OMFPII Large Group Session 4 PDF

WesternU Health CDM Mark Mintline DDS Copyright © WesternU Health CDM, Mark Mintline, Elizabeth Andrews All right reserved. Required reading assignment Chapter 13 Chapter 17 GOALS AND OBJECTIVES •Review clinical and microscopic features of common oral lesions from Ch. 13, 17 •Discuss the clini...

WesternU Health CDM Mark Mintline DDS Copyright © WesternU Health CDM, Mark Mintline, Elizabeth Andrews All right reserved. Required reading assignment Chapter 13 Chapter 17 GOALS AND OBJECTIVES •Review clinical and microscopic features of common oral lesions from Ch. 13, 17 •Discuss the clinical management and diagnoses of small group cases •Review classic clinical presentations of oral pathology lesions from Ch. 13, 17 •Discuss clinical tips for pathology cases OVERVIEW OF TOPICS •#1: Top 10 takeaways •#2: Oral pathology consults •#3: Small group cases (8) •#4: Kahoot! questions •Review Boards-type facts! Chapter 13 Chapter 17 Hematologic disorders Oral manifestations of systemic diseases CPC cases and discussion CPC cases and discussion TOP 10 TAKEAWAYS Common clinical presentations and tips Clinical tip 1: hyperparathyroidism Bone lesions called “brown tumors” resemble central giant cell granulomas HYPERPARATHYROIDISM • Condition where one or more of the parathyroid glands secrete too much parathyroid hormone (PTH) • PTH helps regulate the amount of calcium in blood • Primary: an enlargement of one or more parathyroid glands results in ↑PTH Hyperparathyroidism •Can lead to osteoporosis, • Secondary: disease causes low kidney stones, bone and joint pain, nausea levels of calcium (ex. renal failure) resulting in ↑PTH Hyperparathyroidism Primary Pituitary adenoma Hyperplasia (enlargement) Neoplasm Secondary Severe calcium deficiency Severe vitamin D deficiency Chronic kidney failure Hereditary states of hyperparathyroidism MEN type I MEN1, CDKN1B loss-of-function Parathyroid tumors, pituitary tumors, pancreatic endocrine tumors MEN type 2A RET gain-of-function (affects neural crest cells) Pheochromocytomas, parathyroid tumors, medullary thyroid carcinoma Hyperparathyroidsm-jaw tumor syndrome CDC73 (HRPT2) loss-of-function Ossifying fibromas of the jaws, renal and uterine tumors, 15-20% develop parathyroid carcinomas Clinical tip 2: Cowden syndrome PTEN mutation Multiple oral papillomatous papules COWDEN SYNDROME • Disorder characterized by multiple noncancerous, tumorlike growths and an increased risk of cancer • Almost all people with CS develop hamartomas, commonly in the mouth and nose (also in GI, other) • Increased risk of cancer: breast, thyroid, endometrium, kidney, melanoma • Macrocephaly Cowden syndrome •Multiple trichilemmomata are seen in a majority of patients Increased cancer risk Patients often develop cancer at early ages (before age 50) Lifetime risk of cancer development Breast: 85% Thyroid: 35% Endometrial cancer: 28% Colorectal cancer, kidney cancer, and melanoma are also associated PTEN hamartoma tumor syndrome spectrum Cowden syndrome Bannayan-Riley-Ruvalcaba syndrome Proteus syndrome* (ATK1) Proteus-like syndrome Caused by mutations in the PTEN gene and is inherited in an autosomal dominant manner Clinical tip 3: pyostomatitis vegetans and oral ulcers Case courtesy of Leticia Ferreira DDS May represent an oral expression of inflammatory bowel disease (ex. ulcerative colitis, Crohn disease) PYOSTOMATITIS VEGETANS • Rare pustular eruption of the mouth may be associated with inflammatory bowel diseases • Most often associated with ulcerative colitis, but also Crohn disease • In the mouth, pustules (microabscesses) rupture and form shallow ulcerations Pyostomatitis vegetans •Snail track ulcerations, a biopsy should be performed • Other oral manifestations: to rule out other erosive swelling and thickening, cobblestone appearance, growths conditions Clinical tip 4: oral melanotic pigmentations Addison disease Kumar, R., Kumari, S., & Ranabijuli, P. K. (2008). Generalized pigmentation due to Addison disease. Dermatology Online Journal, 14(2). Retrieved from https://escholarship.org/uc/item/0zx6x6s6 Peutz-Jeghers syndrome Image from NIH: https://ghr.nlm.nih.gov/condition/peutzjeghers-syndrome ADDISON DISEASE • Deficiency of aldosterone and cortisol production from adrenal glands • Characterized by hypotension, metabolic acidosis, and hyperpigmentation of skin and/or mucosa • Hyperpigmentation seen in primary adrenal insufficiency Addison disease •Hyperpigmentation due to MSH, a byproduct of ↑ACTH • Most cases in the Western world production from proare due to autoimmunity opiomelanocortin Adrenal insufficiency Deficiency of aldosterone and cortisol due to loss of gland function Hypotension, hyperkalemia, metabolic acidosis, skin and mucosal hyperpigmentation Acute: sudden onset (ex. hemorrhage) Chronic: aka Addison disease adrenal atrophy due to disease (ex. autoimmune, TB, metastasis) PEUTZ-JEGHERS SYNDROME • Autosomal dominant condition (STK11) characterized by hamartomatous polyps in the GI tract and increased risk of developing certain types of cancer • Children often develop small, dark macules on the lips, inside the mouth, near the eyes and nostrils, and around the anus PJS • Spots can also occur on hands and •Around half of patients undergo surgery by age 18 feet • Increased cancer risk because of a polyps-related complication Peutz-Jeghers syndrome Credit: Elements of Morphology, National Human Genome Research Institute Freckles around the mouth Increased cancer risk Lifetime risk of developing cancer can be as high as 93% Gastrointestinal Breast Cervical Uterine Pancreas Lung Credit: Juan Gaertner/Shutterstock.com PJS •Hamartomatous polyps of the gastrointestinal tract, hyperpigmentation of mouth/feet/hands/genitalia Clinical tip 5: Premature exfoliation Hypophosphatasia/odontohypophosphatasia HYPOPHOSPHATASIA • Rare group of genetic disorders characterized by abnormal development of bones and teeth • Caused by the mutation in the tissue nonspecific alkaline phosphatase TNSALP gene (also called ALPL gene) • Highly variable, six clinical forms of HPP • Premature exfoliation of teeth deciduous teeth may be seen Hypophosphatasia •Microscopic examination of premature exfoliated teeth lack cementum Clinical tip 6: Hypothyroidism Cretinism Myxedema Primary: thyroid Secondary: no TSH World: decreased iodine USA: hypoplasia or agenesis Delayed eruption Hashimoto thyroiditis Gupta R, Goel K, Solanki J, Gupta S.Oral Manifestations of Hypothyroidism: A Case Report [Internet].2014 May [Cited November18, 2020];8(5):ZD20-ZD22. Clinical tip 7: Graves’ disease Autoimmune disease characterized by hyperthyroidism due to circulating autoantibodies against thyrotropin (TSH receptor) that activates the receptor, leading to increased thyroid hormone synthesis and secretion and growth of the thyroid gland A. B. C. D. goiter exophthalmos (proptosis) pretibial dermatopathy clubbing Teprotumumab Fully human monoclonal antibody Insulin-like growth factor I receptor (IGF-IR) inhibitor IGF-IR is overexpressed by orbital fibroblasts and B and T cells in Graves’ disease Clinical tip 8: Vitamin Dresistant rickets Most cases associated with PHEX gene (X-linked dominant) (X-linked hypophosphatemia) Delayed eruption of teeth Enlarged pulp horns: increased endodontic problems SOUZA, Andreia Pereira et al. Dental manifestations of patient with Vitamin D-resistant rickets. J. Appl. Oral Sci. [online]. 2013, vol.21, n.6 [cited 2020-11-18], pp.601-606. Clinical tip 9: Hodgkin lymphoma Reed-Sternberg cells (CD30+, CD15+, B-cell origin) Extremely rare in the oral cavity, but common in the H&N Reed-Sternberg cell https://www.webpathology.com/image.asp?n=5&Case=388 Classic Hodgkin lymphoma histologic subtypes Lymphocyte rich CHL -Best prognosis Nodular sclerosis -Most common form Mixed cellularity Lymphocyte depleted LDCHL -Worse prognosis, EBV more common Clinical tip 10: lipoid proteinosis ECM1 gene Autosomal recessive Deposition of waxy material in dermis and submucosal tissue Larynx and vocal cords are most common affected sites A. Eyelid, B. tongue, C. lip, D. buttock Zhang, Rong & Liu, Yang & Xue, Yang & Wang, Yinan & Wang, Xinwen & Shi, Songtao & Cai, Tao & Wang, Qintao. (2014). Treatment of lipoid proteinosis due to the p.C220G mutation in ECM1, a major allele in Chinese patients. Journal of translational medicine. 12. 85. 10.1186/1479-5876-12-85. Practice cases Oral pathology consults Bleeding disorders Always ask about any clotting or bleeding problems prior to invasive dental treatment Prevention of medical emergencies in dentistry Proper physical examination of all prospective dental patients would be capable of preventing 90% of life threatening situations “To be forewarned is to be forearmed.” McCarthy FM: Sudden, unexpected death in the dental office, J Am Dent Assoc 83:1091-1092, 1971. Representative case Case courtesy of Dr Paresh K Desai, Radiopaedia.org, rID: 5743 Acromegaly Excess GH in adults Typically caused by a pituitary adenoma Clinical findings Dental: macroglossia, prognathism, teeth gaps Deep voice Large hands and feet Coarse facial features Impaired glucose tolerance Increased risk or colorectal polyps ACROMEGALY • Excess growth hormone in adults • Typically caused by pituitary adenoma • Deep voice, coarse facial features, large hands and Acromegaly feet, impaired glucose •Oral manifestations: tolerance, increased risk prognathism, macroglossia, of colorectal polyps and increased spacing between cancer teeth Acromegaly diagnosis Imaging Pituitary mass on brain MRI (95% of cases) Insulin-like growth factor-1 (IGF-1) Elevated (normal range: 90-360 ng/mL) Oral glucose tolerance test (OGTT) Failure to suppress GH after very sugary drink GH doesn’t drop to < 1 ng/mL Acromegaly treatment Surgery Pituitary adenoma resection Octreotide Somatostatin analog Pegvisomant Growth hormone receptor antagonist OMFPII small group cases Case 1 25-year-old female presents to the WesternU Health Dental Clinic for a routine dental examination. Patient wants to make sure she doesn’t have any cavities. No masses or lesions were detected on clinical examination. Case courtesy of Ashtin Alves DMD2020 Case 1 7 months prior Present Case 1 Radiographic examination Case 1 A periapical dental radiograph of the #26-27 area demonstrates a (>2 cm) unilocular radiolucent lesion with ill-defined borders. The lesion exhibits aggressive behavior: the lamina dura and PDL of #26, 27 are lost. The roots of #26 and #27 appear intact. Radiographic examination An axial section of a CBCT reveals a low-density (radiolucent lesion) of the right anterior mandible near the #27 area. The lesion perforates the buccal cortical plate and disrupts the internal trabecular architecture of the mandible. Case 1 Differential diagnosis Malignancy (metastatic, hematologic, odontogenic) Central giant cell granuloma Desmoplastic fibroma Diagnosis Diffuse large B-cell lymphoma, (germinal center phenotype) NOS, CD30+ NON-HODGKIN LYMPHOMA • Diverse and complex group of hematologic malignancies • Numerous subtypes Large groupings include: B-cell, T-cell/NK-cell neoplasms • 70,000 cases are diagnosed in the USA annually • The vast majority (85%) of nonHodgkin lymphomas are B-cell derived • USA: 20-40% develop in extranodal sites Non-Hodgkin lymphoma •Oral cases most often present as extranodal disease, may develop in soft tissues or the jaws Diffuse large B-cell lymphoma Epidemiology Affects all ages, most common in 60-70y Most common non-Hodgkin lymphoma 30-40% of cases are extranodal Most common oral hematologic malignancy Etiology Arises de novo (common) or due to transformation of less aggressive NH lymphoma IHC: germinal center B-cell like or NGC DLBCL workup Referral to patient’s physician and hematologist-oncologist Staging (Ann Arbor staging system) Imaging studies: PET-CT scan, etc. IPI, R-IPI calculation Blood tests: LDH, HIV, HepB, HepC Renal and hepatic tests, performance status Pregnancy test OMFPII small group cases Case 2 38-year-old female presents to a periodontist as a referral from a general dentist to evaluate gingival pockets. During examination, the periodontist notes bruising on the forearms. Case courtesy of Todd Jenny DDS, MS Case courtesy of Todd Jenny DDS, MS Case 2 Case 2 Case courtesy of Todd Jenny DDS, MS Case courtesy of Todd Jenny DDS, MS Case 2 Clinical examination Case courtesy of Todd Jenny DDS, MS Generalized gingival enlargement of the maxilla and mandible is noted. The gingival tissue appears to be edematous and loosely attached to the teeth (boggy). Case courtesy of Todd Jenny DDS, MS Case courtesy of Todd Jenny DDS, MS Case 2 Differential diagnosis Hematologic malignancy Metastatic lesion Drug-related gingival hyperplasia Gingival fibromatosis SLL/CLL Further testing confirmed CLL LEUKEMIA • Hematologic malignancy that begins in bone marrow • • Myeloid vs. lymphoid Acute vs. chronic • All forms 13/100,000 • ALL: common childhood malignancy • CML: characterized by BCRABL gene translocation Leukemia •Oral manifestations: diffuse, hemorrhagic gingival involvement, myeloid sarcoma Leukemia Unregulated growth and differentiation of leukocytes in bone marrow Can lead to bone marrow failure, anemia, Infection, and hemorrhage Types Lymphoid neoplasms Myeloid neoplasms Leukemia: lymphoid neoplasms Acute lymphoblastic leukemia/lymphoma (ALL) Most common pediatric cancer, < 15 years Peripheral blood and bone marrow: ↑ lymphoblasts Small lymphocytic lymphoma (SLL)/chronic lymphocytic leukemia (CLL) >60 years, most common adult leukemia Peripheral blood smear shows smudge cells SLL and CLL are the same histologically, different clinically Hairy cell leukemia Mature B-cell tumor of elderly Peripheral blood smear shows “hairy cells” Leukemia: myeloid neoplasms Acute myelogenous leukemia (AML) Median age 65 years Peripheral blood smear: ↑myeloblasts, Auer rods M3 subtype responds to all-trans retinoic acid Chronic myelogenous leukemia (CML) Median age 64 years (45-85 years peak incidence) Defined by the Philadelphia chromosome (t[9;22], BCR-ABL), responds to imatinib Can transform to AML or ALL! OMFPII small group cases Case 3 66-year-old female presents to an oral surgeon for an evaluation of facial swelling. Patient reports lower lip paresthesia on the left side. Case 3 Case 3 Case 3 Clinical examination A diffuse gingival and vestibular swelling of the left posterior mandible is noted. The pink exophytic lesion measures ≈(2.5 x 1.2 x 1.0) cm. On extraoral examination, the aforementioned lesion is apparent. Case 3 Case 3 Radiographic examination A multilocular radiolucent with a probable punched out lytic component is noted in the left posterior mandible and ramus. The lesion measures ≈ (4.0 x 2.0) cm. Case 3 Differential diagnosis Metastatic lesion (breast carcinoma, etc.) Hematologic malignancy Osteosarcoma (little matrix) Odontogenic lesion (ameloblastoma, carcinoma?) Plasma cell neoplasm CD138 Plasma cell neoplasm Plasmacytoma Monoclonal expansion of plasma cells No “CRAB” findings Plasma cell (multiple) myeloma Requires clinical, laboratory, radiologic and histologic findings: serum or urine M protein, clonal expansion in bone marrow, end organ involvement Plasma cell (multiple) myeloma pneomonics CRAB Hypercalcemia Renal involvement Anemia Bone pain/lytic lesions MM Monoclonal M protein spike Plasma cell neoplasm workup Additional lytic bone lesions, urine M protein, hypercalcemia, elevated IL6 Final diagnosis Plasma cell (multiple) myeloma (IgG subtype) PLASMA CELL (MULTIPLE) MYELOMA • Multifocal, bone marrow based plasma cell neoplasm associated with M-protein in serum and/or urine • Common, 1% of all malignancies • If metastatic disease is excluded, MM >50% of bone malignancies • In US, MM 2x more common in black persons than white persons Multiple myeloma •Bone pain, weakness, recurrent infections, renal failure, hypercalcemia, anemia OMFPII small group cases Case 4 27-year-old male presents to an oral surgeon for an evaluation of a lesion on the left lateral border of the tongue. Case 4 Clinical examination Case 4 A pink sessile papule with a smooth surface measuring (0.8 x 0.4 x 0.2) cm is noted on the left posterior lateral border of the tongue. Differential diagnosis Lymphoid hyperplasia, lymphoid aggregate Foliate papillae Case 4 Fibroma or other soft tissue papule/nodule Reactive lymphoid hyperplasia Reactive germinal center LYMPHOID HYPERPLASIA • Reactive proliferation of lymphoid tissue • H&N: lymph nodes, Waldeyer's ring, lymphoid tissue of the oropharynx, soft palate, lateral tongue, and FOM • Lymphoid hyperplasia •Tonsillar asymmetry is Oral lesions primarily worrisome and needs further involve the lateral border evaluation of tongue and FOM Lymphoid hyperplasia Oral lymphoepithelial cyst OMFP II small group cases Case 5 16-year-old female presents to an oral surgeon complaining of pain in the left posterior mandible. Case 5 Case 5 Radiographic examination A panoramic radiograph reveals ≈ (3.0 x 1.2) cm well-defined unilocular radiolucent lesion in the left posterior body of the mandible. Case 5 Differential diagnosis Central giant cell granuloma Peripheral nerve sheath tumor Simple bone cyst Lesion not in alveolar process Hematologic malignancy Fibroblastic OS Odontogenic cyst/tumor Langerhans cell histiocytosis Coffee bean nuclei CD1a Birbeck granules “Tennis racket” or rod shaped cytoplasmic organelles found in Langerhans cells on EM By Yale Rosen from USA - Langerhans cell histiocytosis - Birbeck granules, CC BY-SA 2.0, https://commons.wikimedia.org/w/i ndex.php?curid=33936857 IHC now used S-100, CD1a, CD207 (langerin) LANGERHANS CELL HISTIOCYTOSIS • Neoplastic proliferation of Langerhans cells • Rare tumor, 5 cases per million population • Peak incidence is 3-5 years, slight male predominance • H&N involvement in 60%-80% of cases LCH •Patients without high-risk organ involvement have a mortality rate <10% Jaws involved in 10%-20% of cases Floating teeth of the left mandible Langerhans cell histiocytosis Clinical subtypes Acute-generalized (Letterer-Siwe) Aggressive with high morbidly and mortality Multifocal-chronic (Hand-Schuler-Christian) Lower mortality rate than LS Focal-chronic (eosinophilic granuloma) Localized lesion, very good prognosis OMFPII small group cases Case 6 53-year-old female presents to an oral surgeon for an evaluation of a recently enlarged tongue. On clinical examination, the surgeon notes several small skin lesions. The patient reports they appeared recently and plans to see a dermatologist soon. Case 6 Acquired macroglossia Clinical examination Case 6 An enlarged tongue (macroglossia) with a coated dorsal surface and scalloped lateral borders is noted. The coated surface is yellowbrown and can be scraped off. Case 6 Clinical examination Case 6 Multiple yellow-orange papules are noted on the tip and right ala of the nose. The lesions are waxy and firm. The lesions are slightly elevated and are approximately (3 x 2 x 1) mm in size. Case 6 Differential diagnosis Differential diagnosis Amyloidosis Amyloidosis Sebaceous hyperplasia Lipoid proteinosis Lichen amyloidosis Tumor (lymphoma, rhabdomyoma, etc.) Beckwith-Wiedemann syndrome Amyloidosis Acellular, amorphous, and eosinophilic material Congo red Normal light Congo red Apple-green birefringence under polarized light AMYLOIDOSIS • Heterogeneous group of conditions characterized by the deposition of an acellular extracellular protein • β-pleated sheet molecular configuration Amyloidosis • Congo red staining method is considered the •Need to determine the type of amyloidosis present “gold standard” for diagnosis Amyloid protein designations AX A = amyloid X = protein AL = light chain molecules AA = acute phase reactant protein Aβ2M = β2 microglobulin Hereditary amyloidosis (most are AD) ATTR-wild type Amyloidosis work up Lytic bone lesions, urine M protein, hypercalcemia, elevated IL6, Bone marrow biopsy confirmed MM AL amyloidosis Xanthelasma may resemble amyloidosis University of Iowa Health Care Contributor(s): Austin R. Fox, MD, Angela Mahoney, and Audrey C. Ko, MD Most common cutaneous xanthoma (1% of population) Cholesterol and lipid levels may need to be evaluated OMFPII small group cases Case 7 3-year-old male presents to an oral surgeon for a biopsy of the gingiva. On clinical examination, all four quadrants have gingival lesions. Case 7 Case 7 Clinical examination Multiple purple exophytic nodules on the gingiva are noted. The sessile nodules are lobulated, ulcerated, and hemorrhagic. The nodule pictured is located in the left posterior mandibular quadrant and measures (>2.5 x 2 x 2) cm. Case 7 Differential diagnosis Leukemia (ALL most common) Malignant tumor (rhabdomyosarcoma, metastatic lesion) Vitamin C deficiency (scurvy) Non-specific hemorrhage Scurvy diagnosis Plasma levels Ascorbic acid >0.6 mg/dL rules out scurvy Leukocyte levels Level of 0 is latent scurvy, 0-7 mg/dL is deficiency Urinary levels after ascorbic acid tolerance test Measures ascorbic acid over 6 hours after 1 g of ascorbic acid dissolved in water Radiographic changes SCURVY • Deficiency of vitamin C • In US, usually limited to people whose diets lack fresh fruits and vegetables • Inter-city Scurvy infants/children and •Gingival swelling and older men who live alone spontaneous hemorrhage: are most commonly scorbutic gingivitis affected Collagen synthesis Inside fibroblasts Hydroxylation (RER): hydroxylation of specific proline and lysine residues (requires vitamin C) Vitamin C deficiency leads to inadequate collagen synthesis Scurvy (vitamin C deficiency) Early features General weakness Fatigue Aching limbs Late features Anemia Gum disease Hemorrhage Osteopenia 10 days later! Treatment with Vitamin C Vitamin deficiencies Vitamin A severe deficiency during infancy can lead to blindness Thiamin (B1): beriberi cardiovascular and neurologic problems Western world: alcoholics, odd diets Southeast Asia: polished rice Riboflavin (B2) Glossitis, angular cheilosis Niacin (B3): pellagra (rough skin) Corn based diet (little niacin) Dermatitis, dementia, diarrhea, death Pyridoxine (B6) Isoniazid (acts as pyridoxine antagonist) Weakness, dizziness, cheilosis, glossitis Vitamin deficiencies (continued) Vitamin D Rickets Osteomalacia Dark-skinned children, infants that are solely breast fed Many foods are supplemented with Vitamin D Vitamin E Most commonly seen in children with chronic cholestatic liver disease (malabsorption of fat-soluble vitamins) Vitamin K Malabsorption syndromes, long-term antibiotic uses Coagulopathy: inadequate synthesis of prothrombin and clotting factors OMFPII small group cases Case 8 19-year-old male presents to an a periodontist for evaluation of reddened gingiva. Patient reports a history of aphthous ulcers and that the oral lesions coincide with bouts of gastrointestinal pain. Case courtesy of Todd Jenny DDS, MS Case 8 Case courtesy of Todd Jenny DDS, MS Case 8 Clinical examination Generalized erythematous gingiva. Of note, an erythematous plaque (erythroplakia) is noted on the attached and alveolar mucosa of #6-8. The lesion measures approximately (2.5 x 1.2) cm. Case 8 Differential diagnosis Epithelial dysplasia, squamous cell carcinoma Erosive lichen planus, blistering disease Plasma cell gingivitis, contact mucositis Oral manifestation of GIrelated pathology: Crohn disease, ulcerative colitis Crohn disease Noncaseating granulomas CROHN DISEASE • Transmural granulomatous disease affecting any portion of the GI tract but discontinuous • Noncaseating granulomas (Th1 mediated) • Tx: corticosteroids, immune modulators Crohn disease •Oral manifestations: linear ulcerations, cobblestone appearance, aphthous ulcerations, erythema Vegetative growth associated with Crohn disease OMFPII REVIEW SESSION: 12/09/2022 OMFPII FINAL EXAM (CUMULATIVE): 12/14/2022