Hiirthle Cell Thyroid Tumor

Hurthle cell thyroid tumors comprise 1% to 5% of all thyroid neoplasms and have been classified as variants of follicular thyroid tumors. They differ from follicular thyroid carcinomas by their inability to trap radioiodine and by

Hürth le cell adenomas

Left: losses Right: gains

Hürthle cell carcinomas

13 14 15 16 17 18

19 20

X 21

13 14 15

11 12

FIGURE 36-6. Summary of chromosomal aberrations analyzed by comparative genomic hybridization in 15 Hiirthle cell adenomas and 13 Hiirthle cell carcinomas.

17 18 19 20 21 22

the accumulation of mitochondria and eosinophilic cytoplasm on histology. They are also more likely to be multifocal, have nodal metastasis, and appear to be clinically aggressive. Hiirthle cell carcinomas are similar to follicular thyroid carcinomas in that they usually cannot be diagnosed by fine-needle aspiration biopsy or frozen section. It is also difficult to distinguish Hiirthle cell adenomas from carcinomas preoperatively or intraoperatively. Some investigators previously recommended that all Hiirthle cell tumors should be considered as malignant and be treated aggressively because of their malignant potential.27-28 Others suggested that Hiirthle cell tumors are separated into adenomas (which have no capsular and vascular invasion) and carcinomas, using similar criteria as used for follicular tumors.29-32 Some studies have suggested that patients with Hiirthle cell carcinoma do not necessarily have a worse prognosis than patients with follicular thyroid carcinoma.33'34

Hemmer and coworkers24 reported 3 of 4 Hiirthle cell adenomas had chromosomal aberrations. Frisk and associates25

also reported that 2 of 3 Hiirthle cell adenomas had chromosomal aberrations, as did 3 of 4 Hiirthle cell carcinomas. Similarly, Tallini and colleagues35 documented that 6 of 7 adenomas and 3 of 4 carcinomas had chromosomal aberrations. We found chromosomal aberrations in 9 of 15 Hiirthle cell adenomas and in 8 of 13 Hiirthle cell carcinomas.36 The mean number of chromosomal gains and losses were 2.1 and 0.7 in 15 adenomas versus 4.2 and 0.8 in 13 carcinomas. Although Hiirthle cell adenomas were more likely to have fewer chromosomal aberrations than Hiirthle cell carcinomas, in our study, this difference was not significant (P > 0.05) (Fig. 36-6 and Table 36-2).

Our investigations have found that whole or focal chromosomal gains are relatively common in chromosomes 5, 7, 12, 17, 19, and 20 and losses are in chromosomes 2 and 9 in both Hiirthle cell adenomas and carcinomas (see Fig. 36-6).36 Frisk and colleagues25 reported that loss of 9ql3-q21.3 was a specific aberration in Hiirthle cell carcinomas. In our study, gains in chromosome 12 were more common in Hiirthle cell

| TABLE 36-2. Comparison of Chromosomal Aberrations in Hiirthle Cell Thyroid Tumors

Study (Year)

Histologic Type

NCA

Mean NCA

GAINS

LOSSES

ANY ABERRATIONS

GAINS

LOSSES

Hemmer et al (1998p>

4 adenomas

3/4

0/4

3/4

2.8

0

Frisk et al (1999)25

4 carcinomas

1/4

3/4

3/4

1,8

1.8

3 adenomas

2/3

2/3

2/3

1.0

0.8

Tallini et al (1999)35

4 carcinomas

3/4

1/4

3/4

4.8

1.3

7 adenomas

5/7

3/7

6/7

4.1

1.3

Wada et al (2002)36

13 carcinomas

8/13

4/13

8/13

4.2

0.8

15 adenomas

8/15

6/15

9/15

2.1

0.7

NC A = number of chromosomal aberrations.

TABLE 36-3. Clinicopathologic Features Influence Frequency of Chromosomal Aberrations and Number of Chromosomal Gains and Losses in 13 Hiirthle Cell Carcinomas

Frequency of Chromosomal No. of Chromosomal No. of Chromosomal

Clinicopathologic Features Aberrations Gains Losses

TNM stage

Frequency of Chromosomal No. of Chromosomal No. of Chromosomal

Clinicopathologic Features Aberrations Gains Losses

TNM stage

i + n

3/8 (37.5%)

1.6

0,5

m

5/5 (100%)

8.4*

1.2

Differentiated

Well

4/9 (44.4%)

2.6

0.4

Moderately to poorly

4/4 (100%)

8.0*

1.5

Invasive

Minimally

2/7 (28.6%)

1.7

0.1

Intermediately to widely

6/6 (100%)*

7.2*

1.5

Recurrence

Negative

3/8 (37.5%)

1.3

1.0

Positive

5/5 (100%)

9.0*

0.4

Fisher's exact test for frequencies and Mann-Whitney test for numbers were used with the following results: *P < 0.05; 1P< 0.005.

Fisher's exact test for frequencies and Mann-Whitney test for numbers were used with the following results: *P < 0.05; 1P< 0.005.

carcinomas than in Hiirthle cell adenomas and, in particular, gains in I2q occurred more frequently in patients with Hiirthle cell carcinomas who developed recurrent disease (P < O.OOl).36 Roque and coworkers37 have reported an increased frequency of gains in chromosome 7 and 12 among different thyroid tumors (e.g., goiters, follicular adenomas, and follicular carcinomas). These findings support the concept that some thyroid neoplasms develop in a multistep process. We also found that gains in 5p, 7, 19p, 19q, and 20p were associated with a higher risk of tumor recurrence as well as 12q in patients with Hiirthle cell carcinoma (Table 36-4).36 The presence of these chromosomal aberrations in primary Hiirthle cell carcinoma may predict developing recurrent disease. Erickson and associates38 reported that loss of chromosome 22, by FISH, was associated with deaths due to Hiirthle cell carcinoma.

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