ABSTRACT
BACKGROUND: Papillary thyroid carcinoma (PTC) often extends to adjacent organs. According to the 8th Tumor-Node-Metastasis Classification, extension to the strap muscles was graded as T3b. We investigated the prognostic impact of T3b and the appropriateness of T3b in patients aged ≥55 years who were classified as stage II. METHODS: We enrolled 7811 patients with M0 PTC who underwent initial surgery at the Kuma Hospital (Kobe, Japan) between January 2007 and December 2016. Tumor extension was divided into T3b, T4a1 (extension to the tracheal adventitia, tracheal cartilage, esophageal muscle layer, recurrent laryngeal nerve, cricothyroid, and inferior constrictor muscles), and sT4a2 (extension to the subcutaneous soft tissues, tracheal mucosa, esophageal mucosa, internal jugular vein, brachiocephalic vein, larynx, pharynx, and sternocleidomastoid muscle). RESULTS: In patients ≥55 years, the local recurrence-free survival (LR-FS), distant recurrence-free survival (DR-FS), and cause-specific survival (CSS) rates of T3bN0M0 were significantly poorer than those of T1/T2N0M0 but did not significantly differ from those of T3aN0M0. The LR-FS, DR-FS, and CSS rates of T3b stage II patients did not differ from those of T4a1 stage III patients but were significantly better than those of T4a2 stage III patients. T3b was an independent predictor of local recurrence and distant recurrence but not of death due to carcinoma in the multivariate analysis. In patients aged <55 years with M0 PTC, T3b had no prognostic value in both analyses. CONCLUSIONS: T3bM0 patients are appropriate to be classified as stage II in patients ≥55 years but be kept in stage I in patients <55 years.
ABSTRACT
BACKGROUND: Patients with intermediate-risk papillary thyroid carcinoma (PTC) have a favorable prognosis with standard treatment of total thyroidectomy (TT) and adjuvant radioactive iodine therapy (RAIT). However, the benefits of TT or adjuvant RAIT remain undetermined, and they are often omitted in Japan. We investigated risk factors for life-threatening distant recurrence in patients with intermediate-risk PTC who are optimal candidates for adjuvant RAIT. PATIENTS AND METHODS: Outcomes without RAIT were retrospectively examined in 4030 intermediate-risk conventional PTC cases underwent initial surgery from 2005 to 22 (IRB approval 20200709-1). RESULTS: Lobectomy (LT) and TT was performed in 11.5% and 88.5%, respectively. Recurrent laryngeal nerve paralysis and hypoparathyroidism was less commonly observed in LT (1.3% and 0%) than TT (2.4% and 3.5 %). Fifty-six cases (1.4%) had distant recurrence. Recurrence-free survival rates at 10 years was 93.5%. There was no significant difference in recurrence rate between LT and TT. Age ≥55, cN1b, and tumor diameter >30 mm significantly associated with distant recurrence. There was a strong relationship between the number of positive risk factors and recurrence; the distant recurrence rate in cases of 0, 1, 2, and 3 positive factors was 0.3% (4/1203), 1.3% (25/1889), 2.7% (23/830) and 7.1% (4/52) (HR 6.46 (2.34-17.86), Log-rank <0.001). CONCLUSION: For intermediate-risk conventional PTC, there is no difference in prognosis even if LT was selectively conducted. However, in patients with risk factors for distant metastatic recurrence, such as age ≥55 years, cN1b, and tumor size >30 mm, adjuvant RAIT was considered eligible.
ABSTRACT
This multi-institutional study investigated non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) frequency and its diagnostic significance in Japan. We reviewed 4008 thyroid nodules resected in six institutions before NIFTP was proposed. Overall, 26 cases diagnosed as non-invasive encapsulated follicular variant of papillary thyroid carcinoma (PTC) and 145 cases of follicular thyroid adenoma (FTA) were included. Of these nodules, 80.8% and 31.0%, respectively, were NIFTPs. In five institutions, NIFTPs were more commonly found in FTA than in PTC nodules. When NIFTP was included with PTC, the overall prevalence was 2.3%, with rates in five institutions below 5.0% (0.8%-4.4%). One NIFTP case with nuclear score 3 revealed nodal metastasis 2.5 years post-resection, and the carcinoma cells were immunohistochemically positive for BRAF. FTAs or NIFTPs with nuclear score 2 did not metastasize. NIFTP was more common among FTA than among PTC nodules, possibly due to underdiagnosis of PTC on nuclear findings. Considering the clinical findings, molecular pathogenesis, and therapeutic strategy in Japan, NIFTP with nuclear score 2 is not different from FTA, and use of this entity terminology is not meaningful. In contrast, NIFTP with nuclear score 3 has potential for metastasis and BRAFV600E mutation. Therefore, in NIFTP cases, nuclear scores 2 and 3 should be separately reported.
Subject(s)
Thyroid Neoplasms , Humans , Japan/epidemiology , Prevalence , Proto-Oncogene Proteins B-raf/genetics , Thyroid Cancer, Papillary/diagnosis , Thyroid Cancer, Papillary/epidemiology , Thyroid Cancer, Papillary/pathology , Thyroid Neoplasms/diagnosis , Thyroid Neoplasms/epidemiology , Thyroid Neoplasms/pathologyABSTRACT
Activating rearranged during transfection (RET) proto-oncogene alterations can be identified using next-generation sequencing (NGS) of tumor DNA/RNA. We assessed factors associated with NGS (Oncomine Dx Target Test [ODxTT]) success for resected thyroid cancer (TC) specimens, including sample age, processing conditions, and DNA/RNA quality. TC samples were from three Japanese hospitals, with sample age <1-<10 years, fixative 10%/15% neutralized buffered formalin (NBF), and fixation time ≤48 h/>48 h-≤72 h. NGS success rate was defined as the percentage of samples returning validated NGS results (RET fusion-positive/negative [RNA] or RET mutation-positive/negative [DNA], detected using ODxTT). DNA/RNA quality was assessed with indexes based on electrophoresis (DNA/RNA integrity number, DV200 ) and quantitative polymerase chain reaction (DNA/RNA integrity score [ddCq/ΔCq]). NGS success rate (N = 202) was 90%/93% (DNA/RNA) overall, 98%-100% (DNA and RNA) for samples <3 years old, and 91% (DNA and RNA) for samples ≥3-<5 years old fixed in 10% NBF for ≤48 h. Multivariate logistic regression analysis identified ddCq and ΔCq as significant predictors of DNA and RNA NGS success rates, respectively. Quality assessment of nucleic acid extracted from archival tissue samples is important for achieving high NGS success rates in clinical practice, especially for samples ≥3 years old.
Subject(s)
DNA, Neoplasm , Thyroid Neoplasms , Humans , Child , Child, Preschool , Fixatives , Mutation , RNA , Thyroid Neoplasms/genetics , Thyroid Neoplasms/surgery , High-Throughput Nucleotide Sequencing/methodsABSTRACT
Active surveillance (AS) for low-risk papillary thyroid microcarcinoma (PTMC), which was initiated at Kuma Hospital (Kobe, Japan) in 1993 and Cancer Institute Hospital (Tokyo) in 1995, is now gradually being adopted worldwide, and several prospective studies have described the favorable outcomes of PTMC patients who underwent AS. The most important factor predicting PTMC growth is young age, and PTMC enlargement in young patients may be affected by high serum levels of thyroid-stimulating hormone. This review notes that one patient showed lung metastasis after conversion surgery (CS) following AS, but there are no reports of patients dying of thyroid carcinoma during or after AS. Some PTMCs enlarge or show newly appeared metastatic nodes requiring CS, and findings on the postoperative prognosis and incidence of significant surgical complications (e.g., permanent vocal cord paralysis, hypoparathyroidism) do not differ significantly between patients who underwent CS after AS and those who underwent immediate surgery (IS). IS has been associated with significantly higher incidences of these complications compared to AS as the initial management. Several studies have examined the quality of life (QoL) of patients who underwent AS versus IS, and reported discrepant findings regarding various psychological conditions (including anxiety). Medical costs for AS and IS vary regionally, and in Japan, the 10-year total cost of IS was 4.1 times greater than that of AS in 2017. Taken together, the existing findings demonstrate that AS can be appropriate for the initial management of patients with PTMC.
Subject(s)
Carcinoma, Papillary , Quality of Life , Thyroid Neoplasms , Adult , Humans , Watchful Waiting , Prospective Studies , Thyroid Neoplasms/surgery , Thyroid Neoplasms/epidemiology , Thyroidectomy , Retrospective StudiesABSTRACT
Subclinical hyperthyroidism (SHyper) is defined as normal levels of free thyroxine (fT4) and free triiodothyronine (fT3) with suppressed levels of TSH. Previous studies have reported the individual pathophysiology of endogenous SHyper patients and athyreotic patients receiving TSH suppression therapy with levothyroxine; however, apparently no studies have compared the two conditions. Five-hundred-forty untreated endogenous SHyper patients and 1,024 patients receiving TSH suppression therapy who underwent total thyroidectomy for papillary thyroid carcinoma were sampled. Thyroid hormone profiles and peripheral indices related to thyrotoxicosis were investigated in endogenous SHyper patients, athyreotic patients receiving TSH suppression therapy, and healthy participants. Endogenous SHyper patients showed significantly higher thyroid hormone levels (fT4 [p < 0.001] and fT3 [p < 0.001]), and peripheral indices showed a significant tendency towards thyrotoxicosis (strong TSH suppression: alkaline phosphatase [ALP, p < 0.001], creatinine [Cre, p < 0.001], pulse rate [p < 0.05]; and mild TSH suppression: Cre [p < 0.05]) than healthy participants. In contrast, athyreotic patients receiving TSH suppression therapy showed a significant tendency towards thyrotoxicosis than healthy participants only when TSH was strongly suppressed (fT3 [p < 0.001] and Cre [p < 0.001]). Endogenous SHyper patients showed significantly higher fT3 levels (p < 0.001) than athyreotic patients receiving TSH suppression therapy; however, there was a significant tendency towards thyrotoxicosis only when TSH was strongly suppressed (ALP [p < 0.05] and pulse rate [p < 0.05]). The effects of endogenous SHyper and TSH suppression therapy on target organ function are different. Although the serum thyroid hormone profile is similar to that of the thyrotoxic state, athyreotic patients receiving TSH suppression therapy with mildly suppressed serum TSH levels are not thyrotoxic.
Subject(s)
Hyperthyroidism , Thyroidectomy , Thyrotropin , Thyroxine , Triiodothyronine , Humans , Hyperthyroidism/blood , Hyperthyroidism/physiopathology , Hyperthyroidism/complications , Female , Male , Adult , Middle Aged , Thyroxine/therapeutic use , Thyroxine/blood , Triiodothyronine/blood , Thyrotropin/blood , Thyroid Neoplasms/blood , Thyroid Neoplasms/physiopathology , Thyroid Neoplasms/complications , Thyrotoxicosis/blood , Thyrotoxicosis/physiopathology , Thyrotoxicosis/complications , Thyroid Function Tests , Aged , Thyroid Cancer, Papillary/blood , Thyroid Cancer, Papillary/physiopathology , Thyroid Cancer, Papillary/complicationsABSTRACT
Methotrexate (MTX) is a well-known agent that can potentially cause lymphoproliferative disorder (LPD), known as MTX-related LPD (MTX-LPD). Only two cases of thyroid MTX-LPD have been reported to date. This study aimed to report 11 cases of MTX-LPDs arising in the thyroid gland and discuss their clinicopathological characteristics. Of the 747 patients with cytologically suspected lymphoma, 11 had received MTX. The mean age of the patients with MTX-LPD was 70.2 years (range: 51-82 years), and all were female. The duration of MTX administration ranged from 5 to 31 years (mean: 19.5 years). Nine patients (81.8 %) tested positive for anti-thyroglobulin antibody and/or anti-thyroid peroxidase antibody. In three patients, the tumor decreased in size or disappeared without surgery or chemotherapy after withdrawal of MTX therapy. Histologically, all eight nodules examined were B-cell lymphomas, and seven were mucosa-associated lymphoid tissue (MALT) lymphomas. Epstein-Barr virus-encoded small RNA in situ hybridization showed negative results for all six nodules examined. All five patients who were followed-up at our hospital exhibited progression-free survival for >3 years without chemotherapy. Six patients were transferred to other hospitals, and their follow-up details are unknown. MTX-LPDs occurring in the thyroid are characterized by a high female predominance, positivity for anti-thyroid autoantibodies, high prevalence of MALT lymphomas, negativity for Epstein-Barr virus, and good outcomes without chemotherapy. We recommend that patients with thyroid lymphoma should be checked for a history of MTX.
ABSTRACT
INTRODUCTION: The basic nature of cancer includes unlimited growth, invasion, and metastasis. The TNM staging system is very simple and popular. It indicates the degree of the anatomical spread of the disease but does not include tumor growth. Collins reported that human tumors grow exponentially, which can be expressed in doubling time. PATIENTS AND METHODS: We found that in patients with medullary thyroid carcinoma (MTC) and papillary thyroid carcinoma (PTC) serum calcitonin and thyroglobulin levels changed exponentially over time, respectively, and that doubling times of these values were very strong prognostic factors. Doubling time has two major limitations. Doubling rate resolves these limitations. Using doubling rate, we performed kinetic analyses on tumor volume during active surveillance of micro-PTC. RESULTS: Our kinetic studies on patients with biochemically persistent disease revealed that 17% of MTC and 51% of PTC showed decrease in serum tumor marker levels over time. During active surveillance of micro-PTC, 17% of the patients showed clear decrease in their tumor volume. The evidences currently available are limited. However, our data indicate the following: Growth slowdown and regression are very common phenomena in the natural history of micro-PTC, clinical PTC in young and middle-aged patients, and hereditary MTC. The biologic characteristics of cancers of the same name, such as PTC, are diverse and vary widely with age. CONCLUSIONS: Doubling time and doubling rate are very powerful tools to provide the most appropriate management for the patients with thyroid cancers. Knowing the natural history of thyroid cancer is essential for the best disease management of thyroid cancer.
Subject(s)
Carcinoma, Papillary , Thyroid Neoplasms , Middle Aged , Humans , Kinetics , Carcinoma, Papillary/pathology , Thyroid Neoplasms/pathology , Thyroid Cancer, Papillary , Retrospective StudiesABSTRACT
BACKGROUND: Active surveillance (AS) of low-risk papillary thyroid microcarcinoma (PTMC) was initiated at Kuma Hospital in 1993 and is gradually spreading worldwide. We assessed the effect of thyroid-stimulating hormone (TSH) levels on PTMC enlargement in patients on AS. METHODS: We enrolled 2705 patients with cytologically diagnosed PTMC who had undergone AS between January 2005 and July 2019. Patients with Graves disease were excluded. The median AS period was 5.5 years (range 1.0-15.7 years). Tumor enlargement was defined as a size increase ≥3 mm. Chi-square test, Kaplan-Meier method, log-rank test, Cox proportional hazard, and logistic regression were used to compare variables. RESULTS: Ninety-two patients (3.4%) experienced tumor enlargement; the 5-, 10-, and 15-year enlargement rates were 3.0%, 5.5%, and 6.2%, respectively. Young age (<40 years, p < 0.001), large tumor size (≥9 mm, p = 0.017), and high detailed TSH score (≥3, higher than the lower normal limit, p = 0.011) were significant factors relating to tumor enlargement in the multivariate analysis. In a subset of patients aged <40 years, a low detailed TSH score (<3) was an independent factor against tumor enlargement (p = 0.039). Only 22 patients (0.8%) experienced novel lymph node metastasis; the 5-, 10-, and 15-year node metastasis rates were very low, at 0.9%, 1.1%, and 1.1%, respectively. CONCLUSIONS: Young patients with PTMC are more likely to experience tumor growth. Mild TSH suppression to achieve a low normal range may prevent carcinoma enlargement; however, prospective studies are needed to draw more reliable conclusions.
Subject(s)
Thyroid Neoplasms , Thyrotropin , Humans , Adult , Watchful Waiting , Thyroid Neoplasms/surgery , Thyroid Neoplasms/pathology , Risk Factors , Retrospective StudiesABSTRACT
A preoperative diagnosis of metastatic renal cell carcinoma to the thyroid (MRCCT) is important for determining clinical management but is challenging even in cases with a clinical history of renal cell carcinoma (RCC). This study aimed to elucidate the clinical, cytological, and pathological characteristics of MRCCT. Fourteen MRCCT cases extracted from 18 320 malignant thyroid tumors were included in this study. Twelve MRCCT (85.7%) occurred as solitary lesions and the most frequently suspected lesions on ultrasonography were follicular tumors. On cytology, 46.2% of cases were reported as RCC or suspected RCC; a medical history of RCC and immunocytochemistry were helpful in interpretation. RCC metastasized to a follicular adenoma in 50.0% of the solitary lesions. MRCCTs with a long interval from the initial presentation, solitary lesion, and Ki-67 labeling index <10% showed significantly longer disease-free survival. MRCCT is characterized by a long interval from the initial presentation of RCC, appearance as a solitary nodule, ultrasonographic similarity to follicular tumors, sharing cytological findings with primary thyroid tumors, and high frequency of metastasis within follicular adenoma. A long interval from the initial presentation, occurrence as a solitary lesion, and low Ki-67 labeling index may be favorable prognostic factors.
Subject(s)
Adenocarcinoma, Follicular , Carcinoma, Renal Cell , Kidney Neoplasms , Thyroid Neoplasms , Humans , Adenocarcinoma, Follicular/secondary , Carcinoma, Renal Cell/pathology , East Asian People , Ki-67 Antigen , Kidney Neoplasms/pathology , Thyroid Neoplasms/secondaryABSTRACT
Active surveillance (AS) is an accepted management option for patients with low-risk papillary thyroid microcarcinoma (PTMC), although some patients undergo immediate surgery (IS). At surgery, patients may have risky features such as adhesion or invasion to the adjacent organs. The surgical outcomes of this subset of patients are unknown. Here, we investigated the surgical and oncological outcomes of these patients in comparison with others. Between 2005 and 2019, 4,635 patients were diagnosed with low-risk PTMC at our institute. Of these, 1,739 patients underwent IS. In total, 114 patients had risky features at surgery (risky feature group), while the remaining 1,625 did not (no-risky feature group). The median follow-up periods in the risky and no-risky feature groups were 8.5 and 7.6 years, respectively. The risky feature group had higher incidences of tracheal invasion (8.8%), recurrent laryngeal nerve invasion (RLN) (7.9%), and permanent vocal cord paralysis postoperatively (10.0%) and higher frequency of pathological lateral lymph node metastasis (6.1%) than the no-risky feature group (0%, 0%, and 0.2%, and 0%, respectively [p < 0.01]). However, unexpectedly, the former had a lower incidence of high Ki-67 labeling index (1.1%) and lower locoregional recurrence rate (0%) than the latter (8.3% and 0.7, respectively [p < 0.01], not calculable). None of the groups developed distant metastasis or died of the disease. The risky feature group required resection of the trachea and/or the RLN more often than the no-risky feature group. However, unexpectedly, the tumor growth activity in the risky feature group was low, and their oncological outcome was excellent.
Subject(s)
Thyroid Neoplasms , Thyroidectomy , Humans , Thyroidectomy/adverse effects , Neoplasm Recurrence, Local/epidemiology , Neoplasm Recurrence, Local/surgery , Thyroid Neoplasms/epidemiology , Thyroid Neoplasms/surgery , Thyroid Neoplasms/diagnosis , Risk Factors , Retrospective StudiesABSTRACT
Although the outcomes of active surveillance (AS) for low-risk papillary thyroid microcarcinoma (PTMC) are generally excellent, some patients undergo conversion surgery for various reasons, including disease progression. We studied the outcomes of PTMC patients who underwent AS, who underwent conversion surgery after AS, and who underwent immediate surgery. Between 2005 and 2019, 4,635 patients were diagnosed with low-risk cT1aN0M0 PTMC at Kuma Hospital: 2,896 opted for AS (AS group) and 1,739 underwent immediate surgery (Surgery group). In the AS group, 242 patients underwent conversion surgery (Conversion group): 72 owing to disease progression (Conversion-prog group) and 170 for other reasons (Conversion-non-prog group). Of the 1,739 patients in the Surgery group, 1,625 had no high-risk features (Surgery-low-risk group). Locoregional recurrence (LRR) occurred in 9, 1, 1, and 0 patient in the Surgery-low-risk group, the Conversion-prog group, the AS group, and the Conversion-non-prog group, respectively. The LRR rate of the AS group was significantly lower than that of the Surgery-low-risk group (0.1% vs. 0.7% at 10 years, p = 0.006). Additionally, the LRR rate of the Conversion group (0.6% at 10 years, p = 0.741) and that of the Conversion-prog group (3.3% at 10 years, p = 0.103) did not significantly differ from the LRR of the Surgery-low-risk group. As the postoperative prognosis of patients with progressive PTMC who underwent conversion surgery did not significantly differ from that of patients who underwent immediate surgery, we think that AS may have resulted in efficient identification of the small proportion of patients with progressive PTMC that require surgical treatment.
Subject(s)
Thyroid Neoplasms , Thyroidectomy , Humans , Watchful Waiting , Neoplasm Recurrence, Local/surgery , Thyroid Neoplasms/diagnosis , Thyroid Neoplasms/surgery , Thyroid Neoplasms/pathology , Risk Factors , Disease Progression , Retrospective StudiesABSTRACT
INTRODUCTION: We aimed to clarify the clinical and pathological characteristics of papillary thyroid carcinoma (PTC) with unique honeycomb-like growth (HLG) and discuss its diagnostic significance. METHODS: Among the 12,745 PTCs that were resected and histologically diagnosed, 28 PTC cases with HLG components (0.2%) were included. RESULTS: PTC-HLG was subclassified into pure (9 cases), which consisted of only HLG components, and mixed (19 cases), which consisted of conventional PTC and HLG components, types. HLG components were histologically characterized by (1) neoplastic cyst aggregation with intervening normal thyroid follicles, (2) the cyst wall composed of single-layered carcinoma cells, (3) low papillary growth, and (4) ball-like granulation tissues. Compared with the mixed type, the pure type occurred in older people (p < 0.05), had a smaller tumor size (p < 0.0001), was more interpreted as being benign by ultrasound (p < 0.05), and had a lower lymph node metastasis rate (p < 0.005). In the mixed type, 44.4% of conventional PTCs showed a Ki-67 labeling index of >5%. All and 10.5% of the mixed type showed lymph node and lung metastases, respectively. CONCLUSION: The pure type could be a nonaggressive variant of PTCs with a unique honeycomb growth pattern and tended to be clinically interpreted as benign. The mixed type is pathogenetically different from the pure type and is slightly aggressive compared with conventional PTCs.
Subject(s)
Carcinoma, Papillary , Thyroid Neoplasms , Aged , Carcinoma, Papillary/diagnosis , Carcinoma, Papillary/pathology , Humans , Lymphatic Metastasis , Thyroid Cancer, Papillary/diagnosis , Thyroid Neoplasms/diagnosis , Thyroid Neoplasms/pathologyABSTRACT
Intrathyroidal thymic carcinoma (ITTC) is a rare malignancy of the thyroid. It is thought to originate from ectopic thymic tissue or embryonic thymic rest, in, or adjacent to, the thyroid. We analyzed the backgrounds, clinicopathological features, and prognosis of 20 patients with ITTC, treated at our hospital. Thirteen of the 15 patients (86%) who underwent ultrasonography were diagnosed as malignant, based on imaging findings. 16 of the 17 patients (93%) who underwent cytology, were diagnosed or suspected to be malignant. Locally curative surgery (thyroidectomy and lymph node dissection) was performed for 19 patients. Large tumor size (>4 cm) was positively related to pathological node metastasis (p = 0.0389). Fourteen patients, including nine Ex-positive patients, underwent adjuvant external beam radiotherapy (EBRT) of the neck after surgery. Two patients showed recurrence of thyroid bed after and neither of them underwent adjuvant EBRT after surgery. Two patients who underwent EBRT showed recurrences of the lateral nodes (level V and level II), but they were easily dissected by re-operation. Ten- and 20-year local recurrence-free survival rates were 84.9% and 60.6%, respectively. To date, four patients showed distant recurrence, and 10- and 20-year distant recurrence-free survival rates were 75.0% and 75.0%, respectively. Our findings indicate that 1) the prognosis of ITTC is generally favorable, and 2) large tumor size is significantly related to lymph node metastasis. Two patients showing recurrence of the central region did not undergo EBRT; thus, further comparative studies are desirable to elucidate whether EBRT can prevent significant local recurrence.
Subject(s)
Carcinoma, Papillary , Thymoma , Thymus Neoplasms , Thyroid Neoplasms , Humans , Carcinoma, Papillary/pathology , Thyroid Neoplasms/diagnosis , Thyroid Neoplasms/surgery , Thyroid Neoplasms/pathology , Thymoma/diagnostic imaging , Thymoma/surgery , Thyroidectomy/methods , Prognosis , Thymus Neoplasms/diagnosis , Thymus Neoplasms/surgery , Neoplasm Recurrence, Local/pathology , Neck Dissection , Retrospective StudiesABSTRACT
Hypoparathyroidism is a major complication of thyroid surgery. To avoid this complication, visual identification of the parathyroid glands is essential. However, its effectiveness depends heavily on the surgeon's expertise. Here, we describe a novel method, the gauze blotting technique, to immunochemically identify the parathyroid glands during thyroid surgery. Twenty-three patients who underwent thyroid lobectomy were enrolled in this study; 16 and 7 had benign and malignant thyroid diseases, respectively. After visually identifying candidate nodules for the parathyroid gland, a piece of dry gauze (5 mm × 10 mm) was applied to each tissue until it was moistened by exudates from the tissue. Pieces of gauze were also applied to the thyroid gland and adipose tissue located away from the candidate nodules. The gauze was immersed in saline, and the intact PTH (i-PTH) level of the supernatant was measured. The median PTH level for the parathyroid glands was 1,060 pg/mL, which was significantly higher than that for the thyroid gland (34 pg/mL) and adipose tissue (28 pg/mL) (p < 0.001). The cut-off value to distinguish the parathyroid gland from other tissues was 68 pg/mL with a positive predictive value, negative predictive value, sensitivity, and specificity of 84.6%, 88.8%, 86.8%, and 86.7%, respectively. A value ≥250 pg/mL yielded a 100% positive predictive value. Our novel gauze blotting technique can identify the parathyroid glands without damaging tissues during thyroid surgery.
Subject(s)
Hypoparathyroidism , Parathyroid Glands , Humans , Parathyroid Glands/pathology , Thyroid Gland/surgery , Thyroid Gland/pathology , Parathyroid Hormone , Hypoparathyroidism/etiology , Hypoparathyroidism/pathology , Hypoparathyroidism/surgery , Thyroidectomy/adverse effects , Thyroidectomy/methodsABSTRACT
Nephrotic syndrome (NS) is characterized by massive urinary protein leakage and associated hypoproteinemia due to increased protein permeability caused by impaired renal glomerular connections. Although there have been several sporadic reports regarding the relationship between NS and thyroid dysfunction, a consensus has yet to be reached. The mechanism of hypothyroidism in NS is attributed to the loss of protein-bound thyroid hormones, such as thyroxine-binding globulin, transthyretin, and albumin, into the urine. Herein, we report four adults with hypothyroidism that developed or worsened due to the onset of NS. The patients' underlying thyroid status was post-total thyroidectomy with supplemental levothyroxine (L-T4) in two patients, hypothyroidism with supplemental L-T4 due to Hashimoto's disease in one patient, and Hashimoto's disease with normal thyroid function in one patient. Our results suggest that the presence of a reduced thyroid reserve may predispose patients to hypothyroidism in NS. We conclude that NS may cause or exacerbate hypothyroidism. In such cases, an NS assessment, including a urine test, is required.
Subject(s)
Hashimoto Disease , Hypothyroidism , Nephrotic Syndrome , Adult , Hashimoto Disease/complications , Humans , Nephrotic Syndrome/complications , Thyroxine/therapeutic useABSTRACT
Older age is recognized as a predictor of poor prognosis in papillary thyroid carcinoma (PTC) patients. However, young age is associated with disease progression of PTC measuring 1 cm or smaller in patients on active surveillance. In this study, we investigated the relationship between patient age and prognosis of PTC belonging to very low-, low-, and intermediate-risk groups based on the guidelines published by the Japan Association of Endocrine Surgery in 2018. We enrolled 4,870 PTC patients with no high-risk features and assigned each to one of three categories: very low risk (N = 1,161), low risk (N = 1,746), and intermediate risk (N = 1,963). In very low-risk patients, the local recurrence-free survival (RFS) rate of young patients (<55 years) was significantly worse (p = 0.0437) than that of older patients (≥55 years). In low-risk patients, although age did not affect local recurrence, older patients were more likely to show distant recurrence on univariate (p = 0.0005) and multivariate analyses (p = 0.0017). In the intermediate-risk series, the local RFS rate of older patients tended to be poor (p = 0.0538), and older age was significantly associated with distant RFS (univariate, p = 0.0356; multivariate, p = 0.0439) and carcinoma death (univariate, p < 0.0001; multivariate, not done because of no other suitable factors). The prognostic significance of patient age depends on risk classification: younger age significantly predicts local recurrence in very low-risk PTC, while older age predicts worse prognosis in low- and intermediate-risk patients. These findings indicate that young age is related to rapid growth in early-phase PTC.
Subject(s)
Carcinoma, Papillary , Carcinoma , Thyroid Neoplasms , Carcinoma/diagnosis , Carcinoma/epidemiology , Carcinoma/surgery , Carcinoma, Papillary/diagnosis , Carcinoma, Papillary/epidemiology , Carcinoma, Papillary/surgery , Humans , Middle Aged , Neoplasm Recurrence, Local/surgery , Prognosis , Retrospective Studies , Thyroid Cancer, Papillary/diagnosis , Thyroid Cancer, Papillary/surgery , Thyroid Neoplasms/diagnosis , Thyroid Neoplasms/epidemiology , Thyroid Neoplasms/surgery , ThyroidectomyABSTRACT
The World Health Organization (WHO) classifies follicular thyroid carcinoma (FTC) into three categories: minimally invasive (mFTC), encapsulated angioinvasive (eaFTC), and widely invasive (wFTC). This study investigated whether this classification is appropriate. We enrolled 523 patients who underwent initial surgery at Kuma Hospital between 1998 and 2015 and were diagnosed with FTC. Capsular invasion (CI) was classified as none, minimal (microscopic), or wide (macroscopic) invasion. Vascular invasion (VI) was divided according to the number of invasive foci into three degrees: VI(-), VI(1+), and VI(2+). For 507 M0 patients, age ≥55 years (p = 0.004), non-oxyphilic histology (p = 0.043), and male sex (p < 0.001) predicted poor distant recurrence-free survival (DR-FS) on univariate analysis; however, tumor size >4 cm and wide CI did not. The DR-FS rates significantly decreased from VI(-) to VI(2+) in a step-by-step fashion, including VI(-) vs. VI(1+) (p = 0.011) and VI(1+) vs. VI(2+) (p = 0.014). Multivariate analysis revealed that older age (p = 0.0004), non-oxyphilic histology (p = 0.041), male sex (p = 0.0052), VI(1+) (p = 0.017), and VI(2+) (p < 0.001) independently predicted distant recurrence. The DR-FS rates did not significantly differ among mFTC, wFTC/VI(-), and eaFTC/VI(1+). The DR-FS rate of eaFTC/VI(2+) was worse than that of eaFTC/VI(1+) (p = 0.042), but did not differ from that of wFTC/VI(1+/2+). Our findings suggest that subclassifying eaFTC according to the degree of VI and restricting wFTC to VI-positive cases would be better in the WHO classification. Revising the definition for wide CI is recommended.
Subject(s)
Adenocarcinoma, Follicular , Thyroid Neoplasms , Adenocarcinoma, Follicular/diagnosis , Adenocarcinoma, Follicular/surgery , Female , Humans , Male , Middle Aged , Multivariate Analysis , Neoplasm Invasiveness/pathology , Prognosis , Thyroid Neoplasms/diagnosis , Thyroid Neoplasms/surgeryABSTRACT
Thyroid tumors arising from follicular cells can generally be divided into malignant and benign tumors. However, some cases are difficult to clearly diagnose whether they are benign or malignant. Therefore, in the most recent version of World Health Organization (WHO) classification, some borderline lesions such as follicular tumor of uncertain malignant potential (FT-UMP), well-differentiated tumor of uncertain malignant potential (WDT-UMP), and noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) were proposed. In this study, we investigated the clinical aspects, including the prognosis, of FT-UMP patients. We investigated the clinical features of 339 patients with FT-UMP. On ultrasound, 68% of the tumors were diagnosed as intermediate, and only 5% of those tumors were diagnosed as malignant. On cytology, 40% of the tumors were diagnosed as follicular neoplasm, and only 1% of these were suspected to be or diagnosed as malignancy. The diagnosis was based on questionable capsular invasion for 332 patients, questionable vascular invasion for 2 patients, and both for 5 patients. Eighty-six percent of the tumors showed low cell proliferation activity. To date, five patients (1%) have shown distant recurrence during postoperative follow-up and underwent various treatments such as radioactive iodine therapy, orthopedic surgery, and denosumab injection. None of these patients have died due to thyroid carcinoma. Our findings suggest that FT-UMP is generally an indolent disease, but some patients show distant recurrence. Physicians should carefully follow patients, although it remains unknown how long they should be observed after surgery.
Subject(s)
Adenocarcinoma, Follicular , Carcinoma, Papillary , Thyroid Neoplasms , Humans , Adenocarcinoma, Follicular/diagnosis , Adenocarcinoma, Follicular/pathology , Adenocarcinoma, Follicular/therapy , Carcinoma, Papillary/pathology , Iodine Radioisotopes , Retrospective Studies , Thyroid Neoplasms/diagnosis , Thyroid Neoplasms/pathology , Thyroid Neoplasms/therapyABSTRACT
Preoperative flow cytometry is recommended to prove the monoclonality and confirm the diagnosis of thyroid lymphoma. However, lymphoma cases without light chain restriction may also have monoclonality. The aim of our study was to identify a novel marker for thyroid lymphomas using aspirated materials for flow cytometry. We retrospectively analyzed 26 patients with primary thyroid lymphomas and 16 patients with benign lymphoproliferative lesions. The materials for flow cytometry were obtained by fine-needle aspiration cytology using a 22-gauge needle under ultrasound guidance. Light chain restriction was defined as a κ to λ ratio of less than 0.5 or more than 3.0. According to the light chain-positive rate, 25% or less and more than 25% were classified as the low and high light chain-positive rate groups, respectively. B-cell predominance was defined as a CD19 to CD4 ratio (B- to T-cell ratio) of more than 2.0. B-cell predominance was more frequently observed in lymphomas (88.5%) than in benign lymphoproliferative lesions (25.0%; p < 0.001). Light chain restriction based on the κ/λ ratio was detected in 69.2% of lymphomas, but not in benign lymphoproliferative lesions. Among lymphomas belonging to the low light chain-positive rate group, 88.9% did not exhibit light chain restriction and B-cell predominance was present. In contrast, benign lymphoproliferative lesions with B-cell predominance were not detected in the low light chain-positive rate group. B-cell predominance was a useful indicator for diagnosing thyroid lymphoma in the low light chain-positive rate group without light chain restriction.