior lower legs. Subsequent blood test revealed WBC count 2900/μL, C-reactive protein 0.21 mg/dL and anti-cyclic citrullinated peptide antibody titer 148 U/mL. Although the antibody titers were high, the C-reactive protein level was within the normal range, which was consistent with controlled progression of RA by methotrexate. Tumor markers were within the normal limits. Plain X-ray and CT-scan revealed almost imperceptible bone destruction. Thoracic spine X-ray showed a soft-tissue mass on the left of Th9-10 and a differential diagnosis included mediastinal tumor. Plain CT revealed a soft tissue density mass lesion on the left of Th10. Additionally, a partial sclerotic change of the vertebral body was visualised adjacent to the tumor. In contrast enhanced CT, the mass lesion was well enhanced on the left of epidural space and paravertebral muscle and several lymph nodes swelling were detected in the retrocrural space and mediastinum. At that time, differential diagnoses included malignant lymphoma and spinal metastasis. Subsequent MRI showed a low signal intensity in the Th10 vertebral body on both T1and T2weighted images and a high signal intensity in the short-tau inversion recovery images and the signal change covered posterior elements through the pedicle. Paravertebral lesion showed the same signal intensity as the bone lesion in each image. The mass lesion was found to be extended to the epidural space, mediastinal area and paravertebral muscle through intervertebral foramen and intercostal space. It was noted that, the epidural mass lesion compressed the spinal cord, which led to spinal canal stenosis from the unilateral dorsal site, which lead to spinal paralysis. These radiological findings were similar to those for primary spinal lymphoma. MRI findings suggested not only malignant lymphoma and spinal metastasis but also myeloma and inflammatory changes as differential diagnoses. On the basis of these imaging findings, the differential diagnosis included malignant lymphoma, haematologic tumor, metastatic spinal tumor and inflammatory changes. Blood tests showed no significant increase in the inflammatory response or abnormal tumor markers. Additionally, she had no history of cancer, and a CT scan of the whole body showed no malignant tumors in the major organs. Therefore, a biopsy was planned. On hospital day 3, she exhibited rapid progression of muscle weakness in the bilateral iliopsoas, which prevented her from walking. It was accompanied by bladder and bowel dysfunctions. Therefore, she underwent emergent posterior spinal decompression with laminectomy and posterolateral fixation of the Th9-11 vertebrae. An intraoperative examination confirmed a dark brown neoplastic lesion on the dorsal side of the dura mater at the Th10 vertebral level. The epidural lesion strongly adhered to the dura mater and could not be removed without damaging the dura. Therefore, only a pathological specimen was obtained. Thus, most of the epidural mass lesion was retained. Subsequent pathological examination revealed the proliferation of atypical large round cells accompanied by small lymphocytes in a nodular fashion. The nuclei in the atypical large cells were irregularly shaped and a few cells were multinucleated. The immunostaining returned positive for CD30 and Pax5; partially positive for CD4, CD8, CD15, an d CD79a and negative for CD20, pankeratin and EMA, consistent with histological features similar to classical Hodgkin lymphoma. The EBV-encoded RNA in situ hybridisation of pathological specimens were returned negative. Based on both pathological findings and methotrexate treatment history, a diagnosis of methotrexate associated lymphoproliferative disorder was established [durations of treatment to reactions onsets not stated]. Postoperatively, she had an improvement in bilateral iliopsoas muscle weakness and bladder rectal dysfunction. At that time, she was able to resume walking. Postoperative investigation demonstrated a high level of anti-EBV capsid antigen-IgG, at 320 times the normal level, suggestive of a history of an infection. Following diagnosis of methotrexate associated lymphoproliferative disorder, the woman’s methotrexate was discontinued. Her RA symptoms did not worsen. After 1 week of the surgery, she received prednisolone as an alternative to methotrexate. After 3 weeks of methotrexate discontinuation, the MRI revealed a partially resected epidural tumor mass with decompressed spinal cord. Moreover, a remnant tumor was noted on the lateral side of the vertebral body. Within 6 months of the surgery, disappearance of both tumors was confirmed. After 18 months of the surgery, she was able to walk independently and did not show tumor recurrence.