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Indeterminate Thyroid Nodules and Advances in Molecular Pathology

Belovarac, Brendan; Zhou, Fang; Sharma, Jake; Brandler, Tamar C
Thyroid cytology has in recent years been augmented by molecular testing for indeterminate lesions. Three commercial molecular tests are available which provide variable amounts of detail regarding the genetic alterations identified in a sample. This paper will describe these tests, as well as the common molecular drivers associated with papillary thyroid carcinoma (PTC) and follicular patterned lesions, in order to help the practicing pathologist and clinician better interpret the results of these tests and incorporate this information into their management of cytologically indeterminate thyroid lesions.
PMID: 37173165
ISSN: 0740-2570
CID: 5525372

Malignant and Benign Tracheobronchial Neoplasms: Comprehensive Review with Radiologic, Bronchoscopic, and Pathologic Correlation

Girvin, Francis; Phan, Alexander; Steinberger, Sharon; Shostak, Eugene; Bessich, Jamie; Zhou, Fang; Borczuk, Alain; Brusca-Augello, Geraldine; Goldberg, Margaret; Escalon, Joanna
Tracheobronchial neoplasms are much less common than lung parenchymal neoplasms but can be associated with significant morbidity and mortality. They include a broad differential of both malignant and benign entities, extending far beyond more commonly known pathologic conditions such as squamous cell carcinoma and carcinoid tumor. Airway lesions may be incidental findings at imaging or manifest with symptoms related to airway narrowing or mucosal irritation, invasion of adjacent structures, or distant metastatic disease. While there is considerable overlap in clinical manifestation, imaging features, and bronchoscopic appearances, an awareness of potential distinguishing factors may help narrow the differential diagnosis. The authors review the epidemiology, imaging characteristics, typical anatomic distributions, bronchoscopic appearances, and histopathologic findings of a wide range of neoplastic entities involving the tracheobronchial tree. Malignant neoplasms discussed include squamous cell carcinoma, malignant salivary gland tumors (adenoid cystic carcinoma and mucoepidermoid carcinoma), carcinoid tumor, sarcomas, primary tracheobronchial lymphoma, and inflammatory myofibroblastic tumor. Benign neoplasms discussed include hamartoma, chondroma, lipoma, papilloma, amyloidoma, leiomyoma, neurogenic lesions, and benign salivary gland tumors (pleomorphic adenoma and mucous gland adenoma). Familiarity with the range of potential entities and any distinguishing features should prove valuable to thoracic radiologists, pulmonologists, and cardiothoracic surgeons when encountering the myriad of tracheobronchial neoplasms in clinical practice. Attention is paid to any features that may help render a more specific diagnosis before pathologic confirmation. ©RSNA, 2023 Quiz questions for this article are available in the supplemental material.
PMID: 37561643
ISSN: 1527-1323
CID: 5560812

The contribution of amyloid deposition in the aortic valve to calcification and aortic stenosis

Sud, Karan; Narula, Navneet; Aikawa, Elena; Arbustini, Eloisa; Pibarot, Philippe; Merlini, Giampaolo; Rosenson, Robert S; Seshan, Surya V; Argulian, Edgar; Ahmadi, Amir; Zhou, Fang; Moreira, Andre L; Côté, Nancy; Tsimikas, Sotirios; Fuster, Valentin; Gandy, Sam; Bonow, Robert O; Gursky, Olga; Narula, Jagat
Calcific aortic valve disease (CAVD) and stenosis have a complex pathogenesis, and no therapies are available that can halt or slow their progression. Several studies have shown the presence of apolipoprotein-related amyloid deposits in close proximity to calcified areas in diseased aortic valves. In this Perspective, we explore a possible relationship between amyloid deposits, calcification and the development of aortic valve stenosis. These amyloid deposits might contribute to the amplification of the inflammatory cycle in the aortic valve, including extracellular matrix remodelling and myofibroblast and osteoblast-like cell proliferation. Further investigation in this area is needed to characterize the amyloid deposits associated with CAVD, which could allow the use of antisense oligonucleotides and/or isotype gene therapies for the prevention and/or treatment of CAVD.
PMID: 36624274
ISSN: 1759-5010
CID: 5410352

Molecular Profiles of Noninvasive, Minimally Invasive, and Invasive Follicular Patterned Thyroid Neoplasms with Papillary Nuclear Features

Brandler, Tamar C; Zhou, Fang; Liu, Cheng Z; Serrano, Antonio; Sun, Wei; Nikiforov, Yuri E; Hodak, Steven P
PMID: 37014083
ISSN: 1557-9077
CID: 5540792

Extensive fibrosis in mediastinal seminoma is a diagnostic pitfall in small biopsies: two case reports

Liccardi, Anthony R.; Thomas, Kristen; Narula, Navneet; Azour, Lea; Moreira, Andre L.; Zhou, Fang
Background: In mediastinal biopsies that show fibrosis, the differential diagnosis includes fibrosing mediastinitis, immunoglobulin G subclass 4-related disease, Hodgkin lymphoma, as well as reactive fibrotic and inflammatory changes adjacent to other processes including neoplasms. Cases Description: We report two cases of incidentally detected mediastinal seminoma that contained extensive areas of paucicellular fibrosis, which precluded accurate preoperative biopsy diagnosis. The fibrosis consisted of mildly inflamed, densely scarred tissue with thin dilated vessels, and was present to a significant extent that is suggestive of spontaneous regression. These features are not currently described in the World Health Organization Classification of Thoracic Tumors. In both patients, needle and open biopsies sampled only the fibrotic areas of the tumors, and the final diagnosis was not achieved until surgical excision was performed. After surgery, both patients received chemotherapy, and were alive without evidence of disease at 3.4 years and 1 year post-operatively, respectively. Tumor fibrosis composed approximately 95% and 50% of each patient"™s tumor, respectively. In one of the patients, correlation of the needle biopsy position with the positron emission tomography (PET) scan revealed that the biopsy needle had sampled a non-metabolically active portion of the tumor. Conclusions: While pathologic spontaneous regression is well-described in gonadal germ cell tumors, it is not well-reported in extragonadal locations. Prospective knowledge of this diagnostic pitfall and targeting PET-avid regions of the tumor may increase the diagnostic yield and help to avoid non-indicated surgical interventions.
ISSN: 2522-6711
CID: 5499892

Case Report: Giant Thyroid Angiolipoma-Challenging Clinical Diagnosis and Novel Genetic Alterations

Wilkins, Reid; Zan, Elcin; Leonardi, Olga; Patel, Kepal N; Jacobson, Adam S; Jour, George; Liu, Cheng Z; Zhou, Fang
BACKGROUND:A 64-year-old man presented with a 7.8 cm lipomatous thyroid mass discovered on magnetic resonance imaging. METHODS:After two non-diagnostic fine needle aspirations (FNAs) were performed, computed tomography (CT) revealed features concerning for malignancy including central necrosis and infiltrative borders. A third FNA was still non-diagnostic. Total thyroidectomy was performed. RESULTS:Upon pathologic examination, the final diagnosis was primary thyroid angiolipoma. The lesion contained central fat necrosis with ischemic features, attributable to the FNAs. CONCLUSION/CONCLUSIONS:Ours is the third published case report of this rare entity. To date, no lipomatous thyroid tumor has undergone extensive genomic testing. Next-generation sequencing of our case revealed multiple genetic alterations, supporting the concept of angiolipomas being true neoplasms. Whereas the two previously reported cases in the literature were radiographically much smaller and appeared indolent, the large tumor in our case exhibited radiographic features concerning for liposarcoma, which belied the benign final pathologic diagnosis. Our case demonstrates that conservative surgical management (partial thyroidectomy) may be considered for lipomatous thyroid tumors, with further interventions to be determined only after final pathologic diagnosis.
PMID: 36255668
ISSN: 1936-0568
CID: 5360392

Author Correction: The contribution of amyloid deposition in the aortic valve to calcification and aortic stenosis (Nature Reviews Cardiology, (2023), 10.1038/s41569-022-00818-2)

Sud, Karan; Narula, Navneet; Aikawa, Elena; Arbustini, Eloisa; Pibarot, Philippe; Merlini, Giampaolo; Rosenson, Robert S.; Seshan, Surya V.; Argulian, Edgar; Ahmadi, Amir; Zhou, Fang; Moreira, Andre L.; Côté, Nancy; Tsimikas, Sotirios; Fuster, Valentin; Gandy, Sam; Bonow, Robert O.; Gursky, Olga; Narula, Jagat
In the version of this article initially published, Giampaolo Merlini (IRCCS Foundation Policlinico San Matteo, Pavia, Italy) was shown with an incorrect affiliation, which has now been corrected in the HTML and PDF versions of the article.
ISSN: 1759-5002
CID: 5425822

Salivary Gland Neoplasm of Uncertain Malignant Potential (SUMP) (Milan IVB) and its Subgroups: Analysis of Risk of Neoplasm and Malignancy [Meeting Abstract]

Hindi, Issa; Brandler, Tamar; Belovarac, Brendan; Szeto, Oliver; Hernandez, Osvaldo; Sun, Wei; Liu, Cheng; Zhou, Fang; Simsir, Aylin
ISSN: 0023-6837
CID: 5525452

The Milan System for Reporting Salivary Gland Cytopathology

Hindi, Issa; Simsir, Aylin; Szeto, Oliver; Hernandez, Osvaldo; Sun, Wei; Zhou, Fang; Brandler, Tamar C
OBJECTIVES/OBJECTIVE:Our study assesses whether the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) offers any benefit over the original cytology classification, and measures interobserver agreement. METHODS:Four cytopathologists retrospectively blindly classified preoperative cytology by MSRSGC from 101 resected salivary tumors. Consensus MSRSGC diagnoses were correlated with surgical pathology diagnoses and compared with the original cytology classification. Diagnostic parameters were calculated for both systems. Interobserver variability was assessed. RESULTS:The original cytology classification vs MSRSGC had sensitivity, specificity, positive predictive value, and negative predictive value of 75.0% vs 78.3%, 97.1% vs 98.0%, 91.2% vs 94.7%, and 90.1% vs 90.0%, respectively. The original cytology classification risk of neoplasm (RON) was 91.7% for "negative for malignancy" and 100.0% for other categories. The MSRSGC RON was 71.4% in category II (nonneoplastic) and 100.0% in all other categories. The original cytology classification risk of malignancy (ROM) ranged from 0.0% for "atypical" to 100.0% for "positive for malignancy." The MSRSGC ROM ranged from 0.0% in categories I (nondiagnostic) and III (nonneoplastic) to 100.0% in category VI (malignant). Weighted agreement using the MSRSGC was 92% (Gwet AC1, 0.84); unweighted agreement was 69% (Gwet AC1, 0.64). MSRSGC category IVA (benign neoplasm) was most likely to show interobserver agreement, with complete agreement in 67% of cases. CONCLUSIONS:The MSRSGC performs similarly to the original cytology classification and shows relatively high interobserver agreement.
PMID: 35849113
ISSN: 1943-7722
CID: 5278882

Cervicovaginal cytology, HPV testing and vaginal flora in transmasculine persons receiving testosterone

Lin, Lawrence Hsu; Zhou, Fang; Elishaev, Esther; Khader, Samer; Hernandez, Andrea; Marcus, Alan; Adler, Esther
BACKGROUND:Testosterone is one of the strategies that transmasculine persons can elect in order to align physical traits to their gender identity. Previous studies have shown morphologic changes in the genital tract associated with testosterone. Here, we aim to evaluate cervicovaginal cytology specimens (Pap tests) and high-risk HPV (HR-HPV) testing from transmasculine individuals receiving testosterone. METHODS:This is a retrospective cohort of 61 transmasculine individuals receiving testosterone from 2013 to 2021. Cytologic diagnoses from 65 Pap tests were correlated with HPV status and histologic follow-up and compared with the institutional data and a cohort of cisgender women with atrophic changes. RESULTS:The median age was 28 years and median time of testosterone use was 3 years. Transmasculine persons showed significantly higher rates of HSIL (2%) and unsatisfactory (16%) when compared with the institutional data and atrophic cohort of cisgender women. After reviewing slides of 46 cases, additional findings were noted: atrophy was present in 87%, glycogenated cells were seen in 30%, and Lactobacilli were substantially decreased in 89%. Among 32 available HPV tests, 19% were positive for HR-HPV and 81% were negative. On histologic follow-up, all HR-HPV-positive cases with abnormal cytology showed HSIL, while none of the HPV-negative cases revealed HSIL. CONCLUSION/CONCLUSIONS:Our study cohort demonstrated a high percentage of abnormal Pap tests in transmasculine persons receiving testosterone. Testosterone seems to induce changes in squamous cells and shifts in vaginal flora. HR-HPV testing can be a useful adjunct in the workup of abnormal Pap tests from transmasculine individuals.
PMID: 36181432
ISSN: 1097-0339
CID: 5334732