-
Journal of Clinical and Diagnostic... Mar 2016Diagnosing follicular-patterned thyroid neoplasm can be quiet challenging in some cases, where an immunohistochemical profiling becomes mandatory. Galectin-3 may be a...
INTRODUCTION
Diagnosing follicular-patterned thyroid neoplasm can be quiet challenging in some cases, where an immunohistochemical profiling becomes mandatory. Galectin-3 may be a helpful tool for classical PTC diagnosis, but it cannot be considered as a diagnostic marker of malignancy. Glypican-3, in contrast, is not thoroughly studied in thyroid neoplasms.
AIM
Determine the sensitivity and specificity of galectin-3 and glypican-3 in diagnosing thyroid carcinoma and follicular-patterned thyroid carcinoma.
MATERIALS AND METHODS
A retrospective study was conducted on archival blocks diagnosed from pathology department between 2010 and 2012 including 17 cases of follicular adenoma, 16 cases of Classic Papillary Thyroid Carcinoma (PTC), 6 cases of Follicular Variant of Papillary Thyroid Carcinoma (FVPTC), 3 cases of follicular carcinoma, 5 cases of medullary carcinoma and 1 case of Hürthle cell carcinoma. The nearby non neoplastic (normal) thyroid follicles present in both adenoma and carcinoma cases were also evaluated.
STUDY DESIGN
Evaluation of both galectin-3 and glypican-3 expression using standard immunohistochemical techniques.
STATISTICAL ANALYSIS USED
Descriptive analysis of the variables and statistical significances were calculated by non-parametric chi-square test using the Statistical Package for the Social Sciences version 12.0 (SPSS).
RESULTS
Five (30%) and 4 (24%) out of the 17 studied follicular adenoma cases, were positively stained by galectin-3 and glypican-3 respectively, while 30 (97%) and 25 (81%) cases out of the studied 31 carcinoma cases were positively stained by galectin-3 and glypican-3 respectively. The sensitivity, specificity and diagnostic accuracy of galectin-3 vs. glypican-3 in discrimination between thyroid carcinoma and adenoma was 96.8%, 70.6%, and 87.5%vs. 81% 76.5% and 79% respectively. As for the discrimination between follicular-patterned thyroid carcinoma and follicular adenoma it was 90%, 71% and 78% vs. 90% 76.5% and 82%.
CONCLUSION
Glypican-3 is more specific while galectin-3 is more sensitive in diagnosing thyroid carcinoma while glypican-3 is more specific than galectin-3 in discriminating follicular-patterned neoplasm.
PubMed: 27134876
DOI: 10.7860/JCDR/2016/18375.7430 -
Surgical Case Reports Aug 2021Metastasis to the breast is rare. We herein report a patient with metastatic medullary thyroid carcinoma to the breast for whom measuring the calcitonin level was an...
BACKGROUND
Metastasis to the breast is rare. We herein report a patient with metastatic medullary thyroid carcinoma to the breast for whom measuring the calcitonin level was an important clue to the correct diagnosis.
CASE PRESENTATION
A 54-year-old woman visited our hospital for the treatment of recurrent metastatic medullary thyroid carcinoma due to multiple endocrine neoplasia 2A and breast cancer. Positron emission tomography performed before the operation for metastatic medullary thyroid carcinoma recurrence in the neck showed the accumulation of F-fluorodeoxyglucose in the bilateral breast at sites other than the disease in the neck. Ultrasonography revealed multiple tumors in both breasts. A core needle biopsy of three breast tumors was performed. Microscopically, the tumor cells showed solid growth and did not show a tubular structure. She was diagnosed with triple-negative invasive ductal carcinoma. Post-operative positron emission tomography was performed as the serum calcitonin level increased after the operation. The accumulation of F-fluorodeoxyglucose in the bilateral breast tumors and lymph nodes in the neck was noted. The possibility of the breast tumors being metastasis of metastatic medullary thyroid carcinoma was considered. Needle aspiration was performed for three breast tumors. The calcitonin level of the washout fluid was measured and found to be ≥ 17,500 pg/mL. Immunohistochemistry showed that the tumor cells were calcitonin-positive and gross cystic disease fluid protein-15-negative. Vandetanib was started as recurrent metastatic medullary thyroid carcinoma with breast metastasis was finally diagnosed. The serum calcitonin level decreased after 1 month.
CONCLUSION
Although breast metastasis of medullary thyroid carcinoma is rare, a correct diagnosis is indispensable for appropriate treatment. When a breast tumor shows atypical morphological features for breast cancer according to the histopathology in a patient with a history of cancer, metastasis to the breast should be considered. Calcitonin measurement of the needle washout fluid was useful for confirming metastatic medullary thyroid carcinoma.
PubMed: 34410532
DOI: 10.1186/s40792-021-01273-w -
Turk Patoloji Dergisi 2015Fine needle aspiration of thyroid has been used for years in a multidisciplinary approach, to diagnose different entities, in preventing over or under treatment of... (Review)
Review
Fine needle aspiration of thyroid has been used for years in a multidisciplinary approach, to diagnose different entities, in preventing over or under treatment of thyroid nodules. The widespread use of this methodology can be confirmed if "thyroid fine needle aspiration" is searched on PubMed, which results in over 5000 papers. In this manuscript, we aimed to focus on pitfalls in the evaluation of thyroid aspirations, covering cystic, inflammatory lesions, follicular lesions, oncocytic lesions, papillary carcinoma, and medullary carcinoma of thyroid.
Topics: Biopsy, Fine-Needle; Diagnosis, Differential; Diagnostic Errors; Humans; Predictive Value of Tests; Prognosis; Thyroid Neoplasms; Thyroid Nodule
PubMed: 26177315
DOI: 10.5146/tjpath.2015.01312 -
Biomedicines Mar 2022Mutations in subunits of the SWItch Sucrose Non-Fermentable (SWI/SNF) complex occur in 20% of all human tumors. Among these, the core subunit SMARCB1 is the most... (Review)
Review
Mutations in subunits of the SWItch Sucrose Non-Fermentable (SWI/SNF) complex occur in 20% of all human tumors. Among these, the core subunit SMARCB1 is the most frequently mutated, and SMARCB1 loss represents a founder driver event in several malignancies, such as malignant rhabdoid tumors (MRT), epithelioid sarcoma, poorly differentiated chordoma, and renal medullary carcinoma (RMC). Intriguingly, SMARCB1-deficient pediatric MRT and RMC have recently been reported to be immunogenic, despite their very simple genome and low tumor mutational burden. Responses to immune checkpoint inhibitors have further been reported in some SMARCB1-deficient diseases. Here, we will review the preclinical data and clinical data that suggest that immunotherapy, including immune checkpoint inhibitors, may represent a promising therapeutic strategy for SMARCB1-defective tumors. We notably discuss the heterogeneity that exists among the spectrum of malignancies driven by SMARCB1-loss, and highlight challenges that are at stake for developing a personalized immunotherapy for these tumors, notably using molecular profiling of the tumor and of its microenvironment.
PubMed: 35327458
DOI: 10.3390/biomedicines10030650 -
European Thyroid Journal Mar 2015Papillary thyroid carcinoma is the most common thyroid cancer (85%). Follicular thyroid carcinoma is the second most common type of thyroid cancer, accounting for up to...
BACKGROUND
Papillary thyroid carcinoma is the most common thyroid cancer (85%). Follicular thyroid carcinoma is the second most common type of thyroid cancer, accounting for up to 10% of all thyroid cancers. Medullary thyroid carcinoma accounts for only 5-8% of thyroid cancers. Concurrent medullary, follicular, and papillary carcinomas of the thyroid gland are extremely rare and reported scarcely.
CASE REPORT
A 72-year-old male presented with nonspecific neck pain. The workup revealed a nodular thyroid gland with a follicular lesion on fine-needle aspiration. Total thyroidectomy was performed and pathological examination identified a 25-mm follicular carcinoma, two papillary microcarcinomas, and two medullary microcarcinomas. The genetic workup was negative and no other family members were diagnosed with any endocrinopathy. Two months after surgery, the patient was diagnosed with Cushing's syndrome that was treated with laparoscopic left adrenalectomy. On 3-year follow-up, the patient is asymptomatic with no evidence of recurrent disease.
CONCLUSION
We present a rare case of a patient with follicular, papillary, and medullary thyroid carcinoma, and Cushing's syndrome. To date, no known genetic mutation or syndrome can account for this combination of neoplastic thyroid and adrenal pathologies, although future research may prove differently.
PubMed: 25960965
DOI: 10.1159/000368750 -
Archives of Endocrinology and Metabolism 2018The advent of multikinase inhibitor (MKI) therapy has led to a radical change in the treatment of patients with advanced thyroid carcinoma. The aim of this manuscript is...
OBJECTIVE
The advent of multikinase inhibitor (MKI) therapy has led to a radical change in the treatment of patients with advanced thyroid carcinoma. The aim of this manuscript is to communicate rare adverse events that occurred in less than 5% of patients in clinical trials in a subset of patients treated in our hospital.
SUBJECTS AND METHODS
Out of 760 patients with thyroid cancer followed up with in our Division of Endocrinology, 29 (3.8%) received treatment with MKIs. The median age at diagnosis of these patients was 53 years (range 20-70), and 75.9% of them were women. Sorafenib was prescribed as first-line treatment to 23 patients with differentiated thyroid cancer and as second-line treatment to one patient with advanced medullary thyroid cancer (MTC). Vandetanib was indicated as first-line treatment in 6 patients with MTC and lenvatinib as second-line treatment in two patients with progressive disease under sorafenib treatment.
RESULTS
During the follow-up of treatment (mean 13.7 ± 7 months, median 12 months, range 6-32), 5/29 (17.2%) patients presented rare adverse events. These rare adverse effects were: heart failure, thrombocytopenia, and squamous cell carcinoma during sorafenib therapy and squamous cell carcinoma and oophoritis with intestinal perforation during vandetanib treatment.
CONCLUSIONS
About 3 to 5 years after the approval of MKI therapy, we learned that MKIs usually lead to adverse effects in the majority of patients. Although most of them are manageable, we still need to be aware of potentially serious and rare or unreported adverse effects that can be life-threatening.
Topics: Adult; Aged; Antineoplastic Agents; Carcinoma; Carcinoma, Medullary; Female; Follow-Up Studies; Heart Failure; Humans; Intestinal Perforation; Kaplan-Meier Estimate; Male; Middle Aged; Oophoritis; Phenylurea Compounds; Piperidines; Protein Kinase Inhibitors; Quinazolines; Quinolines; Retrospective Studies; Risk Factors; Sorafenib; Thrombocytopenia; Thyroid Neoplasms; Time Factors; Young Adult
PubMed: 30624504
DOI: 10.20945/2359-3997000000090 -
Cureus Apr 2024The first categorization for renal tumours was made by the WHO in 1981 and included only renal cell carcinoma (RCC). After that, classification was continuously altered... (Review)
Review
The first categorization for renal tumours was made by the WHO in 1981 and included only renal cell carcinoma (RCC). After that, classification was continuously altered over five decades. The WHO 2022 Classification of Urinary and Male Genital Tumours 2022 (5 edition) is molecular-driven and contains major revisions compared to the earlier classification from 2016. This revised edition divided renal tumours into four major broad categories: clear cell renal tumours, papillary renal cell tumours, oncocytic and chromophobe renal tumours, and collecting duct tumours. 'Other renal tumours' and 'molecularly defined renal carcinomas' are two other categories that were also included. Transcription factor binding to IGHM enhancer 3 (TFE3)-rearranged, TFEB-altered, elongin C (ELOC)-mutated (formerly TCEB1)-mutated, fumarate hydratase (FH)-deficient, succinate dehydrogenase (SDH)-deficient, anaplastic lymphoma kinase (ALK)-rearranged, and SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1)-deficient renal cell carcinomas are molecularly defined entities. Eosinophilic vacuolated tumours and low-grade oncocytic tumours are classified as emerging entities. Molecularly characterized renal tumours include those with SMARCB1 deficiencies, TFE3 rearrangements, TFEB alterations, ALK rearrangements, ELOC mutations, etc. Thyroid-like follicular carcinoma, eosinophilic vacuolated tumour, and low-grade oncocytic tumour are a few emerging entities of renal tumours. Improved therapy targets for each kidney tumour can be achieved using immunohistochemistry (IHC) and molecular definition updates. This study aims to highlight new developments in the WHO 2022 categorization of renal tumours with regard to diagnostic, morphological, molecular, IHC, clinical, and prognostic updates.
PubMed: 38765391
DOI: 10.7759/cureus.58470 -
Clinical Genitourinary Cancer Dec 2017Renal medullary carcinoma (RMC) is a rare and aggressive type of kidney cancer that primarily affects young adults with sickle cell trait; outcomes are poor despite...
BACKGROUND
Renal medullary carcinoma (RMC) is a rare and aggressive type of kidney cancer that primarily affects young adults with sickle cell trait; outcomes are poor despite treatment. Identifying molecular features of this tumor could provide biologic rationale for novel targeted therapies. The objective was to report on clinical outcomes with systemic therapy and characterize molecular features.
PATIENTS AND METHODS
This was a retrospective analysis on 36 patients given a pathologic diagnosis of RMC at one institution from 1995 to 2015. Tumors were analyzed for expression of SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1 (SMARCB1) through immunohistochemistry and for genomic alterations with fluorescence in situ hybridization for SMARCB1, and targeted next-generation sequencing. Time from initiation of therapy to progression of disease and overall survival were calculated using the Kaplan-Meier method.
RESULTS
The median age in the cohort was 28 (range, 12-72) years, and all patients tested had sickle cell trait. Overall survival was 5.8 months (95% confidence interval [CI], 4.1-10.9) and for 12 patients who received platinum-based therapy, median progression-free survival was 2.5 months (95% CI, 1.2-not reached). A total of 10 available tumors underwent analysis with fluorescence in situ hybridization for SMARCB1; this revealed loss of heterozygosity with concurrent translocation in 8, and biallelic loss in 2. Next-generation targeted sequencing showed no recurring mutations.
CONCLUSIONS
Outcome was generally poor in this cohort of patients with RMC. Uniform loss of SMARCB1 is a key molecular feature in this tumor and mechanism of loss appears to be mostly through translocations and deletions.
Topics: Adolescent; Adult; Aged; Carcinoma, Medullary; Child; Female; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Kidney Neoplasms; Male; Middle Aged; Pharmacogenomic Variants; Platinum; Retrospective Studies; SMARCB1 Protein; Sequence Analysis, DNA; Survival Analysis; Translocation, Genetic; Treatment Outcome; Young Adult
PubMed: 28558987
DOI: 10.1016/j.clgc.2017.04.012 -
Acta Clinica Croatica Jun 2020Medullary thyroid carcinoma (MTC) is a rare malignancy that originates from parafollicular (C cells) of the thyroid and accounts for 2-4% of all thyroid malignancies.... (Review)
Review
Medullary thyroid carcinoma (MTC) is a rare malignancy that originates from parafollicular (C cells) of the thyroid and accounts for 2-4% of all thyroid malignancies. MTC may be sporadic or inherited, the latter as part of the MEN 2 syndromes. Germline mutations in the proto-oncogene (REarranged during Transfection) are driver mutations in hereditary MTC, whereas somatic mutations and, less frequently, mutations, have been described in tumor tissues of sporadic MTC. Genetic screening for germline mutations in proto-oncogene identifies gene carriers of germline mutations. That enables primary prevention (the avoidance of disease onset by total prophylactic thyroidectomy), or at least secondary prevention (early detection) of the disease. Radical surgery with complete tumor resection is still pivotal in attaining cure for MTC. Despite recent advances, the treatment of advanced, metastatic, and progressive MTC remains challenging. Metastatic MTC can have an indolent clinical course; therefore, it is necessary to assess which patient to cure and when to initiate the treatment. Multidisciplinary boards of various specialists involved in the diagnostics and therapy of the patients with MTC in highly specialized centers with a high volume of patients provide optimal patient management. Multikinase inhibitors (MKI) vandetanib and cabozantinib were approved for the treatment of progressive or symptomatic metastatic/unresectable MTC. Although these treatments have been shown to improve progression-free survival (PFS) with higher overall response rates (ORR) compared with placebo, no MKI has been shown to increase the overall survival (OS) yet, except in the subgroup of patients with -mutations on cabozantinib therapy. As these drugs are nonselective, significant off-target toxicities may occur. Recently, next-generation small-molecule tyrosine kinase inhibitors (TKIs) have been developed. These highly selective RET-inhibitors are specifically designed for highly potent and selective targeting of oncogenic RET alterations, making them promising drugs for the treatment of advanced MTC. The selective RET-inhibitor selpercatinib has been very recently registered for the treatment of -mutated thyroid cancer.
Topics: Carcinoma, Medullary; Carcinoma, Neuroendocrine; Humans; Proto-Oncogene Mas; Proto-Oncogene Proteins c-ret; Pyrazoles; Pyridines; Thyroid Neoplasms
PubMed: 34219884
DOI: 10.20471/acc.2020.59.s1.06 -
Indian Journal of Ophthalmology Oct 2023The most common cause of intraocular mass is metastasis from other tumors. Renal malignancies, though rare, have a substantial number of cases with ocular metastasis,... (Review)
Review
The most common cause of intraocular mass is metastasis from other tumors. Renal malignancies, though rare, have a substantial number of cases with ocular metastasis, few of which were misdiagnosed. Many a times renal malignancies present with ocular manifestations before the primary diagnosis. Here in this article, we comprehensively reviewed 106 cases of ocular metastasis from renal malignancies published till date to the best of our knowledge. The eye is a rare site for distant metastasis because of the lack of a lymphatic system. The most common ocular structures to get involved in distant metastasis are the uveal tract, i.e., choroid, iris, and ciliary body. The most common renal tumor which metastasizes to eyes is renal cell carcinoma (RCC). RCC accounts for less than 2% of all ophthalmic metastases. Out of total 106 cases, the type of renal malignancy was known in 95 cases only, of which 92 had RCC, 1 Wilm's tumor, 1 rhabdoid tumor, and 1 medullary carcinoma. The age ranged widely from 2 weeks old to 81 years old. The male to female ratio was 3.4:1. In total, 67.4% of cases had a previous history of RCC, while the rest 32.6% primarily presented with ophthalmic manifestations first. Treatment modalities included enucleation of the eye, debulking surgery followed by radiotherapy and/or chemotherapy and/or immunotherapy.
Topics: Humans; Male; Female; Infant, Newborn; Carcinoma, Renal Cell; Uveal Neoplasms; Kidney Neoplasms; Eye Neoplasms; Ciliary Body
PubMed: 37787223
DOI: 10.4103/IJO.IJO_3073_22