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research-article2015

IJSXXX10.1177/1066896915617026International Journal of Surgical PathologySquillaci et al

Case Reports

Mucinous Variant of Follicular Carcinoma of the Thyroid Gland: Case Report and Review of the Literature

International Journal of Surgical Pathology 1­–7 © The Author(s) 2015 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/1066896915617026 ijs.sagepub.com

Salvatore Squillaci, MD1, Antonio Pitino, MD2, Cinzia Spairani, MD2, Mauro Ferrari, MD2, Eugenio Carlon, MD3, and Maria Fabia Cosimi, MD2 Abstract The rare reports of mucinous variant of follicular carcinoma of the thyroid gland have not provided enough evidence to support the recognition of these tumors as a distinct clinicopathologic entity or to understand their etiopathogenesis. We report the fourth case of mucinous variant of follicular carcinoma displaying a minimally invasive tumor with diffuse expression of thyroglobulin, TTF-1, CD56, PAX-8, cytokeratins 7 and 19, in the absence of monoclonal carcinoembryonic antigen (CEA), cytokeratin 20, chromogranin, HBME-1, P63 expression, and BRAF gene mutation, in a 51-year-old woman who is alive without signs of disease 13 months after total thyroidectomy, bilateral neck dissection, and radioactive iodine. Herein, fine-needle aspiration cytology disclosed “worrisome” cytologic features consisting of large epithelial cells arranged in clusters or singularly, with high nucleocytoplasmic ratio, nuclear grooves and evident nucleoli which were shared by those of mucin-producing papillary thyroid carcinoma. Therefore, knowledge of the cytological and histopathological spectrum of this lesion is important to avoid misdiagnosis. The morphologic clues leading to the correct diagnosis of mucinous variant of follicular neoplasm have been correlated with the data of the literature, and the differential diagnosis is briefly discussed. Keywords thyroid tumors, mucin, follicular carcinoma, fine-needle aspiration

Introduction Mucinous tumors represent a subgroup of carcinomas exhibiting large amounts of mucus, forming gelatinous lakes into which more or less aggregated tumor cells are enmeshed. This morphological statement applies with some modifications to about 10% to 20% of colonic, 5% of breast, 3% of ovarian, and 1% of pancreatic, vesical, and prostatic carcinomas. Common phenotypic and genetic patterns may be shared by mucinous cancers from colon, pancreas, breast, and ovary, among which preferential expression of the MUC2 gene, uncommon p53 gene mutation and frequent K-ras gene mutation, but marked prognostic differences have been reported.1 In the thyroid, the occasional production of mucin-like substances by cells of primary neoplasms is a well-known phenomenon; however, true primitive mucinous adenocarcinomas of the thyroid gland are extremely rare and their place in the classification of thyroid tumors has been long a matter of debate.2-8 Mucoepidermoid carcinomas of the thyroid have been rarely described and, in addition, mucins have been found in lymph node metastases from papillary carcinomas, as well as in medullary and poorly

differentiated cancers.5,9-11 There are also several published examples of mucin-producing follicular adenomas of the thyroid.12-14 In addition, prevalently extracellular acid mucin-like material has been occasionally reported in nonneoplastic thyroid conditions, such as nodular hyperplasia and Basedow’s disease.6,15 Extracellular mucinous pools in follicular carcinomas, including Hürthle cell tumors, are an exceptional event first described in 1980 by Deligdisch et al,16 only 2 further cases have been reported so far.17,18 In this study, we describe the clinical and pathologic features of a follicular carcinoma of the thyroid showing extensive areas of stromal mucin deposition. In analogy with the neoplasm

1

Division of Anatomic Pathology, Hospital of Vallecamonica, Esine (Bs), Italy Division of Anatomic Pathology, Hospital “San Giacomo”, Novi Ligure (AL), Italy 3 Division of Radiology, Hospital of Acqui Terme (AL), Italy 2

Corresponding Author: Salvatore Squillaci, Division of Anatomic Pathology, Hospital of Vallecamonica, Via Manzoni 142, 25040 Esine, Italy. Email: [email protected]

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Figure 1.  Ultrasonography shows a 23 mm hypodense solid lesion in the right lobe of the thyroid.

Figure 2.  Fine-needle aspiration cytology. High magnification shows cluster of tumor cells having vesicular nuclei with occasional nucleoli (hematoxylin and eosin stain).

reported by Cretney et al,17 we designated this tumor as a mucinous variant of follicular carcinoma (MVFC).

Case Report In May 2014, a 51-year-old woman was admitted to the Hospital of Acqui Terme (AL), Italy, because of a painless solitary nodule in the right lobe of the thyroid. Ultrasonography identified a solid hypodense lesion of 23 mm in the greatest diameter (Figure 1). The patient was euthyroid; clinical and laboratory workup was otherwise unremarkable. Fine-needle aspiration cytology of the thyroid nodule was carried out. Fine-needle aspiration cytology smears were fixed in 95% alcohol and stained with both Papanicolaou and hematoxylin and eosin stains. The aspirate was quite cellular, characterized by several cell clusters and single epithelial cells of the thyroid in a bloody background, with rare colloid, and abundant mucinous matrix enmeshing the elements. The cells were large, round to polyhedral, with high nucleocytoplasmic ratio, nuclear grooves and evident nucleoli. These features were suspicious of malignancy (Tir 4), suggesting a follicular variant of papillary carcinoma (Figure 2). Therefore, the patient was submitted to total thyroidectomy and bilateral cervical lymphadenectomy, followed by radioactive iodine. After surgery, the patient had an uneventful recovery and there is no evidence of recurrence 13 months later. The gross specimen (measures of the right thyroid lobe: 4.5 × 2.4 × 1.8 cm) showed a well-demarcated round to oval shaped mass measuring 2.5 cm in largest diameter. On cut surface, the lesion was pale yellow to whitish and translucent, with a myxoid and stringy appearance. No lesions were observed in the isthmus or the left lobe. There was no evidence of metastatic disease in the bilateral cervical lymph nodes.

Figure 3.  The tumor is encapsulated and consists of anastomosing cords of cells.

Microscopically, the tumor was encapsulated and mainly characterized by a striking microcystic and reticular architecture, consisting of anastomosing cords and sheets of neoplastic cells that coexisted with occasional follicular structures, floating in abundant extracellular basophilic mucin pools (Figure 3). Only focal minimal capsular invasion was observed. There was no evidence of extrathyroid extension or vascular invasion. The neoplastic cells were polygonal, uniform, with round to oval nuclei, scant ill-defined cytoplasm, and evenly distributed chromatin. Evident nucleoli were also detected at high magnification; intracytoplasmatic vacuoles with compression and displacement of nuclei (signet-ring cell change) was rarely seen (Figure 4A). Neither nuclear grooves nor inclusions were observed. The mucoid material present

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Figure 4.  (A) Reticular growth pattern of the tumor cells and abundant mucinous stroma are seen. (B) Diffuse thyroglobulin immunoexpression is observed in the cytoplasm of tumor cells. (C) The neoplastic cells are diffusely positive for cytokeratin 19. (D) The tumor cells are diffusely stained with CD56.

both within follicular lumens and in the spaces among neoplastic cell cords, was positive for Alcian-PAS (pH 2.5), but not for PAS (periodic acid-Schiff reaction with previous diastase digestion [D-PAS]) thus demonstrated to be acidic mucin. Intracytoplasmic mucin was rarely identified. Immunohistochemically, the neoplastic cells were diffusely positive for thyroglobulin, TTF-1, CD56, PAX-8, CK7, and CK19 and negative for chromogranin, CK20, monoclonal carcinoembryonic antigen (CEA), HBME-1, P63 (Figure 4B-D). Mutation status in the BRAF gene was tested using polymerase chain reaction and reverse dot blot for V600A, V600D, V600E, V600G, V600K, V600M, V600R, and K601E. No mutation was detected in the neoplastic cells. Based on the light microscopic morphology, immunostaining profile and molecular features, the neoplasm was classified as a minimally invasive MVFC.

Discussion Mucinous variant of follicular carcinoma is a very unusual histological variant of follicular thyroid neoplasm included in the current World Health Organization (WHO)

classification of thyroid tumors that represents a diagnostic challenge to the pathologist who must answer several questions.19 First, its morphological features resemble a large spectrum of malignant extrathyroid conditions, which should be ruled out in the diagnostic process. The striking microcystic and reticular architecture with mucin deposition featured by the present case and by those previously reported (Table 1) prompts differential diagnosis with a metastasis from bronchial, mammary, ovarian, gastrointestinal, salivary gland, or renal carcinoma, an uncommon situation generally associated to widespread neoplastic diffusion.2 Moreover, the presence of solid and follicular clusters of neoplastic cells progressively merging with mucin pools and usually preserving a thyroidspecific immunoprofile should favor a diagnosis of MVFC.2 A thorough clinical and histopathological workup could be therefore mandatory to definitely exclude a metastasis to the thyroid especially in cases with clinical and/or immunophenotypic unexpected findings.7 Another important point is to be certain that the mucin producing neoplasm fully belongs to the category of “follicular thyroid carcinoma” reported in the WHO classification.19

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Kim et al20

Kim et al20

Present case

4

5

6

51/F

47/F

58/M

50/F

64/M

54/F

Age (Years)/ Gender

2,5

1,5

0,6

3,5

6,5

2,5

Tumor Size (cm)

Right thyroid lobe

Right thyroid lobe

Right thyroid lobe / lower pole

Right thyroid lobe

Left thyroid lobe

Right thyroid lobe

Location

Discohesive single cells and clusters of elements with nuclear grooves and prominent nucleoli, suggestive of papillary carcinoma

Minimally invasive follicular carcinoma

Follicular adenoma

Scattered discohesive and occasional clusters of cells with nuclear inclusions, scanty to abundant granular cytoplasm and rare atypical mitoses within a sticky mucinous background suggestive of papillary carcinoma vs follicular neoplasm NA

NA

Thyroglobulin+, TTF1+, cyclin D1−, Cam5.2−, CD56−, p53−, calcitonin−, CK19−, galectin3−, HBME1−, synaptophysin−, chromogranin−, CEA−, 34βE12 cytokeratin−, SMA− TTF1+, thyroglobulin+, CK7+, CK19+, CD56+, PAX-8+, CK20−, CEA−, chromogranin−, HBME-1−, P63−

TTF1+, thyroglobulin+, NSE+ weak, calcitonin−, chromogranin−, synaptophysin−, CEA−, S100− Thyroglobulin+, TTF1+, cyclin D1−, Cam5.2−, CD56−, p53−, calcitonin−, CK19−, galectin 3−, HBME-1−, synaptophysin−, chromogranin−, CEA−, 34βE12 cytokeratin−, SMA−

BRAF mutation (-)

BRAF mutation (-)

BRAF mutation (-)

NA

NA

Thyroglobulin+, synaptophysin+, CD56+, CEA+, CKMNF116+, calcitonin−

Many poorly cohesive sheets, clumps, and single cells enmeshed within a mucinous matrix with large, sometimes eccentric, nuclei and conspicuous nucleoli suggestive of primary mucinous neoplasm

NA

NA

NA

Molecular Analysis

Immunohistochemical Findings

Cytologic Features

Follicular adenoma

Minimally invasive follicular carcinoma

Follicular carcinoma with extensive areas of mucin production Follicular carcinoma with lymph node metastasis

Histologic Diagnosis

Abbreviations: Ref., reference; F, female; M, male; NA, not available; ANED, alive with no evidence of disease; SMA, smooth muscle actin; CK, cytokeratin; CEA, carcinoembryonic antigen.

Cretney et al17

Levine et al18

2

3

Deligdisch et al16

Authors

1

Case No. Treatment

Total thyroidectomy, neck dissection, oral radioactive iodine

Total thyroidectomy

Lobectomy

Total thyroidectomy, left radical neck dissection, oral radioactive iodine, external beam radiotherapy Subtotal thyroidectomy

Partial thyroidectomy

Table 1.  Clinicopathologic Characteristics and Immunohistochemical Profile of Thyroid Follicular Neoplasms Showing Extracellular Mucin Deposition.

ANED at 13 months

ANED at 27 months

ANED at 28 months

NA

ANED at 14 months

NA

Followup

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Squillaci et al The occurrence of the mucinous substances in thyroid tumors is considered to be extremely low. A mucinous adenocarcinoma of the thyroid was first described by Diaz-Perez et al3 in 1976. In subsequent years, other reports have found that focal extracellular and intracellular mucin expression was significantly higher in medullary carcinomas (from 42% to 50% of the cases) and papillary types (up to 57.5%) than in follicular (35%) and anaplastic variants (21%).10,11,21 In contrast to the rare presence of mucin deposits in the majority of primitive thyroid carcinomas, this was an inherent feature of extremely rare examples of primary mucinous adenocarcinoma, that was identical to colloid carcinoma of other sites, and more frequent less aggressive mucoepidermoid carcinoma.2-5,7-9 Mucinous adenocarcinoma is very heterogeneous with various characteristic histological patterns, and nonspecific morphological findings as those seen in a subset of poorly differentiated thyroid carcinomas.4,6 The importance of histological subtyping lies in its significance bearing on survival, with MVFC and mucoepidermoid carcinoma similarly having the best prognosis, whereas mucinous adenocarcinomas reportedly have poor outcomes.4 In addition, extensive mucinous differentiation has also been demonstrated in single examples of “mixed mucus-secreting and oncocytic carcinoma” and “primary mucin-producing adenosquamous carcinoma” of the thyroid.5,22 Even in adenoma of the thyroid gland, there have been reports that have shown mucin production; almost all of these cases revealed mucin in the intracellular district causing a signet-ring appearance in signet-ring cell adenomas.12-14,23 These changes can be quite dramatic, creating a diagnostic dilemma.23 This phenomenon is often attributed to the intracytoplasmic storage of altered thyroglobulin, which is a glycoprotein containing carbohydrates such as sialic acid, mannose, and galactosamine.6,12,23-25 A second theory raises the possibility of dual differentiation of tumor cells such as the combination of mucin secretion and endocrine function that has already been increasingly reported in tumors arising from lung, pancreas, and gastrointestinal tract.26,27 Other possible explanations of mucinous thyroid tumors gave rise to four alternative theories for their origin: (a) development from the ultimobranchial gland, (b) origin from intrathyroidal embryonal nests of salivary gland, (c) thyroglossal duct cyst, or (d) solid cell nests.* Recently, a new turn in the discussion of this matter arose when Bieche et al28 published a study on the recognition of the mucin gene (MUC1) in papillary thyroid carcinomas and demonstrated overexpression of MUC1 RNA in these neoplasms in comparison to normal thyroid tissues. Furthermore, it was successively reported underglycosylated MUC1 expression in papillary thyroid carcinomas that suggested the presumptive role of a defective glycosylation pathway of MUC1 leading to the accumulation of acid molecules in the apical membranes of the tumor cells.24,29 *References 3-5, 7, 8, 16, 17, 20, 22, 23, 27.

The primary and novel finding in the present case and the others of this review is that the evidence of abundant mucin deposition is exclusively found in extracellular location. Extracellular mucin derived from tumor epithelial cells generally exhibits a pattern of uniformly sulphated acid mucins, which are stained with mucicarmine and Alcian blue at pH 2.5 but not with periodic acid-Schiff, with or without diastase treatment.12,25 Likewise, scattered myxoid stromal components containing hyaluronic acid and acid mucopolysaccharides negative with mucicarmine and PAS are recognized in various nonepithelial mesenchymal tumors and are closely connected to stromal fibroblasts or myofibroblasts that represent their source. The presence of a prominent myxoid stroma may be very rarely encountered in epithelial tumors such as squamous cell carcinoma and renal cell carcinoma; so far, few thyroid epithelial tumors, as well as nonneoplastic conditions as nodular hyperplasia and Basedow’s disease, with abundant extracellular myxoid material have been reported and are considered as a nonspecific appearance of probable degenerative nature with no clinical significance.6,23,30 To our knowledge, to date, extensive extracellular mucin deposition has only been recognized in 3 cases of follicular thyroid carcinoma (MVFC) and 2 cases of follicular adenoma.16-18,20 Most lesions, including our case, are oval to round, well circumscribed and/or encapsulated, with a lobulated solid-cystic growth pattern, heterogeneous appearance with gelatinous areas, grayish-white to green, cut surface and measure up to 6.5 cm.16-18 The most striking histological feature is the presence of a reticular growth pattern, with anastomosing cords and trabeculae of polygonal cells intermixed with a mucin-rich stroma. Besides, 2 cases reported in literature as follicular adenomas with extensive extracellular mucin deposition were characterized by atypical nuclear changes (frequent nuclear inclusions) and mucin spillage into the capsule.20 According to authors these features do not fully belong to mucinous variant of follicular adenoma reported in the WHO classification and may also be described with not fully accepted terms as “follicular neoplasm of uncertain malignant potential or atypical follicular adenoma.”19,20 Despite some sharing histologic findings with those of papillary carcinoma, the possibility of an encapsulated follicular variant of papillary carcinoma with extensive extracellular mucin deposition, never previously described, could be excluded in these cases by poor follicular differentiation with prevalently reticular architecture and no expression of HBME-1 and BRAF mutation.6,20 As regards BRAF mutation, few and contrasting data have been reported until now regarding the frequency of the mutational status in this subtype of thyroid papillary neoplasm; however, BRAF V600E seems to be infrequently expressed, whereas BRAF K601E has been recently reported to be strongly associated with encapsulated papillary follicular-patterned

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cancer.31 All the reported cases of MVFC pursued an innocent course even though one of them exhibited cervical lymph node metastases.18 Follow-up information was available in 4 patients, two with malignancy including the present case, for a mean period of 20.5 months.18,20 Given the rarity and uncertainty of these mucin-rich follicular thyroid neoplasms, it is unknown whether extensive mucin deposition confers a different biologic behavior. Mucinous changes are one of several clear cell changes occurring in thyroid neoplasms of different histological types as a consequence of variable histogenetic mechanisms, also of degenerative type.6,23 Mucin alterations may influence the invasive and metastatic properties of neoplastic cells by changing cancer cell growth regulation, immune recognition, and cell adhesion.28,29 However, treatment and clinical prognosis of follicular thyroid neoplasms producing extracellular mucin deposits are not different to that of their more typical thyroid counterpart. Nowadays, the clinical course and therapeutic management of these tumors is determined by their basic histologic nature -absence or presence and extension of unequivocal capsular and/or vascular invasion- rather than cytoplasmic clearing and/or myxoid stromal change. Furthermore, pathologists should be aware of the existence of this variant of follicular thyroid neoplasm to avoid the cytologic and histologic pitfalls associated with such lesion and to ensure the more accurate diagnosis. Studying more cases and long-term follow-up are important to define its clinical course, especially for the rare cases that have been reported. Acknowledgments The authors would like to thank Prof Juan Rosai for his consultative opinion on this case, for his kind review of the article and the valuable suggestions that he made.

Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding The author(s) received no financial support for the research, authorship, and/or publication of this article.

References 1. Hanski C, Hofmeier M, Schmitt-Gräff A, et  al. Overexpression or ectopic expression of MUC2 is the common property of mucinous carcinomas of the colon, pancreas, breast, and ovary. J Pathol. 1997;182:385-391. 2. D’Antonio A, Addesso M, De Dominicis G, Boscaino A, Liguori G, Nappi O. Mucinous carcinoma of thyroid gland. Report of a primary and a metastatic mucinous tumour from ovarian adenocarcinoma with immunohistochemical study and review of literature. Virchows Arch. 2007;451:847-851.

3. Diaz-Perez R, Quiroz H, Nishiyama RH. Primary mucinous adenocarcinoma of thyroid gland. Cancer. 1976;38:1323-1325. 4. Kondo T, Kato K, Nakazawa T, Miyata K, Murata S-I, Katch 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. 5. 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;189:608-612. 6. Rosai J, DeLellis RA, Carcangiu ML, Frable WJ, Tallini G. Tumors of the thyroid and parathyroid glands. Atlas of Tumor Pathology. 4nd Series, Fasc 21. Silver Spring, MD; American Registry of Pathology; 2014:221-239. 7. Sobrinho-Simões MA, Nesland JM, Johannessen JV. A mucin-producing tumor in the thyroid gland. Ultrastruct Pathol. 1985;9:277-281. 8. Sobrinho-Simões M, Stenwig AE, Nesland JM, Holm R, Johannessen JV. A mucinous carcinoma of the thyroid. Pathol Res Pract. 1986;181:464-469. 9. Wenig BM, Adair CF, Heffess CS. Primary mucoepidermoid carcinoma of the thyroid gland: a report of six cases and a review of the literature of a follicular epithelial-derived tumor. Hum Pathol. 1995;26:1099-1108. 10. Chan JK, Tse CCH. Mucin production in metastatic papillary carcinoma of the thyroid. Hum Pathol. 1988;19:195-200. 11. Zaatari GS, Saigo PE, Huvos AG. Mucin production in medullary carcinoma of the thyroid. Arch Pathol Lab Med. 1983;107:70-74. 12. Gherardi G. Signet ring cell “mucinous” thyroid ade noma: a follicle cell tumour with abnormal accumulation of thyroglobulin and a peculiar histochemical profile. Histopathology. 1987;11:317-326. 13. Mendelsohn G. Signet-cell-simulating microfollicular adenoma of the thyroid. Am J Surg Pathol. 1984;8:705-708. 14. Rigaud C, Peltier F, Bogomoletz WV. Mucin produc ing microfollicular adenoma of the thyroid. J Clin Pathol. 1985;38:277-280. 15. Magro G, Torrisi A, Ippolito O, Torrisi A, Bisceglia M. Unusual non-neoplastic lesions in the “surgical pathology” of the thyroid. Pathologica. 2006;98:119-138. 16. Deligdisch L, Subhani Z, Gordon RE. Primary mucinous carcinoma of the thyroid gland. Report of a case and ultrastructural study. Cancer. 1980;45:2564-2567. 17. Cretney A, Mow C. Mucinous variant of follicular carcinoma of the thyroid gland. Pathology. 2006;38:184-186. 18. Levine TS, Hore I, Stearns M, Brown C. Cytological findings in a mucin-secreting follicular carcinoma of the thyroid. Cytopathology. 2000;11:185-190. 19. DeLellis RA, Lloyd RV, Heitz PU, Eng C. WHO Classification of Tumours. Pathology and Genetics of Tumours of Endocrine Organs. Lyon, France: IARC Press; 2004. 20. Kim NR, Cho HY, Pińa-Oviedo S, De La Roza G, Lee YD, Ro JY. Follicular adenoma with extensive extracellular mucin deposition: report on two cases. Clin Med Insights Case Rep. 2012;5:155-162. 21. Mlynek M-L, Richter HJ, Leder L-D. Mucin in carcinomas of the thyroid. Cancer. 1985;56:2647-2650.

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Squillaci et al 22. Uccella S, La Rosa S, Finzi G, Erba S, Sessa F. Mixed mucussecreting and oncocytic carcinoma of the thyroid. Pathologic, histochemical, immunohistochemical, and ultrastructural study of a case. Arch Pathol Lab Med. 2000;124:1547-1552. 23. Murakami S, Sakata H, Okubo K, Tsuji Y, Kayano H. Thyroid adenoma with extensive extracellular mucin deposition: report of a case. Surg Today. 2007;37:226-229. 24. Alves P, Soares P, Fonseca E, Sobrinho-Simōes M. Papillary thyroid carcinoma overexpresses fully and underglycosylated mucins together with native and sialylated simple mucin antigens and histo-blood group antigens. Endocr Pathol. 1999;10:315-324. 25. Rigaud C, Bogomoletz WV. “Mucin secreting” and “mucinous” primary thyroid carcinomas: pitfalls in mucin histochemistry applied to thyroid tumours. J Clin Pathol. 1987;40:890-895. 26. Golouh R, Us-Krasovec M, Auersperg M, Jancar J. Amphicrine-composite calcitonin and mucin-producing- carcinoma of the thyroid. Ultrastruct Pathol. 1985;8:197-206.

27. Harach HR. Thyroglobulin in human thyroid follicles with acid mucin. J Pathol. 1991;164:261-263. 28. Biėche I, Ruffet E, Zweibaum A, Vildė F, Lidereau R, Franc B. MUC1 mucin gene, transcripts, and protein in adenomas and papillary carcinomas of the thyroid. Thyroid. 1997;7:725-731. 29. Alves P, Soares P, Rossi S, Fonseca E, Sobrinho-Simōes M. Clinicopathologic and prognostic significance of the expression of mucins, simple mucin antigens and histo-blood group antigens in papillary thyroid carcinoma. Endocr Pathol. 1999;10:305-313. 30. Kuma S, Hirokawa M, Miyauchi A, Kakudo K. Oncocytic thyroid carcinoma with extensive myxoid stroma. Histopathology. 2003;42:514-516. 31. Coyne C, Afkhami M, Karunamurthy A, et  al. Histopathologic and clinical characterization of thyroid tumors carrying the BRAF K601E mutation [published online September 30, 2015]. Thyroid. doi:10.1089/thy.2015.0227.

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Mucinous Variant of Follicular Carcinoma of the Thyroid Gland: Case Report and Review of the Literature.

The rare reports of mucinous variant of follicular carcinoma of the thyroid gland have not provided enough evidence to support the recognition of thes...
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