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inervous invasion. Tumour cells showed positive staining
for CD5, p63, HMWK (high molecular weight keratin)
and CEA. One lymph node (among 3) was found to be
involved by the tumoral process. Overall, the pathological
pattern was highly suggestive of CASTLE disease.
Post-operatively, the clinical condition of the patient worsened,
with severe dysphagia and complete vocal cord palsy.
Enteral feeding was initiated. Because of the positive margins,
adjuvant radiotherapy by IMRT was delivered for a
dose of 66 Gy on the tumour bed and 52,8 Gy on lymph
nodes. Six weeks after irradiation, dysphagia and vocal cord
palsy regressed, and enteral feeding was maintained during
the night only. Nine months after surgery and six months
after irradiation, enteral feeding could be interrupted. The
patient is free of disease one year after treatment, without
any functional or aesthetic sequelae.
Discussion
CASTLE «Carcinoma showing thymus-like differentiation
of thyroid» is a rare malignant disease with resemblance
to thymic epithelial tumors, which was �rst described in
1985 (1) and is now recognized by the WHO as a unique
entity among the tumors of the endocrine organs (2). It
is generally accepted that CASTLE originate from ectopic
thymus tissue in or adjacent to the thyroid. However
the precise histogenesis remains hypothetical. Inside the
thyroid, CASTLE could arise from solid cell nests (SCN),
which are the third cellular component of the thyroid (in
addition to follicular cells and C cells), are thought to be
the remnants of ultimobranchial pouches, and are found
in about 10% of the thyroids, in the posterior part and
middle third lateral of the gland (3). When arising outside
the thyroid gland, CASTLE is thought to develop from
the thymopharyngeal duct or branchial pouches capable of
thymic differentiation (4). And, indeed, the pathological
pattern of CASTLE is very similar to thymic carcinoma,
with a lobular architecture due to �brous bands separating
solid islands of epithelial cells surrounded and/or invaded
by lymphocytes. The squamoid tumour cells with
pale cytoplasm, oval vesicular nuclei and well de�ned
nucleoli, show only a few number of mitosis. Thymic differentiation
with whorls resembling Hassall corpuscles
can also be observed. The thymic nature of the disease is
further supported by the frequent expression of CD5 by
tumour cells (5). CD5 is a surface glycoprotein expressed
by normal T-cells, some subtypes of B-cells lymphomas
and thymic carcinoma (6-8). The CD5 expression is particularly
useful in the differential diagnosis with more aggressive
squamous cell carcinoma (primary or metastatic)
or undifferentiated thyroid carcinoma with squamous differentiation.
Tumour cells are also stained in most cases
with antibodies to p63 and HMWK (as thymic carcinoma
cells), and CEA. The diagnosis is rarely considered in �rst
DER SELTENE FALL
instance, but the combination of clinical (slow growing
tumour, thyroid or parathyroid location), pathological
(thymic carcinoma like) and immunohistochemical (CEA,
p63, HMWK and CD5+) features is highly suggestive.
However, this neoplasm remains extremely rare, with
about 50 reported cases only, mainly from Asia (9). CAS-
TLE mostly occurs in the �fth decade of life, with a slight
female predominance (male to female ratio = 1 / 1.3) (10).
Interestingly, most intrathyroidal CASTLE tumors are located
in the inferior part of the thyroid gland, as SCN
from which they are thought to originate (7). The global
outcome of patients with CASTLE seems to be quite favorable,
much better than that with squamous cell or undifferentiated
carcinoma of the thyroid (11). In the largest
retrospective series performed by the Japanese society of
thyroid surgery, the 5- and 10-year cause speci�c survivals
for patients treated by surgery were 90% and 82%,
respectively (7). The prognosis is less favourable in case
of lymph node metastasis (10-year survival 57% versus
100% without lymph node involvement) and/or tumour
extension to adjacent organs (7). Interestingly, 10 patients
of this series underwent radiation therapy after curative
surgery for nodal involvement or tumour extension. No
relapse was observed, suggesting that radiotherapy might
be effective for preventing local relapse including for patients
at high risk. Similar results were reported in another
review (6). In the present case, the clinical and functional
improvement was obviously induced by radiation therapy,
further supporting the use of this treatment modality in
case of lymph node involvement, incomplete resection or
extension to adjacent organs.
Relapses may occur very late after the initial diagnosis,
sometimes more than 10 years. Most of them are local recurrences,
for which salvage surgery may still be successful
(4). For rare metastatic diseases, there is only anecdotal
usage of various drugs, with very limited effect, making
any recommendation impossible (6) (8, 12).
In conclusion, CASTLE «Carcinoma showing thymus-like
differentiation of the thyroid» is a very rare tumor developing
in the cervical area, probably originating from ectopic
thymus tissue in or adjacent to the thyroid. This diagnosis
should be advocated when facing a slowly growing tumor
in or adjacent to the thyroid, exhibiting thymic carcinoma
characteristics (including CD5 positivity). Complete surgery
is the treatment of choice and adjuvant radiotherapy is
recommended in cases of incomplete resection, extension to
adjacent organs or lymph node involvement.
References
1. Miyauchi A, Kuma K, Matsuzuka F et al. Intrathyroidal epithelial
thymoma: an entity distinct from squamous cell carcinoma of the
thyroid. World J Surg 1985;9:128-35.
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