Publications by authors named "I G Koutlas"

81 Publications

Cemental tear: An overlooked finding associated with rapid periodontal destruction. A case series.

Aust Dent J 2021 Apr 17. Epub 2021 Apr 17.

Division of Endodontics, School of Dentistry, University of Minnesota, Minneapolis, MN, USA.

Cemental tear is defined as cementum fragment completely or partially detached from the root surface, and it has been associated with localized rapid periodontal breakdown. Although history of trauma and/or attrition may be risk factors, the etiopathology of cemental tear remains unknown. This case series aims to discuss the clinical, radiographic and histopathologic features of cemental tears to aid clinicians in making differential diagnosis. Three teeth from three patients presenting a periradicular lesion underwent an exploratory surgery to determine the cause and provide treatment. Soft and hard tissue biopsies were obtained from each lesion and forwarded for histopathologic evaluation. Two patients received a guided tissue regeneration (GTR) procedure, which allowed the tooth to be retained. One patient received an extraction with simultaneous guided bone regeneration (GBR) due to a hopeless prognosis of the tooth. The results after histopathologic evaluation yielded a final diagnosis of cemental tear for all three patients. Cemental tears may be overlooked, and therefore, they should be included in the differential diagnosis of periapical periodontitis, endodontic-periodontal lesion and vertical root fracture (VRF).
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http://dx.doi.org/10.1111/adj.12844DOI Listing
April 2021

Salivary Mucinous Adenocarcinoma Is a Histologically Diverse Single Entity With Recurrent AKT1 E17K Mutations: Clinicopathologic and Molecular Characterization With Proposal for a Unified Classification.

Am J Surg Pathol 2021 Feb 24. Epub 2021 Feb 24.

*Departments of Pathology and Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD †Department of Biochemistry, Molecular Biology, and Biophysics, College of Biological Sciences ‡Howard Hughes Medical Institute, University of Minnesota §Division of Oral and Maxillofacial Pathology, School of Dentistry, University of Minnesota, Minneapolis, MN ∥Southern California Permanente Medical Group, Department of Pathology, Woodland Hills Medical Center, Woodland Hills **Departments of Orofacial Sciences, Pathology, and Radiation Oncology, University of California San Francisco, San Francisco, CA ¶Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX #Department of Pathology, Icahn School of Medicine at Mount Sinai Hospital, New York, NY.

Mucin-producing salivary adenocarcinomas were historically divided into separate colloid carcinoma, papillary cystadenocarcinoma, and signet ring cell carcinoma diagnoses based on histologic pattern, but have recently been grouped together in the adenocarcinoma not otherwise specified category. It is currently unclear if these tumors represent 1 or more distinct entities and how they are related to well-circumscribed papillary mucinous lesions with recurrent AKT1 E17K mutations that were recently described as salivary intraductal papillary mucinous neoplasm. Here, we sought to evaluate the clinicopathologic and molecular features of salivary mucinous adenocarcinomas to clarify their classification. We identified 17 invasive mucin-producing salivary adenocarcinomas, 10 with a single histologic pattern, and 7 with mixed patterns. While most tumors demonstrated papillary growth (n=15), it was frequently intermixed with colloid (n=6) and signet ring (n=3) architecture with obvious transitions between patterns. All were cytokeratin 7 positive (100%) and cytokeratin 20 negative (0%). Next-generation sequencing performed on a subset demonstrated recurrent AKT1 E17K mutations in 8 cases (100%) and TP53 alterations in 7 cases (88%). Of 12 cases with clinical follow-up (median: 17 mo), 4 developed cervical lymph node metastases, all of which had colloid or signet ring components. Overall, overlapping histologic and immunohistochemical features coupled with recurrent AKT1 E17K mutations across patterns suggests that mucin-producing salivary adenocarcinomas represent a histologically diverse single entity that is closely related to tumors described as salivary intraductal papillary mucinous neoplasm. We propose a unified mucinous adenocarcinoma category subdivided into papillary, colloid, signet ring, and mixed subtypes to facilitate better recognition and classification of these tumors.
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http://dx.doi.org/10.1097/PAS.0000000000001688DOI Listing
February 2021

Endogenous APOBEC3B overexpression characterizes HPV-positive and HPV-negative oral epithelial dysplasias and head and neck cancers.

Mod Pathol 2021 02 6;34(2):280-290. Epub 2020 Jul 6.

Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA.

The DNA cytosine deaminase APOBEC3B (A3B) is a newly recognized endogenous source of mutations in a range of human tumors, including head/neck cancer. A3B inflicts C-to-T and C-to-G base substitutions in 5'-TCA/T trinucleotide motifs, contributes to accelerated rates of tumor development, and affects clinical outcomes in a variety of cancer types. High-risk human papillomavirus (HPV) infection causes A3B overexpression, and HPV-positive cervical and head/neck cancers are among tumor types with the highest degree of APOBEC signature mutations. A3B overexpression in HPV-positive tumor types is caused by the viral E6/E7 oncoproteins and may be an early off-to-on switch in tumorigenesis. In comparison, less is known about the molecular mechanisms responsible for A3B overexpression in HPV-negative head/neck cancers. Here, we utilize an immunohistochemical approach to determine whether A3B is turned from off-to-on or if it undergoes a more gradual transition to overexpression in HPV-negative head/neck cancers. As positive controls, almost all HPV-positive oral epithelial dysplasias and oropharyngeal cancers showed high levels of nuclear A3B staining regardless of diagnosis. As negative controls, A3B levels were low in phenotypically normal epithelium adjacent to cancer and oral epithelial hyperplasias. Interestingly, HPV-negative and low-grade oral epithelial dysplasias showed intermediate A3B levels, while high-grade oral dysplasias showed high A3B levels similar to oral squamous cell carcinomas. A3B levels were highest in grade 2 and grade 3 oral squamous cell carcinomas. In addition, a strong positive association was found between nuclear A3B and Ki67 scores suggesting a linkage to the cell cycle. Overall, these results support a model in which gradual activation of A3B expression occurs during HPV-negative tumor development and suggest that A3B overexpression may provide a marker for advanced grade oral dysplasia and cancer.
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http://dx.doi.org/10.1038/s41379-020-0617-xDOI Listing
February 2021

FET(EWSR1)-TFCP2 Rhabdomyosarcoma: An Additional Example of this Aggressive Variant with Predilection for the Gnathic Bones.

Head Neck Pathol 2021 Mar 5;15(1):374-380. Epub 2020 Jun 5.

Pediatric Hematology and Oncology, Children's Minnesota, Minneapolis, MN, USA.

An example of a mandibular rhabdomyosarcoma in a 15-year-old male is described featuring EWSR1-TFCP2 fusion with homolateral lymph node metastasis and apparent metastasis to the thoracic vertebra T7. This type of rhabdomyosarcoma has preference for the craniofacial skeleton. Histologically, the tumor was composed of spindle and epithelioid cells characterized by nuclear pleomorphism, cytologic atypia and brisk mitotic activity. Immunohistochemically, it featured diffuse positive nuclear staining MYOD1, only focal staining for myogenin and patchy cytoplasmic staining for desmin. Tumor cells were positive for keratins and nuclear staining for SATB2 was also observed. Interestingly, tumor cells were diffusely positive for calponin. Currently, the patient is under chemotherapy treatment.
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http://dx.doi.org/10.1007/s12105-020-01189-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010041PMC
March 2021

Segmental Ipsilateral Odontognathic Dysplasia (Mandibular Involvement in Segmental Odontomaxillary Dysplasia?) and Identification of PIK3CA Somatic Variant in Lesional Mandibular Gingival Tissue.

Head Neck Pathol 2021 Mar 4;15(1):368-373. Epub 2020 Jun 4.

Division of Oral and Maxillofacial Pathology, School of Dentistry, University of Minnesota, 515 Delaware Street SE #16-116B, Minneapolis, MN, 55455, USA.

Segmental odontomaxillary dysplasia (SOD) is a developmental condition of the middle and posterior maxilla featuring dysplastic bone overgrowth, dental abnormalities and, occasionally, various homolateral cutaneous manifestations. Herein, we describe an individual with maxillary abnormality akin to SOD and associated ipsilateral segmental odontomandibular dysplasia. Also, the result of the evaluation of lesional mandibular gingival tissue for overgrowth-related gene variants is reported. An 8-year-old girl presented clinically with congenital maxillary and mandibular alveolar soft tissue enlargement in the area of the premolars. A panoramic radiograph revealed abnormal trabeculation essentially similar to SOD in the maxilla and mandible with congenitally missing maxillary and mandibular first and second premolars and mandibular canines. Diagnostic mandibular bone biopsy was performed and lesional mandibular gingival hyperplastic tissue was obtained for variant analysis of somatic overgrowth genes PIK3CA, AKT1, AKT3, GNAQ, GNA11, MTOR, PIK3R2. Cone beam computerized tomography (CBCT) disclosed osseous abnormalities on the left side of the maxilla and mandible and very mild osseous expansion in the mandible. Histologically, abnormal bone exhibiting prominent reversal lines was present and associated with fibrocollagenous tissue. Genomic DNA analysis disclosed PIK3CAc.1571G>A; pArg524Lys which was seen at a low mosaic level in the blood, indicating a post-zygotic change. Although this case may be a unique disorder, by sharing features with SOD, one can suggest the possibility of mandibular involvement in SOD. The presence of a PIK3CA variant may support the hypothesis that these segmental disorders could be part of the PIK3CA-related overgrowth spectrum.
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http://dx.doi.org/10.1007/s12105-020-01185-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010023PMC
March 2021