Spontaneous Regeneration of the Mandible after Hemimandibulectomy: Report of a Case

Mandibular defects may result from many conditions such as trauma, inflammatory diseases and tumors. There are rare cases reported in the literature that have demonstrated spontaneous bone regeneration after resection of the mandible. Several factors such as age, preservation of the periosteum and genetics seem to influence spontaneous bone regeneration capacity in individuals. Evaluation of these factors may lead to a better understanding of the mechanism of spontaneous bone regeneration and also help to create new methods for bone reconstruction. The purpose of this article was to describe the spontaneous regeneration of the hemi-mandible with a well shaped condyle and coronoid after resecting a mandibular pathologic lesion in a young man

Genomic profiling of primary and recurrent Adult Granulosa Cell Tumors of the Ovary

Adult-type granulosa cell tumor (aGCT) is a rare malignant ovarian sex cord-stromal tumor, harboring recurrent FOXL2 c.C402G/p.C134W hotspot mutations in 97% of cases. These tumors are considered to have a favorable prognosis, however aGCTs have a tendency for local spread and late recurrences, which are associated with poor survival rates. We sought to determine the genetic alterations associated with aGCT disease progression. We subjected primary non-recurrent aGCTs (n = 7), primary aGCTs that subsequently recurred (n = 9) and their matched recurrences (n = 9), and aGCT recurrences without matched primary tumors (n = 10) to targeted massively parallel sequencing of ≥410 cancer-related genes. In addition, three primary non-recurrent aGCTs and nine aGCT recurrences were subjected to FOXL2 and TERT promoter Sanger sequencing analysis. All aGCTs harbored the FOXL2 C134W hotspot mutation. TERT promoter mutations were found to be significantly more frequent in recurrent (18/28, 64%) than primary aGCTs (5/19, 26%, p = 0.017). In addition, mutations affecting TP53, MED12, and TET2 were restricted to aGCT recurrences. Pathway annotation of altered genes demonstrated that aGCT recurrences displayed an enrichment for genetic alterations affecting cell cycle pathway-related genes. Analysis of paired primary and recurrent aGCTs revealed that TERT promoter mutations were either present in both primary tumors and matched recurrences or were restricted to the recurrence and absent in the respective primary aGCT. Clonal composition analysis of these paired samples further revealed that aGCTs display intra-tumor genetic heterogeneity and harbor multiple clones at diagnosis and relapse. We observed that in a subset of cases, recurrences acquired additional genetic alterations not present in primary aGCTs, including TERT, MED12, and TP53 mutations and CDKN2A/B homozygous deletions. Albeit harboring relatively simple genomes, our data provide evidence to suggest that aGCTs are genetically heterogeneous tumors and that TERT promoter mutations and/or genetic alterations affecting other cell cycle-related genes may be associated with disease progression and recurrences

TERT promoter hotspot mutations and gene amplification in metaplastic breast cancer.

Metaplastic breast cancers (MBCs) are characterized by complex genomes, which seem to vary according to their histologic subtype. TERT promoter hotspot mutations and gene amplification are rare in common forms of breast cancer, but present in a subset of phyllodes tumors. Here, we sought to determine the frequency of genetic alterations affecting TERT in a cohort of 60 MBCs with distinct predominant metaplastic components (squamous, 23%; spindle, 27%; osseous, 8%; chondroid, 42%), and to compare the repertoire of genetic alterations of MBCs according to the presence of TERT promoter hotspot mutations or gene amplification. Forty-four MBCs were subjected to: whole-exome sequencing (WES; n = 27) or targeted sequencing of 341-468 cancer-related genes (n = 17); 16 MBCs were subjected to Sanger sequencing of the TERT promoter, TP53 and selected exons of PIK3CA, HRAS, and BRAF. TERT promoter hotspot mutations (n = 9) and TERT gene amplification (n = 1) were found in 10 of the 60 MBCs analyzed, respectively. These TERT alterations were less frequently found in MBCs with predominant chondroid differentiation than in other MBC subtypes (p = 0.01, Fisher's exact test) and were mutually exclusive with TP53 mutations (p < 0.001, CoMEt). In addition, a comparative analysis of the MBCs subjected to WES or targeted cancer gene sequencing (n = 44) revealed that MBCs harboring TERT promoter hotspot mutations or gene amplification (n = 6) more frequently harbored PIK3CA than TERT wild-type MBCs (n = 38; p = 0.001; Fisher's exact test). In conclusion, TERT somatic genetic alterations are found in a subset of TP53 wild-type MBCs with squamous/spindle differentiation, highlighting the genetic diversity of these cancers

Photobiomodulation in Oral Medicine

Objective: To provide a review of the literature about the photobiomodulation therapy (PBMT) dental treatment protocols in oral medicine based on validated clinical studies that have been published so far. Background data: The lack of effective therapies for the treatment of various types of oral diseases or the presence of invasive therapeutic methods along with the use of a wide range of medications has had a significant impact on the quality of life of these patients. PBMT as a noninvasive and nondrug method can play an influential role in the treatment of oral diseases. Methods: In this study, published clinical studies up to April 2019 were reviewed from library sources, Google Scholar, PubMed and Medline, Elsevier, Embase, Cochrane, Scopus, and Web of science (ISI). Results: In general, the findings of this study showed that PBMT has had a positive effect on the treatment of oral lichen planus, recurrent aphthous stomatitis, hyposalivation, pemphigus vulgaris, recurrent herpes simplex, burning mouth syndrome, bisphosphonate-related osteonecrosis of the jaw, trigeminal neuralgia, facial nerve paralysis, geographic tongue, and chronic sinusitis. Conclusions: PBMT can be effective (as an alternative treatment or in combination with other therapies) in improving symptoms or in the complete treatment of oral diseases. However, further clinical studies are still necessary to achieve more robust results

Pleomorphic adenomas and mucoepidermoid carcinomas of the breast are underpinned by fusion genes

Primary pleomorphic adenomas (PAs) and mucoepidermoid carcinomas (MECs) of the breast are vanishingly rare. Here we sought to determine whether breast PAs and MECs would be underpinned by the fusion genes reported to occur in their salivary gland counterparts. Our study included three breast PAs and one breast MEC, which were subjected to RNA sequencing (PAs, n = 2; MEC, n = 1) or to Archer FusionPlex sequencing (PA, n = 1). Our analyses revealed the presence of the HMGA2-WIF1 fusion gene in breast PA3, the CTNNB1-PLAG1 fusion gene in breast PA2, and the CRTC1-MAML2 fusion gene in the breast MEC analyzed (1/1). No oncogenic fusion genes were detected in breast PA1, and no additional oncogenic fusion genes were detected in the cases studied. The presence of the fusion genes identified was validated by fluorescence in situ hybridization (n = 1), reverse transcription-PCR (n = 1), or by both methods (n = 1). Taken together, our findings indicate that PAs and MECs arising in the breast resemble their salivary gland counterparts not only phenotypically but also at the genetic level. Furthermore, our data suggest that the molecular analysis of breast PAs and MECs might constitute a useful tool to aid in their differential diagnosis

Immunohistochemical Assessment of HRAS Q61R Mutations in Breast Adenomyoepitheliomas

AIMS Breast adenomyoepitheliomas (AMEs) are uncommon tumors. Most estrogen receptor (ER)-positive AMEs have mutations in PI3K pathway genes, whereas ER-negative AMEs usually harbor concurrent mutations affecting the HRAS Q61 hotspot and PI3K pathway genes. Here, we sought to determine the sensitivity and specificity of RAS Q61R immunohistochemical (IHC) analysis for detection of HRAS Q61R mutations in AMEs. METHODS AND RESULTS 26 AME (14 ER-positive, 12 ER-negative) previously subjected to massively parallel sequencing (n=21) or Sanger sequencing (n=5) of the HRAS Q61 hotspot locus were included in this study. All AMEs were subjected to IHC using a monoclonal (SP174) RAS Q61R-specific antibody, in addition to detailed histopathologic analysis. Nine ER-negative AMEs harbored HRAS mutations, including Q61R (n=7) and Q61K (n=2) mutations. 5/7 (71%) AMEs with HRAS Q61R mutations were positive by IHC, whereas none of the AMEs lacking HRAS Q61R mutations (n=17) were immunoreactive. RAS Q61R immunoreactivity was restricted to the myoepithelium in 80% (4/5) of cases, whereas one case displayed immunoreactivity in both the epithelial and myoepithelial components. RAS Q61R IHC-positive AMEs were associated with infiltrative borders (P<0.001), necrosis (P<0.01) and mitotic index in the epithelial (P<0.05) and myoepithelial (P<0.01) components. RAS Q61R IHC assessment did not detect Q61K mutations (0/2). CONCLUSIONS IHC analysis of RAS Q61R displays a high specificity (100%) and moderate sensitivity (71%) for detection of HRAS Q61R mutations in breast AMEs, and appears not to detect HRAS Q61K mutations. IHC analysis of RAS Q61R may constitute a useful marker in the diagnostic workup of ER-negative AMEs

Immunohistochemical assessment of HRAS Q61R mutations in breast adenomyoepitheliomas

Aims: Breast adenomyoepitheliomas (AMEs) are uncommon tumours. Most oestrogen receptor (ER)-positive AMEs have mutations in phosphoinositide 3-kinase (PI3K) pathway genes, whereas ER-negative AMEs usually harbour concurrent mutations affecting the HRAS Q61 hotspot and PI3K pathway genes. Here, we sought to determine the sensitivity and specificity of RAS Q61R immunohistochemical (IHC) analysis for detection of HRAS Q61R mutations in AMEs. Methods and results: Twenty-six AMEs (14 ER-positive; 12 ER-negative) previously subjected to massively parallel sequencing (n&nbsp;=&nbsp;21) or Sanger sequencing (n&nbsp;=&nbsp;5) of the HRAS Q61 hotspot locus were included in this study. All AMEs were subjected to IHC analysis with a monoclonal (SP174) RAS Q61R-specific antibody, in addition to detailed histopathological analysis. Nine ER-negative AMEs harboured HRAS mutations, including Q61R (n&nbsp;=&nbsp;7) and Q61K (n&nbsp;=&nbsp;2) mutations. Five of seven (71%) AMEs with HRAS Q61R mutations were immunohistochemically positive, whereas none of the AMEs lacking HRAS Q61R mutations (n&nbsp;=&nbsp;17) were immunoreactive. RAS Q61R immunoreactivity was restricted to the myoepithelium in 80% (4/5) of cases, whereas one case showed immunoreactivity in both the epithelial component and the myoepithelial component. RAS Q61R immunohistochemically positive AMEs were associated with infiltrative borders (P&nbsp;&lt;&nbsp;0.001), necrosis (P&nbsp;&lt;&nbsp;0.01) and mitotic index in the epithelial (P&nbsp;&lt;&nbsp;0.05) and myoepithelial (P&nbsp;&lt;&nbsp;0.01) components. RAS Q61R IHC assessment did not reveal Q61K mutations (0/2). Conclusions: IHC analysis of RAS Q61R shows high specificity (100%) and moderate sensitivity (71%) for detection of HRAS Q61R mutations in breast AMEs, and appears not to detect HRAS Q61K mutations. IHC analysis of RAS Q61R may constitute a useful technique in the diagnostic workup of ER-negative AMEs

Immunohistochemical assessment of HRAS

AIMS Breast adenomyoepitheliomas (AMEs) are uncommon tumors. Most estrogen receptor (ER)-positive AMEs have mutations in PI3K pathway genes, whereas ER-negative AMEs usually harbor concurrent mutations affecting the HRAS Q61 hotspot and PI3K pathway genes. Here, we sought to determine the sensitivity and specificity of RAS Q61R immunohistochemical (IHC) analysis for detection of HRAS Q61R mutations in AMEs. METHODS AND RESULTS 26 AME (14 ER-positive, 12 ER-negative) previously subjected to massively parallel sequencing (n=21) or Sanger sequencing (n=5) of the HRAS Q61 hotspot locus were included in this study. All AMEs were subjected to IHC using a monoclonal (SP174) RAS Q61R-specific antibody, in addition to detailed histopathologic analysis. Nine ER-negative AMEs harbored HRAS mutations, including Q61R (n=7) and Q61K (n=2) mutations. 5/7 (71%) AMEs with HRAS Q61R mutations were positive by IHC, whereas none of the AMEs lacking HRAS Q61R mutations (n=17) were immunoreactive. RAS Q61R immunoreactivity was restricted to the myoepithelium in 80% (4/5) of cases, whereas one case displayed immunoreactivity in both the epithelial and myoepithelial components. RAS Q61R IHC-positive AMEs were associated with infiltrative borders (P<0.001), necrosis (P<0.01) and mitotic index in the epithelial (P<0.05) and myoepithelial (P<0.01) components. RAS Q61R IHC assessment did not detect Q61K mutations (0/2). CONCLUSIONS IHC analysis of RAS Q61R displays a high specificity (100%) and moderate sensitivity (71%) for detection of HRAS Q61R mutations in breast AMEs, and appears not to detect HRAS Q61K mutations. IHC analysis of RAS Q61R may constitute a useful marker in the diagnostic workup of ER-negative AMEs