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Year : 2015  |  Volume : 4  |  Issue : 3  |  Page : 191-194

Poorly differentiated carcinoma of thyroid: A cytological dilemma

Department of Pathology, Shri Satya Sai Medical College and Research Institute, Ammapettai, Chengalpattu, Tamil Nadu, India

Date of Web Publication16-Jul-2015

Correspondence Address:
Dost Mohamed Khan
Department of Pathology, Shri Satya Sai Medical College and Research Institute, Ammapettai, Chengalpattu, Kanchipuram - 603 108, Tamil Nadu
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2278-344X.160899

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Poorly differentiated thyroid carcinoma (PDTC) is a neoplasm of follicular cell that show limited evidence of structural follicular cell differentiation. They occupy both morphologically and behaviorally an intermediate position between differentiated (follicular and papillary) and undifferentiated (anaplastic) carcinomas. Preoperative fine-needle aspiration cytology can be helpful in planning treatment options and patient management. According to WHO, the occurrence is around 4-7% of all the clinically evident thyroid tumors. We report a case of PDTC with clinicopathological correlation.

Keywords: Follicular neoplasm, papillary thyroid carcinoma, poorly differentiated thyroid carcinoma

How to cite this article:
Khan DM, Manimaran D, Hemanathan G, Anuradha S. Poorly differentiated carcinoma of thyroid: A cytological dilemma. Int J Health Allied Sci 2015;4:191-4

How to cite this URL:
Khan DM, Manimaran D, Hemanathan G, Anuradha S. Poorly differentiated carcinoma of thyroid: A cytological dilemma. Int J Health Allied Sci [serial online] 2015 [cited 2023 May 30];4:191-4. Available from: https://www.ijhas.in/text.asp?2015/4/3/191/160899

  Introduction Top

Burman et al. [1] define poorly differentiated thyroid carcinoma (PDTC) as carcinomas of thyroid follicular epithelium that retains sufficient differentiation to produce scattered small follicular structures and some thyroglobulin (Tg), but generally lack the usual morphological characteristics of papillary and follicular carcinoma. But it occupies an intermediate position between differentiated (follicular and papillary carcinomas) and undifferentiated (anaplastic) carcinomas." (Sobrinho-Simυes et al.). [2]

PDTC, first described by Sakamoto et al., [3] and Carcangia et al., [4] are rare, aggressive tumors, morphologically, and biologically placed between follicular carcinoma/papillary thyroid carcinoma (PTC) and anaplastic carcinoma.

PDTC is now recognized as a distinct thyroid neoplasm, and it is more common in women and in patients older than 50 years. [4] It presents as a rapidly growing, large mass, cold on radioiodine scintigraphy with associated nodal and distant metastasis in 30% of cases. [5] Many cases have radioiodine refractory metastases, resulting in death. Concomitant well-differentiated thyroid carcinoma in both anaplastic carcinoma and PDTC suggests progressive dedifferentiation.

  Case report Top

A 65-year-old male, moderately built, presented with a progressively increasing swelling in the neck of 4-year duration, hoarseness of voice and intermittent cough. On local examination confirmed an irregular, firm, fixed mass was seen in front the neck measuring 11 cm × 6 cm [Figure 1]. Indirect laryngoscopy showed right vocal cord paralysis.
Figure 1: Enalarged thyroid gland in front of the neck measuring 11 cm × 6 cm

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Thyroid function tests were normal and I 131 scan revealed cold nodules. X-ray chest posterioranterior view shows bilateral lung parenchyma with increased brochovascular markings. No hypo/hyperdense areas noted. Ultrasonography neck showed a well-defined heteroechoic nodule measuring 11 cm × 6 cm. On Doppler study showed hypoechoic areas with necrosis and minimal vascularity. No evidence of any cervical lymphadenopathy. Fine needle aspiration cytology of the mass showed high cellularity composed of follicular epithelial cells arranged in microfollicles, trabeculae pattern [Figure 2] and as single cells. The cells composed of round nuclei with granular chromatin showed scanty fragile cytoplasm, indistinct cell margins, nuclear crowding, nuclear inclusion and increased mitosis [Figure 3] and [Figure 4]. A diagnosis of follicular neoplasm (FN) was made initially.
Figure 2: Follicular epithelial cells arranged in insular, microfollicular and trabecular pattern (H and E, ×40)

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Figure 3: Follicular epithelial cells arranged in insular pattern. Inset shows nuclear inclusions (H and E, ×40)

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Figure 4: Both lobes of thyroid coalesced to form a single large mass measuring 11 cm × 6 cm × 6 cm. The external surface was bosselated, encapsulated and congested

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A total thyroidectomy was performed and grossly it showed coalescence of both the lobes of thyroid into a single large mass measuring 11 cm × 6 cm × 6 cm. The external surface was bosselated, encapsulated and congested areas were seen [Figure 5]. The cut surface showed an infiltrating lobulated, firm, gray-white tumor replacing the entire thyroid separated by thin and thick septa. Hemorrhage and light yellowish areas were also noted. Periphery showed a thin rim of thyroid tissue [Figure 6].
Figure 5: Cut section shows infiltrating lobulated, firm, gray white tumor replacing the entire thyroid separated by thin and thick septa. Periphery showed a thin rim of thyroid tissue

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Figure 6: Follicular epithelial cells arranged in insular pattern (H and E, ×10)

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Microscopically showed apparently encapsulated lesion with microscopically widely invasive, a cellular tumor with cells arranged in insular, microfollicles and trabecular pattern and individual cells having indistinct borders, scanty cytoplasm, and round nuclei with finely granular chromatin [Figure 7] and [Figure 8]. Some follicles showed cells with orphan Annie eye nuclei, nuclear crowding, and nuclear grooves. Areas of confluent necrosis were also seen. Many mitosis, lymphatic and vascular invasion along with focal capsular invasion were seen [Figure 9],[Figure 10]. The residual thyroid showed features of the compressed thyroid follicle. A diagnosis of follicular variant of PTC transforming to PDTC with capsular, vascular invasion was made.
Figure 7: Follicular epithelial cells arranged in microfollicular pattern (H and E, ×10) shows mitosis 2-3/hpf

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Figure 8: Confluent necrosis. Inset shows lymphatic invasion (H and E, ×10)

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Figure 9: Vascular invasion (H and E, ×40)

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Figure 10: Capsular invasion (H and E, ×40)

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{Figure 11}{Figure 12}

  Discussion Top

Although PDTC can be diagnosed histologically, cytological diagnosis is problematic [6] Due to its rarity, lack of experience and subtle cytological findings, most are initially misdiagnosed as FNs, [7] as was in our case.

Pietribiasi et al. [8] described the cytological features of 6 cases of poorly differentiated carcinoma of the thyroid with the histopathological diagnosis. "The cytological features were high cellularity, relatively monomorphic, round, small malignant cells in crowded nests, loosely cohesive groups, microfollicles with or without colloid and as dispersed cells. They have round to oval nuclei with the high nucleocytoplasmic ratio, finely granular chromatin, micronucleoli, mitotic figures, and necrosis. Atypia is usually mild, but when obvious with abundant necrosis, should help in the prompt diagnosis of anaplastic carcinoma." The author concluded that fine-needle aspiration biopsy could suggest a diagnosis of PDTC but cannot make a definitive preoperative diagnosis.

PDTC arising from well-differentiated thyroid carcinoma may demonstrate cytological features of the latter, with the former becoming evident only on excision. Rarely, thorough sampling shows both components. [7] Immunocytochemically, PDTC cells are positive for Tg and Bcl-2, but negative for calcitonin and will have a high Ki-67 index. The presence of microfollicles leads to a misdiagnosis of FN. Smaller tumor cells are key to the diagnosis. [7],[8] FN cells have a repetitive microfollicular pattern, fewer single cells, coarsely granular chromatin, no necrosis or mitoses. Like PTC, PDTC cells appear relatively monotonous, contain cytoplasmic vacuoles and may possess occasional nuclear grooves, inclusions and possibly, psammoma bodies. Metaplastic cytoplasm and papillae are absent in PDTC. When there is a dedifferentiation from PTC, PDTC may show overlapping features. Necrosis is a frequent finding in PDTC, which will be useful in differentiating it from FN and PTC. Medullary thyroid carcinoma shows red cytoplasmic granularity, salt and pepper chromatin, amyloid, and calcitonin positivity. Intact insulae along with necrosis, increased mitoses, and Tg positivity helps in differentiating PDTC from medullary thyroid carcinoma. [7]

Metastatic deposits from the breast, lung, prostate, etc., can cause confusion with PDTC but clinical findings and immunocytochemistry for Tg will be helpful for clinching the diagnosis. [7] Because of the aggressive nature of this tumor, total thyroidectomy is the main treatment modality. If there is a metastatic deposit in the regional lymph nodes, modified radical neck dissection can be considered. Additional treatment modalities include radioactive iodine, external beam radiation therapy (EBRT) and chemotherapy, depending on the characteristics of the tumor and the patient. EBRT will be helpful in patient with incomplete excision, unresectable lesion, and recurrences. [9],[10]

In our case, the patient is followed-up with cross-sectional imaging of the neck and chest, I 131 and serum Tg on thyroid stimulating hormone (TSH) suppression every 6 months. His routine chest radiographs were normal for the following year. His serum Tg on TSH was <1 μ units/ml with negative anti-Tg antibodies for a year now.

  Conclusion Top

Valuable cytological features in diagnosing PDTC comprises of small tumor cells arranged in insular, microfollicles, and trabecular pattern, nuclear atypia, mitotic figures, necrosis and Tg positivity. The preoperative diagnosis will help in deciding the proper treatment modality.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Burman KD, Ringel MD, Wartofsky L. Unusual types of thyroid neoplasms. Endocrinol Metab Clin North Am 1996;25:49-68.  Back to cited text no. 1
Sobrinho SM, Sambade C, Fonseca E, Soares P. Poorly differentiated carcinomas of the thyroid gland; a review of the clinicopathological features of a series of 28 cases of a heterogeneous clinically aggressive group of thyroid tumours. Int Surg Pathol 2002;10:123-130.  Back to cited text no. 2
Sakamoto A, Kasai N, Sugano H. Poorly differentiated carcinoma of the thyroid. A clinicopathologic entity for a high-risk group of papillary and follicular carcinomas. Cancer 1983;52:1849-55.  Back to cited text no. 3
Carcangiu ML, Zampi G, Rosai J. Poorly differentiated ("insular") thyroid carcinoma. A reinterpretation of Langhans′ "wuchernde Struma". Am J Surg Pathol 1984;8:655-68.  Back to cited text no. 4
Livolsi VA. Surgical Pathology of the Thyroid. Philadelphia, Pa: Saunders; 1990.  Back to cited text no. 5
Barwad A, Dey P, Nahar Saikia U, Gupta N, Rajwanshi A, Nijhawan R, et al. Fine needle aspiration cytology of insular carcinoma of thyroid. Diagn Cytopathol 2012;40 Suppl 1:E43-7.  Back to cited text no. 6
Kini SR. Thyroid Cytopathology an Atlas and Text. Philadelphia: Lippincott Williams and Wilkins; 2008. p. 220-32.  Back to cited text no. 7
Pietribiasi F, Sapino A, Papotti M, Bussolati G. Cytologic features of poorly differentiated ′insular′ carcinoma of the thyroid, as revealed by fine-needle aspiration biopsy. Am J Clin Pathol 1990;94: 687-92.  Back to cited text no. 8
Brierley JD, Tsang RW. External-beam radiation therapy in the treatment of differentiated thyroid cancer. Semin Surg Oncol 1999;16:42-9.  Back to cited text no. 9
Asakawa H, Kobayashi T, Komoike Y, Maruyama H, Nakano Y, Tamaki Y, et al. Chemosensitivity of anaplastic thyroid carcinoma and poorly differentiated thyroid carcinoma. Anticancer Res 1997;17:2757-62.  Back to cited text no. 10


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10]


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