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Hyalinizing trabecular adenoma feigning papillary carcinoma thyroid: case report with review of literature.

INTRODUCTION: Hyalinizing trabecular tumors are benign or low-malignant-potential tumors of the thyroid that were originally reported in 1905; however, they were not described in detail until 1987 by Carney et al. (1) It is characterized by circumscription or encapsulation, trabecular growth pattern, polygonal and elongated cells, nuclear cytoplasmic inclusions and grooves, hyaline material, dilated sinusoids, laminated calcospherites, and cytoplasmic yellow bodies. (2) HTA is misdiagnosed almost uniformly in fine-needle aspiration cytology(FNAC) ,biopsy specimens, because of the confusing similarity of its nuclear features to those of PTC and the presence of a misleading hyaline material in the tumor that mimics amyloid, and often is diagnosed as medullary thyroid carcinoma (MTC). (3-5)

This difficulty with the pathologic diagnosis often results in an overtreatment for what is almost universally a benign disease. Some of the authors (6) considered this tumor to be a variant of papillary thyroid carcinoma (PTC). However, several subsequent reports considered HTA as a separate entity and highlighted the unique features that distinguish it from other well-recognized thyroid lesions, including papillary thyroid carcinoma (PTC) and Medullary thyroid carcinoma (MTC). In this paper, we report the clinical and pathologic features of a female patient presenting with HTA and discuss the differential diagnosis with other mimickers within the thyroid, as well as in the head and neck area.

CASE REPORT: A 36 year old female presented with complains of swelling in the neck since 2 years. Swelling has grown in size since noticed. There was mild pain on and off, pain during deglutition. Patient also reported weight loss, increased appetite, irregular bowel habits and oligomenorrhoea. On general physical examination, there was enlargement of left lobe of thyroid. No other swellings noted in the neck. Patient was advised to undergo Fine needle aspiration cytology (FNAC) and Ultrasonography of the neck.

Ultrasonology Diagnosis: Papillary thyroid carcinoma.

FNAC diagnosis: Smears show sheets and clusters of thyroid follicular cells with individual cells are oval to round, hyperchromatic nuclei and indistinct cell borders. There are nuclear inclusions, nuclear indentations and nuclear grooving. There are tiny foci showing pinkish material (colloid). Features are suggestive of papillary carcinoma thyroid. (Figure 1 & 2)



Based on the ultrasonography and FNAC the clinical diagnosis wa confirmed as papillary thyroid carcinoma. Total thyroidectomy was done and the specimen was sent for Histopathological examination (HPE).

Gross Findings: We received thyroidectomy specimen, with enlarged lobe measuring 7x5x4 cm. (Figure 3).

Cut section swelling is well circumscribed with homogenous gray white solid areas with foci of cystic areas. (Figure 4)



Microscopic Examination: Sections studied show tumor tissue arranged in a trabecular pattern with individual cells showing indistinct cell borders and abundant pale eosinophilic cytoplasm. There was extensive hyalinization between the cellular trabeculae. Nuclear findings included perinucleolar clearing, nuclear pseudoinclusions, and nuclear grooves. Based on these findings a diagnosis of hyalinizing trabecular adenoma was given.





DISCUSSION: Hyalinizing trabecular tumors are rare tumors that are often mistaken for thyroid carcinomas cytologically. On FNAC, both hyalinizing trabecular tumors and papillary thyroid carcinomas can demonstrate hypercellularity, psammoma bodies, and cellular atypia including cytoplasmic invaginations, nuclear grooves, and nuclear pseudoinclusions causing diagnostic difficulty. In the largest case series published so far, 81% of 55 patients undergoing FNAC had lesions diagnosed as carcinoma or suspicious for carcinoma (diagnoses of papillary thyroid carcinoma or suspicious forpapillary thyroid carcinoma accounted for 60% of all cases) (7). Additionally, on FNAC, the hyaline of hyalinizing trabecular adenomas stains similar to amyloid, potentially causing misdiagnosis of medullary thyroid carcinoma.

Findings on FNAC should raise the suspicion of hyalinizing trabecular tumor include a bloody background, cells with a low nuclear to-cytoplasmic ratio, cellular aggregates around the hyaline material, fine chromatin (rather than the optically clear chromatin of papillary thyroid carcinoma), and numerous nuclear inclusions and grooves. (8, 9)

On gross examination, hyalinizing trabecular adenomas are usually well circumscribed and encapsulated. Their color typically ranges from yellow to tan, although variations have beendescribed. In comparison, papillary thyroid carcinomas are classically homogenous white with tiny excrescences on cut section and they lack a well-defined capsule. Extensive variation in their appearance has been described by some of the authors. In our patient, presence of well-defined capsule, homogenous gray white appearance and absence of tiny excrescences suggested a gross diagnosis of benign lesion. In our case, swelling was over diagnosed as papillary carcinoma thyroid based on the FNAC and Ultrasonological correlation.

A frozen section would have prevented the over diagnosis, but due to the non-availability of frozen section in our institute an over diagnosis of papillary carcinoma was made and total thyroidectomy was performed. The histological appearance of hyalinizing trabecular tumors on frozen and permanent section has been described in exquisite detail by Carney and colleagues. Briefly, the tumors have polygonal to elongated cells arranged in a trabecular or alveolar pattern.

Hyaline material is present extensively in both intracellular and extracellular locations. The cell nuclei often have perinucleolar clearing, nuclear grooves, and nuclear inclusions similar to papillary thyroid carcinoma. Yellow cytoplasmic inclusions called 'yellow bodies' found in hyalinizing trabecular tumor are a distinctive feature unique from papillary thyroid carcinomas and represent lysosomes. Due to the concern of a possible relationship with papillary thyroid carcinoma and case reports of malignant variants, the term 'hyalinizing trabecular tumors' was proposed and is currently the classification accepted by the World Health Organization.

The possibility that hyalinizing trabecular tumors represent a variant of papillary thyroid carcinoma has been considered given their similar cytological findings, RET/PTC rearrangements in some tumors, (10) and variable expression of the galectin-3 molecular marker. (11) Cheung et al. (12) have previously reported that the RET/PTC gene rearrangements found in hyalinizing trabecular tumors confirmed the 'long-standing suspicion' that these tumors are in fact a variant of papillary thyroid carcinoma.

However, on further genetic analysis, hyalinizing trabecular tumors have since been shown to be a discrete entity from papillary thyroid carcinoma with an absence of BRAF mutations, differential expression of micro RNAs, and unique staining patterns for molecular markers including CD56 and MIB-1. Hyalinizing trabecular tumors have an exceedingly low to nonexistent malignant potential. Although malignant variants have previously been described in case reports, a review of the cases raises the possibility of misdiagnosis of thyroid carcinoma with a focal hyalinized or trabecular growth pattern. (13) In the largest case series by Carney et al (7) including 119 cases, 118 were benign and found to meet the strict diagnostic criteria for hyalinizing trabecular adenomas. The single malignant tumor was classified as a hyalinizing trabecular carcinoma and was clinically distinct. This tumor did not meet the diagnostic criteria for an adenoma due to evidence of capsular invasion, numerous mitoses, and pulmonary metastasis at presentation. The 118 tumors categorized as hyalinizing trabecular adenomas behaved benignly without recurrence or metastases with up to 48 years of follow-up. Therefore, those tumors meeting the diagnostic criteria for hyalinizing trabecular tumors can be viewed as benign or at least of minimal malignant potential.

Given the primarily benign nature of hyalinizing trabecular tumors, they are appropriately and adequately treated with thyroid lobectomy alone. Due to the difficulty in distinguishing these tumors from thyroid carcinomas on FNAC, the literature shows that 44-71% of patients receive overtreatment with total or subtotal thyroidectomy. (7, 9) For this particular reason, it is extremely important that clinicians should be aware of hyalinizing trabecular adenomas as a benign etiology of thyroid masses masquerading as thyroid carcinomas.

CONCLUSION: Hyalinizing trabecular tumors are characterized by a trabecular or alveolar architecture with extensive hyaline and colloid deposits. Their cytological features often mimic papillary and medullary carcinoma thyroid which have to be differentiated. An awareness of hyalinizing trabecular tumors and their characteristic features is valuable for their recognition and management as well as for the possible prevention of over treatment for benign disease.

DOI: 10.14260/jemds/2014/2610


(1.) Carney JA. Hyalinizing trabecular tumors of the thyroid gland: quadruply described but not by the discoverer. Am J Surg Pathol 2008; 32: 622-634.

(2.) Rothenberg HJ, Goellner JR, Carney JA. Hyalinizing trabecular adenoma of the thyroid gland: recognition and characterization of its cytoplasmic yellow body. Am J Surg Pathol. 1999; 23: 118-125.

(3.) Akin MR, Nguyen GK. Fine-needle aspiration biopsy cytology of hyalinizing trabecular adenomas of the thyroid. Diagn Cytopathol. 1999; 20: 90-94.

(4.) Cerasoli S, Tabarri B, Farabegoli P, et al. Hyalinizing trabecular adenoma of the thyroid: report of two cases, with cytologic, immunohistochemical and ultrastructural studies. Tumori. 1992; 78: 274-279.

(5.) Katoh R, Kakudo K, Kawaoi A. Accumulated basement membrane material in hyalinizing trabecular tumors of the thyroid. Mod Pathol. 1999; 12: 1057-1061.

(6.) Fonseca E, Nesland LM, Sobrinho-Simoes M. Expression of stratified epithelial-type cytocheratins in hyalinizing trabecular adenomas supports their relationship with papillary carcinomas. Histopathology. 1997; 31(4): 330-5.

(7.) Carney JA, Hirokawa M, Lloyd RV, Papottie M, Sebo TJ.Hyalinizing trabecular tumors of the thyroid gland are almost all benign. Am J Surg Pathol 2008; 32: 1877-1889.

(8.) Casey MB, Thomas JS, Carney JA. Hyalinizing trabecular adenoma of the thyroid gland: cytologic features in 29 cases. Am J Surg Pathol 2004; 28: 859-867.

(9.) Kim T, Oh YL, Shin YH. Diagnostic dilemmas of hyalinizing trabecular tumors on fine needle aspiration cytology: a study of seven cases with BRAF mutation analysis. Cytopathology 2011; 22: 407-413.

(10.) Salvatore G, Chiappetta G, Nikiforov YE, Decaussin-Petrucci M, Fusco A, Carney JA, Santoro M. Molecular profile of hyalinizing trabecular tumours of the thyroid: high prevalence of RET/PTC rearrangements and absence of B-raf and N-ras point mutations. Eur J Cancer 2005; 41: 816821.

(11.) Gaffney RL, Carney JA, Sebo TJ, Erickson LA,Volante M, Papotti M, Lloyd RV. Galectin-3 expression in hyalinizing trabecular tumors of the thyroid gland. Am J Surg Pathol 2003; 27: 494-498.

(12.) Cheung CC, Boerner SL, MacMillan CM, Ramyar L, Asa SL. Hyalinizing trabecular tumor of the thyroid: a variant of papillary carcinoma proved by molecular genetics. Am J Surg Pathol 2000; 24: 1622-1626.

(13.) Galgano MT, Mills SE, Stelow EB. Hyalinizing trabecular adenoma of the thyroid revisited: a histologic and immunohistochemical study of thyroid lesions with prominent trabecular architecture and sclerosis. Am J Surg Pathol 2006; 30: 1269-1273.

Kandukuri Mahesh Kumar [1], V. Indira [2], Sudhir Kumar Vujhini [3], Kishori D [4]


[1.] Kandukuri Mahesh Kumar

[2.] V. Indira

[3.] Sudhir Kumar Vujhini

[4.] Kishori D.


[1.] Assistant Professor, Department of Pathology, Malla Reddy Institute of Medical Sciences, Suraram, Hyderabad, Andhra Pradesh, India.

[2.] Professor and HOD, Department of Pathology, Malla Reddy Institute of Medical Sciences, Suraram, Hyderabad, Andhra Pradesh, India.

[3.] Associated Professor, Department of Pathology, Malla Reddy Institute of Medical Sciences, Suraram, Hyderabad, Andhra Pradesh, India.

[4.] Assistant Professor, Department of Pathology, Malla Reddy Institute of Medical Sciences, Suraram, Hyderabad, Andhra Pradesh, India.


Dr. Kandukuri Mahesh Kumar, Assistant Professor, Malla Reddy Institute of Medical Sciences, Suraram, Hyderabad.


Date of Submission: 29/04/2014.

Date of Peer Review: 30/04/2014.

Date of Acceptance: 09/05/2014.

Date of Publishing: 14/05/2014.
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Title Annotation:CASE REPORT
Author:Kumar, Kandukuri Mahesh; Indira, V.; Vujhini, Sudhir Kumar; Kishori, D.<
Publication:Journal of Evolution of Medical and Dental Sciences
Date:May 19, 2014
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