ORAL BIOMEDIS PATOLOGI ANATOMI

By dr. Agus Suharto, Sp. PA, edited by CR #01

I. Diseases of the Mouth & Jaw II. Diseases of the Salivary Glands A. Congenital Disorders A. Sialadenitis B. Inflammatory disorders B. Acute parotitis C. Tumors and tumor-like conditions C. Sjogren syndrome D. Mucocele E. Ranula F. Tumors of the salivary gland NEOPLASMA MALIGNA Squamous cell carcinoma Karsinoma epidermoid dengan pertandukan Common, derived from keratinocytes in epidermal layer Usually men, associated with sun exposure (UV light may induce p53 mutations and diminish surveillance function of Langerhans cells in epidermis), PUVA treatment for psoriasis, arsenic, tars/oils, chronic ulcers, draining osteomyelitis, old burn scars, necrobiosis lipoidica, hidradenitis suppurativa, Were bigger than we ever dreamed | 119

ionizing radiation Risk factors: immunosuppression (post-transplant or HIV), xeroderma pigmentosa (disorder with diminished capacity for DNA repair after UV light exposure, due to gene at 9q22.3; associated with squamous cell, basal cell carcinoma and melanoma), lack of pigmentation in skin, actinic keratosis (precursor lesion), epidermodysplasia verruciformis; very rare in blacks 5% are node positive at diagnosis; metastatic rate is 5-10% in transplant patients, who do poorly with metastatic disease Slow growing, locally invasive but rarely metastasizes outside nodes (but see above); most common site is lung

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Metastases more likely in tumors that originate in scars or ulcers

SQUAMOUS CELL CARCINOMA

Prognosis : excellent; metastases uncommon if tumor < 1.5 cm deep; 5% metastasize if 2 cm or more and definite dermal invasion Good prognostic factors : low stage, no/superficial dermal invasion, small vertical tumor thickness (< 4 mm), well differentiated, short duration, location other than scalp, ears, lips, nose, eyelids or soft tissue (which readily invade subcutaneous tissue) Treatment: surgical excision with adequate margins; also curettage, electrodesiccation, cryotherapy, radiation therapy Gross : often white plaque (leukoplakia); may have induration, ulceration, hemorrhage Micro : atypia at all levels of epidermis; 80% are well differentiated with keratin pearls, intercellular bridges and no/rare keratohyaline granules; invade dermis by definition; may contain non-neoplastic melanocytes that transfer melanin to tumor cells; occasionally clear cells, rarely signet ring cells Spindle, adenoid and verrucous variants are described separately Other variants are acantholytic (pseudoglandular, tumor clefts produed by acantholysis of tumor cells) and pseudoangiosarcomatous (clefts separate neoplastic lobules) Low grade (well differentiated) : cell differentiation, uniform cell size, intact intercellular bridges, no/rare mitotic figures, no/mild pleomorphism High grade (poorly differentiated): little cell differentiation, pleomorphism with spindle cells, necrosis, marked mitotic activity, deep invasion

Positive stains: high molecular weight keratin, Were bigger than we ever dreamed | 121

EMA, involucrin, p53 (50%), variable CEA

Negative stains: Ber-EP4, usually CK7 and CK20 (head and neck tumors, Mod Path 2004;17:407) Diagnosis Differential : keratoacanthoma (for well differentiated tumors)

Squamous Cell Ca Squamous cell carcinoma (HE) x 75

Squamous cell carcinoma (HE) x 150

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Selected cases of squamous cell carcinoma: (a) a representative case of moderately differentiated squamous cell carcinoma (H&E, X 40); (b) intranuclear staining for human telomerase reverse transcriptase activity (X 200); (c) intracytoplasmic COX-2 stain (X 200); (d) strong intranuclear p53 expression (X 400).

Selected cases of keratoacanthoma: (a) a representative case of early keratoacanthoma with overhanging lips and central horn-filled crater (H&E, 40); (b) negative for telomerase activity ( 400); (c) basal staining for p53 ( 100); (d) negative COX-2 stain ( 200).

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Histopathologic criteria to differentiate early keratoacanthoma from a well to moderately differentiated squamous cell carcinoma (Ackerman et al and Cribier et al)

Keratoacanthoma Exoendophytic lesion with a central hornfilled crater Overhanging 'lips' of epithelium Rarely ulcerated Abundant pale staining cytoplasm of keratinocytes Intraepithelial abscesses within the lesion Acantholytic cells within the intraepithelial abscesses often Gland-like formations rare

Squamous cell carcinoma Predominantly endophytic with no horn-filled crater No epithelial 'lips' Commonly ulcerated Less common

Rare Acantholytic cells form without associated neutrophils Pseudoglandular formations often Common Indistinct

Lack of anaplasia Sharp outline between tumor nests and stroma Absence of stroma desmoplasia

Present

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Immunohistochemical expression of telomerase activity, COX-2, and p53 in keratoacanthoma (KA) and squamous cell carcinoma (SCC). TABLE .. KA a (n=24) Telomerase Negativeb Weakc Strongd Negative Weak Strong Negative Weak Strong 01(4.2) 20(83.3) 03(12.5) 16(66.7) 07(29.2) 01(4.2) 10(41.7) 13(54.2) 01 (4.2) SCC a (n=17) 0 (0) 06(35.3) 11(64.7) 04(23.5) 04(23.5) 09(52.9) 02(11.8) 04(23.5) 11(64.7) 'P' value 0.001
Jadi maksud table disamping ini itu jelasin pewarnaan yg digunakan buat SCC nya, ada yg gunain telomerase, COX-2 dan p53.

COX-2

0.001

p53

0.000

a b c d

Number of samples (percentage in brackets). Negative no staining. Weak Combined score of <= 3. Strong Combined score of >3.

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BASAL CELL CARCINOMA

Disebut basal cell carcinoma karena yang mengalami perubahan adalah sel epitel basal, kan epitel itu ada beberapa jenis (epitel propium, granulosum, spinosum dan basale) Most frequent form of skin cancer Usually sun exposed skin (not mucosal surfaces), in proportion to number of pilosebaceous units present Rosai claims these tumors attempt to differentiate toward pilosebaceous units, but often this is not readily apparent Often multiple tumors Usually older adults Slow and indolent, untreated cases may invade subcutis, skeletal muscle and bone; facial tumors may invade skull, nares, orbit or temporal bone; only 100 metastatic cases described, often associated with basal cell nevus syndrome or basosquamous histology, on sunlight-protected skin Metastases are rare; 60% to regional lymph nodes, also lung, liver, bone Risk factors: Basal cell carcinoma (HE) x 75 fair skin, blue eyes, immunosuppression (higher incidence, more aggressive tumors), xeroderma pigmentosum

Basal cell carcinoma ini disebut juga dengan karsinoma basoselulare. Semua karsinoma basoselulare ini sifatnya progresif, prognosisnya jelek, dan membutuhkan terapi radiasi (kemoterapi). Mudah metastasis, namun untuk metastasis membutuhkan banyak proses. Metastasisnya dapat melalui limfe, pembuluh darah, dll. Jika metastasisya di pembuluh darah, maka akan membuat pembuluh darah baru (neovaskularisasi) oleh karena itu, saat ini banyak dikembangkan obat-obatan untuk mencegah pembentukan pembuluh darah baru, yaitu Anti VEGF (Vaskuler Endotelial Growth Faktor)

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Also associated with nevus sebaceus of Jadassohn, chronic venous stasis of lower leg, arsenic, X rays, skin injury, chickenpox scars, tattoos, hair transplant scars, immunosuppression Less common in children or young adults, sunlight-protected skin; rarely coexists with benign nevus Basal cell carcinoma Disebut juga dengan ulkus rodent. Gambaran histologis tepinya seperti pagar (palisade)

MALIGNANT MELANOMA Melanoma Pada dasarnya pewarnaan pada kulit itu disebabkan oleh dua factor ada factor instrinsik dan ekstrinsik. Kalo yang ekstrinsik contohnya karena paparan sinar UV, sedangkan kalo instrinsik adanya pigmen melanin. Keabnormalan melanin ini mula-mula akan jinak (melanoma) tapi lamakelamaan akan berubah ganas dan menjadi malignan melanoma. Sel-selnya banyak yang anaplasi (polimorfik dan atipi). Malignan melanoma yang terjadi pada daerah sel yang tidak ada melaninnya disebut juga dengan amelanotic melanoma. Keganasan malignat melanoma ini tergantung dengan kedalaman invasinya.

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 Incidence increasing worldwide - 48,000 cases and 9,200 deaths in US in 2000 Usually due to sun (UV light) exposure Warning signs : change in color of pigmented lesion, enlargement of existing mole, itching or pain in preexisting mole, development of new pigmented lesion in adult life, irregular borders in pigmented lesion, variegation of color in pigmented lesion Head and neck, lower extremities (particularly in women); rarely subungual (melanotic whitlow), palm, sole. Also oral and anogenital mucosa, esophagus, meninges, eye Populations at higher risk: whites with fair skin, red hair, tendency to burn or freckle from sun exposure, large number of melanocytic nevi, xeroderma pigmentosum, familial dysplastic nevi, melanosis, vitiligo, possibly neurofibromatosis type I Up to 10% may be familial due to CMM1 gene at 1p36 Blacks have low risk, their common melanoma sites are palms, soles, nail beds or mucous membranes Usually after puberty, occasionally children - all have same morphology 5% are multiple, although prognosis is related to type and stage of largest lesion, not number of lesions; must distinguish multiple lesions from hot nevi / nevus activation Achilles tendon tumors are often spindled Tend to grow laterally and deep; common metastases to regional lymph nodes, also liver, lungs, GI tract, bone, CNS, heart (50% at autopsy), skin (satellite tumors within 2 cm of primary tumor), other sites Overall 5 year survival is 60% Poor prognostic factors:

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increased Breslow (vertical) thickness in primary tumor, high stage (TNM), males (do worse than females), high mitotic rate, ulceration, microscopic satellites (tumor nests 50 microns or larger and separated from main tumor mass), deeper level of invasion for T1 tumors, higher % tumor area/volume in sentinel node, increased density of dendritic leukocytes in nodal paracortex (associated with risk of tumor in non-sentinel nodes, recurrence and death, Mod Path 2004;17:747) Overall behavior is variable, with occasional late deaths or long survival even with widespread satellite nodules Melanoma S100: nuclear and cytoplasmic, 90%+ sensitive but not specific (although usually negative in tumors considered in the differential) HMB45: less sensitive but more specific than S100; negative in desmoplastic melanoma MelanA/Mart1: sensitive, but also stains steroid-producing cells in ovary, testis, adrenal cortex Tyrosinase:

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sensitive, but also stains peripheral nerve sheath and neuroendocrine tumors Microphthalmia transcription factor: sensitive, but also stains dermatofibroma and smooth muscle tumors; negative in spindle cell / desmoplastic melanoma NKI-C3 and NSE: nonspecific Negative stains: p53
Nevus Pigmentosus Melanoma steps of tumor progression in dysplastic nevi

Melanocytic hyperplsia, B. Junctional nevus, C. Dysplastic nevus (compound nevus with abnormal architectural and cytologic freatures, D. early melanoma (radial growth phase melanoma large dark cells in epidermis), E.advanced melanoma (vertical growth phase)

Malignant Melanoma Lesions are irregular in contour and pigmentation. Macular areas correlated with the

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radial growth phase, while raised areas usually correspond to nodular aggregation of malignant cells in the vertical cell growth Malignant Melanoma

Beberapa gambar disamping adalah gambaran histologis perbesaran lemah maupun kuat, kan di praktiukum udah yaa, jadi recall aja materi praktikum nya Malignant Melanoma radial growth phase of melanoma Irregular nested and single cell growth of melanoma cells within the epidermis and an underlying inflammatory response within the dermis.

Malignant Melanoma vertical phase growth Nodular aggregates of infiltrating cells

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Malignant Melanoma High-power view of malignant melanoma cells

Nodular malignant melanoma (HE) x 10

Superficial spreading melanoma (HE) X 100

MALIGNANT MELANOMA

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Undifferentiated carcinoma Pada dasarnya, carcinoma terdapat tida macam differensiasi, diferensiasi baik, sedang, dan buruk. Nasopharynx Inflammation Acute Chronic Neoplasm Juvenile angiofibroma Undifferentiated carcinoma

a McIvor mouth gag is applied and a left nasopharyngeal mass is visible behind the soft palate and left posterior pillar. The final diagnosis was lymphoepithelioma

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Nasopharingeal Ca, non-keratinizing, undiff.

Sering disebut juga NPC (Nasopharink Carcinoma) Sel ini murni berasal dari sel epitel yang mengalami keabnormalan, tetapi gambaran histologis banyak terlihat sebukan limfosit yang berfungsi membunuh sel-sel tumornya, hiperkromatid

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EBV (IH; LMP-1) x 600

Gambaran disamping adalah gambaran histologis dari undifferentiated carcinoma yang terinfeksi Epstein Bar Virus, dilihat dengan menggunakan pewarnaan LMP (Laten Membran Protein)

Anaplastic (undifferentiated) Carcinoma

Pada NPC ini, carcinomanya tersembunyi, pada saat pemeriksaan AJH (Aspirasi Jarum Halus) dia tidak terlihat, namun NPC ini mudah bermetastasis Pada gambaran histologis terlihat gumpalan sel tumor yang dikelilingi oleh limfosit

Metastasic tumor LARYNX: benign vs malignant

Pada penyanyi dengan suara seriousa biasanya ada nodus singer, sedangkan papilloma yang terdapat diplica vokalis itu merupakan infeksi dari HPV Were bigger than we ever dreamed | 135

Laryngeal papillomatosis

Laryngeal Carcinoma

Gross: fungating/papillar

Adenoid cystic carcinoma

Most characteristic appearance consists of cribriform pattern with masses of small, dark-staining cells arrayed arround cystic spaces Adenoid cystic carcinoma ini, memiliki gambaran histologis pada otot luriknya terdapat abnormalitas/tumor. Tumor epithelial ini tersusun Kribiformis seperti jaringan. Lumen ini memiliki massa mucoid sehingga disebut mucoepidermoid tumor. Were bigger than we ever dreamed | 136

Mucoepidermoid tumor (Palatal gland) Mucoepidermoid tumor (Low grade)

Comprised of mucus-producing and epidermoid omponents and cells intermediate between the two Mucoepidermoid tumor (moderate grade)

Mucoepidermoid tumor (High grade)

Jadii, jangan lupa yaa teman-teman tentang terminology pada tumor dan kanker, kalo ditulisan belakangnya : ..oma : jinak .carcinoma : ganas dari sel epitel .sarkoma : ganas dari sel mesenkimal

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