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Pathology Department Neoplasia

“New Growth”; From Latin Word for Crab
❑ Cancer: Neoplasms are not controlled by the body
– Continue to replicate indefinitely
– Tumors may flourish, even while the host is wasting away
– Cancers induce increased blood supply
Overview ❑ Cancer: 2nd leading cause of US deaths → After cardiovascular disease

Oral Neoplasia ❑ Oncology = study of tumors (“oncos” = tumor, “logos” = study of)
-- Oncologist = physician who treats cancer exclusively
– Hemoncologist = specializes in leukemias, lymphomas, etc.
-- Hematologist = blood doctor, treats leukemias, lymphomas, etc.
– Surgical oncologist; Radiation oncologist

❑ Typically monoclonal

❑ Malignant (cancers): invade, destroy, metastasize (distant spread)

❑ Benign: nonmalignant neoplasm; add suffix “-oma”
Prepared by: LokDonLub 1

Neoplasia
Neoplasia
• Tumors are like organs:
– All have parenchyma and stroma.
– Cells usually look similar to cells in the organ where the
• All tumors have two basic components:
tumor arose. – Parechyma: made up of neoplastic cells
– Cells will continue to perform some of the functions of
the parent organ. – Stroma: made up of non-neoplastic, host-
derived connective tissue and blood vessels
• Tumors are different from organs: The parenchyma: The stroma:
– They don't contribute to the homeostasis of the body. Determines the Carries the blood supply
– They usually grow more rapidly than surrounding biological behavior of Provides support for the
tissues. the tumor growth of the
– Some benign and all malignant tumors never cease to From which the tumor parenchyma
grow. derives its name
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Features of Neoplasms Neoplasia

Benign v. Malignant
Benign vs. Malignant
Benignant Malignant
Rate of growth Slow Rapid
Type of growth Expansile only Expansile and/or invasive
Similarity to original Very similar Not similar
tissue/cells
Uniformity of cells Uniform Cells vary in shape
(pleomorphic) and size
Mitotic rate Low (few mitoses) Medium to high (many
mitoses), may be abnormal
or in abnormal location
Nuclear/cytoplasmic Normal High
ratio
Nuclei Normal, uniform Enlarged, pleomorphic, Leiomyoma
dark (hyperchromatic) Benign Smooth Muscle Neoplasm

Photos: Kumar, Cotran, Robbins. Robbins Basic pathology, 7th ed., Saunders, Philadelphia, 2003; Stevens A, Lowe J. Slide atlas of pathology. Mosby, London, 1995.
.

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Tumor Names
Tissue of Origin Benign Malignant
Fibrous Fibroma Fibrosarcoma Classification according to biological behavior
Bone Osteoma Osteosarcoma
Cartilage Chondroma Chondrosarcoma
Adipose Lipoma Liposarcoma
Nerve Neurofibroma Neurofibrosarcoma
Smooth muscle Leiomyoma Leiomyosarcoma benign borderline malignant
Skeletal muscle Rhabdomyoma Rhabdomyosarcoma
Gland Adenoma Adenocarcinoma
Squamous
Papilloma Squamous cell carcinoma
epithelium
Melanocyte Nevocellular nevus Malignant melanoma
Lymphoid Lymphoid hyperplasia Lymphoma

Neoplasia Neoplasia
• Dysplasia : • Dysplasia does not mean cancer
– Definiton: a loss in the uniformity of the individual • Dyplasia does not necessarily progress to
cells and a loss in their architectural orientation. cancer
– Non-neoplastic
• Dysplasia may be reversible
– Occurs mainly in the epithelia
• If dysplastic changes involve the entire
– Dysplastic cells shows a degree of : pleomorphism,
hyperchrmasia,increased mitosis and loss of
thickness of the epithelium it is called :
polarity. CARCINOMA IN-SITU

Dysplasia Features:
Dysplasia
• Nuclear abnormality
• Increased rate of
multiplication. – Increased N/C ratio • Clinical significance:
– Irregular nuclear membrane – It is a premalignant condition.
• Disordered
maturation. – Increased chromatin content – The risk of invasive cancer varies with:
✓ grade of dysplasia (mild, moderate, sever)
• Cytoplasmic abnormalities due
to failure of normal ✓ duration of dysplasia
✓ site of dysplasia

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The malignant looking tumor cell has;

✓Increased nuclear DNA
✓Increased nuclear/cytoplasmic ratio
✓Hyperchromatic nucleus
✓Coarsening of chromatin
✓Wrinkled nuclear edges
✓Multinucleation
✓Macronucleoli
✓Numerous and bizarre mitotic figures
✓Failure to mature along normal functional lines
✓Cells of widely varying sizes
✓Loss of orientation of cells to one another

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Anaplastic cells
Hallmarks of Cancer
• Self-sufficiency in growth signals
• Insensitivity to antigrowth signals
• Evading apoptosis
• Limitless replicative potential
• Sustained angiogenesis
• Tissue invasion and metastasis

Incidence of Cancer
More than 100 Different Types of Cancer
Hallmarks of Cancer

Photo: Kumar, Cotran, Robbins. Robbins Basic pathology, 7th ed., Saunders, Philadelphia, 2003. Photo: Kumar, Cotran, Robbins. Robbins Basic pathology, 7th ed., Saunders, Philadelphia,

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Cancer Risk Increases with Age Oral Cancer

Long-term exposure & less effective immune system Age- & Gender-Specific Incidence Rates

Photo: Stevens A, Lowe J. Slide atlas of pathology. Mosby, London, 1995.

Photo: Neville, et al. Oral and maxillofacial pathology, 2002.

Carcinogenesis Factors in Cancer Development

• Genetic • Inflammation
– Protooncogenes • Family history: 2 possibilities
– Tumor suppressor genes
• Viruses
– Apoptosis genes
– DNA repair genes • Bacteria: H. pylori
• Stages • Environmental factors
– Initiation: mutation
– Promotion: increased cell growth
– Progression: invasiveness, angiogenesis

Genetically Associated Cancers

The cancer may not be in the mouth

❑ Acanthosis nigricans
❑ Ataxia-Telangiectasia
❑ Cowden syndrome
❑ Dyskeratosis congenita
❑ Gardner’s syndrome
❑ Gorlin syndrome (nevoid basal
cell carcinoma syndrome)
❑ Mucosal neuroma syndrome
(MEN IIB, MEN III)
❑ Neurofibromatosis
❑ Peutz-Jeghers syndrome
❑ Trisomy 21 (Downs syndrome)
MEN (Multiple Endocrine Neoplasia) IIB or III.
❑ Tuberous sclerosis
Painless yellow-white nodules of the tongue.
Photo: ESTOP. ❑ Xeroderma pigmentosum

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Carcinogenesis
Viruses Implicated in Human Neoplasia
Virus
Epstein-Barr virus (EBV)
Hepatitis B virus (HBV)
Human papillomavirus (HPV)
Human papillomavirus (HPV)
HTLV-1
Causes of Oral Carcinoma
The happy, toothless smoker
Neoplasm
Burkitt’s lymphoma
Nasopharyngeal carcinoma
Some B-cell lymphomas
Some Hodgkin’s disease
Hepatocellular carcinoma
Cervical carcinoma
Some skin carcinomas
Some oral and laryngeal carcinomas
T-cell leukemia/lymphoma
• Tobacco smoking
• Tobacco chewing
• Betel/pan/areca chewing
• Alcohol abuse
• Precancer
• Plummer-Vinson disease
(severe Fe deficiency)
• Human papillomavirus 16/18
• Chronic infection?
• Syphilitic glossitis
• History of irradiation
• History of sun damage (lip)
• History of H&N carcinoma
• Increasing age
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Human Papillomaviruses in Oral Lesions
24 genotypes have been isolated from oral lesions & mucosa
Lesion Genotype(s) *
Normal mucosa 6, 7, 11, 16, 18, 31, 33, etc.
Verruca vulgaris (common wart) 2 a – e, 4, 6, 40
Papilloma (squamous papilloma) 6 a – f, 11 a, b
Condyloma acuminatum 2, 6, 11 a, b, 16, 18, 53, 54
Focal epithelial hyperplasia (Heck’s disease) 13, 32
Smokeless tobacco keratosis 2, 6
Leukoplakia, no dysplasia 2, 6,11,16,18
Leukoplakia with epithelial (koilocytic) dysplasia 2, 6, 11, 16, 18, 31, 33, 35
Carcinoma in situ 2, 6, 11, 16, 18, 31, 33, 35
Keratoacanthoma 26, 37
Verrucous carcinoma 2 a – e, 6, 11, 16, 18
Squamous cell carcinoma 16, 18, 31, 33, 35
* genotypes in bold yellow are isolated in at least 1/3 of all cases with HPV
Precancers and Preneoplastic Conditions
❑ Cancer development is NOT inevitable!
❑ Chronic atrophic gastritis
-- Gastric carcinoma in pernicious anemia
i.e. vitamin B12 deficiency
❑ Chronic ulcerative colitis
-- Colorectal carcinoma
❑ Villous adenoma of colon
-- Colorectal carcinoma
❑ Leukoplakia of mouth, vulva, penis
-- Squamous cell carcinoma
Photo: E. Lalonde, West Virginia University, Morgantown, West Virginia.
Clinical Appearance Matters
Verruciform Leukoplakia, Granular leukoplakia, Verrucous Leukoplakia
Carcinoma in situ
Hyperkeratosis
Photo: J. Pindborg, Univ. Copenhagen,
Copenhagen, Denmark.
Photo (left): J. Pindborg, Royal College of Dentistry, Copenhagen, Denmark.
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Oral Precancers
Erythroleukoplakia Increased Risk (Not 100%!)
Speckled Leukoplakia

❑ Leukoplakia
❑ Erythroplakia
❑ Smokeless tobacco keratosis
❑ Lichen planus (erosive)
❑ Reverse smoker’s palate
❑ Oral submucous fibrosis
❑ Smooth, red tongue in Plummer-
Vinson disease
❑ Actinic cheilosis

Corrugated thick and thin leukoplakia of the oral floor and Leukoplakia in syphilitic glossitis
ventral tongue, with pink areas surrounded by white. From: Schwimmer, 1876, Budapest

The TNM Staging System

Staging of Cancers
Clinical Classification Tumor size:
T0 = no tumor
❑ Stage shows severity of clinical features of the tumor T1 = <2 cm. in size
❑ Usually staged without sophisticated imaging technologies T2 = 2-4 cm. in size
-- This may change soon T3 = >4 cm. in size
❑ Stage I = small, localized tumor
❑ Stage IV = huge or metastatic tumor Lymph node involvement:
❑ Not bad at forming prognosis N0 = no positive nodes
-- Stage I is good N1 = few ipsilateral nodes
-- Stage IV is very bad N2 = many ipsilateral nodes
❑ TNM staging system: or contralateral nodes
– T = tumor size, in cm.
– N = presence of tumor in local/regional lymph nodes Distant metastasis:
– M = presence of tumor at a distant site M0 = no metastasis
(beyond local lymph nodes; e.g. “below the clavicles”) M1 = metastasis below the
❑ Tables used to establish the stage, combining the TNM evaluations clavicle
Mx = suspected metastasis

Photo: Stevens A, Lowe J. Slide atlas of pathology. Mosby, London, 1995.

Prognosis Varies with Cancer Site Cancer

5-Year Survival Rates Once Uniformly Lethal

❑ 1900: <5% survival

❑ 1945: 20% survival
❑ 1986: 50% survival
❑ 2003: 63% survival
❑ ACS 2015 goal: 50% reduction in
mortality rates
❑ ACS 2015 goal: 25% reduction in
incidence
Adenocarcinoma at autopsy, rates
circa 1856
❑ How: prevention, early detection,
Photo: Stevens A, Lowe J. Slide atlas of pathology. Mosby, London, 1995.
quality management, research

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Causes of jaw swelling

• Odontogenic cysts
Overview ODONTOGENIC and • Odontogenic tumors
NON ODONTOGENIC TUMOR • Giant cell lesions
• Fibro-osseous lesions
• Primary (non-odontogenic) tumors of bone
• Metastatic neoplasms
• Chronic osteomyelitis

Odontogenic tumors Odontogenic tumors

• derived from epithelial, ectomesenchymal,
• 1. Epithelial
mesenchymal elements of tooth forming apparatus • 2. Epithelial+mesenchymal
• ameloblastoma
• central (intraosseous) • ameloblastic fibroma
• squamous odontogenic
– maxillofacial skeleton tumor • odontoma
• peripheral (extraosseous) • calcifying epithelial • dentinogenic ghost cell tumor
– soft tissue - gingiva + alveolar mucosa odontogenic tumor • primordial odontogenic
• ethiology unknown, from some odontogenic cysts • adenomatoid odontogenic tumor
• RTG tumor
– uni-, multi-locular radiolucencies ~ cysts x radiopacities
• !!! biopsy !!!

Classification of Non Odontogenic Tumours

Odontogenic tumors
• 3. Mesenchymal
• odontogenic fibroma
• odontogenic myxoma
• cementoblastoma
• Epithelial
• 4. Carcinomas
• ameloblastic carcinoma
• primary intraosseous squamous
cell carcinoma
• clear cell odontogenic
carcinoma
• ghost cell odontogenic
carcinoma
• sclerosing odontogenic
carcinoma
• 5. Odontogenic carcinosarcoma
• 6. Odontogenic sarcoma
– Malignant
• Benign • Basal Cell Carcinoma
• Epidermoid carcinoma or
• Papilloma
Squamous cell carcinoma
• Squamous Acanthoma
• Verrucous Carcinoma
• Keratoacanthoma
• Spindle Cell Carcinoma
• Pigmented Cell Nevus
• Adenoid Squamous cell
• Premalignant Carcinoma
• Leukoplakia • Lymphoepithelioma and
• Leukoedema Transitional cell
• Intraepithelial Carcinoma carcinoma
or Carcinoma in situ • Malignant Melanoma
• Erythroplakia
• Oral Sub Mucous Fibrosis

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Classification of Non Odontogenic Tumours.. Classification of Non Odontogenic Tumours…

• Connective Tissue – Malignant • Vascular Tissue – Malignant

– Benign • Fibrosarcoma – Benign • Haemangioendothelioma
• Adipose tissue • Haemangiopericytoma
• Fibroma • Hemangioma
• Kaposi’s Sarcoma
• Giant Cell Fibroma – Benign • Hereditary Haemorrhagic
• Peripheral Ossifying • Lipoma
Talengiectasia • Cartilage tissue
Fibroma • Encephalo-trigeminal
• Verruciform Xanthoma – Benign
• Central Ossifying Fibroma Angiomatosis
– Malignant • Chondroma
• Peripheral Giant cell • Nasopharyngeal
• Liposarcoma Angiofibroma • Benign Chondroblastoma
Granuloma (GCG)
• Lmphangioma • Chondromyxoid Fibroma
• Central GCG
• Aneursmal Bone Cyst – Malignant
• Myxoma • Chondrosarcoma

Classification of Non Odontogenic Tumours… Classification of Non Odontogenic Tumours…

• Bone tissue • Lymphoid Tissue • Nerve Tissue • Tumours of Disputed
– Benign – Benign
• Osteoma
– Malignant
• Neurofibroma
Origin
• Malignant Lymphoma • Granular Cell
• Osteoid Osteoma • Neurolemmoma/schwanno
• Non-Hodgkin’s Lymphoma Myoblastoma
• Benign Osteoblastoma ma
• Reticular Cell Sarcoma • Congenital Epulis
– Malignant – Malignant
• Burkitt’s Lymphoma
• Osteosarcoma • Malignant peripheral nerve • Alveolar Soft Part
• Hodgkin’s Disease sheath tumor Sarcoma
• Muscle tissue • Leukaemias
• Tumour Like Lesions • Melanotic
– Benign • Ewings Sarcoma Neuroectodermal tumour
• Peripheral Giant Cell
• Leiomyoma • Plasma Cell Tumours of infancy
Granuloma
• Angiomyoma – Multiple Myeloma
• CGCG • Kaposi’s Sarcoma
• Rhabdomyoma – Plasmacytoma
• Exostoses • Ewing’s Sarcoma
– Malignant • Pyogenic Granuloma
• Leiomosarcoma • Anurysmal Bone Cyst
• Rhabdomyosarcoma • Traumatic Neuroma