Head and Neck Pathology
Moderators: Dr. Christina MacMillan and Dr. Nina Gale
Case 3 -
Carcinoma Showing Thymus-like Differentiation (CASTLE)
Dr. Loretta Tse
The tumor comprises discrete nests of poorly differentiated carcinoma cells with smooth contour to
jagged borders, surrounded or traversed by keloidal fibrous septa; resulting in an organoid and vaguely
lobulated growth pattern. Lymphocytic infiltrates are readily evident. The tumor cells exhibit round to
oval vesicular nuclei, prominent nucleoli, ill-defined cytoplasmic borders and eosinophilic to
amphophilic cytoplasm. Immunoreactivity with cytokeratin, CD5 and Bcl-2 are demonstrated. The carcinoma
cells do not expressed thyroglobulin and thyroid transcription factor (TTF-1).
Case 3 - Slide 1
Diagnosis: 'Carcinoma showing thymus-like differentiation' (CASTLE)
In 1985, Miyauchi et al. described a rare neoplasm: an intrathyroidal epithelial neoplasm that showed
evidence of squamous differentiation and features of thymic epithelial tumor . Chan and Rosai coined
the term 'carcinoma showing thymus-like differentiation' (CASTLE).
CASTLE is a tumor found among
adults predominantly in their forties to sixties (mean age, 51.5 years) without significant sex
predilection. This tumor is often presented as a neck mass with or without symptoms of upper airway
obstruction. Duration of symptoms before initial diagnosis ranges from weeks to ten years. CASTLE is
not infrequently associated with advance locoregional disease with extrathyroidal involvement and nodal
Morphologically, CASTLEs show well-delineated borders with invasive but pushing fronts, although
infiltrative irregular edges are often seen at focal areas. CASTLEs are typified by multiple discrete
tumor islands separated by hyalinized fibrous septa and variable amount of inflammatory infiltrates. The
tumor islands comprise undifferentiated carcinoma cells with indistinct cell borders, vesicular nuclei,
mild to moderate degree of nuclear atypia, moderate amount of amphophilic cytoplasm, and variable number
of mature lymphoplasmacytic infiltrates. The presence of focal keratinization and focal squamoid
appearance of the tumor cells in CASTLE are sometimes observed. CASTLEs do not express thyroglobulin or
TTF-1, but demonstrate immunoreactivity with cytokeratin, CD5 and Bcl-2
the markers that
are also expressed by thymic carcinomas
CASTLE is not associated with EBV . CASTLE is an
indolent malignancy with local recurrence rate of 29% and mortality rate of 13.3%. The patients died at
6 months to 8 years after initial diagnosis (mean: 39 months)
'Carcinoma showing thymus-like differentiation' (CASTLE) is often confused with anaplastic carcinoma
of thyroid (ACT) in particular the lymphoepithelioma-like carcinoma and the squamous cell carcinoma
variants; the architecture, growth pattern and degree of nuclear anaplasia of these two entities are very
different. In contrast to CASTLEs, ACTs are widely invasive malignant tumor with permeative destructive
growth pattern, prominent coagulative necrosis, vascular permeation and high nuclear grade. CASTLEs do
not show conspicuous and extensive squamous differentiation that seen in squamous cell carcinoma of
thyroid. A differentiated thyroid carcinoma component that can be seen in 50-90% of anaplastic
carcinomas was never found in CASTLEs. Morphologically, CASTLE is an organoid carcinoma but ACT is a
sarcomatoid carcinoma. ACT is a very lethal malignancy comparing with CASTLE. Most patients present
with local aggressive disease or even distant metastasis. Despite the advances of oncological treatment,
the mean survival of anaplastic carcinoma is only in terms of months
and less than 10% of
patients can survive more than 2 years
CASTLE is more akin to that of thymic carcinoma
morphologically, immunohistochemically and in terms of biological behavior. The author prefers to
consider CASTLE as an intrathyroidal thymic carcinoma.
- Miyauchi, A., Kuma, K., Matsuzuka, F., Matsubayashi, S., Kobayashi, A., Tamai, H., and Katayama, S. Intrathyroidal epithelial thymoma: an entity distinct from squamous cell carcinoma of the thyroid. World J Surg, 9: 128-135, 1985.
- Chan, J. K. and Rosai, J. Tumors of the neck showing thymic or related branchial pouch differentiation: a unifying concept. Hum Pathol, 22: 349-367, 1991.
- Tse, L. L., Chow, S. M., Shek, W. H., Lo, C. Y., Lam, K. Y., Ko, Y. H., Lau, P., and Chan, J. K. C. Carcinoma showing thymus-like differentiation (CASTLE) - an unfamiliar intrathyroidal poorly differentiated carcinoma distinctly different from Anaplastic Carcinoma of Thyroid: a report of 8 new cases and comprehensive review - In Preparation. Am J Surg Pathol, 2006.
- Dorfman, D. M., Shahsafaei, A., and Miyauchi, A. Intrathyroidal epithelial thymoma (ITET)/carcinoma showing thymus-like differentiation (CASTLE) exhibits CD5 immunoreactivity: new evidence for thymic differentiation. Histopathology, 32: 104-109, 1998.
- Da, J., Shi, H., and Lu, J. [Thyroid squamous-cell carcinoma showing thymus-like element (CASTLE): a report of eight cases]. Zhonghua Zhong Liu Za Zhi, 21: 303-304, 1999.
- Damiani, S., Filotico, M., and Eusebi, V. Carcinoma of the thyroid showing thymoma-like features. Virchows Arch A Pathol Anat Histopathol, 418: 463-466, 1991.
- Mizukami, Y., Kurumaya, H., Yamada, T., Minato, H., Nonomura, A., Noguchi, M., and Matsubara, F. Thymic carcinoma involving the thyroid gland: report of two cases. Hum Pathol, 26: 576-579, 1995.
- Attaran, S. Y., Omrani, G. H., and Tavangar, S. M. Lymphoepithelial-like intrathyroidal thymic carcinoma with foci of squamous differentiation. Case report. Apmis, 104: 419-423, 1996.
- Asa, S. L., Dardick, I., Van Nostrand, A. W., Bailey, D. J., and Gullane, P. J. Primary thyroid thymoma: a distinct clinicopathologic entity. Hum Pathol, 19: 1463-1467, 1988.
- Kakudo, K., Mori, I., Tamaoki, N., and Watanabe, K. Carcinoma of possible thymic origin presenting as a thyroid mass: a new subgroup of squamous cell carcinoma of the thyroid. J Surg Oncol, 38: 187-192, 1988.
- Nassar, A., Saqi, A., Baloch, Z., and LiVolsi, V. Carcinoma showing thymuslike element of the thyroid. Acta Cytol, 47: 313-315, 2003.
- Roka, S., Kornek, G., Schuller, J., Ortmann, E., Feichtinger, J., and Armbruster, C. Carcinoma showing thymic-like elements-a rare malignancy of the thyroid gland. Br J Surg, 91: 142-145, 2004.
- Watanabe, I., Tezuka, F., Yamaguchi, M., Sagawa, J., and Kaise, N. Thymic carcinoma of the thyroid. Pathol Int, 46: 450-456, 1996.
- Berezowski, K., Grimes, M. M., Gal, A., and Kornstein, M. J. CD5 immunoreactivity of epithelial cells in thymic carcinoma and CASTLE using paraffin-embedded tissue. Am J Clin Pathol, 106: 483-486, 1996.
- Dorfman, D. M., Shahsafaei, A., and Miyauchi, A. Immunohistochemical staining for bcl-2 and mcl-1 in intrathyroidal epithelial thymoma (ITET)/carcinoma showing thymus-like differentiation (CASTLE) and cervical thymic carcinoma. Mod Pathol, 11: 989-994, 1998.
- Dorfman, D. M., Shahsafaei, A., and Chan, J. K. Thymic carcinomas, but not thymomas and carcinomas of other sites, show CD5 immunoreactivity. Am J Surg Pathol, 21: 936-940, 1997.
- Aldinger, K. A., Samaan, N. A., Ibanez, M., and Hill, C. S., Jr. Anaplastic carcinoma of the thyroid: a review of 84 cases of spindle and giant cell carcinoma of the thyroid. Cancer, 41: 2267-2275, 1978.
- Venkatesh, Y. S., Ordonez, N. G., Schultz, P. N., Hickey, R. C., Goepfert, H., and Samaan, N. A. Anaplastic carcinoma of the thyroid. A clinicopathologic study of 121 cases. Cancer, 66: 321-330, 1990.
- Giuffrida, D. and Gharib, H. Anaplastic thyroid carcinoma: current diagnosis and treatment. Ann Oncol, 11: 1083-1089, 2000.
- Haigh, P. I., Ituarte, P. H., Wu, H. S., Treseler, P. A., Posner, M. D., Quivey, J. M., Duh, Q. Y., and Clark, O. H. Completely resected anaplastic thyroid carcinoma combined with adjuvant chemotherapy and irradiation is associated with prolonged survival. Cancer, 91: 2335-2342, 2001.
- Amodeo, C., Caglia, P., Gandolfo, L., Veroux, M., Donati, M., and Imme, A. [Undifferentiated carcinoma of the thyroid]. Tumori, 89: 205-206, 2003.
- Nilsson, O., Lindeberg, J., Zedenius, J., Ekman, E., Tennvall, J., Blomgren, H., Grimelius, L., Lundell, G., and Wallin, G. Anaplastic giant cell carcinoma of the thyroid gland: treatment and survival over a 25-year period. World J Surg, 22: 725-730, 1998.
- Tennvall, J., Lundell, G., Wahlberg, P., Bergenfelz, A., Grimelius, L., Akerman, M., Hjelm Skog, A. L., and Wallin, G. Anaplastic thyroid carcinoma: three protocols combining doxorubicin, hyperfractionated radiotherapy and surgery. Br J Cancer, 86: 1848-1853, 2002.