Treatment modalities and outcomes of granular cell tumors and spindle cell oncocytomas of the pituitary gland: an analysis of two national cancer databases.

BACKGROUND: Spindle cell oncocytomas (SCO) and granular cell tumors (GCT) are rare primary pituitary neoplasms; the optimal treatment paradigms for these lesions are unknown and largely unexplored. Thus, using national registries, we analyze the epidemiology, management patterns, and surgical outcomes of SCOs and GCTs. METHODS: The National Cancer Database (NCDB; years 2003-2017) and the Surveillance, Epidemiology, and End Results Program (SEER; years 2004-2018) were queried for patients with pituitary SCOs or GCTs. Incidence, extent of surgical resection, and rate of postoperative radiation use for subtotally resected lesions comprised the primary outcomes of interest. All-cause mortality was also analyzed via time-to-event Kaplan-Meier curves. RESULTS: SCOs and GCTs have an annual incidence of 0.017 and 0.023 per 1,000,000, respectively. They comprise 0.1% of the benign pituitary tumors registered in NCDB. A total of 112,241 benign pituitary tumors were identified in NCDB during the study period, of which 83 (0.07%) were SCOs and 59 (0.05%) were GCTs. Median age at diagnosis was 55 years, 44% were females, and median maximal tumor diameter at presentation was 2.1 cm. Gross total resection was achieved in 54% patients. Ten patients (7%) had postoperative radiation. Comparing patients with GCTs versus SCOs, the former were more likely to be younger at diagnosis (48.0 vs. 59.0, respectively; p < 0.01) and female (59% vs. 34%, p = 0.01). GCTs and SCOs did not differ in terms of size at diagnoses (median maximal diameter: 1.9 cm vs. 2.2 cm, respectively; p = 0.59) or gross total resection rates (62% vs. 49%, p = 0.32). After matching SCOs and GCTs with pituitary adenomas on age, sex, and tumor size, the former were less likely to undergo gross total resection (53% vs. 72%; p = 0.03). Patients with SCOs and GCTs had a shorter overall survival when compared to patients with pituitary adenomas (p < 0.01) and a higher rate of thirty-day mortality (3.1% vs 0.0%; p = 0.013). CONCLUSION: SCOs and GCTs are rare pituitary tumors, and their management entails particular challenges. Gross total resection is often not possible, and adjuvant radiation might be employed following subtotal resection.

Oncocytoid Salivary Tumors: Differential Diagnosis and Utility of Newly Described Immunohistochemistry.

BACKGROUND: Oncocytoid salivary tumors include several entities such as oncocytoma, Warthin tumor, secretory carcinoma (SC), salivary duct carcinoma (SDC), acinic cell carcinoma (AciCC), oncocytic mucoepidermoid carcinoma (OMEC), intraductal carcinoma, and epithelial myoepithelial carcinoma (EMC). This review investigates the differential diagnosis of oncocytoid salivary tumors and explore the role of newly described immunostains as valuable tools for their diagnosing and potentially guiding treatment options. METHODS: We assess the utility of incorporating new immunohistochemical markers in routine practice to aid in diagnosing oncocytoid salivary tumors and potentially provide treatment options. RESULTS: In SDC, AR and Her2 immunostains are utilized as diagnostic tools and biomarkers for selecting patients who might benefit from Androgen-deprivation therapy (ADT) and HER2-targeted therapy. Furthermore, nuclear Pan-Trk immunostaining can aid in diagnosing SC. Additionally, NR4A3 immunostaining has been shown high sensitivity and specificity in identifying AciCC in both surgical and cytologic specimens. Similarly, RAS Q61R mutant-specific immunostaining, detected in EMC, may offer a cost-effective diagnostic marker for this tumor. Although further studies are required to evaluate the role of BSND, this marker has been reported to be positive in Warthin tumor and oncocytoma, aiding in differentiating them from other oncocytoid tumors, particularly OMEC. In addition, BRAFV600E mutant-specific immunostaining can serve as a diagnostic and potentially therapeutic marker for oncocytic intraductal carcinoma in mutation positive cases. CONCLUSION: Oncocytoid salivary tumors may have overlapping morphologies, posing diagnostic challenges for pathologists. Recently described immunohistochemical markers may offer valuable tools for diagnosing and potentially guiding treatment options for these tumors.

Case of clear-cell oncocytoma of parotid gland and literature review.

Oncocytoma is a benign tumor of the salivary gland. Its incidence is very low and very seldom documen-ted in literature. Clear-cell dominant oncocytoma is even less common. The tumor's clinical symptoms and imaging results are nonspecific, so distinguishing other salivary gland tumors (such as oncocytic carcinoma) from clear-cell renal carcinoma is difficult, possibly leading to misdiagnosis and maltreatment. Here, a case of clear-cell dominant oncocytoma was presented, and the relevant literature was evaluated to investigate the diagnosis and management of clear-cell dominant oncocytoma.

Characterization of a Molecularly Distinct Subset of Oncocytic Pleomorphic Adenomas/Myoepitheliomas Harboring Recurrent ZBTB47-AS1::PLAG1 Gene Fusion.

Recurrent gene fusions are common in salivary gland tumors including benign tumors, such as pleomorphic adenoma (PA) and myoepithelioma (ME). In cases where chromosomal rearrangement is identified in the pleomorphic adenoma gene 1 (PLAG1) gene, different gene partners are found. Oncocytic metaplasia, characterized by oncocytes with abundant eosinophilic granular cytoplasm and hyperchromatic nuclei, is a well-known phenomenon in salivary gland neoplasms. However, the pure oncocytic variant of PA/ME showed PLAG1 gene rearrangements involving various gene partners at the molecular level, without any recurrent fusion being found. Our study includes 20 cases of PA/ME, with 11 females and 9 males. The age of patients ranged from 37 to 96 years, with a median age of 62.8 years. Most tumors originate from the parotid gland. The median size of the tumor was 26.5 mm (range: 13 to 60 mm). Among the 20 cases, 14 were a pure oncocytic variant of PA/ME, whereas 6 cases showed focal oncocytic or oncocytic-like aspects. Molecular studies on 20 cases of PA/ME were conducted. A novel recurrent ZBTB47-AS1::PLAG1 fusion was identified in 6 of 12 cases with pure oncocytic metaplasia, whereas the other cases had PLAG1 gene fusion with different gene partners. The transcriptomic analysis of the cases harboring ZBTB47-AS1::PLAG1 fusion demonstrated that these tumors have a distinct molecular profile from conventional PA/ME. This study reveals a unique subset in the oncocytic PA/ME spectrum characterized by pure oncocytic morphology with larger oncocytic cells and recurrent ZBTB47-AS1::PLAG1 fusion. It also highlights the transcriptomic distinctness of salivary gland adenomas with pure oncocytic metaplasia in the spectrum of salivary gland neoplasms. Further studies are needed to better understand the oncocytic variant of PA/ME and to determine the true nature of oncocytic cells in PA/ME.

Low grade oncocytic renal tumor (LOT): Clinicopathological characterization of 13 cases.

CONTEXT: Low grade oncocytic tumor (LOT) is a recently recognized renal oncocytic neoplasm with unique morphologic and immunohistochemical pattern (CK7 +, CD117 -) that differentiates them from oncocytoma and chromophobe renal cell carcinoma (ChrRCC). OBJECTIVE: To further evaluate the histomorphological characteristics as well as the clinical outcome of low grade oncocytic tumors, retrospectively. DESIGN: Thirteen cases of LOT were identified from 463 cases of renal oncocytic neoplasm in our pathology archive. All tumors were immunostained with CK7, CD117 and other relevant markers. The pathohistological features and follow up data of these cases were recorded. RESULTS: Median age of patients was 76 years old (range from 36 to 86), with male to female ratio of 2:11. None of the patients had a syndromic association/hereditary condition. Eleven tumors were unifocal in each affected kidney, and two were multifocal with 2 and 3 separated tumors, respectively. On microscopic examination, tumors show variety of growth patterns, namely solid, compact nested, focal tubular/tubuloreticular and trabecular patterns. The stroma can be hypocellular and edematous where the tumor cells are loosely arranged exhibiting cords and scattered single cell arrangement. Immunohistochemically, all thirteen cases displayed strong and diffuse CK7 positivity in tumor cells. Eleven cases were CD117 negative and the other two showed focal and weak CD117 positivity (< 5% of tumor cells). Uniform tumor cell positivity was found for AE1/3, EMA, PAX8, and e-cadherin. Negative staining results include CAIX, AMACR, CD10 and vimentin. All cases in our cohort demonstrate indolent behavior and show no evidence of disease recurrence, progression, or metastases during the follow-up period up to 96 months. CONCLUSION: LOT is an emerging new entity of renal oncocytic neoplasm and demonstrates indolent clinical behavior. Its unique morphologic features and immunohistochemical patterns (CK7 +, CD117 -) set them apart from oncocytoma and ChrRCC.

Forward Genetic Screens Identify Mechanisms of Resistance to Small-Molecule Lactate Dehydrogenase Inhibitors.

Altered metabolism is a hallmark of cancer; however, it has been difficult to specifically target metabolism in cancer for therapeutic benefit. Cancers with genetically defined defects in metabolic enzymes constitute a subset of cancers where targeting metabolism is potentially accessible. Hürthle cell carcinoma of the thyroid (HTC) tumors frequently harbor deleterious mitochondrial DNA (mtDNA) mutations in subunits of complex I of the mitochondrial electron transport chain (ETC). Previous work has shown that HTC models with deleterious mtDNA mutations exhibit mitochondrial ETC defects that expose lactate dehydrogenase (LDH) as a therapeutic vulnerability. Here, we performed forward genetic screens to identify mechanisms of resistance to small-molecule LDH inhibitors. We identified two distinct mechanisms of resistance: upregulation of an LDH isoform and a compound-specific resistance mutation. Using these tools, we demonstrate that the anticancer activity of LDH inhibitors in cell line and xenograft models of complex I mutant HTC is through on-target LDH inhibition.

Molecular Alterations and Comprehensive Clinical Management of Oncocytic Thyroid Carcinoma: A Review and Multidisciplinary 2023 Update.

Importance: Oncocytic (Hürthle cell) thyroid carcinoma is a follicular cell-derived neoplasm that accounts for approximately 5% of all thyroid cancers. Until recently, it was categorized as a follicular thyroid carcinoma, and its management was standardized with that of other differentiated thyroid carcinomas. In 2022, given an improved understanding of the unique molecular profile and clinical behavior of oncocytic thyroid carcinoma, the World Health Organization reclassified oncocytic thyroid carcinoma as distinct from follicular thyroid carcinoma. The International Thyroid Oncology Group and the American Head and Neck Society then collaborated to review the existing evidence on oncocytic thyroid carcinoma, from diagnosis through clinical management and follow-up surveillance. Observations: Given that oncocytic thyroid carcinoma was previously classified as a subtype of follicular thyroid carcinoma, it was clinically studied in that context. However, due to its low prevalence and previous classification schema, there are few studies that have specifically evaluated oncocytic thyroid carcinoma. Recent data indicate that oncocytic thyroid carcinoma is a distinct class of malignant thyroid tumor with a group of distinct genetic alterations and clinicopathologic features. Oncocytic thyroid carcinoma displays higher rates of somatic gene variants and genomic chromosomal loss of heterozygosity than do other thyroid cancers, and it harbors unique mitochondrial DNA variations. Clinically, oncocytic thyroid carcinoma is more likely to have locoregional (lymph node) metastases than is follicular thyroid carcinoma-with which it was formerly classified-and it develops distant metastases more frequently than papillary thyroid carcinoma. In addition, oncocytic thyroid carcinoma rarely absorbs radioiodine. Conclusions and Relevance: The findings of this review suggest that the distinct clinical presentation of oncocytic thyroid carcinoma, including its metastatic behavior and its reduced avidity to radioiodine therapy, warrants a tailored disease management approach. The reclassification of oncocytic thyroid carcinoma by the World Health Organization is an important milestone toward developing a specific and comprehensive clinical management for oncocytic thyroid carcinoma that considers its distinct characteristics.

Scars Run Deep: Problematic Morphology and Immunoprofile of Scars in Renal Oncocytomas.

In some instances, the central scar of renal oncocytoma can demonstrate entrapped cells with unusual morphology and aberrant immunoprofile creating potential diagnostic confusion. Herein, 100 renal oncocytomas containing scars with embedded epithelial cells were identified from 6 institutions, including nephrectomies (64% partial, 36% radical) of similar laterality (left = 51%) and sex distribution (male = 56%), with patient ages ranging from 38 to 86 years (mean = 64.3years) and tumor sizes ranging from 2 to 16 cm (mean = 5.3 cm). Immunohistochemistry was performed on all tumors for KRT7, KIT, vimentin, and CA9 with staining intensity and extensity separately analyzed. Of 4 architectural patterns of cells within the scar, 60% showed tubular pattern. Of 4 cytologies within the scar, flat/elongated (49%) and cuboidal cells (40%) predominated. Within the scar, 62% showed eosinophilic cytoplasm, with 38% showing both cleared and eosinophilic cytoplasm; notably, 79% showed higher grade nuclei than typical oncocytes. A subset of scar cells showed mucinous-like basophilic secretions (19%). Compared to background renal oncocytoma, tumor cells within the scar were more often positive for vimentin, KRT7, and CA9 and more frequently negativity for KIT. Specifically, of the notable "aberrant" immunoprofiles, 79% showed KRT7 positivity/KIT negativity/vimentin positive, 84% showed vimentin positivity/CA9 positivity, and 78% showed KIT negativity/vimentin positivity/CA9 positivity. While encountering scars within renal oncocytomas is not uncommon, what is not well appreciated is the unique morphology and immunohistochemistry of tumor cells within the scar. Comparing tumor morphology and immunoprofile of the scar to the background oncocytoma is helpful to avoid interpretative confusion.

Radiomics analysis based on single phase and different phase combinations of radiomics features from tri-phasic CT to distinguish renal oncocytoma from chromophobe renal cell carcinoma.

OBJECTIVES: To investigate different radiomics models based on single phase and the different phase combinations of radiomics features from 3D tri-phasic CT to distinguish RO from chRCC. METHODS: A total of 96 patients (30 RO and 66 chRCC) were enrolled in this study. Radiomics features were extracted from unenhanced phase (UP), corticomedullary phase (CMP), and nephrographic phase (NP) CT images. Feature selection was based on the least absolute shrinkage and selection operator regression (LASSO) method. The selected features were used to develop different radiomics models using logistic regression (LR) analysis, including model 1 (UP), model 2(CMP), model 3(NP), model 4(UP+CMP), model 5(UP+NP), model 6(CMP+NP), and model 7(UP+CMP+NP). The radiomics model demonstrating the highest discrimination performance was utilized to construct the combined model (model 8) with clinical factors. A nomogram based on the model 8 was established. To evaluate the diagnostic performance of the different models, the receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were used. Delong's test was utilized to assess the statistical significance of the AUC improvement across the models. RESULTS: Among the seven radiomics models, model 7 exhibited the highest AUC of 0.84 (95% CI 0.69, 0.99), and model 7 demonstrated a significantly superior AUC compared to the other radiomics models (all P < 0.05). The AUC values of radiomics models based on two phases (model4, mode5, mode6) were greater than the models based on single phase (model1, mode2, mode3) (all P < 0.05). Model 3 illustrated the best performance of the three radiomics models based on single phase with an AUC of 0.76 (95% CI 0.57, 099). Model 6 illustrated the best performance of the three radiomics models based on two-phases combination with an AUC of 0.83 (0.66, 0.99). Model 8 achieved an AUC of 0.93 (95% CI 0.83, 1.00) which is higher than those all radiomics models. CONCLUSION: Radiomics models based on combination of radiomics features from UP, CMP, and NP can be a useful and promising technique to differentiate RO from chRCC. Moreover, the model combining clinical factors and radiomics features showed better classification performance to distinguish them.

Hybrid Oncocytic Tumors (HOTs) in Birt-Hogg-Dubé Syndrome Patients-A Tale of Two Cities: Sequencing Analysis Reveals Dual Lineage Markers Capturing the 2 Cellular Populations of HOT.

Birt-Hogg-Dubé (BHD) syndrome is associated with an increased risk of multifocal renal tumors, including hybrid oncocytic tumor (HOT) and chromophobe renal cell carcinoma (chRCC). HOT exhibits heterogenous histologic features overlapping with chRCC and benign renal oncocytoma, posing challenges in diagnosis of HOT and renal tumor entities resembling HOT. In this study, we performed integrative analysis of bulk and single-cell RNA sequencing data from renal tumors and normal kidney tissues, and nominated candidate biomarkers of HOT, L1CAM, and LINC01187 , which are also lineage-specific markers labeling the principal cell and intercalated cell lineages of the distal nephron, respectively. Our findings indicate the principal cell lineage marker L1CAM and intercalated cell lineage marker LINC01187 to be expressed mutually exclusively in a unique checkered pattern in BHD-associated HOTs, and these 2 lineage markers collectively capture the 2 distinct tumor epithelial populations seen to co-exist morphologically in HOTs. We further confirmed that the unique checkered expression pattern of L1CAM and LINC01187 distinguished HOT from chRCC, renal oncocytoma, and other major and rare renal cell carcinoma subtypes. We also characterized the histopathologic features and immunophenotypic features of oncocytosis in the background kidney of patients with BHD, as well as the intertumor and intratumor heterogeneity seen within HOT. We suggest that L1CAM and LINC01187 can serve as stand-alone diagnostic markers or as a panel for the diagnosis of HOT. These lineage markers will inform future studies on the evolution and interaction between the 2 transcriptionally distinct tumor epithelial populations in such tumors.

Prospective evaluation of core number of biopsy for renal tumor: are multiple cores preferable?

PURPOSE: This single-center, single-arm, prospective, open-label study was conducted to evaluate the optimal number of cores (single or multiple) in renal tumor biopsy. MATERIALS AND METHODS: Forty-four biopsies of 44 tumors (mean diameter, 2.7 ± 1.0 cm; range, 1.6-5.0 cm) were included. Biopsy was performed under ultrasound or computed tomography fluoroscopy guidance using an 18-gauge cutting needle and the co-axial method. Two or more specimens were obtained, which were divided into first and subsequent specimens. "First specimen" and "all specimens" were histologically evaluated (i.e., appropriateness of specimen, histological diagnosis, subtype, and Fuhrman grade of renal cell carcinoma [RCC]) blindly and independently by two board-certified pathologists. RESULTS: Multiple specimens were successfully and safely obtained in all the biopsies. All tumors were histologically diagnosed; 40 malignancies included 39 RCCs and 1 solitary fibrous tumor, and 4 benign lesions included 2 angiomyolipomas, 1 oncocytoma, and 1 capillary hemangioma. In all RCCs, the subtype could be determined (32 clear cell RCCs, 4 chromophobe RCCs, and 3 papillary RCCs), and the Furman grade was determined in 38 RCCs. When only the first specimen was evaluated, 22.7% of the specimens were inappropriate for diagnosis, and 34 (77.3%) were histologically diagnosed. The diagnostic yield was significantly lower than that of all specimens (P = 0.0044). Univariate analysis revealed that smaller lesions were a significant predictor of diagnostic failure (P = 0.020). CONCLUSION: Biopsy with multiple cores significantly improved diagnostic yield. Thus, operators should obtain multiple cores during renal tumor biopsy.

Thyroid-stimulating hormone receptor (TSHR) as a target for imaging differentiated thyroid cancer.

BACKGROUND: Of the half a million cases of thyroid cancer diagnosed annually, 95% are differentiated thyroid cancers. Although clinical guidelines recommend surgical resection followed by radioactive iodine ablation, loss of sodium-iodine symporter expression causes up to 20% of differentiated thyroid cancers to become radioactive iodine refractory. For patients with radioactive iodine refractory disease, there is an urgent need for new diagnostic and therapeutic approaches. We evaluated the thyroid-stimulating hormone receptor as a potential target for imaging of differentiated thyroid cancer. METHODS: We immunostained tissue microarrays containing 52 Hurthle cell carcinomas to confirm thyroid-stimulating hormone receptor expression. We radiolabeled chelator deferoxamine conjugated to recombinant human thyroid-stimulating hormone analog superagonist TR1402 with 89Zr (t1/2 = 78.4 h, ß+ =22.7%) to produce [89Zr]Zr-TR1402. We performed in vitro uptake assays in high-thyroid-stimulating hormone receptor and low-thyroid-stimulating hormone receptor-expressing THJ529T and FTC133 thyroid cancer cell lines. We performed in vivo positron emission tomography/computed tomography and biodistribution studies in male athymic nude mice bearing thyroid-stimulating hormone receptor-positive THJ529T tumors. RESULTS: Immunohistochemical analysis revealed 62% of patients (27 primary and 5 recurrent) were thyroid-stimulating hormone receptor membranous immunostain positive. In vitro uptake of 1nM [89Zr]Zr-TR1402 was 38 ± 17% bound/mg in thyroid-stimulating hormone receptor-positive THJ529T thyroid cancer cell lines compared to 3.2 ± 0.5 in the low-expressing cell line (P < .01), with a similar difference seen in FTC133 cell lines (P < .0001). In vivo and biodistribution studies showed uptake of [89Zr]Zr-TR1402 in thyroid-stimulating hormone receptor-expressing tumors, with a mean percentage of injected dose/g of 1.9 ± 0.4 at 3 days post-injection. CONCLUSION: Our observation of thyroid-stimulating hormone receptor expression in tissue microarrays and [89Zr]Zr-TR1402 accumulation in thyroid-stimulating hormone receptor-positive thyroid cancer cells and tumors suggests thyroid-stimulating hormone receptor is a promising target for imaging of differentiated thyroid cancer.

Family history of malignant or benign thyroid tumors: implications for surgical procedure management and disease-free survival.

Background: Current guidelines lack a standardized management for patients with family history of thyroid carcinoma (fTC),particularly benign thyroid neoplasm (fBTN). Our objective was to investigate the influence of various family histories on the selection of surgical approaches and disease-free survival (DFS). Methods: A cohort study was conducted involving 2261 patients diagnosed with differentiated thyroid carcinoma including those with fTC (n=224), fBTN (n=122), and individuals without a family history of thyroid carcinoma (nfTC; n=1915). Clinicopathological characteristics were collected. DFS was estimated using Kaplan-Meier analysis and factors affecting DFS were identified using Cox proportional hazard model. Results: Compared to nfTC, small tumor size, clinically lymph node-positive, extrathyroidal extension, vascular invasion, Hashimoto's disease and nodular goiter were more common in fTC and fBTN groups. They had lower T stage and a lower rate of good response to TSH suppression therapy but received more radioiodine therapy. It is worth noting that fTC is associated with male, bilateral and multifocal tumors, as well as central lymph node metastasis and distant metastasis. Both fTC (aHR = 2.45, 95% CI=1.11-5.38; P = 0.03) and fBTN (aHR = 3.43, 95% CI=1.27-9.29; P = 0.02) were independent predictors of DFS in patients who underwent lobectomy, but not total thyroidectomy. For 1-4 cm thyroid carcinomas with clinically node-negative, fTC was identified as an independent predictor, whereas fBTN was not. Conclusion: Our findings indicate that a family history, particularly of malignancy, is associated with a more aggressive disease. Family history does not affect the prognosis of patients who undergo total thyroidectomy, but it may increase the risk of postoperative malignant events in those who have a lobectomy. Additionally, it may be necessary to monitor individuals with a family history of benign thyroid neoplasms.

Renal oncocytoma in a 13-year-old girl: A case report and literature review.

Renal oncocytoma is a benign renal neoplasm which has mostly been reported in adults. Occurrence in children is infrequent. To date, there are only six pediatric cases of renal oncocytoma reported previously. Herein, we report a 13-year-old girl presented with hematuria for a week. Abdominal computed tomography showed a well-defined heterogeneous solid mass with a stellate central scar in the left kidney. The patient underwent a nephron sparing surgery. Histopathological and immunohistochemical findings confirmed the diagnosis of renal oncocytoma. Though uncommon, renal oncocytoma should be considered as the differential diagnosis of renal tumor in children. In addition, intranuclear inclusions were firstly described in this pediatric patient with unclear significance, which need a large cohort to summarize and analyze.

[Morphological and molecular portrait hybrid renal tumors].

A hybrid tumor is not officially included in the latest International Histological Classification of Kidney Tumors (WHO, 2022), however, according to the literature, a number of researchers still consider a hybrid tumor as an independent nosological unit. In this regard, the development of morphological and molecular genetic criteria for a hybrid tumor, today, is the main task in the differential diagnosis of oncocytic renal tumors. AIM: Our aim was to carry out to identify immunohistochemical, ultrastructural features and determine the molecular profile of hybrid renal tumors. PATIENTS AND METHODS: The study was performed on the surgical material of 12 patients with a hybrid tumor of the kidney. Immunohistochemical study was carried out on paraffin sections according to the standard protocol. Antibodies CK7, CD117, Cyclin D1, EpCAM, Caveolin1, EABA, and S100A1 were used. To study tumor tissues on semi-thin and ultra-thin sections, an electron microscope Philips TECNAI 12 BioTwinD-265 is used. For in situ fluorescent diagnostic detection, defined centromere probes, LSI 13/21, LSI N25 /LSI ARSA and TelVysion telomeric probe. RESULTS: In some cases, a hybrid tumor is represented by a solid structure of monomorphic oxyphilic cells with a characteristic immuno-, ultraphenotype and molecular profile. CONCLUSION: The results of a comprehensive study confirm that the hybrid tumor is an intermediate link in the process of malignant transformation of oncocytoma into chromophobe renal cell carcinoma.

Primary hydatid cyst of the thyroid glands: two case reports and a review of the literature.

INTRODUCTION: Although hydatid cyst remains one of the prevalent parasitic infections in humans, hydatid cyst of the thyroid is extremely rare, even in endemic areas. Here we present two cases of thyroid hydatid cysts. CASE PRESENTATION: A 35 and a 50 year-old Iranian female with a positive history of animal contact were presented with a neck lump without any compressive symptoms. A physical exam revealed neck masses that elevated with swallowing. Thyroid gland ultrasonography showed cystic thyroid lesions, and fine needle aspiration (FNA) suggested a thyroid hydatic cyst. Thyroid lobectomy and isthmectomy were done for the first patient, and near-total thyroidectomy was done for the other. The pathology report confirmed the diagnosis of a hydatid cyst. None of the patients had hydatid cysts in other sites. Patients were discharged without an antiparasitic drug, and no recurrence was detected at the six-month follow-up. CONCLUSION: It is necessary to consider hydatid cysts in the differential diagnosis of cystic lesions of the thyroid gland in endemic areas, especially in people with a positive history of animal contact.

Improving CNNs classification with pathologist-based expertise: the renal cell carcinoma case study.

The prognosis of renal cell carcinoma (RCC) malignant neoplasms deeply relies on an accurate determination of the histological subtype, which currently involves the light microscopy visual analysis of histological slides, considering notably tumor architecture and cytology. RCC subtyping is therefore a time-consuming and tedious process, sometimes requiring expert review, with great impact on diagnosis, prognosis and treatment of RCC neoplasms. In this study, we investigate the automatic RCC subtyping classification of 91 patients, diagnosed with clear cell RCC, papillary RCC, chromophobe RCC, or renal oncocytoma, through deep learning based methodologies. We show how the classification performance of several state-of-the-art Convolutional Neural Networks (CNNs) are perfectible among the different RCC subtypes. Thus, we introduce a new classification model leveraging a combination of supervised deep learning models (specifically CNNs) and pathologist's expertise, giving birth to a hybrid approach that we termed ExpertDeepTree (ExpertDT). Our findings prove ExpertDT's superior capability in the RCC subtyping task, with respect to traditional CNNs, and suggest that introducing some expert-based knowledge into deep learning models may be a valuable solution for complex classification cases.