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Current Approaches to the Treatment of Well-Differentiated Thyroid Cancer

Current Approaches to the Treatment of Well-Differentiated Thyroid Cancer

ABSTRACT: The management of well-differentiated thyroid cancer requires a multidisciplinary approach. The majority of patients are diagnosed only after a nodule is palpable. A cytologic evaluation can readily diagnose a papillary thyroid carcinoma but a follicular carcinoma requires determination of capsular or vascular invasion. Surgical considerations in well-differentiated thyroid cancer are frequently complicated by the need to operate on patients with indeterminate nodules. Also, the extent of surgery remains controversial. A total or near-total thyroidectomy has several advantages: (1) radioactive iodine can be used to ablate any residual thyroid tissue or cancer cells; (2) thyroglobulin levels can be used to follow a patient for recurrence; (3) the risk of leaving a focus of carcinoma in the remaining lobe is eliminated. [ONCOLOGY 16:309-324, 2002]

The contemporary management of well-differentiated
thyroid cancer requires a multidisciplinary approach involving primary care
physicians, endocrinologists, surgeons, pathologists, nuclear medicine
specialists, and sometimes radiologists and oncologists for diagnosis,
treatment, and long-term surveillance. Well-differentiated thyroid carcinoma
includes papillary and follicular thyroid carcinomas. These two types of cancer
comprise approximately 85% to 90% of all thyroid malignancies.[1] Managing these
cancers raises common concerns that will be addressed later.

Despite the fact that most cases of well-differentiated thyroid carcinoma
have an excellent prognosis, optimal treatment of the disease remains
controversial. Perhaps because of the slow growth of the tumors and the
infrequency with which patients die of the disease, no studies have been large
enough or of long-enough duration to definitively answer some of the central
questions in the treatment of well-differentiated thyroid cancer. The optimal
extent of surgical resection continues to be debated, as does the question of
which patients should receive radioactive iodine. Various authors have
questioned whether a lymph node dissection is beneficial to patients, and if so,
how extensive such a dissection should be.

Regardless of the answer to these questions, most patients with
well-differentiated thyroid cancer will do well, but only a large study with
several decades of follow-up will be able to discern any advantages among the
treatment options presented above. To date, there have been no randomized
studies to evaluate the comparative benefits of various treatment modalities.


Most patients with well-differentiated thyroid cancer initially present with
a thyroid nodule. The role of the primary care physician is critical at this
stage, because the majority of patients are diagnosed only after a nodule is
palpable on physical examination. Nevertheless, the increasing use of diagnostic
imaging such as carotid duplex scanning and computed tomography (CT) scanning
(for other reasons) has led to more frequent identification of thyroid nodules
before they are palpable.

Once a nodule is identified, the appropriate diagnostic work-up includes a
careful history with attention to risk factors such as radiation exposure,
previous thyroid cancer, or less commonly, family history of well-differentiated
thyroid cancer.[2] Hoarseness or lymphadenopathy associated with a palpable
thyroid mass is particularly suspicious for carcinoma.

Numerous imaging modalities are available for evaluating thyroid nodules. In
most instances, an ultrasound of the neck will provide accurate and detailed
information about the nodule as well as the status of the remainder of the
thyroid, including any possible lymphadenopathy in the cervical region.
Increasingly, microcalcifications in association with a thyroid nodule have been
identified as suspicious for papillary thyroid carcinoma.[3]

Thyroid scintigraphy continues to be helpful if the functionality of a nodule
is being questioned. CT scanning and magnetic resonance imaging (MRI) are
generally less helpful in the initial evaluation. Positron-emission tomography
(PET) scanning in conjunction with fluorine-18 fluorodeoxyglucose (FDG) has
shown promise in identifying thyroid malignancies, but it is not yet clear what
the most appropriate role for this imaging modality will be.[4,5]

Cytologic Evaluation

A diagnosis of well-differentiated thyroid cancer is often made
preoperatively with the use of fine-needle aspiration (FNA) cytology. A
diagnosis of papillary thyroid carcinoma is readily made on cytologic
evaluation. The cells characteristically have enlarged nuclei with dense
chromatin and, frequently, intranuclear cytoplasmic inclusions.

The cytologic diagnosis of follicular thyroid carcinoma is more problematic.
The distinction between benign adenoma and malignant carcinoma for this type of
tumor is not based primarily on cellular features, but rather, on the presence
of capsular or vascular invasion.[6] In other words, the cells in a benign
follicular adenoma and a malignant follicular carcinoma may be identical. The
distinction between benign and malignant depends largely on where the cells are
located. If there is no capsular or vascular invasion, then the lesion is
considered benign.

The nature of this distinction often leads to an indeterminate cytologic
evaluation, even when a follicular thyroid carcinoma has been aspirated. Such
nodules are usually characterized as "follicular neoplasms," since
benign lesions cannot be distinguished from malignant lesions on the basis of
cytology alone. When the results of the aspiration are indefinite, and because
the issue of capsular or vascular invasion cannot be determined no matter how
many times the cells in a nodule are sampled, most physicians recommend at least
a partial thyroidectomy (lobectomy or hemithyroidectomy). Only after the
pathologist has completely evaluated the entire nodule for capsular and vascular
invasion can such a tumor be categorized as a benign follicular adenoma.

Hürthle Cell Neoplasm

Follicular neoplasms can be further subcategorized into Hürthle cell
neoplasms. These uncommon tumors consist of large acidophilic or oncocytic
cells. Some authors have suggested that Hürthle cell carcinomas have a worse
prognosis than the usual follicular carcinoma.[7,8] This finding may be related
to the greater likelihood that Hürthle cell carcinomas are locally invasive and
concentrate radioiodine less avidly.


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