Benign lesions of the mediastinum: A review with emphasis on cytology and small biopsy specimens.

This review focuses on the diagnosis of select benign processes, ranging from reactive entities to heterotopic tissues to neoplasms, which may occur in the mediastinum. Currently, the mediastinum can be evaluated and biopsied with endoscopic procedures. Therefore, cytopathology specimens, fine needle aspirations, and small biopsies play an important role in the diagnosis of these lesions. In this review, an emphasis is given to relevant clinical presentations, histologic and cytologic findings, differential diagnoses, ancillary testing, and interpretation. Pitfalls are reviewed and discussed in each section. It is important for both surgical pathologists and cytopathologists to be familiar with these entities and their cytologic and histologic features that may be helpful in reaching a diagnosis.

Gastric Plexiform Fibromyxoma: A Great Mimic of Gastrointestinal Stromal Tumor (GIST) and Diagnostic Pitfalls.

Through a multicenter study, we collected seven cases of gastric plexiform fibromyxoma including four females and three males, 21 to 79 y old (46.1 ± 10.1). All cases showed a unilocular lesion measuring 0.3 to 17 cm (5.3 ± 2.4), arising from antrum (5/7) or body (2/7). Six of the seven cases had intraoperative frozen sections and/or endoscopic ultrasound fine needle aspiration (EUS-FNA), and all of them were preoperatively or intraoperatively diagnosed as gastrointestinal stromal tumor (GIST). EUS-FNA material showed markedly elongated spindle cells with streaming oval to elongated nuclei with rounded ends. Histologically, the tumors exhibited a plexiform growth pattern and were composed of a rich myxoid stroma and cytologically bland uniform spindle cells without mitotic figures, with the exception of one case which displayed nuclear pleomorphism and increased mitosis. Immunostains showed the tumor cells to be focally positive for SMA (6/6), focally and weakly positive for desmin (3/6) and caldesmon (2/3), negative for CD117 (0/7), CD34 (0/7), DOG1 (0/4), and S100 (0/5). No mutations were identified on Next-Generation Sequencing test, and no loss of SDHB immunoreactivity was identified in the tumor with nuclear pleomorphism. One case was treated with Gleevec because of the initial diagnosis of GIST. All patients had a follow-up for up to 11 y, with no tumor recurrence or metastasis reported. Our results suggest that gastric plexiform fibromyxoma is rare and may be underrecognized and misinterpreted as GIST during intraoperative frozen section or preoperative EUS-FNA diagnosis without immunostains leading to inappropriate treatment.

Sinonasal small round blue cell tumors: An approach to diagnosis.

The differential diagnosis for small round cell tumors in the sinonasal tract is diverse and as the body of literature documenting not only uncommon presentations but also availability of ancillary studies grows, so does the need for a reminder to take a conservative and thorough approach before rendering a diagnosis. Small tissue samples are particularly problematic, with limitations that include volume of tumor cells available for studies, lack of architectural context and a non-specific gross description. Incorporation of patient history and presentation, radiologic findings, clinical impression and concurrent studies often guide the course of studies performed by the pathologist. If these are non-specific, the pathologist may need to perform ancillary studies, including a broad panel of immunohistochemical stains and molecular studies. If tissue is limited, a precise classification may not be achievable. Although the expectation to render a definitive diagnosis is high, the pathologist should never feel compelled to go further with a diagnosis than the tissue itself supports.

Molecular Assays in Cytopathology for Thyroid Cancer.

BACKGROUND: Despite lack of adequate, validated, independently performed clinical studies, several molecular tests are commercially available on the market and are being used on indeterminate thyroid nodules to guide patient-care decisions. METHODS: We summarize the current evidence on the role and limitations of molecular tests used in combination with thyroid cytopathology to refine the presurgical diagnosis of thyroid nodules. RESULTS: The clinical performance of molecular tests depends on the pretest risk of malignancy within the specific cytological group being assessed. This risk is variable and should be assessed at each institution to optimize the selection of the molecular test and the interpretation of its results. Next-generation sequencing has increased the sensitivity of oncogene panels while maintaining high specificity. Tests assessing the gene expression pattern have shown promising results, with high sensitivity but low specificity. The impacts of molecular markers on clinical practice remains in flux and their effect on health care costs remains poorly understood. CONCLUSIONS: Further large, independent, confirmatory, clinical validation studies and real-world, cost-effectiveness studies are necessary before the widespread adoption of these tests can be endorsed as standard of care.

Understanding and Overcoming the Pitfalls in Cytopathological Diagnosis of Hyalinizing Trabecular Tumor of Thyroid.

Hyalinizing trabecular tumor (HTT), a rare low-malignant-potential thyroid neoplasm, is usually treated with conservative surgery. However, cytomorphological diagnosis of HTT is challenging due to the significant overlap of nuclear features with more common malignancies such as papillary thyroid carcinoma (PTC), which usually requires more radical surgical intervention. To avoid unnecessary overtreatment, a precise diagnosis of HTT is therefore essential. Advances in molecular diagnostics provide the opportunity to overcome the limitations of cytological analysis. We present a case of HTT in a 71-year-old male who was initially suspected to be PTC based on cytopathology. However, further molecular analysis revealed PAX8::GLIS3 gene fusion, classifying the lesion as HTT and preventing surgical overtreatment. We discuss the diagnostic pitfall of cytopathology in HTT and suggest using emerging molecular genetic tools to avoid it.

Altruism in terminal cancer patients and rapid tissue donation program: does the theory apply?

Rapid tissue donation (RTD) is an advancing oncology research procedure for collecting tumors, metastases, and unaffected tissue 2-6 h after death. Researchers can better determine rates of progression, response to treatment, and polymorphic differences among patients. Cancer patients may inquire about posthumous body donation for research to offer a personal contribution to research; however, there are barriers to recruiting for an RTD program. Physicians must reassure the patient that their treatment options and quality of care will not be compromised due to participating in RTD. In this commentary we discuss how theories of altruism may explain cancer patients' desire to participate in an RTD program, the ethical concerns of health care professionals and patients and the use of altruism as a recruitment strategy. We offer recommendations for examining the cultural and ethical climate of the institution prior to initiating such a program such as examining the relationship of healthcare professionals and patients, identifying ethical concerns, and examining ways to promote acceptance and buy-in across professionals, patients, and families.

Diagnostic difficulties in non-tuberculous mycobacterial infection in lung transplant recipients.

Despite antimicrobial prophylaxis, 34% to 59% of lung transplant recipients experience severe life-threatening opportunistic infections, sometimes caused by Nontuberculous Mycobacteria (NTM) and Nocardia. Although differentiating these infections is of utmost importance for effective treatment, it can be challenging as they share morphological and growth characteristics. Therefore, culture remains the gold standard for laboratory confirmation. With the aid of novel molecular methods performed on the cultured organisms, diagnosis may be accomplished rapidly and precisely. We present a case of a lung transplant recipient with a pulmonary infection where long, thin, beaded, branching filamentous organisms were seen with Acid-Fast Bacilli (AFB) and Modified Gomori's Methenamine Silver (GMS) stains in bronchoalveolar lavage sample. Cytological characteristics led to the suspicion of a Nocardia species infection. However, culture and the PCR-restriction fragment length polymorphism analysis (PRA) identified M. fortuitum. Additionally, antibiotic resistance was detected, which aided in choosing the appropriate treatment. Therefore, to overcome such diagnostic difficulties to differentiate NTM and Nocardia, a multidisciplinary approach including culture, molecular methods, and cytology is needed to enhance clinical outcomes.

A 65-Year-Old Woman With Intractable Cough.

CASE PRESENTATION: A 65-year-old woman was referred for a second opinion regarding a 7-month history of a persistent, progressive, nonproductive cough. Her cough occurred several times a minute, causing a significant impact on her daily activities. She denied fever, chills, weight loss, chest pain, wheezing, symptoms of gastroesophageal reflux, or postnasal drip. She was a never smoker with no history of asthma, allergies, sinus disease, or dermatitis. She had never taken an angiotensin-converting enzyme inhibitor. Her medical history included rheumatoid arthritis, for which she was treated with methotrexate for 3 years. She denied any occupational or environmental exposures. She was previously treated with a short-acting ß-agonist, inhaled corticosteroid/long-acting ß-agonist, montelukast, nasal steroids, a proton pump inhibitor, gabapentin, and azithromycin without relief. She also received codeine, which provided mild relief.

Leiomyosarcoma of the Nasal Cavity and Paranasal Sinuses: A Case Report and Comprehensive Review of the Literature.

Sinonasal leiomyosarcoma (LMS) is a rare and aggressive mesenchymal tumor with smooth muscle differentiation. The sinonasal tract is an unusual primary site for LMS, as scant smooth muscle exists in this location, with only 75 cases reported in the English literature including the case presented herein. Sinonasal LMS is considered an aggressive head and neck tumor with significant potential for recurrence and metastasis. Since recurrence is high and the potential for late metastasis exists, lifelong follow-up in these patients would be beneficial, especially among those with previous history of RB.

Sinonasal IgG4-related sclerosing disease: A rare entity and challenging diagnosis.

Objectives: To describe the rare presentation, imaging and histological findings, and treatments in patients with IgG4-related disease (IgG4-RD) and diagnostic pitfalls and difficulties. Methods: Cases of sinonasal IgG4-RD were retrieved, and clinicopathological features were reviewed. Results: Seven cases of sinonasal IgG4-RD were identified over an 11-year period, including four males and three females, with an age range of 19-66 years (median 58 years). Patients presented with symptoms related to the mass effect of the lesions or the destructive nature of the disease including fullness, swelling, obstruction, and pain. Serum IgG and IgG4 levels, IgG/IgG4 ratios, storiform fibrosis, obliterative phlebitis, and plasma cell infiltration were seen in varying proportions. Bony erosion and tissue inflammation were present in some cases. Conclusion: Sinonasal IgG4-RD is exceedingly rare among other IgG4-RD and varied in its clinical presentation thus posing as a clinically difficult disease to diagnosis. Proper clinical, pathological, and immunohistopathological analysis is required for accurate diagnosis. Such disease should be considered in all cases of similar presentation to those in this study.Level of Evidence: 4.

Rapid SARS-CoV-2 diagnosis using disposable strips and a metal-oxide-semiconductor field-effect transistor platform.

The SARS-CoV-2 pandemic has had a significant impact worldwide. Currently, the most common detection methods for the virus are polymerase chain reaction (PCR) and lateral flow tests. PCR takes more than an hour to obtain the results and lateral flow tests have difficulty with detecting the virus at low concentrations. In this study, 60 clinical human saliva samples, which included 30 positive and 30 negative samples confirmed with RT-PCR, were screened for COVID-19 using disposable glucose biosensor strips and a reusable printed circuit board. The disposable strips were gold plated and functionalized to immobilize antibodies on the gold film. After functionalization, the strips were connected to the gate electrode of a metal-oxide-semiconductor field-effect transistor on the printed circuit board to amplify the test signals. A synchronous double-pulsed bias voltage was applied to the drain of the transistor and strips. The resulting change in drain waveforms was converted to digital readings. The RT-PCR-confirmed saliva samples were tested again using quantitative PCR (RT-qPCR) to determine cycling threshold (Ct) values. Ct values up to 45 refer to the number of amplification cycles needed to detect the presence of the virus. These PCR results were compared with digital readings from the sensor to better evaluate the sensor technology. The results indicate that the samples with a range of Ct values from 17.8 to 35 can be differentiated, which highlights the increased sensitivity of this sensor technology. This research exhibits the potential of this biosensor technology to be further developed into a cost-effective, point-of-care, and portable rapid detection method for SARS-CoV-2.

The CRTC1-MAML2 fusion is the major oncogenic driver in mucoepidermoid carcinoma.

No effective systemic treatment is available for patients with unresectable, recurrent, or metastatic mucoepidermoid carcinoma (MEC), the most common salivary gland malignancy. MEC is frequently associated with a t(11;19)(q14-21;p12-13) translocation that creates a CRTC1-MAML2 fusion gene. The CRTC1-MAML2 fusion exhibited transforming activity in vitro; however, whether it serves as an oncogenic driver for MEC establishment and maintenance in vivo remains unknown. Here, we show that doxycycline-induced CRTC1-MAML2 knockdown blocked the growth of established MEC xenografts, validating CRTC1-MAML2 as a therapeutic target. We further generated a conditional transgenic mouse model and observed that Cre-induced CRTC1-MAML2 expression caused 100% penetrant formation of salivary gland tumors resembling histological and molecular characteristics of human MEC. Molecular analysis of MEC tumors revealed altered p16-CDK4/6-RB pathway activity as a potential cooperating event in promoting CRTC1-MAML2-induced tumorigenesis. Cotargeting of aberrant p16-CDK4/6-RB signaling and CRTC1-MAML2 fusion-activated AREG/EGFR signaling with the respective CDK4/6 inhibitor Palbociclib and EGFR inhibitor Erlotinib produced enhanced antitumor responses in vitro and in vivo. Collectively, this study provides direct evidence for CRTC1-MAML2 as a key driver for MEC development and maintenance and identifies a potentially novel combination therapy with FDA-approved EGFR and CDK4/6 inhibitors as a potential viable strategy for patients with MEC.

Proliferative Verrucous Leukoplakia: An Expert Consensus Guideline for Standardized Assessment and Reporting.

The many diverse terms used to describe the wide spectrum of changes seen in proliferative verrucous leukoplakia (PVL) have resulted in disparate clinical management. The objective of this study was to produce an expert consensus guideline for standardized assessment and reporting by pathologists diagnosing PVL related lesions. 299 biopsies from 84 PVL patients from six institutions were selected from patients who had multifocal oral leukoplakic lesions identified over several years (a minimum follow-up period of 36 months). The lesions demonstrated the spectrum of histologic features described in PVL, and in some cases, patients developed oral cavity squamous cell carcinoma (SCC). An expert working group of oral and maxillofacial and head and neck pathologists reviewed microscopic features in a rigorous fashion, in combination with review of clinical photographs when available. The working group then selected 43 single slide biopsy cases for whole slide digital imaging (WSI) review by members of the consensus conference. The digital images were then reviewed in two surveys separated by a washout period of at least 90 days. Five non-PVL histologic mimics were included as controls. Cases were re-evaluated during a consensus conference with 19 members reporting on the cases. The best inter-observer diagnostic agreement relative to PVL lesions were classified as "corrugated ortho(para)hyperkeratotic lesion, not reactive" and "SCC" (chi-square p = 0.015). There was less than moderate agreement (kappa < 0.60) for lesions in the "Bulky hyperkeratotic epithelial proliferation, not reactive" category. There was ≥ moderate agreement (> 0.41 kappa) for 35 of 48 cases. This expert consensus guideline has been developed with support and endorsement from the leadership of the American Academy of Oral and Maxillofacial Pathology and the North American Society of Head and Neck Pathologists to recommend the use of standardized histopathologic criteria and descriptive terminology to indicate three categories of lesions within PVL: (1) "corrugated ortho(para)hyperkeratotic lesion, not reactive;" (2) "bulky hyperkeratotic epithelial proliferation, not reactive;" and (3) "suspicious for," or "squamous cell carcinoma." Classification of PVL lesions based on a combination of clinical findings and these histologic descriptive categories is encouraged in order to standardize reporting, aid in future research and potentially guide clinical management.

Inter-observer Variability in the Diagnosis of Proliferative Verrucous Leukoplakia: Clinical Implications for Oral and Maxillofacial Surgeon Understanding: A Collaborative Pilot Study.

The use of diverse terminology may lead to inconsistent diagnosis and subsequent mistreatment of lesions within the proliferative verrucous leukoplakia (PVL) spectrum. The objectives of this study were: (a) to measure inter-observer variability between a variety of pathologists diagnosing PVL lesions; and (b) to evaluate the impact of diverse terminologies on understanding, interpretation, and subsequent treatment planning by oral and maxillofacial surgeons (OMFS). Six oral pathologists (OP) and six head and neck pathologists (HNP) reviewed 40 digitally scanned slides of PVL-type lesions. Inter-observer agreement on diagnoses was evaluated by Fleiss' kappa analysis. The most commonly used diagnostic terminologies were sent to ten OMFS to evaluate their resulting interpretations and potential follow-up treatment approaches. The overall means of the surgeons' responses were compared by Student t test. There was poor inter-observer agreement between pathologists on the diagnosis of PVL lesions (κ = 0.270), although there was good agreement (κ = 0.650) when diagnosing frankly malignant lesions. The lowest agreement was in diagnosing verrucous hyperplasia (VH) with/without dysplasia, atypical epithelial proliferation (AEP), and verrucous carcinoma (VC). The OMFS showed the lowest agreement on identical categories of non-malignant diagnoses, specifically VH and AEP. This study demonstrates a lack of standardized terminology and diagnostic criteria for the spectrum of PVL lesions. We recommend adopting standardized criteria and terminology, proposed and established by an expert panel white paper, to assist pathologists and clinicians in uniformly diagnosing and managing PVL spectrum lesions.

Prospective evaluation of DNA mismatch repair protein expression in primary endometrial cancer.

OBJECTIVES: Immunohistochemical (IHC) stains for mismatch repair (MMR) proteins help screen for Lynch syndrome and identify microsatellite unstable colorectal carcinomas, providing prognostic information. It has been suggested that colorectal and endometrial carcinomas should be screened routinely for a MMR defect, but data are lacking on the practical application of this policy. We report our experience with the prospective evaluation of MMR protein expression in endometrial cancer. METHODS: All cases of primary endometrial cancer at a single institution regardless of age, family history or histologic features were prospectively stained for the MMR proteins MLH1, MSH2, MSH6 and PMS2. Clinical and pathologic correlates were collected from the medical record. RESULTS: A total of 140 endometrial cancer cases were studied. Over 90% of cases were of endometrioid histology. 119 patients had stage I/II disease, and 21 stage III/IV. Nineteen percent of patients were < age 50. Overall, there was loss of 1 or more MMR proteins in 30 patients (21%), including MLH1 and PMS2 in 24, MSH2 and MSH6 in 4, and MSH6 in 2 patients. None of the patients met clinical criteria for Lynch syndrome. However, using MMR protein expression, age and family history, 11% of patients were referred for genetic counseling. Of these patients, three (20%) scheduled an appointment: one canceled and two tested negative. CONCLUSIONS: Prospective staining for MMR proteins is feasible and allows for primary triage for the evaluation of Lynch syndrome in women with endometrial cancer. However, acceptance of genetic consultation and testing is surprisingly low and deserves further investigation.

Metastatic squamous cell carcinoma of the vulva to the lung confirmed with allelotyping.

A squamous-cell carcinoma (SCC) of the lung can be indistinguishable from metastatic SCC of gynecologic origin using common histopathologic techniques; however, establishing tumor origin can be clinically relevant. A patient with a Bartholin gland SCC was found to also have a pulmonary SCC, concerning for metastasis versus synchronous pulmonary primary. Hematoxylin and eosin and immunohistochemistry alone could not differentiate the lesion, and both tumors were human papilloma virus positive. Allelotyping for loss of heterozygosity established the pulmonary lesion as a rare event of vulvar pulmonary metastasis. The patient received palliative chemotherapy instead of curative treatment. Allelotyping for loss of heterozygosity is an effective tool to establish metastasis versus synchronous primary tumors in the presence of multiple lesions, helping to direct appropriate clinical management.

Multiple neuroenteric cysts at cerebello-pontine angle and foramen magnum: a case report and review of the literature.

Neuroenteric cysts of the CNS are uncommon benign lesions usually involving the spinal cord or rarely the cerebellopontine angle (CPA). We report a rare example of multiple neuroenteric cysts arising from the CPA and foramen magnum in a 20-year-old Caucasian woman who presented with headaches and dizziness. An MRI showed three separate lesions, not communicating with each other. The first lesion, within the left posterior lateral aspect of the CPA, demonstrated isointensity to gray matter on the fluid-attenuated inversion recovery (FLAIR) sequence. The second lesion, within the left foramen of Luschka at the level of the CPA, demonstrated hyperintensity on the T(2)-weighted sequences, intermediate to slightly hyperintense on T(1)-weighted sequence and hyperintensity on FLAIR. The third lesion, within the anterior/inferior left cerebellum at the level of the foramen magnum, followed CSF signal intensity throughout. None of the lesions demonstrated significant enhancement or bone lesions. Due to compression effect, surgery was performed. Pathologic examination revealed cystic structures lined by a single layer of non-ciliated well-differentiated mucin-producing columnar epithelium with eosinophilic to amphophilic cytoplasm and round to oval nuclei with focal pseudostratification. Immunohistochemical studies showed focal positivity for cytokeratin 7, CK 5/6, synaptophysin, and carcinoembryonic antigen (CEA), diffuse positive staining for epithelial membrane antigen (EMA) and BerEP4; and negative staining for cytokeratin 20, TTF-1, and GFAP. The MIB-1 proliferation index was < 1%. One-year follow-up has shown no recurrence. The differential diagnosis and a brief review of the literature are also presented.

An unusual case of chylothorax.

Pleural effusions occur in up to 70% of cases of malignant pleural mesothelioma (MPM). However, MPM rarely presents as a chylous effusion making it a diagnostic challenge. There are only six reported cases to date. Most cases of chylothoraces due to malignancy are due to lymphoma or bronchogenic carcinoma. We report an interesting case of MPM in a 75-year-old man who presented with recurrent chylothorax. He reported a four-month history of dyspnea and chest discomfort. Chest x-ray revealed a pleural effusion. Pleural fluid analysis was consistent with a chylothorax. Pleural fluid cytology was negative for malignancy. Computed tomography of the chest showed pleural calcifications, mediastinal adenopathy and left lung infiltrate. A fine needle aspirate of the lymph node and transbronchial biopsy specimen (TBBX) of the left lung infiltrate showed extensive reactive appearing mesothelial cells but none that appeared malignant. A video assisted thoracoscopic surgery was suggested but the patient declined. He returned 3 months later with recurrent pleural effusion and worsening airspace disease. Thoracentesis revealed a chylothorax again. Repeat analysis of TBBX and lymph node specimens showed extensive reactive appearing mesothelial cells. Due to concern for MPM, ancillary testing was obtained - loss of BRCA1 associated protein (BAP-1) and CDKN2A/p16 gene deletion. BAP1 staining was lost in the mesothelial cells supporting MPM. This case highlights a rare cause of MPM presenting as a chylous effusion. In a patient with an unknown etiology of chylothorax, MPM must remain in the differential.

Clinical performance of endobronchial ultrasound-guided transbronchial needle aspiration for assessing programmed death ligand-1 expression in nonsmall cell lung cancer.

BACKGROUND: Pembrolizumab was recently approved as a first line agent for metastatic NSCLC in patients with high programmed death-ligand 1 (PD-L1) expression. OBJECTIVES: Since a significant portion of lung cancer is diagnosed by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS TBNA); there is a need for PD-L1 testing in these specimens. However, to date few studies have evaluated performance of cytology specimens from EBUS TBNA for PD-L1 analysis. METHODS: Patients who had a diagnosis of NSCLC and in whom ancillary testing, i.e., next generation sequencing (NGS), anaplastic lymphoma kinase (ALK), and PD-L1 expression was requested between January and May 2017 were reviewed. RESULTS: Fifty of the 112 patients reviewed had the diagnosis of NSCLC for which ancillary testing was requested. Twelve patients (24%) had squamous cell carcinoma, twenty-seven had adenocarcinoma (54%), five had NSCLC favor adenocarcinoma (10%), two had NSCLC favor squamous cell cancer (4%), and four had NSCLC not otherwise specified (NOS) (8%). Size of the lymph nodes or lesion sampled ranged from 10 to 50 mm. Four (8%) patients had insufficient number of tumor cells in the cell block for any of the ancillary molecular testing. Forty-one (82%) patients had an adequate sample for all three ancillary tests. Satisfactory results for PD-L1 expression for all cases was 86% with 14 (32%) patients having levels of PD-L1 expression >50%. CONCLUSION: EBUS TBNA is effective and has a high proportion of satisfactory results for testing PD-L1 expression on tumor cells in addition to NGS and ALK FISH.

Impact of oncogene panel results on surgical management of cytologically indeterminate thyroid nodules.

BACKGROUND: The impact of oncogene panel results on the surgical management of indeterminate thyroid nodules (ITNs) is currently unknown. METHODS: Surgical management of 649 patients consecutively evaluated from October 2008 to April 2016 with a single nodule biopsied and indeterminate cytology (193 evaluated with and 456 without oncogene panels) was assessed and compared. Histological features of 629 consecutively resected ITNs (164 evaluated with and 465 without oncogene panels) were also characterized and compared. RESULTS: Oncogene panel evaluation was associated with higher rates of total thyroidectomy (45% vs 28%; P = .006), and central lymph node dissection (19% vs 12%; P = .03) without increasing the yield of malignancy or decreasing the rate of completion thyroidectomy. Most malignancies (64%), including 83% of those with driver mutation identified, were low-risk cancers for which a lobectomy could have been sufficient initial treatment. CONCLUSION: Current oncogene panel results seem insufficient to guide the surgical extent of solitary ITNs.