V A LiVolsi

William Penn University, Filadelfia, Pennsylvania, United States

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Publications (278)1199.31 Total impact

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    ABSTRACT: Because of the unique systems and skills involved in patient care by the pathologist, it is challenging to design and implement relevant training in patient safety for pathology trainees. We propose a patient safety curriculum for anatomic pathology (AP) residents based on our institutional experience. The Hospital of the University of the Pennsylvania employs a self-reporting safety database. The occurrences from July 2013 to June 2015 recorded in this system that involved the division of AP were reviewed and cataloged as preanalytic, analytic, and postanalytic. The distribution of these occurrences was then used to create a framework for curriculum development in AP. We identified areas in which trainees are involved in the identification and prevention of common patient safety errors that occur in our AP department. Using these data-proven target areas, and employing current Accreditation Council for Graduate Medical Education recommendations and patient safety literature, a strategy for delivering relevant patient safety training is proposed. Teaching patient safety to pathology trainees is a challenging, yet necessary, component of AP training programs. By analyzing the patient safety errors that occur in the AP department, relevant and actionable training can be developed. This provides quality professional development and improves overall performance as trainees are integrated into laboratory systems.
    No preview · Article · Mar 2016 · Advances in Anatomic Pathology
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    ABSTRACT: Objectives: Management of early superficial lesions in the head and neck remains complex. We performed a phase 1 trial for high-grade premalignant and early superficial lesions of the head and neck using photodynamic therapy (PDT) with Levulan (ALA). Materials and methods: Thirty-five subjects with high grade dysplasia, carcinoma in situ, or microinvasive (⩽1.5mm depth) squamous cell carcinoma were enrolled. Cohorts of 3-6 patients were given escalating intraoperative light doses of 50-200J/cm(2) 4-6h after oral administration of 60mg/kg ALA. Light at 629-635nm was delivered in a continuous (unfractionated) or fractionated (two-part) schema. Results: PDT was delivered to 30/35 subjects, with 29 evaluable. There was one death possibly due to the treatment. The regimen was otherwise tolerable, with a 52% rate of grade 3 mucositis which healed within several weeks. Other toxicities were generally grade 1 or 2, including odynophagia (one grade 4), voice alteration (one grade 3), and photosensitivity reactions. One patient developed grade 5 sepsis. With a median follow-up of 42months, 10 patients (34%) developed local recurrence; 4 of these received 50J/cm(2) and two each received 100, 150, and 200J/cm(2). Ten (34%) patients developed recurrence adjacent to the treated field. There was a 69% complete response rate at 3months. Conclusions: ALA-PDT is well tolerated. Maximum Tolerated Dose appears to be higher than the highest dose used in this study. Longer followup is required to analyze effect of light dose on local recurrence. High marginal recurrence rates suggest use of larger treatment fields.
    No preview · Article · Feb 2016
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    ABSTRACT: Peutz-Jeghers syndrome (PJS) is an autosomal-dominant disorder, in which germline mutation of serine threonine-protein kinase 11 (STK11) is identified in up to 90 % of the patients who meet clinical criteria for PJS. Hematoxylin and eosin (H&E) slides of the tumor were reviewed to confirm areas with at least 25 % of tumor cellularity. Then, the designated area was extracted for genomic DNA. Targeted next-generation sequencing analysis was performed using a 47-gene panel. Case 1 is a 71-year-old man with high grade follicular thyroid carcinoma with clear cell and oncocytic features. The carcinoma showed a missense mutation in TP53 (p.R342G, c.1024C > G) and a 16-nucleotide intronic deletion started next to the 3' of exon 6 (involving the canonical +1 and +2 bases of the splice donor site) in STK11 (p.?, c.862 + 1_862 + 16delGTGGGAGCCTCATCCC). Case 2 is a 76-year-old woman with tall cell variant papillary thyroid carcinoma. The carcinoma demonstrated a missense mutation in BRAF (p.V600E, c.1799T > A) and a missense mutation in STK11 (p.F354L, c.1062C > G). In summary, we present two elderly patients with thyroid carcinoma harboring STK11 mutation without clinical manifestation of PJS. The findings suggest that STK11 may play a role in thyroid carcinoma development.
    No preview · Article · Dec 2015 · Endocrine Pathology

  • No preview · Article · Aug 2015 · Cancer Research
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    Mark Yarchoan · Virginia A LiVolsi · Marcia S Brose

    Preview · Article · Jun 2015 · Journal of Clinical Oncology
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    ABSTRACT: The proposed diagnostic criteria for poorly differentiated thyroid carcinoma (known as the Turin classification) were defined based on growth pattern (solid, trabecular, or insular) and high-grade morphologic features (nuclear pleomorphism, mitoses including abnormal forms, and coagulative tumor necrosis). The development of this classification specifically did not include tumors with oncocytic or Hürthle cell cytology, and only sparse literature describing poorly differentiated oncocytic carcinomas is available. In this study, we examined a cohort of 284 cases of oncocytic follicular carcinoma/Hürthle cell carcinoma (OFC/HCC) and identified 17 cases of oncocytic variant of poorly differentiated carcinoma (OV-PDTC) based on Turin criteria. Compared to minimally invasive and angioinvasive OFC/HCC, these tumors arose in older patients (range 44-88 years; average 71 years), were larger (average size 4.5 cm), and all had extensive vascular invasion (5-15 foci), and coagulative tumor necrosis and the tumor cells were arranged in a trabecular or solid growth pattern. All showed an admixture of oncocytic follicular/Hürthle cells arranged in solid and trabecular growth pattern. Aggregates of small sized cells with minimal eosinophilic cytoplasm, comprising 10-20 % of the entire tumor mass were also seen in 16/17 cases. Clinical follow-up was available in 12 cases and ranged from 6 to 120 months (average 41 months). Distant metastases were seen in 10/12 (83 %) patients; two had lung and one had bone metastases at the time of thyroid surgery, and four subsequently developed cervical lymph node metastases. Two patients died of disease, and ten are alive either with or free of tumor. The OV-PDTC is a distinct entity which can be identified based on Turin criteria and the presence of a distinct "small cell" component. It is frequently associated with regional recurrence and distant metastases and can lead to tumor-related demise.
    No preview · Article · Apr 2015 · Endocrine Pathology
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    ABSTRACT: Pheochromocytomas and paragangliomas (PCC/PGL) are the solid tumour type most commonly associated with an inherited susceptibility syndrome. However, very little is known about the somatic genetic changes leading to tumorigenesis or malignant transformation. Here we perform whole-exome sequencing on a discovery set of 21 PCC/PGL and identify somatic ATRX mutations in two SDHB-associated tumours. Targeted sequencing of a separate validation set of 103 PCC/PGL identifies somatic ATRX mutations in 12.6% of PCC/PGL. PCC/PGL with somatic ATRX mutations are associated with alternative lengthening of telomeres and clinically aggressive behaviour. This finding suggests that loss of ATRX, an SWI/SNF chromatin remodelling protein, is important in the development of clinically aggressive PCC/PGL.
    Full-text · Article · Jan 2015 · Nature Communications
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    ABSTRACT: Objective: Parathyroid gland malignancies are considered rare. The most common of these tumor types is primary parathyroid carcinoma. Metastatic spread from other cancers may also occur with up to 10% of cancers from other sites showing parathyroid involvement at autopsy. Tumor-to-tumor metastases (metastatic spread to parathyroid neoplasm) from remote cancers to the parathyroid gland have been described. Methods: We did a PubMed literature review and analysis of our own experience of 392 consecutive parathyroidectomies. Results: Primary and secondary parathyroid malignancies can be grouped into three categories: primary parathyroid carcinoma (PPCa), spread of carcinoma into parathyroid glands by contiguous extension from the thyroid gland or other head and neck cancer, and metastatic disease to the parathyroid gland from distant cancers. Studies of tumor-to-tumor spread indicate a predilection of spread to endocrine tumors possibly because of the rich blood supply that is present in endocrine tumors. Two of our 392 parathyroidectomies (0.5%) had cancer: one metastatic (thymic neuroendocrine tumor) and another PPCa. Conclusion: Metastatic disease to the parathyroid gland is poorly documented. When performing surgery for primary thyroid cancer, the search for parathyroid gland metastases is often overlooked because of the desire to preserve parathyroid function. Metastatic disease from other cancers to a benign parathyroid gland or to a parathyroid adenoma probably suggests a grave prognosis because it likely indicates widespread metastatic disease; however, isolated metastases to the parathyroid may occur. Although these lesions may be uncommon they may not be as rare as once thought.
    No preview · Article · Dec 2014 · Journal of Clinical Endocrinology & Metabolism
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    Mark Yarchoan · Virginia A LiVolsi · Marcia S Brose

    Preview · Article · Nov 2014 · Journal of Clinical Oncology
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    ABSTRACT: Pancreatic neuroendocrine tumors (PNETs) are rare, indolent tumors that may occur sporadically or develop in association with well-recognized hereditary syndromes, particularly multiple endocrine neoplasia type 1 (MEN-1). We previously demonstrated that the hedgehog (HH) signaling pathway was aberrantly up-regulated in a mouse model that phenocopies the human MEN-1 syndrome, Men1l/l;RipCre, and that inhibition of this pathway suppresses MEN-1 tumor cell proliferation. We hypothesized that the HH signaling pathway is similarly upregulated in human PNETs. We performed immunohistochemical (IHC) staining for PTCH1 in human fresh and archival PNET specimens to examine whether human sporadic and MEN-1-associated PNETs revealed similar abnormalities as in our mouse model and correlated the results with clinical and demographic factors of the study cohort. PTCH1 staining was positive in 12 of 22 PNET patients (55%). Four of five MEN-1 patients stained for PTCH1 (p = 0.32 as compared with sporadic disease patients). Nine of 16 patients with metastatic disease stained for PTCH1 as compared with zero of three with localized disease only (p = 0.21). No demographic or clinical features appeared to be predictive of PTCH 1 positivity and PTCH 1 positivity per se was not predictive of clinical outcome. PTCH1, a marker of HH pathway up regulation, is detectable in both primary and metastatic tumors in more than 50% of PNET patients. Although no clinical or demographic factors predict PTCH1 positivity and PTCH1 positivity does not predict clinical outcome, the frequency of expression alone indicates that perturbation of this pathway with agents such as Vismodegib, an inhibitor of Smoothened (SMO), should be examined in future clinical trials.
    No preview · Article · Nov 2014 · Cancer biology & therapy
  • Sylvia L Asa · Thomas J Giordano · Virginia A LiVolsi

    No preview · Article · Nov 2014 · Thyroid: official journal of the American Thyroid Association
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    Virginia LiVolsi · Anjali Saqi · Aziza Nassar · Zubair Baloch

    Full-text · Dataset · Sep 2014

  • No preview · Conference Paper · Apr 2014
  • Virginia A. LiVolsi

    No preview · Article · Jan 2014 · Human pathology
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    ABSTRACT: Objective: To describe a unique case of a metastatic thymic carcinoma to the hyperplastic parathyroid gland, and to present a challenging management dilemma.Methods: Patient is 60 year-old, mentally retarded male with history of the multiple endocrine neoplasia type 1 (MEN1) syndrome, a surgery in 1985 for hypercalcemia with removal of one parathyroid gland, surgery in 2007 with findings of extensively necrotic well differentiated neuroendocrine carcinoma (carcinoid tumor) of the thymus. In 2012, he presented with persistent hypercalcemia (calcium level 11.7 mg/dL (8.6-10.2), parathyroid hormone (PTH) level - l225 pg/mL (15-65)). He underwent a repeat neck exploration with removal of 2 small inferior, and a large left superior 4.5x2.5x1.5cm parathyroid glands (all showed hyperplasia on intraoperative frozen section). A small portion of the superior gland was reimplanted into the patient's forearm. Final pathology showed the presence of a focus of neuroendocrine tumor within the left superior parathyroid gland with immunostain identical to the thymic carcinoma. His postoperative PTH level was 14 pg/mL and calcium 8.5 mg/dL. A PET CT and Octreotide scans revealed an extensive metastatic disease within the lung, mediastinum and bones.Results: We have decided to leave a portion of the reimplanted parathyroid gland, with possible metastatic thymic carcinoid, in his forearm because of the presence a widespread metastatic disease, and his mental retardation that would result in non-compliance with calcium replacement in case of permanent hypocalcemia.Conclusion: Metastatic thymic carcinoma to the parathyroid gland has never been reported in the literature. We have described the first case and presented a challenging management dilemma.
    No preview · Article · Sep 2013 · Endocrine Practice
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    ABSTRACT: Oncocytic follicular (OF) cells can be a prominent component of fine needle aspiration (FNA) specimens from neoplasms (adenomas and carcinomas) and nodules arising in multinodular goiter and chronic lymphocytic thyroiditis (CLT). Because OF cells can be present in non-neoplastic and neoplastic thyroid lesions it can be challenging to differentiate between these two in FNA specimens. The aims of this study were to determine the risk of malignancy in cases diagnosed as either oncocytic follicular neoplasm (OFN) or hyperplastic/adenomatoid nodule with OF on FNA and to identify clinicopathologic features that may help in predicting malignancy in such cases, especially the presence or absence of CLT. We retrospectively searched the computerized laboratory information system at our institution between 1998 and 2009 for thyroid US guided FNA specimens in which the term "oncocytic/oncocytes" was mentioned in the final cytopathologic diagnosis. A total of 340 cases were selected for this study. The following data points were collected: Patient demographics, site of thyroid biopsy, size of lesion, FNA diagnosis, histopathologic follow-up and presence of CLT. Surgical pathology follow-up (SPFU) was available in 269 (79%) cases. Two hundred and sixty patients were females and 80 males (average age 53 years). The lesion size was <3.0 cm in 241 (71%) and ≥ 3.0 cm in 99 (29%) cases. Cytologic diagnoses included: Follicular neoplasm with oncocytic features (FNOF) 321 and suggestive of FNOF 19 cases; a secondary cytologic diagnosis of CLT was made in 20 cases. SPFU was available in 269 (79%) cases; it was benign in 213 (213/267 = 79%) and malignant in 56 (56/269 = 21%) cases. The background thyroid showed CLT in 67 (25%) cases; 24% (48/196) neoplasms occurred with versus 76% (147/196) without CLT. The rate of malignancy was lower in nodules measuring less than 3.0 cm as compared to those equal or greater than 3.0 cm in size (17% vs. 28% respectively). The presence of CLT did not significantly alter the rate of malignancy in both FNA and surgical pathology specimens. Based on this study, nodule size and not CLT appears to be an important clinicopathologic features in the management of thyroid FNA specimens diagnosed as OFN.
    Full-text · Article · Jan 2013 · CytoJournal
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    Full-text · Article · Dec 2012 · American Journal of Clinical Pathology
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    ABSTRACT: To evaluate local control following transoral robotic surgery (TORS) with the da Vinci Surgical System (Intuitive Surgical Inc) as a single treatment modality for oropharyngeal squamous cell carcinoma (OSCC). Prospective, single-center, observational study. Academic university health system and tertiary referral center. Thirty adults with previously untreated OSCC. Transoral robotic surgery with staged neck dissection as indicated. Local control and margin status. Thirty patients were enrolled with previously untreated OSCC and no prior head and neck radiation therapy. Follow-up duration was at least 18 months. At the time of diagnosis, 9 tumors were T1 (30%); 16 were T2 (53%); 4 were T3 (13%); and 1 was T4a (3%). The anatomic sites of these primary tumors were tonsil in 14 (47%), tongue base in 9 (30%), glossotonsillar sulcus in 3 (10%), soft palate in 3 (10%), and oropharyngeal wall in 1 (3%). There was only 1 patient (3%) who had a positive margin after primary resection; further resection achieved a final negative margin. Perineural invasion was noted in 3 tumors (10%). No patient received postoperative adjuvant therapy. At a mean follow-up of 2.7 years (range, 1.5-5.1 years), there was 1 patient with local failure (3%). As the only modality used for treatment of pathologically low-risk OSCCs, TORS provides high local control and is associated with low surgical morbidity.
    No preview · Article · Jul 2012 · Archives of otolaryngology--head & neck surgery

  • No preview · Article · Jun 2012 · Journal of neuro-ophthalmology: the official journal of the North American Neuro-Ophthalmology Society
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    ABSTRACT: To report the case of a 78-year-old woman with mixed corticomedullary carcinoma of the adrenal gland, and to review other reported lesions that exhibit clinical and/or histopathologic features of both adrenal cortical and medullary differentiation. We describe the patient's clinical findings and laboratory test results, as well as the gross and histopathologic features of her tumor. We also review the literature pertaining to mixed corticomedullary adenomas and cortical tumors with clinical features of pheochromocytoma, and vice versa. A 78-year-old woman with a 10-cm left adrenal mass was hospitalized for management of hypertensive urgency. Laboratory workup revealed elevated urinary metanephrine excretion and elevated serum dehydroepiandrosterone sulfate levels. She underwent left adrenalectomy. Pathologic examination of the lesion showed mixed cortical and medullary histologic characteristics, as well as gross and microscopic evidence of malignancy. Including the present case, we identified 17 cases of neoplasms that exhibit features of mixed corticomedullary differentiation. This report represents the first documented case of mixed corticomedullary carcinoma. Several benign lesions combine clinical, biochemical, and/or histopathologic evidence of both adrenal cortical and medullary differentiation, including mixed corticomedullary adenomas and corticotropin-secreting pheochromocytomas. The differential diagnosis of a lesion with mixed cortical and medullary features should also include a malignant neoplasm.
    No preview · Article · May 2012 · Endocrine Practice

Publication Stats

10k Citations
1,199.31 Total Impact Points


  • 1998-2015
    • William Penn University
      Filadelfia, Pennsylvania, United States
    • Queen Mary Hospital
      Hong Kong, Hong Kong
  • 1987-2015
    • University of Pennsylvania
      • • Department of Pathology and Laboratory Medicine
      • • Department of Pathology
      • • Department of Medicine
      • • Division of Gynecologic Oncology
      Filadelfia, Pennsylvania, United States
    • National Cancer Institute (USA)
      • Epidemiology and Biostatistics
      베서스다, Maryland, United States
  • 1986-2014
    • Hospital of the University of Pennsylvania
      • • Department of Pathology and Laboratory Medicine
      • • Department of Obstetrics and Gynecology
      • • Department of Radiology
      • • Department of Radiation Oncology
      Philadelphia, Pennsylvania, United States
  • 2004
    • University of Pittsburgh
      • Department of Pathology
      Pittsburgh, Pennsylvania, United States
  • 2002
    • State University of New York Upstate Medical University
      • Department of Pathology
      Syracuse, New York, United States
  • 2001
    • The Chester County Hospital
      West Chester, Pennsylvania, United States
  • 2000-2001
    • Catholic University of the Sacred Heart
      • • Institute of Surgical Semeiotics
      • • Institute of Pathological Anatomy
      Milano, Lombardy, Italy
    • Roswell Park Cancer Institute
      • Department of Pathology
      Buffalo, New York, United States
  • 1999
    • Università di Pisa
      Pisa, Tuscany, Italy
    • Memorial Sloan-Kettering Cancer Center
      • Department of Surgery
      New York, New York, United States
  • 1995
    • University of Toronto
      • Mount Sinai Hospital
      Toronto, Ontario, Canada
  • 1994
    • Royal Melbourne Hospital
      Melbourne, Victoria, Australia
  • 1978-1988
    • Yale University
      New Haven, Connecticut, United States
  • 1979-1984
    • Yale-New Haven Hospital
      • Department of Pathology
      New Haven, Connecticut, United States
  • 1983
    • University of Massachusetts Amherst
      • Department of Public Health
      Amherst Center, Massachusetts, United States
  • 1979-1980
    • CUNY Graduate Center
      New York City, New York, United States
  • 1974-1979
    • New York Presbyterian Hospital
      • Department of Pathology
      New York City, New York, United States