Idris Tolgay Ocal

Tissue microarray‐based studies of patients with lymph node negative breast carcinoma show that met expression is associated with worse outcome but is not correlated with epidermal growth factor family receptors

It has been shown that receptor tyrosine kinases (RTKs) predict outcome in patients with breast carcinoma. Although RTKs are a large family, HER‐2, epidermal growth factor receptor (EGFR), Met (hepatocyte growth factor receptor), and others all have shown the ability to predict outcome. However, it remains unclear whether these markers are defining the same subpopulation of patients with breast carcinoma. In this study, the authors attempted to determine the correlation between RTKs on the basis of their ability to stratify a population according to outcome.

Gene Expression Profiling of Benign and Malignant Pheochromocytoma

Abstract:  There are currently no reliable diagnostic and prognostic markers or effective treatments for malignant pheochromocytoma. This study used oligonucleotide microarrays to examine gene expression profiles in pheochromocytomas from 90 patients, including 20 with malignant tumors, the latter including metastases and primary tumors from which metastases developed. Other subgroups of tumors included those defined by tissue norepinephrine compared to epinephrine contents (i.e., noradrenergic versus adrenergic phenotypes), adrenal versus extra‐adrenal locations, and presence of germline mutations of genes predisposing to the tumor. Correcting for the confounding influence of noradrenergic versus adrenergic catecholamine phenotype by the analysis of variance revealed a larger and more accurate number of genes that discriminated benign from malignant pheochromocytomas than when the confounding influence of catecholamine phenotype was not considered. Seventy percent of these genes were underexpressed in malignant compared to benign tumors. Similarly, 89% of genes were underexpressed in malignant primary tumors compared to benign tumors, suggesting that malignant potential is largely characterized by a less‐differentiated pattern of gene expression. The present database of differentially expressed genes provides a unique resource for mapping the pathways leading to malignancy and for establishing new targets for treatment and diagnostic and prognostic markers of malignant disease. The database may also be useful for examining mechanisms of tumorigenesis and genotype–phenotype relationships. Further progress on the basis of this database can be made from follow‐up confirmatory studies, application of bioinformatics approaches for data mining and pathway analyses, testing in pheochromocytoma cell culture and animal model systems, and retrospective and prospective studies of diagnostic markers.

Medullary Thyroid Carcinoma without Marked Elevation of Calcitonin : A Diagnostic and Surveillance Dilemma

Calcitonin is a sensitive tumor marker for medullary thyroid cancer (MTC) and is useful in preoperative diagnosis and postoperative surveillance for recurrent disease. Calcitonin-negative MTC is a rare occurrence. We present the case of a 68-year-old man with a 6.5 cm sporadic MTC with a 5-cm metastasis in the neck, but only minimally elevated serum calcitonin levels. He underwent total thyroidectomy, resection of internal jugular vein, and limited ipsilateral lymph node dissection. He remains disease-free 12 months after surgery. We review the literature on calcitonin-negative MTC and discuss methods of postoperative surveillance in this subset of patients.

Special Variants of Differentiated Thyroid Cancer: Does It Alter the Extent of Surgery Versus Well-Differentiated Thyroid Cancer?

IntroductionRecently, more aggressive variants of so-called well-differentiated thyroid carcinomas have been identified such as the tall cell variant, columnar cell variant, diffuse sclerosing variant, insular carcinoma, and Hürthle cell (oncocytic, oxyphilic) carcinomas.MethodsAn evidence-based review was performed to identify the optimal treatment recommendations for these thyroid cancers of intermediate differentiation.ConclusionsAlthough some variation exists within the group, aggressive surgical and medical management are recommended for these neoplasias. Any such recommendations should, however, be viewed in the light of the fact that the current literature mainly consists of case reports, case series, and limited reviews. The clinical presentation, pathophysiology, diagnosis, and surgical and medical management for these thyroid cancers with intermediate differentiation are discussed.

Microvessel area using automated image analysis is reproducible and is associated with prognosis in breast cancer.

Microvessel density may be one measure of tumor associated angiogenesis but is methodologically difficult to standardize and reproduce. We used our automated quantitative image analysis system, AQUA, to more objectively assess microvessel area. Cytokeratin and CD31 were used to create tumor and vessel compartments respectively with AQUA. Microvessel area was defined as CD31 compartment area normalized to the tissue spot area (CD31 area/area of entire tissue spot). Consecutive breast cancer whole sections were stained with CD31 to compare pathologist-based microvessel density with AQUA microvessel area. Microvessel areas of 3-fold redundant tissue microarrays of 652 primary breast cancers were also assessed. CD34 and factor VIII-related antigen were also tested. There was nearly linear correlation between pathologists microvessel density and AQUA microvessel area with regression coefficient R = 0.846. On the redundant arrays, of the 67% evaluable cases, 52% were microvessel area high and 48% low with good reproducibility of scores (Spearman rho 0.551). AQUA microvessel area was associated with larger tumors, node positivity, and estrogen receptor negativity, with 20 year survival at the univariate and multivariate levels (P < .0001 and P = .0121, respectively). CD34 or factor VIII-related antigen were more heterogenous, had poor association with CD31, and did not correlate with outcome. AQUA-based microvessel area was significantly correlated with both standard breast cancer prognostic parameters as well as with clinical outcome. In the future, it may also allow the use of the AQUA-based algorithms to quantify the expression of angiogenic biomarkers to either tumor or microvessel area-specific compartments.

Primary Leiomyosarcoma of the Thyroid Gland

Primary leiomyosarcomas of the thyroid gland are rare. We present the case of a 65-year-old woman with a rapidly enlarging neck mass for 2 months. The preoperative differential diagnosis included medullary thyroid cancer, anaplastic thyroid cancer, and primary versus metastatic sarcoma. The patient underwent total thyroidectomy, bilateral central neck dissections, and cervical thymectomy; she is currently being treated with ifosfamide and adriamycin. We review the literature on leiomyosarcoma of the thyroid, including the differential diagnoses, pathology, and alternative treatment strategies, including surgery and adjuvant therapy.

Desmoplastic Infantile Ganglioglioma: cytologic findings and differential diagnosis on aspiration material

Background Desmoplastic infantile ganglioglioma (DIG) is a rare WHO Grade I tumor of infancy that is characterized by large volume, superficial location, invariable supratentoriality, fronto-parietal lobe predilection and morphologically, by an admixture of astroglial and neuroepithelial elements in a desmoplastic milieu. With over 50 cases described, the histologic and radiographic spectrum of DIG has been well-characterized. The superficial location of DIGs may render them greatly amenable to preoperative assessment utilizing aspiration cytology; however, the cytologic features of this rare tumor have only been reported once previously. Case Presentation We present herein cytomorphologic findings from the intraoperative aspiration of a typical case of DIG diagnosed in a 1-year-old male. As evaluated on a single liquid-based preparation, the specimen showed low cellularity and was comprised predominantly of a population of dispersed (occasionally clustered) large neuronal cells with eccentrically located hyperchromatic nuclei (which were occasionally binucleated) and abundant unipolar cytoplasm. Rare smaller astroglial cells were intermixed. Despite the tumors characteristic desmoplastic histologic appearance, no stromal fragments were identified on the aspiration material. Conclusions A differential diagnosis is presented and analyzed in detail and it is concluded that when these large neuronal cells are encountered in an aspirate of a brain mass in a child, a combination of clinical, radiologic and immunohistochemical parameters can eliminate most of the differential possibilities.

Leiomyosarcoma of the Adrenal vein: a novel approach to surgical resection

BackgroundLeiomyosarcomas typically originate within smooth muscle cells. Leiomyosarcomas arising from the adrenal vein are rare malignancies associated with delayed diagnosis and poor prognosis. The most common vascular site of origin is the inferior vena cava.Case presentationThis is a 64-year old woman who presented with a 13 × 6.5 × 6.6 cm heterogeneous mass arising in the region of the right adrenal gland and extending into the inferior vena cava (IVC) and the right atrium. Biochemical evaluation excluded a functional tumor of the adrenal gland, and multiple tumor markers were negative. We present the novel use of deep hypothermic circulatory arrest (DHCA) in the resection of an adrenal vein leiomyosarcoma extending into the right atrium. The patient remains free of disease ten months after surgery. DHCA afforded a bloodless operative field for optimal resection of disease from within the IVC.ConclusionThe diagnosis of leiomyosarcomas of the adrenal vein is one of exclusion and involves preoperative radiological imaging and biochemical evaluation to exclude other functional tumors of the adrenal gland. Aggressive surgical resection is associated with improved survival and may be best achieved via collaboration among different surgical subspecialties.

Fine needle aspiration of poorly differentiated oxyphilic (Hürthle cell) thyroid carcinoma: a case report.

BACKGROUND Poorly differentiated oxyphilic (Hürthle cell) carcinomas are a more recently described variant of poorly differentiated thyroid carcinoma and are characterized by a prominent Hürthle cell component in a solid or trabecular arrangement. Clinically, poorly differentiated oxyphilic carcinomas behave more aggressively as compared to classic Hürthle cell carcinomas, which have a predominantly follicular pattern. Although the histology of these rare thyroid tumors has been reported in the literature, the cytologic features on fine needle aspiration biopsy have not been described before. CASE A 73-year-old man with a long history of radioactive iodine and levothyroxine therapy for multinodular goiter presented with a painful, rapidly expanding, 6-cm, left thyroid mass with aggressive radiologic features. Fine needle aspiration biopsy of the mass yielded extremely cellular smears with a dual population of medium-sized follicular cells and numerous Hürthle cells. Subsequent thyroidectomy confirmed the malignant nature of this Hürthle cell-rich tumor, warranting a diagnosis of poorly differentiated oxyphilic (Hürthle cell) thyroid carcinoma. CONCLUSION Poorly differentiated oxyphilic thyroid carcinoma is an aggressive variant of Hürthle cell carcinomas and must enter the differential diagnosis when fine needle aspiration biopsy of a radiologically aggressive thyroid mass yields extremely hypercellular smears with a prominent Hürthle cell component.

Medullary Thyroid Carcinoma: A Brief Review of Pathogenesis, Diagnosis, and Treatment

Medullary thyroid carcinoma (MTC) is a differentiated form of thyroid carcinoma that, in contrast to the more common follicular cell–derived carcinomas, arises from the calcitonin-secreting parafollicular C cells. The majority are sporadic, presenting as a solitary thyroid nodule in adulthood, whereas the less common hereditary forms present at an earlier age, typically as multifocal disease. In unsuspected patients, MTC is often at an advanced stage at the time of diagnosis. The diagnosis of MTC is almost always made by fine-needle aspiration (FNA) cytology in sporadic cases and often by serum calcitonin measurement in patients known to be at risk of hereditary disease. The variety of cytologic presentations of MTC introduces many possibilities in the differential diagnosis. The diagnostic accuracy of FNA can be enhanced by ancillary testing, specifically calcitonin and carcinoembryonic antigen immunohistochemistry or measurement of these tumor markers in serum or FNAwashout fluid. Recognition of the role of mutations in the RET (REarranged during Transfection) proto-oncogene in the pathogenesis of MTC has led to the development of tests for screening, diagnosis, and prognostication. The mainstay of treatment is thyroidectomy with central neck lymph node dissection, whichmay be performed as a prophylactic procedure in patients with germlineRETmutations. Given the suboptimal results of radiotherapy and chemotherapy, treatments that specifically target RET such as vandetanib and cabozantinib have shown promise in phase 3 clinical trials.