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Jennifer L Hunt

Publications and source records attributed to Jennifer L Hunt.

At least 55 records · Page 3Linked to original sources
PubMed2004

Tumor suppressor gene allelic loss profiles of the variants of papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTCa) is a relatively common, indolent tumor that usually has an excellent prognosis. While the diagnosis of conventional PTCa is relatively straightforward, encapsulated tumors with follicular growth pattern and unusual or incomplete cytologic features of papillary carcinoma can be diagnostically challenging. Encapsulated, noninvasive tumors are particularly controversial as the differential diagnosis includes a nonneoplastic nodule, a benign follicular adenoma, and papillary carcinoma. In this study, we performed molecular genotyping to identify loss of heterozygosity of tumor suppressor genes in conventional PTCa and in several different morphologic variants, including follicular variant, tall cell variant, and oncocytic variant. Our data demonstrate that conventional PTCas have the lowest frequency of allelic loss (7%), as compared with follicular, oncocytic, and tall cell variants (19%, 34%, and 20%, respectively). Frequency of allelic loss increased with increasing size of the tumors, but did not correlate with age, gender, extrathyroidal extension, or lymph node metastases. Though it is unlikely that these results will enable the distinction between different variants of papillary carcinoma, the finding of significant rates ofallelic loss in the variants of PTCa provides additional evidence of malignancy and may be useful in distinguishing encapsulated tumors from nonneoplastic or benign nodules.

Adult↗
PubMed2004

Simultaneous diffuse sclerosis variant of papillary thyroid carcinoma and diffuse toxic hyperplasia (Graves' disease).

Diffuse sclerosis variant of papillary thyroid carcinoma (DSVPTC) is an unusual malignant neoplasm that typically permeates the entire gland resulting in diffuse thyroid enlargement. In the absence of a dominant nodule, DSVPTC can be histologically deceiving because of exuberant inflammation and the scattered distribution of the microscopic tumor islands. The difficulty in diagnosing this tumor is compounded by its rarity and unusual clinical and histologic features. Herein, we describe a unique case of DSVPTC that was clinically masked by a co-existing second diffuse thyroid process--Graves' disease (GD). A subtotal thyroidectomy was performed in a 27-yr-old Caucasian female who presented with symmetrical diffuse thyromegaly with neck compressive symptoms, thyrotoxicosis, and biochemical signs of GD. Histologic examination of the thyroid gland unexpectedly revealed extensive involvement by DSVPTC in addition to the diffuse hyperplastic non-malignant thyroid follicles. This report illustrates the histologic features as well as the diagnostic challenge encountered in a rare simultaneous occurrence of DSVPTC and GD.

Adult↗
PubMed2004

Microdissection techniques for molecular testing in surgical pathology.

OBJECTIVE: To describe the techniques for microdissection of paraffin-embedded and frozen tissue sections for the use in molecular applications. DATA SOURCES: Original research papers and review papers and the authors' personal experiences. DATA SYNTHESIS: Manual and laser-capture microdissection are described in detail, with specific protocols for sample preparation and instructions for performing the microdissection. A section addressing frequently asked questions is also included. CONCLUSIONS: Microdissection is a technique that is very useful both in the research setting and for clinical molecular testing in paraffin-embedded tissue samples. The available techniques range from simple and inexpensive (manual microdissection) to complex and expensive (laser-capture microdissection). All of the techniques, however, require the user to be familiar with microscopy and histology.

Genetic Techniques↗
PubMed2004

Molecular analysis to demonstrate that odontogenic keratocysts are neoplastic.

CONTEXT: Odontogenic keratocysts (OKCs) are unique odontogenic lesions that have the potential to behave aggressively, that can recur, and that can be associated with the nevoid basal cell carcinoma syndrome. Whether they are developmental or neoplastic continues to be debated. OBJECTIVES: To identify loss of heterozygosity of tumor suppressor genes in OKCs and to suggest a pathogenetic origin for these lesions. DESIGN: We examined 10 OKCs for loss of heterozygosity of tumor suppressor genes, using a microdissection and semiquantitative genotyping analysis. The genes analyzed included 10 common tumor suppressor genes, as well as the PTCH gene, which is mutated in nevoid basal cell carcinoma syndrome. RESULTS: Loss of heterozygosity was seen in 7 of 10 cases, with a frequency between 11% and 80% of the genes studied. The genes that exhibited the most frequent allelic losses were p16, p53, PTCH, and MCC (75%, 66%, 60%, and 60%, respectively). Daughter cysts were associated with a higher frequency of allelic loss (P =.02), but epithelial budding was not. CONCLUSIONS: Our study indicates that a significant number of OKCs show clonal loss of heterozygosity of common tumor suppressor genes. The finding of clonal deletion mutations of genomic DNA in these cysts supports the hypothesis that they are neoplastic rather than developmental in origin.

Adolescent↗
PubMed2003

Myoepithelial neoplasia of the submandibular gland: case report and therapeutic considerations.

Tumors of the submandibular gland typically arise from the seromucinous acini, which make up the majority of the gland. The most common benign tumor of this structure is the pleomorphic adenoma, whereas the most common malignancy of the submandibular gland is adenoid cystic carcinoma. We describe an unusual case of a neoplastic process of the myoepithelial cells of the submandibular gland in a middle-aged woman. This rare tumor is most commonly diagnosed in the parotid gland and in the minor salivary glands of the hard palate; a review of the literature uncovered only 5 previous reports of myoepithelioma of the submandibular gland. Distinguishing myoepithelioma from benign pleomorphic adenoma and malignant myoepithelial carcinomas can be challenging. Immunohistochemical staining can help to distinguish between the benign neoplasms, but histologic features remain the "gold standard" for diagnosing the malignant tumors. Increasing use of immunohistochemistry panels to assess parotid neoplasms also suggests that myoepithelioma may be underrecognized.

Adenoma, Pleomorphic↗
PubMed2003

Loss of heterozygosity of the VHL gene identifies malignancy and predicts death in follicular thyroid tumors.

BACKGROUND: Follicular thyroid tumors (FTT) usually require resection to distinguish adenoma from carcinoma. Better markers that predict histologic subtype and prognosis are needed for FTT. METHODS: Seventeen benign and malignant FTT with follow-up were selected. Pathologic diagnosis was confirmed, tumor and normal tissue were microdissected, and DNA was extracted. Polymerase chain reaction (PCR) products for a microsatellite marker at the von Hippel Lindau gene (VHL) gene locus (3p26) were analyzed with semiquantitative capillary gel electrophoresis to detect loss of heterozygosity (LOH). Data were assessed for statistical significance with chi(2). RESULTS: Mean follow-up was 77 months (range 29 to 120 months). Four cases were uninformative (homozygous microsatellite). Among 13 evaluable patients (6 adenomas, 7 follicular cancers) LOH of VHL was present only in carcinomas (P=.013). LOH was present in 4/4 patients with recurrence and 0/3 patients without recurrence (P=.017). Death from disease has occurred in 3 patients. LOH of VHL was strongly associated with death from disease (P=.034). CONCLUSIONS: FTT can be analyzed for LOH at the VHL gene locus. In this initial study, LOH of VHL was highly specific for malignancy and predicted death from disease. The analysis of VHL may provide for preoperative detection in cytologic samples with potential impact on clinical management of FTT.

Adenocarcinoma, Follicular↗
PubMed2003

A novel microdissection and genotyping of follicular-derived thyroid tumors to predict aggressiveness.

Distinguishing thyroid follicular adenoma from minimally invasive or encapsulated angioinvasive carcinoma can be diagnostically challenging. In some cases, tumors are distorted, fragmented, or stripped of their capsule, and a definitive diagnosis becomes nearly impossible. In other cases, the foci of capsular and/or vascular invasion are subtle, thus making the diagnosis of carcinoma difficult. We developed a microdissection genotyping assay for assessing a panel of tumor-suppressor genes for loss of heterozygosity mutations. The frequency of allelic loss (FAL) in follicular-derived neoplasms correlates with the histologic aggressiveness of the tumor. Furthermore, we calculated the amount of genetic heterogeneity within each tumor, as a second important measure of a tumor's ability for clonal expansion and a surrogate marker for its malignant potential. The follicular adenomas had a low FAL (average 9%) and low intratumoral heterogeneity (5% variability). The minimally invasive and encapsulated angioinvasive carcinomas had an intermediate FAL (average 30%) and intermediate intratumoral heterogeneity (10% variability). The widely invasive carcinomas had a high FAL (average 53%) and high intratumoral heterogeneity (24% variability). Although a larger retrospective study is needed to correlate genotyping studies with patient outcome and prognosis, our results indicate that performing a mutational genotyping assay can stratify tumors into the histologically well-defined categories of adenomas, minimally invasive/angioinvasive carcinomas, and widely invasive follicular carcinomas.

Adenoma↗
PubMed2003

Microscopic papillary thyroid carcinoma compared with clinical carcinomas by loss of heterozygosity mutational profile.

The clinical significance of microscopic papillary thyroid carcinoma (PTCa) is controversial. Many authors think that microscopic PTCa (<1 cm) have the same pathogenetic origin as clinically sized papillary carcinomas (>1 cm). Despite the fact that all clinical risk prognostication schemes have the size of the tumor as a primary category, small tumors do have malignant potential and can metastasize. There is growing evidence that small PTCa have the molecular translocations between the proto-oncogene RET and various activating partner genes that are characteristic of clinically sized PTCa. This study used a microdissection and genotyping assay to study the patterns of loss of heterozygosity of tumor suppressor genes in microscopic and clinically sized PTCa. Our results indicate that all PTCa harbor mutations with similar frequencies and distribution patterns, regardless of the size of the tumor. These data are further evidence that microscopic and clinically sized PTCa are pathogenetically related.

Carcinoma, Papillary↗
PubMed2003

Molecular evidence of anaplastic transformation in coexisting well-differentiated and anaplastic carcinomas of the thyroid.

Anaplastic thyroid cancer is a rare but nearly universally fatal tumor. Epidemiologic data suggest that many anaplastic thyroid carcinomas arise from transformation of preexisting or coexisting well-differentiated thyroid carcinomas. At the molecular level, the mutations responsible for the anaplastic transformation are incompletely understood, although the mutational events are thought to involve tumor suppressor genes. To examine transformation from a well-differentiated thyroid carcinoma to anaplastic carcinoma, we studied coexisting well-differentiated (Hürthle cell and papillary carcinoma) and anaplastic tumors with a molecular genotyping panel of tumor suppressor genes associated with thyroid neoplasia. The patterns of allelic loss in our results showed that the majority of cases have a core of conserved mutations in the two morphologically distinct areas and substantial increases in mutation rates in the anaplastic components.

Adenoma, Oxyphilic↗
PubMed2003

Non-tumor-associated psammoma bodies in the thyroid.

Psammoma bodies in the thyroid are common in glands with papillary thyroid carcinoma. Psammoma bodies that are not associated with tumor cells, however, represent a diagnostic problem for pathologists. Should we treat isolated psammoma bodies as representing metastatic disease? This study included patients who had non-tumor-associated psammoma bodies in their thyroids or in the perithyroidal lymph nodes. Clinical, pathologic, and follow-up information was obtained for the patients. Our results indicate that 27 of 29 patients had a contralateral or an ipsilateral tumor, the majority of which were papillary. We noted a high frequency of microscopic carcinomas (12/27) and of tall cell variants of papillary thyroid carcinoma (8/27 cases). Based on these findings, we recommend that thyroid glands with non-tumor-associated psammoma bodies and no histologically identified carcinoma be entirely submitted to identify any microscopic carcinoma. If no carcinoma is identified in a lobectomy, discussion with the surgeon should indicate the need for close clinical follow-up.

Adult↗
PubMed2003

A microdissection and molecular genotyping assay to confirm the identity of tissue floaters in paraffin-embedded tissue blocks.

CONTEXT: A recurring problem in surgical pathology practice is specimen mix-up and floater contamination. While many cases can be resolved histologically, a significant number remain unclear and may have serious clinical and medicolegal implications. OBJECTIVES: To design a microdissection and genotyping assay to identify contaminating floater tissues in paraffin-embedded tissues that is optimized for small samples, and to use the assay to resolve a series of clinical cases with floater tissues. MATERIALS AND METHODS: Twenty-one cases of possible tissue floater contamination in paraffin-embedded tissue blocks were included. Using 4 unstained, 4-microm-thick histologic sections, multiple sites were microdissected under direct visualization either by hand or by laser capture microdissection. Nonneoplastic and neoplastic tissues were sampled. Polymerase chain reaction was performed for a panel of 10 polymorphic microsatellite markers at 1p34, 3p26, 5q21, 9p21, 10q23, and 17p13. Allele size and content were analyzed semiquantitatively by fluorescent capillary electrophoresis, and the genotypes for the tissues in the paraffin-embedded tissue blocks were compared for identity. RESULTS: Tissue identification was successful in all cases, despite small tissue sample size and fixation effects. Comparative analysis of neoplastic tissue floaters and the presumptive source tumor was performed when possible to control for possible allelic loss or microsatellite instability. CONCLUSIONS: Microdissection and genotyping are effective and reliable means to objectively resolve problems of possible floater contamination. Even minute tissue samples provide sufficient DNA template for polymerase chain reaction microsatellite analysis. Because of the potential clinical implications of floaters, we recommend that all suspected floaters that would change a diagnosis from benign to malignant be subjected to genotyping assay to confirm the identity of the floater tissue.

Biopsy↗
PubMed2002

Bone formation in carotid plaques: a clinicopathological study.

BACKGROUND AND PURPOSE: Bone formation and dystrophic calcification are present in carotid endarterectomy plaques. The clinical significance of these findings is unknown. The purpose of this study was to determine whether bone formation and extensive dystrophic calcification are associated with stable plaques and protective against ischemic vascular events. METHODS: Carotid endarterectomy plaques were collected from 142 patients (94 men) with carotid stenosis. The specimens were evaluated for lamellar bone formation, dystrophic calcifications, inflammatory infiltrates, neovascularization, and histological type or grade of plaque according to a standard AHA grading system. Immunohistochemical staining was performed to identify vascular endothelial cells in neovascularization (factor VIII) and lymphocytes. Clinical data, including history of cerebrovascular and cardiovascular events, were recorded at the time of surgery. RESULTS: Patients with calcification of carotid plaques had fewer symptoms of stroke and transient ischemic attack (P=0.042) than those without calcification. Stroke and transient ischemic attack occurred less frequently in patients with plaques with large calcific granules (P=0.021). Of the patients, 13% had lamellar bone formation, which directly correlated with the presence of sheetlike calcifications (P=0.0001) and inversely correlated with ulcerated lesions (P=0.048). The presence of bone also correlated with diabetes (P<0.01) and coronary artery disease (P<0.01). Of the 20 patients with bone, 6 had a history of stoke and transient ischemic attack (P=0.5). CONCLUSIONS: The results indicate that bone formation tends to occur in heavily calcified carotid lesions devoid of ulceration and hemorrhage. Patients with extensive calcification of the carotid plaques are less likely to have symptomatic disease.

Adult↗
PubMed2002

Molecular mutations in thyroid carcinogenesis.

Molecular mutations in thyroid carcinomas have been well characterized and studied and consist of both germline and somatic genetic events. Mutations that are associated with tumorigenesis can be divided into 2 general categories: oncogene mutations and tumor suppressor gene mutations. Thyroid tumors and their characteristic molecular mutations are discussed in this review. The current practice in diagnostic testing for thyroid tumors also is examined.

Humans↗
PubMed2002

Loss of heterozygosity mutations of tumor suppressor genes in cytologically atypical areas in chronic lymphocytic thyroiditis.

The relationship between chronic lymphocytic thyroiditis (CLT) and papillary thyroid carcinoma (PTC) is a subject of controversy. Some investigators suggest a causal relationship, whereas others regard the two as only a coincidental occurrence. An additional complicating factor is the presence of atypical nuclei frequently found within lymphoid infiltrates in CLT, which resemble those in PTC. The finding of the RET-PTC translocations in CLT has been reported by two independent groups of investigators, suggesting that the areas of nuclear atypia in CLT are neoplastic rather than reactive. In the present study, we report additional molecular findings that support the hypothesis that the atypical nuclear changes in CLT may be preneoplastic or neoplastic. We microdissected small areas with atypical nuclei in glands with CLT and observed loss-of-heterozygosity mutations of tumor suppressor genes. These genetic mutations are evidence of clonal preneoplastic or neoplastic changes in the follicular cells of CLT. The clinical malignant potential of these minute foci is likely to be very small but remains to be determined.

Carcinoma, Papillary↗
PubMed2002

Histologic features of surgically removed fallopian tubes.

CONTEXT: The fallopian tube is a common specimen in a pathology laboratory. It may be examined either alone as a salpingectomy or tubal ligation specimen, or as part of a more complex specimen from a hysterectomy and/or oophorectomy operation. Although the common histologic findings in the fallopian tube have been described previously, to our knowledge no study has documented the frequency of histologic changes in fallopian tubes removed for all reasons or associations with clinical history. DESIGN: Hematoxylin-eosin-stained slides from 287 fallopian tube specimens were reviewed without knowledge of the clinical history. Three categories and associated subcategories of histologic findings were identified (listed in descending order of frequency): stromal and architectural alterations (fibrosis, intramuscular edema, cellular luminal contents, inclusion cysts, Walthard nests, pigmentosis tubae, Wolffian duct remnants, decidualized stroma, endosalpingiosis, and metastatic carcinoma), epithelial characteristics (cytologic atypia, vacuolization, metaplasia, and tufting), and inflammatory changes (intramuscular mast cells, plasma cells, neutrophils, and lymphoid follicles). Histologic findings were correlated with clinical history, surgery type, and age. RESULTS: Intramuscular edema was identified in 12.5% of specimens, most frequently in postpartum women. Plical fibrosis (35.5% of specimens), epithelial atypia (7.3%), epithelial vacuolization (6.6%), and epithelial tufting/stratification (3.5%) correlated with increased patient age. Inflammatory cells were relatively common; 69% of specimens contained intramuscular mast cells, 19.9% had stromal plasma cells, 10.5% had neutrophils, and 2.1% had lymphoid follicles. CONCLUSIONS: This study provides data that may be valuable for surgical pathologists involved in identifying and characterizing common histologic changes in surgically removed fallopian tubes.

Adolescent↗