Hagen Klieb

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.

Ameloblastic fibrosarcoma: report of a case, study of immunophenotype, and comprehensive review of the literature.

Ameloblastic fibrosarcoma (AFS) is a rare odontogenic neoplasm exhibiting a benign ameloblastomatous epithelial component admixed within a sarcomatous mesenchyme. It is considered the malignant counterpart of ameloblastic fibroma (AF) and can arise de novo or from transformed AF. 1 AFS is a locally aggressive tumor that seldom metastasizes. According to the World Health Organization classification, AFS is considered an odontogenic sarcoma. Other entities that fall under this category include ameloblastic fibrodentinosarcoma (AFDS), ameloblastic fibro-odontosarcoma (AFOS), and odontogenic carcinosarcoma (OCS). AFDS and AFOS are considered counterparts of AFS because they share the same histologic features, but they have additional dysplastic dentin and enamel and dentin, respectively. OCS has both a malignant ameloblastomatous component and a malignant mesenchyme. Clinically, all assume the same locally aggressive course as AFS. Previous studies have considered AFDS, AFOS, and AFS as 1 entity known as ameloblastic sarcoma. 2 However, in the context of this report, we will consider AFS as an entity that possesses ameloblastomatous epithelium within a sarcomatous mesenchyme, with no evidence of dentin or enamel elements present (Table 1).

Congenital melanocytic nevus of the oral mucosa: report of a rare pigmented lesion and review of the literature

Oral pigmented lesions are uncommon and congenital melanocytic nevi are especially rare. We report a case of a patient with multiple congenital melanocytic nevi including a palatal lesion. This is reported to add to the scant literature that exists on this subject. Prognosis and management are discussed.

Painful palatal swelling

Department of Anatomic Pathology and Department of Dentistry, Sunnybrook Health Sciences Centre, Toronto, Canada (H B E Klieb DMD); Department of Oral Pathology and Oral Medicine, University of Toronto, Toronto, Canada (M Duchnay DMD); Department of Anatomic Pathology (D Skeete MD, I T Leong BDS), Department of Dentistry (I T Leong BDS), and Department of Medicial Oncology (M E Blackstein MD), Mt Sinai Hospital, Toronto, Canada.

Using quantitative tissue phenotype to assess the margins of surgical samples from a pan-Canadian surgery study

The purpose of this study was to use quantitative tissue phenotype (QTP) to assess the surgical margins to examine if a fluorescence visualization‐guided surgical approach produces a shift in the surgical field by sparing normal tissue while catching high‐risk tissue.

An actionable test using loss of heterozygosity in identifying high-risk oral premalignant lesions

OBJECTIVES To develop an actionable test using fluorescence capillary electrophoresis (FCE) to assess loss of heterozygosity (LOH) of histologically similar low-grade lesions (LGLs) to identify high-risk lesions for oral cancer progression. STUDY DESIGN To determine the cutoffs of LOH, the FCE results of 52 surgical margin samples were used to compare with the existing LOH results from the previously validated 32 P-GE approach. Using the developed FCE workflow, an independent set of 102 LGLs with known progression status was used to determine the LOH molecular risk (MR) patterns and associated risk of progression. RESULTS Using 65% cutoff LOH-FCE, the agreement of LOH-32 P-GE had an average of 82.3% (76.8-87.8). Compared with nonprogressors (n = 61), anatomic site and MR patterns (LOH at 9 p21, 3 p14, or 17 p13) were independent risk factors. High-risk profile of tongue and MR3 (LOH at 9 p21 and/or 3 p14 and 17 p13) was significantly associated with progression (hazard ratio [HR] 6.7; 95% confidence interval [CI] 2.6-17.6) with specificity of 98.4% at identifying progressors. CONCLUSIONS We have developed an objective test using LOH to stratify the risk of LGLs. With further validation, it can be used in the clinical settings to provide clinicians additional information guiding the management of these lesions.

An Atypical Case of Mucocutaneous Blastomycosis in the Greater Toronto Area

Blastomycosis is an uncommon infection caused by Blastomyces dermatitidis. While management is fairly straightforward, diagnosis can be quite challenging. We describe a case of a healthy 37-year-old man who presented with progressive mucocutaneous lesions, without lung or other systemic involvement. Treatment with itraconazole resulted in complete resolution of signs and symptoms. This case showcases the variety of blastomycosis clinical presentation and the importance of blastomycosis in the differential diagnosis of verrucous and papillomatous mucocutaneous lesions.

Florid Cutaneous and Mucosal Papillomatosis: Mucocutaneous Markers of an Underlying Gastric Malignancy

Case Report An 86-year female patient was referred to us for assessment of lip lesions and numerous cutaneous warty growths of 6-month duration. She had mild dysphagia but no systemic symptoms, including weight loss. Her only medication was risedronate for osteoporosis and she was otherwise healthy. Examination revealed confluent fine papillomatosis across the lip vermillion (Fig 1), which diffusely affected the mucosa of the oral cavity and oropharynx. There were several wartlike papules affecting the skin of her face, neck, and extremities (Fig 2). There was no cutaneous hyperpigmentation or velvety thickening. Histologic examination of cutaneous and mucosal lesions showed hyperkeratosis, acanthosis, and papillomatosis but no viral inclusion or vacuolar degeneration of keratinocytes. There was no evidence of human papillomavirus (HPV) by polymerase chain reaction. Results of complete blood count and serum chemistry were normal but tumor markers showed elevated carcinoembryonic antigen (19.3 ug/L; normal, 0 to 4 ug/L), which was suggestive of a gastrointestinal tract neoplasm. A computed tomography scan showed marked mural thickening of the gastric body and antrum and several enlarged, confluent upper abdominal lymph nodes. Upper gastrointestinal endoscopy revealed gastric mucosal friability and ulceration. Biopsies demonstrated a poorly differentiated carcinoma. Palliative measures were provided when the patient experienced a rapid deterioration in health, and she died after 3 months. The eruption of wart-like papules was suggestive of a viral genesis but, surprisingly, there was no evidence to support the presence of HPV. Florid cutaneous papillomatosis (FCP) is a rare condition characterized by the rapid onset of numerous warty papulonodules that may be widespread and result in facial disfigurement and social exclusion. Lesions are clinically indistinguishable from viral papillomas, yet have no evidence of HPV infection. FCP may occur with other cutaneous markers of malignancy, such as sign of Leser-Trélat and acanthosis nigricans (AN). Mucosal papillomatosis was exuberant in our patient and the appearance was similar to that seen with oral AN, which lacks hyperpigmentation. Though other cutaneous manifestations of AN were not identified, oral mucosal changes may have represented the primary sign, as has been previously reported.

A lateral neck mass

CLINICAL PRESENTATION A 50-year-old man was referred for assessment of a right lateral neck mass. Four months earlier, a right submandibular space infection was managed with antibiotic therapy and extraction of several grossly decayed teeth in the right posterior mandible. A focal painless swelling persisted. He was otherwise healthy and did not take any medication. On examination, there was a subcutaneous swelling affecting the right submandibular region that measured 2 cm in maximum dimension (Figure 1). On bimanual palpation, this was nontender, firm, ovoid, and mobile. The oral soft tissues were normal, and extraction sockets had completely healed. Clear and ample saliva was expressed from the Wharton ducts. Plain films showed no osseous abnormalities or sialolith.