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Year : 2011  |  Volume : 7  |  Issue : 2  |  Page : 189-191

Cytology of hyalinising trabecular adenoma-like variant of medullary thyroid carcinoma

Department of Pathology, Vydehi Institute of Medical Sciences and Research Center, Bangalore, India

Date of Web Publication12-Jul-2011

Correspondence Address:
K V Santosh
12, 3rd Main, Venkatamma Ramaiah Layout, Mathikere, Bangalore-560 054
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0973-1482.82916

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 > Abstract 

Medullary thyroid carcinoma is a rare thyroid neoplasm that can be either sporadic or familial. It occurs in adults, presenting as a solitary cold nodule on thyroid scan. Most are solid, firm, and non-encapsulated, and occur in the mid portion or upper half of the thyroid gland, corresponding to areas with greater numbers of C cells. We present a case of a 36-year-old female with a swelling in the front of her neck for six years. Fine needle aspiration done elsewhere revealed spindle cells, suggestive of a 'spindle cell neoplasm'. The histopathology of the thyroidectomy specimen showed features of a hyalinizing trabecular adenoma-like variant of medullary carcinoma. Subsequently, we performed aspiration on the received specimen and studied the cytological findings. The cytological diagnosis of this variant requires identification of the dual spindle and ovoid cell population and the granular neuroendocrine chromatin.

Keywords: Fine needle aspiration cytology, hyalinizing trabecular, medullary carcinoma, thyroid

How to cite this article:
Santosh K V, Raychaudhuri S, Subramanya H, Naveen Kumar B J. Cytology of hyalinising trabecular adenoma-like variant of medullary thyroid carcinoma. J Can Res Ther 2011;7:189-91

How to cite this URL:
Santosh K V, Raychaudhuri S, Subramanya H, Naveen Kumar B J. Cytology of hyalinising trabecular adenoma-like variant of medullary thyroid carcinoma. J Can Res Ther [serial online] 2011 [cited 2022 May 26];7:189-91. Available from: https://www.cancerjournal.net/text.asp?2011/7/2/189/82916

 > Introduction Top

Medullary carcinoma of the thyroid can display variants, such as, papillary, pseudo-papillary and follicular. The hyalinising trabecular adenoma-like or paraganglioma-like tumor is a rare variant. Diagnosis of this variant, based on fine needle aspiration (FNA) findings, requires a combination of strong suspicion, careful attention to nuclear features, and also immunoreactivity for calcitonin.

 > Case Report Top

A 36-year-old female presented with a swelling in the front of her neck for six years. There were no associated symptoms. No history suggestive of a hyperthyroid state was elicited. Examination revealed a well-defined swelling of size 4 x 4 cm, which moved with deglutition and was located in the right lobe of the thyroid. The swelling was nontender and firm. The left lobe of thyroid was within normal limits. No cervical lymphadenopathy was evident.

The thyroid hormonal profile revealed a euthyroid state. A thyroid scan depicted a moderately enlarged gland with a hypofunctional nodule on the right lobe of the thyroid. FNA was performed elsewhere and was reported as a 'spindle cell neoplasm'. A right hemithyroidectomy was performed.

On gross examination, the right hemithyroidectomy specimen measured 55 x 40 x 30 mm; the external surface was tan brown and showed a circumscribed nodule 30 mm in diameter. The cut section confirmed the presence of a well-encapsulated nodule with a uniform, gray-white, solid appearance. No papillary formations were evident. On microscopy, the encapsulated tumor was seen to be composed of cells in nests and trabeculae [Figure 1]. The individual cells were polygonal to spindly, with round to elongated nuclei, having granular chromatin [Figure 2]. Fibrous septae divided the cells into clusters; in places hyalinization of the septae was noted. A Congo Red stain for amyloid was negative. However, the immunohistochemistry for calcitonin was strongly positive in the tumor cells [Figure 3]. The final diagnosis was 'Medullary carcinoma thyroid - hyalinising trabecular adenoma-like variant'. Thereafter, total thyroidectomy was performed and did not reveal any residual tumor. At the time of writing, 15 months since the presentation, no evidence of metastasis or recurrence was evident.
Figure 1: Histopathology showed nests and trabecular patterns of tumor cells separated by fi brous septae (H and E, ×100)

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Figure 2: Ovoid to elongated nuclei with granular chromatin (H and E, ×400)

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Figure 3: Strong immunopositivity for calcitonin in tumor cells (IHC – Calcitonin, ×100)

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Subsequent to the histopathological diagnosis, the initial FNA slides were retrieved from the patient and reviewed. Also, to confirm and study the cytological features, an FNA was performed on the specimen received. The cut surface was mop dried using filter paper and aspiration from both halves of the nodule was done using the routine FNA procedure. Air-dried smears and fixed smears were stained using May-Grünwald-Giemsa (MGG) and Hematoxylin-Eosin (H and E), respectively. All the smears were cellular, composed of cell clusters in cohesive groups [Figure 4]. There was a mixture of predominantly spindle cells with scant cytoplasm, along with a smaller population of ovoid cells with eccentric nuclei [Figure 5]. The cells were characterized by a fine granular nuclear chromatin pattern, suggestive of neuroendocrine differentiation. No colloid or amyloid-like material was noted. The smears from the postoperative specimen were more cellular and showed a mild distortion of the cellular architecture but sufficiently preserved, for the nuclear characteristics to be recognized. No significant nuclear atypia was discernible.
Figure 4: FNA showed cohesive clumps of cells with ovoid to spindly appearance (MGG, ×100)

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Figure 5: Ovoid to elongated nuclei with inconspicuous cytoplasm (MGG, ×400)

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 > Discussion Top

Medullary carcinoma of the thyroid is a neoplastic lesion originating from the parafollicular C cells, occurring in sporadic and familial forms. The familial form may be a component of the multiple endocrine neoplasia type 2 syndrome and is seen to occur at a younger age. The presence of RET oncogene mutations in medullary carcinomas has given rise to the theory that they represent a variant of papillary thyroid carcinoma. A large study provided a 75% 10-year survival rate for medullary carcinoma. [1]

The classical medullary thyroid carcinoma displays polygonal to spindle cells arranged in nests, trabeculae, and follicles. However, several variants have been described including glandular, papillary, small-cell, and giant-cell types. [2]

On cytology, medullary thyroid carcinoma is generally diagnosed by a combination of features: (1) polygonal cells with eccentric plasmacytoid nuclei, ovoid cells or spindled cells, (2) speckled nuclear chromatin, (3) amyloid fragments, and (4) on MGG, the cells display fine pink cytoplasmic granularity. Granularity can also be seen in Hurthle cell neoplasms, however, the denser cytoplasm and nucleoli of Hurthle cell tumors help to differentiate these cases from medullary carcinoma. [3] The Hurthle cell neoplasm is an important differential diagnosis, when plasmacytoid cells predominate. The amyloid appears as a fibrillar blue to magenta amorphous material in MGG and as a pink to orange staining material in PAP, which can be confused for a colloid. [3],[4] Amyloid, however, is not found in all cases of medullary thyroid carcinoma. Speckled chromatin, although characteristic, is also not found in all cases. [4] The presence of a mixed population of cells is said to be a diagnostic pointer to medullary thyroid carcinoma. [3]

The hyalinising trabecular adenoma-like or paraganglioma-like variant of medullary thyroid carcinoma is extremely rare, with only a handful of cases reported so far. This variant is characterized by microscopic features indistinguishable from a benign hyalinising trabecular adenoma. [5] The first description of this variant was provided by Huss and Mendelsohn, in 1990, whereby their two cases were distinguished from follicular adenomas by calcitonin positivity and negative staining for thyroglobulin. [6] Unequivocal diagnosis, therefore, mandates calcitonin positivity. Melanin pigment-containing 'sustentacular cells' may also be observed. [7]

Recently, Ryska et al., reported, for the first time, the findings of FNA in two cases of paraganglioma-like medullary thyroid carcinoma. They noted ovoid to spindle cells in cohesive clusters with rare discohesive cells. The nuclear chromatin was granular and the cytoplasm was inconspicuous. The need for immunohistochemistry in order to make a confident cytological diagnosis was emphasized. [8]

In view of its rarity, it is difficult to make a confident diagnosis of a hyalinising trabecular adenoma-like or paraganglioma-like variant of medullary thyroid carcinoma on FNA. The absence of amyloid in the aspiration smears compounds this problem. However, an awareness of the existence of this variant, coupled with a careful scrutiny of the cellular morphology may assist in arriving at the correct diagnosis. The presence of a varied population of ovoid to spindly cells is helpful. Also, the classical granular chromatin must be looked for in wet-fixed smears stained with H and E or Papanicolaou. In doubtful cases, a repeat aspiration followed by immunohistochemistry may be warranted. Given the different prognostic connotations and the possible genetic associations, it is vital to differentiate this variant from a benign hyalinising trabecular adenoma. Other differential diagnoses include a spindle cell, soft tissue tumor in cases with dominant spindle cells; and follicular adenoma in cases of a plasmacytoid cell population. In hyalinising trabecular adenoma-like or paraganglioma-like variant of medullary thyroid carcinoma, the observation of a dual population of ovoid to spindle cells with fine nuclear chromatin, and the calcitonin immunopositivity will enable an accurate cytological diagnosis.

 > Acknowledgment Top

The authors wish to thank Dr. D. Hazarika for providing calcitonin immunohistochemical staining.

 > References Top

1.Hundahl SA, Fleming ID, Fremgen AM, Menck HR. A National Cancer Data Base report on 53,856 cases of thyroid carcinoma treated in the U.S., 1985-1995. Cancer 1998;83:2638-48.  Back to cited text no. 1
2.Scopa CD. Histopathology of thyroid tumors. An overview. Hormones (Athens) 2004;3:100-10.  Back to cited text no. 2
3.Buley ID. The thyroid gland. Chapter 23. In: Gray W, McKee GT, editors. Diagnostic Cytopathology. 2 nd ed. London: Churchill Livingstone; 2003. p. 1042.  Back to cited text no. 3
4.DeMay RM. The Art and Science of Cytopathology. Chicago: ASCP Press; 1996. p. 1208.  Back to cited text no. 4
5.Bockhorn M, Sheu SY, Frilling A, Molmenti E, Schmid KW, Broelsch CE. Paraganglioma-like medullary thyroid carcinoma: A rare entity. Thyroid 2005;15:1363-7.  Back to cited text no. 5
6.Huss LJ, Mendelsohn G. Medullary carcinoma of the thyroid gland: An encapsulated variant resembling the hyalinizing trabecular (paraganglioma-like) adenoma of thyroid. Mod Pathol 1990;3:581-5.  Back to cited text no. 6
7.Ikeda T, Satoh M, Azuma K, Sawada N, Mori M. Medullary thyroid carcinoma with a paraganglioma-like pattern and melanin production: A case report with ultrastructural and immunohistochemical studies. Arch Pathol Lab Med 1998;122:555-8.  Back to cited text no. 7
8.Ryska A, Cap J, Vaclavikova E, Dvorakova S, Bendlova B, Hovorkova E, et al. Paraganglioma-like medullary thyroid carcinoma: Fine needle aspiration cytology features with histological correlation. Cytopathology 2009;20:188-94.  Back to cited text no. 8


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]

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