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Diagnosis of medullary thyroid carcinoma by calcitonin measurement in
fine-needle aspiration biopsy specimens.Thyroid.
2007 Jul;17(7):635-8.
Medullary thyroid
carcinoma (MTC) is a thyroid malignancy originating from C cells. To
date, serum calcitonin measurement and fine-needle aspiration biopsy (FNAB)
have been prominent diagnostic approaches to these lesions. Although
an elevated serum calcitonin level strongly suggests the presence of
MTC, this examination cannot identify the origin of the calcitonin
overexpression, especially in patients demonstrating multiple thyroid
nodules. For the treatment planning, it is important to know which
nodule is MTC, especially in nonhereditary MTC. In this study, we
propose calcitonin measurement in the washout of FNAB needles after
sampling each tumor (FNAB-CT) as a new approach to diagnosis of MTC.
We performed FNAB-CT for five MTC cases. Although only one of these
cases was definitively diagnosed as having MTC by FNAB cytology, FNAB-CT
values ranged from 17,000 to 560,000 pg/mL, which were exceedingly
higher than those of 11 controls (seven papillary carcinomas, two
adenomatous nodules, one chronic thyroiditis, and one normal thyroid),
which showed values ranging from <10 to 67 pg/mL. In patients with MTC,
FNAB-CT values were 74 to 1888 times greater than serum calcitonin
values. These findings suggest that FNAB-CT can be an additional
approach to diagnosis of MTC.
Molecular characterization of the desmoplastic tumor
stroma in medullary thyroid carcinoma.Int
J Oncol. 2007 Jul;31(1):59-67.
Medullary thyroid
carcinomas are aggressive neoplasias that metastasize very early to
loco-regional lymph nodes, and tumors with a desmoplastic stromal
reaction have a higher incidence of lymph node metastasis. In order to
characterize the desmoplastic response in thyroid cancers, we
evaluated the expression pattern of three molecular markers of
activated fibroblasts/myofibroblasts, namely, fibroblast activation
protein alpha (FAPalpha), tenascin-C (Tn-C), and alpha-smooth muscle
actin (alpha-SMA), as well as the endothelial markers endoglyx-1, CD34
and CD31 in a series of 28 metastatic and non-metastatic medullary
thyroid cancers. Immunohistochemical studies demonstrated that the
three fibroblast activation markers (FAPalpha, Tn-C, alpha-SMA) are
consistently expressed in the peritumoral and intratumoral stromal
compartment of medullary thyroid carcinomas and expression of FAPalpha
and Tn-C correlated with the degree of desmoplasia determined
histologically (p=0.001 for FAPalpha and p<0.001 for Tn-C). Moreover,
the extent of desmoplasia as well as the expression of FAPalpha and Tn-C
correlated with the presence of lymph node (LN) metastases (p=0.002,
p=0.005 and p=0.002, respectively). No correlation was found between
the microvessel density (neoangiogenesis) in the tumor stroma,
assessed with the endoglyx-1, CD34 and CD31 markers, and the degree of
desmoplasia or incidence of LN metastases. Using a
bioinformatics-based search of the BioExpresstrade mark database we
found in a series of 48 thyroid cancers a significant correlation
between FAPalpha RNA expression and incidence of LN metastases also in
papillary cancers. These findings suggest that the link between
specific molecular markers of tumor stromal reaction and locoregional
metastasis extends from medullary to other thyroid cancer types.
Current approaches to medullary thyroid carcinoma,
sporadic and familial.J
Surg Oncol. 2006 Dec 15;94(8):737-47.
Medullary thyroid
carcinoma (MTC) is a rare malignancy of the thyroid C cells. It occurs
in hereditary (25% of cases) and sporadic forms, and aggressiveness is
related to the clinical presentation (hereditary vs. sporadic) and the
type of RET mutation present. In hereditary cases, early diagnosis
makes preventative surgery possible. In established cases, thorough
surgical extirpation of the primary tumor and nodal metastases has
been the mainstay of treatment. Radioactive iodine, external beam
radiation therapy (EBRT), and conventional chemotherapy have not been
effective. Newer systemic treatments, with agents that target abnormal
RET proteins, hold promise and are being tested in clinical trials for
patients with metastatic disease.
Natural history, diagnosis, treatment and outcome of
medullary thyroid cancer: 37 years experience on 157 patients. Eur
J Surg Oncol. 2007 May;33(4):493-7.
AIM: The analysis
of a 37-year retrospective study on diagnosis, prognostic variables,
treatment and outcome of a large group of medullary thyroid cancer (MTC)
patients was conducted, in order to plan a possible evidence-based
management process. METHODS: Between Jan 1967 to Dec 2004, 157
consecutive MTC patients underwent surgery in our centre: 60 males and
97 females, mean age 47.3 years (range 6-79). Total thyroidectomy was
performed in 143 patients (91.1%); central compartment (CC) node
dissection (level VI) in 41 patients; central plus lateral compartment
(LC) node dissection (levels II, III, and IV) in 82 patients. Subtotal
thyroidectomy was initially performed in 14 cases: 10 of them were
re-operated because of persistence of elevated serum calcitonin
levels. RESULTS: After a median post-surgical follow-up of 68 months
(range 2-440 months), 42.9% of patients were living disease-free,
39.8% were living with disease, 3.1% were deceased due to causes
different from MTC, and 3.2% were deceased due to MTC. The overall
10-year survival rate was 72%. At uni-variate statistical analysis (a)
patient's age at initial treatment (>45 years; >/=45 years), (b)
sporadic vs. hereditary MTC, (c) disease stage, and (d) the extent of
surgical approach resulted as significant variables. Instead, at
multivariate statistical analysis, only (a) patient's age at initial
diagnosis, (b) disease stage, and (c) the extent of surgery resulted
as significant and independent prognostic variables influencing
survival. CONCLUSION: The presence of lymph node and distant
metastases at first diagnosis significantly worsened prognosis and
survival rate in our series. Early diagnosis of MTC is very important,
allowing complete surgical cure in Stages I and II patients. Due to
the relatively bad prognosis of MTC, especially for disease Stages III
and IV, it appears reasonable to recommend radical surgery including
total thyroidectomy plus CC lymphoadenectomy as the treatment of
choice, plus LC lymphoadenectomy in patients with palpable and/or
ultrasound enlarged neck lymph nodes.
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