Kanji Kuma

An Observation Trial Without Surgical Treatment in Patients with Papillary Microcarcinoma of the Thyroid

The recent prevalence of ultrasound-guided fine-needle aspiration biopsy has resulted in a marked increase in the number of patients with papillary microcarcinoma (maximum diameter, </= 10 mm) of the thyroid detected by this sophisticated tool. On the other hand, it is debatable whether patients with papillary microcarcinoma should always undergo surgery after diagnosis, because a high incidence of occult papillary carcinoma has been observed in autopsy studies. Thus, we proposed observation without surgical therapy as a treatment option in 732 patients diagnosed with papillary microcarcinoma by the above technique from 1993 to 2001. One hundred sixty-two patients chose observation and were classified as the observation group. During the follow-up period for patients in the observation group, more than 70% of tumors either did not change or decreased in size compared to their initial size at diagnosis. They enlarged by more than 10 mm in 10.2%, and lymph node metastasis in the lateral compartments appeared in only 1.2% of patients during follow-up. On the other hand, 570 patients chose surgical treatment at diagnosis and 56 patients in the observation group who underwent surgery after a period of follow-up were classified as the surgical treatment group. Of these 626 patients, lymph node dissection was performed in 594 patients, and metastasis was confirmed histologically in 50.5%. Multiple tumor formation was seen in 42.8% of patients. In this group, the rate of recurrence was 2.7% at 5 years and 5.0% at 8 years after surgery. Our preliminary data suggest that papillary microcarcinomas do not frequently become clinically apparent, and that patients can choose observation while their tumors are not progressing, although they are pathologically multifocal and involve lymph nodes in high incidence.

Clinical Significance of Metastasis to the Central Compartment from Papillary Microcarcinoma of the Thyroid

We previously demonstrated that for papillary microcarcinoma (PMC), (1) patients with lateral lymph node metastasis detected on preoperative ultrasonography (US) are more likely to develop recurrence, and (2) dissection of the lateral compartment does not improve the prognosis of patients without US-detectable lateral metastasis. In this study, we focused on metastasis from PMC to the central compartment. We investigated the clinical significance of lymph nodes in the central compartment using the same series of 600 patients as used in the previous study. Ultrasound-diagnosed central node metastasis could be found in 30 patients (20.0%). Although the specificity of US for detecting central node metastasis was 99.1%, sensitivity was only 10.9%. Neither US-diagnosed nor pathologically confirmed central node metastasis affected the disease-free survival (DFS) rate of PMC patients. Furthermore, in cases where PMC was located only in one lobe, central node dissection in the contralateral lobe did not improve the DFS rate. These findings suggest that, for PMC, (1) US is an insensitive technique for detecting the central node metastasis, (2) the presence of central node metastasis is unrelated to DFS of patients, and (3) when performing lobectomy for PMC involving only one lobe, dissection of the central compartment in the contralateral lobe is optional.

Papillary Microcarcinoma of the Thyroid: How Should It Be Treated?

We previously demonstrated that (1) most papillary microcarcinomas can be followed without surgical treatment and (2) when surgery is performed, patients with lateral lymph node metastasis detected on preoperative ultrasonography (US) are more likely to develop recurrence. In this study, we further investigated the application of these strategies. To date, we have observed 211 patients (average follow-up 47.9 months). In more than 70% of these patients the tumor size did not increase during the follow-up period. There were no clinicopathologic features linked to tumor enlargement except in tumors ≥ 7 mm, which tended to enlarge in patients followed for 4 years. To evaluate not only whether observation can continue but also how to dissect the lymph nodes optimally at surgery, US diagnosis for lateral node metastasis is essential because the presence of US-diagnosed lateral metastasis is an even stronger predictive marker for recurrence than the presence of pathologically confirmed node metastasis. The positive predictive value (PPV) was 80.6% for US but reached 100% if fine-needle aspiration biopsy (FNAB) of nodes or FNAB-thyroglobulin measurement is added. Furthermore, carcinomas occupying the upper region of the thyroid more frequently showed US-diagnosed and pathologically confirmed lateral metastasis, and those measuring ≥ 7 mm were more likely to show pathologically confirmed lateral metastasis. These findings suggest that, for papillary microcarcinoma: (1) US-diagnosed lateral metastasis is a strong marker predicting a worse relapse-free survival; (2) FNAB of nodes and FNAB-thyroglobulin measurement are useful tools for evaluating lymph node metastasis; and (3) careful US evaluation for lateral metastasis is necessary in patients with a tumor measuring ≥ 7 mm or that is located in the upper region of the thyroid both during observation and preoperatively.

INTERNAL FISTULA AS A ROUTE OF INFECTION IN ACUTE SUPPURATIVE THYROIDITIS

Seven cases of acute suppurative thyroiditis are described. Six patients had a recurrent painful swelling of the left anterior neck and one was seen at her first episode of the disease. A barium meal revealed a fistula originating from the apex of the left pyriform sinus in all cases. The fistula, a remnant of the fourth pharyngeal pouch, thus seems to be a common route of infection in acute suppurative thyroiditis, allowing bacterial infection to begin in the perithyroidal space and spread to the thyroid gland. Complete extirpation of the fistula is required for a permanent cure.

Risk Factors for Recurrence to the Lymph Node in Papillary Thyroid Carcinoma Patients without Preoperatively Detectable Lateral Node Metastasis: Validity of Prophylactic Modified Radical Neck Dissection

BackgroundAlthough papillary carcinoma usually shows mild characteristics, it metastasizes and shows recurrence to the lymph node in high incidences. Of the two representative lymph node compartments to which papillary carcinoma metastasizes, the central compartment can be routinely dissected via the surgical incision made for thyroidectomy. However, the routine application of prophylactic lateral node dissection (modified radical neck dissection [MND]) remains controversial. In this study, we investigated risk factors for lymph node recurrence of papillary carcinoma to determine the appropriate application of prophylactic MND.MethodsWe investigated risk factors for lymph node recurrence in 1,231 patients without preoperatively detectable lateral node metastasis who underwent thyroidectomy, central node dissection, and prophylactic MND for papillary carcinoma between 1987 and 1995.ResultsThe incidence of lateral node metastasis and the number of metastatic lateral nodes significantly increased with carcinoma size. The lymph node disease-free survival (LN-DFS) was also significantly worse in carcinoma with a maximal diameter greater than 3 cm. Massive extrathyroid extension, male gender, and age 55 years or older also reflected a poorer LN-DFS. The 10-year LN-DFS rates of patients with carcinoma having two and three or four of these features were low at 88.5% and 64.7%, respectively, although the rates of those with carcinoma having no or only one characteristic were better than 95%.ConclusionsProphylactic MND is recommended for cases of papillary carcinoma demonstrating two or more of the following four characteristics; male gender, age 55 years or older, maximal tumor diameter larger than 3 cm, and massive extrathyroid extension.

Prognostic Significance of Extrathyroid Extension of Papillary Thyroid Carcinoma: Massive but Not Minimal Extension Affects the Relapse-free Survival

ObjectivesExtrathyroid extension has been recognized as a prognostic factor in papillary thyroid carcinoma. In the most recent version of the UICC TNM classification system, extrathyroid extension has been classified into two grades, minimal extension (extension to sternothyroid muscle or perithyroid soft tissues) and massive extension (extension to subcutaneous soft tissue, larynx, trachea, esophagus, or recurrent laryngeal nerve). In this study, we investigated the prognostic significance of each of the two types of extension.Patients and MethodsOne thousand and sixty-seven patients with papillary thyroid carcinoma without distant metastasis at surgery, who underwent surgical treatment in Kuma hospital between 1990 and 1995 and had been followed postoperatively for 60 months or more, were enrolled in this study. The grading of extrathyroid extension was based on both pathological findings and intraoperative surgical findings.ResultsIn univariate analysis, although patients with massive extension showed a significantly worse relapse-free survival (RFS) rate than those with no or minimal extension (P < 0.0001), there was no difference in the RFS rate between patients with no extension and those with minimal extension. Among patients with massive extension, the RFS rate tended to be worse in those with posterior extension than in those with anterior extension (P = 0.0562). Furthermore, the RFS rate of patients with massive posterior extension only to the recurrent nerve demonstrated a better RFS rate than those with extension to other posterior organs (P = 0.0052). Multivariate analysis demonstrated that massive extrathyroid extension is recognized as an independent prognostic factor for RFS (P = 0.0003).ConclusionsThese findings suggest that (1) upgrading of T category for tumors with massive extension is appropriate, whereas that for tumors with only minimal extension is not, and (2) careful surgical treatment and postoperative follow-up are required for tumors with massive extension to posterior organs other than the recurrent laryngeal nerve.

Preoperative ultrasonographic examination for lymph node metastasis: usefulness when designing lymph node dissection for papillary microcarcinoma of the thyroid.

ABSTRACTPapillary microcarcinoma has an excellent prognosis after surgical treatment, but how to dissect the lymph nodes remains an open question. In this study, we investigated whether modified radical neck dissection (MND) affected the lymph node recurrence-free survival (LN-RFS) rate for 590 patients with papillary microcarcinoma and recurrence in the lateral compartment who underwent surgery in our hospital between 1993 and 2001. MND was performed in 316 patients, and metastasis in lateral compartment was preoperatively detected on ultrasonography in 67. These 67 patients showed significantly worse LN-RFS (p = 0.0038) than the remaining 249 patients without preoperatively detectable lateral node metastasis. Of the 523 patients (590 minus the 67 patients) whose lateral node metastasis was not detected preoperatively, 249 underwent MND; the remaining 274 patients did not. There was no significant difference in LN-RFS between these two groups. Our preliminary data suggest that with papillary microcarcinoma: (1) MND is not necessary in patients without lateral node metastasis detected on ultrasonography preoperatively, and (2) patients with preoperatively detected lateral node metastasis are more likely to develop recurrence in the lymph nodes so careful MND should be performed.

Two Germline Missense Mutations at Codons 804 and 806 of the RET Proto-oncogene in the Same Allele in a Patient with Multiple Endocrine Neoplasia Type 2B without Codon 918 Mutation

Multiple endocrine neoplasia (MEN) type 2B is a clinically distinct entity among the autosomal dominant MEN 2 syndromes. Most patients with MEN 2B carry a germline mutation (M918T) of the RET proto‐oncogene, while a few carry A883F. We examined a patient with MEN 2B, but without M918T or A883F, and her relatives. Here, we report the presence in this patient of 2 germline mutations, V804M and Y806C in the same allele. While the novel Y806C was inherited from her father, its carriers (her father and brother) was not affected by MEN 2. In contrast, V804M was a de novo mutation, that has been reported in patients with familial medullary thyroid carcinoma. Combinations of mutations of the RET proto‐oncogene may cause oncogenic activities different from those of single mutations.

Clinical Significance of Lymph Node Metastasis of Thyroid Papillary Carcinoma Located in One Lobe

BackgroundPrevious studies have shown that lymph node metastasis can be of prognostic value. In this study, we investigated the clinical significance of node metastasis focusing on metastasis in the central compartment for patients with papillary carcinoma located in one lobe.Patients and MethodsWe investigated the frequency of lymph node metastasis in 759 patients with papillary carcinoma to determine whether and how such metastasis affects disease-free survival (DFS).ResultsCentral node metastasis was observed in 63% of patients, and the frequency was increased in relation to tumor size. The frequency of lateral node metastasis was 62.0%, which was also directly related to tumor size. On multivariate analysis of cases showing tumor larger than 1 cm, central node metastasis was recognized as an independent prognostic factor of DFS. The frequency of metastasis to the paratracheal nodes contralateral to the tumor was drastically elevated for tumors larger than 1 cm, but metastasis to this region did not independently predict worse DFS.ConclusionCentral node metastasis independently predicts a worse DFS for patients with papillary carcinoma larger than 1 cm.

Malignant lymphomas of the thyroid gland: Analysis of 79 patients with emphasis on histologic prognostic factors

Prognostic factors in 79 patients with malignant lymphomas involving the thyroid gland were analyzed. These patients suffered from progressively enlarging goiter with over 6 months duration in 60% of patients. The age at operation ranged from 16 to 80 years (median, 58 years). Male to female ratio was 1:1.8. Serum tests for antithyroid antibodies were positive in 83% of the patients, who also showed histologic evidence of chronic lymphocytic thyroiditis. Histologically, 52 cases (66%) were germinal center cell tumors with follicular or follicular and diffuse pattern in 9 cases. By the Working Formulation, 5‐year survival rate of immunoblastic type (IBL) (13%) was much poorer than those of intermediate (79%) and low grade cases (92%) (P < 0.001). The cases of IBL usually had a goiter of short duration, and frequently presented as advanced disease. Cancer 58:100–104, 1986.