Loss of primary cilia promotes mitochondria-dependent apoptosis in thyroid cancer

The primary cilium is well-preserved in human differentiated thyroid cancers such as papillary and follicular carcinoma. Specific thyroid cancers such as Hürthle cell carcinoma, oncocytic variant of papillary thyroid carcinoma (PTC), and PTC with Hashimoto’s thyroiditis show reduced biogenesis of primary cilia; these cancers are often associated the abnormalities in mitochondrial function. Here, we examined the association between primary cilia and the mitochondria-dependent apoptosis pathway. Tg-Cre;Ift88flox/flox mice (in which thyroid follicles lacked primary cilia) showed irregularly dilated follicles and increased apoptosis of thyrocytes. Defective ciliogenesis caused by deleting the IFT88 and KIF3A genes from thyroid cancer cell lines increased VDAC1 oligomerization following VDAC1 overexpression, thereby facilitating upregulation of mitochondria-dependent apoptosis. Furthermore, VDAC1 localized with the basal bodies of primary cilia in thyroid cancer cells. These results demonstrate that loss-of-function of primary cilia results in apoptogenic stimuli, which are responsible for mitochondrial-dependent apoptotic cell death in differentiated thyroid cancers. Therefore, regulating primary ciliogenesis might be a therapeutic approach to targeting differentiated thyroid cancers.

A Case of Low-Grade Oncocytic Tumor/Chromophobe Renal Cell Carcinoma (Oncocytic Variant) of the Kidney

The oncocytic variant of chromophobe renal cell carcinoma (oChRCC) and low-grade oncocytic tumor (LOT) is introduced as new renal disease entity. Both of these tumors are low-grade malignancies consisting of cells with eosinophilic cytoplasm. Distinguishing between eosinophilic variant of chromophobe renal cell carcinoma (eCRCC) and oncocytoma is often a diagnostic challenge in routine surgical pathology. However, oChRCC and LOT might be independent disease entities that might not fit completely into any of these categories. Histologically, these tumors have greater morphological similarity with oncocytoma than with ChRCC. However, immunohistochemically, they exhibit diffuse and dense positivity for CK7 and are negative for CD117. In the present case, we initially had difficulty distinguishing among oncocytoma, eCRCC, and type 2 papillary renal cell carcinoma (2-pRCC). However, after learning about new disease entities such as oChRCC and LOT, we were able to diagnose this tumor.

Oncocytic variant, a novel subtype of chromophobe renal cell carcinoma: a report of two cases and a literature review

A novel variant of chromophobe renal cell carcinoma showing an oncocytic phenotype is proposed. Two new cases of this rare entity are presented and discussed along with six previous cases from our colleagues. A 76-year-old man and a 78-year-old man had a 3.4-cm and a 3.2-cm-diameter renal mass, respectively. On histopathological examination of surgical specimens, uniform eosinophilic cuboidal cells without a perinuclear halo growing in a tubular pattern were seen, and differential diagnosis from oncocytoma was necessary. Immunohistochemical staining for cytokeratin 7 and E-cadherin showed diffusely positive patterns in both, as in the previous reports. Although monosomy of chromosomes 7, 10, 13, and 17 was commonly observed in the previous reports, gains of chromosome 19 were observed in the two present cases. Immunohistochemical and cytogenetic approaches lead to exclusion of oncocytoma and the diagnosis of an oncocytic variant of chromophobe renal cell carcinoma.

The Oncocytic Variant of Poorly Differentiated Thyroid Carcinoma Shows a Specific Immune-Related Gene Expression Profile

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.

Oncocytic Variant of Adrenocortical Carcinoma: Case Report of a Rare Malignancy

Adrenocortical carcinoma is a rare cancer. Oncocytic tumors of the adrenal gland are rarer. Most Oncocytic Adrenal Neoplasms are benign and carry favourable prognosis. They are classified as oncocytoma, oncocytic neoplasm of uncertain malignant potential and oncocytic adrenal carcinoma. The malignant nature of oncocytic neoplasm of adrenal gland can only be confirmed on histopathology. We report a case of a 55-year-old male with newly diagnosed hypertension being evaluated for left adrenal mass concerning for adrenocortical carcinoma. Open radical left adrenalectomy and nephrectomy was done and histopathology confirmed oncocytic variant of adrenocortical carcinoma based on Lin-Weiss-Bisceglia scoring system which has been developed particularly for oncocytic type of tumor. Though rare, oncocytic neoplasm has to be considered as one of the differential diagnoses of adrenocortical mass, especially those presenting as a large mass because malignant oncocytic neoplasm of adrenal gland as large as 23cm have been reported. Imaging modalities like ultrasonography, computed tomography or magnetic resonance imaging, though useful in evaluating an adrenocortical mass, cannot predict malignant nature of an oncocytic neoplasm. Diagnosis of adrenocortical carcinoma is therefore reliably made only after histopathological examination of the surgical specimen. Surgical resection in those presenting with nonmetastatic resectable disease remains the mainstay of ACC treatment. Oncocytic ACC compared with conventional ACCs matched for age, gender, disease stage and status of surgical resection, shows significant better overall survival thus representing more indolent variant of an aggressive and often fatal disease.

SUN-179 Oncocytic Adrenocortical Carcinoma: A Case Report

Adrenocortical carcinoma (ACC) is a rare tumor with a poor prognosis. Oncocytic variant of adrenocortical carcinoma is considered to be an even more rare malignancy with four reported in the literature in 2002 and thirty-six documented in 2015 i ii. This case report illustrates the case of oncocytic ACC. A 40-year-old woman post-hysterectomy from cervical cancer presented to the ER with severe left flank and back pain for two weeks. There was no weight loss or early satiety. CT scan revealed a large left adrenal mass measuring 12x9x13 cm, displacing the left kidney inferiorly with no metastasis to nearby structures. We ruled out functional adrenal mass through a 24-hour urine collection and blood work, then performed open left adrenalectomy. Grossly, it was a large, tan-colored mass, weighing approximately 2,500 grams. On biopsy, we incidentally found the mass to be oncocytic adrenocortical carcinoma. Using the Lin-Weiss-Bisceglia criteria, it met two major and one minor criteria, when only one major criterion is required to indicate malignancy. Immunohistochemical stains showed that the tumor cells were positive for Mart-1, inhibin, and synaptophysin. Quantitative Ki-67 showed a proliferation index of 10% in average (>5% is considered malignant). Even though adrenocortical carcinoma, specifically the oncocytic variant of ACC, is a very rare occurrence, it should be on the differential diagnosis for a chief complaint of unilateral flank pain with a large adrenal mass on CT due to its poor prognosis. Endnotes i Hoang, M., Ayala, A. & Albores-Saavedra, J. Oncocytic Adrenocortical Carcinoma: A Morphologic, Immunohistochemical and Ultrastructural Study of Four Cases. Mod Pathol 15, 973-978 (2002) doi:10.1038/modpathol.3880638 ii Kalra S, Manikandan R, Srinivas BH. Oncocytic adrenocortical carcinoma--a rare pathological variant. BMJ Case Rep. 2015;2015:bcr2014208818. Published 2015 Apr 24. doi:10.1136/bcr-2014-208818