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PART ONE REVISION. > PATHOLOGY - Cell Growth and Neoplasia > Flashcards

PATHOLOGY - Cell Growth and Neoplasia Flashcards

1
Q

What is the difference between lentigo maligna and melanoma?

A

both show proliferation of atypical spindle shaped melanocytes, but melanoma has dermal involvement, and lentigo only has involvement of the epidermis

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2
Q

What type of cell is in a Kaposi sarcoma? Which layer does it involve? What is it caused by?

A

Proliferation of spindle shaped cells and vessels in the dermis layer

Human herpesvirus HPV type 8.

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3
Q

What are the 3 main features of malignant tumours?

A
  1. Cellular and nuclear pleomorphism
  2. Nuclear hyperchromatism
  3. Decreased cytoplasmic:nuclear ratio
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4
Q

What is the definition of neoplasm?

A

Proliferation of cells independent of the surroudn tissue integrity which is progressive, even after initial stimulus has ceased

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5
Q

What are the main physiological differences between benign and malignant tumours?

A

Malignant are irregular, non-encapsulated, and fast-growing.

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6
Q

What are the main environmental carcinogenic factors (3)

A
  1. Chemicals
  2. Radiation
  3. Viruses
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7
Q

Which viruses contribute to ocular neoplastic tumours?

A
  1. HPV - 6 and 11 - conjunctival papillomas (16,18 high risk for carcinoma)
  2. EBV - orbital Burkitt’s lymphoma.
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8
Q

What is the difference in pathophysiology behind HPV and EBV?

A

HPV - produces E6 protein which binds and inactivates p53 –> uncontrolled DNA replication

EBV - produces protein that makes cell resistant to apoptosis

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9
Q

What is the pathophysiology behind xerderma pigmentosum? What are the systemic manifestations?

A

Autosomal recessive - deficiency in DNA nucleotide excision repair (NER) mechanisms leading to multiple skin tumours

Symptoms: Photosensitivity, solar keratoses, skin cancers

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10
Q

What is the difference in mutation in NF1 and NF2?

A

NF1 gene - 17q
NF2 gene (merlin) - 22q

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11
Q

What are the differences between NF1 and NF2 in systemic findings?

A

NF1
Ocular: Lisch nodules, optic nerve glioma, lid neurofibroma, choroidal naevi, retinal astrocytoma

Systemic: cafe-au-lait spots, axillary freckling, risk of sarcoma, phaeochromocytoma

NF2:
Ocular: Glioma, haematoma of RPE, early cataract

Systemic: schwannoma, meningioma

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12
Q

What is the difference in histology between neurofibroma and schwannoma?

A

Neurofibroma: derived from endoneurium - spindle cells seen on histology

Schwannoma: derived from Schwann cells. Palisaded spindle cells and myxoid areas.

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13
Q

What is the mutation in Li-Fraumeni syndrome? What are the clinical manifestations?

A

Germ-line mutation of p53.
High risk of childhood sarcoma and breast cancer

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14
Q

What is Von Hippel-Lindau syndrome genetic mutation? What are the clinical manifestations?

A

Mutation on chromosome 3 - AD

Capillary haemangiomata of retina, renal cell carcinoma, phaeochromocytoma, haemangioblastoma of cerebellum

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15
Q

What are the 3 mechanisms by which benign processes can become premalignant states?

A
  1. Benign tumours - can undergro malignant change after aquiring genetic mutations (pleomorphic lacrimal gland adenoma can transform to adenocarcinoma)
  2. Chronic inflammation: Chronic lymphocytic infiltrates in lacrimal gland can develop into lymphoma
  3. Intraepithelial neoplasia (carcinoma in situ): actinic keratosis can become squamous cell carcinoma if it breaches the basement membrane
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16
Q

What is a harmatoma? What cells does it normally involve?

What are the different types of harmatomas?

A

Non-neoplastic tumour of normal tissues of the site - typically involves blood vessels and melanocytes

  1. haemangiomas: proliferation of blood vessels
  2. naevi: proliferation of melanocytes (neural crest derived cells)
  3. benign astrocytic harmatomas - seen in tuberous sclerosis
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17
Q

What ocular conditions can cause haemangiomas?

A
  1. Sturge-Weber syndrome - extensive haemangiomas caused by mutation in GNAQ gene –> causes choroidal haemangiomas and vascular poliferation in the angle –> glaucoma.
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18
Q

Where are naevi typically found? What are their benign features?

A

Conjunctiva iris, choroid, retina

Benign features: Clear margins, no overlying subretinal fluid, no orange pigment/lipofuscin

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19
Q

What are benign astrocytic harmartomas? What are its associations? What are its ocular findings?

A

Astrocytes forming a matrix of caclification.

Associated with tuberous sclerosis

Can project into vitreous and stimulate retinoblastoma. ONE OF TWO OPTIC NERVE LESIONS that exhibit true autoflourescence (the other is drusen).

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20
Q

What are chroistomas? What are its ocular associations?

A

Non-neoplastic tumour of ectrodermal tissue in an abnormal location

  1. dermoid on bulbar conjunctiva - white/pale/yellow lesions associated with Goldenhar’s syndrome
  2. Phakomatous choristoma: eyelid nodule composed of lens capsular material
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21
Q

What are the common benign tumours in ophthalmology? (2)

What are some examples of these

A

Papilloma - benign tumor of epithelial surface
Adenoma - benign tumor of glandular tissue

Papilloma
- eyelids: basal cell papilloma (seborrhoeic keratosis)
- eyelids: squamous cell papiloma (molluscum contagiosum - poxvirus and viral warts - HPV) - most common epithelial benign eyelid tumour
- conjunctiva: pendunculated or sessile (HPV)

Adenoma
- Arise from sweat glands, sebaceous glands (yellow mass at caruncle), meibomian glands

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22
Q

What is a keratoacanthoma

What are its histological findings?

A

Rapidly growing but sponatenously resolving tumor of epidermis - can mimic an SCC
It is a nodule that grows over a few weeks - has central ulcer/crater with elevated shoudler, resolves within 2-3 months but can leave a scar

Histological findings
1. Central keratin mass (pink stain with H&E)
2. hyperplastic epidermis with clear demarcation between raised edge and normal skin seurface

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23
Q

What are the main associations/risk factors of basal cell carcinoma (BCC) ?

A
  1. Sunlight exposure
  2. Arsenic exposure
  3. Male
  4. Fair skin
  5. Immunosuppresion
  6. Genetic syndrome predisposition (Gorlin-Goltz, Xeroderma pigmentosa, albinism, bazex syndrome)
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24
Q

What are the main histological features of BCC? (4)

A
  1. Nodular - well-definding islands of proliferating basal cells with peripheral tumour cells arranged as palisades, cystic degeneration
  2. Superficial - scaly plaque lobules of cells budding into superficial dermis
  3. Infiltrating/sclerosing - small strands of tumour cells in fibrous stroma and ill-defined/no border with reduced peripheral palisading - more aggresive / morphoeic.
  4. Micronodular - multiple small nodular basiloid cells similar to infiltrative
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25
Q

What are the main associations / risk factors of SCC? (2)

A
  1. Sunlight exposure
  2. Immunosuppression (conjunctiva and cornea with AIDS)
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26
Q

What is the clinical appearance of SCC?

A

Fast growing nodular ulcer with papillomatous growth, has overlying keratinous horn.

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27
Q

What are the main histological features of SCC?

A
  1. Keratin pearls
  2. Spindle cell morphology is rare.
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28
Q

What are the symptoms of sebaceous cell/gland carcinoma? What are the histological findings? What staining is used?
What condition is associated with this?
Risk of recurrence is high or low? What is its prognosis?

A

Blepharoconjunctivitis, mimics chalazion, BCC, SCC

Nodular: lobules with foamy and vacuolated cytoplasm
Diffuse: Pagetoid spread through epithelium

Stained with oil red O.

Muir-Torre syndrome (associated with visceral tumours).

Risk of recurrence: High
Prognosis: Poorer than other eyelid tumours.

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29
Q

What is the most common ocular lymphoma?

A

Extranodal marginal zone lymphoma - low grade B-cell lymphoma derived from MALT

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30
Q

What is the histological appearance of conjunctival lymphoma?

A

Salmon patch appearance of conjunctiva with multiple small cells seen on histology

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31
Q

What are the two most common lacrimal gland neoplasias?

A
  1. pleomorphic adenoma - most common epithelial tumour
  2. adenoid cystic carcinoma
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32
Q

What is the difference in histology between pleomorphic adenoma and adenoid cystic carcinoma?

A

Pleomorphic: Mixed epithelial, myoepithelial components with myxoid stroma. slow-growing, fibrous pseudocapsule

Adenoid: cribiform swiss cheese pattern

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33
Q

What are the main tumours of the lacrimal gland (5)

A
  1. Pleomorphic adenoma
  2. Adenoid cystic carcinoma
  3. Sarcoidosis (infiltrative)
  4. Sjogren’s
  5. Lymphomas
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34
Q

What are the most common orbital sites of metastases?

A
  1. Uvea
  2. Orbit (more common in children)
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35
Q

What is the most common primary orbital malignancy in childhood?

A

Orbital rhabdomyosarcoma

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36
Q

What are the histological types of orbital rhabdomyosarcoma? Which cells do they originate from

A

Originate from primitive pleuripotent mesenchymal cells

  1. Embryological : cellular and myxoid areas - striated muscle differentiation with highly eosinophilic cytoplasm - good prognosis and most common
  2. Alveolar: loosly adherent eosinophilic rhabdomyoblasts, less striated muscle differentiation, worst prognosis
  3. Pleomorphic: rare
  4. Botyroid:
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37
Q

What are the immunohistochemical stains for orbital rhabdomyosarcoma? (3)

A
  1. Desmin
  2. Muscle-specific actin
  3. Myoglobin
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38
Q

What are the clinical features of orbital rhabdomyosarcoma? (3)

A

Rapid onset ptosis, chemosis and ophthalmoplegia

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39
Q

What is the pathophysiology of orbital pseudotumour?

A

Non-granulomatous inflammation within the orbit, usually infiltrate of lymphocytes and plasma cells with lymphoid follicles

Responds to steroids unless fibrosis has occured

40
Q

Whatare the main features of conjunctival melanoma?
1. What are its characteristics
2. Where does it metastasize to
3. What is its mortality rate?

A
  1. Raised pigmented fleshy conjunctival lesion, usually >5mm thickness and forniceal/palpebral or caruncular lesions carry worse prognosis
  2. Metastasizes to lymph nodes, brain and other organs
  3. 10% at 5 years, 25% at 10 years
41
Q

What are the different sites for uveal melanomas?

A
  1. Choroid (80%)
  2. Ciliary body (12%) - poorest prognosis
  3. Iris (8%) - slow growing nodular tumours which can cause secondary glaucoma
42
Q

What are the histological types of uveal melanomas? (3) What stain can be used? Which pattern carries worst prognosis

A
  1. spindle A and spindle B - thin elongated and organised in tight bundles (good prognosis)
  2. Epithelioid (worst prognosis)
  3. Mixed

Periodic acid schiff stain can be used to assess histolological pattern - closed loop vascular patterns carry worse prognosis

43
Q

What are the ocular findings associated with uveal melanoma (4)

A
  1. Neovascular glaucoma
  2. Angle closure
  3. Spontaneous necrosis with endophthalmitis
  4. Proptosis
  5. Exudative retinal detachment
44
Q

Where does metastastic spread most commonly go to of uveal melanoma?

A

Liver.

45
Q

What gene changes are involved in uveal melanoma?

A
  1. Loss of chromosome 3 heterozygosity (monosomy 3)
  2. Additional copies of 8q
46
Q

What is the incidence of retinoblastoma? Which cells does it arise from?

A
  1. 1 in 20,000
  2. Arises from embryonal retinal cells
47
Q

What is the appearance of retinoblastoma on clinical examination (4)

A
  1. Smooth white mass
  2. Yellow areas of necrosis
  3. White flecks of calcification
  4. Endophytic growth into vitreous / exophytic growth into subretinal space
48
Q

What are the rosettes are involved in retinoblastoma?

A
  1. Homer-Wright rossettes - multilayered circle of nuclei with no central lumen (most immature cells in a retinoblastoma)
  2. Flexner-Wintersteiner rosettes - circle of tumour cells with internal membrane around a central lumen
  3. Fleurettes: primitive photoreceptor bodies arranged in fleur de lys shape.
49
Q

What are the main prognostic factors for retinoblastoma (5)

A
  1. Size
  2. Differentiation
  3. Invasion to choroid, optic nerve and extrascleral sites
50
Q

What is an optic nerve glioma? What is the neuroradiological finding? Which condition is is associated with?

A

Fusiform enlargement of the nerve with kinking within the orbit - affects the orbital portion of the nerve causing proptosis and optic disc swelling

Associated with NF-1.

51
Q

What do limbal stem cells differentiate into?

A

Corneal epithelial cells

52
Q

What are the main growth factors seen in cell growth (4)

A
  1. Epidermal growth factor
  2. TGF-beta
  3. Platelet derived growth factor
  4. Fibroblast growth factor
53
Q

What is the role of epidermal growth factor? What is the role of fibroblast growth factor?

A

Epidermal: stimulates control of corneal epithelial migration and proliferation

Fibroblast: Epithelial and fibroblast proliferation

54
Q

What are the roles of TGF-beta (4)

A
  1. Inhibits epithelial proliferation
  2. Proliferation of stromal fibroblasts
  3. Increased collagen snthesis
  4. Transdifferentiation of conjunctival to corneal epithlium
55
Q

What is the role of platelet derived growth factor?

A

Limbal stem cell proliferation

56
Q

What are the components of the extracellular matrix? (4)

A
  1. Collagen
  2. Laminin
  3. Fibronectin
  4. Integrins
57
Q

What are the main functions of fibronectin? Where are they found in the eye?

A

Found on the stromal side of Descemet’s membrane and are stimulated by EGF and TGF.

They deposit on bare stromal surface within moments of epithelial injury to act as temporary scaffold

They promote adhesion between cells via integrins

58
Q

What is the function of laminin in the cornea?

A

Located in the basal lamina and are re-synthesised within 48 hours of corneal trauma under migrating cells

59
Q

What are integrins? What is their role in the eye

A

Transmembrane glycoproteins present in almost all cells

  1. Promote cell-ECM and cell-cell attachments
  2. Convey biochemical signals

Disruption of nromal integrin-ECM interactions prevents normal eye development

60
Q

What is the most common benign epithelial tumour of the eyelid?

A

Squamous papilloma

61
Q

What are the ocular manifestations of ionising radiation?

A
  1. SPKs, dry eyes
  2. Scleral necrosis (mitomycin C)
  3. Cataracts (20 years after exposure)
  4. Radiation retinopathy (2-3 years for optic neuropathy)
62
Q

What is the most radiosensitive structure in the eye?

A

The lens - latent period of 2-3 years - young patients more susceptible as there are more active lens cells growing

63
Q

What is the most common primary intraocular tumour in adults?

What is the most common primary intraocular tumour in children?

Most common malignant orbital tumour in children?

A
  1. Adults - uveal melanoma
  2. Children - Retinoblastoma
  3. Children - Rhabdomyosarcoma
64
Q

Most common benign orbital tumour in adults?

Most common benign orbital tumour in children?

A

Adults: cavernous haemangioma
Children: Capillary haemangioma

65
Q

Whats the difference in cells between granulomatous and non-granulomatous inflammation?

A

Granulomatous: Epithelioid histiocytes
Non-granulomatous: Lymphocytes / plasma cells

66
Q

What histological cells are seen in optic nerve sheath meningioma?

What histological cells are seen in Neurilemmoma (Schwann cell tumour)

What histological cells are seen in sarcoidosis?

A
  1. Meningioma : psammoma bodies, meningothelial cells,
  2. Neurilemmoma - verocay bodies
  3. Sarcoidosis: Asteroid bodies, Schaumann bodies
67
Q

What is an optic nerve meningioma? Whats the difference with this and optic nerve glioma?

A

Meningioma arises from arachnoid cap of optic nerve sheath

In contrast to glioma, meningioma is more aggressive in children as compared to adults

Glioma is more aggressive in adults.

Associated with NF-2 (two m’s in meningioma)

68
Q

What is the histological appearance of optic nerve glioma?

A

Fusiform swelling of the optic nerve

Pilocytic appearance with Rosenthal fibres and myxoid degeneration (similar to intracranial astrocytoma)

Associated with NF1

69
Q

Polypeptide amyloid is found in…
Prealbumin amyloid is found in…

A
  1. Polypeptide amyloid - endocrine tumours
  2. prealbumin amyloid - deposits in heart, joints, brain
70
Q

What tumours are associated with patients who have retinoblastoma? (3)

A
  1. Osteosarcoma
  2. Soft-tissue sarcoma
  3. Melanoma
71
Q

What are the histolopathological features of squamous papilloma? (3)

A

Appearance: Sessile, pedunculated, papillary shaped, keratinised

Histopathology: Epithelial acanthosis, hyperkeratosis, central fibrovascular core

72
Q

What germline mutation is involved in choroidal melanoma?

A

BAP1 germline mutation

73
Q

What are OCT / A scan / B scan findings of choroidal melanoma?

A

OCT - increased autoflourescence, degenerative RPE/photoreceptor change

A scan - low internal reflectivity

Collar-stud appearance.

74
Q

What are the histological findings of seborrheic keratosis? (4)

A
  1. Acanthotic proliferation of basaloid cells
  2. Varying degrees of hyperkeratosis
  3. Keratin filled cystic inclusion
75
Q

Where are iris colobomas located?

A

Inferonasal.

76
Q

Which condition is associated with fundal astrocytomas? (2)

A

Tuberous sclerosis
NF1

77
Q

What are the other ocular manifestations in a retinoblastoma?

A
  1. Leukocoria
  2. Strabismus
  3. Uveitis/endophthalmitis
  4. Hyphaema
78
Q

What are the main poor prognostic factors for melanoma (6)

What is the 5 year survival for uveal melanoma?

A
  1. Big size
  2. Extrascleral spread
  3. Anterior location (ciliary body)
  4. Close loop vascular patterns on PAS staining
  5. Genetic: monosomy 3, 8q gain
  6. Epithelioid subtype

Survival rate: 80%

79
Q

Which lymphoma ocular location is most associated with systemic disease?

A

Eyelid, then lacrimal gland, then orbit, then conjunctiva

80
Q

Recurrent chalazia and unilateral blepharitis is associated with which cancer? Which stain is used?

A

Sebaceous cell carcinoma - commonly upper eyelid.

Oil Red O / Sudan black stain is used.

81
Q

Recurrent chalazia and unilateral blepharitis is associated with which cancer? Which stain is used?

A

Sebaceous cell carcinoma - commonly upper eyelid.

Oil Red O / Sudan black stain is used.

82
Q

Gorlin-Gotz syndrome is associated with what malignancy?

What mutation?

A

BCC in the young (2nd decade)
Autosomal dominant PTCH1 mutation affecting sonic hedgehog pathway.

83
Q

Which HPV are associated with conjunctival carcinoma?

Which HPV are associated with conjunctival papilloma?

A

HPV carcinoma: 16 and18
HPV papilloma: 6 and 11

84
Q

When does a capillary haemangioma typically present?

A

After 6 months

85
Q

What is Burkitt’s lymphoma? What are its associations?

A

Burkitt’s: B cell non-Hodgkin’s lymphoma

Associations: EBV, HIV and chromosomal translocations

86
Q

Where are the most common sites of a BCC?

A
  1. Lower eyelid
  2. Medial canthus (risk of orbital extension)
87
Q

Epidermoid cysts are lined with what epithelium? When do they occur?

A

Keratinising squamous epithelium

Usually occur as result of epithelial inclusion following trauma or surgery

88
Q

What are the ocular manifestations of Sturge-Weber syndrome?

What are the non ocular manifestations of Sturge-Weber syndrome?

A

Ocular: haemangioma (episcleral, ciliary body, iris, choroidal), glaucoma

Non-ocular: Facial port-wine stain in trigeminal V1 distribution, CNS haemangiomas, childhood seizures.

89
Q

What are the mutations involved in pyogenic granuloma?

What are the main risk factors of pyogenic granuloma?

A

mutations: RAS, VEGF

risk factors: Sturge-Weber, Trauma, Medications (retinoids, retroviral, anti-neoplastic)

90
Q

What are the characteristic histological features of squamous cell carcinoma?

A
  1. variable sized epithelial cells
  2. Prominent nuclei, prominent cytoplasm
  3. Central keratin pearls
91
Q

What is the pathophysiology behind Coat’s disease?

A

Abnormal endothelium in arterioles and venules –> MASSIVE leakage of LIPID-rich plasma into the retina and subretinal space

Affects young males.

Causes massive macular exudation and retinal detachment

92
Q

What is the staining process useful for sebaceous gland carcinoma?

A

Oil Red O -stains lipids red

93
Q

What is the process of dysplasia? Is it reversible?

A
  1. Increased cell number
  2. Pleomorphism (altered nuclear size and shape)
  3. Hyperchromasia (incresed staining with haematoxylin)
  4. It is REVERSIBLE in its early stages.
94
Q

Which BCC type is associated with low risk of recurrence?

Which BCC type is associated with high risk of recurrence?

A

Low risk: Nodular and superficial

High risk: Infiltrative and squamous

95
Q
A

PART ONE REVISION. (78 decks)

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