SMARCB1 (INI1)-deficient carcinoma of the sinonasal tract is a rare and distinct entity characterized by the loss of INI1 immunostain expression. These tumors are morphologically diverse, with ...isolated cases of yolk sac differentiation reported. We report the first case of SMARCB1-deficient sinonasal carcinoma that demonstrated co-loss of SMARCA4 immunostain, and reduced SMARCA2 and ARID1A staining, with the entire tumor showing histological and immunohistochemical evidence of yolk sac differentiation. The clinical, histological, immunohistochemical and molecular features were discussed and compared against SMARCB1-deficient sinonasal carcinomas with yolk sac differentiation and SMARCA4-deficeint sinonasal carcinomas reported in the literature. With a highly aggressive clinical course leading to mortality two months after presentation, the behavior of this tumor appears to be more comparable to that of SMARCA4-deficient sinonasal carcinomas. A comprehensive immunopanel including SMARCB1, SMARCA4, SMARCA2 and ARID1A may be advisable for assessment and prognostication of SWI/SNF-deficient tumors.
Soft tissue sarcoma of the tongue represents a very rare head and neck cancer with connective tissue features, and the genetics underlying this rare cancer are largely unknown. There are less than 20 ...cases reported in the literature thus far. Here, we reported the first whole-exome characterization (>×200 depth) of an undifferentiated sarcoma of the tongue in a 31-year-old male. Even with a very good sequencing depth, only 19 nonsynonymous mutations were found, indicating a relatively low mutation rate of this rare cancer (lower than that of human papillomavirus (HPV)-positive head and neck cancer). Yet, among the few genes that are somatically mutated in this HPV-negative undifferentiated tongue sarcoma, a noticeable deleterious frameshift mutation (with a very high allele frequency of >93%) of a gene for DNA replication and repair, namely
(DNA polymerase delta interacting protein 2), and two recurrent mutations of the adipogenesis and adipocyte differentiation gene
(retinol saturase), were identified. Thus, somatic events likely affecting adipogenesis and differentiation, as well as potential stem mutations to
, may be implicated in the formation of this rare cancer. This identified somatic whole-exome sequencing profile appears to be distinct from that of other reported adult sarcomas from The Cancer Genome Atlas, suggesting a potential unique genetic profile for this rare sarcoma of the tongue. Interestingly, this low somatic mutation rate is unexpectedly found to be accompanied by multiple tumor protein p53 and
germline mutations of the patient's blood DNA. This may explain the very early age of onset of head and neck cancer, with likely hereditary predisposition. Our findings are, to our knowledge, the first to reveal a unique genetic profile of this very rare undifferentiated sarcoma of the tongue.
•Foxp3 inhibition decreases cell proliferation and migration, but increases cell apoptosis.•Foxp3 inhibition led to the elevation of PPARγ expression and activity.•Targeting Foxp3 in thyroid cancer ...cells is a novel therapeutic option for thyroid cancer.
Foxp3+ regulatory T cells (Tregs) in lymphocytes facilitate the thyroid tumor growth and invasion. Very limited information is available on Foxp3 expression in thyroid cancer cells and its function is totally unknown. This study demonstrated that Foxp3 expression was increased in thyroid cancer cells. Inhibition of Foxp3 decreased cell proliferation and migration, but increased apoptosis, suggesting a positive role of Foxp3 in cancer growth. Interestingly, Foxp3 inhibition enhanced PPARγ expression and activity. In addition, Foxp3 inhibition downregulated NF-κB subunit p65 and cyclin D1 but upregulated caspase-3 levels. These molecular changes are in line with Foxp3 shRNA-mediated alteration of cell functions. Collectively, our study demonstrates that thyroid cancer cells express a high level of functional Foxp3 and that the inhibition of the Foxp3 suppresses the proliferation and migration but promotes apoptosis, suggesting that targeting Foxp3 in thyroid cancer cells may offer a novel therapeutic option for thyroid cancer.
Introduction
Cystic changes, calcification, colloid material, and multinucleated giant cells are frequently associated with primary and metastatic papillary thyroid carcinoma (PTC). These features ...are sometimes present in negative lymph node fine‐needle aspiration cytology (FNAC). This study aims to review nodal aspirates of PTC to elucidate the significance of these cytological features in aspirates without tumor cells.
Methods
FNAC specimens from patients with PTC confirmed on thyroidectomy were reviewed for cystic changes, tumor‐associated features, and lymphoid components. Histologic follow‐up of the lymph nodes were retrieved for correlation.
Results
A total of 113 aspirates were retrieved, of which 79 showed tumor cells on the FNAC specimen, and 95 were matched to a positive lymph node histology. At univariable analysis, calcification (n = 18/113, p = .044), colloid material (n = 40/113, p = .001), multinucleated giant cells (n = 29/113, p = .028), tumor cells (n = 79/133, p < .001), foamy histiocytes (n = 36/113, p = .002) and pigmented histiocytes (n = 62/113, p < .001) were associated with a positive histology. Presence of lymphoid fragments (n = 11/113, p < .001) and abundant background lymphocytes correlated with a negative histologic follow‐up (n = 45/113, p = .005). In aspirates without tumor cells, multivariable analysis demonstrated colloid material (p < .001) and pigmented histiocytes (p = .003) to be independently predictive of metastatic PTC, whereas lymphoid fragments (p < .001) were independently associated with a negative histologic follow up.
Conclusion
Colloid material and pigmented histiocytes, and to lesser degree calcification and multinucleated giant cells, when seen in an aspirate without tumor cells, raises suspicion metastatic disease. On the contrary, the lymphoid fragments can be regarded as supportive evidence of adequate sampling and a true negative result.
Introduction
Blood proteins are emerging as candidate biomarkers for Alzheimer's disease (AD). We systematically profiled the plasma proteome to identify novel AD blood biomarkers and develop a ...high‐performance, blood‐based test for AD.
Methods
We quantified 1160 plasma proteins in a Hong Kong Chinese cohort by high‐throughput proximity extension assay and validated the results in an independent cohort. In subgroup analyses, plasma biomarkers for amyloid, tau, phosphorylated tau, and neurodegeneration were used as endophenotypes of AD.
Results
We identified 429 proteins that were dysregulated in AD plasma. We selected 19 “hub proteins” representative of the AD plasma protein profile, which formed the basis of a scoring system that accurately classified clinical AD (area under the curve = 0.9690–0.9816) and associated endophenotypes. Moreover, specific hub proteins exhibit disease stage‐dependent dysregulation, which can delineate AD stages.
Discussion
This study comprehensively profiled the AD plasma proteome and serves as a foundation for a high‐performance, blood‐based test for clinical AD screening and staging.
DEK::AFF2
fusion-associated papillary squamous cell carcinoma is a recently characterized sinonasal malignancy defined by its unique translocation.
DEK::AFF2
carcinomas may be deceptively monotonous ...and lack keratinization, resembling transitional epithelium. The lack of traditional cytological atypia presents diagnostic challenges. Our case describes the first report of fine-needle aspiration cytology of a lymph node involved by
DEK::AFF2
carcinoma in a patient with previously resected sinonasal inverted papilloma with carcinomatous transformation six years prior to presentation. This aspirate consisted of a lymphoid-rich background admixed with a moderate amount of epithelial cells arranged in cohesive structures of variable size, including large sheets. The tumor cells resembled those of the corresponding biopsy, featuring mildly hyperchromatic nuclei with fine to vesicular chromatin. Lesional cells lacked keratinization, mitoses, or hyperchromasia. Our finding suggests that in nodal aspirates of patients with a history of sinonasal-type papillomas, especially those with prior malignant transformation or atypia, there should be consideration for the possibility of
DEK::AFF2
-related primary. When in doubt,
DEK
FISH of AFF2 immunohistochemistry should be performed for confirmation.
Head and neck squamous cell carcinoma (HNSCC) has high morbidity and mortality, and its relationship with tumor angiogenesis as measured by microvessel density (MVD) or vascular endothelial growth ...factor (VEGF) expression has shown mixed results, with some, but not others, reporting correlation with outcome.
A retrospective study of 186 patients with HNSCC was performed. Patients were evaluated for MVD and VEGF and to correlate the levels with clinical parameters, including age at diagnosis, sex, site of tumor, stage, survival (disease free and overall), pathological tumor grade, and the presence of lymph node metastases.
The 186 cancers included the following sites: oral tongue (n = 69), palate (n = 9), maxillary sinus (n = 8), floor of mouth (n = 13), oropharynx (n = 27), hypopharynx (n = 26) and larynx (n = 34). Over three-quarters of patients had advanced tumor (stage III/IV) and 58.6% had lymph node metastases. MVD and VEGF were assessed in 166 and 164 cases, respectively, but these were not correlated with site and grade. The 3-year overall and disease-free survival rates were 55.4% and 53.2%, respectively. Both univariate and multivariate survival analysis showed that advanced T stage, nodal metastasis, and strong VEGF intensity were independent adverse predictors for overall and disease-free survival. In stage IV disease, strong VEGF immunoreactivity was found to be the single adverse factor affecting the overall survival and a contributory factor for disease-free survival.
VEGF immunoreactivity is a strong predictor of adverse outcome, particularly in locoregionally advanced disease.
Objective
Squamous metaplasia is not uncommonly observed in salivary gland neoplasms, including pleomorphic adenomas (PAs). It poses as a diagnostic pitfall with cytomorphologic features overlapping ...with low‐grade epithelial malignances and carcinoma ex‐PA. We report series of aspirates of PAs with squamous metaplasia and review the literature for the clinicopathological and cytologic features of this diagnostically challenging entity.
Methods
Three cases including index aspiration cytology, post‐aspiration specimen cytology, cell block immunohistochemistry (IHC), histologic correlation, and clinical data were reviewed. Literature search was performed for cases of PAs with squamous metaplasia, yielding 22 case reports including 11 with aspiration cytology performed.
Results
Metaplastic squamous components were seen in all index aspirations, but foreign body reaction and cystic changes were observed only after aspiration or in irritated lesions. PLAG1 IHC demonstrated reliable immunoreactivity in cell block preparations. Summarizing cases in this series and in the literature, cytologic features reported were variable and no consistent diagnostic feature was identified. Most reported cases were initially diagnosed as suspicious or malignant, but all ran a benign clinical course. Significant morbidity was reported only in one case due extensive surgery based on a malignant diagnosis.
Conclusions
Squamous metaplasia in PAs is not associated with adverse outcomes, but may induce reactive changes upon aspiration/irritation, resulting in worrisome cytologic features. PLAG1 IHC is a useful adjunct when characteristic cytologic features for PAs are absent or obscured. Prudent use of the diagnostic category salivary gland neoplasm of uncertain malignant potential (SUMP) in the Milan system can avoid overtreatment.
We conducted a retrospective study to assess the accuracy of fine-needle aspiration cytology (FNAC) in the diagnosis of Warthin tumor and to evaluate the subsequent risk of conservative nonsurgical ...management. We reviewed the records of 75 patients (76 tumors) with a parotid mass that had been diagnosed as a Warthin tumor by FNAC. This patient population was made up of 64 men and 11 women, aged 46 to 93 years (mean: 67). Of the 76 tumors, 40 were treated with surgical excision and 36 with conservative measures. Histology of the 40 excised parotid masses revealed that 38 (95%) were indeed Warthin tumors, 1 (2.5%) was a low-grade adenocarcinoma, and 1 was benign-not otherwise specified. None of the 36 tumors underwent malignant transformation either clinically or on repeat FNAC (if performed) during a follow-up of 4 to 120 months (mean: 55.5 ± 32.2). We conclude that conservative management of Warthin tumors confidently diagnosed on FNAC may be an option for patients who are unwilling or unable to undergo surgical excision.
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