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Fibrous variant of Hashimoto’s thyroiditis as a sign of IgG4-related disease, mimicking thyroid lymphoma: Case report
Tiroiditis de Hashimoto variante fibrosante como manifestación de enfermedad por IgG4, simulando un linfoma tiroideo: reporte de un caso
Pamela Benítez Valderramaa,
Corresponding author
, Alejandro Castro Calvob, Laura Rodrigañez Riescob, Rita Regojo Zapatac, Paola Parra Ramíreza
a Servicio de Endocrinología y Nutrición, Hospital Universitario La Paz, Madrid, Spain
b Servicio de Otorrinolaringología, Hospital Universitario La Paz, Madrid, Spain
c Servicio de Anatomía Patológica, Hospital Universitario La Paz, Madrid, Spain
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was first described by Li et al&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> in 2009&#44; manifesting as a single entity or as a part of multisystem involvement in IgG4-RD&#46; We report the case of a patient with IgG4-RTD mimicking thyroid lymphoma&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">The patient was a 47-year-old Caucasian man&#44; with no history of thyroid disease or cervical radiation&#44; who consulted for a four-month history of non-painful&#44; rapidly growing anterior cervical tumour associated with progressive dysphonia&#44; dysphagia and dyspnoea&#46; Physical examination revealed grade III goitre without palpable nodules&#46; An initial neck ultrasound showed a markedly enlarged thyroid gland with hypoechoic areas and thin hyperechoic septa featuring increased vascularisation on colour Doppler imaging&#44; suggestive of thyroiditis&#46; Laboratory results were consistent with overt primary hypothyroidism of autoimmune origin &#40;thyroid-stimulating hormone &#91;TSH&#93; 100&#46;9<span class="elsevierStyleHsp" style=""></span>&#956;IU&#47;ml &#91;normal range &#40;NR&#41; 0&#46;55&#8211;4&#46;78&#93;&#44; free thyroxine &#91;T4&#93; 0&#46;38<span class="elsevierStyleHsp" style=""></span>ng&#47;dl &#91;NR 0&#46;89&#8211;1&#46;76&#93; and peroxidase antibodies 443&#44;012 IU&#47;ml &#91;NR<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>60&#93;&#41;&#44; so treatment with levothyroxine was started&#46; One month after the onset of signs and symptoms&#44; the patient presented with right thyroid lobe &#40;RTL&#41; enlargement spreading to the ipsilateral submandibular region&#46; Computed tomography &#40;CT&#41; of the neck showed a large goitre affecting the RTL &#40;4<span class="elsevierStyleHsp" style=""></span>cm<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>4&#46;6<span class="elsevierStyleHsp" style=""></span>cm<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>12<span class="elsevierStyleHsp" style=""></span>cm &#91;AP<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>T<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>L&#93;&#59; left thyroid lobe &#91;LTL&#93; 4&#46;3<span class="elsevierStyleHsp" style=""></span>cm<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>4<span class="elsevierStyleHsp" style=""></span>cm<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>4<span class="elsevierStyleHsp" style=""></span>cm&#41;&#44; with spread towards the retropharyngeal space compressing the larynx and the ipsilateral pyriform sinus&#44; associated with displacement of the glottal and supraglottal portion&#44; including the vocal cords&#46; Due to the mass&#8217;s rapid growth&#44; fine needle aspiration biopsy was performed&#44; yielding results consistent with Hashimoto&#8217;s thyroiditis&#46; However&#44; given that thyroid lymphoma was suspected&#44; a decision was made to perform open glandular biopsy&#44; which revealed a pattern of thyroiditis&#44; inflammatory myofibroblastic tumour or IgG4-related sclerosing disease&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">The case was presented to the Endocrine Tumours Committee&#46; It was decided to order IgG4 521<span class="elsevierStyleHsp" style=""></span>mg&#47;dl &#40;NR 3&#8211;200&#41;&#44; beta-2 microglobulin 2&#46;6<span class="elsevierStyleHsp" style=""></span>mg&#47;l &#40;NR 1&#46;1&#8211;2&#46;5&#41; and lactate dehydrogenase &#40;LDH&#41; 247 IU&#47;l &#40;NR 100&#8211;190&#41; plus a positron emission tomography&#47;computed tomography &#40;PET&#47;CT&#41; scan with 18F-fluorodeoxyglucose &#40;<span class="elsevierStyleSup">18</span>F-FDG&#41;&#44; which corroborated the presence of a large goitre with diffuse uptake in relation to lymphocytic thyroiditis&#46; In light of the rapid growth and the compressive symptoms reported&#44; it was decided to perform a total thyroidectomy&#46; The only post-operative complication was a seroma that required drainage on two occasions&#46; Pathology showed a thyroid gland weighing 182<span class="elsevierStyleHsp" style=""></span>g &#40;NR 25&#8211;30<span class="elsevierStyleHsp" style=""></span>g&#41; with IgG4-related fibrous variant of Hashimoto&#8217;s thyroiditis &#40;with IgG4 staining &#62;28 plasma cells per high-power field and IgG4&#47;IgG ratio &#60;30&#37;&#44; without observing areas of diffuse lymphoid proliferation through antigen receptor rearrangement analysis&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; IgG4 values decreased by 55&#37; &#40;290<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#41; two weeks after the operation and normalised two months later&#46; Two years after surgery&#44; the patient has not presented with compromise of other organs or systems and maintains normal IgG4 serum levels&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">Our case represents a clear example of IgG4-RTD&#44; a recently recognised benign thyroid disease that may mimic a neoplastic condition&#46; The link between thyroid compromise and IgG4-RD was initially suggested based on the observation that hypothyroidism was highly prevalent in patients with autoimmune pancreatitis&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Taking these observations as a starting point&#44; Li et al&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> found that patients with Hashimoto&#8217;s thyroiditis could be subcategorised as patients with IgG4 &#40;&#43;&#41; or IgG4 &#40;&#8211;&#41; infiltrates&#44; with the former characterised by fibrosis and lymphoplasmacytic infiltration and the apparent absence of systemic extrathyroid involvement&#46; Typically&#44; patients with IgG4-RTD had higher rates of hypothyroidism&#44; had high levels of thyroid peroxidase &#40;TPO&#41; antibodies&#44; were younger&#44; were mostly male and had disease with a surprisingly progressive course compared to patients with IgG4 &#40;&#8211;&#41; disease&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;5</span></a> Thus&#44; the case reported had the typical characteristics of this condition&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">At present&#44; it is known that IgG4-RTD can encompass cases of &#40;a&#41; chronic autoimmune thyroiditis&#44; &#40;b&#41; a fibrotic variant of this disease&#44; &#40;c&#41; Riedel&#8217;s thyroiditis and &#40;d&#41; some uncommon cases of Graves&#8217; disease&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Regarding diagnosis of IgG4-RTD&#44; although there are mixed criteria&#44; the most commonly accepted criteria are those of the Japan Thyroid Association and the Japan Endocrine Society&#44; which include&#58; &#40;1&#41; gland enlargement&#44; &#40;2&#41; hypoechoic lesions on ultrasound&#44; &#40;3&#41; elevated serum IgG4 levels &#40;&#8805;135<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#41;&#44; &#40;4&#41; thyroid histopathology findings such as infiltration of &#62;20 IgG4&#43; plasma cells per high-power field and a proportion of IgG4&#43;&#47;IgG&#43; plasma cells &#62;30&#37;&#41; and &#40;5&#41; involvement of other organs&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> As such&#44; a patient is considered to have definitive IgG4-RTD when criteria 1&#8211;4 are met&#44; probable IgG4-RTD when criteria 1<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>2&#43;4 or 1<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>2&#43;5 are met and possible IgG4-RTD when criteria 1<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>2&#43;3 are met&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">On the one hand&#44; it should be stressed that histopathological findings are the most important elements for demonstrating IgG4&#43; plasma cell infiltration and for ruling out malignancy or other entities&#46; On the other hand&#44; it is important to note that elevated serum IgG4 levels are not sufficient by themselves to diagnose this entity&#44; since elevated IgG4 is also characteristic of other diseases&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> Although histology in the case reported revealed a proportion of IgG4&#43;&#47;IgG&#43; plasma cells &#60;30&#37;&#44; based on meeting all the other criteria&#44; the clinical presentation&#44; the epidemiological data and the fact that lymphoid clonality had been ruled out&#44; the patient was considered to have definitive IgG4-RTD&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Concerning treatment&#44; glucocorticoids and immunomodulators such as azathioprine&#44; mycophenolate mofetil and methotrexate are treatments of choice in IgG4-RD&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> However&#44; thyroid gland enlargement with significant compression of adjacent organs&#44; constrictive symptoms or suspected malignancy lend themselves to a surgical strategy&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">In conclusion&#44; knowledge of this condition is indispensable given that it will help physicians to decide the best strategy for diagnosis and treatment&#44; since many of these lesions involve a mass raising clinical suspicion of malignancy&#44; and in some cases unnecessary surgery may be avoided&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Funding</span><p id="par0055" class="elsevierStylePara elsevierViewall">This research has not received specific funding from public sector agencies&#44; the commercial sector or non-profit organisations&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Conflicts of interest</span><p id="par0060" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest in relation to the publication of this scientific article&#46;</p></span></span>"
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Original language: English
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es en pt

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?

Você é um profissional de saúde habilitado a prescrever ou dispensar medicamentos