Abstract The purpose of this study was to assess histo-pathological findings after a bilateral near-total thyroidec-tomy (residual thyroid tissue about 4 to 5 g) for multinodu-lar goiter (MNG). The 270 patients included 238 womenand 32 men with a mean age of 52 years (range: 19–82years) who had MNG involving the entire gland and hadundergone a primary bilateral surgical procedure between1993–1998. There was no intra- or postoperative mortal-ity. Indications for the MNG surgery were suspected ma-lignancy (7.7%), thyrotoxicosis (27.7)%, pressure on cer-vical structures with tracheal deviation (38%), significantcosmetic deformity in young female patients (6.6%) andintrathoracic extension of the MNG (19.6%). Grave’s dis-ease was not included in our study. The surgical specimenweight ranged from 60 to 560 g (average 120 g). Finalpathological findings were benign in 237 patients (87.8%)and malignant in 33 patients (12.2%). Nineteen patientswere diagnosed with macroscopic (ten patients) or micro-scopic (nine patients) types of papillary carcinoma: therewere two patients with the follicular variant of papillarycarcinoma, three with lymphoma and Hashimoto’s thyroid-itis, three with medullar carcinoma, three with anaplasticcarcinoma, two with follicular carcinoma and one withHürthle cell carcinoma. A true total completion thyroidec-tomy was performed only for the medullary carcinomapatients and for four of the “high-risk” papillary carcinomapatients. Permanent (>12 months) unilateral recurrent

paralysis occurred in four patients (1.4%), permanent(>12 months) hypoparathyroidism in ten patients (3.7%)and hypertrophic or keloid scar in 14 patients (5.1%). Ourresults suggest that near total thyroidectomy with minimalresidual tissue is a versatile surgical procedure for varioushistopathological features in MNG patients. Low rates ofpostoperative complications were observed.

Keywords Multinodular goiter · Papillary carcinoma ·Thyroid gland · Thyroidectomy

Introduction

Few subjects in surgery have generated so much contro-versy as the surgical management of multinodular goiter(MNG) [31]. Autopsy studies have demonstrated a highprevalence of benign nodular thyroid disease present inapproximately 37% of the general population. In nodularthyroid disease the overall incidence of malignancy rangesbetween 10%–30% depending on the selectivity of surgi-cal indications [27, 31]. By clinical definition MNG is adiffuse thyroid enlargement, which usually represents theend stage of benign disease, with nodules of various sizes.Regionally, differing growth is a constant feature of MNG[33]. Nodularity is the inevitable consequence of unequalgrowth potential among epithelial cells of the follicles. In-trathyroidal scar formation because of local necrosis andrepair by fibrous tissue result in a network [26]. However,MNG may harbor a wide spectrum of different histopath-ological features that require appropriate management andfollow-up. We undertook this retrospective study to assesshistopathological findings after a near-total thyroidec-tomy for MNG as the standard procedure.

Materials and methods

Studied population

During the period from 1993 to 1998, 270 patients with MNG in-volving the entire gland were admitted to the Department of Otorhi-

Jean-Michel Prades · Jean-Marc Dumollard ·Andrei Timoshenko · Larbi Chelikh · Frederic Michel ·Bruno Estour · Christian Martin

Multinodular goiter: surgical management and histopathological findings

Eur Arch Otorhinolaryngol (2002) 259 :217–221DOI 10.1007/s00405-002-0455-0

Received: 12 April 2001 / Accepted: 17 January 2002 / Published online: 19 March 2002

MISCELLANEOUS

J.-M. Prades (✉ ) · A. Timoshenko · L. Chelikh · F. Michel ·C. MartinDepartment of Otolaryngology, Head and Neck Surgery, Bellevue Hospital, St-Etienne University Hospital Center, Boulevard Pasteur, 42055, Saint-Etienne Cedex 2, Francee-mail: christian.martin@chu-st-etienne.fr, Tel.: +33-477-127794, Fax: +33-477-127854

J.-M. DumollardDepartment of Pathology, St-Etienne University Hospital Center,Saint-Etienne, France

B. EstourDepartment of Endocrinology, St-Etienne University Hospital Center, Saint-Etienne, France

© Springer-Verlag 2002

nolaryngology at the University of Saint-Etienne for bilateral sur-gical procedure, and 238 women and 32 men (mean age: 52 years,range: 19–82 years) underwent a near-total thyroidectomy. No pa-tient had undergone any thyroid surgery prior to this event. Preop-erative investigations and algorithm are given in Table 1. A tumorwas clinically suspected as a thyroid mass with a hard/fixed nod-ule, neck nodes, paralysis of the vocal cords and rapid changes inthe size or history of irradiation of the neck [31]. Prior to referralto this study, the endocrinology department evaluated patients withhyperthyroidism that would require surgical intervention. Patientswith Grave’s disease were not included in our study. Table 2 showsthe current accepted indications for MNG surgery.

Surgical technique for near-total thyroidectomy (NTT)

A slightly curvilinear transverse incision 3 cm above the head ofclavicles is made in the natural skin creases. The superior pole of thelobe is dissected first on the most diseased side with individual liga-tion of the vessels [14, 20]. The technique developed by Thompsonallows mobilization of the superior pole in a manner preserving theexternal branch of the superior laryngeal nerve [34]. The recurrentlaryngeal nerve (RLN) is identified below the level of the inferiorthyroid artery, because the nerve may be bifurcated before enteringthe larynx [19]. The thyroid capsule is swept away from the ves-sels, which are clamped, as they become adherent to the capsule.Therefore, blood supply to the parathyroid gland may be preservedlaterally. Progressively, resection of the lobe, the isthmus and thepyramidal lobe is performed with a thorough excision of all palpa-ble nodules recommended [33]. Dividing the inferior thyroid veinscompletes the inferior mobilization of the lobe. On the oppositeside of the thyroid, identification of the recurrent laryngeal nerve isalso performed in the inferior area. To avoid direct trauma anddevascularisation, the nerve is never skeletonised. On each side inthe adherent area, the recurrent laryngeal nerve may be incorpo-

rated in the lateral ligament (ligament of Berry-Gruber) [34]. Thecapsule is transected medially, and dissection is carried to the mid-line above the branches of the inferior thyroid artery. Approxi-mately 4 to 5 g (1cm3) of macroscopically healthy thyroid tissue isleft on the less diseased side of the superior pole. It is preferable toleave a small remnant of thyroid on one side to which the parathy-roid is adherent to prevent any accidental injury to the parathyroidgland. Bilaterally, 48 h wound drainage is considered useful for eachpatient.

Histopathological analysis

Surgical specimens were examined histologically to confirm thenature of the MNG lesion [32]. They were fixed in formaline for24 h, and the blocks were then embedded in paraffin overnight.Sections were cut, mounted and stained with hematoxylin andeosin. Routine gross examination of the serial cut sections pointedout diffuse or nodular enlargement, with such a nodular pattern en-compassing both solitary nodular goiter and multinodular goiter.Some lesions that appeared firm, partially or completely encapsu-lated, white to tan colored and occasionally calcified, hemorragicor necrotic might be indicative of cancer. Also, there were well-en-capsulated microcystic lesions in which the cavity was speculated,sometimes representative of papillary carcinoma, whereas totallysmooth-walled cysts were uncommonly cancerous [17]. Histologi-cally, follicular patterns were predominant in both adenomas andadenomatous goiters or multinodular goiters. The separation ofpapillary carcinoma from nodular goiter with prominent papillaryor pseudopapillary hyperplasias represented one of the differentialdiagnoses; a second was the distinction of the follicular variant ofpapillary carcinoma from follicular carcinoma [16]. The histopath-ological features for diagnosis of papillary carcinoma includedpapillae, characteristic cell patterns and sometimes psammomabodies and desmoplastic or inflammatory stroma.

Neoplastic papillae are usually formed by a central core of fi-brovascular stromal tissue surrounded by tumor cells, and theyhave been compared to ears of corn. Cells of papillary cancer ofthe thyroid are often characterized by the presence of enlarged wa-ter-clear or round-glass, grooved nuclei that are crowded and over-lap one another [4, 11]. They need to be distinguished frompseudo-clear nuclei where visible chromatin is still encountered inthe benign lesions [11].

Psammoma bodies are classically found in the tumor stroma.These lamellated structures apparently represent calcified “ghosts”of focal areas of papillae infarction, and their presence should leadto a careful search for papillary carcinoma, even if the thyroidgland appears benign. Despite the almost total or complete follicu-lar architectural pattern, identical findings are observed in the fol-licular variant of papillary cancer [11].

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Table 1 Algorithm in themanagement of thyroid multi-nodular disease. (TT total thy-roidectomy, NTT near totalthyroidectomy)

Investigations

Routine History, physical examinationIndirect laryngoscopySerum level of TSH, T3, T4, calcium, phosphorus, thyroid antibodiesUltrasonography of the neck, chest roentgenogram

Special studies Abnormal TSH → iodine scintigraphy. NTT if surgical indication.Compressive signs or intrathoracic extension → CT scan or MRI → NTTCalcitonin serum level (CL)Fine-needle aspiration (FNA)

Clinically suspected tumor Abnormal CL → TTFNA malignant or suspicious → NTT and frozen sections; if malignant → TTFNA benign/inadequate → NTT if surgical indication or FNA repeated and clinical follow up

Table 2 Indications for surgery

n %

Suspected malignancy 21 7.7(by fine-needle aspiration and/or clinically)

Thyrotoxicosis (toxic MNG) 75 27.7Pressure on cervical structures (tracheal deviation) 103 38Significant cosmetic deformity 18 6.6Intrathoracic extension of thyroid goiter (MRI) 53 19.6

Total 270 100

Follicular carcinoma of the thyroid is not diagnosable by fine-needle aspiration cytology since the diagnosis requires the demon-stration of invasion at the edges of the lesion. Similar problems ex-ist in evaluating such lesions from frozen sections. The gross ap-pearance of minimally invasive follicular carcinoma may differslightly from a benign nodule because of the thickness of the cap-sule. Histologically, follicles are predominantly round and smalland are often laid back to back, with trabecular areas also ob-served. Characteristically, the cells display numerous large and oc-casionally touching nuclei as well as low nuclear soundness withpossible mitotic activity [11, 17]. More significantly, invasion of thecapsule, invasion through the capsule and invasion into the veinsin or beyond the capsule represent the diagnostic criteria for carci-noma in a follicular thyroid neoplasm [17]. Diagnostic criteria forfollicular carcinoma are identical for oxyphilic tumors (Hürthlecells) and primary clear-cell neoplasms of the thyroid [10, 17].

Results

The weight of the surgical specimens ranged from 60 to560 g (mean: 120 g). Final pathological findings were be-nign in 237 cases (87.8%) (Table 3) and malignant in 33cases (12.2%) (Table 4). The definitions of the risk groupsin differentiated carcinoma of the thyroid have been de-fined according to the data from the Memorial Sloan-Ket-tering Cancer Center [31]: the “high-risk” patients includepatients over 45 years of age and with a tumor size greaterthan 4 cm, a follicular tumor or capsular effraction anddistant metastasis; the “low-risk” patients include thosebelow 45 years of age and with a tumor size less than 4 cm,papillary tumor and no distant metastasis; the “intermedi-ate-risk” group has been defined to include young patients

with aggressive tumors or elderly patients with less aggres-sive tumors. The decisions regarding the extent of thy-roidectomy and postoperative adjuvant therapy have beenindividualized based on these risk groups. A completethyroidectomy was performed when frozen sections con-firmed malignancy in the initial or controlateral lobe forthe three medullar carcinoma patients and for the twohigh-risk papillary carcinoma patients. When our patholo-gist was unable to confirm the diagnosis of suspected ma-lignancy, the neck was closed. When the final histologicexamination later confirmed the presence of malignancy,two high-risk papillary carcinoma patients underwent acompletion thyroidectomy within a week. No completionthyroidectomy was performed for the nine patients withmicroscopic or multicentric papillary carcinoma. Table 5shows complications following near total surgery in pa-tients with MNG.

Discussion

MNG is a common, benign disease with the incidence ofgoiter occurring at a rate of approximately 0.1% to 1.5%per year (female to male ratio: 6.4 to 1.5) [8, 31]. Themain indications for surgery in MNG are compressionsymptoms, which may be associated with intrathoracicextension of the goiter and cosmetic deformity, thyrotoxi-cosis and fear of malignancy [2, 8]. The serum TSH levelis a sensitive and reliable index of thyroid function. Chestradiography, ultrasonography and CT scan help to delin-eate the size and extent of a MNG in evaluating the symp-toms of compression [8, 31]. Although thyroid nodularityis common, the incidence of thyroid cancer is not high.The surgical decision in MNG has to be selective for thesuspicion of malignancy. Fine-needle aspiration (FNA)results are pivotal in assessing the cancer risk of promi-nent palpable and suspicious nodules [4, 8, 11]. Certainclinical features raise the clinical index of suspicion for athyroid nodule being malignant; these include hard, fixednodules, neck nodes, vocal cord paralysis and rapid growthof the nodule [31]. If there is a strong clinical suspicionthat the patient has a malignant problem, FNA biopsy canbe repeated. A clear cut relationship between thyroid can-

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Table 4 Final malignant pathology

n

Usual type of papillary carcinoma 19≥10 mm 10<10 mm (in one lobe) 6Microscopic multicentric disease 3

( in one lobe and opposite)

Follicular variant of papillary carcinoma 2

Undifferentiated (anaplastic) carcinoma 3

Medullary carcinoma 3

Lymphoma and Hashimoto’s thyroiditis 3

Follicular carcinoma 2

Hürthle cell carcinoma 1

Total 33 (12.2%)

Table 5 Postoperative complications

n %

Unilateral recurrent paralysisTemporary 9 3.3Permanent (>12 months) 4 1.4

Bilateral recurrent paralysis 0 0

HypocalcemiaTransient 31 11.4Permanent (>12 months) 10 3.7

Hematoma 5 1.8

Wound infection 2 0.7

Hypertrophic or keloid scar 14 5.1

Table 3 Final benign pathology

n %

Adenoma, follicular or microfollicular 148 62.4and colloid goiter

Hürthle cell adenoma 10 4.2Hashimoto’s thyroiditis 4 1.6Toxic multinodular goiter (hyperthyroidism) 75 31.6

Total 237 87.8

cer and previous neck radiotherapy has been well estab-lished [30, 31]. In our series no patient had a history ofneck irradiation, and many patients were treated withlevothyroxin for a long period prior to surgery. The levothy-roxin suppression therapy is often unsuccessful and is notadvocated for MNG patients [27].

The extent of thyroidectomy in the management ofMNG patients continues to be a major controversial issue[21, 24, 31]. Total thyroidectomy as a treatment for a be-nign thyroid disease was first advocated in 1976 by Perzik[24]. More surgeons now adopt this procedure [2, 3, 21].Total thyroidectomy is routinely advocated because of thehigh recurrence rate of benign MNG and the difficultiesof secondary procedures. The recurrence rate for partialbilateral thyroidectomy (a remnant tissue of 1 × 1×3 cm)is 32%, and the average time for recurrence is approxi-mately 9 years [3]. Near total thyroidectomy can be con-sidered as an intermediate procedure between total thy-roidectomy and partial bilateral thyroidectomy, with neartotal thyroidectomy requiring thorough excision of all in-traoperative palpable nodules and guided by preoperativeultrasonography. The thyroid tissue that is not removedmust be minimal, approximately 1 cm3, and postoperativetreatment with levothyroxin is required [7, 12, 33]. Use ofthese surgical and medical regimes results in only 2.5% ofthe patients experiencing recurrence [12]. A recurrent goi-ter may occur because of the development of new nodules(true recurrence) or because of the growth of a persistentmacroscopic or microscopic nodule remaining from a pre-vious thyroid operation [12]. No nodule recurrence oc-curred in our series, but the mean time of follow-up is in-sufficient. Well-trained surgeons have reported low mor-bidity rates for total thyroidectomy [2, 21]. In a review of540 thyroidectomies, Chonkich reported a 0.49% inci-dence of permanent vocal cord paralysis for subtotal thy-roidectomy and 1.4% for total thyroidectomy. Permanenthypoparathyroidism did not occur in any patient withsubtotal thyroidectomy and did occur in 5.9% of the pa-tients requiring total procedure for benign MNG [2]. Forpatients with malignant disease the two major argumentsproposed for a total thyroidectomy are the presence of mi-croscopic disease in the opposite lobe and the need of ra-dioactive iodine follow-up [31]. In patients with well-dif-ferentiated thyroid cancer the clinical incidence of recur-rence in the controlateral lobe is less than 5%, even thoughthe incidence of microscopic multicentric disease may befound in 66%, particularly in young patients [29, 30]. Withan adequate dose of I-131, all remaining thyroid tissue af-ter total or near total thyroidectomy can be ablated with-out causing excessive damage to surrounding tissues [30].

MNG surgical management has to be appropriate to thevarious histopathological findings. In our series, 12.2% ofMNG patients (33 of 270) have a final malignant pathol-ogy. Nineteen out of 33 patients had an usual type of pap-illary carcinoma. Microscopic papillary carcinoma occurredin only 3% of patients with MNG. In autopsy and surgicalseries the incidence of occult papillary thyroid carcinoma(microcarcinoma) varies from 2.7% to 35.6% [6, 17, 23].A high rate of prevalence of occult papillary carcinoma is

found by means of an accurate histologic examination,but many studies include lesions up to 15 mm in diameter.There is no clear association between the occurrence ofmicrocarcinoma and the underlying thyroid disease [6].Nevertheless, the presence of incidental occult papillarycarcinoma has little prognostic implication, and radioac-tive iodine is not advocated [31]. Factors including olderage, larger tumor size, distant metastases, capsular inva-sion and multifocality indicate an unfavorable prognosis[23]. Many variants of papillary carcinoma have been de-scribed based on the predominant histological pattern[17], including tall cell carcinoma with an increased riskof extrathyroid invasion [25] or the follicular variant, themost common variant of papillary carcinoma [17]. Al-though this neoplasm has nuclear features of usual papil-lary carcinoma, morphologically it is organized in a pre-dominantly follicular architectural pattern [16, 17]. Fine-needle aspiration and frozen sections have low sensitivityin the diagnosis of the follicular variant, and a surgeonmust be aware of this diagnostic difficulty [16]. In our se-ries some rare histopathological findings occurred: Hürthlecell carcinoma, also known as “oncocytic” variant of fol-licular carcinoma, has failure and survival rates very sim-ilar to those of follicular carcinoma [10]. A MNG associ-ated with Hashimoto’s thyroiditis must suggest to the sur-geon a possible evolution of a primary thyroid lymphoma[5, 18]. The choice of treatment in toxic MNG has longbeen a matter of controversy [15]. Antithyroid drugs, ra-dioiodine and surgery have been selected individually foreach patient, taking into consideration the age, the size ofthe goiter, the degree of hyperthyroidism and the patients’wish [1]. The advantages of surgery include a rapid curefor the disease and a permanent cure in more than 90% ofthe cases [1, 9, 22]. Surgery can be considered the treat-ment of choice in all patients with large toxic MNG [1, 15].To avoid the recurrence of thyrotoxicosis, a remnant of 4to 8 g of thyroid tissue seems to be preferable, even thoughthere is a higher incidence of hypothyroidism [9, 22].

Thus, in our experience, performing a near-total thy-roidectomy appears to be a suitable surgical procedure forpatients with MNG. Minimal residual thyroid tissue pro-vides a low rate of postoperative complications and allowsfurther appropriate management for the wide spectrum ofthe histopathological features that were witnessed.

Acknowledgement The authors would like to thank Anna Milan,PhD, Research Fellow from the University of Liverpool, UK, forrevising the English manuscript.

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