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Annales d’Endocrinologie 73 (2012) 492–496

Clinical case

Nodular sclerosing Hodgkin’s disease mimicking Riedel’s invasive fibrousthyroiditis

Maladie de Hodgkin scléronodulaire mimant une thyroïdite fibreuse invasive de Riedel

Philippe Oriot a,∗, Philippe Malvaux b, Frédéric Waignein c, Anne Delcourt d, Charles Doyen e,Emmanuel Rousseau f, Gubin Baudry g, Stéphane Dechambre g

a Department of Endocrinology, Mouscron Hospital, Mouscron, Belgiumb Department of Endocrine Surgery, Notre Dame Hospital, Tournai, Belgium

c Department of Histopathology, Notre Dame Hospital, Tournai, Belgiumd Department of Nuclear Medicine, Mouscron Hospital, Mouscron, Belgium

e Department of Pneumology, Mouscron Hospital, Mouscron, Belgiumf Department of Histopathology, Mouscron Hospital, Mouscron, Belgium

g Department of Radiology, Mouscron Hospital, Mouscron, Belgium

bstract

Riedel’s thyroiditis appears in the form of a hard cervical mass with rapid onset, and it is associated with extensive fibrosis that compresses nearbytructures, such as the trachea and supra-aortic vessels; its diagnosis is essentially histopathological. Although its histological characteristics haveeen well established, there are some diagnostic pitfalls. We report here the case of a 37-year-old woman, with clinical and histopathological datauggesting Riedel’s disease. Fibrosis regressed after treatment with corticosteroids, relieving the compressed airways. However, in contrast with theatest knowledge on this disease, the IgG4 serum levels were consistently normal, and positron emission tomography in search of extensive fibrosisevealed an abnormal metabolic activity of the bone marrow. The final diagnosis revised by the histopathologist was that of nodular sclerosingodgkin’s lymphoma. This case allows us to review the diagnostic approach when facing a thyroid mass with extremely rapid evolution.

2012 Elsevier Masson SAS. All rights reserved.

ésumé

La thyroïdite de Riedel se présente sous la forme d’une masse cervicale ferme d’apparition rapide associée à une fibrose extensive comprimantes structures avoisinantes comme la trachée et les vaisseaux supra aortiques ; son diagnostic est essentiellement anatomopathologique. Bien quea description histologique soit bien établie, des pièges diagnostics existent. Nous rapportons le cas d’une femme de 37 ans dont la présentationlinique et anatomopathologique plaidait pour une maladie de Riedel. La fibrose a régressé sous corticoïdes, libérant ainsi les voies respiratoiresui étaient comprimées. Cependant, en contraste avec les dernières connaissances au sujet de cette maladie, nous constations que les taux sériques

’immunoglobulines IgG4 était constamment normaux et que la tomographie d’émission de positrons réalisée à la recherche d’une fibrose extensiveévélait une activité métabolique anormale au niveau de la moelle osseuse. Le diagnostic final révisé par l’anatomopathologiste fut celui d’unymphome Hogdkinien scléronodulaire. Ce cas nous permet de revoir une démarche diagnostique devant une masse thyroïdienne d’évolutionorpide.

2012 Elsevier Masson SAS. Tous droits réservés.

∗ Corresponding author. Service d’endocrinologie–diabétologie, centreospitalier de Mouscron, avenue de Fécamp, 49, 7700 Mouscron, Belgium.

E-mail address: p.oriot@chmouscron.be (P. Oriot).

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003-4266/$ – see front matter © 2012 Elsevier Masson SAS. All rights reserved.ttp://dx.doi.org/10.1016/j.ando.2012.06.001

. Introduction

Riedel’s thyroiditis (RT) is a rare disease with a low inci-ence, estimated by some authors to be between 0.04 and 0.30%

eople [1]. The incidence reported was 0.06% people in theayo clinic’s series of thyroidectomies performed between

920 and 1955. More recently, between 1976 and 2008, the

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P. Oriot et al. / Annales d’En

ayo clinic [2] reported 21 cases with diagnosis of RT, accord-ng to its database. Despite its low incidence, the number ofeported cases of RT is increasing, and authors are refining theireans for diagnosis or proposing new therapeutic alternativesith glucocorticoids [3], such as tamoxifen [4], colchicine [5],

zathioprine [6], mycophenolate mofetil [7] or, more recently,ituximab [8].

RT is characterized by lymphoplasmacytic infiltration of thehyroid, associated with extensive, systemic and local fibrosis9]. It can be suspected in case of rapidly progressing, induratednd immobile goiter. The evolution can be marked by theppearance of symptoms such as tracheal compression withtridor, dysphonia due to laryngeal nerve damage, superior venaava syndrome and, more rarely, clinical signs of hypocal-emia associated with infiltration of the parathyroid glands [10].hyroid dysfunction can also occur, most often as hypothy-

oidism (30% people) [1], with low serum levels of autoanti-odies to thyroid peroxidase (TPO) in half of the patients.

Remotely, systemic fibrosis can occur, mainly in the form ofetroperitoneal fibrosis, orbital pseudotumor, mediastinal fibro-is, pleuropericarditis or sclerosing cholangitis [6,11,12]. Basedn this observation, some authors even propose to include RTn a more systemic pathology: hyperimmunoglobulinemia IgG4yndrome or IgG4-related disease [13–17].

To date, only a histological examination can confirm RT, withhe exception, perhaps, of an MRI, as hypodense signals on1- and T2-weighted images could be pathognomonic [18,19].here is no serum marker for the disease, apart from high IgG4

evels (usually over 1.35 g/L), although this point remains toe confirmed [13,17]. Fine-needle aspiration does not allow forefinite diagnosis.

The differential diagnosis of a very hard thyroid mass alsoemains difficult to establish, as it includes sclerosing-typeashimoto’s thyroiditis [20], sarcoma [21], sclerosing-type

naplastic carcinoma [22] and thyroid lymphoma [18,23–25].

. Case report

We report the case of a 37-year-old woman who presentedith a rapidly growing goiter, which had appeared 2 months ear-

ier. Her family history revealed that her mother had undergone thyroidectomy for benign nodules. The patient complained ofsthenia and daytime hot flushes, and had recently presentedith inspiratory dyspnea with stridor. She smoked one pack of

igarettes per day. No fever or general health deterioration wasoted. Palpation revealed a hard, painless, immobile mass. Labo-atory tests revealed TPO antibodies less than 10 UI/mL (< 35),ree T4 at 11.9 pmol/L (7.8–18), thyroid-stimulating hormoneTSH) at 2.87 mU/L (0.2–3.5), normal values for carcinoem-ryonic antigen (2.7 ng/mL, so < 4), and some calcitonin andalcemia.

Goiter ultrasonography revealed a lumpy heteronodular massf 4.4 × 2.7 × 5 cm at the level of the isthmus and left lobe.

his poorly vascularized mass comprised hypo- and hypere-hogenic areas, as well as several small cystic areas. There waso adenopathy. The mass appeared as a cold spot by Technetium9m scintigraphy. Fine-needle aspiration revealed an acellular

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uscle with atrophic fibers closely associated with nodular lymphoplasmacyticnfiltrates.

aterial, and the absence of a definite diagnosis led to propose thyroidectomy, which was finally impossible because of theighly adherent and fibrous aspects of the tissues.

Histological examination revealed a dense fibrous tissuelong the striated muscle with atrophic fibers closely associatedith nodular lymphoplasmacytic infiltrates, sparsely scattered

ig. 2. CT scan showed an infiltration process at the cervical and mediastinalevels, he mass was compressing the trachea and deflecting it to the right.

494 P. Oriot et al. / Annales d’Endocrinologie 73 (2012) 492–496

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ig. 3. The (18)F-FDG-PET-CT confirmed the hypermetabolism of the bulkyediastinal mass.

Staging by cervicothoracic CT scan (Fig. 2) in search of sys-emic fibrosis revealed an infiltration process at the cervical and

ediastinal levels, displacing and surrounding the supra-aorticrterial structures connecting to the pleura and extending alonghe left paraspinal line. The mass was compressing the trachea,eflecting it to the right.

Moderate abnormalities of pulmonary function (but typi-al of tracheal obstruction) were noted, with inspiratory andostly expiratory limitation of the flow-volume loop. By tra-

heobronchial endoscopy, a 4-cm long extrinsic stenosis with aarrowing of more than 50% was detected, 5 cm below the vocalords.

Positron emission tomography ((18)F-FDG-PET-CT) con-rmed the hypermetabolism of the bulky mediastinal massFig. 3), with moderate tracer uptake. Tracer uptake was mostrominent in the liver and particularly in the right hepatic lobe,hich could be consistent with sclerosing cholangitis, although

t was not confirmed by MRI. Moreover, the appearance of theone marrow on (18)F-FDG-PET-CT was abnormal.

Treatment with glucocorticoids (methylprednisolone) at2 mg/day and colchicine at 1 mg/day was started to slow downhe fibrotic process [3,5], and smoking cessation was initiated4].

After eight weeks of treatment, the spirometry indicated clear improvement of the flow-volume loop. The CT scanevealed that the lesion had decreased in size, both at the cervical65 × 60 mm vs. 85 × 75 mm) and mediastinal (80 × 60 mm vs.0 × 73 mm) levels.

However, laboratory tests showed serum IgG4 levels lesshan 1 g/L from the onset of the disease, and (18)F-FDG-PET-T revealed an unusual bone marrow activity. Therefore, other

iagnoses were considered.

To conciliate paraclinical and histopathological findings, aecond analysis of the sample was performed. A predominance

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ig. 4. Reed-Sternberg variant cells (black arrow) were noted, pathognomonicf nodular sclerosing Hodgkin’s lymphoma.

f lymphocytes over plasma cells was noted, as well as numerousosinophils, mummified cells and, notably, a few lacunar cellsReed-Sternberg variants), pathognomonic of nodular scleros-ng Hodgkin’s lymphoma (Fig. 4), positive for CD15 and CD30

arking, hence confirming nodular sclerosing Hodgkin’s dis-ase. The final diagnosis was a mediastinal nodular sclerosingodgkin’s lymphoma.The patient was then treated with BEACOPP chemotherapy

bleomycin, etoposide, doxorubicin, cyclophosphamide, vin-ristine, procarbazine and prednisone), which is the conventionalreatment for stage III and IV of Hodgkin’s lymphoma.

. Discussion

The differential diagnosis of a thyroid mass is complicated,specially between Riedel’s disease and mediastinal Hodgkin’sisease, as already discussed by Vigouroux et al. in 1993 [18].owever, the differential diagnosis was recently enriched byew data on Riedel’s disease. Indeed, some authors considerhe latter as an entity of the IgG4-related disease, described inhe early 2000s [13,17]. The etiology of this disease remainsnclear. It is characterized by high levels of IgG4 (> 1.35 g/L).

The diagnosis can also be confirmed by immunolabelinghe lesion with an IgG4 antibody (with a ratio IgG4-positivelasma cells/IgG-positive plasma cells greater than 50% orgG4-positive plasma cells greater than 10 at a strong magni-cation) [17]. IgG4-related disease is associated with certain

nflammatory and fibrosclerosing pseudotumors, likely to reachifferent tissues: pancreatitis, interstitial nephritis, sclerosingholangitis and thyroid gland.

The clinical, biological and radiological evolution is favor-ble under treatment with corticosteroids and is associated with

decrease of IgG4 levels. In the present case, serum IgG4 levelsemained within the normal range from the start, which, a priorileaded against the diagnosis of RT.

Moreover, positron emission tomography is a medical imag-

ng technique that is increasingly used to assess RT extent andreatment efficacy [4]. In the present case, (18)F-FDG-PET-CTevealed mediastinal lesions, as well as a high agent uptake at the

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one marrow, usually observed when the marrow was stimulatedecause of an inflammatory syndrome, anemia or lymphoma26], but usually not in case of RT.

The first histological analysis performed on a tissue samplef 1 cm2 revealed dense, fibrous tissue dissecting the musclen the absence of thyroid tissue (Fig. 2). Due to the suggestinglinical aspect and important fibrosis, a diagnosis of Riedel’sisease was first proposed. It should be noted that the closestntity of the disease linked to IgG4 in histopathological termss lymphoma, characterized by the presence of a majority ofnfiltrating B cells, detectable if the tissue is not too fibrous,hich was the case here.However, the lymphoid inflammatory response in hyper-

gG4 is mainly composed of T cells. In the present case, it washus difficult to confirm Hodgkin’s disease, and even more soecause Reed-Sternberg cells were sparse in the sample. Reed-ternberg cells are malignant cells specific of Hodgkin’s diseasend of lymphoid origin [17].

The patient thus suffered from a highly fibrogenic Hodgkin’sisease, as indicated above. This type of lymphoma is more fre-uently found at the mediastinal level. Most affected patients areoung women, in whom the disease can be detected by symp-oms of compression (cough, dyspnea, chest pain), and in rareases by a thyroid mass [18,23,25], similar to that observed inatients with Riedel’s disease.

Accurate diagnosis is important because the treatment ofhese two diseases is very different. Indeed, RT treatmentemains highly controversial because of the absence of ran-omized studies due to the rarity of the disease. Surgerys only performed to free the respiratory system in case ofevere tracheal stenosis. Treatment with corticosteroids remainshe standard treatment, although there is no consensus onhe initial dose or duration of treatment. Tamoxifen aloner in combination with corticosteroids, with a mean dosef 40 mg/day, was proposed because it could inhibit fibro-is. Conversely, the treatment of the lymphoma consists ofhemotherapy followed by radiotherapy delivered to the initialumor bed.

. Conclusions

The case reported here emphasizes the difficulty ofifferential diagnosis of a thyroid mass, especially betweeniedel’s invasive fibrous thyroiditis, a condition with unknowntiology, perhaps indicating the localization of a more systemicbrosclerotic disease or a sclerosing form of lymphoma.

The therapeutic outcome of both diseases after treatment withorticosteroids is similar at first, with a decrease in the size ofnflammatory tissue and of the fibrosis, which is very confusing.o specific examination that can easily differentiate betweenoth diseases has been reported in the literature. However, serumgG4 level is a good indicator, and should form part of the tests

erformed when facing a case of thyroid fibrosis. Finally, asentioned before, (18)F-FDG-PET-CT be used to estimate the

xtension of the fibro-inflammatory process, but also to redirecthe diagnosis, as other spots can be detected, e.g., of the bones,

[

nologie 73 (2012) 492–496 495

hich are not described in Riedel’s thyroiditis and are consistentith a diagnosis of lymphoma.

uthor contribution

P.O. wrote and edited the manuscript.P.O. and P.M. reviewed the manuscript.P.O., C.D., E.R. and A.D. contributed to the discussion.P.O., P.M., F.W., A.D., C.D. and E.R. contributed to the data

ollection.

isclosure of interest

The authors declare that they have no conflicts of interestoncerning this article.

cknowledgments

We would like to give special thanks to Professor Dominiqueaiter (Department of Endocrinology and Nutrition, Saint-Luccademic Hospital, UCL, Brussels, Belgium) for his precious

eview of this article.

eferences

[1] Perimenis P, Marcelli S, Leteurtre E, Vantyghem MC, Wemeau JL. Riedel’sthyroiditis: current aspects. Presse Med 2008;37:1015–21.

[2] Fatourechi MM, Hay ID, McIver B, Sebo TJ, Fatourechi V. Invasive fibrousthyroiditis (Riedel thyroiditis): the Mayo clinic experience, 1976–2008.Thyroid 2011;21:765–72.

[3] Vaidya B, Harris PE, Barrett P, Kendall-Taylor P. Corticosteroid therapy inRiedel’s thyroiditis. Med J 1997;73:817–9.

[4] Hennessey JV. Clinical review: Riedel’s thyroiditis: a clinical review. J ClinEndocrinol Metab 2011;96:3031–41.

[5] De Socio G, Verrecchia E, Fonnesu C, Giovinale M, Gasbarrini GB, MannaR. Effectiveness of colchicine therapy in 4 cases of retroperitoneal fibrosisassociated with autoinflammatory diseases. J Rheumatol 2010;37:1971–2.

[6] Erdogan MF, Anil C, Türkcapar N, Ozkaramanli D, Sak SD, Erdogan G. Acase of Riedel’s thyroiditis with pleural and pericardial effusions. Endocrine2009;35:297–301.

[7] Levy JM, Hasney CP, Friedlander PL, Kandil E, Occhipinti EA, Kahn MJ.Combined mycophenolate mofetil and prednisone therapy in tamoxifenand prednisone resistant Reidel’s thyroiditis. Thyroid 2010;20:105–7.

[8] Khosroshahi A, Carruthers MN, Deshpande V, Unizony S, Bloch DB, StoneJH. Rituximab for the treatment of IgG4-related disease: lessons from 10consecutive patients. Medicine (Baltimore) 2012;91:57–66.

[9] Papi G, LiVolsi VA. Current concepts on Riedel thyroiditis. Am J ClinPathol 2004;121:50–63.

10] Yasmeen T, Khan S, Patel SG, Reeves WA, Gonsch FA, de Bustros A, et al.Clinical case seminar: Riedel’s thyroiditis: report of a case complicatedby spontaneous hypoparathyroidism, recurrent laryngeal nerve injury, andHorner’s syndrome. J Clin Endocrinol Metab 2002;87:3543–7.

11] Meier P, et al. La fibrose rétropéritonéale, une maladie inflammatoireméconnue. Observations cliniques et revue de la littérature. Nephrologie2003;24:173–80.

12] Stoica I, Selvais P, Oriot P. Thyroïdite fibreuse de Riedel et pleuro-péricardite. Ann Endocrinol (Paris) 2011;72:375–401.

13] Dahlgren M, Khosroshahi A, Nielsen GP, Deshpande V, Stone JH. Riedel’sthyroiditis and multifocal fibrosclerosis are part of the IgG4-related sys-

temic disease spectrum. Arthritis Care Res 2010;62:1312–8.

14] Ebbo M, Grados A, Daniel L, Vély F, Harlé JR, Pavic M, et al. IgG4-relatedsystemic disease: emergence of a new systemic disease? Literature review.Rev Med Interne 2012;33:23–34.

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96 P. Oriot et al. / Annales d’En

15] Kakudo K, Li Y, Taniguchi E, Mori I, Ozaki T, Nishihara E, et al. IgG4-related disease of the thyroid glands. Endocr J 2012;59(4):273–81.

16] Cheuk W, Tam FK, et al. Idiopathic cervical fibrosis: a new memberof IgG4-related sclerosing diseases: report of 4 cases, 1 complicated bycomposite lymphoma. Am J Surg Pathol 2010;34:1678–85.

17] Stone JH, Zen Y, Deshpande V. IgG4-related disease. N Engl J Med2012;366:539–51.

18] Vigouroux C, Escourolle H, Mosnier-Pudar H, et al. Riedel’s thyroiditisand lymphoma. Diagnostic difficulties. Presse Med 1996;25: 28–30.

19] Fontan, et al. Riedel thyroiditis US, CT and MR evaluation. J ComputAssist Tomogr 1993;17:324–5.

20] Junik R, Juraniec O, Pypkowski J, Krymer A, Marszałek A. A difficult diag-

nosis: a case report of combined Riedel’s disease and fibrosing Hashimoto’sthyroiditis. Endokrynol Pol 2011;62:351–6.

21] Torres-Montaner A, Beltran M, de la Osa R, Oliva H. Sarcoma of the thyroidregion mimicking Riedel’s thyroiditis. J Clin Pathol 2011;54:570–2.

nologie 73 (2012) 492–496

22] Shahi N, Abdelhamid MF, Jindall M, Awad RW. Riedel’s thyroiditis mas-querading as anaplastic thyroid carcinoma: a case report. J Med CaseReports 2010;20:4–15.

23] Campanelli P. Scleronodular retrosternal Hodgkin’s disease with cervicalprotrusion. Ann Ital Chir 1993;64:429–36.

24] Rathnam K, Karpurmath S, Cyriac S, Gnana ST, Sundersingh S.Composite Hodgkin lymphoma and chronic lymphocytic leukemia: a rarecase. J Cancer Res Ther 2011;7:484–5.

25] Guohua, et al. Composite lymphoma in the anterior mediastinum:a case report and review of the literature. DiagnPathol 2011;6:60.

26] Salaun PY, Gastinne T, Bodet-Milin C, Campion L, et al. Analy-

sis of (18)F-FDG-PET diffuse bone marrow uptake and splenic uptakein staging of Hodgkin’s lymphoma: a reflection of disease infiltra-tion or just inflammation? Eur J Nucl Med Mol Imaging 2009;36:1813–21.