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Sylvia L Asa

University Health Network / University of Toronto, Pathology, Faculty Member

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Dr. Sylvia Asa is an Endocrine Pathologist at University Health Network and Professor in the Department of Laboratory Medicine and Pathobiology at the University of Toronto. A Clinician-Scientist with a focus on Endocrine Pathology, her research aims to identify the basis for development of endocrine tumors, to improve diagnostic tests and to identify targets for therapy of those diseases.
Phone: 416-340-4802
Address: 200 Elizabeth Street
11th Floor
Toronto, Ontario M5G 2C4

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Papers by Sylvia L Asa

Null Cell Tumor

Encyclopedia of Pathology, 2020

Clinically Non-Functioning Human Pituitary Adenomas

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques, 1992

ABSTRACT:Clinically non-functioning pituitary adenomas are morphologically classified into two gr... more ABSTRACT:Clinically non-functioning pituitary adenomas are morphologically classified into two groups, those which have hormone immunoreactivity and ultrastructural features of known adenohypophysial cell types but are clinically silent, and those composed of cells that do not resemble nontumorous adenohypophysial cell types. Among the fomer are the silent somatotroph adenomas, silent corticotroph adenomas and silent gonadotroph adenomas; the latter include the silent type III adenomas, null cell adenomas and oncocytomas. We review their histological, immunohistochemical and ultrastructural features, the results of in situ hybridization to determine hormone synthesis by these tumors and data obtained from tissue culture characterizing their hormone release in vitro. Non-functioning adenomas represent a heterogeneous group. The discrepancies between morphology, immunoreactivity and lack of endocrine activity of silent adenomas are not clear. Oncocytomas are variants of null cell aden...

Rhabdoid tumor of the thyroid gland: a variant of anaplastic carcinoma

Archives of pathology & laboratory medicine, 2005

Rhabdoid tumor of the thyroid gland is a very rare neoplasm, characterized by significant metasta... more Rhabdoid tumor of the thyroid gland is a very rare neoplasm, characterized by significant metastatic potential. All of the 6 cases reported in the recent literature had poor outcomes. We report an additional case involving, to our knowledge, the oldest patient reported so far. A 67-year-old woman had a nodular goiter for all of her adult life and presented with a rapidly growing mass in the right lobe. Histologic examination showed a highly cellular neoplasm with a solid infiltrative growth pattern. Extracapsular invasion was evident. Rhabdoid cells were large, with abundant cytoplasm, eosinophilic inclusions, and eccentric nuclei containing distinct nucleoli. Immunohistochemistry identified vimentin, sarcomeric actin, myoglobin, and cytokeratin expression in the tumor cells; they were negative for desmin, thyroglobulin, and calcitonin. Scattered follicles with nuclear features of papillary thyroid carcinoma were detected; these cells were immunoreactive for thyroglobulin and TTF-1....

Concurrent Medullary and Papillary Carcinomas of Thyroid with Lymph Node Metastases

The American Journal of Surgical Pathology, 1996

The simultaneous occurrence of two distinct neoplasms derived from different cells of origin is a... more The simultaneous occurrence of two distinct neoplasms derived from different cells of origin is a recognized, albeit rare, entity. In the thyroid, such lesions could consist of medullary carcinoma composed of parafollicular C cells and well-differentiated carcinoma showing follicular epithelial cell differentiation. We report a patient whose thyroid contained calcitonin-immunoreactive medullary carcinoma and thyroglobulin-positive papillary carcinoma, clearly separated from each other. The tumors metastasized to regional lymph nodes, where they formed foci of composite medullary and papillary carcinoma, with each component maintaining a distinct immunophenotypic profile. The composite metastases are best regarded as collision tumors, as each primary neoplasm exhibited only one line of differentiation. Given the high incidence of papillary carcinoma, the occurrence of the two tumors may be a coincidence. Alternatively, a common tumorigenic stimulus triggering neoplastic transformation of both parafollicular C cells and follicular epithelial cells is a plausible explanation for such a phenomenon.

ref/PTC-1, -2, and -3 Oncogene Rearrangements in Human Thyroid Carcinomas: Implications for Metastatic Potential?

The Journal of Clinical Endocrinology and Metabolism, Apr 1, 1997

The Clinicopathological Spectrum of Parathyroid Carcinoma

Frontiers in Endocrinology, Oct 23, 2019

Molecular interactions during pregnancy

Molecular human reproduction, 1996

Dual Inhibition of <i>RET</i> and <i>FGFR4</i> Restrains Medullary Thyroid Cancer Cell Growth

Clinical Cancer Research, Feb 1, 2005

Medullary thyroid cancer is frequently an aggressive form of carcinoma for which there are curren... more Medullary thyroid cancer is frequently an aggressive form of carcinoma for which there are currently no effective forms of systemic therapy. These carcinomas arise as a result of activating mutations in the RET proto-oncogene transmembrane tyrosine kinase receptor. We, therefore, examined the potential efficacy of the tyrosine kinase inhibitor STI571 on the growth of human TT medullary cancer cells in vitro and in xenografted severe combined immunodeficiency mice. Treatment with STI571 resulted in inhibition of RET phosphorylation, cell proliferation, tumor growth and invasiveness. Based on the profile of expression of fibroblast growth factor receptors (FGFR), we examined the effects of FGFR tyrosine kinase inhibition using the small molecule FGFR inhibitor PD173074. This inhibitor resulted in abrogation of fibroblast growth factor-1-mediated FGFR4 phosphorylation in TT cells, an effect that was accompanied by significant arrest of cell proliferation and tumor growth in vivo. Moreover, the combination of STI571 and PD173074 resulted in greater suppression of cell proliferation in vitro and tumor control in vivo than that achieved with either agent alone. These data highlight RET and FGFR4 as therapeutic targets and suggest a potential role for the combined use of tyrosine kinase inhibitors in the management of inoperable medullary thyroid cancers.

A single-arm, phase II, multicenter trial of sunitinib (SU) in locally advanced or metastatic pheochromocytoma/paraganglioma (PC/PG): Updated interim results

Journal of Clinical Oncology, May 20, 2014

e15621 Background: Metastatic PC/PG is rare, may be sporadic or have a genetic basis. Treatment r... more

Osteopontin (OPN) expression in thyroid carcinoma

PubMed, May 1, 2010

Background: Osteopontin (OPN) and its interacting partner CEA-cell adhesion molecule (CEACAM1) me... more Background: Osteopontin (OPN) and its interacting partner CEA-cell adhesion molecule (CEACAM1) mediate similar biological functions and have been expressed in several types of cancer. Here we investigated the prognostic significance of OPN in thyroid tumours and correlated our findings with the expression of CEACAM1. Materials and methods: 297 human thyroid samples were collected in a tissue microarray and as fresh frozen samples to perform immunohistochemistry and western blotting for OPN and to compare these data with our previously published data on CEACAM1 expression. Results: Nearly all normal samples were negative for OPN. Some thyroid adenomas were weakly OPN positive whereas many carcinomas were strongly positive. In contrast to CEACAM1, which was preferentially expressed in metastatic papillary carcinomas, no associations were found between OPN expression and patient age, gender and tumour size. Conclusion: These results may have future implications for the diagnosis and management of patients with thyroid cancers.

Interobserver Variability in the Histopathologic Assessment of Extrathyroidal Extension of Well Differentiated Thyroid Carcinoma Supports the New American Joint Committee on Cancer Eighth Edition Criteria for Tumor Staging

Thyroid, May 1, 2019

Background: Extrathyroidal extension (ETE) by papillary and follicular thyroid carcinoma can be a... more Background: Extrathyroidal extension (ETE) by papillary and follicular thyroid carcinoma can be associated with increased risk of tumor recurrence and mortality. In the seventh edition of its Cancer Staging Manual, the American Joint Committee on Cancer (AJCC) defined minimal ETE as the involvement of skeletal muscle (i.e., strap muscles) or perithyroidal soft tissue. The eighth edition of the AJCC Cancer Staging Manual has changed the criteria so that only grossly evident (macroscopic) ETE involving strap muscles (not microscopic ETE involving perithyroidal soft tissue) affects tumor staging. Summary: Concordance of identifying microscopic ETE (as well as extranodal extension by carcinoma metastatic to lymph nodes) was previously evaluated among 11 expert endocrine pathologists. The overall agreement rate was slight when rendering a diagnosis of ETE. Concordance was highest when pathologists assessed the spatial relationship of carcinoma to skeletal muscle. This article discusses the significance of these findings. It also reviews relevant anatomic and developmental considerations related to the boundaries of the thyroid. Conclusions: The results of the concordance study provide additional rationale supporting stringent criteria for diagnosing ETE, as proposed by the eighth edition of the AJCC Cancer Staging Manual. It is expected that these rigid morphologic criteria will potentially reduce interobserver variability and enhance consistency in the diagnosis and staging of thyroid carcinoma.

An unusual case of an ACTH-secreting macroadenoma with a germline variant in the aryl hydrocarbon receptor-interacting protein (AIP) gene

Endocrinology, Diabetes & Metabolism Case Reports, 2015

Pituitary Tumors; Diagnosis and Treatment

Elsevier eBooks, 2018

Cystic Lesions of the Pituitary: Clinicopathological Features Distinguishing Craniopharyngioma, Rathke’s Cleft Cyst, and Arachnoid Cyst

Obstetrical & Gynecological Survey, Apr 1, 2000

Endoscopic Endonasal Pituitary Surgery For Nonfunctioning Pituitary Adenomas: Long-Term Outcomes and Management of Recurrent Tumors

World Neurosurgery, Feb 1, 2021

Molecular Predictors of Clinical Behavior in Pituitary Adenohypophysial Tumors

Contemporary Endocrinology, 2019

Pituitary adenohypophysial tumors range from small indolent incidental findings to progressive ne... more Pituitary adenohypophysial tumors range from small indolent incidental findings to progressive neoplasms that invade the base of the brain. This chapter focuses on biomarkers that have been examined to help distinguish between these differing behaviors. This is particularly relevant in childhood cases where treatment and surveillance plans can have far-reaching implications. We review the familial syndromes that predispose to tumor development. We emphasize the histological subtypes that can be diagnosed using morphologic and immunophenotyping techniques. We then review candidate biomarkers including proliferation markers, metalloproteinases, growth factors and their receptors, as well as hormone and cytokine receptors. We conclude with larger chromosomal aberrations and microRNAs that have been implicated in epigenetic dysregulation. These data provide an integrated approach to formulate a risk stratification system for patients with pituitary tumors.

The Pangenomic Classification of Pituitary Neuroendocrine Tumors: Quality Histopathology is Required for Accurate Translational Research

Endocrine Pathology, Mar 3, 2021

Pathology of pituitary growth hormone excess

Elsevier eBooks, 2021

The Next Steps for Endocrine Pathology

Endocrine Pathology, Feb 28, 2022

Significance of Crooke's Hyaline Change in Nontumorous Corticotrophs of Patients With Cushing Disease

Frontiers in Endocrinology, Mar 18, 2021

Null Cell Tumor

Encyclopedia of Pathology, 2020

Clinically Non-Functioning Human Pituitary Adenomas

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques, 1992

ABSTRACT:Clinically non-functioning pituitary adenomas are morphologically classified into two gr... more ABSTRACT:Clinically non-functioning pituitary adenomas are morphologically classified into two groups, those which have hormone immunoreactivity and ultrastructural features of known adenohypophysial cell types but are clinically silent, and those composed of cells that do not resemble nontumorous adenohypophysial cell types. Among the fomer are the silent somatotroph adenomas, silent corticotroph adenomas and silent gonadotroph adenomas; the latter include the silent type III adenomas, null cell adenomas and oncocytomas. We review their histological, immunohistochemical and ultrastructural features, the results of in situ hybridization to determine hormone synthesis by these tumors and data obtained from tissue culture characterizing their hormone release in vitro. Non-functioning adenomas represent a heterogeneous group. The discrepancies between morphology, immunoreactivity and lack of endocrine activity of silent adenomas are not clear. Oncocytomas are variants of null cell aden...

Rhabdoid tumor of the thyroid gland: a variant of anaplastic carcinoma

Archives of pathology & laboratory medicine, 2005

Rhabdoid tumor of the thyroid gland is a very rare neoplasm, characterized by significant metasta... more Rhabdoid tumor of the thyroid gland is a very rare neoplasm, characterized by significant metastatic potential. All of the 6 cases reported in the recent literature had poor outcomes. We report an additional case involving, to our knowledge, the oldest patient reported so far. A 67-year-old woman had a nodular goiter for all of her adult life and presented with a rapidly growing mass in the right lobe. Histologic examination showed a highly cellular neoplasm with a solid infiltrative growth pattern. Extracapsular invasion was evident. Rhabdoid cells were large, with abundant cytoplasm, eosinophilic inclusions, and eccentric nuclei containing distinct nucleoli. Immunohistochemistry identified vimentin, sarcomeric actin, myoglobin, and cytokeratin expression in the tumor cells; they were negative for desmin, thyroglobulin, and calcitonin. Scattered follicles with nuclear features of papillary thyroid carcinoma were detected; these cells were immunoreactive for thyroglobulin and TTF-1....

Concurrent Medullary and Papillary Carcinomas of Thyroid with Lymph Node Metastases

The American Journal of Surgical Pathology, 1996

The simultaneous occurrence of two distinct neoplasms derived from different cells of origin is a... more The simultaneous occurrence of two distinct neoplasms derived from different cells of origin is a recognized, albeit rare, entity. In the thyroid, such lesions could consist of medullary carcinoma composed of parafollicular C cells and well-differentiated carcinoma showing follicular epithelial cell differentiation. We report a patient whose thyroid contained calcitonin-immunoreactive medullary carcinoma and thyroglobulin-positive papillary carcinoma, clearly separated from each other. The tumors metastasized to regional lymph nodes, where they formed foci of composite medullary and papillary carcinoma, with each component maintaining a distinct immunophenotypic profile. The composite metastases are best regarded as collision tumors, as each primary neoplasm exhibited only one line of differentiation. Given the high incidence of papillary carcinoma, the occurrence of the two tumors may be a coincidence. Alternatively, a common tumorigenic stimulus triggering neoplastic transformation of both parafollicular C cells and follicular epithelial cells is a plausible explanation for such a phenomenon.

ref/PTC-1, -2, and -3 Oncogene Rearrangements in Human Thyroid Carcinomas: Implications for Metastatic Potential?

The Journal of Clinical Endocrinology and Metabolism, Apr 1, 1997

The Clinicopathological Spectrum of Parathyroid Carcinoma

Frontiers in Endocrinology, Oct 23, 2019

Molecular interactions during pregnancy

Molecular human reproduction, 1996

Dual Inhibition of <i>RET</i> and <i>FGFR4</i> Restrains Medullary Thyroid Cancer Cell Growth

Clinical Cancer Research, Feb 1, 2005

Medullary thyroid cancer is frequently an aggressive form of carcinoma for which there are curren... more Medullary thyroid cancer is frequently an aggressive form of carcinoma for which there are currently no effective forms of systemic therapy. These carcinomas arise as a result of activating mutations in the RET proto-oncogene transmembrane tyrosine kinase receptor. We, therefore, examined the potential efficacy of the tyrosine kinase inhibitor STI571 on the growth of human TT medullary cancer cells in vitro and in xenografted severe combined immunodeficiency mice. Treatment with STI571 resulted in inhibition of RET phosphorylation, cell proliferation, tumor growth and invasiveness. Based on the profile of expression of fibroblast growth factor receptors (FGFR), we examined the effects of FGFR tyrosine kinase inhibition using the small molecule FGFR inhibitor PD173074. This inhibitor resulted in abrogation of fibroblast growth factor-1-mediated FGFR4 phosphorylation in TT cells, an effect that was accompanied by significant arrest of cell proliferation and tumor growth in vivo. Moreover, the combination of STI571 and PD173074 resulted in greater suppression of cell proliferation in vitro and tumor control in vivo than that achieved with either agent alone. These data highlight RET and FGFR4 as therapeutic targets and suggest a potential role for the combined use of tyrosine kinase inhibitors in the management of inoperable medullary thyroid cancers.

A single-arm, phase II, multicenter trial of sunitinib (SU) in locally advanced or metastatic pheochromocytoma/paraganglioma (PC/PG): Updated interim results

Journal of Clinical Oncology, May 20, 2014

e15621 Background: Metastatic PC/PG is rare, may be sporadic or have a genetic basis. Treatment r... more

Osteopontin (OPN) expression in thyroid carcinoma

PubMed, May 1, 2010

Background: Osteopontin (OPN) and its interacting partner CEA-cell adhesion molecule (CEACAM1) me... more Background: Osteopontin (OPN) and its interacting partner CEA-cell adhesion molecule (CEACAM1) mediate similar biological functions and have been expressed in several types of cancer. Here we investigated the prognostic significance of OPN in thyroid tumours and correlated our findings with the expression of CEACAM1. Materials and methods: 297 human thyroid samples were collected in a tissue microarray and as fresh frozen samples to perform immunohistochemistry and western blotting for OPN and to compare these data with our previously published data on CEACAM1 expression. Results: Nearly all normal samples were negative for OPN. Some thyroid adenomas were weakly OPN positive whereas many carcinomas were strongly positive. In contrast to CEACAM1, which was preferentially expressed in metastatic papillary carcinomas, no associations were found between OPN expression and patient age, gender and tumour size. Conclusion: These results may have future implications for the diagnosis and management of patients with thyroid cancers.

Interobserver Variability in the Histopathologic Assessment of Extrathyroidal Extension of Well Differentiated Thyroid Carcinoma Supports the New American Joint Committee on Cancer Eighth Edition Criteria for Tumor Staging

Thyroid, May 1, 2019

Background: Extrathyroidal extension (ETE) by papillary and follicular thyroid carcinoma can be a... more Background: Extrathyroidal extension (ETE) by papillary and follicular thyroid carcinoma can be associated with increased risk of tumor recurrence and mortality. In the seventh edition of its Cancer Staging Manual, the American Joint Committee on Cancer (AJCC) defined minimal ETE as the involvement of skeletal muscle (i.e., strap muscles) or perithyroidal soft tissue. The eighth edition of the AJCC Cancer Staging Manual has changed the criteria so that only grossly evident (macroscopic) ETE involving strap muscles (not microscopic ETE involving perithyroidal soft tissue) affects tumor staging. Summary: Concordance of identifying microscopic ETE (as well as extranodal extension by carcinoma metastatic to lymph nodes) was previously evaluated among 11 expert endocrine pathologists. The overall agreement rate was slight when rendering a diagnosis of ETE. Concordance was highest when pathologists assessed the spatial relationship of carcinoma to skeletal muscle. This article discusses the significance of these findings. It also reviews relevant anatomic and developmental considerations related to the boundaries of the thyroid. Conclusions: The results of the concordance study provide additional rationale supporting stringent criteria for diagnosing ETE, as proposed by the eighth edition of the AJCC Cancer Staging Manual. It is expected that these rigid morphologic criteria will potentially reduce interobserver variability and enhance consistency in the diagnosis and staging of thyroid carcinoma.

An unusual case of an ACTH-secreting macroadenoma with a germline variant in the aryl hydrocarbon receptor-interacting protein (AIP) gene

Endocrinology, Diabetes & Metabolism Case Reports, 2015

Pituitary Tumors; Diagnosis and Treatment

Elsevier eBooks, 2018

Cystic Lesions of the Pituitary: Clinicopathological Features Distinguishing Craniopharyngioma, Rathke’s Cleft Cyst, and Arachnoid Cyst

Obstetrical & Gynecological Survey, Apr 1, 2000

Endoscopic Endonasal Pituitary Surgery For Nonfunctioning Pituitary Adenomas: Long-Term Outcomes and Management of Recurrent Tumors

World Neurosurgery, Feb 1, 2021

Molecular Predictors of Clinical Behavior in Pituitary Adenohypophysial Tumors

Contemporary Endocrinology, 2019

Pituitary adenohypophysial tumors range from small indolent incidental findings to progressive ne... more Pituitary adenohypophysial tumors range from small indolent incidental findings to progressive neoplasms that invade the base of the brain. This chapter focuses on biomarkers that have been examined to help distinguish between these differing behaviors. This is particularly relevant in childhood cases where treatment and surveillance plans can have far-reaching implications. We review the familial syndromes that predispose to tumor development. We emphasize the histological subtypes that can be diagnosed using morphologic and immunophenotyping techniques. We then review candidate biomarkers including proliferation markers, metalloproteinases, growth factors and their receptors, as well as hormone and cytokine receptors. We conclude with larger chromosomal aberrations and microRNAs that have been implicated in epigenetic dysregulation. These data provide an integrated approach to formulate a risk stratification system for patients with pituitary tumors.

The Pangenomic Classification of Pituitary Neuroendocrine Tumors: Quality Histopathology is Required for Accurate Translational Research

Endocrine Pathology, Mar 3, 2021

Pathology of pituitary growth hormone excess

Elsevier eBooks, 2021

The Next Steps for Endocrine Pathology

Endocrine Pathology, Feb 28, 2022

Significance of Crooke's Hyaline Change in Nontumorous Corticotrophs of Patients With Cushing Disease

Frontiers in Endocrinology, Mar 18, 2021