Pulmonary Artery Angiomatoid Fibrous Histiocytoma Mimicking a Large Pulmonary Embolism.

ABSTRACT: A 39-year-old man presented with progressive dyspnea and lower extremity edema. Doppler ultrasound demonstrated bilateral leg partially occluded venous thromboses. A V/Q scan revealed a mismatched perfusion defect involving the entire right middle and lower lobes. Subsequent CT pulmonary angiogram revealed a mass lesion occluding the right interlobar pulmonary artery. Endobronchial ultrasound-guided fine-needle aspiration of the mass was concerning for neoplasm. 18 F-FDG PET/CT demonstrated marked hypermetabolism of the mass lesion. Patient underwent transmediastinal right pneumonectomy with histopathologic diagnosis of pulmonary artery angiomatoid fibrous histiocytoma, a rare etiology mimicking large pulmonary artery embolism.

Cytomorphology of NUTM1-rearranged sarcoma involving pleural fluid.

We describe an exceedingly rare cytology case of a NUTM1-rearranged sarcoma involving pleural fluid. A 48-year-old female presented with progressive abdominal pain. Computed tomography (CT) scan of the abdomen revealed a 5.6 cm soft tissue mass in the right hemi-abdomen. Needle core biopsy of the mass showed a small round cell tumor. Extensive work-up including next generation sequencing (NGS) demonstrated a NUTM1:MXI1 rearranged sarcoma. The patient was first treated with ifosfamide, carboplatin, and etoposide (ICE) chemotherapy. She responded initially and then progressed with multiple masses in the abdomen and pleural effusion. The cytology of the pleural effusion showed clusters and single small round blue cells. Some of them displayed rhabdoid morphology. Immunostains of NUT antibody on cell block demonstrated strong positivity of NUT. NUTM1-rearranged sarcoma is an emerging class of mesenchymal neoplasm and the cytomorphology of this neoplasm in liquid-based cytology (LBC) is yet to be described. We herein reported the first cytology case of NUTM1-rearranged sarcoma in pleural fluid.

Improving Oncology-Pathology Collaboration in Resource-Limited Settings: An American Society of Clinical Oncology/College of American Pathologists Initiative.

Accurate pathologic evaluation is essential for proper diagnosis and treatment of patients with cancer. ASCO and the College of American Pathologists have successfully collaborated over the last 15 years to improve collaboration between clinical oncologists and pathologists and to standardize pathologic assay techniques. Cancer is an increasingly recognized societal burden in low- and middle-income countries. In 2015, ASCO and the College of American Pathologists implemented an initiative to identify countries that could benefit from peer insights by jointly convening an international workshop among members of both organizations and pathologists and clinical oncologists from Haiti, Honduras, Vietnam, and Uganda. Honduras was chosen as a pilot site, and representatives of ASCO, the College of American Pathologists, and the Honduras pathology and clinical oncology communities have identified areas in which collaboration might be productive. Multiple barriers, including high poverty levels, poor cancer awareness educational programs, lack of human resources, and delayed diagnosis and treatment, have resulted in a higher cancer mortality rate in Honduras compared with high/moderate-income countries and are shared by other low-income countries. ASCO and the College of American Pathologists member faculty supported a symposium led by Honduras colleagues for interested Honduran pathologists and oncologists. The Honduran communities are now working to establish national resource-appropriate guidelines for both pathology and clinical oncology. Taken together, these efforts indicate that barriers to meet the needs of the clinical oncologists in a low-income country such as Honduras are challenging but not insurmountable.

Transcriptomic and Immunophenotypic Characterization of Tumor Immune Microenvironment in Squamous Cell Carcinoma of the Oral Tongue.

The tumor immune microenvironment of oral tongue squamous cell carcinoma may be accountable for differences in clinical behavior, particularly between different age groups. We performed RNA expression profiling and evaluated tumor infiltrating lymphocytes (TILs) and their T-cell subsets in order to assess the functional status of oral tongue squamous cell carcinoma tumor microenvironment and detect potentially clinically useful associations. Archival surgical pathology material from sixteen oral tongue squamous cell carcinoma patients was microscopically evaluated for TIL densities. RNA was extracted from macrodissected whole tumor sections and normal controls and RNA expression profiling was performed by the NanoString PanCancer IO 360 Gene Expression Panel. Immunostains for CD4, CD8 and FOXP3 were evaluated manually and by digital image analysis. Oral tongue squamous cell carcinomas had increased TIL densities, numerically dominated by CD4 + T cells, followed by CD8 + and FOXP3 + T cells. RNA expression profiling of tumors versus normal controls showed tumor signature upregulation in inhibitory immune signaling (CTLA4, TIGIT and PD-L2), followed by inhibitory tumor mechanisms (IDO1, TGF-ß, B7-H3 and PD-L1). Patients older than 44 years showed a tumor microenvironment with increased Tregs and CTLA4 expression. Immunohistochemically assessed CD8% correlated well with molecular signatures related to CD8 + cytotoxic T-cell functions. FOXP3% correlated significantly with CTLA4 upregulation. CTLA4 molecular signature could be predicted by FOXP3% assessed by immunohistochemistry (R2 = 0.619, p = 0.026). Oral tongue squamous cell carcinoma hosts a complex inhibitory immune microenvironment, partially reflected in immunohistochemically quantified CD8 + and FOXP3 + T-cell subsets. Immunohistochemistry can be a useful screening tool for detecting tumors with upregulated expression of the targetable molecule CTLA4.

Cytologic grading of primary malignant salivary gland tumors: A blinded review by an international panel.

BACKGROUND: Fine needle aspiration (FNA) is commonly used for the preoperative evaluation of salivary gland tumors. Tumor grade is a key factor influencing clinical management of salivary gland carcinomas (SGCs). To assess the ability to grade nonbasaloid SGCs in FNA specimens, an international panel of cytopathologists convened to review and score SGC cases. METHODS: The study cohort included 61 cases of primary SGC from the pathology archives of 3 tertiary medical centers. Cases from 2005 to 2016 were selected, scanned, and digitized. Nineteen cytopathologists blinded to the histologic diagnosis reviewed the digitized cytology slides and graded them as low, high, or indeterminate. The panelists' results were then compared to the tumor grades based on histopathologic examination of the corresponding resection specimens. RESULTS: All but 2 of the 19 (89.5%) expert panelists review more than 20 salivary gland FNAs per year; 16 (84.2%) of the panelists work at academic medical centers, and 13 (68.4%) have more than 10 years' experience. Participants had an overall accuracy of 89.4% in the grading of SGC cases, with 90.2% and 88.3% for low- and high-grade SGC, respectively. Acinic cell carcinoma and mucoepidermoid carcinoma had the highest degree of accuracy, while epithelial-myoepithelial carcinoma and salivary duct carcinoma had the lowest degree of accuracy. As expected, the intermediate-grade SGC cases showed the greatest variability (high-grade, 42.1%; low-grade, 37.5%, indeterminate, 20.4%). CONCLUSION: This study confirms the high accuracy of cytomorphologic grading of primary SGC by FNA as low- or high-grade. However, caution should be exercised when a grade cannot be confidently assigned.

Histopathological characteristics of surgical tissue from primary vs recurrent chronic rhinosinusitis with nasal polyposis patients.

OBJECTIVE: The histopathological characteristics of primary vs recurrent nasal polyps in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) have not been studied comprehensively. Identification of these features may be helpful for prognostication, postoperative management, and consideration of novel eosinophil-targeting biologic therapy. This study investigates the histopathological differences in primary vs recurrent CRSwNP tissue. METHODS: Patients undergoing endoscopic sinus surgery for CRSwNP were included if all 13 histopathological and mucin characteristics on a standardized report were available. Histopathology parameters were compared in surgical tissue and mucin from primary vs recurrent CRSwNP. RESULTS: Complete structured histopathology reports were available for 96 patients (39 primary polyps and 57 recurrent polyps). Compared to primary polyp tissue, recurrent CRSwNP mucin was significantly more likely to feature eosinophil aggregates (57.9% vs 35.9%; P = .047). Tissue eosinophilia (using a threshold >10 per high power field [HPF]) was not significantly different in primary and recurrent CRSwNP tissue. Other histopathologic parameters and clinical characteristics were similar. CONCLUSION: Eosinophil aggregates on histopathology are significantly more likely to be present in recurrent CRSwNP. In the limited series, tissue eosinophilia (>10 per HPF) was not significantly different in primary and recurrent CRSwNP. Therefore, in addition to the study of tissue eosinophilia levels, Rhinologic surgeons should also direct attention to CRSwNP mucin. Mucin eosinophilic aggregates are an independent marker of severe inflammation that is associated more likely with recurrent vs primary polyposis. Further study of this marker may help determine its role of choice of postoperative medical therapies, including anti-eosinophilic biologics. LEVEL OF EVIDENCE: 4.

Inflammatory cell predominance and patterns in chronic rhinosinusitis with and without nasal polyposis patients.

OBJECTIVES: There is interest in identifying chronic rhinosinusitis (CRS) endotypes that align pathophysiology with clinical observation and outcomes. CRS with polyps (CRSwNP) has classically been studied with reference to tissue eosinophilia, but the role of other cellular infiltrates remains uncharacterized. No particular tissue prognosticators have been described for CRS without nasal polyps (CRSsNP). Predominance of leukocytes seen in surgical tissue may be useful for differentiating CRS subtypes, severity of inflammation, and outcomes. METHODS: Structured histopathology reports were examined for 277 patients undergoing endoscopic sinus surgery for CRSwNP (n = 115), CRSsNP (n = 141), and recurrent acute rhinosinusitis (RARS, n = 21). Inflammatory predominance was examined for associations with nasal polyposis, asthma, allergic rhinitis, aspirin exacerbated respiratory disease (AERD), immune deficiency, preoperative Lund-Mackay score, and outcome (SNOT-22 score change). RESULTS: In order of frequency, the prevalence of predominant inflammatory patterns accounting for 93.5% of CRS patients were: lymphoplasmocytic (n = 111), lymphocytic (n = 74), eosinophilic (n = 50), and lymphoplasmocytic with eosinophilic (n = 24). Eosinophilic predominance was 97.4% specific for nasal polyps (95% confidence interval [CI], 93.4%-99.3%), although sensitivity was 43.4% (95% CI, 33.8%-53.4%). The absence of eosinophilic predominance was 100% sensitive for RARS (95% CI, 82.4%-100%), however specificity was 30.8% (95% CI 25.1%-37.1%). There were no significant differences in preoperative SNOT-22 scores or change postoperatively. CONCLUSIONS: Eosinophilic inflammatory predominance was predictive for nasal polyps and against RARS. Nevertheless, the majority of CRSwNP patients had a different inflammatory predominance, demonstrating heterogeneity in CRS, even among patients with nasal polyps. Symptomatic outcomes were not associated with inflammatory predominance through 12 months follow up. LEVEL OF EVIDENCE: 4.

Amyloid-Beta-Related Angiitis with Distinctive Neuro-Ophthalmologic Features.

Amyloid beta-related angiitis (ABRA) is a subtype of cerebral amyloid angiopathy-related inflammation, with distinctive pathology and prognosis compared with cerebral amyloid angiopathy (CAA). On a spectrum of increasing severity, ABRA is considered to be in-between the less aggressive inflammatory-CAA and the more severe primary central nervous system (CNS) angiitis. Whereas retinal pathological changes were described in subjects with primary or secondary CNS angiitis, and non-inflammatory CAA, bilateral posterior pole superficial and peripapillary retinal hemorrhages have not been reported as initial signs in patients with pathology-confirmed ABRA, accompanying neurological spells and characteristic neuroimaging findings.

Analysis of histologic follow-up and risk of malignancy for salivary gland neoplasm of uncertain malignant potential proposed by the Milan System for Reporting Salivary Gland Cytopathology.

BACKGROUND: The Milan System for Reporting Salivary Gland Cytopathology is a tiered classification scheme that includes 6 diagnostic categories. Neoplasm, which is 1 of the 6 proposed categories, consists of benign neoplasm and neoplasm of uncertain malignant potential (NUMP). NUMP is reserved for a salivary gland neoplasm without clear distinction between benign and malignant. The objective of this study was to assess the risk of malignancy (ROM) of NUMP. METHODS: A retrospective analysis was conducted on 656 salivary gland fine-needle aspiration specimens from 2010 to 2016. Cases that qualified as NUMP and had follow-up surgical resections were reviewed and reclassified into basaloid neoplasm (BN) and salivary gland neoplasm with predominant oncocytic cell (SGNOC) groups. The ROM for each group was calculated. Fifty-four salivary gland fine-needle aspirations of NUMP that had surgical follow-up were identified, which included 29 BNs and 25 SGNOCs. RESULTS: Histologic follow-up for the BN group identified 14 cellular pleomorphic adenomas, 5 basal cell adenomas, 2 benign cystadenomas, 3 adenoid cystic carcinomas, 3 epithelial and myoepithelial carcinomas, 1 basal cell adenocarcinoma, and 1 myoepithelial carcinoma. Histologic follow-up for the SGNOC group revealed 7 nodular oncocytoses, 6 Warthin tumors, 5 oncocytomas, 1 sebaceous adenoma, 1 mucinous cystadenoma, 2 acinic cell carcinomas, 2 mucoepidermoid carcinomas, and 1 mammary analog secretory carcinoma. The ROM was calculated at 24.1% for the NUMP category overall (27.6% for BNs and 20.0% for SGNOCs). CONCLUSIONS: The ROM of the SGNOC group is similar to that of the BN group but lower than the ROM (35%) proposed by the Milan system. Cancer Cytopathol 2018. © 2018 American Cancer Society.

Use of intraoperative negative margins reduces inverted papilloma recurrence.

BACKGROUND: Recurrence of inverted papilloma (IP) is a problem in 12-17% of tumors. Controversy exists regarding benefits of intraoperative frozen section histopathology (IFSH) for IP resection; however, to our knowledge, no study has specifically investigated this. IFSH for IP resection is the standard of care in our practice. We, therefore, reviewed our outcomes of using IFSH for IP resection. A secondary goal was to assess the reliability of IFSH. METHODS: Patients with IP who underwent surgical resection (2010-2016) with minimum 9-month follow-up were included. RESULTS: Twenty-two adults with IP met inclusion criteria. All underwent surgery via endoscopic techniques, supplemented by external ports in five patients. At the time of presentation, 36% IPs were recurrent tumors; 68% were graded as Krouse stage 3. Resection was conducted until "clear" (negative) mucosal margins were achieved on IFSH. In 6 (27%), a "positive" IFSH result dictated additional resection to clear margins. Final negative margins were achieved in all the patients. Both positive and negative predictive values for IFSH were 100% (concordance with final pathology results). Surveillance was performed every 1-6 months with nasal endoscopy by using imaging when necessary. No recurrences were noted (0%) at mean follow-up of 40 months (range, 10-73 months). CONCLUSIONS: Positive IFSH results led to increased resection in 27% of the patients, with a 0% recurrence rate in this cohort. The reliability of IFSH for IP is very high. No recurrence of IP was noted in any patient at a mean follow-up of 3.3 years. IFSH may help reduce recurrence rates of IP, but additional studies with longer follow-up are warranted.

Mosaic-pattern dedifferentiation in liposarcoma and chondrosarcoma: imaging features of an uncommon form of dedifferentiation.

The term "dedifferentiation" was classically used in sarcoma pathology to refer to tumors in which a high-grade, undifferentiated sarcoma, or a high-grade sarcoma showing heterologous differentiation, arises from a pre-existing neoplasm of borderline or low-grade malignancy. The best recognized examples of this include dedifferentiated liposarcoma, arising from atypical lipomatous tumor/well-differentiated liposarcoma, and dedifferentiated chondrosarcoma, arising from grade 1 hyaline chondrosarcoma of bone. In the overwhelming majority of cases, this dedifferentiated, high-grade sarcoma presents as a macroscopically visible mass, adjacent to and clearly distinct from the pre-existing low-grade lesion. It is less well appreciated that dedifferentiation may also occur in a so-called "mosaic pattern,' in which the high-grade component is intimately admixed with elements of the precursor lesion, forming only microscopically apparent foci. This mosaic or co-mingling pattern of dedifferentiation is also reflected in the MR imaging appearance. In contrast to the classic pattern of dedifferentiation in which there are two distinct juxtaposed masses with different signal intensities and enhancement patterns, such changes are not seen in mosaic dedifferentiation. The imaging features of this pattern of dedifferentiation have not been described. In this report we describe the imaging features of two patients with mosaic pattern dedifferentiation, one with liposarcoma and one with chondrosarcoma. In both cases the precursor lesion was correctly diagnosed by pre-biopsy imaging, but the presence of high-grade sarcoma was not recognized.

The largest CAP-certified Chinese reference laboratory experience with the Bethesda system for reporting thyroid cytopathology: correlation with histologic and BRAF data.

INTRODUCTION: Thyroid fine needle aspiration biopsy (FNAB) has not been widely used in most areas of China. We investigated a large cohort of thyroid FNAB using the Bethesda system for reporting thyroid cytopathology (TBSRTC) from the largest College of American Pathology (CAP)-certified reference laboratory in China. MATERIALS AND METHODS: Patients with thyroid FNAB between 2014 and 2016 from Guangzhou Kingmed Diagnostics were retrospectively retrieved and the histologic follow-up results and BRAF results were collected and analyzed. RESULTS: A total of 7355 thyroid FNAB cases were identified. The average age of these patients was 48.03 years (range: 5-90 years). A total of 875 cases (11.9%) were reported as nondiagnostic, 4041 (54.9%) cases were benign, 736 cases (10.0%) were atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS), 53 cases (0.7%) were suspicious for follicular neoplasm, 615 cases (8.4%) were suspicious for malignancy, and 1035 cases (14.1%) were positive for malignancy. Histologic follow-up was available on 552 patients. Among 13 cases of AUS/FLUS, 8 (61.5%) had malignancy on histology; 195 (92.0%) of the suspicious for malignancy cases had malignancies on histology, and 320 (98.5%) of the positive for malignancy cases had malignancies on histology. BRAF analysis was performed on 578 cases. Sixty cases with BRAF data had histologic follow-up, all 4 benign cases had negative BRAF, one follicular adenoma had negative BRAF, and 37 of the 55 PTC cases (67.3%) had positive BRAF. BRAF mutation has a 100% positive predictive value of malignancy for the indeterminate thyroid FNABs. CONCLUSIONS: This is the largest cohort of thyroid FNA reported using TBSRTC in China and the data are helpful for better understanding the status of thyroid FNA in China.

Gender-specific differences in serum immunoglobulin E levels and prevalence of fungus in sinonasal tissue noted in patients with chronic rhinosinusitis who underwent endoscopic sinus surgery.

BACKGROUND: We previously presented that women with chronic rhinosinusitis (CRS) who elected endoscopic sinus surgery (ESS) have a higher symptom burden than men. Causes of these gender-based differences warranted further study. OBJECTIVES: To study gender differences in another cohort of adult patients with CRS who underwent ESS and to compare key histopathologic and serologic features Methods: Patients with CRS who underwent ESS (from 2011 to 2014) with structured histopathology reports on surgical samples were studied. The 13-item structured histopathology report detailed key metrics of inflammation and the presence of fungal elements. Clinical, 22-item Sino-Nasal Outcome Test (SNOT-22) score, Lund-Mackay computed tomography (CT) score, serologic (immunoglobulin E [IgE] level, absolute eosinophil count) and histopathologic data were compared between male and female patients by using statistical software. RESULTS: We studied 130 eligible subjects (mean age, 54.7 years; 49.2% women). Compared with the men, the women had significantly higher preoperative SNOT-22 scores (women, 48.7; men 38.0 [p = 0.004]) but similar CT scores. Serum IgE levels were significantly higher among women versus men (peak, 433.3 versus 190.8 kU/L [p = 0.03]; closest to surgery, 435.0 versus 190.8 kU/L [p = 0.03]). Tissue fungal elements were significantly more prevalent in women versus men (19.0 versus 5.2%; p = 0.02). Up to this point, the analysis was agnostic of clinical details of the subjects. Further analysis was conducted regarding clinical features. Allergic fungal sinusitis (AFS) was found significantly more commonly in the female versus male patients (21.9 versus 9.1%; p = 0.04). Women versus men had a higher prevalence of migraine (19.4 versus 4.6%; p = 0.01) or any primary headache disorders (23.0 versus 6.2%; p = 0.007). CONCLUSION: Women who underwent ESS for CRS had higher SNOT-22 symptom burden. Worsened symptomatology may be secondary to a higher prevalence of primary headache disorders in women. However, surgeons should also be aware that female patients with CRS who seek ESS may have a higher prevalence of severe disease endotypes (more tissue fungal elements, elevated serum IgE levels) and phenotypes.

Relapse Rates With Surgery Alone in Human Papillomavirus-Related Intermediate- and High-Risk Group Oropharynx Squamous Cell Cancer: A Multi-Institutional Review.

PURPOSE: To evaluate whether historic risk categories and indications for adjuvant therapy in the pre-human papillomavirus (HPV) and pre-transoral surgery (TOS) era were associated with clinically significant relapse rates in HPV+ oropharyngeal squamous cell cancer patients undergoing TOS. METHODS AND MATERIALS: A multi-institutional retrospective review of intermediate- and high-risk HPV+ oropharyngeal squamous cell cancer patients not receiving adjuvant therapy after TOS was performed. Perineural invasion, lymphovascular invasion, T3-T4, or ≥N2 disease were considered to be intermediate-risk factors, and extracapsular extension or positive margins were considered to be high-risk features, according to established risk categories. RESULTS: Median follow-up was 42.9 months. Among all 53 patients, the 3-year cumulative incidence of relapse was 26.0%. The 3-year cumulative incidence was 11.8% in the 37 intermediate-risk patients and 52.4% in the 16 high-risk patients. On univariate analysis only high-risk status was significantly associated with an increased risk of relapse (hazard ratio 3.9; P=.018). The salvage rate for relapse was 77%, with 10 of 13 patients undergoing salvage therapy. CONCLUSIONS: Risk category was associated with clinically significant relapse rates after TOS alone in HPV+ oropharyngeal cancer, comparable to historical data and traditional indications for adjuvant therapy for all oropharyngeal cancer.

Mucosal Sparing Radiation Therapy in Resected Oropharyngeal Cancer.

PURPOSE: To report the outcomes of patients with favorable risk oropharyngeal cancer that underwent adjuvant radiation therapy with omission of the primary site from the clinical target volume (CTV). MATERIAL/METHODS: A retrospective study of 40 patients treated with transoral surgery (TOS) followed by neck only radiation using intensity modulated radiation therapy (IMRT) with exclusion of the primary site. For all patients, a CTV of the primary surgical bed was contoured to obtain the estimated incidental dose to the primary site. RESULTS: Median follow-up was 51 months (range, 13-155 months). The median radiation therapy (RT) dose to the neck was 6000 cGy (range, 5400-6400 cGy). The mean incidental dose to the primary tonsillar site was 4320 cGy (SD ± 480 cGy) and to the primary base of tongue site was 4060 cGy (SD ± 420 cGy). There were no local failures and only 1 regional failure, resulting in 97.5% locoregional control rate at 4 years. Two patients developed distant metastases, without evidence of locoregional recurrence, for a 4-year overall survival rate of 97%. CONCLUSIONS: Our analysis suggests that mucosal sparing RT after TOS in favorable risk oropharyngeal cancer patients may provide comparable oncologic and improved functional outcomes compared to conventional treatment in selected patients.

Median Lingual Lymph Nodes: Prevalence on Imaging and Potential Implications for Oral Cavity Cancer Staging.

OBJECTIVE: This study sought to estimate the prevalence of median lingual lymph node (MLLN) metastases from oral cavity squamous cell carcinoma (OCSCC) and determine the frequency with which MLLNs can be identified with magnetic resonance imaging (MRI) in control subjects. METHODS: Pathology reports were used to identify patients with surgically treated OCSCC who underwent preoperative positron emission tomography-computed tomography to define the prevalence of MLLN metastases. As a control group, 500 consecutive face-neck MRIs from noncancer patients were reviewed for structures consistent with MLLNs. RESULTS: In the study group, 1 (0.95%) of 105 OCSCC cases demonstrated a single MLLN metastasis from a lateral tongue tumor (T4aN2c). The MLLN exceeded 1 cm in all planes and was abnormal in morphology. The frequency of suspected MLLNs in controls was 1.0%, with a maximum measurement of 0.9 cm. CONCLUSIONS: Median lingual lymph nodes are infrequently identified with MRI in controls, concordant with the low prevalence of metastases from OCSCC to this inconstant nodal group.

Pleural "drop metastases" 21 years after resection of a thymoma.

INTRODUCTION: We describe an unusual case of pleural drop metastases 21 years after complete resection of an encapsulated thymoma in a Southeast Asian patient with myasthenia gravis (MG). METHODS: This investigation includes a case report and brief review of the literature. RESULTS: The patient presented in 2015 with generalized weakness, fatigue, and shortness of breath, but no diplopia, ptosis, dysphagia, or dysarthria. Because these symptoms were atypical for an MG exacerbation, a de-novo work-up was performed. Chest computed tomography (CT) showed numerous pleural nodules ("drop metastases"), and CT-guided biopsy revealed metastatic thymoma. CONCLUSIONS: The average disease-free interval for thymoma ranges from 68 to 86 months. Pleural and mediastinal recurrence are more common than distant hematogenous recurrence. Adverse prognostic factors include an initial higher Masaoka stage, incomplete resection, older age, and pleural or pericardial involvement. Despite apparent complete resection of thymoma, clinicians should remain vigilant for recurrence for as long as 20 years after initial management. Long-term follow-up with radiologic surveillance is recommended. Muscle Nerve 56: 171-175, 2017.