Tumor-to-Tumor Metastasis of Medullary Thyroid Carcinoma to Paraganglioma in a Multiple Endocrine Neoplasia Type 2B Patient: A Case Report and Literature Review.

Tumor-to-tumor metastasis is a rare phenomenon in which primary tumor cells metastasize to other tumors. Herein, we report an extremely rare case of tumor-to-tumor metastasis of medullary thyroid carcinoma to a paraganglioma in a patient with multiple endocrine neoplasia type 2B. Based on genetic examination, a 36-year-old woman was diagnosed with multiple endocrine neoplasia type 2B when she was 24 years old. She had a history of total thyroidectomy for medullary thyroid carcinoma and bilateral adrenalectomy for pheochromocytomas, which were performed when she was 15 years and 29 years old, respectively. Follow-up computed tomography demonstrated a retroperitoneal tumor of 30 mm in diameter beside the left kidney and a liver tumor of 16 mm in diameter located in segment 6. The retroperitoneal and liver tumors were surgically resected and examined by a pathologist. Histological examination revealed the classic Zellballen pattern in the retroperitoneal tumor, rendering the diagnosis of a paraganglioma recurrence. Inside the tumor, a white nodule positive for carcinoembryonic antigen, weakly positive for calcitonin, and negative for tyrosine hydroxylase, was identified and diagnosed as a metastatic medullary thyroid carcinoma with high malignant potential. The liver lesion was diagnosed as a metastasis of the medullary thyroid carcinoma. This is the first report of tumor-to-tumor metastasis of medullary thyroid carcinoma to paraganglioma in a patient with multiple endocrine neoplasia type 2B twenty years after total thyroidectomy.

Chinese siblings with hereditary medullary thyroid carcinoma caused by RET mutation: implications for RET oncogene detection.

BACKGROUND: Hereditary medullary thyroid carcinoma (MTC) is mainly caused by germline mutations in the RET proto-oncogene, which accounts for 20-30% of all MTC according to foreign studies. However, no English literatures have reported Chinese hereditary MTC. Here, we reported two Chinese brothers with MTC that caused by germline RET mutation. CASE PRESENTATION: The younger brother was diagnosed with MTC at 29 years ago and suffered recurrence more than 10 years. For elder brother, the diagnosis of MTC was made by postoperative pathological examination at age 61. Both patients received total thyroidectomy and lymph node dissection. Since they had a significant family history for MTC, genetic detection was performed and identified a germline mutation in RET exon 10 (p.C620Y). This mutation was also detected in their offspring, indicating a moderate risk of MTC. CONCLUSIONS: This is the first report presenting a Chinese family with hereditary MTC caused by the RET p.C620Y variant. This case series emphasize the importance of genetic detection of RET proto-oncogene for MTC patients, and bring out managements for individuals after detection of RET mutations.

Mucinous versus medullary breast carcinoma: mammography, ultrasound, and MRI findings.

Mucinous and medullary breast cancers (BCs) have different histological substrates that manifest as different imaging features on mammography, ultrasound, and MRI. The aim of the present review is to demonstrate the differences between these two rare BC subtypes and to describe the microscopic features, review the imaging methods for detection of both cancer subtypes, illustrate the imaging findings and present useful pearls and pitfalls. Out of a total of 30 patients with mucinous BC and nine with medullary BC, we have selected typical and also unusual imaging features that best represent these cancers. The patients underwent a mammography and breast ultrasound followed by magnetic resonance imaging. We briefly exhibit histological characteristics for a better understanding of the imaging aspects.

Clinical and ultrasonographic features of medullary thyroid microcarcinomas compared with papillary thyroid microcarcinomas: a retrospective analysis.

BACKGROUND: To identify the sonographic features that help to differentiate medullary thyroid microcarcinomas (MTMCs) from papillary thyroid microcarcinomas (PTMCs). METHODS: A total of 46 MTMCs in 41 patients and 136 PTMCs in 104 patients that were proven by surgery and pathology were included in the study. Patient age and nodule size were analyzed by independent sample t-tests, and sex, multiplicity and cervical lymph node metastases were analyzed by χ2 or Fisher's exact tests. Univariate analysis and multivariate logistic regression analysis were performed on the sonographic features of thyroid nodules, including location, shape, boundary, margin, peripheral halo ring, echogenicity, composition, calcifications and vascularization. RESULTS: Compared with the corresponding number of patients with PTMCs, more MTMC patients had cervical lymph node metastases (P = 0.040). There were no significant differences in age, sex, nodule size, multiplicity, location, boundary, margin, peripheral halo ring, echogenicity or microcalcifications between MTMCs and PTMCs (P > 0.05 for all). However, significant differences were found in shape (P = 0.000), composition (P = 0.032), macrocalcifications (P = 0.004) and vascularity (P = 0.000) between the two groups. CONCLUSIONS: There were some overlapping sonographic features between MTMCs and PTMCs. However, MTMCs tended to have a > 50% solid composition, be ovoid to round nodules with macrocalcifications and be hypervascular. Cervical lymph node metastases were more common in MTMC patients.

Breast metastasis from medullary carcinoma of thyroid: A case report with literature view.

Primary Breast cancer is the most common malignancy in females but secondary involvement of breast is very rare. The Most common sites of primaries for breast metastasis are breast carcinoma of contra lateral side, Lymphoma and leukaemia. Medullary Thyroid Carcinoma (MTC) itself is rare and commonly metastasises to liver, lung and bones. Secondary breast involvement by MTC is very rare with only few case reports in literature. Clinically and radiographically breast secondaries mimic benign lesions and may cause diagnostic challenges. To avoid unnecessary surgery and for appropriate treatment decision,accurate diagnosis is important. We present here our experience of a similar case of secondary breast carcinoma from MTC seen at MINAR cancer hospital Multan. The patient presented clinically and radiologically with benign breast lumps. Fine needle aspiration (FNAC) showed atypical cells and Ultra sound guided Trucut biopsy confirmed it to be a secondary from MTC. Patient is under treatment of an oncologist, has been treated with chemotherapy and is on follow up till date.

Renal medullary carcinoma in a young mixed-race man in Japan.

Renal medullary carcinoma (RMC) is a rare and aggressive cancer associated with the sickle cell trait. The diagnosis of RMC depends on recognition of its histologic features and immunohistochemical deficiency of INI1, but correct diagnosis is sometimes difficult, especially if a patient's information on race, past, and family medical history is unclear. At present, this is the first report on RMC in Japan.

mRECIST criteria to assess recurrent thyroid carcinoma treatment response after radiofrequency ablation: a prospective study.

PURPOSE: Surgical removal is recommended for recurrent thyroid carcinomas (RTCs) unable to uptake radioiodine and/or not responsive to chemotherapy. However, repeated neck dissection is difficult for surgeons. Thus, radiofrequency ablation (RFA) was proposed for RTCs. The aim of this prospective study is to assess RTC treatment response after RFA, according to well-established criteria. METHODS: Sixteen lesions in 13 patients were treated by RFA. All patients refused/were excluded from repeated surgery or other conventional therapy. CT and US examinations were performed before RFA to evaluate lesion volume and vascularization. All RFA procedures were performed under US-guidance by an 18-gauge, electrode. Treatment response was evaluated by CT, according to RECIST 1.1 and to mRECIST guidelines; CT examinations were performed during follow-up (6-18 months); the volume of residual vital tumour tissue and the percentage of necrotic tissue were estimated by contrast enhanced CT. RESULTS: RFA was well tolerated by all patients; in two cases laryngeal nerve paralysis was observed. Mean pre-treatment volume was 4.18 ± 3.53 ml. Vital tumour tissue and percentage of necrosis at 6, 12 and 18 months were 0.18 ± 0.25, 0.11 ± 0.13, 0.29 ± 0.40 ml and 91.9 ± 11.1, 90.4 ± 13.3, 80.8 ± 23.1%. According to RECIST 1.1, target lesion response was classified as complete response (CR) in one case, partial response (PR) in 11/16, stable disease in 4/16 cases. According to mRECIST, 11/16 cases were classified as CR and the remaining 5 as PR. CONCLUSION: RFA is a safe procedure to treat the viable tumour tissue and to reduce the RTC volume; as to the criteria to assess treatment response, mRECIST appears to be more accurate.

Overall survival analysis of EXAM, a phase III trial of cabozantinib in patients with radiographically progressive medullary thyroid carcinoma.

BACKGROUND: Primary analysis of the double-blind, phase III Efficacy of XL184 (Cabozantinib) in Advanced Medullary Thyroid Cancer (EXAM) trial demonstrated significant improvement in progression-free survival with cabozantinib versus placebo in patients with progressive medullary thyroid cancer (MTC). Final analysis of overall survival (OS), a key secondary endpoint, was carried out after long-term follow-up. PATIENTS AND METHODS: EXAM compared cabozantinib with placebo in 330 patients with documented radiographic progression of metastatic MTC. Patients were randomized (2:1) to cabozantinib (140 mg/day) or placebo. Final OS and updated safety data are reported. RESULTS: Minimum follow-up was 42 months. Kaplan-Meier analysis showed a 5.5-month increase in median OS with cabozantinib versus placebo (26.6 versus 21.1 months) although the difference did not reach statistical significance [stratified hazard ratio (HR), 0.85; 95% confidence interval (CI), 0.64-1.12; P = 0.24]. In an exploratory assessment of OS, progression-free survival, and objective response rate, cabozantinib appeared to have a larger treatment effect in patients with RET M918T mutation-positive tumors compared with patients not harboring this mutation. For patients with RET M918T-positive disease, median OS was 44.3 months for cabozantinib versus 18.9 months for placebo [HR, 0.60; 95% CI, 0.38-0.94; P = 0.03 (not adjusted for multiple subgroup analyses)], with corresponding values of 20.2 versus 21.5 months (HR, 1.12; 95% CI, 0.70-1.82; P = 0.63) in the RET M918T-negative subgroup. Median treatment duration was 10.8 months with cabozantinib and 3.4 months with placebo. The safety profile for cabozantinib remained consistent with that of the primary analysis. CONCLUSION: The secondary end point was not met in this final OS analysis from the trial of cabozantinib in patients with metastatic, radiographically progressive MTC. A statistically nonsignificant increase in OS was observed for cabozantinib compared with placebo. Exploratory analyses suggest that patients with RET M918T-positive tumors may experience a greater treatment benefit with cabozantinib. TRIAL REGISTRATION NUMBER: NCT00704730.

Lenvatinib induces early tumor shrinkage in patients with advanced thyroid carcinoma.

Although advanced thyroid carcinoma patients who cannot be cured by conventional therapy have lacked effective treatment, multitargeted tyrosine kinase inhibitors have recently become available. Phase 3 trials of lenvatinib showed a median time to objective response of 2 (95 % confidence interval (CI) 1.9-3.5) months, demonstrating that shrinks tumors rapidly. The phenomenon of immediate tumor shrink is known as early tumor shrinkage (ETS) which is related to clinical outcome in other malignancies. However, precisely when within 8 weeks lenvatinib starts to affect tumors remains unclear. In tumors near the carotid arteries, trachea, or esophagus, a rapid therapeutic effect can induce fistula formation or arterial bleeding. To prevent such treatment-emergent serious adverse events (SAE), early imaging evaluation seems to be very important. In this study, the point in time when lenvatinib started to shrink tumors was retrospectively investigated. The subjects were 16 patients who started lenvatinib administration between May and August 2015. Tumor size was evaluated by computed tomography (CT) scans frequently within the first 8 weeks according to the Response Evaluation Criteria In Solid Tumors (RECIST) guideline. Initial tumor response was defined as ≥ 10% tumor reduction. Serum thyroglobulin (Tg) level was monitored in 8 differentiated thyroid carcinoma (DTC) without TgAb patients. At the first evaluation, 13 patients (83.3 %) showed tumor reduction and that decreased with time. Thirteen patients (83.3 %) showed >10 % tumor reduction within 8 weeks. In all DTC patients, serum Tg level was markedly decreased. In conclusion, lenvatinib immediately shrinks tumors, the so-called ETS phenomenon. Therefore, careful attention should be paid to fistula formation from the early phase.

Imaging of renal medullary carcinoma in children and young adults: a report from the Children's Oncology Group.

BACKGROUND: Renal medullary carcinoma is a rare renal malignancy of childhood. There are no large series describing the imaging appearance of renal medullary carcinoma in children. OBJECTIVE: To characterize the clinical and imaging features of pediatric renal medullary carcinoma at initial presentation. MATERIALS AND METHODS: We retrospectively analyzed images of 25 pediatric patients with renal medullary carcinoma enrolled in the Children's Oncology Group renal tumors classification, biology and banking study (AREN03B2) from March 2006 to August 2016. Imaging findings of the primary mass, and patterns of locoregional and distant spread were evaluated in correlation with pathological and surgical findings. RESULTS: Median age at presentation was 13 years (range: 6-21 years), with a male predominance (3.2:1). The overall stage of disease at initial presentation was stage 1 in 1, stage 2 in 2 and stage 4 in 22. Maximum diameter of the primary renal mass ranged from 1.6 to 10.3 cm (mean: 6.6 cm) with a slight right side predilection (1.5:1). Enlarged (>1 cm short axis) retroperitoneal lymph nodes were identified at initial staging in 20/25 (80%) cases, 10 of which were histologically confirmed while the others did not undergo surgical sampling. Enlarged lymph nodes were also identified in the mediastinum (14/25; 56%) and supraclavicular regions (4/25; 16%). Metastatic disease was present in the lungs in 19/25 (76%) and liver in 6/25 (24%). The pattern of lung metastases was pulmonary lymphangitic carcinomatosis: 10 cases (9 bilateral, 1 unilateral), pulmonary nodules with indistinct margins: 6 cases, pulmonary nodules with distinct margins: 2 cases, while 1 case had pulmonary nodules with both indistinct and distinct margins. Pulmonary lymphangitic carcinomatosis was pathologically confirmed in 4/10 cases. All cases with pulmonary lymphangitic carcinomatosis had associated enlarged mediastinal lymph nodes. CONCLUSION: Renal medullary carcinoma in children and young adults presents at an advanced local and distant stage in the majority of patients. The diagnosis of renal medullary carcinoma should be considered when a child or young adult presents with a poorly defined/infiltrative, centrally located renal mass, especially in the setting of known sickle cell hemoglobinopathy. Distant metastases are common at initial presentation in the lungs, distant lymph nodes and liver and often involve multiple sites simultaneously. Pulmonary lymphangitic carcinomatosis, a distinctive and uncommon form of lung metastasis in children, is common in this patient population.

Malignancy risk stratification in thyroid nodules with nondiagnostic results at cytologic examination: combination of thyroid imaging reporting and data system and the Bethesda System.

PURPOSE: To evaluate the malignancy risks of thyroid nodules with nondiagnostic results at ultrasonography (US)-guided fine-needle aspiration biopsy ( FNAB fine-needle aspiration biopsy ) and the criteria for selecting those for repeat US-guided FNAB fine-needle aspiration biopsy according to the thyroid imaging reporting and data system ( TIRADS thyroid imaging reporting and data system ). MATERIALS AND METHODS: This retrospective study was approved by the institutional review board, and the requirement to obtain informed consent was waived. Five hundred forty-eight nondiagnostic nodules were included. US features of internal composition, echogenicity, margin, calcifications, shape, and vascularity were evaluated, and thyroid nodules were classified according to TIRADS thyroid imaging reporting and data system . TIRADS thyroid imaging reporting and data system category 3 included nodules without any suspicious features of solidity, hypoechogenicity or marked hypoechogenicity, microlobulated or irregular margins, microcalcifications, and taller-than-wide shape. Categories 4a, 4b, 4c, and 5 included nodules with one, two, three or four, or five suspicious US features. The malignancy risk was calculated. RESULTS: Of the 548 nodules, 40 (7.3%) were malignant and 508 (92.7%) were benign. The malignancy risks of categories 3 and 4a nodules were 0.8% and 1.8%, respectively, whereas the malignancy risks of categories 4b, 4c, and 5 nodules were 6.1%, 14.4%, and 31%. In the 294 nodules larger than 10 mm, the malignancy risks of categories 3, 4a, 4b, 4c, and 5 nodules were 0.9%, 1.3%, 0%, 15%, and 33%, respectively. In the 254 nodules measuring 10 mm or smaller, the malignancy risks of categories 3, 4a 4b, 4c, and 5 nodules were 0%, 2.7%, 14%, 14.3%, and 31%. CONCLUSION: Nondiagnostic thyroid nodules without suspicious US features and those with one suspicious feature can be followed up with US, but nondiagnostic nodules with two or more suspicious features should undergo repeat US-guided FNAB fine-needle aspiration biopsy.

Impact of axillary ultrasound (AUS) on axillary dissection in breast conserving surgery (BCS).

BACKGROUND AND OBJECTIVES: Preoperative axillary ultrasound (AUS) in clinically node-negative patients may increase axillary lymph node dissection (ALND) in ACoSOG Z0011-eligible patients. We hypothesize that AUS identifies operative axillary disease (>3 positive nodes) in women undergoing breast conserving surgery (BCS). METHODS: After IRB approval, a retrospective review of female breast cancer patients was performed; patients with clinical T1/T2 tumors undergoing BCS were included. Clinical, radiologic, and pathologic data were collected. RESULTS: Of 139 eligible subjects, 119/139 (86%) had nonpalpable axillary nodes. 47/119 patients (40%) had abnormal AUS and 15/47 (32%) had a positive FNA. Fourteen had ALND ;10/14 (71%) had >3 positive nodes. 6/32 (18%) with abnormal AUS but FNA negative were sentinel lymph node (SLN) positive. Of 72 normal AUS, 15 (22%) were SLN positive; 9/15 (60%) had ALND; 1 (11%) had >3 positive nodes. When evaluating for >3 positive nodes, AUS plus FNA had a sensitivity of 91%, specificity of 95%, NPV of 99%, and PPV of 71%. CONCLUSIONS: AUS/FNA has a high NPV for axillary metastasis and remarkable sensitivity for three or more positive axillary nodes, therefore AUS-identified metastasis should be treated as clinically node-positive disease, and is appropriate even in patients planning breast conserving surgery.

Gallium-68 Dotatate PET/CT is superior to other imaging modalities in the detection of medullary carcinoma of the thyroid in the presence of high serum calcitonin.

OBJECTIVE: Medullary carcinoma of the thyroid (MTC) is a rare neuroendocrine tumour (NET) that expresses somatostatin receptors on the cell membrane and secretes calcitonin. Surgery is the primary curative modality but is achieved only when the diagnosis is timely so there is a high rate of persistent and recurrent disease indicated by a rise in the serum calcitonin levels. Successful management of recurrent disease requires accurate localisation with cross sectional and functional imaging. The introduction of gallium-68-Dotatate ((68)Ga-Dotatate) peptides positron emission tomography/computerized tomography (PET/CT) has significantly improved the detection of NET and has been reported as a valuable adjunct in MTC localisation. We retrospectively reviewed our cases of MTC to correlate the detectability of (68)Ga-Dotatate in relation to calcitonin levels and assess suitability of inoperable patients for peptide receptor radionuclide therapy (PRRT). SUBJECTS AND METHODS: Seven patients (age range 31-66 years, M:F 3:4) with raised calcitonin (mean=7,143pg/mL) were referred for (68)Ga-Dotatate PET/CT scan for localisation of persisting recurrent MTC. Six patients were known to have MTC treated with thyroidectomy and one patient was presenting for the first time. All patients had multiple imaging including ultrasound (US), CT, magnetic resonance imaging (MRI), fluorine-18-fluorodeoxyglucose ((18)F-FDG) PET/CT and iodine-123-metaiodobenzylguanidine ((123)I-MIBG). Positive findings were defined as areas of increased uptake other than the organs of normal distribution and were correlated with results of biopsies, other imaging, long term monitoring of calcitonin and clinical follow up. RESULTS: In 6/7 patients with very high serum calcitonin (range= 672-37,180, mean=8,320pg/mL) (68)Ga-Dotatate PET/CT confirmed the presence of active disease seen on other modalities or detected hitherto unsuspected lesions. In at least 3 cases, (68)Ga-Dotatate PET/CT showed many more lesions compared to other imaging combined. In 1/7 patient (68)Ga-Dotatate PET/CT was negative in line with a relatively low calcitonin level (80pg/mL) and negative disease on fine needle aspiration. CONCLUSION: (68)Ga-Dotatate PET/CT is an effective tool for localising metastatic spread of MTC. It appears to be most effective in the presence of higher levels of serum calcitonin, probably in excess of 500pg/mL. The results of our small cohort had an impact on staging and management with the introduction of peptide receptor radionuclide therapy for inoperable disease.

Malignancy risk stratification in thyroid nodules with benign results on cytology: combination of thyroid imaging reporting and data system and Bethesda system.

BACKGROUND: The indications of repeat fine-needle aspiration (FNA) for thyroid nodules with benign results of the Bethesda system were investigated. METHODS: A total of 1,398 nodules were classified according to the Thyroid Imaging Reporting and Data System (TIRADS). TIRADS category 3 included nodules without solidity, hypoechogenicity or marked hypoechogenicity, microlobulated or irregular margins, microcalcifications, and taller-than-wide shape on ultrasonography (US). Categories 4a, 4b, 4c, and 5 included nodules with one, two, three or four, or five suspicious US features, respectively. The malignancy risks, and odds ratio (OR) with 95 % confidence interval (CI) were calculated. Analyses were performed for all nodules, nodules >10 mm, and nodules ≤10 mm. RESULTS: Of 1.398 nodules, 43 (3.1 %) were malignanct. The malignancy risks of benign nodules with categories 3, 4a, and 4b were 0.7, 1.2, and 0.7 %, respectively, whereas those for nodules with categories 4c and 5 were 9.8 and 22.2 %, respectively. The ORs of nodules with categories 4c and 5 were 19.4 (95 % CI 5.0-76.2) and 50.6 (95 % CI 10.4-245.0), respectively. In nodules >10 mm, the malignancy risks of categories 4c and 5 were 2.7 and 20 %, respectively, and the ORs were 10.7 (95 % CI 1.2-93.7) and 236.1 (95 % CI 12.6-4426.4), respectively. In nodules ≤ 10 mm, the malignancy risks of categories 4c and 5 were 12.6 and 22.6 %, respectively, and the ORs were 10.1 (95 % CI 1.3-78.0) and 18.9 (95 % CI 2.1-168.9), respectively. CONCLUSIONS: Repeat US-guided FNA should be considered in benign thyroid nodules with three or more suspicious US features regardless of size.

¹8F-FDG PET predicts survival after pretargeted radioimmunotherapy in patients with progressive metastatic medullary thyroid carcinoma.

PURPOSE: PET is a powerful tool for assessing targeted therapy. Since (18)F-FDG shows a potential prognostic value in medullary thyroid carcinoma (MTC), this study evaluated (18)F-FDG PET alone and combined with morphological and biomarker evaluations as a surrogate marker of overall survival (OS) in patients with progressive metastatic MTC treated with pretargeted anti-CEA radioimmunotherapy (pRAIT) in a phase II clinical trial. METHODS: Patients underwent PET associated with morphological imaging (CT and MRI) and biomarker evaluations, before and 3 and 6 months, and then every 6 months, after pRAIT for 36 months. A combined evaluation was performed using anatomic, metabolic and biomarker methods. The prognostic value of the PET response was compared with demographic parameters at inclusion including age, sex, RET mutation, time from initial diagnosis, calcitonin and CEA concentrations and doubling times (DT), SUVmax, location of disease and bone marrow involvement, and with response using RECIST, biomarker concentration variation, impact on DT, and combined methods. RESULTS: Enrolled in the study were 25 men and 17 women with disease progression. The median OS from pRAIT was 3.7 years (0.2 to 6.5 years) and from MTC diagnosis 10.9 years (1.7 to 31.5 years). After pRAIT, PET/CT showed 1 patient with a complete response, 4 with a partial response and 24 with disease stabilization. The combined evaluation showed 20 responses. For OS from pRAIT, univariate analysis showed the prognostic value of biomarker DT (P = 0.011) and SUVmax (P = 0.038) calculated before pRAIT and impact on DT (P = 0.034), RECIST (P = 0.009), PET (P = 0.009), and combined response (P = 0.004) measured after pRAIT. PET had the highest predictive value with the lowest Akaike information criterion (AIC 74.26) as compared to RECIST (AIC 78.06), biomarker variation (AIC 81.94) and impact on DT (AIC 79.22). No benefit was obtained by combining the methods (AIC 78.75). This result was confirmed by the analysis of OS from MTC diagnosis. CONCLUSION: (18)F-FDG PET appeared as the most potent and simplest prognostic method to predict survival in patients with progressive MTC treated with pRAIT. Biomarker DT before pRAIT also appeared as an independent prognostic factor, but no benefit was found by adding morphological and biomarker evaluation to PET assessment.

Metastasis of colon cancer to medullary thyroid carcinoma: a case report.

Metastasis to the primary thyroid carcinoma is extremely rare. We report here a case of colonic adenocarcinoma metastasis to medullary thyroid carcinoma in a 53-yr old man with a history of colon cancer. He showed a nodular lesion, suggesting malignancy in the thyroid gland, in a follow-up examination after colon cancer surgery. Fine needle aspiration biopsy (FNAB) of the thyroid gland showed tumor cell clusters, which was suspected to be medullary thyroid carcinoma (MTC). The patient underwent a total thyroidectomy. Using several specific immunohistochemical stains, the patient was diagnosed with colonic adenocarcinoma metastasis to MTC. To the best of our knowledge, the present patient is the first case of colonic adenocarcinoma metastasizing to MTC. Although tumor-tumor metastasis to primary thyroid carcinoma is very rare, we still should consider metastasis to the thyroid gland, when a patient with a history of other malignancy presents with a new thyroid finding.

Is basal ultrasensitive measurement of calcitonin capable of substituting for the pentagastrin-stimulation test?

OBJECTIVE: To evaluate a second-generation assay for basal serum calcitonin (CT) measurements compared with the pentagastrin-stimulation test for the diagnosis of inherited medullary thyroid carcinoma (MTC) and the follow-up of patients with MTC after surgery. Recent American Thyroid Association recommendations suggest the use of basal CT alone to diagnose and assess follow-up of MTC as the pentagastrin (Pg) test is unavailable in many countries. DESIGN: Multicentric prospective study. PATIENTS: A total of 162 patients with basal CT <10 ng/l were included: 54 asymptomatic patients harboured noncysteine 'rearranged during transfection' (RET) proto-oncogene mutations and 108 patients had entered follow-up of MTC after surgery. MEASUREMENT: All patients underwent basal and Pg-stimulated CT measurements using a second-generation assay with 5-ng/l functional sensitivity. RESULTS: Ninety-five per cent of patients with basal CT ≥ 5 ng/l and 25% of patients with basal CT <5 ng/l had a positive Pg-stimulation test (Pg CT >10 ng/l). Compared with the reference Pg test, basal CT ≥ 5 ng/l had 99% specificity, a 95%-positive predictive value but only 35% sensitivity (P < 0.0001). Overall, there were 31% less false-negative results using a 5-ng/l threshold for basal CT instead of the previously used 10-ng/l threshold. CONCLUSION: The ultrasensitive CT assay reduces the false-negative rate of basal CT measurements when diagnosing familial MTC and in postoperative follow-up compared with previously used assays. However, its sensitivity to detect C-cell disease remains lower than that of the Pg-stimulation test.

Surgeon-performed ultrasound predictors of malignancy in patients with Hürthle cell neoplasms of the thyroid.

BACKGROUND: Fine-needle aspiration cannot reliably determine malignancy in patients with Hürthle cell neoplasms (HCNs) of the thyroid. Thyroid nodule size and characteristics determined by surgeon-performed ultrasound (SUS) may be useful for predicting malignancy in HCN preoperatively. This study examined whether tumor size and features by SUS can reliably predict malignancy in patients with HCN. MATERIALS AND METHODS: We performed a retrospective review of 84 patients with HCN by fine-needle aspiration, who underwent SUS and thyroidectomy from 2002 to 2010. All patients underwent thyroid lobectomy with isthmusectomy unless there was a history of radiation exposure, familial thyroid cancer, obstructive symptoms, bilateral nodules, and/or patient preference, in which case total thyroidectomy was performed. Tumor size and malignant features by SUS were correlated with final histopathology using multivariate regression analysis. RESULTS: On final histopathology, 29 patients had malignant thyroid nodules and 55 patients had benign ones. There were no statistically significant differences in terms of age, race, ethnicity, or gender between HCN patients who revealed malignant or benign nodules on final pathology. Tumor size ≥ 4 cm measured by SUS did not predict malignancy in HCN. Hypoechogenicity and hyperechogenicity were significantly associated with malignancy, whereas isoechogenicity was predictive of benignity (P = 0.044). No other ultrasonographic features were predictive for thyroid carcinoma by multivariate analysis. CONCLUSIONS: Tumor size and features determined by SUS do not reliably predict malignancy in patients with HCN. Such patients at risk for malignancy should initially undergo thyroid lobectomy for definitive diagnosis.

[Value of contrast-enhanced ultrasound (CEUS) in the differential diagnosis between benign and malignant renal neoplasms].

OBJECTIVE: To investigate the value of contrast enhanced ultrasound (CEUS) imaging in the differential diagnosis between benign and malignant renal neoplasms. METHODS: Two hundred and forty-five cases of renal space-occupying lesions confirmed by biopsy or surgical pathology were included in this study. The CEUS features of the renal space-occupying lesions, i.e., the enhancement degree, homogeneity of enhancement, washing-in and washing-out time and enhancement pattern, were retrospectively analyzed. RESULTS: There were 210 cases of malignant renal tumors and 35 cases of benign lesions. The CEUS modes of the malignant renal tumors included "quick in and quick out" 82 cases, "quick in and slow out" 64 cases, "slow in and quick out" 18 cases and "slow in and slow out" 46 cases; good enhancement 150 cases (71.4%) and inhomogeneous enhancement 180 cases (85.7%).Both the contrast agent filling defect area and solid component enhancement of solid-cystic tumors were important features of malignant renal tumors. In the 35 cases of benign lesions,the CEUS modes included "quick in and quick out" 4 cases, "quick in and slow out" 8 cases, "slow in and quick out" 10 cases and "slow in and slow out" 13 cases. Most of the benign tumors showed low enhancement 51.4% (18/35) and inhomogeneous enhancement 54.3% (19/35). There were significant differences between the malignant and benign renal neoplasms in CEUS mode, degree of enhancement and homogeneity of enhancement (P < 0.05), and in time of increasing, peak time, peak intensity and peak intensity ratio (P < 0.05). The accuracy rates of contrast-enhanced ultrasound for diagnosis of benign and malignant tumors were 77.1% and 83.8%, respectively, while the two-dimensional ultrasound diagnosis of benign and malignant tumors were 68.6% and 76.7%, respectively, with a significant difference (P < 0.05). CONCLUSIONS: CEUS may provide more information to improve the diagnostic accuracy for renal neoplasms, and may play important role in differential diagnosis between benign and malignant renal lesions.