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Unusual primary tumors presenting as papillary carcinomas metastatic to the neck.

Abstract

The presence of a metastatic papillary carcinoma in the neck is presumptive evidence of a primary thyroid neoplasm since neck metastases of other primary tumors are uncommon. Immunohistochemical studies may be required to diagnose these metastases. We report 2 cases in which an unrelated tumor mimicked a thyroid malignancy. Both patients had been referred for evaluation of enlarged lymph neck nodes without any other symptoms. In both cases, a lymph node biopsy identified a metastatic papillary adenocarcinoma that was believed to be consistent with a thyroid primary. Thyroidectomy was not performed in either case. Further investigations led to the diagnosis of other primary tumors that were unrelated to the thyroid; the unrelated primaries were an ovarian serous tumor in one patient and a papillary renal cell carcinoma in the other.

Introduction

Metastases to the cervical lymph nodes, which exhibit the features of papillary adenocarcinoma, are usually interpreted as a thyroid malignancy. However, it is necessary to consider possible primary sites other than the thyroid. In this report, we describe 2 cases of papillary neck metastases that were eventually diagnosed as tumors unrelated to the thyroid: an ovarian carcinoma and a renal cell carcinoma (RCC). These cases illustrate the difficulty encountered in diagnosing these unusual primaries. We also discuss the treatment of these patients, as well as the need to systematically perform immunohistochemical studies.

Case reports

Patient 1. A 49-year-old woman presented with a left neck mass; she reported no other signs or symptoms. Palpation of the thyroid gland revealed the presence of a 2-cm basal nodule on the left lobe. Ultrasonography detected three 3-cm lymph nodes on the left at level III and one 3.1-cm lymph node at level IV. The results of thyroid function testing were normal.

Fine-needle aspiration (FNA) of the basal nodule identified it as a benign vesicular lesion. FNA cytology of the lymph nodes revealed very abundant cells arranged in clusters with nuclear enlargement, mild atypia, and some mitotic figures (figure 1, A). Based on the lymph node findings, the patient was diagnosed with a metastatic adenocarcinoma with papillary architecture.

The presence of cytologic atypia is not typical of papillary thyroid carcinoma, but such a finding is not sufficient to rule out this diagnosis. The association of the papillary metastatic carcinoma and the thyroid nodule led us to suspect a primary thyroid tumor.

To determine the stage of the disease, we obtained computed tomography (CT) of the cervicothoracoabdominal region. In addition to the multinodular goiter and left-sided cervical nodules, CT also demonstrated bilateral axillary adenopathy. An excisional biopsy of the left axillary node identified a moderately differentiated metastatic adenocarcinoma (figure 1, B).

Immunohistochemistry was negative for thyroglobulin (Tg), mammaglobin, and GCDFP-15 and positive for WT1 protein, suggesting that the primary tumor was of gynecologic origin. An abdominal CT detected a solid left ovarian lesion, which led to the diagnosis of an ovarian papillary carcinoma with metastases to the neck.

[FIGURE 1 OMITTED]

After receiving six cycles of chemotherapy with carboplatin and paclitaxel, the patient underwent a bilateral salpingo-oophorectomy, a total abdominal hysterectomy, a pelvic lymphadenectomy, an omentectomy, and an appendectomy. The final diagnosis was a left ovarian serous carcinoma without pelvic metastasis.

After 34 months of follow-up, the patient showed no signs of locoregional recurrence or distant metastasis.

Patient 2. A 42-year-old man was admitted for evaluation of a 3-month history of bilateral supraclavicular lymph nodes that crossed from level III to level IV. He reported no associated signs or symptoms. His thyroid gland was not palpable.

A biopsy of a left supraclavicular lymph node identified a metastatic papillary adenocarcinoma without atypia; some rare follicular structures were filled with eosinophilic material that mimicked a colloid (figure 2). These findings were consistent with a thyroid carcinoma. Immunostaining with anti-Tg, anti-TTF1, and anticytokeratin 7 was negative, and thus we were required to carry out further investigations.

A cervicothoracoabdominal CT demonstrated posterior mediastinal, lomboaortic, and laterocervical adenopathy, but no parenchymal masses. F18-fluorodeoxyglucose (FDG) positron-emission tomography/ computed tomography (PET/CT) detected lymph node metastases. Follow-up thoracoabdominal CT angiography 1 month later led to the identification of a 4-cm nodular lesion in the sinus of the left kidney. Biopsy of the renal mass established a diagnosis of papillary RCC with wide lymphatic spread.

The patient was administered chemotherapy with sunitinib and temsirolimus, but his disease continued to progress. He was subsequently switched to third-line therapy with sorafenib.

Discussion

In a case of cervical lymph node metastatic carcinoma with papillary architecture, thyroid malignancy must be the first consideration. First, thyroid carcinoma is one of the most common neoplasms in the head and neck. In the United States, its incidence from 2004 to 2008 was 5.6 per 100,000 men and 16.3 per 100,000 women, and the incidence continues to increase. (1) Second, palpable cervical node metastasis is a common sign of papillary thyroid carcinoma, and in some cases, the primary tumor is a micropapillary carcinoma. (2)

Chow et al observed lymph node metastasis in 25.7% of patients with micropapillary ([less than or equal to] 5 mm) thyroid carcinoma at diagnosis. (3) However, different carcinomas with papillary architecture have been described, including lymphophilic tumors such as ovarian, renal cell, and lung carcinomas. (4)

[FIGURE 2 OMITTED]

Ovarian tumors with supradiaphragmatic lymphadenopathy are rare; hence, they are frequently misdiagnosed. (5-6) The prognosis varies significantly depending on the stage of the disease, primarily the degree of extension. Therefore, an early histologic diagnosis of an ovarian tumor is especially important.

As far as we know, only 6 cases of papillary RCC presenting as a neck node metastasis have been previously reported in the literature. (7-10) In 4 of these cases, lymph node biopsies identified the metastasis as a papillary carcinoma. Metastatic papillary RCC cannot be distinguished histologically from papillary thyroid carcinoma. In 3 of these cases, the thyroid gland was normal after thyroidectomy. Immunostaining for anti-Tg was negative in 4 cases. (7,8)

RCC is well known for its ability to metastasize to nearly every organ of the body. While metastases usually occur several years after the diagnosis of the renal primary, as many as 30% of patients already have metastatic disease at their initial presentation. (11) The main sites of RCC metastasis are the lung, bone, brain, skin, and thyroid; cervical lymph node involvement is unusual. (12)

Since FDG is excreted renally, FDG-PET/CT may contribute only slightly to the clinical evaluation of urologic tumors. Indeed FDG-PET/CT seldom identifies the primary tumor when RCC initially presents as a metastasis. (13)

In its management guidelines, the American Thyroid Association recommends measuring Tg in the washout of lymph node FNA specimens. (14) Ultrasonography-guided FNA allows pathologists to obtain a cytologic result and to make a valid Tg measurement in the needle washout. Along with imaging results, this allows clinicians to arrive at an early diagnosis of a thyroid neck metastasis. However, 6 to 8% of washout results will be false negatives. (15,16)

In conclusion, for patients who present with a neck mass with papillary carcinoma histology, it is recommended that Tg be measured in the washout of the lymph node FNA specimen and that anti-Tg and anti-TTF1 immunostaining be performed on a lymph node biopsy specimen to avoid a misdiagnosis of a primary papillary thyroid cancer. Total thyroidectomy carries a risk of hypoparathyroidism and injury to the recurrent laryngeal nerve, so unnecessary thyroidectomy should be avoided. Negative results on Tg determination and anti-Tg staining in a neck metastatic papillary carcinoma should prompt the consideration of other potential primary sites of origin, especially the ovary and kidney.

Agnes Dupret-Bories, MD, PhD; Marc Wilt, MD; Pierre Kennel, MD; Anne Charpiot, MD, PhD; Jean-Francois Rodier, MD, FACS

From the Department of Otorhinolaryngology-Head and Neck Surgery, Institut Universitaire du Cancer, Toulouse, France (Dr. DupretBories); the Department of Otorhinolaryngology-Head and Neck Surgery, CHU Hautepierre, Strasbourg, France (Dr. Dupret-Bories and Dr. Charpiot); the Department of Pathology, Centre Paul Strauss, Strasbourg (Dr. Wilt); the Department of Otorhinolaryngology, CHR Pasteur, Colmar, France (Dr. Kennel); and the Department of Surgery, Clinique Saint-Anne, Strasbourg, France (Dr. Rodier). The cases described in the article occurred at CHU Hautepierre and CHR Pasteur.

Corresponding author: A. Dupret-Bories, MD, Department of Otorhinolaryngology-Head and Neck Surgery, Institut Universitaire du Cancer, Avenue Hubert Curien, 31100 Toulouse, France. Email: Dupret-Bories.Agnes@iuct-oncopole.fr

References

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(2.) Bruno R, Giannasio P, Chiarella R, et al. Identification of a neck lump as a lymph node metastasis from an occult contralateral papillary microcarcinoma of the thyroid: Key role of thyroglobulin assay in the fine-needle aspirate. Thyroid 2009;19(5):531-3.

(3.) Chow SM, Law SC, Chan JK, et al. Papillary microcarcinoma of the thyroid--prognostic significance of lymph node metastasis and multifocality. Cancer 2003;98(1):31-40.

(4.) Amin MB, Tamboli P, Merchant SH, et al. Micropapillary component in lung adenocarcinoma: A distinctive histologic feature with possible prognostic significance. Am J Surg Pathol 2002;26(3):358-64.

(5.) Patel SV, Spencer JA, Wilkinson N, Perren TJ. Supradiaphragmatic manifestations of papillary serous adenocarcinoma of the ovary. Clin Radiol 1999;54(11):748-54.

(6.) Rodier JF, Dupret A, Weitbruch D, et al. Prevalent metastatic axillary lymphadenopathy from ovarian cancer: A diagnostic pitfall [in French], J Chir (Paris) 2009;146(2):226-7.

(7.) Giuliani A, Caporale A, Borghese M, et al. Papillary renal cell carcinoma presenting as nodal metastases to the neck. J Exp Clin Cancer Res 1999; 18(4):579-82.

(8.) Homan MR, Gharib H, Goellner JR. Metastatic papillary cancer of the neck: A diagnostic dilemma. Head Neck 1992;14(2): 113-18.

(9.) Arrabal-Polo MA, Merino-Salas S, Arrabal-Martin M. Giant cervical adenopathy as first manifestation of renal cell carcinoma. Int J Dermatol 2013;52(9):1119-20.

(10.) Ozkiris M, Kubilay U, Sezen OS. Cervical lymph node metastasis in renal cell carcinoma. J Oral Maxillofac Pathol 2011;15(2):211-13.

(11.) Wayne M, Wang W, Bratcher J, et al. Renal cell cancer without a renal primary. World J Surg Oncol 2010;8:18.

(12.) Spreafico R, Nicoletti G, Ferrario F, et al. Parotid metastasis from renal cell carcinoma: A case report and review of the literature. Acta Otorhinolaryngol Ital 2008;28(5):266-8.

(13.) Oyama N, Okazawa H, Kusukawa N, et al. 11C-acetate PET imaging for renal cell carcinoma. Eur J Nucl Med Mol Imaging 2009;36 (3):422-7.

(14.) American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer. Falls Church, Va.: American Thyroid Association. In press.

(15.) Pacini F, Fugazzola L, Lippi F, et al. Detection of thyroglobulin in fine needle aspirates of nonthyroidal neck masses: A clue to the diagnosis of metastatic differentiated thyroid cancer. J Clin Endocrinol Metab 1992;74(6):1401-4.

(16.) Boi F, Baghino G, Atzeni F, et al. The diagnostic value for differentiated thyroid carcinoma metastases of thyroglobulin (Tg) measurement in washout fluid from fine-needle aspiration biopsy of neck lymph nodes is maintained in the presence of circulating anti-Tg antibodies. J Clin Endocrinol Metab 2006;91(4):1364-9.
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Title Annotation:ORIGINAL ARTICLE
Author:Dupret-Bories, Agnes; Wilt, Marc; Kennel, Pierre; Charpiot, Anne; Rodier, Jean-Francois
Publication:Ear, Nose and Throat Journal
Article Type:Clinical report
Date:Oct 1, 2015
Words:1840
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