Ann Thorac Surg 2000;70:1390-1392
© 2000 The Society of Thoracic Surgeons
Case report
Extramedullary plasmacytoma presenting with myasthenia gravis and mediastinal mass
Ahmed R. Ahmed, MBBSa,
Adrian J. Marchbank, FRCS (C-Th)a,
Andrew G. Nicholson, MRCPathb,
Andrew C. Wotherspoon, MRCPathb,
George P. Ladas, MDa
a Department of Thoracic Surgery Royal Brompton Hospital, London, England, UK
b Department of Histopathology, Royal Brompton Hospital, London, England, UK
Address reprint requests to Dr Ladas, Department of Thoracic Surgery, Royal Brompton Hospital, Sydney St, London SW3 6NP, England;
e-mail: gladas{at}rbh.nthames.nhs.uk
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Abstract
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A 68-year-old woman presented with myasthenia gravis and an anterior mediastinal mass, which proved to be an extramedullary plasmacytoma in the thymus with associated extracellular light chain deposition. Further specimens revealed plasma cell proliferation in an internal thoracic lymph node and in a subsequent colectomy specimen, indicating systemic disease. This case demonstrates the rare association between a plasmacytoma in the thymus and myasthenia gravis.
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Introduction
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Plasmacytomas are localized accumulations of plasma cells, forming distinct tumors, and they only rarely occur in extramedullary sites. We describe the management of a patient who presented with an anterior mediastinal mass and myasthenia gravis, and was found to have a mediastinal plasmacytoma.
A 68-year-old woman presented with a 7-month history of ptosis with no associated fatigue, weakness, or motor disturbance. No lymphadenopathy or other abnormality was noted on examination. Myasthenia gravis was diagnosed following a positive Tensilon test. She was antiskeletal muscle antibody positive but antiacetylcholine receptor antibody negative. Treatment was commenced with pyridostigmine 30 mg three times a day with marginal improvement.
Past medical history included emphysema, bronchiectasis, and chronic glaucoma treated with levobunalol eye drops. She had stopped smoking 2 years previously. Chest roentgenogram demonstrated emphysema with right upper lobe bulla. Computed tomography of the thorax revealed a well-defined homogeneous anterior mediastinal mass with flecks of calcification (Fig 1). There was a second mixed density mass inferiorly, closely related to fat. Both lungs were emphysematous and mildly bronchiectatic. Hemoglobin, white cell count, platelets, urea and electrolytes, glucose, liver function tests, and serum calcium were normal. Abnormal results were: Immunoglobulin M 3.9 g/l (0.5 to 2.8) and erythrocyte sedimentation rate 61 mm/h. Protein electrophoresis revealed no monoclonal bands, and there were no urinary Bence-Jones proteins.
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Fig 1. Computed tomography of the thorax revealing a well-defined homogeneous anterior mediastinal mass with flecks of calcification.
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A provisional diagnosis of thymoma was made and the patient underwent a left anterior mediastinotomy for confirmatory diagnosis. Microscopically, the specimen was composed of densely eosinophilic acellular material reminiscent of amyloid, although Congo Red staining was negative. There was no evidence of thymoma and further biopsy was advised, but given that there was no evidence of lymphoma, the decision was made to proceed with resection. At operation, a Morgagni hernia was identified and repaired. A multilobulated tumor was arising from the thymus. It was resected en bloc with the thymus, anterior mediastinal fat, and the mediastinal reflection of the parietal pleura to the phrenic nerves on both sides, including the site of previous mediastinotomy. A chain of enlarged lymph nodes was extending along the internal thoracic artery towards the thoracic inlet on the left side and these were resected. The final resection specimen measured 19 x 14 x 3.5 cm, and had a nodular cut surface with a firm waxy texture.
Microscopically, the mass consisted mainly of densely eosinophilic acellular material that attracted a focal foreign body-type granulomatous response together with an abundance of plasma cells, some of which were cytologically atypical. Congo Red staining remained negative (Fig 2). This population of atypical plasma cells was also noted within the internal thoracic lymph nodes and a diagnosis of plasmacytoma was made, confirmed by staining for light chains showing kappa restriction. Polymerase chain reaction studies were suggestive of a B-cell clone, and ultrastructural examination confirmed that many of the plasma cells displayed abnormal features. The densely eosinophilic material proved to be extracellular deposition of light chains.
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Fig 2. The tumor comprises a population of atypical plasma cells, together with abundant acellular eosinophilic material that is eliciting a foreign body-type granulomatous response. On electron microscopy, this material proved to be light chain deposition. (H&E stain; original magnification x100.)
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On the 7th postoperative day, she developed a perforated sigmoid diverticulum, which necessitated emergency laparotomy with sigmoid colectomy and left iliac fossa colostomy. Histology of the large bowel also revealed incidental microscopic foci of atypical plasma cells in the adventitia. She remained in intensive care for 13 days with sepsis. By the 16th day, she had made a near full recovery and was transferred for convalescence. Bone marrow aspirate showed slightly dyserythropoietic marrow but no evidence of myeloma.
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Comment
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Thymic neoplasms are the most common cause of a primary anterior mediastinal mass in adulthood, the majority being thymomas. Lymphomas are the second most common mediastinal tumor followed by endocrine and germ cell tumors. Plasmacytomas are localized accumulations of plasma cells forming distinct tumors. They usually occur in bone marrow, but may rarely present at extramedullary sites including mediastinum [1, 2]. They may represent the initial manifestation of multiple myeloma, making identification important with regard to commencing systemic therapy [2].
Approximately 15% of patients with myasthenia gravis have thymoma, whereas 10% to 50% of patients with thymoma have myasthenia gravis [3]. Myasthenia gravis has less frequently been associated with lymphoma [4], leukemia [5], and plasma cell dyscrasias including multiple myeloma [6, 7]. With myeloma, there is an association with thymoma and myasthenia gravis [6], but myasthenia gravis solely in association with a thymic plasmacytoma is most unusual.
This patient presented with a diagnosis of myasthenia gravis, based on the presence of antiskeletal muscle antibodies and a positive Tensilon test. Despite an inconclusive biopsy with regard to the expected diagnosis of thymoma, resection was still considered to be the appropriate treatment. Diagnosis of plasmacytoma was complicated by the presence of abundant extracellular light chain deposits, which although well described [8], obscured the diagnosis in the biopsy taken at mediastinotomy. Given the presence of plasma cell proliferation in a separate lymph node and in the pericolic fat, this patient has systemic disease and will need to be treated as for myeloma.
As the thymus is the central organ responsible for immunological self-tolerance, thymic abnormalities may be associated with the breakdown in tolerance that causes an immune-mediated attack on acetylcholine receptors in myasthenia gravis. However, an increase in lymphoid and nonlymphoid extrathymic neoplasms is described in patients with myasthenia gravis, most commonly in the year of onset of symptoms [9]. Likewise, following thymectomy, the rate of extrathymic malignancy returns to that of the general population, suggesting that the thymus may play an oncogenic role in myasthenia gravis.
In conclusion, we present a patient with myasthenia gravis who went into symptomatic remission following surgical resection of a thymic plasmacytoma. This association may be coincidental, but the influence of the thymus gland on the immune system and its link to carcinogenesis suggests a relationship. This case also emphasizes that not all anterior mediastinal masses in patients with myasthenia gravis are thymomas.
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References
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Accepted for publication February 10, 2000.
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Abstract
Introduction
