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The Journal of Clinical Endocrinology... Dec 2020Poorly differentiated thyroid cancer (PDTC) is a rare, follicular cell-derived neoplasm with an unfavorable prognosis. The oncocytic variant of PDTC may be associated...
BACKGROUND
Poorly differentiated thyroid cancer (PDTC) is a rare, follicular cell-derived neoplasm with an unfavorable prognosis. The oncocytic variant of PDTC may be associated with even more adverse outcome than classical PDTC cases, but its specific molecular features are largely unknown. Our aim was to explore the immune-related gene expression profile of oncocytic and classical PDTC, in correlation with clinical and pathological characteristics (including programmed death ligand 1 [PD-L1] expression) and outcome, and in comparison with a control group of well-differentiated follicular carcinomas (WDFCs), including conventional follicular carcinomas (FTCs) and Hürthle cell carcinomas (HCCs).
METHODS
A retrospective series of 48 PDTCs and 24 WDFCs was analyzed by means of NanoString technology employing the nCounter PanCancer Immune Profiling panel. Gene expression data were validated using quantitative real-time polymerase chain reaction.
RESULTS
Oncocytic PDTCs showed a specific immune-related gene expression profile, with higher expression of LAIR2, CD274, DEFB1, IRAK1, CAMP, LCN2, LY96, and APOE, and lower expression of NOD1, as compared to conventional PDTCs. This molecular signature was associated with increased intratumoral lymphocytic infiltration, PD-L1 expression, and adverse outcome. Three of these genes, CD274, DEFB1, and IRAK1, as well as PD-L1 expression, were also the hallmarks of HCCs as compared to FTCs. By contrast, the panel of genes differentially regulated in PDTCs as compared to WDFCs was unrelated to the oncocytic phenotype.
CONCLUSIONS
Our results revealed a distinctive immune-related gene expression profile of oncocytic PDTC and confirmed a more aggressive outcome in this cancer subtype. These findings may provide guidance when exploring novel immunotherapeutic options for oncocytic PDTC patients.
Topics: Adenocarcinoma, Follicular; Adenoma, Oxyphilic; Adult; Aged; Aged, 80 and over; Female; Gene Expression Regulation, Neoplastic; Humans; Immunity; Male; Microarray Analysis; Middle Aged; Oxyphil Cells; Retrospective Studies; Thyroid Neoplasms; Transcriptome; Tumor Escape
PubMed: 32936917
DOI: 10.1210/clinem/dgaa655 -
The Malaysian Journal of Pathology Aug 2020Oncocytic carcinoma of the salivary gland is an uncommon tumour in the head and neck region. Owing to its rarity, identifying the histopathological features of a...
Oncocytic carcinoma of the salivary gland is an uncommon tumour in the head and neck region. Owing to its rarity, identifying the histopathological features of a malignant tumour can be difficult and challenging. We report a case of a 70-year-old man who presented with a left facial weakness for six months in a background history of left parotid swelling over the past 10 years. Clinical examination revealed a 3x3cm left parotid mass and grade 4 facial nerve palsy. Fine needle aspiration of the mass showed scattered cohesive, monolayered sheets of uniform oncocytic cells. Subsequently, a left total parotidectomy and selective neck dissection were performed. Histological examination showed sheets of small oncocytes with minimal nuclear atypia. Evidence of nerve entrapment, capsular invasion and perivascular permeation were identified in focal areas. Thus, a final diagnosis of oncocytic carcinoma was rendered.
Topics: Adenoma, Oxyphilic; Aged; Biopsy, Fine-Needle; Head and Neck Neoplasms; Humans; Male; Oxyphil Cells; Parotid Gland; Parotid Neoplasms; Salivary Glands
PubMed: 32860383
DOI: No ID Found -
International Journal of Molecular... Aug 2020The intraductal oncocytic papillary neoplasm (IOPN) of the pancreas has been recognized by WHO classification as a unique intraductal papillary mucinous neoplasm (IPMN)...
The intraductal oncocytic papillary neoplasm (IOPN) of the pancreas has been recognized by WHO classification as a unique intraductal papillary mucinous neoplasm (IPMN) category. IOPN is composed of oxyphil cells, usually expressing MUC5AC, MUC6, and Hep Par-1, and harboring / fusion genes as their genetic hallmark. Although IOPNs are associated with an infiltrative adenocarcinoma in up to 30% of cases, the survival rate after surgical resection approaches 100%. This highlights the importance of the correct IOPN diagnosis, above all in cases with an associated invasive component. In this study, the immunohistochemical expression of CD117 was investigated in 111 IPMNs, including 17 oncocytic, 45 gastric, 20 pancreatico-biliary, and 29 intestinal IPMNs. We also tested the expression of MUC5AC, MUC6, and Hep Par-1 in the IOPN cohort. CD117 positivity was significantly more frequent in IOPNs compared to the other IPMN subtypes ( < 0.0001). Furthermore, within IOPN, a lower or absent CD117, MUC5AC, MUC6, and Hep Par-1 expression tended to be associated with the presence of an infiltrative component. Our findings shed light into the biology of these complex lesions, which are confirmed to be a distinctive IPMN subtype; notably, CD117 emerged as a potential, additional tool in the differential diagnosis of IPMNs.
Topics: Adenocarcinoma, Mucinous; Biomarkers, Tumor; Carcinoma, Papillary; Cell Line, Tumor; Cohort Studies; Humans; Mucins; Oxyphil Cells; Pancreatic Intraductal Neoplasms; Proto-Oncogene Proteins c-kit
PubMed: 32806726
DOI: 10.3390/ijms21165794 -
Journal of Cutaneous Pathology Dec 2020We report a case of tumor-to-tumor metastasis of a cutaneous malignant melanoma to a synchronous thyroid Hurthle cell carcinoma. A 42-year-old male underwent a biopsy of...
We report a case of tumor-to-tumor metastasis of a cutaneous malignant melanoma to a synchronous thyroid Hurthle cell carcinoma. A 42-year-old male underwent a biopsy of right inguinal lymphadenopathy which showed metastatic melanoma. The primary lesion was identified on his right posterior leg, and staging workup discovered a synchronous left thyroid lobe nodule concerning for a follicular neoplasm. He underwent excision of the primary melanoma, right inguinal lymphadenectomy, and total thyroidectomy. The resected thyroid contained a 6.6-cm, well-encapsulated left-sided nodule, red-brown in color and homogenous in consistency, with areas of focal hemorrhage and no grossly identifiable calcification. Microscopically, large tumor cells with distinct cell borders were present, with deeply eosinophilic and granular cytoplasm, large nuclei with prominent nucleoli, and loss of polarity consistent with oncocytes. A microscopic single focus of vascular invasion was identified, and a diagnosis of angioinvasive Hurthle cell carcinoma was made. Within the Hurthle cell carcinoma, multiple deposits of metastatic melanoma were seen. These findings were indicative of tumor-to-tumor metastasis of the cutaneous melanoma to the angioinvasive Hurthle cell carcinoma. Our findings show the ability of melanoma to metastasize to a pre-existing neoplasm.
Topics: Adenoma, Oxyphilic; Adult; Biopsy; Humans; Inguinal Canal; Lymph Node Excision; Lymphadenopathy; Male; Melanoma; Neoplasms, Multiple Primary; Neoplasms, Second Primary; Oxyphil Cells; Skin Neoplasms; Thyroid Neoplasms; Thyroid Nodule; Thyroidectomy; Melanoma, Cutaneous Malignant
PubMed: 32740977
DOI: 10.1111/cup.13829 -
European Journal of Nuclear Medicine... Feb 2021There are controversial debates if patients with Hürthle cell carcinoma, also known as oxyphilic or oncocytic cell follicular thyroid carcinoma, have a poorer outcome....
PURPOSE
There are controversial debates if patients with Hürthle cell carcinoma, also known as oxyphilic or oncocytic cell follicular thyroid carcinoma, have a poorer outcome. In this study, we systematically evaluated the clinical outcome in a large patient cohort following thyroidectomy and initial I-131 radioactive iodine therapy (RIT).
METHODS
We retrospectively evaluated a total of 378 patients with diagnosed oncocytic follicular Hürthle cell carcinoma (OFTC) (N = 126) or with classical follicular thyroid carcinoma (FTC) (N = 252). Patients received thyroidectomy and complementary I-131 RIT. Clinical data regarding basic demographic characteristics, tumor grade, persistent disease and recurrence during follow-up, and disease-free, disease-specific, and overall survival were collected during follow-up of 6.9 years (interquartile range 3.7; 11.7 years). Univariate and multivariate analyses were used to identify factors associated with disease-related and overall survival.
RESULTS
Before and after matching for risk factors, recurrence was significantly more frequently diagnosed in OFTC patients during follow-up (17% vs. 8%; p value 0.037). Likewise, OFTC patients presented with a reduced mean disease-free survival of 17.9 years (95% CI 16.0-19.8) vs. 20.1 years (95% CI 19.0-21.1) in FTC patients (p value 0.027). Multivariate analysis revealed OFTC (HR 0.502; 95% CI 0.309-0.816) as the only independent prognostic factor for disease-free survival. Distant metastases of OFTC patients were significantly less iodine-avid (p value 0.014). Mean disease-specific and overall survival did not differ significantly (p value 0.671 and 0.687) during follow-up of median 6.9 years (3.7; 11.7 years).
CONCLUSIONS
Our study suggests that recurrence is more often seen in OFTC patients. OFTC patients have a poorer prognosis for disease-free survival. Thus, OFTC and FTC behave differently and should be categorized separately. However, patients suffering from OFTC present with the same overall and disease-specific survival at the end of follow-up indifferent to FTC patients after initial RIT.
Topics: Adenocarcinoma, Follicular; Humans; Iodine Radioisotopes; Neoplasm Recurrence, Local; Oxyphil Cells; Prognosis; Retrospective Studies; Thyroid Neoplasms; Thyroidectomy
PubMed: 32683470
DOI: 10.1007/s00259-020-04952-2 -
Medicine Jul 2020Tc-99m sestamibi single-photon emission computed tomography/computed tomography (SPECT/CT) has been used to help surgeons explore the location of parathyroid diseases,...
The Usefulness of Maximum Standardized Uptake Value at the Delayed Phase of Tc-99m sestamibi single-photon emission computed tomography/computed tomography for Identification of Parathyroid Adenoma and Hyperplasia.
Tc-99m sestamibi single-photon emission computed tomography/computed tomography (SPECT/CT) has been used to help surgeons explore the location of parathyroid diseases, but quantitative parameters have not been systemically investigated for this purpose. We aimed to establish objective criteria for adenoma and hyperplasia using the standardized uptake value (SUV) in patients with hyperparathyroidism.Thirty-nine hyperparathyroid patients (male/female: 17/22, age: 58.33 ± 11.69 years) with at least 1 uptake-positive lesion of any degree by visual assessment in preoperative Tc-99m sestamibi quantitative SPECT/CT were included from Oct 2015 to Oct 2017. Pathologically, 44 lesions (32 adenomas and 12 hyperplasia) were identified. All patients experienced normalized levels of intact parathyroid hormone immediately after surgery. Quantitative SPECT/CT was performed at 10 minute and 2 hour post injection of Tc-99m sestabmibi (dose = 740 MBq), and maximum SUV (SUVmax) was measured for the parathyroid lesions. Experienced pathologists evaluated the percentage cellular proportions of chief cells, oxyphil cells, and clear cells.SUVmax (g/mL) of adenomas, hyperplasia, and reference thyroid tissue were 12.92 ± 6.68, 7.90 ± 5.49, and 7.01 ± 2.62 at 10min (early phase), decreasing to 7.46 ± 5.66, 4.65 ± 3.14, and 2.21 ± 1.07 at 2 hour (delayed phase), respectively. The adenomas showed significantly higher SUVmax than both the hyperplasia (P = .0131) and reference thyroid tissue (P < .0001) along the early and delayed phases, but the SUVmax of the hyperplasia did not differ from that of the reference thyroid tissue (P = .4196). The adenomas and hyperplasia were discriminated from the reference thyroid tissue using a cutoff SUVmax of 3.26 at the delayed phase. The adenomas had lower %proportions of oxyphil cells than the hyperplasia (P = .0054), but its SUVmax at the delayed phase was positively correlated with the %proportions of mitochondria-abundant oxyphil cells (rho = 0.418, P = .0173). The hyperplasia showed no correlation between SUVmax and cellular proportions.SUVmax at the delayed phase in the Tc-99m sestamibi quantitative SPECT/CT was useful for the identification and differentiation of parathyroid lesions causing hyperparathyroidism.
Topics: Adenoma; Adult; Aged; Diagnosis, Differential; Female; Humans; Hyperparathyroidism; Hyperplasia; Male; Middle Aged; Parathyroid Glands; Parathyroid Neoplasms; Radiopharmaceuticals; Retrospective Studies; Single Photon Emission Computed Tomography Computed Tomography; Technetium Tc 99m Sestamibi
PubMed: 32664158
DOI: 10.1097/MD.0000000000021176 -
International Journal of Surgical... Dec 2020Thyroid-like follicular carcinoma of kidney (TLFCK) is a morphological subtype of renal cell carcinoma, which is included as an emerging/provisional entity in the... (Review)
Review
Thyroid-like follicular carcinoma of kidney (TLFCK) is a morphological subtype of renal cell carcinoma, which is included as an emerging/provisional entity in the classification of renal tumors, with only about 40 cases reported in literature. It has a distinct histological appearance and immunohistochemical profile as compared with other renal cell cancers. However, these tumors, while appearing distinctive, have not been characterized fully either morphologically or by ancillary techniques. The reported cases show variable demographical and clinical features. Most are indolent, while some present with metastasis. The histological, immunohistochemical, and ultrastructural features of a case of TLFCK with clusters of oncocytic cells and pseudosarcomatous stroma are presented. Follow-up of 5 years was uneventful. A review of literature to analyze features in metastatic as compared with non-metastatic TLFCK is discussed. We report a patient of TLFCK and compare the clinicopathological features of metastatic and non-metastatic tumors.
Topics: Adenocarcinoma, Follicular; Adult; Biomarkers, Tumor; Carcinoma, Renal Cell; Diagnosis, Differential; Humans; Kidney; Kidney Neoplasms; Male; Nephrectomy; Oxyphil Cells
PubMed: 32484016
DOI: 10.1177/1066896920930283 -
Cancer Science Aug 2020Oncocytic cell tumor of the thyroid is composed of large polygonal cells with eosinophilic cytoplasm that is rich in mitochondria. These tumors frequently have the...
Oncocytic cell tumor of the thyroid is composed of large polygonal cells with eosinophilic cytoplasm that is rich in mitochondria. These tumors frequently have the mutations in mitochondrial DNA encoding the mitochondrial electron transport system complex I. However, the mechanism for accumulation of abnormal mitochondria is unknown. A noncanonical mitophagy system has recently been identified, and mitochondria-eating protein (MIEAP) plays a key role in this system. We therefore hypothesized that accumulation of abnormal mitochondria could be attributed to defective MIEAP expression in these tumors. We first show that MIEAP was expressed in all the conventional thyroid follicular adenomas (FAs)/adenomatous goiters (AGs) but not in oncocytic FAs/AGs; its expression was defective not only in oncocytic thyroid cancers but also in the majority of conventional thyroid cancers. Expression of MIEAP was not correlated with methylation status of the 5'-UTR of the gene. Our functional analysis showed that exogenously induced MIEAP, but not PARK2, reduced the amounts of abnormal mitochondria, as indicated by decreased reactive oxygen species levels, mitochondrial DNA / nuclear DNA ratios, and cytoplasmic acidification. Therefore, together with previous studies showing that impaired mitochondrial function triggers compensatory mitochondrial biogenesis that causes an increase in the amounts of mitochondria, we conclude that, in oncocytic cell tumors of the thyroid, increased abnormal mitochondria cannot be efficiently eliminated because of a loss of MIEAP expression, ie impaired MIEAP-mediated noncanonical mitophagy.
Topics: Adenoma, Oxyphilic; Animals; Cell Line, Tumor; Humans; Male; Mice; Mitochondria; Mitochondrial Proteins; Mitophagy; Oxyphil Cells; Retrospective Studies; Thyroid Gland; Thyroid Neoplasms; Thyroidectomy; Ubiquitin-Protein Ligases; Xenograft Model Antitumor Assays
PubMed: 32458504
DOI: 10.1111/cas.14501 -
Head and Neck Pathology Mar 2021Multifocal cystic oncocytosis (MCO) is a rare, benign process accounting for approximately 0.1% of salivary gland lesions. Salivary oncocytosis is characterized by...
Multifocal cystic oncocytosis (MCO) is a rare, benign process accounting for approximately 0.1% of salivary gland lesions. Salivary oncocytosis is characterized by multiple unencapsulated solid nodules of oncocytic cells derived from transformed striated ducts. MCO is a variant of salivary oncocytosis which manifests as cystically dilated striated ducts. It is difficult to obtain a definitive preoperative diagnosis of MCO; therefore, these lesions are commonly treated with surgery. We report the unique case of a 66-year-old male who previously underwent a superficial left parotidectomy for a pleomorphic adenoma. Four years later, he presented with clinical and radiographic suspicion of a multifocal recurrent pleomorphic adenoma. The patient subsequently underwent a revision parotidectomy. However, final pathology confirmed a diagnosis of MCO. Although MCO is commonly treated with surgery due to lack of a definitive preoperative diagnosis, surgery is unnecessary outside of diagnostic, functional or cosmetic considerations. Thus, if a patient with parotid oncocytosis treated by superficial parotidectomy develops disease re-manifestation in the residual deep lobe, further surgery is not indicated. There is no risk of malignant progression in this process. We report on this unusual entity as it may mimic salivary malignancy or, as in this case, recurrence of benign disease.
Topics: Adenoma, Pleomorphic; Aged; Cysts; Humans; Male; Neoplasm Recurrence, Local; Oxyphil Cells; Parotid Diseases; Parotid Neoplasms
PubMed: 32410133
DOI: 10.1007/s12105-020-01170-y -
The Gulf Journal of Oncology Jan 2020Chronic immunosuppression is known to cause an increased risk of cancers in organ transplant recipients leading to the rise in morbidity and mortality among these...
Chronic immunosuppression is known to cause an increased risk of cancers in organ transplant recipients leading to the rise in morbidity and mortality among these patients. Recent studies have observed that thyroid lesions are more frequently encountered in kidney transplant recipients. A 45-year-old woman with history of chronic hypertension, kidney transplant and graft failure, was admitted for assessment for a second renal transplant and detected to have a thyroid nodule by ultrasound (US). A fine needle aspirate (FNA) on the nodule was reported as Hurthle cell neoplasm. Histopathology revealed a Hurthle cell adenoma with an incidental micro papillary carcinoma. On follow up a year later, US investigation revealed another nodule in the inferior pole of the remnant lobe of thyroid. FNA showed sheets of uniform small round cells arranged in micro follicles, intermixed with Hurthle-like cells with absence of colloid, raising the possibility of a parathyroid lesion. Biochemical tests, clinical history, cytomorphological, immunocytochemical and biochemical tests supported a parathyroid adenoma. Advancements in diagnostic techniques and management strategies have not only improved survival rates in patients with chronic renal disease but have also identified an increasing number of multiple primary tumors in these patients. Thyroid lesions have cytomorphological similarities and may masquerade parathyroid neoplasms. Regular thyroid screening in post- transplant patients, meticulous pathological examination and parathormone assay are crucial in the early diagnosis, management and prevention of morbidity and mortality in these patients. Keywords: Fine needle aspiration, kidney transplant, Hurthle cell neoplasm, parathyroid adenoma, micropapillary carcinoma.
Topics: Adenoma; Carcinoma, Papillary; Diagnosis, Differential; Female; Humans; Middle Aged; Oxyphil Cells; Parathyroid Neoplasms; Primary Graft Dysfunction; Transplant Recipients
PubMed: 32342922
DOI: No ID Found