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  Table of Contents    
ORIGINAL ARTICLE  
Year : 2017  |  Volume : 60  |  Issue : 2  |  Page : 167-171
Poorly differentiated thyroid carcinoma: A hospital-based clinicopathological study and review of literature


1 Department of Pathology, School of Medical Sciences, Universiti Sains Malaysia, Kelantan; Pathology Division, School of Medicine, International Medical University, Kuala Lumpur, Malaysia
2 Department of Pathology, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia
3 Department of Otorhinolaryngology, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia

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Date of Web Publication19-Jun-2017
 

   Abstract 

Introduction: Poorly differentiated thyroid carcinoma (PDTC) is a rare aggressive malignancy of thyroid follicular cells and has unique features in morphology and behavior. This study was aimed to describe the experience of a tertiary medical center with PDTC within a 10-year period. Materials and Methods: This is a descriptive retrospective study of eight cases of PDTC among 418 various thyroid carcinomas. All cases of PDTC were retrieved along with the clinicopathological information. Results: Only eight cases (1.9%) of PDTC were diagnosed among 418 thyroid carcinomas. Mean age was 48.12 with 3:5 (male:female) and tumor size ranged 3–12 cm. PDTC were diagnosed coexisting with one or more other pathologies; nodular hyperplasia (four cases), papillary carcinoma (one case), follicular carcinoma (three cases), and Hashimoto thyroiditis (two cases); with ≥60% PDTC component. Six cases associated with high-grade features died within 3 years after diagnosis. Discussion: Mean age in this study was younger including a 20-year-old girl. Younger age was associated with better prognosis. Most of the cases had underlying benign thyroid lesions and differentiated thyroid carcinoma. Most of the PDTC had poor prognosis associated with PDTC component ≥60%, tumor necrosis, high mitotic count, lymph node involvement, vascular invasion and distant metastasis; and these cases died within 3 years after diagnosis. Conclusion: Although treatment of PDTC remains surgery followed by radioiodine therapy, correct histopathological diagnosis is important for clinicians and oncologists to predict the prognosis. All thyroid carcinoma should be sampled thoroughly not to miss small foci of PDTC component.

Keywords: Poorly differentiated thyroid carcinoma, thyroid carcinomas, clinicopathological correlation, Turin

How to cite this article:
Win TT, Othman NH, Mohamad I. Poorly differentiated thyroid carcinoma: A hospital-based clinicopathological study and review of literature. Indian J Pathol Microbiol 2017;60:167-71

How to cite this URL:
Win TT, Othman NH, Mohamad I. Poorly differentiated thyroid carcinoma: A hospital-based clinicopathological study and review of literature. Indian J Pathol Microbiol [serial online] 2017 [cited 2017 Oct 20];60:167-71. Available from: http://www.ijpmonline.org/text.asp?2017/60/2/167/208392



   Introduction Top


Poorly differentiated thyroid carcinoma (PDTC) is an aggressive malignancy of thyroid follicular cells; which occupies both morphologically and behaviorally an intermediate position between well differentiated (follicular and papillary) carcinoma and undifferentiated (anaplastic) carcinoma.[1] It was first described as “wuchernde Struma” by Langhans in 1907 due to its characteristic nesting pattern.[2] In 1983, Sakamoto et al. first described it as PDTC with solid, trabecular, or scirrhous (sclerotic) growth pattern.[3] In 1984, Carcangiu et al. reinterpreted it as PDTC (insular carcinoma) because of its frequent histologic growth pattern, formation of solid clusters (insulae) of uniform tumor cells, together with the presence of mitotic activity, necrotic foci, and capsular and vascular invasions.[4]

In 2004, the World Health Organization (WHO) Classification of Tumours of Endocrine Organs recognized PDTC as a separate entity, defined on the basis of architectural and high-grade features.[1] In 2006, Turin (Italy) consensus conference, attended by an internationally recognized quorum of thyroid pathologists, agreed to a unified series of diagnostic criteria and terminology, and a diagnostic algorithm for PDTC. These criteria consisted of the presence of a solid/trabecular/insular growth pattern, lack of nuclear features of papillary thyroid carcinoma (PTC), and presence of one of the following features: (i) convoluted nuclei, (ii) tumor necrosis, (iii) 3 or more mitoses per 10 high-power field (HPF).[5]

PDTC may be associated with well-differentiated components of either follicular thyroid carcinoma (FTC) or PTC, and less frequently with anaplastic carcinoma. Although it is a rare type of thyroid malignancy, diagnosis of PDTC is important for pathologists, clinicians and oncologists as it may need additional therapeutic strategies. Dettmer et al. reported that the presence of even minor amounts of poorly differentiated areas in a thyroid carcinoma (≥10%) has similar prognostic significance as having a major component.[6]

This study was aimed to describe the experience of a tertiary medical center with PDTC within a 10-year period. We reported eight cases of PDTC and clinicopathological features of these cases were reviewed and compared with previously published literature.


   Materials and Methods Top


We reviewed all cases of thyroid carcinomas diagnosed and archived in Pathology Department of our institution. The clinical, follow-up and previous fine-needle aspiration cytology (FNAC) information were obtained from the medical records of the patients. FNAC smears, hematoxylin and eosin (H and E) stained tissue sections and their immunohistochemical stained slides of all cases were reviewed. The parameter collected were tumor size, associated histopathology, predominant architectural pattern, presence/absence of convoluted nuclei, tumor necrosis, mitotic count, lymph node involvement, vascular invasion, distant metastasis, and outcome of patients were recorded. The estimate proportion of poorly differentiated area was recorded based on the previously published study.[6] Descriptive analysis was done on the data.


   Results Top


There were eight cases (1.9%) of PDTC out of 418 cases of thyroid carcinomas recorded. All cases underwent total thyroidectomy followed by radioactive iodine therapy. The mean age of patients was 48.12 with the age range from 20 to 64 years. Three cases were male and five were female. Most of the cases presented with anterior neck swelling for 1–5 years duration. One case presented with metastatic FTC in gluteal region. No case was diagnosed as PDTC in FNAC smears, and five cases were reported as suspicious for malignancy. Mean tumor size was 6 cm, ranging 3–12 cm in the largest dimension.

Four cases of PDTC showed underlying nodular hyperplasia (NH), two cases showed underlying Hashimoto thyroiditis (HT), and four cases showed foci of well-differentiated thyroid carcinoma (FTC in three cases and PTC in one case). The percentage of foci of PDTC was ≥60% in all cases. Regarding predominant histological pattern; three cases were composed of insular [Figure 1]a, trabecular [Figure 1]b and solid pattern; three cases showed trabecular and insular pattern; one case showed insular pattern only; and one case showed solid pattern only. Convoluted nuclei of tumor cells [Figure 1]c were seen in five cases and necrosis were seen in five cases. Tumor cells of all cases exhibited mitoses (3–20/HPF) and mean mitotic count was 8.5/10 HPF. Tumor cells in all cases were immunohistochemically positive for thyroglobulin and negative for calcitonin and neuroendocrine markers.
Figure 1: Characteristic growth pattern of poorly differentiated thyroid carcinoma: insular (a) trabecular (b) (H and E, ×200). Convoluted nuclei with raisinoid contour (c) of the tumor cells (H and E, ×400)

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Lymph node involvement was seen in six out of eight cases (75%). Five cases had a vascular invasion in histological sections (one of them metastasized to pelvic bone) and lymph node involvement. These six cases died within 3 years after diagnosis. One case showed only lymph node involvement and that case had a recurrence of tumor and died 2 years later. Two cases had no distant metastasis, no vascular invasion, and no lymph node involvement; and these cases survived more than 5 years. Those two cases were of youngest in this study (20- and 36-year-old). Clinicopathological features of all eight cases were summarized in [Table 1].
Table 1: Clinic-pathological features of all cases of poorly differentiated thyroid carcinoma

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   Discussion Top


This study reflected on the clinicopathological correlation of PDTC in our institution. As PDTC is a rare thyroid malignancy, only eight cases (1.9%) of 418 cases of thyroid cancer within 10 years duration in our institution, of which PTC is the most common thyroid malignancy.[7] The proportion of PDTC in our series was lower than seen in Romania [8] and higher than the report from Nigeria.[9] In our series, our patients were younger with the mean age of 48.12 compared to other series, between 55 and 63 years.[10] A case in this study was only 20-year-old girl with underlying NH and HT.

It is generally accepted that PDTC may develop through three pathogenetic pathways: (i) by partial dedifferentiation of PTC, (ii) by partial dedifferentiation of FTC (including oncocytic type) and (iii) de novo, without a preexisting well-differentiated carcinoma precursor.[11] Most of the PDTC develop de novo although some of them arise from preexisting well-differentiated thyroid carcinoma.[12] In some area of endemic goiter, most of the PDTC had a history of goiter.[11] Based on urinary iodine excretion, the iodine intake of the population in our institutional area was suboptimal, and this was associated with a high prevalence of goiter.[13] Rate of malignant transformation is also high in this area, and the majority of thyroid cancer are seen in the background of NH.[7] This study showed that four cases were associated with well-differentiated carcinoma (three cases of FC and one case of PTC). Four cases and two cases had underlying NH and HT, respectively. The association of HT and thyroid carcinoma was reported mainly with PTC [14],[15] but not with PDTC in literature. Two cases associated with HT were youngest in this study. All the cases in this study showed foci of PDTC were (≥60%) of the whole pathology of thyroid. Small foci of PDTC (≥10%) in a thyroid carcinoma are worthy to diagnose PDTC, and it affects the prognosis significantly.[6]

Grossly, most of the PDTC grow as an invasive mass with some partial encapsulation.[11] The mean tumor size in our series is much bigger than reported previously.[16] Encapsulated insular carcinoma in underlying Grave disease was reported in a 51-year-old female with pulmonary metastasis.[17] PDTC was reported as insular carcinoma until the WHO recognized as a separate entity, defined on the basis of architectural and high-grade features in 2004.[1] A uniform diagnostic criterion for PDTC was made by panel of internationally recognized thyroid pathologists in Turin, Italy in 2006. It includes (i) presence of a solid/trabecular/insular pattern of growth, (ii) absence of the conventional nuclear features of PTC, and (iii) presence of at least one of the following features: convoluted nuclei; mitotic activity ≥3/10 HPF; and tumor necrosis.[5] Moreover, PDTC has the presence of conventional diagnostic criteria for thyroid malignancy and follicular cell derivation of tumor cells such as conspicuous capsular and/or vascular invasion and some degree of thyroglobulin positivity.[18]

Insular pattern of growth can be seen in other histological types of thyroid carcinoma. Pascanu et al. reported insular growth pattern in mixed PTC and FTC in an 8-year-old girl.[19] Ifigenia et al. reported mixed papillary, poorly differentiated and anaplastic thyroid carcinoma in a 73-year-old female with multinodular goiter.[20] In our series, the most common histological pattern of PDTC is insular pattern followed by trabecular pattern. However, some authors still prefer on the recognition of high-grade features only, including mitotic index and necrosis, irrespective of the growth pattern.[21]

The presence of convoluted nuclei in tumor cells is one of the features in PDTC. It is defined as small round hyperchromatic nuclei with convolutions of the nuclear membrane. When compared with the typical nuclei of PTC, they are slightly smaller and darker, with irregular raisinoid contours. These changes are believed to reflect dedifferentiation of the papillary carcinoma, with loss of many of its characteristic nuclear features but the preservation of the irregularity of nuclear contours.[5] Convoluted nuclei were seen in five cases in our series including the case associated with PTC. Tumor necrosis and high mitotic activity are high-grade features which associate with PDTC. Five out of eight cases in this series showed foci of tumor necrosis, and all cases showed high mitotic count with mean count 8.6/10 HPF.

Most of the PDTC in this study showed aggressive behavior such as lymph node metastasis and distant metastasis and these features are related to poor prognosis.[1] In our series, six out of eight cases (75%) had lymph node involvement, and evidence of vascular invasion in histological sections was seen in five cases. The patients of all six cases with lymph node involvement, vascular invasion, and distant metastasis died within 3 years after diagnosis. Two cases of youngest in this study including a 20-year-old girl were free of lymph node involvement and distant metastasis at the time of diagnosis and survived more than 5 years. In these two cases, the tumor size was only 3 cm. Therefore, young age group is one of the good prognostic factors in our study.

PDTC is associated with a worse prognosis than well-differentiated thyroid carcinomas but a significantly better prognosis than anaplastic carcinoma.[22] Prognosis depends primarily on lymph node involvement, distant metastasis, tumor-node-metastasis staging, completeness of surgery, and responsiveness to radioiodine therapy.[1]

Differential diagnosis of PDTC include solid variant of PTC, invasive FTC with a predominant solid/trabecular pattern of growth, medullary thyroid carcinoma, compact subtype of small cell undifferentiated thyroid carcinoma and metastatic neoplasms. The absence of typical nuclear features of PTC is used to differentiate between solid variant of PTC and PDTC. Convoluted raisinoid nuclear contour, mitoses and tumor necrosis of PDTC are useful to differentiate it from invasive FTC with a predominant solid/trabecular pattern of growth. Larger nuclear size, “salt and pepper look” nuclear chromatin, calcitonin and carcinoembryonic antigen positivity of medullary carcinoma are used to differentiate it from PDTC. To differentiate from a compact subtype of small cell undifferentiated thyroid carcinoma; the presence of abortive follicles, lack of prominent cellular pleomorphism and thyroglobulin positivity of PDTC are useful features.[17] However, strong diffuse positivity of thyroglobulin is unlikely in PDTC, and it typically highlights the well-differentiated carcinoma component.[11]


   Conclusion Top


Most of the patients in our study presented in an advanced stage with the features correlated with poor prognosis. Young age group is one of the good prognostic factors in our study. All the cases of benign thyroid lesions should be thoroughly examined as most of the cases in this study had underlying NH and differentiated thyroid carcinoma. If the percentage of PDTC is very small, it can be missed, and thorough histopathological sampling is important. Although treatment of PDTC remains surgery followed by radioiodine therapy, correct histopathological diagnosis is important for clinicians and oncologists to predict the prognosis. The diagnosis of PDTC depends mainly on morphologic criteria in H and E sections, and immunohistochemistry is usually not necessary for diagnosis except for the confirmation of follicular cell derivation if needed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
   References Top

1.
Simoes MS, Saavedra AJ, Tallini G, Santoro M, Volante M, Pilotti S, et al. Poorly differentiated carcinoma. In: DeLellis RA, Lloyd RV, Heitz PU, Eng Charis, editors. Pathology and Genetics of Tumors of Endocrine Organs. World Health Organization Classification of Tumors. Lyon: IARC Press; 2004. p. 73-6.  Back to cited text no. 1
    
2.
Langhans T. Über die epithelialen formen der malignen struma. Virchows Archiv Pathol (About the epithelial forms of malignant goiter) Anat Physiol Klin Med 1907;189:69-152.  Back to cited text no. 2
    
3.
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
    
4.
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
    
5.
Volante M, Collini P, Nikiforov YE, Sakamoto A, Kakudo K, Katoh R, et al. Poorly differentiated thyroid carcinoma: The Turin proposal for the use of uniform diagnostic criteria and an algorithmic diagnostic approach. Am J Surg Pathol 2007;31:1256-64.  Back to cited text no. 5
    
6.
Dettmer M, Schmitt A, Steinert H, Haldemann A, Meili A, Moch H, et al. Poorly differentiated thyroid carcinomas: How much poorly differentiated is needed? Am J Surg Pathol 2011;35:1866-72.  Back to cited text no. 6
    
7.
Othman NH, Omar E, Naing NN. Spectrum of thyroid lesions in hospital Universiti Sains Malaysia over 11 years and a review of thyroid cancers in Malaysia. Asian Pac J Cancer Prev 2009;10:87-90.  Back to cited text no. 7
    
8.
Catana R, Boila A, Borda A. Thyroid cancer profile in Mures County (Romania): A 20 years study. Rom J Morphol Embryol 2012;53:1007-12.  Back to cited text no. 8
    
9.
Rahman GA, Abdulkadir AY, Braimoh KT, Inikori AR. Thyroid cancers amongst goiter population in a Nigerian tertiary hospital: Surgical and radiographic perspective. Niger J Med 2010;19:432-5.  Back to cited text no. 9
    
10.
Volante M, Landolfi S, Chiusa L, Palestini N, Motta M, Codegone A, et al. Poorly differentiated carcinomas of the thyroid with trabecular, insular, and solid patterns: A clinicopathologic study of 183 patients. Cancer 2004;100:950-7.  Back to cited text no. 10
    
11.
Nikiforov YE. Poorpy differentiated carcinoma. In: Nikiforov YE, Biddinger PW, Thompson LD, editors. Diagnostic Pathology and Molecular Genetics of the Thyroid: A Comprehensive Guide for Practicing Thyroid Pathology. 2nd ed. Philadelphia: Lippincott Williams & Wilkins; 2012. p. 247-62.  Back to cited text no. 11
    
12.
Pilotti S, Collini P, Mariani L, Placucci M, Bongarzone I, Vigneri P, et al. Insular carcinoma: A distinct de novo entity among follicular carcinomas of the thyroid gland. Am J Surg Pathol 1997;21:1466-73.  Back to cited text no. 12
    
13.
Mafauzy M, Mohamad WB, Anum MY, Musalmah M. Urinary iodine excretion in the northeast of Peninsular Malaysia. Southeast Asian J Trop Med Public Health 1995;26:138-42.  Back to cited text no. 13
    
14.
Repplinger D, Bargren A, Zhang YW, Adler JT, Haymart M, Chen H. Is Hashimoto's thyroiditis a risk factor for papillary thyroid cancer? J Surg Res 2008;150:49-52.  Back to cited text no. 14
    
15.
Lee JH, Kim Y, Choi JW, Kim YS. The association between papillary thyroid carcinoma and histologically proven Hashimoto's thyroiditis: A meta-analysis. Eur J Endocrinol 2013;168:343-9.  Back to cited text no. 15
    
16.
Cherkaoui GS, Guensi A, Taleb S, Idir MA, Touil N, Benmoussa R, et al. Poorly differentiated thyroid carcinoma: A retrospective clinicopathological study. Pan Afr Med J 2015;21:137.  Back to cited text no. 16
    
17.
Foroughi F, Saadat N, Salehian MT. Encapsulated insular carcinoma of the thyroid arising in graves' disease: Report of a case and review of the literature. Int J Surg Pathol 2012;20:636-9.  Back to cited text no. 17
    
18.
Ginesa GR, Manuel SS. Poorly differentiated thyroid carcinoma: An evolving entity. Diagn Histopathol 2011;17:114-23.  Back to cited text no. 18
    
19.
Pascanu I, Borda A, Banescu C. Thyroid nodule with Hashimoto thyroiditis in childhood – A challenging experience. Rom J Morphol Embryol 2008;49:541-5.  Back to cited text no. 19
    
20.
Ifigenia KA, Goudoucas A, Thomas D, Bakola T, Veniou E, Batika P, et al. Mixed papillary, poorly differentiated and anaplastic thyroid carcinoma. 2008;16:814.  Back to cited text no. 20
    
21.
Volante M, Papotti M. Poorly differentiated thyroid carcinoma: 5 years after the 2004 WHO classification of endocrine tumours. Endocr Pathol 2010;21:1-6.  Back to cited text no. 21
    
22.
Baloch ZW, Livolsi VA. Pathology of thyroid and parathyroid disease. In: Mills SE, Carter D, Greenson JK, Reuter VE, Stoler MH, editors. Sternberg's Diagnostic Surgical Pathology. 5th ed. Philadelphia: Lippincott Williams & Wilkins; 2010. p. 575-620.  Back to cited text no. 22
    

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Correspondence Address:
Thin Thin Win
Pathology Division, School of Medicine, International Medical University, 126, Jalan Jalil Perkasa 19, Bukit Jalil, 57000 Kuala Lumpur
Malaysia
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/IJPM.IJPM_457_16

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