Plasma cell granuloma of the thyroid and Hashimoto thyroiditis.

Abstract: Plasma cell granuloma of the thyroid is a rare tumor-like lesion formed by a localized proliferation of inflammatory cells, supported by a stroma of fibrous tissue. Few cases have been previously reported in the medical literature. We report a new case of a 41-year-old man presenting a goiter with primary hypothyroidism (thyroid-stimulating hormone, 70 mIU/L; free thyroxine, < 0.01 pmol/L; triiodothyronine, 0.66 nmol/L) and elevation of thyroid antibodies. Several fine-needle aspiration biopsies of the thyroid were fruitless and total thyroidectomy was performed. Histologic and immunohistochemical study demonstrated the polyclonal nature of the cells and yielded a diagnosis of plasma cell granuloma. Histologic findings of Hashimoto thyroiditis were present too.

Key Words: Hashimoto thyroiditis, plasma cell granuloma of the thyroid

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Plasma cell granuloma (PCG), also called inflammatory pseudotumor, is an infrequent disease. It is a nonneoplastic lesion histologically established by a localized proliferation of mature plasma cells, intermingled with lymphocytes and other inflammatory cells, supported by stroma of fibrous tissue. PCG was initially described in the lung by Bahadori and Liebow. (1) The lung is the organ most often affected, (2) although a number of cases have sporadically been reported in different extrapulmonary sites: liver, stomach, pancreas, spleen, kidney, bladder, heart, tonsil, spinal cord, meninges, and brain. (3) The source of this disease is unknown. It is usually benign and has a good prognosis except in the rare cases in which vital structures have been affected and their function compromised. (4, 5)

Thyroid PCG is a rare condition. The first case demonstrated and confirmed by the immunoperoxidase staining technique did not appear until 1981. (6) Until now, few cases have been reported in English language journals, more frequently in women. (7) This case shows the coexistence of thyroid PCG and Hashimoto thyroiditis in a man.

Case Report

A 41-year-old man with a history of smoking showed progressive enlargement of a nonpainful neck mass during a 3-month period, and dysphonia, anorexia, and a 4-kg weight loss. He had no family history of thyroid disease. Physical examination revealed the following: height, 1.79 m; weight, 92 kg; body mass index, 28.71 kg/[m.sup.2]; and arterial tension, 130/90 mm Hg. He presented a large goiter with both lobes increased in size and consistency, but especially the right one. The lymph nodes were not affected. Blood analysis showed the following: total proteins, 9.48 mg/dL (normal, 6-8 mg/dL); [gamma]-globulin, 44.2% (normal, 11.2-19.9%); fibrinogen, 616 mg/dL (normal, 170-400 mg/dL); erythrocyte sedimentation rate (ESR), 117 (normal, 1-10); immuno-electrophoresis with polyclonal IgG and IgA; thyroid-stimulating hormone, 70.7 mU/L (normal, 0.4-4 mU/L); T4L, <0.2 ng/dL (normal, 0.8-1.9 ng/dL); triiodothyronine, 44 ng/dL (normal, 80-210 ng/dL); antithyroglobulin antibodies, 439,000 UA/mL (normal, 0-10 UA/mL); and antiperoxidase antibodies, 1,280 UA/mL (normal, 0-10 UA/mL). Urine protein electrophoresis and Bence-Jones protein measurements were negative. Fine-needle aspiration was performed and the cellular material obtained was insufficient for diagnosis. A computed tomographic scan confirmed the growth of both lobes with tracheal compression. Neck ultrasonography revealed an increased size of thyroid lobes, which were heterogeneous and hypoechoic, with a right lobe of 43 X 40 X 50 mm and left lobe of 31 X 24 X 41 mm. Bone marrow aspiration and bone scan were normal.

Treatment with 100 [mu]/d of levothyroxine was initiated, and 10 days thereafter a total thyroidectomy was performed without postoperative complications. Macroscopic examination of the surgical specimen showed a firm enlarged thyroid of 11 X 6 X 5 cm and weighing 289 g. The cut surfaces were yellowish-white and firm, with a nodular appearance (Fig. 1). Histologic study showed an intense, diffuse infiltration by inflammatory cells composed of many mature plasma cells and less abundant lymphocytes in a fibrous background (Fig. 2) with only a few residual thyroid follicles and with very scanty lymphoid conglomerates of follicular appearance.

Immunohistochemical study showed that approximately 90% of the plasma cells contained IgG, 20% of the cells contained IgA, and no cells expressed IgM. In contrast, the [kappa] and [lambda] light chains were found to be polyclonal, with a [kappa]/[lambda] ratio of approximately 3:1.

Currently, the patient remains euthyroid under treatment with 200 [mu]/d of levothyroxine. The analytical anomalies (total proteins, [gamma]-globulins, serum immunoelectrophoresis, fibrinogen, and ESR) disappeared 6 months after surgery.

Discussion

The presence of PCG in the thyroid gland is very unusual. Diagnostic criteria of PCG consist of solitary mass and polyclonal nature confirmed by immunohistochemistry with immunoperoxidase technique. (8, 9)

The cause of PCG is unknown, and various hypotheses have been proposed. It could be a manifestation of Hashimoto thyroiditis. The coexistence of PCG and Hashimoto thyroiditis has been described in previous reports (10, 11) but is exceptional in a man. High titers of antithyroglobulin and antimicrosomal antibodies and the presence of oxyphilic cells correlate with the histologic characteristics of PCG and Hashimoto thyroiditis. PCG could be a fibrous variant of Hashimoto thyroiditis. This variation constitutes approximately 12% of Hashimoto thyroiditis and is characterized by extensive fibrosis with atrophy of the thyroid follicles and squamous metaplasia of the residual follicular cells. (11, 12) The second possibility is that PCG is a differentiated initial phase of plasmacytoma, although there is no evidence of posterior evolution to this neoplasia. Clinical findings are similar in the two diseases, but plasmacytoma of the thyroid is a neoplastic lesion with poorly differentiated histology and production of M or monoclonal protein verified by immunohistochemistry. Prognosis is impaired in plasmacytoma, with a much higher recurrence rate. Hashimoto thyroiditis coexists with plasmacytoma in 60 to 85% of the cases. (8)

[FIGURE 1 OMITTED]

Fine-needle aspiration is not a good diagnostic procedure in PCG and occasionally yields false results. (11) The presence of abundant fibrous tissue makes it difficult to aspirate the material, which can therefore be insufficient for diagnosis. The existence of inflammatory infiltrates, which may or may not coincide with Hashimoto thyroiditis, gives rise to diagnostic mistakes. Therefore, a surgical biopsy is essential.

[FIGURE 2 OMITTED]

Our case presented serum hyperproteinemia and hypergammaglobulinemia, and an increase in fibrinogen and the ESR. The existence of similar inflammatory syndromes has been previously shown in an adrenal PCG. (12) The cause of this inflammatory response is not known and could be an exaggerated immunologic reaction to an unknown antigen. (7) It does not seem to modify the prognosis. Altered analytical parameters normalize progressively after treatment.

Treatment is always surgical. Different types of operations have been performed with more or less extensive resectioning, and the evolution has been favorable in all cases. This corroborates the benign nature of the lesion. (13)

Conclusion

Thyroid PCG is an infrequent disease, especially in men. It commonly appears as a mass with subacute or chronic growth that occasionally compresses neighbor structures. Fine-needle aspiration is insufficient to diagnose it, and biopsy is necessary because a histologic study can confirm the diagnosis. PCG can be associated with Hashimoto thyroiditis. The treatment of choice is surgery, after which the evolution is favorable.

Accepted May 5, 2003.

Copyright [c] 2004 by The Southern Medical Association

0038-4348/04/9706-0598

References

1. Bahadori M. Liebow AA. Plasma cell granulomas of the lung. Cancer 1973;31:191-208.

2. Horan TA. Inflammatory pseudotumors of the lung. Ann Thorac Surg 2000;69:1295 (letter).

3. Leroy X, Copin MC, Graziana JP, et al. Inflammatory pseudotumor of the renal pelvis: A report of 2 cases with clinicopathologic and immunohistochemical study. Arch Pathol Lab Med 2000;124:1209-1212.

4. Holck S. Plasma cell granuloma of the thyroid. Cancer 1981;48:830-832.

5. Pettinato G, Manivel JC, De Rosa N, et al. Inflammatory myofibroblastic tumor (plasma cell granuloma): Clinicopathologic study of 20 cases with immunohistochemical and ultrastructural observations. Am J Clin Pathol 1990;94:538-546.

6. Li Voon Chong JS, Burrows CT, Cave-Bigley D, et al. A hard thyroid mass due to plasma cell granuloma. Int J Clin Pract 2001;55:335-336.

7. Rubin J, Johnson JT, Killeen R, et al. Extramedullary plasmacytoma of the thyroid associated with a serum monoclonal gammopathy. Arch Otolaryngol Head Neck Surg 1990;116:855-859.

8. Kovacs CS, Mant MJ, Nguyen GK, et al. Plasma cell lesions of the thyroid: Report of a case of solitary plasmacytoma and a review of the literature. Thyroid 1994;4:65-71.

9. Chan KW, Poon GP, Choi CH. Plasma cell granuloma of the thyroid. J Clin Pathol 1986;39:1105-1107.

10. Yapp R, Linder J, Schenken JR, et al. Plasma cell granuloma of the thyroid. Hum Pathol 1985;16:848-850.

11. Zingrillo M, Tardio B, Bisceglia M. Plasma cell granuloma of the thyroid associated with Hashimoto thyroiditis. J Endocrinol Invest 1995;18:460-464.

12. De Mascarel A, Vergier B, Merlio JP, et al. Plasma cell granuloma of the adrenal gland and the thyroid: Report of two cases. J Surg Oncol 1989;41:139-142.

13. Talmi YP, Finkelstein Y, Gal R, et al. Plasma cell granuloma of the thyroid gland. Head Neck 1989;11:184-187.

RELATED ARTICLE: Key Points

* Plasma cell granuloma of the thyroid is a rare condition, especially in men.

* The coexistence of plasma cell granuloma and Hashimoto thyroiditis has been described in previous reports, but this relationship is unclear.

* This disease has a good prognosis. This is different than with plasmacytoma of the thyroid.

J. C. Ferrer-Garcia, MD, P. Costa-Talens, MD, PHD, J. F. Merino-Torres, MD, PHD, M. Prieto-Rodriguez, MD, PHD, J. F. Vera-Sempere, MD, PHD, and F. Pinon-Selles, MD, PHD

From the Department of Endocrinology and Nutrition and the Department of Pathology, University Hospital La Fe, Valencia, Spain.

Reprint requests to J. C. Ferrer-Garcia, MD, Servicio de Endocrinologia, University Hospital La Fe, Avenida Campanar 21-46009, Valencia, Spain. Email: [e-mail]