V A LiVolsi

William Penn University, Filadelfia, Pennsylvania, United States

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Publications (262)1156.83 Total impact

  • Cancer Research 08/2015; 75(15 Supplement):3892-3892. DOI:10.1158/1538-7445.AM2015-3892 · 9.33 Impact Factor
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    Mark Yarchoan · Virginia A LiVolsi · Marcia S Brose ·

    Journal of Clinical Oncology 06/2015; 33(22). DOI:10.1200/JCO.2015.61.4859 · 18.43 Impact Factor
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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.
    Endocrine Pathology 04/2015; 26(2). DOI:10.1007/s12022-015-9367-6 · 1.76 Impact Factor
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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.
    Nature Communications 01/2015; 6(2):6140. DOI:10.1038/ncomms7140 · 11.47 Impact Factor
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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.
    Journal of Clinical Endocrinology &amp Metabolism 12/2014; 100(3):jc20142760. DOI:10.1210/jc.2014-2760 · 6.21 Impact Factor
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    Mark Yarchoan · Virginia A LiVolsi · Marcia S Brose ·

    Journal of Clinical Oncology 11/2014; 33(1). DOI:10.1200/JCO.2014.59.3657 · 18.43 Impact Factor
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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.
    Cancer biology & therapy 11/2014; 16(2). DOI:10.4161/15384047.2014.987574 · 3.07 Impact Factor
  • Sylvia L Asa · Thomas J Giordano · Virginia A LiVolsi ·

    Thyroid: official journal of the American Thyroid Association 11/2014; 25(1). DOI:10.1089/thy.2014.0540 · 4.49 Impact Factor
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    Virginia LiVolsi · Anjali Saqi · Aziza Nassar · Zubair Baloch ·

  • Virginia A. LiVolsi ·

    Human pathology 01/2014; 45(1):189. · 2.77 Impact Factor
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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.
    Endocrine Practice 09/2013; 19(6):1-14. DOI:10.4158/EP13267.CR · 2.81 Impact Factor
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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.
    CytoJournal 01/2013; 10(1):2. DOI:10.4103/1742-6413.106686

  • American Journal of Clinical Pathology 12/2012; 138(6):907-10. DOI:10.1309/AJCP1BGCA6MFCNKH · 2.51 Impact Factor
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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.
    Archives of otolaryngology--head & neck surgery 07/2012; 138(7):628-34. DOI:10.1001/archoto.2012.1166 · 2.33 Impact Factor

  • Journal of neuro-ophthalmology: the official journal of the North American Neuro-Ophthalmology Society 06/2012; 32(2):167-71. DOI:10.1097/WNO.0b013e3182516cfe · 1.95 Impact Factor
  • Andrew T Turk · Haider Asad · Joseph Trapasso · Gretchen Perilli · Virginia A LiVolsi ·
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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.
    Endocrine Practice 05/2012; 18(3):e37-42. DOI:10.4158/EP11222.CR · 2.81 Impact Factor
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    ABSTRACT: The clinical benefit of postoperative mediastinal radiation for completely resected Masaoka stage 2 thymoma remains controversial. Due to its indolent nature and infrequent recurrences, no study has definitively determined the optimal approach. We retrospectively reviewed 175 consecutive patients who underwent thymic resection from January 1990 to July 2008 at the University of Pennsylvania. The primary endpoint was local recurrence, defined as recurrence within the surgical bed, treated by resection alone versus resection plus radiation. Patients with high recurrence risk were referred for adjuvant radiotherapy. Seventy-four Masaoka stage 2 patients were resected; 62 underwent complete resections with adequate postsurgical follow-up. Thirty-seven patients received adjuvant radiotherapy and 25 patients were observed. The median radiation dose was 5040 cGy. The median follow-up for all patients was 52 months. The local recurrence rate was 3.2%. The proportion of recurrences in patients observed after surgery was 8% versus 0% in those who received adjuvant radiotherapy (P = .15). Size was not an independent predictor of recurrence (P = .81). The tumor-related death rate was 0%, and overall death rate was 3.2%. One death occurred in each group, observation, and radiation. There were no grade 3 or 4 complications with radiation. Recurrence rates were low following resection of stage 2 thymoma either with or without adjuvant radiotherapy. Adjuvant radiotherapy, although well-tolerated, did not significantly decrease the local relapse rate. Differences may be observed in future studies of patients who are at higher risk for local recurrence, based on completeness of resection, World Health Organization histology, and tumor size.
    Cancer 08/2011; 117(15):3502-8. DOI:10.1002/cncr.25851 · 4.89 Impact Factor
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    ABSTRACT: In 1976, Hawk and Hazard described the tall cell variant (TCV) of papillary thyroid carcinoma (PTC). While the lesions they described had cytologic features of papillary carcinoma, they showed more aggressive behavior with a greater propensity for extrathyroid extension and lymphovascular invasion than classic PTC. In 1991, Bronner and LiVolsi described a series of patients with TCV that progressed to spindle cell squamous carcinoma (SCSC), a unique form of anaplastic thyroid carcinoma. This study describes the variable clinical and pathologic presentations in 31 patients with anaplastic SCSC arising in association with TCV. The surgical pathology archives as well as the personal consultation files of one of the authors (V.A.L.) were reviewed to retrieve cases of SCSC arising in association with TCV. The available clinical as well as pathologic information on all patients was reviewed. A total of 31 patients with SCSC arising in association with TCV were retrieved from our files. The average age at primary presentation was 67 (range 32-92) with a female-to-male ratio of 2:1. Three clinical scenarios for SCSC associated with TCV were identified. These were type I, consisting of TCV with SCSC at the time of presentation (18 patients); type II, consisting of SCSC arising as a recurrence in patients with a known history of TCV (5 patients); and type III, consisting of SCSC presenting as a primary laryngeal squamous cell carcinoma in a patient with or without a known history of TCV (8 patients). The type III cases were of most concern since they often were confused with primary laryngeal squamous cell carcinoma and most often were diagnosed after laryngectomy. SCSC of the thyroid is almost exclusively associated with TCV and can have variable clinical presentations. SCSC is most commonly seen associated with a primary diagnosis of TCV. SCSC may be seen, however, in patients with recurrent PTC and most importantly may present in a fashion similar to primary laryngeal SCSC. Therefore, caution should be exercised in evaluating laryngeal squamous lesions in patients with known history of TCV and without known risks factors for head and neck carcinogenesis.
    Thyroid: official journal of the American Thyroid Association 02/2011; 21(5):493-9. DOI:10.1089/thy.2010.0338 · 4.49 Impact Factor
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    ABSTRACT: The Chernobyl accident was followed by a large increase in the incidence of thyroid carcinoma in the areas exposed to high levels of fallout. The Chernobyl Tumor Bank was set up in 1998 to make tumours available for study internationally, and a pathology panel reviewed all the tumours and established an agreed diagnosis. The thyroid tumours that were discovered after the Chernobyl nuclear accident were virtually all (95%) of the papillary carcinoma type. Rare examples of other tumour types were identified. Within the papillary group, several subtypes were noted, including classical or usual type, follicular variant, solid variant and mixed patterns Diffuse sclerosis variant, cribriform/morular type and Warthin-like variant were rare. No tall cell or columnar cell variants were identified. The tumours examined by the Pathology Panel of the Chernobyl Tumor Bank constitute a large representative sample (estimated at about 50%) of the tumours that developed in this population. This overview describes the method adopted by the panel and the different diagnostic categories adopted; illustrates the pathology of these neoplasms; compares the pathological characteristics of the early lesions with those identified after long latency periods and the institution of screening programmes and outlines the possible associated causes for the various morphological patterns seen.
    Clinical Oncology 02/2011; 23(4):261-7. DOI:10.1016/j.clon.2011.01.160 · 3.40 Impact Factor
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    ABSTRACT: Fine-needle aspiration (FNA) biopsies are the cornerstone of preoperative evaluation of thyroid nodules, but FNA diagnostic performance has varied across different studies. In the course of collecting thyroid FNA specimens for the development of a molecular diagnostic test, local cytology and both local and expert panel surgical pathology results were reviewed. Prospective FNAs were collected at 21 clinical sites. Banked FNAs were collected from two academic centers. Cytology and corresponding local and expert panel surgical pathology results were compared to each other and to a meta-review of 11 recently published U.S.-based thyroid FNA studies. FNA diagnostic performance was comparable between the study specimens and the meta-review. Histopathology malignancy rates for prospective clinic FNAs were 34% for cytology indeterminate cases and 98% for cytology malignant cases, comparable to the figures found in the meta-review (34% and 97%, respectively). However, histopathology malignancy rates were higher for cytology benign cases in the prospective clinic FNA subcohort (11%) than in the meta-review (6%, with meta-review rates of 10% at community sites and 2% at academic centers, p < 0.0001). Resection rates for prospective clinic FNAs were also comparable to the meta-review for both cytology indeterminate cases (62% vs. 59%, respectively) and cytology malignant cases (82% vs. 81%, respectively). Surgical pathology categorical disagreement (benign vs. malignant diagnosis) was higher between local pathology and a consensus of the two expert panelists (11%) than between the two expert panelists both pre- (8%) and postconferral (3%). Although recent guidelines for FNA biopsy and interpretation have been published, the rates of false-positive and false-negative results remain a challenge. Two-thirds of cytology indeterminate cases were benign postoperatively and may decrease with the development of an accurate molecular diagnostic test. High disagreement rates between local and expert panel histopathology diagnosis suggests that central review for surgical diagnoses should be used when developing diagnostic tests based on resected thyroid specimens.
    Thyroid: official journal of the American Thyroid Association 12/2010; 21(3):243-51. DOI:10.1089/thy.2010.0243 · 4.49 Impact Factor

Publication Stats

9k Citations
1,156.83 Total Impact Points


  • 1991-2015
    • William Penn University
      Filadelfia, Pennsylvania, United States
  • 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 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
  • 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
    • Memorial Sloan-Kettering Cancer Center
      • Department of Surgery
      New York, New York, United States
  • 1998
    • Queen Mary Hospital
      Hong Kong, Hong Kong
  • 1995
    • University of Toronto
      • Mount Sinai Hospital
      Toronto, Ontario, Canada
  • 1994
    • Royal Melbourne Hospital
      Melbourne, Victoria, Australia
  • 1978-1985
    • Yale University
      New Haven, Connecticut, United States
  • 1979-1984
    • Yale-New Haven Hospital
      • Department of Pathology
      New Haven, Connecticut, 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