Biomedical subjects
Idris Tolgay Ocal
Publications and source records attributed to Idris Tolgay Ocal.
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 tumor's 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.
beta-Catenin and p53 analyses of a breast carcinoma tissue microarray.
BACKGROUND: Aberrant activation of the beta-catenin signaling pathway has been implicated in several malignancies, including breast carcinoma. Recently, it was shown that p53 down-regulated beta-catenin in a complex fashion. The authors examined the expression of beta-catenin, key members of its signaling pathway, and p53 in a large cohort of breast tumors. METHODS: The authors conducted an immunohistochemical analysis of the expression of beta-catenin, upstream modulators (HER-2/neu, Met, and epidermal growth factor receptor [EGFR]), downstream target genes (cyclin D1 and matrix metalloproteinase-7 [MMP7]), and p53 on a tissue microarray of 346 lymph node-negative breast carcinomas. The results were correlated with one another and with standard clinicopathologic parameters. RESULTS: beta-Catenin expression was observed in the membrane and/or cytoplasm without any significant nuclear expression. HER-2/neu and EGFR were observed on the membrane in 21% and 6% of tumors, respectively, and Met stained in a membrane/cytoplasm distribution in 28% of cases. Cyclin D1 was expressed in the nucleus and MMP7 was expressed in the cytoplasm in 26% and 75% of tumors, respectively. Nuclear expression of p53 was noted in 31% of tumors. When each marker was analyzed separately, only p53 and Met demonstrated a significant correlation with survival. However, patients who had tumors that coexpressed high levels of beta-catenin and p53 had markedly worse overall survival (P = 0.0026). In multivariate analysis, only tumor size, Met, and the coexpression of beta-catenin and p53 retained statistical significance. CONCLUSIONS: The current findings support a potential synergistic effect of abnormal beta-catenin regulation and p53 status in the pathogenesis and natural history of lymph node-negative breast carcinoma. Furthermore, the results show that a combined analysis of multiple markers, notably beta-catenin and p53, may enhance the prognostic capabilities compared with individual markers.
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.
BACKGROUND: 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. METHODS: The authors used tissue microarray technology to study 324 patients with lymph node negative breast carcinoma who had 20-40 years of follow-up. Expression was assessed using immunohistochemical stains for Met, EFGR, fibroblast growth factor receptor (FGFR), and HER-2. Expression levels were assessed by two observers, and correlations were analyzed. Standard pathology information, including tumor size, nuclear grade, Ki-67 receptor status, and estrogen and progesterone receptor expression levels, also was collected. RESULTS: RTK expression in the study cohort revealed two strong correlations. Specifically, HER-2 and EGFR showed similar expression patterns (P < 0.0001), and Met cytoplasmic domain and FGFR cytoplasmic staining showed similar expression patterns (P < 0.0001), but no correlation was found between the two groups. Of these RTKs, only high levels of Met cytoplasmic domain showed significance as a prognostic marker defining a shortened survival compared with the rest of the population (P = 0.0035; relative risk, 2.04). In the same group of patients, HER-2, hormone receptor status, and other RTK family receptors were not correlated with outcome. In multivariate analysis, only Met cytoplasmic domain and tumor size showed independent predictive value. CONCLUSIONS: The current results indicate that the cytoplasmic domain of Met shows a unique staining pattern and defines a set of patients unique from the set of patients defined by overexpression of HER-2, EGFR, or hormone receptors. Furthermore, this group of patients is associated tightly and independently with worse outcome.
Tissue microarray analysis of hepatocyte growth factor/Met pathway components reveals a role for Met, matriptase, and hepatocyte growth factor activator inhibitor 1 in the progression of node-negative breast cancer.
Numerous studies have demonstrated that overexpression of Met, the hepatocyte growth factor(HGF) receptor, plays an important role in tumorigenesis. Met activation can either occur through ligand-independent or -dependent mechanisms, both of which are mediated by a series of proteases and modulators. We studied the protein expression of several components of the HGF/Met pathway on a cohort of 330 node-negative breast carcinomas using a tissue microarray annotated with 30-year, disease-specific patient follow-up data. We examined HGF, matriptase (an activator of HGF expressed on mammary epithelial cell surfaces), HAI-I (the cognate inhibitor of matriptase), and the Met receptor itself. Our studies demonstrate tight correlation between the expression of HGF, matriptase, and Met in breast carcinoma. High-level expression of Met, matriptase, and HAI-I were associated with poor patient outcome. Met and HAI-I showed independent prognostic value when compared with traditional breast markers in a multivariate analysis. Intriguingly, antibodies against the intracellular but not the extracellular domain of Met were prognostic, suggesting that overexpression of the cytoplasmic-tail of Met, perhaps through cleavage or truncating mutation, may play an important role in breast cancer progression.
A malignant ovarian tumor with osteoclast-like giant cells.
Neoplasms that are composed focally, predominantly, or exclusively of osteoclast-like giant cells admixed with variably pleomorphic mononuclear cells have been described in a wide variety of organs. In this report, we describe the case of a 76-year-old woman with an 8-cm tumor that appeared to be localized to the ovary, that was composed predominantly of diffusely distributed, bland-appearing osteoclast-like giant cells admixed with pleomorphic mononuclear cells, and that was not associated with an ovarian cystic neoplasm. Hemorrhage, large zones of necrosis, and a high mitotic index were the other characteristics of the tumor. Immunohistochemically, the mononuclear cells were strongly positive for vimentin and proliferating cell nuclear antigen and were negative for keratin AE 1/3, CAM 5.2, cytokeratin 7, epithelial membrane antigen, beta-human chorionic gonadotropin, desmin, smooth muscle actin, p53, leukocyte common antigen, S-100, inhibin, alpha-1-antichymotrypsin, and CD68. The osteoclast-like giant cells displayed immunoreactivity for CD68, vimentin, alpha-1-antichymotrypsin, and leukocyte common antigen only. Ultrastructurally, rare intercellular junctions were present between mononuclear cells, suggestive of an epithelial histogenesis. Less than a dozen ovarian lesions with the "giant cell" designation have been described, and most of these cases are thought to be analogous to the "sarcoma-like" nodules or other such lesions that have a well-known association with ovarian cystic neoplasms. Our case, in contrast, did not have an easily identifiable epithelial component and demonstrated both an infiltrative border and vascular invasion. This is, to the authors' knowledge, the first detailed clinicopathologic description of such a case as an ovarian lesion.
Vulvar basal cell carcinoma: two unusual presentations and review of the literature.
BACKGROUND: Basal cell carcinoma (BCC) of the vulva comprises 2-4% of all vulvar cancers. In general, vulvar BCCs tend to grow at slow rates. Nonetheless, they may be locally invasive and destructive if they are neglected. Eight cases of vulvar BCC metastatic to regional lymph nodes have been documented in the literature. CASES: Two unusual cases of vulvar BCC are presented. Case 1 is an 86-year-old white woman who presented with vulvar BCC metastatic to the femoral head. This is the first report of hematogeneous metastasis of vulvar BCC. The patient was treated with palliative vulvar resection and radiation to the femoral metastasis. At 6 months, she progressed with multiple bony and intraperitoneal metastases and died with disease. Case 2 is vulvar BCC in a 90-year-old African-American woman. She was managed by wide local excision and remains disease free to date. CONCLUSION: Vulvar BCCs are rare tumors with an unclear etiology. They can be aggressive and are capable of causing significant morbidity and occasional mortality if they are neglected or improperly treated. Hematogeneous metastasis at presentation appears to result in rapidly progressive disease. The literature regarding the pathogenesis, biologic behavior, and treatment of vulvar BCC is reviewed.
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.