Created by SEAP-IAP Sociedad Española de Anatomía Patológica on Apr 3, 2013 8:12:18 PM, Last modified by SEAP-IAP Sociedad Española de Anatomía Patológica on May 19, 2013 11:31:32 AM
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Dra. Catarina Eloy. Hospital Saõ João. IPATIMUP. Oporto.Cinical History
24-year-old male with a 5cm nodule in the left lobe of the thyroid. The patient was euthyroid and was submitted to left lobectomy. A couple of months later, following a diagnosis of “poorly differentiated thyroid carcinoma”, the patient was submitted to right lobectomy plus isthmectomy and left cervical lymphadenectomy, followed by radioactive iodine treatment. The case was sent to us for consultation after this second surgery. The patient is alive and well 13 years after the first surgery.
Endocrino. Caso 2. Hospital Saõ João. IPATIMUP. Oporto
Thyroid gland / Tiroides
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3 undefined attribute(s)
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Patological, Immunohistochemical and Molecular Findings: Whitish nodule measuring 5.3cm in its largest dimension. The isthmus and the right lobe (2nd surgery) were apparently normal. The same holds true – no signs of neoplastic disease, i.e., no metastases – in the left cervical lymph nodes. The tumour has pushing borders except in some foci displaying an infiltrative growth pattern. The whole tumour is composed by fairly regular nests of neoplastic cells that present entrapped follicular structures. The neoplastic cells are monotonous, have an epithelioid phenotype, high nucleocytoplasmic ratio and large, uniform nuclei exhibiting prominent nucleoli. The mitotic index is very high and comedo-type necrosis is observed in several neoplastic cell nests. PAS staining was negative in the cytoplasm of the neoplastic cells. The neoplastic cells diffusely expressed AE1.AE3, CAM 5.2, CK19, p63, p53 and CD99. There was focal expression of 34βE12, CEA and bcl2. The neoplastic cells did not express thyroglobulin, calcitonin, TTF-1, CK5, CK7, CK20, chromogranin, synaptophysin, vimentin, S100 protein, desmin, CD5, CD56, WT1 and c-KIT. The Ki67/Mib1 labeling index was about 50%. The cytogenetic study using fluorescent in situ hybridization disclosed the presence of the structural rearrangement EWSR1/FLI1.
CARCINOMA OF THE THYROID WITH EWING FAMILY TUMOUR ELEMENTS.
The diagnosis of poorly differentiated thyroid carcinoma (PDTC) made when the tumour was first seen was not confirmed by the negativity for TTF-1 and thyroglobulin in the neoplastic cells (6,11). After having ruled out the possibility of PDTC we were left with the diagnosis of small cell malignant tumour, primary or metastatic (7,10). The histologic appearance was compatible with the second hypothesis, i.e., it might be an intrathyroidal metastasis from a clinically occult small cell (neuroendocrine?) carcinoma (primary in the lung? other location?). The age of the patient (24y) and the absence of any neuroendocrine immunohistochemical marker did not support, however, such possibility. Total body computed tomography and magnetic resonance imaging excluded the existence of any other primary tumour, contributing to rule definitively out the possibility of a metastatic carcinoma. (The benign course of the disease we are now aware of settles any doubt one might have had about its metastatic nature). Most authors question the existence of bona fide primary small cell neuroendocrine carcinomas of the thyroid, whereas others think they may exist, constituting a sort of almost undifferentiated counterpart of medullary carcinoma (2,6,7,10). The unequivocal absence in the case herein described of any immunohistochemical marker of neuroendocrine differentiation (chromogranin, synoptophysin and CD56 negativity) turned the aforementioned discussion useless in spite of its academic interest. Furthermore, the immunoreactivity for AE1.AE3, CAM5.2, CK19 and 34βE12, showed the carcinomatous (non-neuroendocrine) nature of this primary small cell tumour of the thyroid.
While progressing in the characterization of the neoplastic cells regarding their cytokeratin profile we decided, taking into consideration the young age of the patient and the diffuse CD99 immunoreactivity (and despite the absence of PAS positivity in the neoplastic cells and of any rosette-like pattern in the tumour), to search for the EWSR1 gene translocation. The structural rearrangement EWSR1/FLI1 was detected throughout the tumour and the diagnosis of primary Ewing family tumour (PEFT) of the thyroid was advanced.
There are at least three cases of PEFT/PNET of the thyroid on record (1,4,9) that resemble the case here reported except regarding the prominence of epithelial differentiation. Cruz et al (5) reported a primary small cell tumour with basaloid features in the thyroid that also shares similar morphological, immunohistochemical and molecular features with the present case (e.g. diffuse positivity for cytokeratins, p63 and CD99; negativity of neuroendocrine markers, and presence of the EWSR1/FLI1 rearrangement). The expression of cytokeratins has been variably reported in PEFT/PNET and thought to be related with different PEFT variants (8). Taking all this into consideration we propose to classify our case as “Carcinoma of the thyroid with Ewing family tumour elements (CEFTE)”. The study of a much larger number of cases is necessary to clarify the histogenesis of this (these?) type(s) of thyroid tumours (3,5,9), and to have an idea on its (their?) natural history, namely whether the benign course of the present case, despite its highly malignant histological and immunohistochemical features, is an exception or not.
1. Adapa P, Chung TW, Popek EJ, et al. Extraosseous Ewing sarcoma of the thyroid gland. Pediatr Radiol. 2009;39:1365-8
2. Beach DF, Klump WJ, Haddad G, et al. Extrapulmonary small cell: a novel case of small cell carcinoma of the thyroid gland. Med Oncol. 2011 Jun 5. [Epub ahead of print]
3. Chan JK, Rosai J. Tumors of the neck showing thymic or related branchial pouch differentiation: a unifying concept. Hum Pathol. 1991;22:349-67.
4. Chung CH, Wang CH, Wang TY, et al. Extraskeletal Ewing sarcoma mimicking a thyroid nodule. Thyroid. 2006;16:1065-6.
5. Cruz J, Eloy C, Aragüés JM, et al. Small-cell (basaloid) thyroid carcinoma: a neoplasm with a solid cell nest histogenesis? Int J Surg Pathol. 2011;19:620-6.
6. DeLellis RA, Lloyd RV, Heitz U, Eng C (eds). Pathology and Genetics of Tumors of Endocrine Organs. World Health Organization Classification of Tumors. pp 147-166, Lyon: IARC Press, 2004
7. Eusebi V, Damiani S, Riva C, et al. Calcitonin free oat-cell carcinoma of the thyroid gland. Virchows Arch A Pathol Anat Histopathol. 1990;417:267-71.
8. Machado I, Noguera R, Mateos EA, et al. The many faces of atypical Ewing's sarcoma. A true entity mimicking sarcomas, carcinomas and lymphomas. Virchows Arch. 2010;458:281-90.
9. Maldi E, Monga G, Rossi D, et al. Extraosseuous Ewing Sarcoma of the thyroid gland mimicking a lymphoma recurrence, a case report. Pathol Res Pract (in press)
10.Matias-Guiu X, LaGuette J, Puras-Gil AM, Rosai J. Metastatic neuroendocrine tumors to the thyroid gland mimicking medullary carcinoma: a pathologic and immunohistochemical study of six cases. Am J Surg Pathol. 1997;21:754-62.
11. Sobrinho-Simões M, Albores-Saavedra J, Tallini G, et al. Poorly differentiated carcinoma. In World Health Organization Classification of Tumours. Pathology and genetics of tumours of endocrine organs. Eds RA deLellis, RV Lloyd, PU Heitz & C Eng. Lyon: IARC Press, 2004.