EWSR1-ATF1 fusion is a novel and consistent finding in hyalinizing clear-cell carcinoma of salivary gland.

Hyalinizing clear-cell carcinoma (HCCC) is a rare, low-grade salivary gland tumor with distinctive clear-cell morphology and pattern of hyalinization as well as focal mucinous differentiation. However, histological overlap exists with other salivary gland tumors, such as epithelial-myoepithelial carcinoma (EMCa), salivary myoepithelial carcinoma, and mucoepidermoid carcinoma (MEC). The potential relationship between HCCC and its morphological mimics has not been yet investigated at the genetic level. In this study, we conducted a molecular analysis for the presence of rearrangements in MAML2, commonly seen in MECs, and EWSR1, involved in "soft tissue myoepithelial tumors" (SMET) by fusion with POU5F1, PBX1, or ZNF444. Fluorescence in situ hybridization (FISH) was performed on 23 HCCC cases for abnormalities in MAML2, EWSR1, FUS, POU5F1, PBX1, and ZNF444. FISH for MAML2 was negative in all cases (0 of 14), including those with mucinous differentiation (0 of 7). An EWSR1 rearrangement was identified in 18 of 22 HCCCs (82%), while no break-apart signals were seen in FUS, POU5F1, PBX1, or ZNF444. 3'RACE on an EWSR1 rearranged HCCC identified an EWSR1-ATF1 fusion, which was confirmed by RT-PCR. ATF1 involvement was further confirmed by FISH analysis in 13 of 14 EWSR1-rearranged HCCC cases (93%). In contrast, all control cases tested, including among others 5 EMCa and 3 MEC with clear cells, were negative for EWSR1 and ATF1 rearrangements. The presence of EWSR1-ATF1 fusion in most HCCCs reliably separates these tumors from its histological mimics. The distinction from MEC is particularly important, as conventional MEC grading schemes overgrade these indolent HCCCs, potentially impacting on treatment.

Oral Squamous Cell Carcinoma Associated with Precursor Lesions.

Oral squamous cell carcinoma (OSCC) may be associated with precursor lesions known as oral potentially malignant disorders (OPMD). Few studies have reported on how OPMD diagnosis affects early detection and outcome of OSCC. We reviewed a large series of OSCC to determine the proportion that was associated with preceding OPMD and to compare the outcome of OSCC with or without precursor. Cases of oral-oropharyngeal carcinoma diagnosed between 2005 and 2015 were retrieved from the Ontario Cancer Registry (OCR) and matched to records of OPMD between 2001 and 2015 in two large oral pathology diagnostic services and the pathology databases of two hospitals with oral pathology services, to identify cases with precursor. Of 10,987 cancer cases, 378 (3.44%) had a preceding OPMD. Patients living in Central Ontario were more likely to have OPMD diagnosed before carcinoma than those in North Ontario (4.73% vs. 1.63%, P = 0.05). 329 of 5,257 cases of oral cancer were linked to a precursor, compared with 24 of 4,174 cases of oropharyngeal cancer (6.26% vs. 0.57%, P < 0.0001). Oral cancers with precursor were predominantly diagnosed at stage I (49.30%), compared with those without precursor, where stage IV disease predominated (41.28%). Sixty-nine of 309 (22.33%) patients with precursor-associated oral cancer have died of disease, compared with 1,551 of 4,656 (33.31%) patients without a precursor (P = 0.02). We conclude that patients with OSCC associated with a precursor had significantly lower odds of dying from disease. The beneficial effect of precursor lesion diagnosis on outcome is related to a higher proportion of stage I disease. PREVENTION RELEVANCE: OSCC causes significant morbidity and mortality, especially if diagnosed at late stages. Precursor lesions to OSCC can be recognized by clinical examination. Our study shows that early diagnosis of OSCC at the precursor stage can improve the outcome of oral cancer.

Sclerosing Epithelioid Fibrosarcoma of the Jaw: Late Recurrence from a Low Grade Fibromyxoid Sarcoma.

Sclerosing epithelioid fibrosarcoma (SEF) is an uncommon variant of fibrosarcoma that is characterized by a distinct morphology. It most frequently presents in the deep soft tissues of the lower extremities, often in intimate association with fascia and periosteum, although reports of the head and neck involvement have been reported. A minority of cases show morphological, immunohistochemical and molecular overlap with low grade fibromyxoid sarcoma (LG-FMS). Herein, we describe a case of a bland spindle cell neoplasm presenting in the jaw that was initially incompletely excised. Over the course of 20 years the tumor subsequently recurred with a SEF morphology. Molecular testing performed on both specimens subsequently confirmed the presence of an EWSR1-CREB3L1 gene fusion. This report highlights the diagnostic difficulty with LG-FMS, particularly in unusual anatomic locations; reiterates the potential for the uncommon EWSR1-CREB3L1 fusion product in LG-FMS; and, reaffirms the potential for progression and/or overlap between LG-FMS to SEF over time.

Ewing's family of tumors of the sinonasal tract and maxillary bone.

The Ewing's family of tumors (EFT) are malignant neoplasms affecting children and young adults. Most cases arise in the long bones or the pelvis. Primary EFT of head and neck is uncommon and primary sinonasal EFT is even rarer. Previous studies have not focused on the sinonasal region specifically, and the published literature on sinonasal EFT consists of sporadic case reports. Fourteen cases of sinonasal EFT were available and had H&Es for review and immunohistochemical stains for CD99, S100, keratins, synaptophysin and desmin. FISH or RT-PCR was performed for EWSR1 abnormalities on 8 cases. The 14 identified patients included 5 males and 9 females, ranging from 7-70 years of age (mean 32.4 years). Tumors involved nasal cavity (5), sinuses (5) or both (4). Five patients had dural, orbital or brain involvement. The majority involved bone radiologically and/or microscopically. All cases were composed of small cells with variable cytoplasmic clearing. Focal or prominent nesting was noted in most cases. All cases were positive for CD99. Keratins (AE1/3 and/or CAM5.2), S100 and synaptophysin were positive in 4, 3 and 5 cases, respectively. All cases were negative for desmin. The 8 cases tested by FISH or RT-PCR were positive for EWSR1 abnormalities. Follow-up in 8 patients ranged from 1-168 months (average 11.3 m) showing 1 death due to metastatic disease, 1 death due to local disease, 1 patient alive with metastases and 5 patients disease-free at last follow-up. Interestingly, however, an analysis of the literature suggests a better prognosis for sinonasal EFT than EFT overall.

Refractory erosive oral lichen planus associated with hepatitis C: response to topical tacrolimus ointment.

BACKGROUND: Erosive lichen planus is a painful and disabling disease that is frequently resistant to topical and systemic therapies. Current therapies are considered palliative rather than curative as many patients relapse after discontinuing treatment. An association has been reported between some cases of oral lichen planus (OLP) and chronic hepatitis C infection. OBJECTIVE: We report on a 51-year-old hepatitis C-positive man with corticosteroid refractory erosive lichen planus of the lip who had a rapid resolution of his lesions following a two-week course of topical 0.1% tacrolimus ointment. The patient remains symptom-free at one year post-treatment. CONCLUSION: This case supports the safety and efficacy of topical tacrolimus in patients with steroid-refractory OLP associated with chronic hepatitis C.