GLI1-Altered Soft Tissue Tumors of the Head and Neck: Frequent Oropharyngeal Involvement, p16 Immunoreactivity, and Detectable Alterations by DDIT3 Break Apart FISH.

BACKGROUND: GLI1 is a transcription factor protein that has recently gained recognition in a morphologically distinct group of epithelioid soft tissue tumors characterized by GLI1 fusions or amplifications. The head and neck region, particularly the tongue, is a common location for GLI1-altered tumors. DDIT3 break apart fluorescence in situ hybridization (FISH), commonly used to identify translocations in myxoid/round cell liposarcoma, has been used as a surrogate test to detect both fusions and amplifications of the 12q13.3 region encompassing DDIT3 and GLI1 gene loci. METHODS: We herein report 5 cases of GLI1-altered soft tissue tumors. Three arose in the oropharynx (base of tongue/vallecula, tonsil) and two arose in the tongue. Given the frequent oropharyngeal location and epithelioid morphology, p16 immunohistochemistry was performed on cases with available material. Commercially available DDIT3 break apart FISH, custom GLI1 specific FISH, and RNA sequencing were performed on select cases. RESULTS: Two cases showed amplification using DDIT3 FISH which was confirmed using GLI1 specific FISH. The remaining cases harbored ACTB::GLI1, one of which showed rearrangement of the 12q13.3 region by DDIT3 FISH with absence of amplification by GLI1 specific FISH. STAT6 immunoexpression was positive in the GLI1-amplified cases and negative in the GLI1-rearranged cases while MDM2 expression was positive in the 4 cases tested. CDK4 expression was strong and diffuse in the GLI1-amplified cases. p16 immunohistochemistry showed strong nuclear and cytoplasmic staining in 50-70% of tumor cells in all four tested cases. CONCLUSION: Here we show that GLI1-altered soft tissue tumors are frequently positive for p16 and can occur in tonsillar regions of the oropharynx. As such, positive p16 immunohistochemistry alone cannot be used as evidence for the diagnosis of HPV-related squamous cell carcinoma as strong and diffuse p16 expression may also occur in GLI1-altered soft tissue tumors. Commercially available DDIT3 break apart FISH, which is readily available in many cytogenetic laboratories, may be useful as a sensitive surrogate test for GLI1 fusions and amplifications.

Sialadenoma Papilliferum: Analysis of Seven New Cases and Review of the Literature.

Sialadenoma papilliferum (SP) is a rare benign salivary gland neoplasm that comprises from 0.4 to 1.2% of all salivary gland tumors. The tumor is so named because of its microscopic resemblance to the syringocystadenoma papilliferum, an uncommon benign tumor of sweat gland origin. The purpose of this paper is to report the clinical and microscopic features of seven new cases of SP and combine them with cases previously reported in the English language literature to further define this unusual lesion. Combining our cases with acceptable cases from the literature, the palate (especially the hard palate) was the most common site, with 80% of the cases occurring in this location. Other locations in decreasing order were buccal mucosa, upper lip, retromolar pad, and parotid gland. Age at diagnosis ranged from 18 to 87 years with a peak in the 6th decade and an average age of 56.4 years. Microscopically, the lesions demonstrated a papillary surface morphology, and the papillary projections varied from long and pointed to short and blunted. The supporting connective tissue contained a variable number of convoluted ductal structures, which often fused with the overlying surface epithelium. The ductal structures exhibited papillary infoldings and were lined by a double layer of epithelium consisting of basal cell layer and a luminal layer of cuboidal-to-columnar ductal cells. Immunohistochemical reactivity with p63 and p40 indicated that the basal cell layer was comprised predominantly of neoplastic myoepithelial cells. The luminal cells were immunoreactive with epithelial membrane antigen characteristic of ductal cell differentiation. Conservative surgical treatment was accomplished in most cases and appears to be adequate treatment as only two recurrences were documented. Several case reports of purported malignant transformation in SP have been reported in the literature, but in our opinion, there is insufficient evidence in the publications to unequivocally determine whether any of the malignancies truly originated within a pre-existing SP.

Melanoma of the Oral Cavity: an Analysis of 46 New Cases with Emphasis on Clinical and Histopathologic Characteristics.

Melanoma of the oral cavity is a rare malignancy that carries a poor prognosis. We identified 46 new cases of both primary and metastatic melanoma to the oral cavity. Following IRB approval, these cases were obtained from the Oral Pathology Biopsy Service archives of the UF College of Dentistry (1994-2014), the UK College of Dentistry (1997-2015), and the UM Medical Center (1988-2015). All slides were reviewed. The location, age, race, gender, clinical impression, duration of lesion, histopathologic diagnosis, and histopathologic features were recorded. Cases from the facial skin and those with an ambiguous diagnosis were excluded. Forty-six cases fulfilled the inclusion criteria with 32 primary cases, 11 known metastases, and 3 cases where metastasis could not be excluded. The primary cases included a total of 20 females and 12 males with an average age of 66.7 (range 27-95), and the majority (80 %) of the patients were Caucasian when race was known. Twenty-two of the 32 primary cases (68.8 %) were located in the maxillary mucosa, 5 in the mandibular mucosa or bone, and 5 in other locations. The clinicians' impressions varied from benign fibrous growths to high grade malignancies. The histopathology varied widely among the cases, however two cell types predominated (often in combination): epithelioid cells (50.0 %) and spindle cells (50.0 %). Only 53.1 % demonstrated melanin pigmentation. Oral melanoma remains one of the most diverse clinical and histopathologic diagnoses. Better understanding of this neoplasm may promote earlier diagnosis and may lead to improved outcomes.

Desmoplastic Melanocytic Nevus of Oral Mucosa.

The desmoplastic melanocytic nevus is an uncommon variant that easily may be confused with a fibrohistiocytic neoplasm or a desmoplastic melanoma. It is believed that the following report describes the first known example of a desmoplastic melanocytic nevus arising in the oral mucosa. The histopathologic and immunohistochemical features that allow separation from other microscopically similar pathoses are stressed.