Diagnosis

Histopathology

In 1974, Thompson and colleagues reported a series of 25 patients with Hurthle cell neoplasms in which 75% of these whose lesions were initially described as benign (i.e. adenomas) subsequently died of Hurthle cell carcinoma.12 This led to the suggestion that gross and histopathologic examination of Hurthle cell neoplasms could not reliably predict clinical behavior and that all lesions should be treated as malignant or potentially malignant. Since then, however, several studies have shown that histologic criteria can reliably differentiate between Hurthle cell adenomas and carcinomas.

Grant and colleagues in 1988 reviewed 272 surgically resected Hurthle cell neoplasms at the Mayo Clinic that were deemed to be histologically benign and found that only 1 had an incorrect diagnosis manifested by tumor recurrence, with a mean follow-up of 4 years.13 The criteria currently used to diagnose Hurthle cell carcinoma are capsular or vascular invasion, invasion of adjacent structures, lymph node metastases, and distant metastases. Moreover, Carcangiu and associates found similar results in reviewing 153 cases of Hurthle cell neoplasms.10 In their study, patients were grouped into three categories: benign (90), indeterminate (35), and malignant (28). Malignant lesions had to demonstrate full-thickness capsular invasion, vascular invasion, or invasion into adjacent tissue. Indeterminate lesions had minimal capsular invasion, solid versus follicular growth pattern, marked nuclear atypia, and extensive necrosis. With up to 22 years of follow-up, no tumor recurrences or cause-specific death was seen in the benign or indeterminate groups. From these and other studies,14'15 one can conclude that histologic examination can differentiate benign from malignant Hurthle cell neoplasms and that the sine qua non of Hurthle cell carcinoma is full-thickness capsular and/or vascular invasion (Figs. 14-3 and 14-4).

FIGURE 14-3. A Hiirthle cell carcinoma invading through full-thickness capsule (C). The tumor (T) is present on both sides of the capsule and extends almost beyond the thyroid capsule.

Fine-Needle Aspiration

Fine-needle aspiration (FNA) can reliably detect Hiirthle cell neoplasms (see Fig. 14-1).16-18 FNA can also be helpful in differentiating Hiirthle cell neoplasms from non-neoplastic lesions with Hiirthle cells present. Hiirthle cell tumors are associated with a high percentage of Hiirthle cells; nests of Hiirthle cells; cellular dyshesion; large nucleoli; nuclear pleomorphism; significant nuclear enlargement; and the absence of macrophages, plasma cells, or lymphocytes.19

Although reliable histologic criteria for malignancy exist, FNA cannot accurately distinguish Hiirthle cell adenomas from carcinomas.20,21 Since FNA cannot determine the presence of full-thickness capsular and/or vascular invasion, several studies have focused on determining if any cellular features seen on FNA are associated with malignancy. Unfortunately, cellular atypia, including nuclear size, nuclear mitoses, cellular pleomorphism, necrosis, and percentage of Hiirthle cells, does not have a relationship to malignancy.10 Molecular profiling for expression of ras, p53, mdm-2, p21, cyclin Dl, Bcl-2, and other markers associated with

FIGURE 14-4. Vascular invasion by Hiirthle cell carcinoma (H). An endothelial-lined blood vessel (V) structure is completely occluded by tumor cells (T).

Number of patients (n)

FIGURE 14-5. Tumor size is predictive of malignancy. With increasing size, the chance of malignancy increases. (From Chen H, Nicol TL, Zeiger MA, et al: Hiirthle cell neoplasms of the thyroid: Are there factors predictive of malignancy? Ann Surg 1998; 227:542.)

malignancy have failed to show any correlation with Hiirthle cell carcinomas.7,22,23 DNA aneuploidy has been associated with increased recurrence and distant metastasis in patients with Hiirthle cell carcinoma; however, Hiirthle cell adenomas are also often aneuploid.23 Finally, size of a Hiirthle cell neoplasm has been shown to correlate with malignant potential (Fig. 14-5). In a series of 57 consecutive Hiirthle cell neoplasms, tumors 1 cm or less were found to be malignant in 17% of cases.8 However, 65% of tumors at least 4 cm in diameter proved to be malignant. Thus, other than size, no cytologic characteristics can reliably predict malignancy. Therefore, the cornerstone of diagnostic studies remains careful histologic evaluation.

Frozen Section Evaluation

Intraoperative frozen section evaluation has traditionally been used to assess indeterminate thyroid lesions. There have been no studies specifically addressing the use of frozen section evaluation in the management of Hiirthle cell neoplasms. However, because follicular thyroid carcinomas and Hiirthle cell carcinomas both are diagnosed solely by the presence of capsular and/or vascular invasion, studies addressing follicular lesions appear applicable. In a review of 125 consecutive patients with follicular thyroid lesions, including a small number of Hiirthle cell neoplasms, who underwent surgical exploration, frozen section evaluation was of minimal value, rendering no additional diagnostic information 87% of the time.24 Although providing diagnostic information in 13% of patients, in only 3.3% did frozen section correctly modify the surgical procedure. Notably, in 5% of patients, the frozen section was incorrect and potentially led to misguided interventions. Therefore, frozen section evaluation should play only a minor role in the management of Hiirthle cell neoplasms.

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