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Ronald A DeLellis

Publications and source records attributed to Ronald A DeLellis.

At least 19 recordsLinked to original sources
PubMed2006

Re-operative neck surgery for well-differentiated thyroid cancer of follicular origin.

This review focuses on the pathologic criteria for completion thyroidectomy in well differentiated thyroid cancer as well the diagnosis and treatment of recurrent disease. The roles of ultrasound in the diagnosis of a cervical recurrence, its value in determining the extent of lymph node dissection in the lateral compartment, and the importance of intra-operative ultrasound in re-operative thyroid surgery are discussed.

Adenocarcinoma, Follicular↗
PubMed2006

Pathology and genetics of thyroid carcinoma.

Carcinomas of the thyroid comprise a heterogeneous group of neoplasms with distinctive clinical and pathological characteristics. Over the past 15 years, the application of molecular technologies to the study of these neoplasms has elucidated critical genetic pathways associated with the development of specific thyroid tumor types. In papillary thyroid carcinoma (PTC), genetic events involve RET and TRK (rearrangements) and BRAF and RAS (mutations), although RAS mutations are uncommon except in the follicular variant of PTC. These genetic alterations, which rarely overlap in the same tumor, result in signaling abnormalities in the mitogen-activated protein kinase pathway. In contrast, genetic alterations in follicular carcinomas include PAX8-PPARgamma translocations and RAS mutations while mutations of CTNNB1 and p53 have been implicated in the development and progression of poorly differentiated and undifferentiated (anaplastic) thyroid carcinomas. Germline mutations of RET are responsible for the development of heritable forms of medullary thyroid carcinoma (MTC) while somatic mutations of this oncogene are found in a significant proportion of sporadic MTCs. The results of these studies not only have provided additional approaches to thyroid tumor classification, but also have stimulated the development of novel approaches to tumor diagnosis and additional parameters for prognostic assessment and potential biologic therapeutic strategies.

Adenocarcinoma, Follicular↗
PubMed2006

Distribution of GPR30, a seven membrane-spanning estrogen receptor, in primary breast cancer and its association with clinicopathologic determinants of tumor progression.

PURPOSE: The seven transmembrane receptor, GPR30, is linked to estrogen binding and heparan-bound epidermal growth factor release. Here, the significance of GPR30 in human breast cancer was evaluated by comparing its relationship to steroid hormone receptor expression and tumor progression variables. EXPERIMENTAL DESIGN: Immunohistochemical analysis of a National Cancer Institute-sponsored tumor collection comprised of 361 breast carcinomas obtained at first diagnosis (321 invasive and 40 intraductal tumors). Biopsies from 12 reduction mammoplasties served as controls. The distribution pattern of GPR30, estrogen receptor (ER), and progesterone receptor (PR) was correlated with clinicopathologic variables obtained at diagnosis. RESULTS: GPR30, ER, and PR were positive in all 12 normal controls. In contrast, GPR30 expression varied in breast tumors, in which 62% (199 of 321) of invasive tumors and 42% (17 of 40) of intraductal tumors were positive. Codistribution of ER and GPR30 was measured in 43% (139 of 321) of invasive breast tumors, whereas both receptors were lacking (ER-GPR30-) in 19% (61 of 321) of the tumors analyzed, indicating a significant association between ER and GPR30 (P<0.05). The coexpression of PR and ER did not influence GPR30 expression, yet coexpression of GPR30 and ER was linked to PR positivity. Unlike ER, which varied inversely with HER-2/neu and tumor size, GPR30 positively associated with HER-2/neu and tumor size. In addition, GPR30 showed a positive association with metastasis (P=0.014; odds ratio, 1.9). CONCLUSIONS: GPR30 and ER exhibited distinct patterns of association with breast tumor progression variables, including HER-2/neu, tumor size, and metastatic disease. Thus, these results support the hypothesis that GPR30 and ER have an independent influence on estrogen responsiveness in breast carcinoma.

Biomarkers, Tumor↗
PubMed2005

Parathyroid carcinoma: an overview.

Parathyroid carcinoma is a rare tumor that is responsible for <1% of cases of hyperparathyroidism in most parts of the world. An increased incidence of this tumor has been reported in patients with the hyperparathyroidism-jaw tumor (HPT-JT) syndrome, but the etiology of most other cases is unknown. Parathyroid carcinomas tend to occur a decade earlier than adenomas, and the sex ratio approaches unity in contrast to the female preponderance of adenomas. Most patients with carcinomas present with marked hypercalcemia and are more likely to have associated bone and renal disease than those with adenomas. Although fibrosis and mitotic activity are common in carcinomas, these features are not specific for malignancy. The diagnosis of carcinoma should be restricted to those tumors that show invasion of blood vessels, perineural spaces, soft tissues, thyroid gland, or other adjacent structures or to tumors with documented metastases. Mutations of the HRPT2 gene (1q21-q32), which are responsible for the HPT-JT syndrome, have been implicated in the development of a high proportion of parathyroid carcinomas. A subset of patients with mutation-positive carcinomas have germline mutations of the HRPT2 gene. This finding suggests that some patients with apparent sporadic parathyroid carcinomas may have the HPT-JT syndrome or a variant of this syndrome. Because of the high frequency of local recurrence following incomplete excision, an en bloc resection is the preferred surgical approach for treatment of parathyroid carcinomas.

Carcinoma↗
PubMed2004

Incorporating pathologists' criteria of malignancy into the evolutionary model for cancer development.

A wide variety of alterations in cell and tissue structure still form the basis for cancer diagnosis by pathologists. Cancer development is recognized to be an evolutionary process [Foulds, 1954; Cairns, 1975; Nowell, 1976; Sager, 1982; Tomlinson et al., 1996; Cahill et al., 1999; Tomlinson and Bodmer, 1999], but the phenotypic changes diagnostic of cancer (pathologists' "criteria of malignancy") have not been integrated into the existing evolutionary framework. Since phenotypic changes bear an important relationship to the genetic and physiologic changes underlying Darwinian evolution, we propose that diagnostic structural alterations also bear an important and predictable relation to both the cancer genes and the functional alterations active at any particular step in the development of a cancer. Cancer genes are predicted to mediate the acquisition of cellular-level diagnostic criteria and the diagnostic cellular-level structural changes should reflect in a useful manner the altered cell physiology required for the cell to achieve increased "cellular fitness" at any particular step of colonal evolution. Tissue-level criteria of malignancy should relate less directly to specific cancer genes, but tissue-level criteria should still provide essential insight into the interplay of the altered cellular fitness with the constraints imposed by the cells' microenvironment. The evolutionary framework allows tissue-level criteria of malignancy to be expressed in terms of viable hypotheses for the mechanism of clonal expansion at any particular step in cancer development. This approach to conveying the tissue-level criteria of malignancy complements pattern recognition approaches to diagnosis, and establishes common ground between pathology and cell biology. When viewed from this perspective, the functions of cancer genes appear quite different from those predicted by the "Gatekeeper, Caretaker" or "Hallmarks of Cancer" models. Finally, a full evolutionary framework incorporating the criteria of malignancy restores congruity between the histogenetic classification and the emerging molecular classification of cancer.

Cell Transformation, Neoplastic↗
PubMed2004

Observer variation in the diagnosis of follicular variant of papillary thyroid carcinoma.

The histopathologic diagnosis of follicular variant of papillary thyroid carcinoma (FVPCA) can be difficult. Recent reports have suggested that this neoplasm may be frequently overdiagnosed by pathologists. We examined the observer variation in the diagnosis of FVPCA in 87 tumors by 10 experienced thyroid pathologists. The criteria that the reviewers considered most helpful for making a diagnosis of FVPCA were also assessed. A concordant diagnosis of FVPCA was made by all 10 reviewers with a cumulative frequency of 39%. In this series, 24.1% of the patients had metastatic disease (n = 21). In the cases with metastatic disease, a diagnosis of FVPCA was made by all 10 reviewers with a cumulative frequency of 66.7%, and 7 of the reviewers made a diagnosis of FVPCA with a cumulative frequency of 100%. The most important criteria used to diagnose FVPCA included the presence of cytoplasmic invaginations into the nucleus (pseudo-inclusions), abundant nuclear grooves, and ground glass nuclei. These results suggest that although the diagnosis of FVPCA is variable even among experienced thyroid pathologists, most reviewers agreed on this diagnosis for patients with metastatic disease. The use of well-defined histopathologic features should improve the consistency in diagnosing FVPCA. Since most cases with metastatic disease had obvious invasion, caution should be used in making a diagnosis of FVPCA in the absence of the major histopathologic features or clear-cut invasive growth.

Carcinoma, Papillary, Follicular↗
PubMed2004

Primary carcinoid tumor of the prostate with concurrent adenocarcinoma: a case report.

Prostatic adenocarcinomas commonly exhibit neuroendocrine differentiation as demonstrated by immunohistochemistry. However, true carcinoids of the prostate are rare. We describe herein a case of a primary carcinoid occurring synchronously with a conventional adenocarcinoma in the prostate of a 66-year-old man. The carcinoid measured 0.2 x 0.2 cm and did not show contiguity with adjacent conventional, moderately differentiated adenocarcinoma. Immunohistochemical stains for chromogranin and neuron-specific enolase were strongly immunoreactive in the carcinoid but not in the adenocarcinoma. Both neoplasms demonstrated positive staining for prostatic acid phosphatase and prostate-specific antigen. Owing to the relatively minute size of the carcinoid, the possibility that this tumor will impact negatively on the patient's overall prognosis is not anticipated.

Acid Phosphatase↗
PubMed2003

Calcitonin immunoreactivity in neoplastic and hyperplastic parathyroid glands: an immunohistochemical study.

BACKGROUND: Previous studies have established that calcitonin (CT) and the calcitonin generelated peptide (CGRP) are synthesized and stored in subsets of hyperplastic parathyroid cells that also contain chromogranin B (Schmid, KW, et al. Lab Invest 73:90, 1995). The purpose of the current study was to determine whether other generic but variably expressed neuroendocrine markers, i.e., synaptophysin (SYN) and CD57 (Leu7), are also present in normal, hyperplastic, and neoplastic parathyroid tissue and to assess their relationships to the presence of CT. DESIGN: Immunoperoxidase stains for chromogranin A (CgA), chromogranin B (CgB), SYN, CD57, and CT were performed on 54 hyperplastic, 17 neoplastic (adenoma), and 16 normal parathyroid glands. Sequential sections were stained with antibodies to CgA, CgB, SYN, CD57, and CT using standard avidin-biotin-peroxidase techniques. RESULTS: CgA was diffusely expressed in all normal, hyperplastic, and neoplastic glands. In hyperplasia, CgB was variably expressed in 6 cases (11%), SYN in 6 (11%), CD57 in 15 (28%), and CT in 8 (15%). In adenomas, CgB was variably expressed in 3 (17%), SYN in 3 (17%), CD57 in 4 (23%), and CT in 4 (23%). All normal glands were negative for CgB, SYN, and CT, while CD57 was variably expressed in 17%. Of the 12 glands that were CT positive, 8 were also positive for CgB, 2 for SYN, and 9 for CD57. Four glands that were strongly and diffusely positive for CT were CgB and SYN negative. CONCLUSIONS: CgB, SYN, and CD57 are markers for subsets of hyperplastic and neoplastic parathyroid glands. CT is also expressed in a significant proportion of hyperplastic and neoplastic parathyroid glands, and may be independent of the presence of CgB, SYN, or DD57. The significance of these findings in relationship to the abnormal calcium metabolism in patients with parathyroid hyperplasia remains to be determined.

Adenoma↗
PubMed2003

Paraneoplastic endocrine syndromes: a review.

The paraneoplastic endocrine syndromes ("ectopic" or "inappropriate" hormone production) comprise a wide array of symptom complexes associated with malignant or less commonly benign neoplasms. Most of the syndromes are associated with the production of peptide hormones, which, in some instances, have autocrine stimulatory effects. Hypercalcemia, the most common paraneoplastic endocrine syndrome, may be due to the systemic release of parathyroid hormone-related protein (PTHrP), factors that may be produced locally (cytokines), or by a combination of these mechanisms. A spectrum of other syndromes may be related to the production of specific hormones or growth factors, including insulin-like growth factor and fibroblast growth factor 23. Molecular mechanisms responsible for the development of these syndromes are poorly understood. Mutational events not only may initiate neoplastic transformation but may also lead to the activation (re-expression) of genes responsible for hormone production. Additionally, epigenetic events such as methylation may also be responsible for the development of these syndromes. It is likely that a multiplicity of genetic and epigenetic events may contribute to the development of paraneoplastic endocrine syndromes.

Adrenocorticotropic Hormone↗
PubMed2003

Interpretative problems and preparative technique influence reliability of intraoperative parathyroid touch imprints.

CONTEXT: Identification of parathyroid tissue (PT) is crucial during parathyroid and thyroid surgery. Touch imprint preparation (TIP) examination is potentially a more time-effective and less labor-intensive approach than frozen section examination for identification of PT during intraoperative consultation. However, the reliability of PT-TIP remains controversial, and this fact has hindered its adoption as a replacement for frozen section examination. OBJECTIVE: To assess the factors contributing to the relative lack of reliability of TIP in a retrospective study. METHODS: Fifty randomly selected, alcohol-fixed, hematoxylin-eosin- and/or Diff-Quik-stained TIPs of specimens that had been submitted to confirm PT during intraoperative consultation were retrospectively reviewed by 5 observers. The observers were blinded to the final interpretation (based on hematoxylin-eosin-stained permanent sections), which included PT in 39 (78%) of the 50 specimens, thyroid in 9 (18%), lymph node in 1 (2%), and adipose tissue 1 (2%). Cases in which a unanimous diagnosis was not attained were re-reviewed by 3 observers. RESULTS: Of 50 TIPs reviewed, a unanimous diagnosis was rendered in 33 cases (66%), including 27 (69%) of 39 PT cases, 5 (56%) of 9 thyroid cases, and the 1 lymph node case. Cytologic features observed in the TIPs that were unanimously accepted as being diagnostic of PT included the presence of small uniform cells in isolation or in small groups, round to oval nuclei, salt-and-pepper chromatin, occasional naked nuclei, and delicate vacuoles both within the cytoplasm and in the background. Re-review of the 17 remaining TIPs cases, in which diagnostic unanimity was not achieved, demonstrated that factors hindering assessment of the TIPs included hypocellularity (n = 5 cases), air-drying effect (n = 4), hemorrhagic background (n = 4), and presence of PT cells in follicular (thyroid-like) arrangements (n = 4). CONCLUSIONS: The major factors influencing reliability of TIP of PT during intraoperative consultation are related primarily to interpretative problems and preparative technique. Awareness of interpretative problems and attention to preparation of TIPs may further enhance the accuracy of TIP during intraoperative consultation.

Cytodiagnosis↗
PubMed2002

Aspiration cytology of elastofibroma dorsi: case report with ultrastructural and immunohistochemical findings.

Elastofibroma is a well-recognized tumor-like process which typically occurs in the soft tissue of the shoulder. Although fine-needle aspiration (FNA) represents a quick and simple method for definitive diagnosis, the possibility of a false-negative diagnosis is high due to the hypocellularity of the smears. However, a high index of suspicion based on the clinical presentation of a firm mass in a typical location in an elderly person, usually female, aids in the diagnosis. We describe the FNA findings of elastofibroma dorsi in an 89-yr-old woman which, although hypocellular, contained diagnostic aggregates of petaloid globules within a collagenous matrix. The cytologic material showed a green-yellow autofluorescence of the altered elastic fibers with ultraviolet light. Transmission electron microscopy revealed an elongated beaded appearance with small electron densities and obliteration of the central elastin core. The presence of a hypocellular aspirate with autofluorescent elastic fibers should suggest the possibility of elastofibroma dorsi.

Aged↗
PubMed2002

Observer variation of encapsulated follicular lesions of the thyroid gland.

Although histologic definition of follicular thyroid lesions is readily available, application of the diagnostic criteria and personal experience may lead to disagreement among pathologists. To investigate interobserver variation in assessment of encapsulated follicular lesions, eight pathologists (four American and four Japanese) reviewed the same hematoxylin and eosin-stained slide of each of 21 cases of thyroid lesions showing encapsulation and follicular growth pattern. In 10% of the cases, there was complete agreement. At least seven pathologists agreed on the diagnosis in 29% of the cases, and at least six in 76% of the cases. American and Japanese pathologists agreed among themselves in 33% and 52% of cases, respectively. The frequency of diagnosis of adenomatous goiter among Japanese pathologists (31%) was considerably higher than that among American pathologists (6%). In contrast, the frequency of diagnosis (25%) of papillary carcinoma among American pathologists was considerably higher than that (4%) among Japanese pathologists. Our analysis revealed three main factors affecting observer variation: 1) interpretation of the significance of microfollicles intimately related to capillaries within the tumor capsule, 2) evaluation of what constituted the type of nuclear clearing indicative of papillary carcinoma, and 3) absence of clear morphologic criteria for separation of adenomatous goiter and follicular adenoma. To reduce observer variation of encapsulated follicular lesions, it will be necessary to provide more explicit criteria for diagnosis.

Adenoma↗
PubMed2002

Thyroid gland: international case conference.

The cases of five thyroid tumors were presented and discussed at an international case conference held during the 5th Annual Meeting of the Japanese Endocrine Pathology Society. There was significant disagreement among six pathologists who studied the cases. In this article, we present two of the cases, attempt to explain the reason for disagreement in their diagnoses, and propose what should be done to obtain better consensus in diagnosis.

Adenocarcinoma, Follicular↗