Non-infectious granulomatous disorders of the upper lip: clinicopathological analysis of 11 patients.

BACKGROUND: Non-infectious granulomatous disorders of the upper lip represent a special chapter of oral and maxillofacial pathology. In this work we report a case-series of this process, to analyse its main clinicopathological features and find differential data that allow us improve its diagnosis and understand its pathogenesis. METHODS: We present 11 cases of non-infectious granulomatous disorders of the upper lip, 8 women and 3 men with an age range of 29-84 years, who have been attended at the Oral Medicine Department of the IUCT (France) and the Oral Medicine Unit of the UPV/EHU (Spain). All clinicopathological data were collected in a specific protocol. RESULTS: We recognized 4 different subtypes of non-infectious granulomatous disorders of the upper lip: (1) associated with Crohn's disease (1 case), (2) associated with foreign body (2 cases), (3) associated with gingivitis lichenoid-like (4 cases), (4) idiopathic (4 cases). CONCLUSIONS: Clinicopathological differences were identified between these subtypes. A good differential diagnosis is necessary in all cases to rule out the presence of local or systemic etiopathogenic factors.

How Oral Specialists Can Help Diagnose and Manage Extra-Digestive Inflammatory Bowel Disease Complications.

Identification of extra-digestive manifestations of inflammatory bowel disease (IBD) is essential. The oral cavity is a preferential site in which gingival enlargement may be one of these manifestations. We present, in this article, two original cases and a concept map that highlights the need for a close collaboration between the dental surgeon or oral specialist, the dermatologist, and the gastroenterologist. In the first case, the strictly local management of a systemic IBD oral complication, can relieve and answer the patient's complaint without modifying or disrupting the systemic treatment already implemented by the gastroenterologists. In the second case, the dental surgeon's diagnosis of gingival enlargement turns out to be the inaugural manifestation of Crohn's disease and allows early treatment of the intestinal pathology. These two cases illustrate the close link between the oral cavity and IBD. Knowledge and multidisciplinary management of these manifestations such as proposed in the concept map are essential for clinicians for the early diagnosis and the improvement of the oral and general quality of life of patients suffering from IBD.

Mass spectrometry-based proteomic analysis of parathyroid adenomas reveals PTH as a new human hormone-derived amyloid fibril protein.

BACKGROUND: Congo red-positive material was described in normal and diseased parathyroids (adenoma and hyperplasia) 50 years ago. However, the incidence and the clinical significance of such observation are unknown, and the causal fibril protein has never been convincingly demonstrated. METHODS: We conducted the present study including an exceptional case report accompanied with a retrospective study of 105 parathyroid adenomas. We used histopathological, immunohistochemical, ultrastructural, mass spectrometry-based proteomic analysis of parathyroid adenoma tissue samples, and genetic analysis. RESULTS: We describe a 57-year-old man with mild hypercalcemia and elevated parathyroid hormone (PTH) level for whom histopathological analysis revealed a parathyroid adenoma associated with nodular typical amyloid deposits. Tandem mass spectrometry after laser microdissection (LMD-MS) of amyloid adenoma identified PTH as the fibril protein, and no germline mutation in the PTH gene was detected. Congo red-positive PTH-deposits were further observed in 6.6% of the parathyroid adenomas analyzed, and were associated with complete/incomplete or absent universal amyloid signature, but with fibrillar morphology at ultrastructural level. CONCLUSIONS: Inappropriate PTH production leads to progressive disease-amyloid aggregation of PTH in a subset of parathyroid adenomas, providing new insights into the pathophysiology of this condition and adding PTH to the list of amyloid protein derived from hormones.

Oral acute graft versus host disease after donor lymphocyte infusions: Clinicopathological characterization in a monocenter cohort.

Donor lymphocyte infusions (DLI) are used after hematopoietic stem cell transplant (HSCT) in order to boost the graft-versus-tumor effect. The most significant toxicity is acute or chronic graft-versus-host disease (GVHD), whose clinical symptoms mirror those occurring after HSCT. By contrast, oral acute GVHD lesions have been exceptionally described post-DLI. We report on a monocenter cohort of 12 adult patients that developed oral acute GVHD after DLI. The majority was treated for acute myeloid leukemia. A total of 29 DLI treatments were applied and the median time between the last DLI and the oral mucosal lesions was 42 days. Most patients presented these oral lesions concomitant with skin lesions and none of them had exclusive oral involvement. Oral lichenoid changes were observed in 11 patients, including plaque-like lesions and/or reticulated white streaks consistent with Wickham's striae, affecting mainly the buccal mucosa and dorsal or lateral aspects of the tongue. Mucosal histopathological findings showed a patchy-to-florid lichenoid interface dermatitis for 3 biopsied patients. Eight patients also experienced salivary gland changes. The treatment of oral lesions included high- to very high-potency topical corticosteroids in the majority of patients. Oral GVHD lesions have seldom been described after DLI, and only exceptionally in an acute setting. Our results are not consistent with those reported in the literature evaluating GVHD after DLI. In fact, oral acute GVHD lesions post-DLI appeared very common and similar to the oral lichenoid reactions of chronic GVHD following HSCT. The main limitations of this work are its retrospective design and the relatively small sample size.

RREB1-MKL2 fusion in biphenotypic "oropharyngeal" sarcoma: New entity or part of the spectrum of biphenotypic sinonasal sarcomas?

An increasing number of sarcomas displaying a primitive, monomorphic spindle cell phenotype have been shown to harbor recurrent gene fusions, including biphenotypic sinonasal sarcoma (SNS). Occurring in the sinonasal area of middle-aged patients, SNS is a locally aggressive tumor harboring in 90% of cases recurrent gene fusions involving the PAX3 gene, in which the chimeric transcription factor induces an aberrant dual myogenic and neural phenotype. Here, we report an unusual oropharyngeal monomorphic spindle cell sarcoma in a 53-year-old man that revealed a novel RREB1-MKL2 gene fusion by RNA sequencing with the Illumina TruSight RNA Fusion Panel. The gene fusion was validated by RT-PCR. Although the tumor location is unusual (but head and neck seated), most of the other clinical, morphologic, immunophenotypic (focal combined expression of S100 protein, SMA, desmin, and myogenin) and oncogenic data suggest that this biphenotypic "oropharyngeal" sarcoma is closely related to the biphenotypic SNS spectrum. Notably, the RREB1-MKL2 chimeric transcription factor encoded by this fusion gene produced an increase in MKL2 expression, which regulates both neural and myogenic differentiation, mimicking the crucial role of PAX3 reported in SNS oncogenesis. NGS and especially RNA sequencing may be used to identify new candidate fusion oncogenes in soft tissue tumors, which would help in updating the existing classification. In turn, this would lead to better therapeutic management of patients.

Prospective comparison of 18F-NaF PET/CT versus 18F-FDG PET/CT imaging in mandibular extension of head and neck squamous cell carcinoma with dedicated analysis software and validation with surgical specimen. A preliminary study.

BACKGROUND: The aim of this study is to propose a new method to quantify radioactivity with PET/CT imaging in mandibular extension in head and neck squamous cell carcinoma (HNSCC), using innovative software, and to compare results with microscopic surgical specimens. PATIENTS AND METHODS: This prospective study enrolled 15 patients who underwent 18F-NaF and 18F-FDG PET/CT. We compared the delineations of bone invasions obtained with 18F-NaF PET/CT and 18F-FDG PET/CT with the results of histopathological analysis of mandibular resections (from right and left bone borders). A method for visualization and quantification of PET images was developed. RESULTS: For all patients, a significant difference (p = 0.032 for right limits and p = 0.011 for left limits) was observed between 18F-FDG PET/CT imaging and histopathology results, and no significant difference (p = 0.88 for right limits and p = 0.55 for left limits) was observed between 18F-NaF PET/CT imaging and histopathology results. The right limits were less than 10 mm in 93% of patients, and the left limits were less than 10 mm in 86% of patients. CONCLUSIONS: The dedicated software enabled the objective delineation of radioactivity within the bone. We can confirm that 18F-NaF is a precise and specific bone marker for the assessment of intraosseous mandibular extensions of head and neck cancers. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

No detection of Merkel cell polyomavirus in oral lichen planus: Results of a preliminary study in a French cohort of patients.

Oral lichen planus (OLP) is a chronic inflammatory disease considered as a CD8+ T lymphocyte-mediated autoimmune reaction, which may be triggered by undetermined virus. Recent reports have described the detection of Merkel cell polyomavirus (MCPyV) DNA in oral samples from healthy patients and in patients with different forms of oral cancers. We therefore investigated in a prospective way whether MCPyV was detectable in oral lesions of patients with active OLP. Our preliminary results do not support the hypothesis that OLP may be triggered by MCPyV infection. Further studies are needed to evaluate the involvement of other human polyomaviruses in OLP pathogenesis.

A comparative immunohistochemistry study of diagnostic tools in salivary gland tumors: usefulness of mammaglobin, gross cystic disease fluid protein 15, and p63 cytoplasmic staining for the diagnosis of mammary analog secretory carcinoma?

BACKGROUND: Mammary analog secretory carcinoma (MASC) of the salivary gland has been recently described according to morphological, immunohistochemical, and molecular (ETV6-NTRK3 translocation) similarities with the mammary secretory carcinoma. The most important differential diagnostic considerations of MASC are low-grade adenocarcinoma not otherwise specified (NOS), cystadenocarcinoma, and acinic cell carcinoma (AciCC). These tumors may share an overlapping morphology with MASC, and additional immunohistochemical studies are required to reinforce the diagnosis. Mammaglobin, GCDFP-15, and p63 staining have been reported in MASC. Our study was designed to check the specificity of these antibodies in MASC compared to other frequent tumors of salivary glands. METHODS: A series of 62 salivary gland tumors [10 MASCs, 5 adenocarcinomas NOS and 2 cystadenocarcinomas with MASC features and without ETV6 rearrangement, one low-grade cribriform cystadenocarcinoma (LGCCC), 9 AciCCs, 10 MECs, 10 adenoid cystic carcinomas (AdeCCs), 5 polymorphous low-grade adenocarcinomas (PLGAs), and 10 pleomorphic adenomas (PAs)] was analyzed by immunohistochemistry with mammaglobin, GCDFP-15, and p63 antibodies. RESULTS: Positivity for mammaglobin was observed in all MASCs, cystadenocarcinomas, LGCCC, and PLGAs, in some adenocarcinomas NOS, PAs, and MECs, rarely in AciCCs and never in AdeCCs. Positivity for GCDFP-15 was observed in most of the tumor types except in AdeCCs. Interestingly, cytoplasmic positivity for p63 was observed in most of MASCs and PLGAs while rarely in adenocarcinomas NOS and PAs, and never in the other tumor types. CONCLUSION: Our study revealed the usefulness of mammaglobin and p63 cytoplasmic staining to define which tumors are worth to be screened for ETV6 rearrangement.

High third generation/second generation PTH ratio in a patient with parathyroid carcinoma: clinical utility of third generation/second generation PTH ratio in patients with primary hyperparathyroidism.

BACKGROUND: Primary hyperparathyroidism (PHP) is caused by parathyroid adenomas or hyperplasia, and occasionally by parathyroid carcinoma. Recently a high third generation/second generation PTH ratio has been observed in some patients with parathyroid carcinoma. PATIENTS AND METHODS: We report the case of a 60-year old woman who was presented a fourth episode of PTH-related hypercalcaemia due to a parathyroid carcinoma. Serum PTH levels were measured using a second generation assay and a third generation assay before, 4 and 7 months after the fourth surgery. Then, PTH levels were measured in 294 osteoporotic normocalcaemic patients as well as in 30 consecutive PHP patients. RESULTS: Before surgery of the patient with parathyroid carcinoma, second generation PTH was 229 pg/ml, third generation PTH was 675 pg/ml and third generation/second generation PTH ratio was 2.95. Four and 7 months after surgery the third generation/second generation PTH ratio was 0.70 and 0.66, respectively. All osteoporotic patients had a normal third generation/second generation PTH ratio (0.585 +/- 0.118) whereas only one patient (3.3%) with PHP had a third generation/second generation PTH ratio > 1 (1.54). CONCLUSION: A high third generation/second generation PTH ratio could be observed in patients with parathyroid carcinoma, is uncommon in benign PHP and is absent in osteoporotic patients without PHP. Therefore, PTH level can be measured using second and third generation assays in some PHP patients, and a specific surgical protocol for possible parathyroid carcinoma could be discussed in patients with a high third generation/second generation PTH ratio.