Chapter 10: Epithelial pathology Flashcards
Squamous papilloma
-‐ Most common soft tissue mass of the soft palate
-‐ HPV 6 and 11
-‐ Papillomatosis: extensive coalescing papillary lesions. Seen in acanthosis nigricans, Goltz-‐Gorlin (focal dermal hypoplasia) and nevus unius lateris
-‐ Laryngeal papillomatosis: juvenile-‐onset (aggressive when HPV11, can obstruct airway, related to maternal history of genital warts) and adult-‐onset. Hoarseness common. May progress into SCC (smokers and previous RT)
-‐ Vaccine for HPV 6, 11, 16 and 18
Verruca vulgaris
-‐ HPV 2, 4,6, and 40
-‐ Cutaneous horn: extreme accumulation of compact keratin in verruca vulgaris, SK, AK, and SCC
-‐ Prominent granular cell layer, elongated rete rigdes converge to center of lesion (cupping effect)
Condyloma acuminatum
Multifocal epithelial hyperplasia (Heck’s disease)
-‐ HPV 13, 32
-‐ Association with HLA-‐DR4
-‐ Abrupt and considerable acanthosis of the epithelium (extends upwards, so lesional rete rigdes are at level of the normal epith).
-‐ Mitosoid cell: cell with altered nucleus resembling a mitotic figure
Sinonasal papillomas (Schneiderian papillomas)
Fungiform (exophytic, everted, septal)
-‐ HPV 6, 11
-‐ Almost exclusively found in nasal septum
-‐ No malignant potential
Sinonasal papillomas (Schneiderian papillomas)
Inverted
-‐ Most common; HPV 6, 11, 16, 18
-‐ Most lateral nasal wall and sinuses (usually MX)
-‐ Monoclonal; CD44+ (vs papillary SCC)
-‐ Most aggressive and up to 25% SCC transformation
Sinonasal papillomas (Schneiderian papillomas)
Cylindrical (oncocytic)
-‐ Least common; no association with HPV
-‐ Most lateral nasal wall and sinuses (usually MX)
-‐ Hybrid or mixed: inverted + cylindrical
-‐ Less aggressive and lower potential for malignant transformation
Sinonasal polyps
-‐ Non-‐neoplastic proliferations composed of epithelial and stromal elements
-‐ Inflammatory: adults; history of rhinitis, allergy, aspirin intolerance and diabetes. Multiple, often bilateral. If seen in children, investigate cystic fibrosis
-‐ Antrochoanal: arise in antrum and extend to nasal cavity. 90% single.
-‐ Histo: INF-‐> sessile, thick BM, myxoid or gelatinous stroma which is highly inflamed, may show Charcot-‐Leyden crystals. AA -‐> pedunculated, not as inflamed.
Respiratory epithelial adenomatoid hyperplasia
-‐ Adenomatoid proliferation of resp ciliated cells in the nasal cavity, sinuses and nasopharynx
-‐ Glands often directly communicate with overlying mucosa
-‐ Pink basement membrane material separating glands from edematous inflamed stroma
Molluscum contagiosum
-‐ Caused by Molluscum virus (DNA poxvirus). Risk factors: HIV, atopic dermatitis and Darier’s.
-‐ Multiple papule of skin, which remain small for years and then spontaneously resolve in 6-‐9m
-‐ Histo: Bloated keratinocytes contain large, intranuclear viral inclusions named moluscum bodies
-‐ Moluscum bodies aka Henderson-‐Paterson
Verruciform xanthoma
-‐ Seen with lichen planus, lupus, pemphigus, Warty diskeratoma, GVHD, dysplasia, SCC
-‐ May have a history of trauma
-‐ Xanthoma cells: granules PAS+, diastase resistant; cells CD68+ and cathepsin B+
Seborrheic keratosis
-‐ FGFR3, PIK3CA gene mutation. Related to sun-‐exposure and hereditary tendency
-‐ Dermatosis papulosa nigra: AD form of SK. Found in 30% of AA.
-‐ Types: acanthotic, hyperkeratotic and adenoid
-‐ Inverted follicular keratosis of Helwig: irritated SK. Shows squamous eddies (whorled epithelial pattern due to metaplasia of lesional cells)
-‐ Leser-‐Trelat sign: sudden onset of pruritic SK can signify internal malignancy
Sebaceous hyperplasia
-‐ Sebaceous glands are holocrine
-‐ Associated with cyclosporine, corticoids, hemodyalisis and Muir-‐Torre syndrome
-‐ Muir-‐Torre syndrome: visceral malignancies, sebaceous adenomas/ca, and keratoacanthomas
-‐ Expressed sebum on compression (ddx with BCC)
-‐ Rhinophyma: Hypertrophy of sebaceous glands of nasal dome. Seen in pts with long standing acne roseace. Enlarged, bumpy nasal dome (~ tuberous sclerosis). Hx of facial flushing with driking hot liquids, alcohol and spicy foods. Histo: hyperplasia of sebaceous glds
Ephelis
-‐ MC1R gene mutation
Actinic lentigo
-‐ Age spots on face, hands, and arms (old individuals) due to UV damage
-‐ More common in people with facial freckles
Lentigo simplex
-‐ Clinically equal to non elevated nevus (early nevus?) on skin not exposed to sunlight
-‐ If multiple, consider lentiginosis profuse, Peutz-‐Jeghers and LEOPARD
-‐ LEOPARD: lentigines (multiple), electrocardiographic abnormalities, ocular hypertelorism, pulmonary stenosis, abnormal genitalia, retarded growth and deafness
Melasma (mask of pregnancy)
-‐ Associated with pregnancy, oral contraceptives, and hormonal replacement therapy
Oral melanotic macule
-‐ Focal increase in melanin and possible # of melanocytes. Unrelated to sun exposure.
-‐ Laugier-‐Hunziker syndrome: pigmentation of lips and buccal mucosa and longitudinal melanochyia (linear pigmentation of nail)
Oral melanoacanthoma
-‐ Reactive process. Almost exclusive in blacks and female predilection
Acquired melanocytic nevus
-‐ Junctional (macule, pigmented), compound (papule, less pigment), intradermal/intramucosal (papillary, hair, no pigment). Many involute spontaneously.
-‐ Type A (superficial, epithelioid), type B (middle, lymphocyte-‐like), type C (deeper, spindle cells)
Variants of melanocytic nevus
-‐ Congenital nevus: small <20 cm; large> 20 cm.
-‐ Giant hairy nevus: congenital nevus with hypertrichosis
-‐ Bathing trunk nevus (garment nevus): very large congenital nevus
-‐ Congenital nevus: 3-‐15% transformation into melanoma. Also increased risk CNS melanotic neoplasms
-‐ Halo nevus: shows hypopigmented halo due to destruction of melanocytes by immune system.
Seen in pts with recent melanoma excision
-‐ Spitz nevus: Histo ~ to melanoma (epithelioid and spinde cells), but young age and small size.
S100+ and NSE+. Has Kamino body (eosinophilic globoid seen in Spitz nevus)
-‐ Blue nevus: Tyndal effect gives color. Common and cellular.
-‐ Combined nevus: blue nevus + overlying melanocytic nevus
-‐ LAMB = lentigines, atrial and mucocutaneous myxomas, blue nevi (subset of Carney complex)
-‐ Balloon cell nevus: large, pale, polyhedral balloon cells (clear cells)
-‐ Nevus of Ota: aka oculodermal melanocytosis. Diffuse distribution of prolif melanocytes.
Unilateral facial and/or ocular slate-‐blue pigmentation (follows TN V1/V2)
-‐ Dysplastic nevus: usually develops in light-‐exposed areas, premalignant, melanocytes show nuclear atypia and may be syndrome-‐associated
Leukoplakia
-‐ Dysplasia found in 5-‐25% of cases.
-‐ Sanguinaria-‐associated keratosis: on MX vestibule or alv mucosa
-‐ Microorganisms: syphilis (dorsal tongue leukoplakia), candida, HPV
-‐ Alveolar ridge keratosis: in retromolar pad or alveolar ridge
-‐ Thin (mild) -‐> thick (homogenous) -‐> nodular (granular) -‐> verrucous
-‐ PVL: multiple lesions starting in gingiva and then spreading to other areas in non-‐smoking females. Clinically can become similar to VC and transform into SCC (within 8y)
-‐ Erythroleukoplakia: red areas which are so atrophic that can no longer produce keratin
-‐ Overall SCC progression: 4% (mild), 10% (mod), 35% (sev), 47% (erythrleuko) (in 2-‐4y)
Erythroplakia
-‐ Most in FOM, tongue and soft palate
Smokeless tobacco keratosis (snuff dipper’s keratosis; tobacco pouco keratosis)
-‐ Smokeless tobacco (spit tobacco): chewing tobacco, dry snuff and moist snuff (most pop)
-‐ Causes painless gingival recession, possibly with bone destruction
-‐ Keratosis: thin, gray-‐white plaque with blending borders, on the area where tobacco is placed
-‐ Snuff pouch: pouch revealed by stretching the mucosa with snuff dipper’s
-‐ Chevrons: parakeratin pointed projections above epithelial layers.
-‐ May show amyloid-‐like areas around basement membranes and blood vessels
-‐ Dry snuff higher risk of developing SCC (VC may also develop)
-‐ Should resolve within 2 weeks of habit removal (if more than 6, it’s true leukoplakia)
Oral submucosal fibrosis
-‐ Pale and marble-‐like stiff mucosa in betel quid (areca nut) users (affects ECM equilibrium).
-‐ CC: trismus and pain when eating spicy foods. More in BM, SP and reromolar area
-‐ Betel chewer’s mucosa: brown-‐red mucosa (not pre-‐cancerous).
-‐ Betel quid lichenoid lesions: ~ lichen planus
-‐ Dysplasia n 10-‐15% of cases; SCC in 6%; near 8% progress into SCC
Nicotine stomatitis
-‐ Dry mud appearance
-‐ Reverse smoker’s palate: significant potential for dysplasia and carcinoma
-‐ Should resolve upon discontinuation of habit within 1 month
Actinic keratosis
-‐ Due to sun damage in fair-‐skinned individuals
-‐ Risk factors: immunosuprresion, albinism, xeroderma pigmentosum, Cockayne syndrome, Bloom syndrome and Rothmund-‐Thompson syndrome
-‐ Bowenoid actinic keratosis: when full thickness dysplasia is present
-‐ 10% progress to SCC
Actinic cheilitis
-‐ Similar to actinic keratosis of the skin in behavior and pathophysiology
-‐ Sun damage to lip of fair-‐skinned people and outdoor occupation (farmer’s lip, sailor’s lip)
-‐ Estimated 6-‐10% SCC progression
-‐ Vermiolionectomy may be employed
Keratoacanthoma
-‐ Causes: UV (95% on sun-‐exposed skin), HPV (26 or 37), tar exposure, immunosupp and trauma
-‐ Seen in Muir-‐Torre syndrome
-‐ Phases: growth (6 wks), stationary (6 wks) and involution (6-‐12 mths)
-‐ Fergunson Smith: multiple non-‐involuting KAs, early life, hereditary (AD 9q22-‐31)
-‐ Eruptive Grzybowski: 100’s of small KAs in skin and upper digestive tract; sign of internal malignancy
-‐ Histo: center of lesion is crater-‐like and keratin-‐filled. Surrounding epithelium constricts neck of lesion. Downward proliferation pushes adjacent tissues and its extent is regular (inverted cup)
Squamous cell carcinoma
-‐ US: 3% of all cancers; 35,000 new cases (2011), 5300 deaths per year; 8th M/15th F
-‐ Plummer-‐Vinson (Paterson-‐Kelly): risk of SCC of esophagus, oropharynx and posterior mouth
-‐ Esophageal webs: intertwining fibrous bands of scar in esophagus, higher malignancy rate
-‐ Tertiary syphilis: increased risk dorsal tongue SCC
-‐ HPV: SCC of the oropharynx (16, 18, 31 and 33)
-‐ Locations: tongue, FOM, soft palate, gingiva, cheek, labial mucosa and hard palate
-‐ Gingiva: in post MD, similar to PG or IFH. Least associated with tobacco and most common in F
-‐ Distant mets: lung, liver and bones
-‐ Desmoplasia (scirrhous change): dense fibrosis in CT induced by SCC cells
-‐ Pts with SCC at risk for develop add synchronous (33%) or metachronous (66%; w/in 3y) cancers of the upper aerodig tract, esophagus, stomach and lung
Verrucous carcinoma (Ackerman’s tumor)
-‐ Also seen in larynx, vagina, penis, anus, sinonasal, esophagus, breast, axilla, ear and soles of feet
-‐ Associated with smokeless tobacco. May also arise from PVL
-‐ Oral florid papillomatosis: old name for PLV and VC
-‐ 20% may show concurrent SCC (if so, tx as SCC)
-‐ 90% survival with sx w/ou neck dissection
Papillary squamous cell carcinoma
-‐ Seen posteriorly (oropharynx, hypopharynx, larynx and sinonasal tract-‐worst prognosis)
-‐ Exophytic and looks like papilloma with fibrovascular cores
-‐ Cytologically looks like CIS and is not hyperkeratotic and not highly invasive
-‐ HPV 6,11,16,18+
Spindle cell carcinoma (pseudosarcoma, sarcomatoid SCC)
-‐ SCC (in situ or invasive) + invasive spindle cell component. Oral cavity and larynx.
-‐ Due to dysfunctional cadherin-‐catenin complex
-‐ 1/3 develop as recurrence after RT for WD-‐SCC (dedifferentiation)
-‐ IHC: + for CK (AE1/AE3, CAM 5.2)
-‐ Depth of invasion related to prognosis; tumor size unrelated
Adenosquamous carcinoma
-‐ Combination of adenocarcinoma and SCC (maybe it’s a mucoep). Located posteriorly.
Adenoid squamous cell carcinoma
-‐ Due to acantholysis (not true glandular structures)
-‐ Mostly on lip
Basaloid squamous cell carcinoma
-‐ Most in larynx, pyriform sinus and base of tongue
-‐ Superficial SCC (WD or in situ) + basaloid epithelium. Comedonecrosis common.
Carcinoma of the maxillary sinus
-‐ Weak association with tobacco
Sinonasal adenocarcinoma, intestinal-‐type
-‐ Strong assocation with wood dusts exposure (more in men); sporadic more in women
-‐ Second most common glandular sinonasal malignancy, after adenoid cystic carcinoma
-‐ Most on ethmoid sinus (men), followed by nasal cavity and MX sinus (women)
-‐ Mimics colonic adenoca (glands lined with plemorphic columnar cells in back-‐to-‐back pattern)
-‐ Types: papillary, colonic, solid, mucinous and mixed
-‐ CK20+, CDX2+, CK variable
Sinonasal adenocarcinoma, non intestinal-‐type
-‐ Divided into low-‐grade and high-‐grade
-‐ HG: males, MX sinus, markedly atypical and pleomorphic. LG: no sex predilection, nasal cavity
-‐ Histo: small glands lined with a single layer of uniform cells (seromucinous carcinoma), B2B
Sinonasal undifferentiated carcinoma (SNUC)
-‐ Origin: schneiderian membrane or olfactory epithelium
-‐ Some cases assoc w/ smoking, EBV and RT (weak)
-‐ Histo: nests, trabeculae, ribbons of medium-‐sized polygonal cells with organoid apperance
-‐ Comedonecrosis common
-‐ IHC: CK (7,8,19); negative for chromogranin and synaptophysin
Olfactory neuroblastoma (esthesioneuroblastoma)
-‐ Arises from olfactory epithelium, high in the nasal cavity close to cribiform plate
-‐ Rare <10y (unlike usual neuroblastoma). Bimodal peaks (15y and 50y). Most in adults
-‐ Histo: nests of round cells separated by fibrovascular septa. May have neurofibrillary stroma
-‐ True rosettes (Flexner-‐Wintersteiner) and pseudorosettes (Homer Wright)
-‐ Type: A (in nasal cavity), B (ext to paranasal sinus) and C (beyond nose and paranasal sinuses)
-‐ IHC: CD56, NSE, synaptophysin and chromogranin
Neuroendocrine carcinomas
- Oat cell ca in lung; Carcinoid tumor in GI
- Mills scheme: WDNEC (carcinoid tumor), MDNEC (atypical carcinoid tumor), PDNEC small cell (small cell undiff) and PDNEC large cell (large cell undiff)
- MDNEC: most common non-‐squamous tumor of the larynx, tobacco related
- Histo: “Salt and pepper” nuclei, nuclear molding, crush artifact
- NSE+, chromogranin+, synaptophysin+
Nasopharyngeal carcinoma
-‐ Group of malignancies that arise from lining epithelium of lymphoid-‐rich nasopharynx
-‐ High incidence in China; intermediate in SE Asia; low in US
-‐ Assoc factors: EBV, vitamin C def, salt fish diet (nitrosamines)
-‐ Rule out whenever recurrent persistent otitis media occurs in a middle aged person
-‐ Most common site or origin: lateral wall at Rosenmuller’s fossa
-‐ In 60% of pts, first sign is an enlarged metastatic lymph node
-‐ Types: keratinizing (type 1, SCC); nonkeratizining, differentiated (type 2); nonkeratinizing, undifferentiated (type 3, lymphoepitelioma, lymphoepithelial carcinoma)
-‐ Type 1 has worse prognosis, probably because due to response to radiation
-‐ Lymphoepithelioma: Regaud type (clusters, nests or aggregates of neoplastic epithelial cells with lymphocytes) and Schminke type (dispersed tumor cells forming a syncitial net)
Basal cell carcinoma
-‐ Most common of all cancers
-‐ Mainly due to UV. Also arsenic ingestion, immunosuppresion, PUVA (for psoriasis)
-‐ Seen in Gorlin syndrome, xeroderma pigmentosum, albinism, Rasmussen, Rombo and Bazex-‐ Christol-‐Dupre syndromes
-‐ PTCH (9q22) mutation +p53 mutation+ SMO
-‐ Clinical patterns: noduloulcerative (most common-‐telangiectatic vessels, aka rodent ulcer), pigmented (nodular with melanocytes), sclerosing (morpheaform-‐ mimics scar), superficial (multifocal-‐ mimics psoriasis), and syndromic (sun exposed and not exposed areas)
-‐ Basosquamous carcinoma: “collision” tumor of BCC and SCC
-‐ Mohs micrographic surgery: frozen sections to determine if BCC/SCC was entirely removed
Merkell cell carcinoma
-‐ Merkel cells of the epidermis are primarily associated with nerve endings
-‐ Risk factors: UV light and immunosuppresion (transplant, HIV and lymphocytic leukemia).
-‐ May be caused by the Merkell cell polyoma virus (MCPyV)
-‐ 75% facial skin. Dome shaped nodule with smooth surface and telangiectasias (rarely ulcerates).
-‐ AEIOU: Asymptomatic; Expands rapidly; Immunosuppressed; Older people; UV exposed areas
-‐ IHC: CK20+ (perinuclear dot-‐like); also synapt, chromogr A and NSE; TTF-‐1 to exclude lung met
-‐ Grimelius stain shows granules
-‐ 25% of pts develop additional malignancies (SCC skin, hem malig or breast/ovary adenoca.)
Microcystic adnexal carcinoma (sclerosing sweat duct carcinoma)
-‐ Cytologically bland but locally aggressive
-‐ Plaque-‐like indurated lesion of the upper lip
-‐ Histo: squamous/basaloid cells; horn cysts in superficial portion; ductal structures in deeper portions; neural/vascular invasion; and desmoplastic stroma
Melanoma
-‐ 50-‐70% BRAF mutation (Ras-‐Raf-‐Erk pathyway).
-‐ Types: superficial spreading (most common), nodular (sometimes amelanotic), lentigo maligna melanoma (melanoma in situ, arises from lentigo maligna-‐Hutchinson’s freckle), and acral/mucosal lentiginous melanoma (most common in oral cavity and blacks)
-‐ Superficial spreading: interscapular area in males, back of leg in female
-‐ IHC: HMB-‐45, Melan-‐A, Mart-‐1, Fontana-‐Masson, S-‐100
-‐ Prognosis: Breslow classification (depth of invasion assoc w/ poor prognosis for skin lesions)
-‐ Elevated serum lactic dehydrogenase (LDH) and ulceration: poor prognosis (skin)
-‐ BNAS: worse prognosis (interscapular back, post and lat neck, posterior upper arm, and scalp)
-‐ Better prognosis for women and pts < 50y
-‐ Oral: 13-‐22% survival (better for younger, worse for amelanotic)
