Chatzopoulos, Kyriakos

Soft tissue aneurysmal bone cysts (STABCs) are rare neoplasms histopathologically identical to aneurysmal bone cysts. These benign lesions are characterized by thin, peripheral ossification and no skeletal continuity. STABC may be difficult to distinguish from myositis ossificans (MO) and malignant entities from imaging and fine needle aspiration, due to rarity and overlapping features. We present a case of a STABC occurring in the paraspinal cervical muscles. The imaging, histopathology, molecular analysis, and treatment are discussed. Four other published cases of STABC of the head and neck are reviewed.

IntroductionAdamantinoma‐like Ewing sarcoma (ALES) is a rare aggressive malignancy occasionally diagnosed in the thyroid gland. ALES shows basaloid cytomorphology, expresses keratins, p63, p40, frequently CD99, and harbours the t(11;22) EWSR1::FLI1 translocation. There is debate on whether ALES resembles more sarcoma or carcinoma.MethodsWe performed RNA sequencing from two ALES cases and compared findings with skeletal Ewing's sarcomas and nonneoplastic thyroid tissue. ALES was investigated by in situ hybridization (ISH) for high‐risk human papillomavirus (HPV) DNA and immunohistochemistry for the following antigens: keratin 7, keratin 20, keratin 5, keratins (AE1/AE3 and CAM5.2), CD45, CD20, CD5, CD99, chromogranin, synaptophysin, calcitonin, thyroglobulin, PAX8, TTF1, S100, p40, p63, p16, NUT, desmin, ER, FLI1, INI1, and myogenin.ResultsAn uncommon EWSR1::FLI transcript with retained EWSR1 exon 8 was detected in both ALES cases. Regulators of EWSR1::FLI1 splicing (HNRNPH1, SUPT6H, SF3B1) necessary for production of a functional fusion oncoprotein, as well as 53 genes (including TNNT1, NKX2.2) activated downstream to the EWSR1::FLI1 cascade, were overexpressed. Eighty‐six genes were uniquely overexpressed in ALES, most of which were related to squamous differentiation. Immunohistochemically, ALES strongly expressed keratins 5, AE1/AE3 and CAM5.2, p63, p40, p16, and focally CD99. INI1 was retained. The remaining immunostains and HPV DNA ISH were negative.ConclusionComparative transcriptomic profiling reveals overlapping features of ALES with skeletal Ewing's sarcoma and an epithelial carcinoma, as evidenced by immunohistochemical expression of keratin 5, p63, p40, CD99, the transcriptome profile, and detection of EWSR1::FLI1 fusion transcript by RNA sequencing.

Abstract Objectives To investigate the clinicopathologic and radiologic features of pulmonary hamartomas (PHs) with uncommon clinical presentation. Methods A retrospective clinicopathologic and radiologic review was performed for patients diagnosed (1999-2019) with multiple hamartomas, lesions arising adjacent to a coexisting pulmonary malignancy, and tumors with predominantly extrapulmonary localization. Results Of 979 patients diagnosed with PHs, 6 (0.6%) had multiple hamartomas, 4 (0.4%) had hamartomas adjacent to lung adenocarcinoma, and 2 (0.2%) had large mediastinal masses. Patients with multiple lesions had a median age of 65 years and mean tumor size of 0.9 cm; 1 patient had 3 hamartomas, and 5 patients had 2. Lesions next to adenocarcinomas had a mean size of 1.4 cm, and affected patients had a median age of 69 years. Predominantly mediastinal PHs, diagnosed in a 63-year-old woman and a 68-year-old man, measured 4.1 to 6 cm and were connected to the lung. All lesions were solid on imaging with absence of definitive fat or calcification, concerning for granuloma or malignancy. All cases had typical histology of PH, although one of the mediastinal tumors had an unusual amount of epithelial hyperplasia. Conclusions PHs can be clinically and radiologically challenging to diagnose. Histopathologic examination of biopsies and resection specimens is diagnostically crucial in this setting.

Objectives: LMNA-associated familial partial lipodystrophy (FPLD) is a rare autosomal dominant A-type laminopathy characterized by variable loss and redistribution of subcutaneous adipose tissue, dyslipidemia, and insulin resistance. Though A-type lamins play a key role in nuclear membrane structure and regulation of cell proliferation, an association between cancer and LMNA-associated FPLD has not been reported. Methods and Results: This report outlines the case of two biological sisters with LMNA-associated FPLD who developed hypopharyngeal squamous cell carcinoma in the absence of any other risk factors for head and neck cancer. Conclusion: These observations prompt further investigation into the potential role of A-type lamins in the development and progression of head and neck cancers.

AbstractBackgroundBuccal squamous cell carcinoma (SCC) is a locoregionally aggressive malignancy, representing a small subset of oral cancers in North America. We investigated the prognostic value of several clinicopathologic factors in a cohort of patients diagnosed with buccal SCC.MethodsBetween years 1992 and 2017, 52 patients were diagnosed with conventional buccal SCC. Archival surgical pathology material was retrospectively reviewed for reportable findings according to the latest reporting guidelines published by the College of American Pathologists. Clinical data were obtained through chart review.ResultsThe majority of patients were of older age, current or past smokers, and without specific gender predilection. Most presented at a clinically advanced stage and were treated with surgery alone, or surgery followed by adjuvant radiotherapy. The tumor recurred in about 40% of patients, and almost half of the patients died from the disease by the end of the follow‐up period. The worst pattern of invasion (WPOI) was associated with greater depth of invasion (DOI) (P = .031) and perineural invasion (P < .001). In univariate analyses, older age (P = .004), positive nodal status (P = .047), lymphovascular invasion (P = .012), perineural invasion (P = .05), and WPOI‐5 (P = .015) were adverse predictors of 5‐year overall survival (OS). In multivariate analysis, older age (P = .011), WPOI‐5 (P < .001), and perineural invasion (P = .001) remained statistically significant independent prognosticators of worse 5‐year OS.ConclusionsOlder age, WPOI‐5, and perineural invasion are significant prognosticators of worse OS. WPOI is associated with DOI, a finding which may have important implications for the pathogenesis and biologic behavior of the disease.

BackgroundLymphatic dysfunction is hypothesized to be an underlying factor in the pathophysiology of yellow nail syndrome (YNS) (yellow nails, lymphedema, pleural effusions, and frequently chronic rhinosinusitis [CRS]). It is unclear why some YNS patients develop CRS. We quantified lymphatic and total vasculature of sinonasal mucosa in YNS patients and compared it to controls from CRS patients with (CRSwNP) or without polyps (CRSsNP).MethodsImmunohistochemistry was performed on archival sinonasal mucosal samples from 5 patients with YNS and 14 controls with antibodies against podoplanin and CD31, markers of lymphatics. Morphometric assessment was performed on digital images using ImageJ software.ResultsIn YNS, the number of lymphatics/mm2 ranged from 7 to 18/mm2 (controls: 6 to 43/mm2, p = 0.343), with a mean perimeter between 92 and 201 µm (controls: 42 to 280 µm, p = 0.482). Total vasculature density was higher than lymphatics, ranging between 189 and 1159 vessels/mm2, average 669 (controls: 139 to 1467/mm2, average 503, p = 0.257) with smaller average perimeter, 40 to 117 µm, mean 64.8 µm (controls: 42 to 92 µm, mean 65.3 µm, p = 0.965). Lymphatics constituted only a small fragment of the total vasculature, ranging from 1.15% to 4.76%, average 2.34% (controls: 0.81% to 10.58%, average 4.88%, p = 0.156). CRSwNP patients had significantly higher lymphatic density (p = 0.011) and ratio of lymphatics to total vasculature (p = 0.045) than patients with YNS or CRSsNP.ConclusionThis is the first histological analysis of sinus mucosa in patients with YNS. Vascular type, density, size, and distribution in the sinonasal mucosa of YNS patients are not statistically significantly different from those of the CRSsNP group. Lymphatic density and ratio to total vasculature is higher in CRSwNP patients.

Abstract Objectives Salivary duct carcinoma is a rare high-grade salivary gland tumor, sharing common features with invasive ductal carcinoma of the breast—particularly apocrine type. Increased density of tumor-infiltrating lymphocytes (TILs) is a favorable prognostic factor in many solid tumors and has been correlated with elevated expression of programmed death-ligand 1 (PD-L1), a targetable molecule. We investigated the prognostic role of TILs and PD-L1 expression in salivary duct carcinoma. Methods Clinical records and archived surgical pathology material were evaluated from 28 patients with a diagnosis of salivary duct carcinoma at Mayo Clinic Rochester (between 1961 and 2007). TILs were evaluated on hematoxylin and eosin–stained slides and reported as continuous variables. Immunohistochemistry for PD-L1 (clone 22C3) was performed on unstained slides and evaluated using the Combined Positive Score (CPS). Fisher’s exact test was used to assess frequency distribution differences. Log-rank test and Cox proportional hazards model were used to assess the impact of the variables on survival. Results Twenty-eight patients had salivary duct carcinoma (age range 35-87, mean 61), and follow-up averaged 60 months (range 6-252 months). At the end of the follow-up period, 22 patients (79%) had died of salivary duct carcinoma, while remaining patients were alive (4.14%) or had died of other causes (2.7%). For the entire follow-up period, levels of TILs of 40% or more were associated with favorable overall survival (log-rank test, P = .01) and were predictors of better survival in univariate analysis (hazard ratio: 0.18, P = .02). PD-L1 expression was not significantly different between the high and low TIL groups (Fisher’s exact test, P = .67). Survival analysis regarding PD-L1 expression did not yield statistically significant results (log-rank test, P = .74; hazard ratio: 0.87, P = .74). Conclusion High TIL levels, but not PD-L1 expression as determined using the CPS, predict better survival in patients with salivary duct carcinoma.