Yukiko Yano

Outcomes and Prognostic Factors of 251 Patients with Minimally Invasive Follicular Thyroid Carcinoma

BACKGROUND Radioiodine ablation after total thyroidectomy is the generally accepted treatment for patients with widely invasive follicular thyroid carcinoma (FTC). The therapeutic strategy for minimally invasive FTC, on the other hand, is still a matter of controversy. The histological diagnosis of minimally invasive FTC is often made after lobectomy. The aim of this study was to determine the factors associated with the development of distant metastases in patients with minimally invasive FTC. METHODS Between 1989 and 2006, 251 patients with minimally invasive FTC underwent initial surgery at our hospital. Their median follow-up period was 7.2 years. There were 194 women and 57 men. Their mean age at the time of surgery was 46 years. Distant metastases were diagnosed in 54 patients (21.5%). In 22 of them distant metastases were diagnosed at the time of the initial surgery (M1), and in the other 32 they were diagnosed during the follow-up period. Age at initial surgery, sex, primary tumor size, histological findings (differentiation, and extent of vascular and capsular invasion), completion total thyroidectomy, and distant metastases at initial surgery were assessed as prognostic factors for distant-metastases-free survival (DMFS) and cause-specific survival (CSS). The Kaplan-Meier method and log-rank test were used to analyze time-dependent variables. The Cox proportional hazard model was used to perform the multivariate analysis. RESULTS Univariate analysis showed that age (45 years or older) and primary tumor size (4 cm or more) were significant prognostic factors related to postoperative distant metastases in the group of 229 patients without distant metastases at time of the initial surgery. The cumulative survival rate was significantly poorer in M1 patients, patients aged 45 years or older, and patients whose primary tumor size was 4 cm or more. Multivariate analysis showed that age was a significant prognostic factor both for DMFS and CSS. CONCLUSIONS Age was the most powerful prognostic factor for patients with minimally invasive follicular thyroid cancer. The prognoses of patients younger than 45 years old were excellent and distant metastases rarely occurred. Routine completion total thyroidectomy and radioiodine ablation is thought unnecessary for these patients.

Prognosis and Prognostic Factors for Distant Metastases and Tumor Mortality in Follicular Thyroid Carcinoma

BACKGROUND Distant metastases are more common in patients with follicular thyroid carcinoma (FTC) than in patients with papillary thyroid carcinoma, and the outcome is often poorer in patients with distant metastases. In this study, we attempted to identify the risk factors for distant metastases in FTC. METHODS Between 1989 and 1997, 134 patients with FTC underwent initial surgery, and their median follow-up period was 12.5 years. Seventeen patients had widely invasive FTC, and 117 had minimally invasive FTC. Distant metastases were observed in 36 patients (26.9%). Thirteen of these patients had distant metastases at the time of initial surgery (M1), and in the other 23 patients distant metastases were diagnosed with during their follow-up periods. Risk factors for distant metastases and cause-specific survival were analyzed. The factors analyzed were age at the time of initial surgery, sex, primary tumor size, histological findings (invasiveness, extent of vascular, and capsular invasion), and distant metastases at the time of initial surgery. RESULTS Univariate analysis showed that age and primary tumor size were significant factors related to postoperative distant metastases in the group of 121 patients who did not have distant metastases at the time of initial surgery. When the patients with M1 were included, the cumulative distant metastases-free-survival rate was significantly lower in the group with widely invasive FTC. The cumulative survival rate was significantly higher in the groups of patients with the minimally invasive type, who were under 45 years old, whose primary tumor size was under 4 cm and who did not have distant metastases at the time of the initial surgery. Multivariate analyses showed that tumor size and age were significant risk factors for postoperative distant metastases and that age and the presence of distant metastases at the time of the initial surgery were significant risk factors for poorer cause-specific survival. CONCLUSION Age and primary tumor size were significant risk factors for postoperative distant metastases. Based on the findings in this study, we conclude that conservative management is sufficient for younger patients with minimally invasive FTC whose primary tumor is small.

Histiocytoid breast carcinoma: solid variant of invasive lobular carcinoma with decreased expression of both E-cadherin and CD44 epithelial variant.

Histiocytoid breast carcinoma (HBC) is a rare type of breast carcinoma with morphologic characteristics resembling those of histiocytes. Described herein are cytological and histological findings in a case of HBC. Fine‐needle aspiration cytology revealed numerous loosely cohesive tumor cells with abundant foamy to granular cytoplasm and bland‐appearing nuclei. The resected tumor exhibited a solid growth pattern instead of classic invasive lobular patterns observed in most reported cases of HBC. However, distinct intracytoplasmic lumina and Pagetoid extension to ducts suggested that this tumor was a variant of invasive lobular carcinoma. To determine the cause of the loose cellular cohesiveness of this HBC, its expression of the epithelium‐related cell adhesion molecules E‐cadherin and CD44v8‐10 (CD44 epithelial variant) was examined. Immunohistochemically, E‐cadherin was not detected, similar to most lobular carcinomas. Furthermore, competitive reverse transcription–polymerase chain reaction (RT‐PCR) analyses among alternatively spliced variants of CD44 revealed that the ratio of expression of CD44v8‐10 to that of CD44v10 (dominant variant in leukocytes) was lower than that for the reference breast carcinoma samples. It is concluded that the present case of HBC was a solid variant of invasive lobular carcinoma exhibiting foamy to granular cytoplasmic change. Decreased expression of both E‐cadherin and CD44 epithelial variant may be responsible for the loose cellular cohesiveness observed in HBC.

Long-term changes in parathyroid function after subtotal thyroidectomy for graves' disease.

BackgroundTransient hypocalcemia is one of the postoperative complications of thyroidectomy for Graves’ disease, and perioperative parathyroid hormone (PTH) assays are used to predict postoperative hypocalcemia. We evaluated long-term changes in parathyroid function after surgery for Graves’ disease.MethodsSerum PTH values were measured in Graves’ patients with postoperative hypocalcemia, and those patients were followed postoperatively.ResultsSubtotal thyroidectomy was performed in 275 patients with Graves’ disease. Their serum calcium levels were measured on postoperative day (POD) 1, and patients with transient postoperative hypocalcemia were treated with calcium and vitamin D supplementation and followed up. The amount of calcium and vitamin D supplementation was adjusted to keep the patient’s serum calcium level within the normal range. Measurement of their serum intact PTH value on POD 1 revealed normal value in 18 patients, a below normal level in 22, and an above normal level in the other 2. During the follow-up period, the serum iPTH values remained normal in 12 patients, recovered to the normal level in 21 patients, and rose above the normal range in 9 patients. The serum iPTH values of all patients eventually reached the normal range during the follow-up period. A marked difference in preoperative serum alkaline phosphatase concentration was observed between the high-iPTH patients and the normocalcemic patients.ConclusionsThe phenomenon of an elevated serum PTH level after surgery for Graves’ disease was observed in 21% of the patients with postoperative hypocalcemia despite the achievement of normal serum calcium levels by calcium and vitamin D supplementation.

Altered expression patterns of heterogeneous nuclear ribonucleoproteins A2 and B1 in the adrenal cortex.

Several proteins implicated in hormonogenesis of the adrenal cortex have alternatively spliced isoforms, which respond differently to adrenocorticotropic hormone (ACTH). Heterogeneous nuclear ribonucleoproteins A2 and B1 are among the abundant pre-mRNA-binding proteins involved in alternative splicing. We examined the expression of A2 and B1 in normal adrenal cortex and tumors. B1 was variably expressed in the zona fasciculata-reticularis, although A2 was diffusely expressed in the three zones. B1 was more abundant in compact cells than clear cells, and B1 expression was frequent in the zona reticularis, which consists mainly of compact cells. In three kinds of cortical adenomas autonomously producing hormones, B1 was generally overexpressed and there were no significant differences among them. In cortisol-producing tumors, non-tumor parts of the cortex, which were generally atrophic due to low ACTH, had less B1 protein than normal adrenals. These results suggested a correlation between B1 expression and the hormonal activity responding to ACTH. In vitro ACTH stimulation induced a biphasic expression of B1 in an H295R cortical carcinoma cell line, and it paralleled hormonogenesis. Conclusively, B1 expression varied in relation to the hormonal activity responding to the ACTH, and it may provide a key to elucidating the splicing mechanisms involved in hormonogenesis.

Interventricular methotrexate therapy for carcinomatous meningitis due to breast cancer: a case with leukoencephalopathy

A 46-year-old woman presented with paraplegia and severe lumbago. She had had a radical mastectomy for left breast cancer 10 years earlier, and 6 months prior to presentation she completed CMF chemotherapy for treatment of retroperitoneal metastasis. CT and MRI to identify potential causes of the paraplegia and lumbago showed leptomeningeal carcinomatosis due to dissemination from invasive recurrence of the retroperitoneal tumor. An Ommaya reservoir was inserted, and infusion of intrathecal methotrexate (MTX; 5 mg twice weekly) began. Her clinical symptoms improved after receiving 53 mg MTX. However, after receiving 83 mg MTX, the patient became dizzy from leukoencephalopathy. Although administration of prednisolone mostly resolved her symptom, the patient died 9 months after the diagnosis of carcinomatous meningitis.

Serum Intact Parathyroid Hormone Level After Total Thyroidectomy or Total Thyroidectomy Plus Lymph Node Dissection for Thyroid Nodules: Report From 296 Surgical Cases

Background Transient hypocalcemia is one of the postoperative complications of thyroidectomy for thyroid nodules, and intraoperative and postoperative intact parathyroid hormone (iPTH) assays are used to predict postoperative hypocalcemia. Objectives The current study was conducted to evaluate a single serum iPTH measurement on postoperative day 1 (POD 1) as a means to predict hypocalcemia occurrence after total thyroidectomy (TT). Patients and Methods The subjects consisted of 36 patients who underwent TT and 260 patients who underwent TT plus lymph node (LN) dissection for thyroid nodules treatment. The TT performance procedure to prevent postoperative hypoparathyroidism combines parathyroid gland preservation in situ with autotransplantation of resected or devascularized parathyroid glands. The patients’ serum iPTH level was measured on POD 1, and their serum calcium level was measured on POD 1 and on POD 3 while they were still inpatients. The serum iPTH level was subequently measured at each outpatient clinic visit until it recovered to the normal range. Results Hypoparathyroidism after TT and TT plus LN dissection was ultimately diagnosed in a total of 229 patients, and in 69 of them hypocalcemia was diagnosed on POD 1. All of the 69 patients diagnosed with hypocalcemia received calcium and vitamin D supplementation therapy. The serum iPTH level of 67 of 229 patients was within normal range on POD 1, and four of them developed hypocalcemia on POD 1. Permanent hypoparathyroidism developed in 37 of 296 patients after undergoing TT or TT plus LN dissection for thyroid nodules in the hospital. Conclusions A single serum iPTH measurement on POD 1 is useful to determine whether or not to start calcium and vitamin D supplementation in order to maintain normocalcemia after surgery.

Non-invasive lobular carcinoma within a fibroadenoma, a preoperatively diagnosed case

Breast cancer within a fibroadenoma is rare and usually diagnosed postoperatively from pathological specimens. This paper reports a 54-year-old female with non-invasive carcinoma within a fibroadenoma, diagnosed preoperatively. She underwent a medical examination and mastopathy was suspected. On physical examination a mass 2 cm in diameter was palpated in the left breast. Ultrasonography showed a mass with smooth margins and uniform internal echoes, but cytology showed malignancy. Mammography showed a round mass with distinct margins and no calcification. As fibroadenoma, diagnosed by ultrasonography and mammography, and breast cancer, diagnosed by cytology, were not consistent results several core biopsies were performed. Needle biopsy showed proliferation of atypical epithelial cells; breast cancer within a fibroadenoma was diagnosed. MRI showed a circular mass with distinct, smooth margins and in a dynamic study, the mass showed irregular staining and the presence of early staining. Left lumpectomy and dissection of the left axillary lymph nodes was performed. Histological examination showed non-invasive lobular carcinoma occurring within a fibroadenoma

Expression of heterogeneous nuclear ribonucleoproteins A2 and b1 in the thyroid follicular cells.

Several proteins implicated in hormonogenesis of the thyroid have alternatively spliced isoforms. Alternative splicing of pre-mRNA is considered to be important to regulate the hormonal activity. Heterogeneous nuclear ribonucleoproteins (hnRNP) A2 and B1 are two of the abundant nuclear RNA-binding proteins involved in alternative splicing. We examined the expression of hnRNP A2 and B1 in the thyroid, paying particular attention to the relationship between their function and the cellular morphology. B1 was expressed more frequently in cuboidal follicular cells that are hormonally active than in flat follicular cells in normal thyroid, although A2 expression showed no significant difference in two cell types. In Graves’ disease, the patients who had high serum levels of triiodothyronine and thyroxine showed significantly increased expression of B1. B1 expression did not differ significantly between normal thyroids and thyroid neoplasms, except undifferentiated (anaplastic) carcinoma. Conclusively, B1 expression varied in relation to hormonal activity in thyroid follicular cells. B1 protein is a good immunohistological marker to detect hormonal activity of follicular cells, and may provide a key to elucidate the splicing mechanisms involved in thyroid hormonogenesis.