PRACTICAL INSIGHTS IN ORAL PATHOLOGY. Kirk Y. Hirata, MD January 13, 2017

Transcription

1 PRACTICAL INSIGHTS IN ORAL PATHOLOGY Kirk Y. Hirata, MD January 13, 2017

2 ROAD TO THE PODIUM? : LLUSM : Anatomic and Clinical Pathology Residency, UH John A. Burns School of Medicine : Hematopathology Fellowship, Scripps Clinic, San Diego July 1995: HPL - new business, niche?

3 ORAL PATHOLOGY outpatient biopsies, some were from dentists s/o inflammation, benign odontogenic cyst, etc no service to general dentists or oral surgeons wife was a dentist, residency at QMC idea?

4 ORAL PATHOLOGY telephone calls lunches (marketing) textbooks courses, including microscopy began to acquire cases QMC dental resident teaching once a month

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7 AFTER 21 YEARS established myself in the community as an oral pathologist QMC Dental Residency Program has been recognized 7 TH edition of Jordan (1999) UCSF consultation service

8 Dr. Richard Jordan Professor of Oral Pathology, Pathology & Radiation Oncology UCSF Dermatopathology & Oral Pathology Service I feel fortunate to have joined this group of outstanding dermatopathologists. I believe that my training, experience and expertise in oral and maxillofacial pathology expands the scope and breadth of services that we are able to offer the medical and dental community for their diagnostic pathology needs. I initially trained as a dentist at the University of Toronto that was followed by an internship at the Toronto Western Hospital (now the University Health Network). Following training in anatomic pathology I completed a residency in oral and maxillofacial pathology under the direction of Dr. Jim Main. I also completed a fellowship in oral medicine and then a Master of Science degree in oral pathology. I was fortunate to be able to train with Professor Paul Speight at the University of London were I was awarded a PhD degree in Experimental Pathology. My first faculty position was at the University of Toronto where I practiced oral pathology and oral medicine and developed a research program in oral cancer. In 2000 I relocated to the University of California San Francisco and have been director of the oral pathology service since I have published over 130 peer reviewed publications, many invited reviews and I am the author of two leading textbooks, one in oral pathology (Regezi, Sciubba and Jordan. Oral Pathology: Clinical pathologic correlations 6th ed) and the other in oral medicine (Lewis and Jordan. Color Handbook of Oral Medicine 2nd edition). I am also the Medical Director (working with Dr. Nilsa Ramirez and Dr. Soon Paik) of the NRG Oncology Biospecimen Bank that is based in San Francisco, Columbus OH and Pittsburgh PA supporting phase II and phase III practice changing therapeutic trials for head and neck, breast, colorectal, lung, prostate and brain cancers. Enrolling 5099 patients each year, this biospecimen bank collects, stores, reviews and distributes over 150,000 biospecimens each year as part of the primary trials and translational research. I am delighted to contribute to the UCSF Dermatopathology and Oral Pathology Service and enjoy providing a high level of diagnostic pathology and expert opinion for clinicians and pathologists for lesions in the head and neck.

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10 ACKNOWLEDGEMENTS

11 GOALS/OBJECTIVES community practice, not OM surgeons lesions you are likely to encounter what is the next step? discuss and advise with patient

12 LESION TYPES Mucosal bumps White/red Pigmented Vesiculobullous Jaw cysts and tumors Bone

13 LECTURE SCHEDULE Mucosal bumps White/red lesions - not SCCA Pigmented lesions BREAK Vesiculobullous lesions Jaw cysts (few tumors) Bone lesions - including BRONJ

14 MUCOSAL BUMPS raised lesions, usually with intact mucosa and normal color irritation fibroma mucocele vascular lesions PG/POF/PGCG squamous papilloma neural lesions

15 IRRITATION FIBROMA reactive fibrosis (scar) recurrence with irritation or trauma no malignant potential

16 VARIANTS

17 DENTURE-INDUCED FIBROUS HYPERPLASIA inflammatory fibrous hyperplasia, epulis fissuratum chronic trauma related to ill-fitting denture surgery and new denture

18 MUCOCELE cyst-like collection of mucin that spills from traumatized salivary duct common in 1 st 3 decades excision including salivary gland tissue in vicinity

19 SJÖGREN S SYNDROME Focus = glandular area that contains 50 or more lymphocytes/plasma cells Focus score = # foci in 4 mm2 area Focus score > 1 is consistent with SS

20 VASCULAR LESION bluish bleb, small or large

21 PYOGENIC GRANULOMA reactive proliferation of blood vessels and fibroblasts etiology - plaque, hormone recurrence 5%

22 PERIPHERAL OSSIFYING FIBROMA fibroblast proliferation with mineralized component (woven bone or cementum)

23 PERIPHERAL GIANT CELL GRANULOMA proliferation of mononuclear and multinucleated giant cells excision, remove underlying irritating factor - 15% recurrence

24 SQUAMOUS PAPILLOMA/ VERRUCA VULGARIS exophytic/verrucous growth younger patients HPV subtype 2, 6, 11

25 NEURAL LESION most common benign spindle cell lesion in oral cavity solitary, traumatic etiology granular cell tumor

26 FORDYCE S GRANULES 1 to 3 mm yellowish papules, adults (60%), buccal mucosa and lip

27 ECTOPIC LYMPHOID TISSUE small, yellow-white, dome-shaped elevations normal tissue in unusual location lingual tonsil

28 GINGIVAL LESION/NODULE reactive/inflammatory peripheral (extraosseous) cyst or tumor soft tissue tumor extension of intrabony lesion into gingiva metastasis

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30 WHITE/RED LESIONS (WHO DEFINITIONS) Leukoplakia - persistent white mucosal patch or plaque that cannot be scraped off Erythroplakia - persistent red mucosal patch with or without erosion Erythroleukoplakia - speckled lesion with features of both Verrucous hyperplasia - superficial lesion, white and corrugated

31 ERYTHROLEUKOPLAKIA (SPECKLED)/ERYTHROPLAKIA some leukoplakic lesions develop scattered patches of redness epithelial cells no longer produce keratin and atrophic, allowing underlying microvasculature to show through less common than leukoplakia, but greater potential for dysplasia at the time of biopsy

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33 LEUKOPLAKIA

34 CLINICAL FEATURES older individuals (60 years), males, young? lower lip, buccal mucosa, gingiva (70%) lip vermilion, oral floor, and tongue - more often associated with dysplasia or carcinoma

35 GENERALIZATIONS 16% (5 to 25%) of benign hyperkeratosis will develop into dysplasia and/or carcinoma 16-36% of dysplasias develop into invasive carcinoma

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38 GRADES OF EPITHELIAL DYSPLASIA CIS - absence of invasion, metastasis cannot occur MILD MODERATE SEVERE/CIS

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41 SQUAMOUS CELL CARCINOMA

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52 DENTAL SCREENING all patient exams should include a comprehensive history systematic visual and tactile examination of not only the oral soft tissues, but also those of the head and neck ancillary techniques to aid in the identification of premalignant and malignant oral lesions

53 ORAL CANCER SCREENING DEVICE commercial devices were designed to further assist the dental practitioner identify early tissue changes assess the biological significance of a mucosal lesion explore morphological and biochemical tissue alterations that cannot be observed by normal incandescent light

54 Toluidine Blue

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60 ADA COUNCIL ON SCIENTIFIC AFFAIRS AND THE CDC conclude that these adjunctive aids may not significantly improve the detection and diagnosis of potentially malignant lesions current level of scientific evidence was insufficient to support recommending the routine use of any of these devices in routine practice

61 JADA, Vol. 141, May 2010 until then? increased patient education about the risks for oral cancer clinical vigilance suspicious or persistent lesions should be biopsied histologic examination remains the current gold standard for oral cancer and precancer diagnosis

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63 SALIVA TEST FOR ORAL CANCER SaliMark OSCC (PeriRx, LLC) noninvasive, oral diagnostic technology - salivary exrna biomarker test for oral SCC decade of NIH-funded research and prevalidation work at UCLA and MSU signature mutations (biomarkers) that may be associated with oral cancers screening test for early detection (before symptoms) to reduce morbidity and mortality

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65 TREATMENT AND PROGNOSIS (LEUKOPLAKIA) clinical term, biopsy required for diagnosis and to guide appropriate management tobacco cessation complete excision for moderate dysplasia and greater 10-35% recurrence rate, new lesions clinical evaluation every 6 months, longterm f/u

66 MANAGEMENT

67 SMOKELESS TOBACCO (TOBACCO POUCH KERATOSIS) chewing tobacco, dry snuff, and moist snuff - latter most popular younger age (12 years), highest prevalence in midwestern and SE states gingival recession and bone resorption, increased caries? dysplasia is uncommon, usually mild, regress

68 TOBACCO POUCH KERATOSIS

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70 BETEL HABIT 10-20% of the world s population (WHO estimates 600 million people) cultural, early age, habitually chew 16 to 24 hours daily Indian subcontinent and Asian countries (SE Asia, Taiwan, Southern China, Polynesia, Micronesia including Guam) psychoactive substance - nicotine, alcohol, caffeine, betel nut

71 BETEL QUID (PAAN) quid - leaf wrapped around a mixture of areca nut, slaked lime, possibly tobacco, and sometimes sweeteners and spices commercially available, freeze-dried betel quid substitutes (pan masala, gutkha, mawa) slaked lime releases alkaloids from the areca nut - feeling of euphoria

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74 ORAL SUBMUCOUS FIBROSIS alkaloids also stimulate fibroblasts resulting in oral submucous fibrosis - high risk, precancerous condition chronic, progressive scarring of the oral (buccal) mucosa - interincisal distance of 20 mm inability to open the mouth (trismus) and generalized oral burning sensation (stomatopyrosis) with intolerance to spicy foods

75 ORAL SUBMUCOUS FIBROSIS dysplasia in 10 to 15% of cases carcinoma in 6% does not regress with habit cessation limited treatment 8% rate of malignant transformation (19x risk)

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77 RAISING AWARENESS any evidence of health benefits is limited WHO classifies betel nut as a carcinogen FDA has placed nut on its Poisonous Plants Database CDC warns of addiction, oral fibrosis, and cancer Taiwan - Betel Nut Prevention Day

78 PIGMENTED LESIONS usually brown in color alarming when raised or erosion includes vascular lesions - blanch

79 AMALGAM TATTOO macule, usually localized and evenly pigmented gingiva adjacent to amalgam restorations or crowns, apicoectomy with amalgam retrofill leaches out or traumatically implanted and stains reticulin fibers (argyrophilic)

80 ORAL MELANOTIC MACULE adults, 5 th decade less than 1 cm, evenly pigmented idiopathic, postinflammatory hypermelanosis

81 ORAL MELANOCYTIC NEVUS 3 rd or 4 th decade macule, plaque, or nodule intramucosal, blue nevus excision is curative

82 BLUE NEVUS

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84 MUCOSAL MELANOMA 1-8% of head and neck melanoma, much more common in sinonasal cavity older patients, males (blacks, asians) > 1 cm, irregularly pigmented, borders irregular, nodularity and ulcer excision, recurrence rate is 50%, survival may not be improved with radiotherapy

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86 BREAK

87 VESICULOBULLOUS LESIONS 3 P s - lichen planus, mucous membrane pemphigoid, pemphigus vulgaris Wickham striae middle age females skin findings slough (blister) when rub vs Candida Michele s solution - DIF

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90 LICHEN PLANUS/LICHENOID MUCOSITIS considered autoimmune by some, target lesion not yet identified middle age females skin involvement in 10-15% of patients malignant transformation?

91 LICHEN PLANUS reticulated keratosis with variable erythema T-cell destruction of basal cells (lichenoid) topical antiinflammatory therapy

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93 IMMUNOFLUORESCENCE Shaggy junction Civatte bodies

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95 MUCOUS MEMBRANE PEMPHIGOID subepithelial blistering with autoantibodies desquamative gingivitis DIF shows linear IgG or C3 at basement membrane zone

96 Mucous membrane pemphigoid

97 PEMPHIGUS VULGARIS Ashkenazi-Jewish descent, Caucasian in US, Asians painful erosions/ulcers - palate antibodies against desmoglein-3 DIF - intercellular deposition of IgG

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100 JAW CYSTS

101 TOOTH ANATOMY

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105 PERIAPICAL PATHOLOGY pulpal death from cavity/restoration or trauma accumulation of inflammatory cells at the apex of a nonvital tooth (periodontitis), osteoclast activation with bone resorption (periapical radiolucency) abscess spreads along path of least resistance (parulis)

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108 PERIAPICAL CYST

109 ODONTOGENIC CYSTS cysts within jaw bones lined by odontogenic epithelium developmental or inflammatory in origin although rare, most primary intraosseous carcinomas arise from malignant transformation of the lining of an odontogenic cyst

110 DENTIGEROUS CYST (FOLLICULAR/ERUPTION) originates from follicle around crown (CEJ) of unerupted tooth - impacted wisdom most common (20%) accumulation of fluid, 5 mm 10 to 30 years of age, slight male ameloblastoma, SCC, mucoepidermoid carcinoma

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113 KERATOCYSTIC ODONTOGENIC TUMOR (ODONTOGENIC KERATOCYST) cell rests of the dental lamina associated molecular genetic alterations, so now considered a benign cystic neoplasm 10 to 40 years, slight male, mandible high recurrence rate (30%), mural cysts nevoid basal cell carcinoma (Gorlin) syndrome

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116 OKC TREATMENT enucleation and curettage peripheral ostectomy with a bone bur chemical cauterization with Carnoy s solution marsupialization with drainage tube to allow decompression and reduction in size before removal

117 NEVOID BASAL CELL CARCINOMA SYNDROME

118 ORTHOKERATINIZED ODONTOGENIC CYST orthokeratinized variant of OKC orthokeratinized epithelial lining (as compared to parakeratin of OKC) young adults, male, posterior mandible enucleation with curettage, rarely recurs

119 ORTHOKERATINIZED ODONTOGENIC CYST

120 GINGIVAL CYST newborn (up to 3 months) - rupture spontaneously alveolar mucosa - remnants of dental lamina (rests of Serres) adults - soft tissue counterpart of LPC mandibular canine and premolar area simple surgical excision

121 GINGIVAL CYST

122 LATERAL PERIODONTAL (BOTRYOID) CYST occurs along the lateral root surface rests of dental lamina intrabony counterpart of the adult gingival cyst 5 th to 7 th decade, mandibular premolarcanine-lateral incisor area conservative enucleation, recurrence is unusual

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124 LATERAL PERIODONTAL CYST

125 CALCIFYING ODONTOGENIC CYST (CALCIFYING CYSTIC ODONTOGENIC TUMOR/GORLIN CYST) odontogenic epithelium containing ghost cells which may undergo calcification cystic and/or solid incisor and canine area 2 nd to 4 th decade (30 years) can be extraosseous (peripheral) simple enucleation, few recurrences

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128 GLANDULAR ODONTOGENIC CYST rare, aggressive behavior middle-aged adults, anterior mandible enucleation and curettage, en bloc resection for multilocular lesions recurrence (30%)

129 ODONTOGENIC TUMORS

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132 AMELOBLASTOMA conventional solid or multicystic (intraosseous) unicystic peripheral (extraosseous)

133 SOLID AMELOBLASTOMA CYSTIC AMELOBLASTOMA

134 PERIPHERAL AMELOBLASTOMA

135 ODONTOGENIC TUMORS

136 ODONTOMA mixed tumors composed of both epithelial and mesenchymal tissues compound vs complex

137 MIXED TUMORS ameloblastic fibroma ameloblastic fibro-odontoma

138 ODONTOGENIC TUMORS

139 ODONTOGENIC MYXOMA multilocular with honeycomb pattern recurrence

140 CEMENTOBLASTOMA true cementoma rare neoplasm of cementoblasts fused to root of tooth 2 nd and 3 rd decades mandible > maxilla

141 BONE Tori and exostoses Osteonecrosis and osteomyelitis Fibro-osseous lesions Bone cysts Bone cancer

142 TORI/EXOSTOSES bony outgrowths, bilateral and symmetric developmental, racial predisposition trauma, BRONJ

143 IDIOPATHIC OSTEOSCLEROSIS intraosseous radiopacity not related to teeth dense bone island/scar

144 CONDENSING OSTEITIS children and young adults similar to IO, but at or very close to apices of teeth molar and premolar areas of mandible pulpitis from large carious lesions or deep coronal restorations chronic occlusal trauma or low grade inflammation

145 OSTEONECROSIS/ OSTEOMYELITIS ON, medication-induced is recently recognized and fairly common may result in OM exposed bone OM, usually result of dental infection pain both associated with sequestrum formation and/or sinus tract

146 OSTEOMYELITIS infection of medullary bone with suppuration and sequestra formation bacterial male predominance mandible > maxilla chronic systemic diseases, immunocompromised status are predisposing surgical debridement, antibiotics

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149 FIBRO-OSSEOUS LESIONS proliferation of fibroblast-like cells and deposition of osseous or cementum-like material cemento-osseous dysplasia ossifying fibroma

150 BONE CYSTS nasopalatine duct cyst - anterior midline palate, area of incisive canal simple (idiopathic, traumatic) 1st 2 decades, males mandibular molar-premolar area serosanguineous fluid or empty cavity Stafne bone cavity 5 th to 7 th decade, males entrapped salivary gland tissue, pressure resorption

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153 BRONJ 2003: a pattern of jaw osteonecrosis began to be recognized difficult to treat and associated with certain medications - bisphosphonates (BRONJ) 2011 (ADA): antiresorptive-related, due to association with a monoclonal antibody (denosumab) designed to prevent osteoclastic maturation (ARONJ)

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155 MRONJ 2014 (AAOMS): medication-related due to discovery that antiangiogenic therapies may also be implicated risk is increased if agents are combined with bisphosphonates

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157 MRONJ (Pathogenesis) once in the serum, 50% of bisphosphonates are cleared by the kidneys with the remainder going to bone osteoclasts and osteoblasts have affinity for medication, incorporated into bone matrix - inhibit osteoclastic function resulting in disruption of the basic cellular unit (BMU)

158 MRONJ

159 RISK FACTORS advanced patient age (> 65 years) steroid use or chemotherapy diabetes smoking or alcohol poor oral hygiene duration of drug use > 3 years

160 CLINICAL FEATURES mandible > maxilla necrosis following dental extraction spontaneous, denture pressure, or minor trauma of a torus most are painful serum C-telopeptide (CTX) - not reliable in predicting risk of MRONJ

161 TREATMENT best therapeutic approach is prevention manipulation of bone should be avoided osteonecrosis can be minimized with antibiotic prophylaxis drug holiday (3 months) is controversial annual IV zoledronic acid - surgery in 2 months benefits of antiresorptive therapy greatly outweigh the risk of developing MRONJ

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165 Christopher Klem, MD, FACS Otolaryngology Head and Neck Cancer and Reconstructive Surgeon MD Anderson Cancer Network Certified Physician Christopher Klem, MD, is a Head and Neck Surgeon at the Queen s Head and Neck Institute. He recently served as the Chief of Otolaryngology Head and Neck Surgery at Tripler Army Medical Center and retired as a Colonel from the Army after serving 26 years on active duty. Dr. Klem graduated from the Uniformed Services University of the Health Sciences in 1998 and performed his residency training in Otolaryngology Head and Neck Surgery at Walter Reed Army Medical Center. He served as Clinical Instructor in Otolaryngology at both Walter Reed and the University of Maryland for a year after residency. After completing a two-year fellowship in Head and Neck Oncologic and Microvascular Reconstructive Surgery at MD Anderson Cancer Center in Houston, Texas, Dr. Klem moved to Hawaii and served as an Army physician at Tripler Army Medical Center for 8 years. In 2010, he deployed to Helmand Province in Afghanistan as a Head and Neck Surgeon where he performed more microvascular reconstructive surgeries in a combat zone than anyone ever has. Although he practices the entire spectrum of benign and malignant Head and Neck tumors, Dr. Klem s special interests include oral cavity cancer, salivary gland tumors, thyroid and parathyroid, and complex microvascular reconstruction. He is recognized as one of the leaders in Head and Neck Clinical Ultrasound and instructs frequently for the American College of Surgeons. Dr. Klem holds appointments as Assistant Professor of Surgery at the University of Hawaii John A. Burns School of Medicine and the Uniformed Services University of the Health Sciences. Education & Training Medical School: Uniformed Services University of the Health Sciences Residency: Walter Reed Army Medical Center Professional Credentials Certifications: Otolaryngology Head and Neck Surgery Fellowships: MD Anderson Cancer Center, Head and Neck Oncologic and Microvascular Reconstructive Surgery

166 Daniel Alam, MD, FACS Otolaryngology Head and Neck Cancer and Reconstructive Surgeon MD Anderson Cancer Network Certified Physician Daniel Alam, MD, is a specialist in head and neck reconstructive surgery, including complex microvascular reconstructions to repair major facial injuries and cancer defects. He was the primary microvascular surgeon of the first face transplant procedure in the U.S. at the Cleveland Clinic. Dr. Alam has developed six new surgical procedures over the last five years, from minimally invasive surgeries for facial paralysis to complex facial reconstruction methods. The success rate of microvascular reconstruction in his section at the Cleveland Clinic was unparalleled nationally. Dr. Alam also serves as a Clinical Professor of Surgery at the University of Hawaii John A. Burns School of Medicine. After graduating from the Johns Hopkins University School of Medicine as valedictorian, Dr. Alam received his surgical training with an internship at Massachusetts General Hospital, followed by residency at the Harvard Medical School s Combined Hospitals Program in Otolaryngology/Head and Neck Surgery. He then completed a fellowship in facial plastic and reconstructive surgery at the UCLA Medical Center and served on its faculty as a clinical instructor in facial plastic surgery. Before joining Queen s, Dr. Alam served as the Section Head of Facial Aesthetic and Reconstructive Surgery in the Head and Neck Institute at the Cleveland Clinic and as Professor of Surgery at the Lerner College of Medicine at Case Western Reserve University. He holds senior-level academic positions in the American Academy of Facial Plastic and Reconstructive Surgery (AAFPRS). He is the director of an AAFPRS-sanctioned Fellowship in Facial Plastic Surgery, and serves on the organization s board of directors. Dr. Alam is a member of the AAFPRS National Academic Curriculum Committee, leading the section on facial paralysis and rehabilitation. He also serves on the editorial boards of four major journals. Education & Training Medical School: Johns Hopkins University School of Medicine Residency: Harvard Medical School, Combined Hospitals Program in Otolaryngology/Head and Neck Surgery Professional Credentials Certifications: Otolaryngology/Head and neck reconstructive surgery Fellowships: UCLA Medical Center, facial plastic and reconstructive surgery

167 KIRK Y. HIRATA, MD ANATOMIC/ORAL PATHOLOGY & HEMATOPATHOLOGY 1301 PUNCHBOWL STREET, IOLANI 4 HONOLULU, HAWAII PHONE: (808) /FAX: (808) khirata@queens.org