Axillary node metastasis from differentiated thyroid carcinoma with hürthle and signet ring cell differentiation. A case of disseminated thyroid cancer with peculiar histologic findings
© Chiofalo et al; licensee BioMed Central Ltd. 2012
Received: 29 September 2011
Accepted: 3 February 2012
Published: 3 February 2012
Differentiated thyroid cancer is usually associated with an excellent prognosis and indolent course. Distant metastases are rare events at the onset of thyroid cancer. Among these presentations, metastasis to the axillary lymph nodes is even more unusual: only few cases were previously reported in the literature; there has been no report of axillary lymph node metastasis from follicular thyroid carcinoma. Axillary lymph node metastasis generally arises in the context of disseminated disease and carries an ominous prognosis.
Here we present a case of axillary lymph node metastasis in the context of disseminated differentiated thyroid cancer. The patient underwent near total thyroidectomy and neck and axillary lymph node dissection. A histopathological diagnosis of poorly differentiated follicular carcinoma with "signet ring cells" and Hürthle cell features was established. The patient received radioactive iodine therapy and TSH suppression therapy. Subsequently his serum thyroglobulin level decreased to 44.000 ng/ml from over 100.000 ng/ml.
Discussion and Conclusion
Currently there are only few reported cases of axillary node metastases from thyroid cancer, and to our knowledge, this is the first report on axillary lymph node metastasis from follicular thyroid carcinoma. "Signet ring cell" is a morphologic feature shared by both benign and, more rarely, malignant follicular thyroid neoplasm, and it generally correlates with an arrest in folliculogenesis. Our case is one of the rare "signet ring cells" carcinomas so far described.
KeywordsThyroid cancer Axillary lymph node metastasis Distant metastases Signet ring cells
Differentiated thyroid cancer is usually associated with an excellent prognosis and indolent course. Distant metastases are rare events at the onset of thyroid cancer. Their incidence is about 4%, with an overall risk which is lowest for papillary thyroid cancers (2%) and highest for follicular (11%) and Hürthle cell carcinomas (12%) . Among these presentations, metastasis to the axillary lymph nodes is even more unusual. It generally arises in the context of disseminated disease and carries an ominous prognosis . Herein, we present the first ever reported case of axillary lymph node metastasis from follicular thyroid carcinoma. Interestingly this presentation was associated with peculiar histologic features described, so far, only in four other cases of follicular-derived thyroid carcinoma.
We treated the primary thyroid tumour with a near-total thyroidectomy including central plus right neck dissection and the addition of right axillary lymph node dissection.
On gross pathological examination, the thyroidectomy specimen weighted 74 g; the right lobe was enlarged, measuring 7.5 × 3.5 × 3 cm. The cutting surface showed a solid nodule, 3.8 × 2.5 cm in size at the apex of the right lobe. Microscopic examination of the thyroid tumor showed a follicular neoplasm with two growth patterns: micro- and macrofollicular areas alternating with predominantly cribriform and solid/insular areas. A thick, fibrous capsule was still evident around the nodule although it was completely invaded by the tumor; extensive vascular invasion, within and beyond the tumor capsule, was also observed.
Discussion and Conclusion
Currently there are only few reported cases of metastases to the axillary lymph nodes in patients with thyroid cancer and, to our knowledge, this is the first report on metastasis to the axillary lymph nodes from follicular thyroid carcinoma. In the previously published cases, the primary tumours were mostly papillary thyroid carcinomas [2–9], and less frequently medullary thyroid carcinoma , sclerosing mucoepidermoid carcinoma with eosinophilia , mucin-producing poorly differentiated adenocarcinoma  and muco-epidermoid carcinoma . In most of the previously reported cases, axillary lymph node metastases occurred in the context of disseminated disease, almost always as late recurrence. In our case it occurred at the presentation in the context of a disseminated follicular thyroid carcinoma. Some authors hypothesized that retrograde spread of the tumor into the axilla could be related to the blockage of the cervical lymphatic vessels by metastatic lymph nodes or by surgical manipulation . This hypothesis seems consistent with our case. In our patient, in fact, there was a massive lymph nodes involvement of the neck levels IV and V. The axillary fat is contiguous with that of the inferolateral neck, so we hypothesize that the spread to the axillary lymph nodes could be related to the obstruction of lymphatic vessels. Follicular thyroid cancer has a high propensity to invade blood vessels and show-up as distant metastases, but the role of angiogenesis and lymphangiogenesis in thyroid cancer pathogenesis has not been clarified . So, in the present case, it can't be established whether the axillary lymph node involvement is related to an hematogenous dissemination.
The pathological features of the neoplasm represent the second interesting aspect of our case. Primary mucinous carcinoma of the thyroid is extremely rare . In the WHO classification, mucinous carcinoma of the thyroid is defined as a tumor characterized by clusters of neoplastic cells surrounded by extensive extracellular mucin deposit. On the other hand, many thyroid neoplasms, such as follicular adenoma, may produce mostly intracellular mucins, in particular the "signet ring cell" variant; moreover mucus may be produced also by carcinomas of papillary, follicular, medullary and mucoepidermoid subtypes. Mlynek identified mucin in 50% and 35% of papillary and follicular tumors, respectively, and emphasized that mucin production by follicular-derived tumors can be commoner than usually thought . In the current case, "signet ring cells" and mucin-producing areas were frequently found.
To date, only four cases have been reported of follicular-derived thyroid carcinomas which show signet ring features: three by Schröder et al.  and one by Fellegara et al. in a poorly differentiated Hürthle cell carcinoma . In a previous report, Gherardi et al. has presented convincing evidence that "signet ring cells" contained altered or abnormal thyroglobulin . Fellegara and Rosai  have reported how vacuoles result from intracytoplasmic accumulation of thyroglobulin as demonstrated by immunohistochemistry, while they appear bordered by microvilli on electronic microscopy. This may suggest that they are intracytoplasmic follicular lumina rather than secretion vacuoles and represent the morphologic expression of an arrest in folliculogenesis [17, 18].
In the present case, both thyroglobulin and mucoid secretion were demonstrated in the "signet-ring cells", according to previous reports . Interestingly, microscopic examination of axillary metastases showed neoplastic cells with ample granular eosinophilic cytoplasm and pleomorphic nuclei, the typical features of Hürthle cell carcinomas, similarly to two previously reported cases of "signet ring cells" carcinoma [16, 17]; on the other hand, the "signet ring cell" features, in our case, were prominent in the primary thyroid tumor, while they were lacking in metastases. "Signet-ring cells" are hence to be considered a morphologic feature shared by both benign and, more rarely, malignant follicular thyroid neoplasm, and probably reflect an arrest in folliculogenesis. Our case is one of the rare "signet ring cells" carcinomas so far described.
Written informed consent was obtained from the patient for publication of this case report and any accompanying images.
- Sampson E, Brierley JD, Le LW, Rotstein L, Tshang RW: Clinical management and outcome of papillary and follicular (differentiated) thyroid cancer presenting with distant metastasis at diagnosis. Cancer. 2007, 110: 1451-1456. 10.1002/cncr.22956.View ArticlePubMedGoogle Scholar
- Nakayama H, Wada N, Masudo Y, Rino Y: Axillary lymph node metastasis from papillary thyroid carcinoma: report of a case. Surg Today. 2007, 37: 311-315. 10.1007/s00595-006-3395-2.View ArticlePubMedGoogle Scholar
- Ueda S, Takahashi H, Meihi T, Nakata T, Ueda S, Takahashi H, Meihi T, Nakata T: A case of Axillary lymph nodes recurrence of papillary carcinoma 7 years after operation. Nippon Rinsho Geka Gakkai Zasshi (J Jpn Surg Assoc). 1996, 57: 2934-2937. in Japanese with English abstractGoogle Scholar
- Ers V, Galant C, Malaise J, Rahier J, Daumerie C: Axillary lymph node metastasis in recurrence of papillary thyroid carcinoma: a case report. Wien Klin Wochenschr. 2006, 118 (3-4): 124-127. 10.1007/s00508-006-0533-1.View ArticlePubMedGoogle Scholar
- Kepenekci I, Demirkan A, Cakmak A, Tugbay T, Ekinci C: Axillary lymph node metastasis as a late manifestation of papillary thyroid carcinoma. Thyroid. 2009, 19 (4): 417-419. 10.1089/thy.2008.0296.View ArticlePubMedGoogle Scholar
- Angeles-Angeles A, Chable-Montero F, Martinez-Benitez B, Albores-Saavedra J: Unusual metastases of papillary thyroid carcinoma: report of 2 cases. Ann Diagn Pathol. 2009, 13 (3): 189-196. 10.1016/j.anndiagpath.2008.02.010.View ArticlePubMedGoogle Scholar
- Lal G, Ituarte P, Duh QY, Clark O: The axilla as a rare site of metastatic thyroid cancer with ominous implications. Abstract 74th Annual Meeting of ATA. 2003Google Scholar
- Koike K, Fujii T, Yanaga H, Nakagawa S, Yokoyama G, Yahara T, Hanzawa M, Kato S, Shirouzu K: Axillary lymph node recurrence of papillary thyroid microcarcinoma: report of a case. Surg Today. 2004, 34 (5): 440-443. 10.1007/s00595-003-2735-8.View ArticlePubMedGoogle Scholar
- Krishnamurthy A, Vaidhyanathan A: Axillary lymph node metastasis in papillary thyroid carcinoma: report of a case and review of the literature. J Cancer Res Ther. 2011, 7 (2): 220-222. 10.4103/0973-1482.82936.View ArticlePubMedGoogle Scholar
- Shehadeh NJ, Vernick J, Lonardo F, Madan SK, Jacobs JR, Yoo GH, Kim HE, Ensley JF: Sclerosing mucoepidermoid carcinoma with eosinophilia of the thyroid: a case report and review of the literature. Am J Otolaryngol. 2004, 25 (1): 48-53. 10.1016/S0196-0709(03)00096-6.View ArticlePubMedGoogle Scholar
- Mizukami Y, Nakajima H, Annen Y, Michigishi T, Nonomura A, Nakamura S: Mucin-producing poorly differentiated adenocarcinoma of the thyroid. a case report. Pathol Res Pract. 1993, 189 (5): 608-612. 10.1016/S0344-0338(11)80381-X.View ArticlePubMedGoogle Scholar
- Minagawa A, Iitaka M, Suzuki M, Yasuda S, Kameyama K, Shimada S, Kitahama S, Wada S, Katayama S: A case of primary mucoepidermoid carcinoma of the thyroid: molecular evidence of its origin. Clin Endocrinol. 2002, 57: 551-556. 10.1046/j.1365-2265.2002.01599.x.View ArticleGoogle Scholar
- de la Torre NG, Buley I, Wass JA, Turner HE: Angiogenesis and lymphangiogenesis in thyroid proliferative lesions: relationship to type and tumour behaviour. Endocr Relat Cancer. 2006, 13 (3): 931-944. 10.1677/erc.1.01210.View ArticlePubMedGoogle Scholar
- Kondo T, Kato K, Nakazawa T, Miyata K, Murata S-I, Katoh R: Mucinous carcinoma (poorly differentiated carcinoma with extensive extracellular mucin deposition) of the thyroid: a case report with immunohistochemical studies. Hum Pathol. 2005, 36: 698-701. 10.1016/j.humpath.2005.04.012.View ArticlePubMedGoogle Scholar
- Mlynek MK, Richter HJ, Leder LD: Mucin in carcinomas of the thyroid. Cancer. 1985, 56: 2647-2650. 10.1002/1097-0142(19851201)56:11<2647::AID-CNCR2820561119>3.0.CO;2-8.View ArticlePubMedGoogle Scholar
- Schröder S, Böcker W: Signet ring cell thyroid tumors: a follicle cell tumor with arrest of folliculogenesis. Am J Surg Pathol. 1985, 9: 619-629. 10.1097/00000478-198509000-00001.View ArticlePubMedGoogle Scholar
- Fellegara G, Rosai J: Signet ring cells in a poorly differentiated Hurthle cell carcinoma of the thyroid combined with two papillary microcarcinomas. Int J Surg Pathol. 2007, 15 (4): 388-390. 10.1177/1066896907304993.View ArticlePubMedGoogle Scholar
- Gherardi G: Signet ring "mucinous" thyroid adenoma: a follicle cell tumor with abnormal accumulation of thyroglobulin and a peculiar histochemical profile. Histopathology. 1987, 11: 317-326. 10.1111/j.1365-2559.1987.tb02636.x.View ArticlePubMedGoogle Scholar
- The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/12/55/prepub
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