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CASE REPORT Table of Contents   
Year : 2010  |  Volume : 53  |  Issue : 4  |  Page : 781-784
Spindle epithelial tumor with thymus-like differentiation of thyroid gland: Report of two cases with follow-up


Departments of Pathology and Microbiology, Medical College, The Aga Khan University, Hospital, Stadium Road, Karachi, Pakistan

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Date of Web Publication27-Oct-2010
 

   Abstract 

Spindle epithelial tumor with thymus-like differentiation (SETTLE) is a rare malignant thyroid tumor showing thymic or related branchial pouch differentiation. The tumors are composed predominantly of spindle cells along with focal epithelial component and ductular formations. SETTLE occurs in young patients, with indolent growth and a tendency to develop delayed blood-borne metastases. We herein report two cases of SETTLE with a follow-up period of 64 months and 30 months, respectively.

Keywords: Thymus-like, thyroid tumor, spindle epithelial tumor of thyroid

How to cite this article:
Nisa A, Barakzai A, Minhas K, Kayani N. Spindle epithelial tumor with thymus-like differentiation of thyroid gland: Report of two cases with follow-up. Indian J Pathol Microbiol 2010;53:781-4

How to cite this URL:
Nisa A, Barakzai A, Minhas K, Kayani N. Spindle epithelial tumor with thymus-like differentiation of thyroid gland: Report of two cases with follow-up. Indian J Pathol Microbiol [serial online] 2010 [cited 2019 Sep 17];53:781-4. Available from: http://www.ijpmonline.org/text.asp?2010/53/4/781/72088



   Introduction Top


Spindle epithelial tumor with thymus-like differentiation (SETTLE) is an extremely rare malignant thyroid tumor, formally characterized by Chan and Rosai [1] as a tumor of the neck showing thymic or related branchial pouch differentiation. Isolated reports of this tumor entity under a variety of designations, such as 'thyroid spindle cell tumor with mucous cyst', 'malignant teratoma', 'thyroid thymoma in childhood' and 'unusual thyroid tumor in a child' have previously been published. [2] SETTLE occurs in young patients, with an indolent growth and a tendency to develop delayed blood-borne metastases. We herein report two cases of SETTLE with a follow-up period of 64 months and 30 months, respectively. The tumors were composed predominantly of spindle cells along with focal epithelial component and ductular formations. Awareness of this variant is emphasized to prevent misdiagnosis as a sarcoma of the thyroid.


   Case Reports Top


Case 1

A 5-year-old boy presented with a painless right sided neck swelling of 8 to 9 months' duration. On physical examination, he appeared well and clinically euthyroid. A solid, non-tender palpable mass was noted in the right lobe of the thyroid. There were no bruits or palpable lymph nodes. Computed tomography (CT) scan [Figure 1] in correlation with ultrasound revealed a well-defined heterogeneously enhancing soft tissue nodule in the right lobe of thyroid gland with involvement of the isthmus. Radioactive isotope scan showed it to be a solitary cold nodule. Thyroid function tests were normal. Computed tomography scan of the abdomen and pelvis were within normal limits. Skeletal scintigraphic findings were negative for metastatic involvement of the skeleton. Systemic investigations did not yield any significant findings. A right thyroid lobectomy was performed with clear margins. The patient is alive and well 64 months after the operation.
Figure 1 :Case 1: Computed tomographic scan of the neck, exhibiting well-defined heterogeneously enhancing soft tissue nodule in the right lobe of the thyroid gland with increased vascularity and calcification

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Case 2

A 28-year-old man underwent a total thyroidectomy for thyromegaly of undetermined duration. The patient was euthyroid and did not have any other systemic complaints. Thirty months after the operation, the patient remains well and free of recurrence.


   Materials and Methods Top


One excision was received for frozen section while the other was received in 10% buffered formalin and processed routinely. Immunohistochemistry was performed on the formalin-fixed, paraffin-embedded tissue using the antibodies and the EnVision system (Dako, Germany) and streptavidin-biotin complex with diaminobenzidine (DAB) as chromogen. The following antibodies were used after microwave antigen retrieval; all the antibodies except CKCam 5.2 were procured from Dako, Germany: Cytokeratin-MNF (CK-MNF), CytokeratinAE1/AE3 (CKAE1/AE3), Low Molecular Weight Cytokeratin (LMW-CK CAM5.2, Becton-Dickinson, USA), Epithelial Membrane Antigen (EMA), Carcino-Embryonic Antigen (CEA), Vimentin, S-100 protein, Cytokeratin7 (CK7), Cytokeratin19 (CK19), Thyroglobulin, Leucocyte-Common Antigen (LCA), Neuron-specific Enolase (NSE), Chromogranin A, Synaptophysin, Neurofilament, CD99 (MIC2), Desmin, Bcl-2 oncoprotein, Alfa smooth muscle actin (ASMA), Calcitonin and Thyroid Transcription Factor-1 (TTF-I).

Macroscopic Findings

Case 1

A well-circumscribed tan-colored oval nodule measuring 5.5 3.5 2.8 cm received fresh for frozen section. There appeared to be a capsule separating the nodule from the surrounding thyroid parenchyma. On sectioning, the tumor had a firm to hard, lobulated mucoidy cut surface. Areas of hemorrhage, necrosis or infarction were not apparent.

Case 2

A well-circumscribed oval nodule measuring 3.5 2.5 1.2 cm was received. It had a firm, grayish-white lobulated cut surface. Areas of necrosis were not appreciated.

Lesions in both cases showed similar morphological features. Both were highly cellular, composed of spindle to oval cells showing lobular configuration separated by thick concentric band-like tissue comprising of spindle neoplastic cells [Figure 2]. At the periphery, a fibrous capsule was discerned and beyond this, a compressed thyroid parenchyma was seen. The spindle cells were arranged in sheets, tight to loose streaming fascicles, interlacing bundles, concentric layers and focally showing papillae formation [Figure 3]. Focal reticulated pattern produced by intercellular edema was also seen. The scanty to moderate amount of faintly eosinophilic cytoplasm was ill defined. Spindle cells possessed elongated or oval nuclei with one pointed and other blunted end. The nuclei were characterized by distinct nuclear membranes and finely dispersed chromatin with inconspicuous nucleoli. There were minimal pleomorphism and occasional mitoses (1-2/10 hpf), despite hypercellularity of the lesion. Spindle cells blended imperceptibly with glands, cysts and narrow tubulopapillary structures that were lined by bland-appearing cuboidal to columnar cells. Bubbly myxoid fluid occupied slit like spaces within some spindle cell areas. The cellular areas gradually merged with hypocellualr areas of hyalinized collagen, reminiscent of those seen in the synovial sarcoma. Both stromal and epithelial elements were bland without significant atypia. In case 1, foci of microcalcifications were frequently observed. Angiolymphatic invasion was not identified.
Figure 2 :Case 1: Spindle cells showing lobular configuration separated by thick concentric band like tissue (H and E, ×404)

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Figure 3 :Case 2: Spindle cells showing interlacing bundles and streaming fascicles with papillary projections (H and E, ×404)

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   Immunohistochemistry Top


The spindle cells as well as the glandular cells showed positive staining for epithelial markers including CK AE 1 /AE 3 , CK MNF, CK Cam5.2 and CK7 and vimentin. S-100 protein and ASMA were considered patchy positive [Figure 4]. The tumor cells show negative staining for EMA, CEA, CK19, thyroglobulin, TTF1, calcitonin, LCA, desmin, NSE, Chromogranin A, Synaptophysin, Neurofilament, Bcl2 and CD99 (Mic2).
Figure 4 :Case 1: Periodic acid Schiff and Alcian blue stain showing mucin filled cysts and tubules. Spindle cells are positive with Cytokeratin and Vimentin, while it shows patchy positivity with smooth muscle Actin (PAS and DAB, ×404)

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   Discussion Top


SETTLE, a rare primary tumor of the thyroid, is composed of spindle cells of epithelial nature forming fascicles, merging into glandular structures taking the form of tubules, papillae and cystic spaces. In some cases, cysts or glands lined by mucinous or respiratory epithelium may be present. Rare cases may be predominantly monophasic, with spindle cell predominance. [3] It has been speculated that SETTLE represents a neoplasm arising from branchial pouch remnants or ectopic thymus showing possible differentiation towards embryonic thymus (thymoblastoma). In one case, the SETTLE arose in association with epithelium-lined cysts of possible branchial pouch derivation. [4] The glandular structures lined by mucinous or respiratory epithelium are reminiscent of glandular structures found in the thymus. These are called canals of Kursteiner, which are thought to be remnants of the thymic duct or derivatives of medullary duct epithelium. SETTLE therefore, represents a more primitive level of development and cellular organization than thymoma, since it shows a striking resemblance to developmental thymus. [1] Nonetheless, so far convincing proof of thymic differentiation is lacking.

The differential diagnosis of SETTLE includes several biphasic spindle and epithelial tumors of the head and neck region. Proper diagnosis requires correlation of clinical, radiologic, cytologic and histologic findings. [5] Ectopic hamartomatous thymoma is a benign tumor composed of spindle cells, epithelial islands and tubules and mature fat. In addition to location and patient's age, the presence of intermingled adipose tissue distinguishes ectopic hamartomatous thymoma from SETTLE. Ectopic cervical thymomas are benign encapsulated tumors with a jigsaw puzzle appearance to the lobules and composed of spindled or plump epithelial cells, but they are also more commonly encountered in an older age group. [6] The presence of admixed lymphocytes in most cases differentiates ectopic cervical thymoma from SETTLE. Teratoma of the thyroid gland [7] is another differential. Frankly carcinomatous elements, primitive glands, immature cartilage, neural tissue or neuroepithelium are the differentiating morphologic features. The differential diagnosis also includes spindle cell variant of medullary thyroid carcinoma. [8] Morphologically, the presence of amyloid and positive staining of calcitonin confirms the diagnosis of medullary thyroid carcinoma.

Whilst the light microscopic differential diagnosis of a spindle cell thyroid neoplasm is vast, after immunohistochemistry, only two lesions are serious mimickers of SETTLE: Ectopic cervical thymoma, which may occur wholly in the thyroid gland, and synovial sarcoma. Biphasic synovial sarcoma (SS) of the head and neck, especially those with a predominantly spindle cell pattern (monophasic), is a morphological mimic that needs to be distinguished from SETTLE. [9] However, in SS, the spindle cells are generally more monomorphic and hyperchromatic with mild pleomorphism but manifest more mitoses. Furthermore, immunopositivity for cytokeratins has patchy distribution in sarcomas, while in SETTLE, cytokeratin staining is strong and diffuse. In addition, EMA positivity is regarded as a reliable marker of synovial sarcoma, being negative in SETTLE. Recently, a relatively large study on all 11 cases diagnosed as SETTLE with molecular-genetic methods were revealed to be negative for SS-associated fusion gene (SS18/SSX1 and SS18/SSX2) through reverse transcriptase polymerase chain reaction and SYT rearrangement by fluorescent in-situ hybridization. [10]

SETTLE pursues an indolent course; however, metastasis may not occur until many years after diagnosis (mean, 11.4 years; median, 5 years). The overall rate of metastasis is 33% (5/15) among the reported cases with follow-up information, but increases to a significant 71% (5/7) if analysis is made only on patients who had more than five years of follow-up. The preferential site of metastasis is the lung along with cervical lymph nodes and kidney. Thus long-term follow-up with particular attention to monitoring the lungs with imaging studies is advisable. [11] Although multiple case reports confirmed the low-grade behavior of SETTLE, few reports showed early and widespread metastasis. [12],[13],[14]

 
   References Top

1.Chan JK, Rosai J. Tumors of the neck showing thymic or related branchial pouch differentiation: A unifying concept. Hum Pathol 1991;22:349-67.  Back to cited text no. 1
[PUBMED]    
2.Weigensberg C, Dalsley H, Asa SL, Bedard YC, Mullen JB. Thyroid thymoma in childhood. Endocr Pathol 1990;1:123-70.  Back to cited text no. 2
    
3.Chetty R, Goetsch S, Nayler S, Cooper K. Spindle epithelial tumour with thymus-like element (SETTLE): The predominantly monophasic variant. Histopathology 1998;33:71-4.  Back to cited text no. 3
[PUBMED]  [FULLTEXT]  
4.Saw D, Wu D, Chess Q, Shemen L. Spindle epithelial tumor with thymus-like element (SETTLE), a primary thyroid tumor. Int J Surg Pathol 1997;4:169-74.  Back to cited text no. 4
    
5.Xu B, Hirokawa M, Yoshimoto K, Miki H, Takahashi M, Kuma S, et al. Spindle epithelial tumor with thymus-like differentiation of the thyroid: A case report with pathological and molecular genetics study. Hum Pathol 2003;34:190-3.  Back to cited text no. 5
[PUBMED]  [FULLTEXT]  
6.Harach HR, Day ES, Franssila KO. Thyroid spindle cell tumor with mucous cysts: An intrathyroidal thymoma? Am J Surg Pathol 1985;9:525-30.  Back to cited text no. 6
    
7.Rosai J, Carangiu ML, D eLellis RA. Tumors of the thyroid gland. 3rd series, Vol 5. Atlas of tumor pathology. In: Rosai J, Sobin LH, editors. Washington, D.C: Armed Forces Institute of Pathology; 1992. p. 223-9, 280-4, 135-57.  Back to cited text no. 7
    
8.Su L, Beals T, Bernacki EG, Giordano TJ. Spindle epithelial tumor with thymus-like differentiation: A case report with cytologic, histologic, immunohistologic, and ultrastructural findings. Mod Pathol 1997;10:510-4.  Back to cited text no. 8
[PUBMED]    
9.Roth JA, Enzinger FM, Tannenbaum M. Synovial sarcoma of the neck: A followup study of 24 cases. Cancer 1975;35:1243-53.  Back to cited text no. 9
[PUBMED]    
10.Folpe AL, Lloyd RV, Bacchi CE, Rosai J. Spindle epithelial tumor with thymus-like differentiation: A morphologic, immunohistochemical, and molecular genetic study of 11 cases. Am J Surg Pathol 2009;33:1179-86.  Back to cited text no. 10
[PUBMED]  [FULLTEXT]  
11.Cheuk W, Jacobson AA, Chan JK. Spindle epithelial tumor with thymus-like differentiation (SETTLE): A distinctive malignant thyroid neoplasm with significant metastatic potential. Mod Pathol 2000;13:1150-5.  Back to cited text no. 11
[PUBMED]  [FULLTEXT]  
12.Abrosimov AY, LiVolsi VA. Spindle epithelial tumor with thymus-like differentiation (SETTLE) of the thyroid with neck lymph node metastasis: A case report. Endocr Pathol 2005;16:139-43.  Back to cited text no. 12
[PUBMED]    
13.Raffel A, Cupisti K, Rees M, Janig U, Bernbeck B, Jazbec J, et al. Spindle epithelial tumour with thymus-like differentiation (SETTLE) of the thyroid gland with widespread metastases in a 13-year-old girl. Clin Oncol (R Coll Radiol) 2003;15:490-5.  Back to cited text no. 13
    
14.Erickson ML, Tapia B, Moreno ER, McKee MA, Kowalski DP, Reyes-Mϊgica M. Early metastasizing spindle epithelial tumor with thymus-like differentiation (SETTLE) of the thyroid. Pediatr Dev Pathol 2005;8:599-606.  Back to cited text no. 14
    

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Correspondence Address:
Azizun Nisa
Department of Pathology and Microbiology, Faculty of Health Sciences, Medical College, The Aga Khan University, Hospital, Stadium Road, P. O. Box 3500, Karachi - 74800
Pakistan
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0377-4929.72088

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    Figures

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

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