Publications by authors named "Virginia A LiVolsi"

206 Publications

Neuroendocrine Tumors of the Thyroid and Their Mimics.

Endocr Pathol 2021 Mar 9. Epub 2021 Mar 9.

Department of Pathology and Laboratory Medicine, Perelmann School of Medicine, University of Pennsylvania, Philadelphia, USA.

This paper will review neuroendocrine lesions of the thyroid and the differential diagnosis with the most significant such tumor of the thyroid, that is, medullary thyroid carcinoma. A brief overview of the understanding of this tumor's identification as a lesion of C cells and its familial and syndromic associations will be presented. Then, a discussion of the various mimics of medullary carcinoma will be given with an approach to the types of tests that can be done to arrive at a correct diagnostic conclusion. This review will focus on practical "tips" for the practicing pathologist.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12022-021-09672-3DOI Listing
March 2021

Giant Cell Carcinosarcoma of the Parotid Gland With a PLAG 1 Translocation in Association With a Pleomorphic Adenoma With HMGA2 Translocation.

Am J Clin Pathol 2020 11;154(6):811-815

Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia.

Objectives: Carcinosarcomas of the salivary gland are rare neoplasms and have been described arising de novo or in association with pleomorphic adenoma (PA). PLAG1 and HMGA2 translocations are known to occur in PAs and carcinomas ex PA but are mutually exclusive.

Methods: We report a case of a carcinosarcoma in the parotid gland of a 77-year-old man with unusual anaplastic sarcomatoid giant cell morphology.

Results: Microscopically, a small separate PA was found adjacent to the carcinosarcoma. By conventional notion, the PA and carcinosarcoma would be considered related, as carcinosarcomas are well known to arise from PAs (carcinosarcoma ex PA). However, fluorescence in situ hybridization (FISH) assay demonstrated PLAG1 translocation in the carcinosarcoma and HMGA2 translocation in the separate PA.

Conclusions: These findings support that the carcinosarcoma likely originated from another PA with a PLAG1 translocation or de novo but not from the coexisting PA harboring a different translocation. To our knowledge, the case is the first to demonstrate PLAG1 translocation by FISH in a sarcomatous component of any parotid gland tumor, which may help better classify these tumors. In addition, multiple PAs are commonly found in the salivary gland, and to our knowledge, our case is the first to demonstrate that the same parotid gland can host PAs and PA-related tumors with different translocations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ajcp/aqaa104DOI Listing
November 2020

A case of tumor-to-tumor metastasis of cutaneous malignant melanoma.

J Cutan Pathol 2020 Dec 6;47(12):1196-1199. Epub 2020 Sep 6.

Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

We report a case of tumor-to-tumor metastasis of a cutaneous malignant melanoma to a synchronous thyroid Hurthle cell carcinoma. A 42-year-old male underwent a biopsy of right inguinal lymphadenopathy which showed metastatic melanoma. The primary lesion was identified on his right posterior leg, and staging workup discovered a synchronous left thyroid lobe nodule concerning for a follicular neoplasm. He underwent excision of the primary melanoma, right inguinal lymphadenectomy, and total thyroidectomy. The resected thyroid contained a 6.6-cm, well-encapsulated left-sided nodule, red-brown in color and homogenous in consistency, with areas of focal hemorrhage and no grossly identifiable calcification. Microscopically, large tumor cells with distinct cell borders were present, with deeply eosinophilic and granular cytoplasm, large nuclei with prominent nucleoli, and loss of polarity consistent with oncocytes. A microscopic single focus of vascular invasion was identified, and a diagnosis of angioinvasive Hurthle cell carcinoma was made. Within the Hurthle cell carcinoma, multiple deposits of metastatic melanoma were seen. These findings were indicative of tumor-to-tumor metastasis of the cutaneous melanoma to the angioinvasive Hurthle cell carcinoma. Our findings show the ability of melanoma to metastasize to a pre-existing neoplasm.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cup.13829DOI Listing
December 2020

The significance of mucinous metaplasia in Warthin tumor: a frequent occurrence and potential pitfall.

Hum Pathol 2020 05 26;99:13-26. Epub 2020 Mar 26.

Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, 19104, USA. Electronic address:

Mucinous metaplasia in Warthin tumor (WT) is a recognized phenomenon. Nevertheless, its presence can create a diagnostic challenge in the distinction from the newly proposed variant of mucoepidermoid carcinoma (MEC), Warthin-like MEC. In this study, we evaluated the significance and diagnostic relevance of mucinous metaplasia in WTs. A total of 30 WTs diagnosed based on resection specimens formed the basis of this retrospective study. Mucicarmine staining was performed to identify mucinous metaplasia, and fluorescence in situ hybridization (FISH) analysis was used to detect MAML2 gene rearrangement. After review, one MAML2 rearranged case was reclassified as Warthin-like MEC as the classic bilayered epithelium in WT was not identified. The diagnosis of WT was confirmed in the remaining 29 cases. Mucinous metaplasia was encountered in 24 WTs (83%), with 14% (4/29) having an abundant amount. We found that mucinous metaplasia correlated with tumor size (p < 0.05). Age and sex distribution were similar in WT cases with or without mucinous metaplasia. In addition, neither the presence of squamous metaplasia nor the time interval between fine-needle aspiration and surgery was related to mucinous metaplasia (p > 0.05). The MAML2 FISH analyses performed in 18 WTs with variable amounts of mucinous metaplasia were negative for rearrangement. In conclusion, mucinous metaplasia is fairly common in WTs and shows a significant correlation with tumor size. Therefore, caution should be taken to avoid overinterpretation of WT with mucinous metaplasia as MEC in cases showing the classic bilayered oncocytic lining epithelium.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.humpath.2020.03.008DOI Listing
May 2020

Noninvasive Follicular Tumor With Papillary-like Nuclear Features: A Practice Changer in Thyroid Pathology.

Arch Pathol Lab Med 2020 Mar 30. Epub 2020 Mar 30.

From the Department of Pathology & Laboratory Medicine, the Hospital of the University of Pennsylvania, Philadelphia.

Context.—: This article presents a review of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), including its separation from follicular variant of papillary carcinoma of the thyroid, its evolution, and current definition and pathologic characteristics.

Objectives.—: To emphasize the understanding of the concept of NIFTP as a neoplasm based on molecular analyses, its critical histopathologic features, the microscopic findings that exclude the diagnosis and the importance of complete sectioning of the tumor to exclude neoplasms that should be diagnosed as carcinomas. Important distinctions are discussed including difficulties with literature that shows NIFTP with metastases, inadequacy of sectioning of the tumor, and lack of descriptive histology of the surrounding thyroid and possible other lesions.

Data Sources.—: Review of articles in the English literature on NIFTP, as well as comparative papers showing differences and distinctions between this entity and papillary carcinomas.

Conclusions.—: This article concludes that with the current state of knowledge on NIFTP with studies from all over the world, this entity is a low-risk neoplasm that, when diagnosed using appropriate criteria, should not be associated with metastatic or recurrent disease, at least on intermediate length of follow-up. This review includes discussion of multifocal NIFTP, as well as the recently defined micro-NIFTP (1 cm or less), and describes features of the tumor that remain to be studied and correlated with outcome: oncocytic variants of NIFTP, percentage of allowable solid areas of growth in the lesions, and definitions of true neoplastic papillae and hyperplastic ones and how these should influence the diagnosis of NIFTP.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5858/arpa.2019-0689-RADOI Listing
March 2020

Practice Paradigms Before and After Introduction of the Diagnosis-Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features (NIFTP): an Institutional Experience.

Endocr Pathol 2020 Jun;31(2):174-181

Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, 6 Founders. 3400 Spruce street, Philadelphia, PA, 19104, USA.

The recently adopted terminology of "Noninvasive follicular thyroid neoplasm with papillary-like nuclear features" (NIFTP) reflects the indolent behavior of these tumors. In contrast to conventional papillary thyroid carcinomas, NIFTP can be managed conservatively. The purpose of this study was to investigate changes in surgical and pathologic practice patterns at our institution since the introduction of the NIFTP diagnosis in 2016. A retrospective analysis of all thyroid specimens received in our laboratory between January 2015 and April 2017 was performed. The final cohort consisted of 1508 thyroidectomy specimens from 1508 patients (1153 (76.5%) women and 355 (23.5%) men), of which 1011 (67%) were total thyroidectomies and 497 (33%) were partial thyroidectomies. There were 558 (69.2%) total thyroidectomies and 248 (30.8%) partial thyroidectomies performed prior to introduction of the NIFTP diagnosis and 453 (64.5%) and 249 (35.5%) total and partial thyroidectomies, respectively, after the change in nomenclature. Within a year following the initial use of this diagnosis, 67 NIFTP cases were identified (9.5% of all thyroidectomies), whereas compared with the year preceding it, malignant diagnoses decreased from 54.5 (439) to 44.6% (313), and the benign category remained unchanged from 44.5 (367) to 45.9% (322). For the entirely submitted 67 NIFTP cases, the mean number of blocks submitted was 14.7 (0.98 blocks/g); for malignant lesions 17.7 (0.92 blocks/g); and for benign lesions 16.6 (0.75 blocks/g). The results of our study suggest that NIFTP are encountered in almost 10% of thyroidectomies at our institution with expected shifts in cytology and surgical pathology diagnoses as a result of the change in nomenclature. During this time period, significant shifts towards less aggressive surgical management were not observed. All 67 NIFTP nodules were submitted entirely with no significant difference in the number of cassettes submitted for NIFTP nodules as compared with follicular variant papillary thyroid carcinoma (PTC), classic variant PTC, or follicular adenoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12022-020-09614-5DOI Listing
June 2020

Recurrent glomangioma ("true" glomus tumor) of the middle ear and mastoid.

World J Otorhinolaryngol Head Neck Surg 2019 Dec 13;5(4):175-179. Epub 2019 Dec 13.

Department of Otorhinolaryngology Head and Neck Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.

Objective: To review current literature and experience with glomangiomas, or true glomus tumors of the middle ear and mastoid as well asto report on the exceptionally rare case of a glomangiomastemming from the middle ear space with multiple recurrences.

Methods: Review of existing world literature and description of personal experience with rare cases of a glomangioma of the middle ear and mastoid.

Results: Review of existing literature revealed two cases of patients presenting with tinnitus and hearing loss refractory to medical management. Both patients were ultimately diagnosed with glomangioma on histopathology. Complete surgical excision is thought to be curative.

Patient: A 36-year-old woman presented with a rare case of a glomangioma of the middle ear presenting with unilateral hearing loss. She was noted to have a mass behind the tympanic membrane. Imaging revealed a diffuse mass filling the mastoid air cells. Imaging characteristics and histology were consistent with a glomangioma.

Intervention: Initial resection via mastoidectomy using a postauricular approach. The tympanic membrane was reconstructed with temporalis tissue. Follow-up revision tympanomastoidectomy was performed upon recurrence of disease. The chorda tympani were sacrificed due to tumor involvement. The incus and head of the malleus were removed to gain better access to the tumor. The ossicular chain was reconstructed with a Goldenberg Total Ossicular Prosthesis.

Main Outcome Measure: Recurrence of disease.

Follow-up: In the 67 months since her most recent surgery, there has been no evidence of recurrence by CT or physical exam.

Conclusion: Glomangioma of the middle ear represents an exceptionally rare entity that can present in a similar fashion to a paraganglioma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.wjorl.2019.01.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7015857PMC
December 2019

The American Association of Endocrine Surgeons Guidelines for the Definitive Surgical Management of Thyroid Disease in Adults.

Ann Surg 2020 03;271(3):e21-e93

Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA.

Objective: To develop evidence-based recommendations for safe, effective, and appropriate thyroidectomy.

Background: Surgical management of thyroid disease has evolved considerably over several decades leading to variability in rendered care. Over 100,000 thyroid operations are performed annually in the US.

Methods: The medical literature from 1/1/1985 to 11/9/2018 was reviewed by a panel of 19 experts in thyroid disorders representing multiple disciplines. The authors used the best available evidence to construct surgical management recommendations. Levels of evidence were determined using the American College of Physicians grading system, and management recommendations were discussed to consensus. Members of the American Association of Endocrine Surgeons reviewed and commented on preliminary drafts of the content.

Results: These clinical guidelines analyze the indications for thyroidectomy as well as its definitions, technique, morbidity, and outcomes. Specific topics include Pathogenesis and Epidemiology, Initial Evaluation, Imaging, Fine Needle Aspiration Biopsy Diagnosis, Molecular Testing, Indications, Extent and Outcomes of Surgery, Preoperative Care, Initial Thyroidectomy, Perioperative Tissue Diagnosis, Nodal Dissection, Concurrent Parathyroidectomy, Hyperthyroid Conditions, Goiter, Adjuncts and Approaches to Thyroidectomy, Laryngology, Familial Thyroid Cancer, Postoperative Care and Complications, Cancer Management, and Reoperation.

Conclusions: Evidence-based guidelines were created to assist clinicians in the optimal surgical management of thyroid disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SLA.0000000000003580DOI Listing
March 2020

Executive Summary of the American Association of Endocrine Surgeons Guidelines for the Definitive Surgical Management of Thyroid Disease in Adults.

Ann Surg 2020 03;271(3):399-410

Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA.

Objective: The aim of this study was to develop evidence-based recommendations for safe, effective and appropriate thyroidectomy.

Background: Surgical management of thyroid disease has evolved considerably over several decades leading to variability in rendered care. Over 100,000 thyroid operations are performed annually in the United States.

Methods: The medical literature from January 1, 1985 to November 9, 2018 was reviewed by a panel of 19 experts in thyroid disorders representing multiple disciplines. The authors used the best available evidence to construct surgical management recommendations. Levels of evidence were determined using the American College of Physicians grading system, and management recommendations were discussed to consensus. Members of the American Association of Endocrine Surgeons reviewed and commented on preliminary drafts of the content.

Results: These clinical guidelines analyze the indications for thyroidectomy as well as its definitions, technique, morbidity, and outcomes. Specific topics include Pathogenesis and Epidemiology, Initial Evaluation, Imaging, Fine Needle Aspiration Biopsy Diagnosis, Molecular Testing, Indications, Extent and Outcomes of Surgery, Preoperative Care, Initial Thyroidectomy, Perioperative Tissue Diagnosis, Nodal Dissection, Concurrent Parathyroidectomy, Hyperthyroid Conditions, Goiter, Adjuncts and Approaches Laryngology Familial Thyroid Cancer, Postoperative Care and Complications, Cancer Management, and Reoperation.

Conclusion: Evidence-based guidelines were created to assist clinicians in the optimal surgical management of thyroid disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SLA.0000000000003735DOI Listing
March 2020

Pathologic grading of mucoepidermoid carcinomas of the salivary gland and its effect on clinicopathologic follow-up: an institutional experience.

Hum Pathol 2020 04 6;98:89-97. Epub 2020 Feb 6.

University of Pennsylvania Medical Center, Philadelphia, PA, 19104, USA. Electronic address:

Mucoepidermoid carcinoma (MEC) is the most common malignant salivary gland tumor. Differences inprognosis can be noted owing to the tumor grade determined using multiple grading schemes (2-tier: low- and high-grade vs. 3-tier: low-, intermediate-, and high-grade). We studied clinicopathologic features of MEC using a 3-tier grading system and retrospectively categorized cytologic diagnoses as per the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC).A total of 69 cases of MEC were identified, and most were seen in the parotid gland. Aggressive clinical behavior was seen in high-grade MEC compared with intermediate- and low-grade MEC. By fluorescence in situ hybridization (FISH) analysis, MAML2 rearrangements were seen in 78% of cases.The MSRSGC subcategorized the majority (63.8%) of MEC as salivary gland neoplasm of uncertain malignant potential, suspicious for malignancy, or malignant. Clustering intermediate- with low-grade cases did not significantly impact the clinical behavior. Both high-grade and oncocytic MEC can be MAML2 FISH negative.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.humpath.2020.02.001DOI Listing
April 2020

The Bethesda System for Reporting Thyroid Cytology (TBSRTC): From look-backs to look-ahead.

Diagn Cytopathol 2020 Oct 30;48(10):862-866. Epub 2020 Jan 30.

Perelman School of Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.

The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) was formalized in October 2007 by experts in thyroidology at the National Institute of Health in Bethesda, Maryland. The first edition of the TBSRTC book was published in 2010 and the second edition in 2018. The TBSRTC is widely employed in cytology practices in the United States and has also served as a model for similar tiered classification schemes for reporting thyroid cytopathology specimens. The tremendous success of TBSRTC cannot be underscored, it has provided a diagnostic framework which is well aligned with the present and the future of thyroid nodule management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/dc.24385DOI Listing
October 2020

Fifty years of thyroid pathology: concepts and developments.

Hum Pathol 2020 01 22;95:46-54. Epub 2019 Oct 22.

Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Perelman School of Medicine, 3400 Spruce Street, 6 Founders Pavilion, Philadelphia, PA, 19104.

The past half century has seen a number of advances in pathology of thyroid diseases, especially neoplastic lesions. These include the description of new entities, the definition of prognostically important lesions, the incorporation of fine needle aspiration biopsy and its functional risk stratification of diagnoses into the clinical evaluation and therapeutic recommendations of the patient with thyroid nodules and the understanding of thyroid neoplastic development, diagnostic and prognostic parameters by use of molecular analysis so that such techniques are becoming standard of care for patients with thyroid tumors. The histopathologist and cytopathologist have been and continue to be at the forefront in the definition and understanding of these areas of thyroid disease. This review describes many of the most important advances in this area in an attempt bring the practicing pathologist up to date in these developments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.humpath.2019.09.008DOI Listing
January 2020

The evolving landscape of HPV-related neoplasia in the head and neck.

Hum Pathol 2019 12 22;94:29-39. Epub 2019 Oct 22.

Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA 19104.

Human papilloma virus (HPV) has emerged as the key etiologic driver in the majority of cancers at head and neck mucosal sites. First described in the uterine cervix and subsequently in oropharyngeal squamous cell carcinomas, the morphologic and clinical spectrum of HPV-related neoplasia has continued to expand and now includes a newly described entity in the sinonasal tract. A recent study has also suggested a role of HPV in some ocular adnexal sebaceous carcinomas. Herein, we review and concisely summarize the spectrum of HPV-driven neoplasia in the head and neck, with a focus on variant morphologies and newly-described entities including key differential diagnoses and clinical implications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.humpath.2019.09.001DOI Listing
December 2019

Pembrolizumab-Induced Thyroiditis.

Endocr Pathol 2019 Jun;30(2):163-167

Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, 3400 Spruce Street, Six Founders Pavilion, Philadelphia, PA, 19104-4283, USA.

Immune checkpoint inhibitors act to restore T cell-mediated antitumor immunity. By this nature, these cancer immunotherapy drugs are associated with various immune-related adverse events such as thyroid dysfunction. We describe a case of thyrotoxicosis secondary to a programmed cell death 1 (PD-1) immune checkpoint inhibitor, pembrolizumab. A 30-year-old female was started on pembrolizumab immunotherapy for stage III small cell carcinoma of the ovary, hypercalcemic type. Thirteen days after her second cycle of therapy, she presented with symptoms consistent with thyrotoxicosis. A thyroiditis was diagnosed by thyroid function tests and ultrasonography. She was originally treated with prednisone and metoprolol for possible Grave's disease. Pertechnetate thyroid scan was more consistent with thyroiditis secondary to pembrolizumab. She underwent a total thyroidectomy 10 days after initial presentation for refractory thyrotoxicosis despite maximal medical therapy. Her symptoms resolved and thyroid function tests significantly improved. Pathology was consistent with severe thyroiditis. Immune microenvironment may play a role in the expression of programmed cell death protein 1 ligand 1 (PD-L1). Chronic inflammation surrounding tumor upregulates PD-L1 expression on tumor cells by the release of cytokines, which acts to inhibit tumor destruction. We suggest that our patient had an undetected chronic inflammation of the thyroid, specifically Hashimoto's thyroidits, which predisposed her to thyroid destruction when taking pembrolizumab. Understanding that an inflammatory environment impacts thyroid toxicity to PD-1 inhibitor therapy is novel and should be further studied.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12022-019-9579-2DOI Listing
June 2019

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 2019 05 27;29(5):619-624. Epub 2019 Apr 27.

12 Department of Anatomic Pathology, Moffitt Cancer Center, Tampa, Florida.

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. 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. 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/thy.2018.0286DOI Listing
May 2019

The Pathology of Hyperthyroidism.

Front Endocrinol (Lausanne) 2018 3;9:737. Epub 2018 Dec 3.

Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, PA, United States.

This article reviews those pathologic lesions which are associated with clinical and/or biochemical hyperthyroidism. Beginning with the descriptive pathology of classical Graves' disease and the less common toxic nodular goiter and hyper-functioning thyroid nodules, this paper describes the effects of non-thyroidal hormones, glandular function (including pituitary and hypothalamic lesions), ectopic production of thyroid stimulating proteins by non-thyroidal neoplasms, exogenous drug reactions causing hyper-function and finally conditions associated with a mechanic- destructive cause of hyperthyroidism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fendo.2018.00737DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6286962PMC
December 2018

The utility of the Milan System as a risk stratification tool for salivary gland fine needle aspiration cytology specimens.

Cytopathology 2019 01 12;30(1):91-98. Epub 2018 Nov 12.

Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.

Objective: To perform a retrospective investigation of our institutional experience with salivary gland fine needle aspirations (FNA) through the framework of The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) and assess the risks of neoplasm and malignancy for each diagnostic category.

Methods: All salivary gland FNAs performed from January 2009 to December 2016 were retrospectively categorised according to the MSRSGC. When available, pre-operative cytological results were correlated with subsequent histological follow-up.

Results: In total, 893 FNAs were reviewed. The specimens were retrospectively classified as nondiagnostic (ND: 13.5%), non-neoplastic (NN: 16.1%), atypia of undetermined significance (AUS: 10.8%), benign neoplasm (BN: 34.9%), salivary gland neoplasm of uncertain malignant potential (SUMP: 8.2%), suspicious for malignancy (SM: 2.7%) and malignant (M: 13.8%). Histological follow-up was available for 429 cases (48%); the majority (68.1%) were benign. The risks of neoplasm and malignancy for each category were as follows: ND: 64.5%, 16.1%; NN: 42.9%, 17.9%; AUS: 79.6%, 30.6%; BN: 100%, 2.2%; SUMP: 100%, 46.6%; SM: 94.7%, 78.9%; and M: 100%, 98.5%.

Conclusions: The MSRSGC is a useful classification scheme for stratifying salivary gland lesions according to their associated risk of malignancy and guiding clinicians toward appropriate management. Diagnostic pitfalls are seen in a small proportion of cases and a multidisciplinary approach for assessing salivary gland pathology is essential in their evaluation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cyt.12642DOI Listing
January 2019

Papillary Thyroid Microcarcinoma: Reclassification to Non-Invasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features (NIFTP): a Retrospective Clinicopathologic Study.

Endocr Pathol 2018 Dec;29(4):339-345

Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, 6 Founders, 3400 Spruce Street, Philadelphia, PA, 19104, USA.

Papillary thyroid microcarcinoma (PTMC) accounts for nearly 50% of newly diagnosed PTC cases. There is considerable debate in literature about the clinicopathologic features and prognostic significance of PTMC and whether it should be treated as a separate entity. Due to lack of agreement and supportive data, the consensus study group that established the criteria for non-invasive thyroid neoplasm with papillary-like features (NIFTP) kept its size above 1 cm i.e., excluding PTMC from this new group. As a result, to date, some patients diagnosed with PTMC get aggressive treatments such as partial or total thyroidectomy and even radioactive iodine ablation. We retrospectively studied clinicopathologic features and long-term follow-up of 48 cases of papillary thyroid microcarcinoma. Of these, 7 cases (15%) had capsular invasion, 2 cases (4%) had extrathyroidal extension, 1 case (2%) had lymphovascular invasion, 5 cases (25%) had lymph node metastases, no case (0%) had any distant metastases, and 1 case had recurrence after long-term follow-up (mean 13.7 years, range 1-21 years). Upon slide review, 8 cases fulfilled the criteria for NIFTP and were sub-classified under this new category. These 8 cases had no recurrence after long-term follow-up (mean 12.1 years, range 7-19 years). In this study, we confirmed the previous published reports exhibiting indolent nature of PTMC and also suggested that PTMC cases that fulfill all the criteria for NIFTP can be sub-classified under this term in order to avoid unnecessary aggressive treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12022-018-9546-3DOI Listing
December 2018

Performance of a Genomic Sequencing Classifier for the Preoperative Diagnosis of Cytologically Indeterminate Thyroid Nodules.

JAMA Surg 2018 09;153(9):817-824

Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Importance: Use of next-generation sequencing of RNA and machine learning algorithms can classify the risk of malignancy in cytologically indeterminate thyroid nodules to limit unnecessary diagnostic surgery.

Objective: To measure the performance of a genomic sequencing classifier for cytologically indeterminate thyroid nodules.

Design, Setting, And Participants: A blinded validation study was conducted on a set of cytologically indeterminate thyroid nodules collected by fine-needle aspiration biopsy between June 2009 and December 2010 from 49 academic and community centers in the United States. All patients underwent surgery without genomic information and were assigned a histopathology diagnosis by an expert panel blinded to all genomic information. There were 210 potentially eligible thyroid biopsy samples with Bethesda III or IV indeterminate cytopathology that constituted a cohort previously used to validate the gene expression classifier. Of these, 191 samples (91.0%) had adequate residual RNA for validation of the genomic sequencing classifier. Algorithm development and independent validation occurred between August 2016 and May 2017.

Exposures: Thyroid nodule surgical histopathology diagnosis by an expert panel blinded to all genomic data.

Main Outcomes And Measures: The primary end point was measurement of genomic sequencing classifier sensitivity, specificity, and negative and positive predictive values in biopsies from Bethesda III and IV nodules. The secondary end point was measurement of classifier performance in biopsies from Bethesda II, V, and VI nodules.

Results: Of the 183 included patients, 142 (77.6%) were women, and the mean (range) age was 51.7 (22.0-85.0) years. The genomic sequencing classifier had a sensitivity of 91% (95% CI, 79-98) and a specificity of 68% (95% CI, 60-76). At 24% cancer prevalence, the negative predictive value was 96% (95% CI, 90-99) and the positive predictive value was 47% (95% CI, 36-58).

Conclusions And Relevance: The genomic sequencing classifier demonstrates high sensitivity and accuracy for identifying benign nodules. Its 36% increase in specificity compared with the gene expression classifier potentially increases the number of patients with benign nodules who can safely avoid unnecessary diagnostic surgery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamasurg.2018.1153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6583881PMC
September 2018

Characteristics of Follicular Variant Papillary Thyroid Carcinoma in a Pediatric Cohort.

J Clin Endocrinol Metab 2018 04;103(4):1639-1648

Division of Endocrinology and Diabetes, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.

Context: In adults, noninvasive follicular variant of papillary thyroid carcinoma (FVPTC) is considered a low risk for metastasis and persistent/recurrent disease.

Objective: The goal of this study was to assess the clinical, sonographic, and histopathologic features of FVPTC in a pediatric cohort.

Design: A retrospective review of subjects <19 years of age with papillary thyroid carcinoma (PTC) who underwent thyroidectomy between January 2010 and July 2015.

Setting: Multidisciplinary academic referral center.

Patients: Patients with FVPTC, defined as a tumor ≥1 cm in the largest dimension with predominant follicular growth, complete lack of well-formed papillae, and nuclear features of PTC.

Main Outcome Measures: Tumor size and location, presence of a tumor capsule, capsule and vascular invasion, lymph node invasion, and distant metastasis.

Results: Eighteen patients with FVPTC were identified from a case cohort of 110 patients with PTC. On histopathology, 13 (72%) had unifocal nodules and 14 (78%) had completely encapsulated FVPTC. Capsule invasion was frequent (nine of 14; 64%), and vascular invasion was found in one-third of patients (six of 18; 33%). No lymph node metastases were found in the 13 patients (72%) who had a central neck lymph node dissection. One patient with vascular invasion had distant metastases.

Conclusion: When strictly defined, FVPTC in pediatric patients has a low risk for bilateral disease and metastasis. Prospective studies are needed to confirm whether lobectomy with surveillance is sufficient to achieve remission in pediatric patients with low-risk FVPTC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/jc.2017-02454DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6436765PMC
April 2018

Special types of thyroid carcinoma.

Histopathology 2018 Jan;72(1):40-52

Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Perelman School of Medicine, Philadelphia, PA, USA.

This article reviews the small percentage of thyroid tumours that are not classified as classic papillary thyroid carcinoma, follicular thyroid carcinoma, and medullary thyroid carcinoma. It includes subtypes of papillary thyroid carcinoma, including, tall-cell, hobnail/micropapillary, columnar cell, diffuse sclerosing and solid variants. Poorly differentiated carcinoma, high-grade carcinoma and anaplastic thyroid carcinoma are reviewed. Also discussed are entities that are unusual but need to be recognized as primary thyroid neoplasms, i.e. mucoepidermoid carcinoma, sclerosing mucoepidermoid carcinoma with eosinophilia, and mammary analogue secretory carcinoma/secretory carcinoma. The pathological features and prognostic factors are described; a brief review of molecular correlates of these neoplasms is included.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/his.13348DOI Listing
January 2018

Noninvasive follicular thyroid neoplasm with papillary-like nuclear features: a review for pathologists.

Mod Pathol 2018 01 20;31(1):39-55. Epub 2017 Oct 20.

Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.

The rising incidence of papillary thyroid carcinoma is linked in part to inclusion of noninvasive follicular variant of papillary thyroid carcinoma. Despite its designation as carcinoma, noninvasive follicular variant of papillary thyroid carcinoma appears to be exceptionally indolent, often over treated by current treatment practices. Additionally, criteria for diagnosis have historically been subjective and challenging. Recently, an international multidisciplinary collaborative group performed a clinicopathologic survey of such cases with extended follow-up and concluded based on the outcome data that a revision in nomenclature was warranted, proposing 'Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP).' This monograph is a synopsis and guide for pathologists on NIFTP and focuses on histologic features, including inclusion and exclusion criteria used to define NIFTP, as well as grossing guidelines, reporting practices, and potential diagnostic limitations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/modpathol.2017.130DOI Listing
January 2018

Pathologic Reporting of Tall-Cell Variant of Papillary Thyroid Cancer: Have We Reached a Consensus?

Thyroid 2017 12 7;27(12):1498-1504. Epub 2017 Nov 7.

1 Department of Anatomic Pathology, Moffitt Cancer Center , Tampa, Florida.

Background: Tall-cell variant (TCV) is widely believed to be a more aggressive subtype of papillary thyroid carcinoma (PTC). Despite the significance of TCV with respect to risk stratification and therapeutic decision making, its diagnosis is subject to inter-observer variability. This study aimed to determine the level of agreement among expert pathologists in the identification and reporting of TCV.

Methods: Seventeen surgical resections for thyroid cancer containing the diagnostic term "tall cell" in their pathology reports and 22 cases diagnosed as classical PTC were selected. Cases were digitalized, and 14 expert pathologists reviewed the scanned slides blinded to the original interpretation. Each pathologist designated each case as TCV or not and answered multiple questions about diagnostic histopathologic features of TCV.

Results: The overall strength of agreement for identifying TCV was fair (Fleiss kappa 0.34), and the proportion of observed agreement was 0.70. Of 22 cases originally diagnosed as PTC classical variant, 15 (68%) were reclassified as TCV by at least one expert pathologist. It was noted that four different definitions for TCV were used by the participants based on various combinations of cell height to width (H:W) ratio and the percentage of tumor cells showing that specific ratio. All pathologists agreed that the diagnosis of TCV does not rely solely on a specific H:W ratio.

Conclusions: Pathologic reporting of TCV varies among pathologists. This disagreement is a result of the lack of unanimous diagnostic criteria and variation in individual pathologists' interpretations. These discrepancies lead to over- and under-diagnosis of TCV, which has significant implications in patient management. It is imperative to understand this variability in diagnosis TCV as it relates to risk stratification and interpretation of clinical studies related to this histologic subtype of PTC. Further studies are needed to reach consensus on the diagnostic criteria of TCV.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/thy.2017.0280DOI Listing
December 2017

Giant Parotid Carcinosarcoma Arising in a Pleomorphic Adenoma: Facial Nerve Preservation by Retrograde Dissection.

OTO Open 2017 Jul-Sep;1(3):2473974X17719416. Epub 2017 Jul 3.

Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/2473974X17719416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6239038PMC
July 2017

Non-invasive follicular neoplasm with papillary like nuclear features (NIFTP): If it ain't broke, don't fix it. The cytopathologist's dilemma.

Diagn Cytopathol 2017 06 16;45(6):479-480. Epub 2017 Apr 16.

Professor of Pathology & Laboratory Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/dc.23732DOI Listing
June 2017

Reporting of fine needle aspiration (FNA) specimens of salivary gland lesions: A comprehensive review.

Diagn Cytopathol 2017 Sep 31;45(9):820-827. Epub 2017 Mar 31.

Department of Pathology and Laboratory Medicine, University of Pennsylvania, Perelman School of Medicine, 3400 Spruce Street, 6th Floor Founders Building, Philadelphia, Pennsylvania, 19104.

Currently, there is no uniform classification scheme available for reporting of salivary gland fine-needle aspiration (FNA) specimens. Recently, an International group of pathologists has recommended a tiered classification scheme for reporting of salivary gland FNA results known as the "Milan System for Reporting Salivary Gland Cytopathology (MSRSGC)." We performed a comprehensive review of the published literature on FNA of salivary gland lesions by employing the diagnostic categories of the MSRSGC to evaluate their reliability in the management of salivary gland lesions. A comprehensive review of the literature was carried out through PubMed from 1987 to 2015 to identify studies which categorized the cytologic diagnoses and included surgical follow-up. Only cases with histopathologic follow-up were included in the analysis. Twenty-nine studies comprising 4514 cases of salivary gland FNAs with surgical follow-up were included in this study. The cytologic diagnoses were categorized into the following categories proposed by MSRSGC. The number of cases in each diagnostic category and the risk of malignancy (ROM) were as follows: Non-Diagnostic-100 cases (ROM- 25.0% ± 16.7%), Non-Neoplastic-587 cases (ROM: 10.2% ± 5.5%), Benign Neoplasm -2673 cases (ROM: 3.4% ± 1.3%), Salivary Gland Neoplasm of Undetermined Malignant Potential (SUMP)-64 cases(ROM: 37.5% ± 24.7%), Suspicious for Malignant neoplasm-70 cases(ROM: 58.6% ± 19.5%), and Malignant-1012 cases(ROM: 91.9% ± 3.5%). A tiered classification scheme as proposed by MSRSGC may prove helpful in effectively guiding clinical management of patients with salivary gland lesions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/dc.23716DOI Listing
September 2017

Inflammatory and Infectious Lesions of the Sinonasal Tract.

Surg Pathol Clin 2017 Mar 28;10(1):125-154. Epub 2016 Dec 28.

Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, 3400 Spruce Street, 6 Founders, Philadelphia, PA 19104, USA.

The sinonasal tract is frequently affected by nonneoplastic inflammatory diseases. Inflammatory lesions of the sinonasal tract can be divided into 3 main categories: chronic rhinosinusitis, which encompasses a heterogeneous group of entities, all of which result in mucosal inflammation with or without polyps-eosinophils; infectious diseases; and autoimmune diseases and vasculitides, which can result in midline necrosis and facial deformities. This article reviews the common inflammatory lesions of the sinonasal tract with emphasis on infectious diseases, vasculitis, iatrogenic, and diseases of unknown cause. Many of these lesions can result in midline destruction and result in facial deformity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.path.2016.11.002DOI Listing
March 2017

NIFTP: COMMENTARY ON AN EVOLVING ENTITY.

Endocr Pract 2017 04 17;23(4):501-502. Epub 2017 Jan 17.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4158/EP171749.CODOI Listing
April 2017

Transoral Robotic Surgery-Assisted Endoscopy With Primary Site Detection and Treatment in Occult Mucosal Primaries.

JAMA Otolaryngol Head Neck Surg 2017 03;143(3):267-273

Department of Otorhinolaryngology-Head & Neck Surgery, University of Pennsylvania School of Medicine, Philadelphia.

Importance: Management of cervical lymph node metastasis without a known primary tumor is a diagnostic and treatment challenge for head and neck oncologists. Identification of the occult mucosal primary tumor minimizes the morbidity of treatment.

Objective: To analyze the role of transoral robotic surgery (TORS) in facilitating the identification of a primary tumor site for patients presenting with squamous cell carcinoma of unknown primary (CUP). In addition, we assessed treatment deintensification by determining the number of patients who did not undergo definitive radiation therapy and chemotherapy.

Design, Setting, And Participants: In this retrospective case series from January 2011 to September 2015, 60 consecutive patients with squamous cell CUP who underwent TORS-assisted endoscopy and ipsilateral neck dissection were included from an academic medical center and studied to study the rate success rate of TORS identifying occult mucosal malignancy.

Main Outcomes And Measures: Success rate of identifying occult mucosal malignancy; usage of radiation therapy and chemotherapy.

Results: Overall, 60 patients (mean [SD] age, 55.5 [8.9] years) were identified; 48 of the 60 patients (80.0%) had a mucosal primary identified during their TORS-assisted endoscopic procedure. The mean (SD) size of the identified mucosal primary lesions was 1.3 (0.1) cm. All mucosal primaries, when found, originated in the oropharynx including the base of tongue in 28 patients (58%), palatine tonsil in 18 patients (38%), and glossotonsillar sulcus in 2 patients (4%). Among patients in this study, 40 (67%) did not receive chemotherapy, and 15 (25%) did not receive radiation therapy.

Conclusions And Relevance: Advances in transoral surgical techniques have helped identify occult oropharyngeal malignancies that traditionally have been treated with comprehensive radiation to the entire pharyngeal axis. We demonstrate the efficacy of a TORS-assisted approach to identify and surgically treat the primary tumor in patients presenting with CUP. In addition, patients managed with the TORS-assisted endoscopic approach benefit from surgical and pathological triage, which in turn results in deintensification of treatment by eliminating the need for chemotherapy in the majority of patients, as well as avoiding radiation therapy in select patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamaoto.2016.3419DOI Listing
March 2017