The Journal of Clinical Endocrinology & Metabolism Vol. 89, No. 4 1534-1537
Copyright © 2004 by The Endocrine Society
Medical Cure of Plasma Cell Granuloma of the Thyroid Associated with Hashimoto’s Thyroiditis: A Case Report and Review
Silvana Laurent,
Luc Mouthon,
Elisabeth Longchampt,
Marie Roudaire,
Sylvia Franc,
Alain Krivitzky and
Régis Cohen
Internal Medicine and Endocrinology Unit (S.L., L.M., S.F., A.K., R.C.), Laboratory of Anatomical Pathology (E.L.), and Oto-Rhino-Laryngology Unit (M.R.), University Paris XIII and Hôpital Avicenne, Assistance Publique-Hôpitaux de Paris, 93009 Bobigny, France
Address all correspondence and requests for reprints to: Dr. Régis Cohen, Service de Médecine Interne et d’Endocrinologie, Hôpital Avicenne, 125 route de Stalingrad, 93009 Bobigny Cedex, France. E-mail: regis.cohen{at}avc.ap-hop-paris.fr.
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Abstract
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Plasma cell granuloma (PCG) is a rare, benign inflammatory tumor composed of myofibroblasts, abundant plasma cells, and lymphocytes combined with collagen. A thyroid localization of PCG is extremely rare, and surgical therapy is indicated. We report the case of a 35-yr-old woman with a thyroid PCG, associated with Hashimoto’s thyroiditis, that was responsible for tracheal compression. Surgery was performed, but the thyroid could not be removed because of the fibrotic process. The patient was treated with corticosteroids and immunosuppressive therapy. Dyspnea and dysphagia improved within 1 month, whereas thyroid volume returned to normal within 3 yr. We also review other reports of thyroid PCG in the literature and discuss the differential diagnosis and treatment. Although the use of immunosuppressive therapy has never been reported for thyroid PCG until now, this treatment may represent a good alternative to surgery in life-threatening, unresectable PCG.
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Introduction
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PLASMA CELL GRANULOMA (PCG), also called inflammatory pseudotumor, is a rare nonneoplastic lesion that was first described in 1973 (1). Histologically, PCG is characterized by cellular proliferation predominantly of polyclonal plasma cells, with a variable number of lymphocytes, neutrophils, eosinophils, and histiocytes, against a fibrovascular background (2). PCG can be localized in the lungs and less commonly in the mesentery, genital and urinary tracts, kidney, pelvis, and mediastinum (3). The etiology, biological characteristics, and management of these lesions remain a matter of debate, and conflicting results have been reported.
Endocrine localizations of PCG are rare and include the pituitary (4), thyroid (5), and adrenal gland (6). To our knowledge, only nine cases of PCG localized in the thyroid have been reported to date (2, 5, 6, 7, 8, 9, 10, 11, 12). Here, we report the case of a 35-yr-old woman with a thyroid PCG associated with Hashimoto’s thyroiditis. The thyroid could not be removed because of the fibrotic process, and improvement was obtained with corticosteroids and immunosuppressive therapy. We will also review the available literature on thyroid PCG and discuss the differential diagnosis and treatment.
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Case Report
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In May 1998, a 35-yr-old woman complained of asthenia and dysphagia. She had no previous medical history and had smoked 30 pack-years. Physical examination revealed normal thyroid volume and the absence of enlarged lymph nodes. There were no other symptoms such as fever or weight loss. Serum TSH was high (61.82 mIU/liter; normal, 0.1–3.4 mIU/liter), whereas serum free T3 (1.75 pg/ml; normal, 1.8–3.6 pg/ml) and T4 (6.6 pg/ml; normal, 8.5–17.1 pg/ml) were low. Antimicrosomal antibodies (Abs) were positive at 10,000 IU/ml (normal, 0–200 IU/ml), and antithyroglobulin Abs were negative. A thyroid ultrasound demonstrated a hypoechogenic gland, with the right and left lobes measuring 26 x 22 x 25 and 33 x 25 x 32 mm, respectively. Chest x-ray was normal. The erythrocyte sedimentation rate was increased at 68/104 mm. The patient was treated with oral L-T4 (150 µg/d) and acetylsalicylic acid (2 g/d), with a suspected diagnosis of painful Hashimoto’s disease.
In September 1998, the thyroid gland enlarged rapidly and became painful, and the patient developed right chin hypoesthesia. C-Reactive protein levels were raised at 30 mg/liter (normal, <5 mg/liter), and TSH remained elevated at 32.3 mIU/liter. The L-T4 dose was increased to 200 µg/d, and the TSH level was undetectable. Methylprednisolone (16 mg/d) was prescribed for 10 d without improvement, and the patient was referred to our hospital. In view of the rapid growth of the goiter and clinical signs of tracheal compression, it was decided to use surgical treatment. However, the thyroid could not be removed, because of the fibrotic process. Biopsies revealed inflammatory myofibroblastic proliferation without thyroid cells (thyroglobulin negative). The lesion consisted of cytologically bland spindle cells (fibroblasts and myofibroblasts expressing vimentin, desmin, and actin) and variable amounts of collagen, admixed with inflammatory cells (Fig. 1
). Numerous plasma cells, macrophages, and scattered T lymphocytes (CD3+) and B lymphocytes (CD20+) or arranged in a few small reactive lymphoid follicles were present throughout the infiltrate. These plasma cells were polyclonal as assessed by the 
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ratio of intracytoplasmic Igs.
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FIG. 1. A, Spindle cells with inflammatory cells and fibrosis (hematoxylin and eosin stain; x40). B, Antiactin antibody. Strong positivity of myofibroblasts (hematoxylin and eosin stain; x40).
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There was no evidence of any other PCG localization on chest and abdominal computed tomography scan. Antinuclear, anti-DNA, antitopoisomerase 1, and anti-TSH receptor Abs were negative. Antithyroid peroxidase (anti-TPO) Abs were positive at 4500 IU/ml. Analysis of peripheral blood lymphocytes by cytofluorometry revealed no malignant B cell population and a normal - ratio.
In November 1999, the goiter enlarged (left lobe, 40 x 48 x 95 mm; right lobe, 30 x 40 x 80 mm), and the patient developed dyspnea secondary to a 50% tracheal stenosis, as documented by magnetic resonance imaging (MRI; Fig. 2A). The patient was treated with iv methylprednisolone (15 mg/kg·d) for 3 d, then oral prednisone (1 mg/kg·d) together with L-T4 therapy. After 1 month, MRI revealed a 30% decrease in thyroid volume, and only 10% tracheal stenosis (Fig. 2B). Six iv cyclophosphamide infusions (0.6 g/kg) were performed from December 1999 to March 2000, meanwhile the prednisone dose was progressively tapered. Thyroid volume and tracheal stenosis remained stable, and the patient was then treated with azathioprine (2 mg/kg·d) for 6 months after discontinuation of cyclophosphamide therapy. The patient’s general condition improved, the thyroid volume and anti-TPO titer (69.3 mIU/liter; normal, <60 mg/liter) decreased, and C-reactive protein levels returned to normal.
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FIG. 2. A, Magnetic resonance imaging (MRI) before treatment (November 1999; left lobe, 40 x 48 x 95 mm; right lobe, 30 x 40 x 80 mm). Note the 50% tracheal stenosis. B, MRI after 1 month of corticosteroid treatment (January 2000; left lobe, 37 x 34 x 94 mm; right lobe, 35 x 28 x 78 mm). C, MRI after 3 yr of immunosuppressive treatment (2002); left and right lobe dimensions are 40 x 30 x 20 mm.
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The patient became pregnant and gave birth to a 2600-g girl in August 2002. The prednisone dose was 7 mg/d throughout pregnancy. In December 2002, thyroid volume returned to normal, as measured by MRI (left and right lobes, 40 x 20 x 30 mm; Fig. 2C
). In May 2003, the patient remained well on prednisone (6 mg/d) and L-T4 (225 µg). As the thyroid volume was stable, corticosteroid therapy was stopped in November 2003.
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Discussion
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PCG of the thyroid is extremely rare, and to our knowledge only 10 cases including ours (eight females and two males; mean age, 49.3 ± 13 yr) have been published to date (Table 1) (2, 5, 6, 7, 8, 9, 10, 11, 12). Thyroid involvement was nodular (six patients) or diffuse (four patients). Only one patient had PCG localized to extrathyroid sites (marrow plasmacytosis) (7). Tracheal deviation, paratracheal adhesions, or a combination of both were observed in three patients including ours. Hypothyroidism was noted in five patients (5, 9, 11, 12), three had Hashimoto’s thyroiditis (9, 11), including ours, and one had type 1 diabetes mellitus (10).
PCG is a rare pseudotumor of unknown origin characterized by a polyclonal plasmocytic infiltrate. Histological analysis is the only way to establish the diagnosis. PCG is usually diagnosed after surgery for goiter or a nodule (six of 10 cases) and is rarely responsible for tracheal compression (only three of 10 cases). In the context of a compressive goiter, several other differential diagnoses should be considered: malignant lymphoma, anaplastic cancer, fibrotic forms of lymphocytic thyroiditis (13), Riedel’s thyroiditis, and plasmacytoma of the thyroid. Over 50 cases of thyroid plasmacytoma have been reported (14). Thus, in the context of the histological appearance of PCG, the polyclonal nature of the plasma cell infiltrate must always be demonstrated to rule out a plasmacytoma (2). Thyroid PCG is a mixture of spindle fibroblasts, myofibroblasts, collagen, and inflammatory cells, mainly lymphocytes and abundant plasma cells. In thyroid, unlike other localizations, myofibroblastic infiltration is limited (2). In fibrotic forms of lymphocytic thyroiditis and Riedel’s thyroiditis, the predominance of lymphocytes and fibrosis is helpful in establishing the diagnosis. In addition, identification of other fibrotic sites, such as a retroperitoneal site, helps in diagnosing Riedel’s thyroiditis.
The pathophysiology of PCG is incompletely understood. It has been suggested that it might be the consequence of abnormalities of plasma cell differentiation secondary to an underlying chronic inflammatory or infectious condition. Thus, Li Voon Chong et al. (10) reported a patient who presented with fever, sore throat, neck tenderness, and dysphagia. Symptoms partially improved with a combination of erythromycin, ofloxacin, and amoxicillin plus clavulanic acid, and this patient further developed a PCG thyroid hard mass (10). An autoimmune origin of this disease can be discussed, supported by the nature of the cell infiltrate, positivity for anti-TPO antibodies, and cure by immunosuppressive therapy, as in the present case. Predisposition of patients to autoimmune diseases might play a role, because most of the patients are female, and as three of 10 patients had Hashimoto’s thyroiditis and one had type 1 diabetes mellitus. Alternatively, in the context of thyroid inflammation, alterations of antigen presentation can occur and an autoimmune response to TPO might occur as a result, and not a cause, of thyroid inflammation. Thyroid damage could lead to the release of sequestered antigens and induce an immune response (e.g. infections and radiotherapy) (15). Although the primary event triggering thyroid autoimmune disease remains elusive, several cytokines and other locally produced immunoregulatory substances could be involved in the autoimmune process from the initial presentation of antigen to the complete activation of the autoimmune response. As in Hashimoto’s thyroiditis, cytotoxic properties of anti-TPO antibodies or apoptosis mediated by T lymphocytes could explain thyroid hypofunction as observed in the case of our patient.
The therapeutic approach to PCG in other localizations (e.g. pulmonary) may be difficult. Although in most cases these lesions are indolent, in some the course may be aggressive and surgery, immunosuppressive therapy, or irradiation can be proposed to prevent relapses (3). Thus, early work on lung PCG suggested that steroid therapy was ineffective in stopping progression (1). Although immunosuppressive therapy had not been proposed before in the treatment of thyroid PCG, it has been reported to be efficient in the treatment of lung PCG (16, 17, 18, 19, 20). In thyroid PCG, two of the four patients with dyspnea underwent thyroidectomy. One of them improved rapidly after an attempt at thyroidectomy (4 wk) and previous antibiotic treatment (10). In the case presented here, the thyroid gland could not be removed because of fibrosis and the disease was successfully treated with immunosuppressive drugs. Corticosteroid therapy was continued during 4 yr, slowly tapering the dose to avoid a flare of tumoral growth. T4 suppressive treatment, rather than replacement therapy, was prescribed to avoid a stimulation of tumoral growth by TSH, and we plan to maintain T4 therapy for the moment, under careful monitoring of thyroid volume and function. However, as thyroid volume is stable, the dose of T4 will be decreased to normalize the TSH concentration and avoid the harmful effects of subclinical hyperthyroidism. Medical treatment allowed us to avoid a tracheal endoprosthesis in this young patient.
In conclusion, in PCG localized in the thyroid, corticosteroid and immunosuppressive therapy could avoid mutilating surgery.
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Acknowledgments
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We thank Prof. Antoine Martin (Laboratory of Anatomical Pathology, Avicenne Hospital) for his help in the preparation of this manuscript.
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Footnotes
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Abbreviations: Ab, Antibody; MRI, magnetic resonance imaging; PCG, plasma cell granuloma; TPO, thyroid peroxidase.
Received August 4, 2003.
Accepted January 14, 2004.
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References
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Abstract
Introduction
