ENT Pathology Flashcards

Question

HERPES SIMPLEX VIRUS xxx

Answer 1

**Tsanck cells:** Viral nuclear inclusions in multinucleated giant cell formed by the fusion of acantholytic keratinocytes (viral lesions such as VZV, HSV, pemiphigus) Acantholysis, Keratinocyte necrosis, ballooning degeneration Inflammatory cell infiltrate **Erythema multiform:** - Symmetrical widespread target lesions - Start on hands and feet then spread towards trunk - Mild form of Stevens-Johnson syndrome --- blisters, ulcers, eyey lesions - HSV, Mycoplasma, Carbamazepine, Sulfonamides, Ceclor

Answer 2

Heterophile antibodies are produced by EBV-infected B Lymphocytes - cross react to antigens occurring in several species that are not phylogenetically related. They agglutinate sheep or horse RBCs but don't react with any EBV antigens **Pathogenesis**: Infects both epithelial cells and B-lymphocytes 1. **Epithelial cells -** Infected during active phase of infection, allowing for viral replication - Oropharyngeal epithelial cells 'burst' due to replication of EBV - Periodic reactivation of virus may occur without symptoms 2. **Memory B-lymphocytes** - This is where latent EBV virus resides - Swollen LN's are due to infection spreading to resting B-cells  Investigations Test for heterophile antibodies or for specific antibodies Haematology- Lymphocytosis 12-25, \>10% atypical - EBV = heteregenous enlarged lymphocytes, lymphocytosis of 12-25 - Acute myeloid leukaemia = homogenous enlarged lymphocytes, lymphocytosis of 50-100 - Atypical Lymphs seen in - Toxoplasmosis, acute HIV, Rubella, Hepatitis A, seroconversion illness - Thrombocytopenia is not uncommon in EBV mononucleosis Biochem - Elevated transaminases (up in 2nd/3rd week, return to normal by 5th week) Microbiology- Secondary bacterial infection in 30% Immunology - Paul-Bunnell test: sheep glycoproteins from red cell membranes bind heterophile antibodies causing agglutination - False -ve 25% in 1st week and 5-10% in 2nd week Monospot test - sensitivity 50% in children, 70-90% in adults (like the PB test, tests for heterophile antibodies - horse) Antibody testing - Viral Capsid Antigen (VCA) present early at onset (used if heterophile ab tests are -ve but still clinical suspicion)

Answer 3

**B Lymphotrophic human DNA herpes virus (HHV-4)** **Dual strategy of:** - Latency in B Lymphocytes (ie. like most herpes viruses causes a life-long latent infection) - Intermittent replication in oropharyngeal epithelial cells to enable transmission **EBV associated diseases**: 1. Infectious Mononucleosis 2. Burkitt's Lymphoma 3. Oral Hairy Leukoplakia 4. Hodgkin's Disease 5. T-Cell Lymphomas 6. Nasopharyngeal Carcinoma 7. Smooth muscle tumours in HIV patients **Epidemiology** 2 peaks of infection, age 1-6 and 14-20 --- 80-90% of adults seropositive - Developing countries = 99% seroconversion by 6 yrs - Developed countries = 50% seroconvert in teens/early adulthood Transmission via saliva containing infected squamous epithelial cells Infectious mononucleosis occurs in 50% of seronegative 17-25 year olds who become infected with EBV, the other 50% seroconvert without symptoms. **Clinical Features:** Incubation period typically of 4 wks from contact, then the prodrome starts of 2-5 days (note - antibody graph shows day 0 as the beginning of incubation) **General** - Malaise, fevers/chills, sweating, headache, stiff neck, anorexia —\> prodrome = 2-5 days **ENT** - Pharyngitis/exudative tonsillitis, generealised lymphadenopathy, petechie of SP **Skin** - Rash - occurs in nearly all patients (80-90%) given Amoxycillin (immune complex deposition in skin most likely mechanism) **GIT** - Splenomegaly (50%), hepatomegaly (25%) **Eyes** - Periorbital oedema seen in upto 30% **Complications of EBV** Haem - haemolytic anaemia, splenic rupture, aplastic anaemia Neurological- encephalitis, CN palsies, GBS, seizures, sudden SNHL Liver - 90% have mild elevation of LFTs, jaundice in 10%, hepatic failure rare Cardiac - Pericarditis, myocarditis Respiratory - Airway obstruction, laryngitis, epiglottitis, tracheitis, quinsy **Management**: Supportive care Antibiotics to cover secondary bacterial infection present in 30% Steroids - hasten resolution of pharyngitis, fever, haem abnormalities. Use selectively for severe tonsillitis Avoid contact sports for \> 1 month in all confirmed EBV cases

Answer 4

1. **IgE-mediated IgE (Type I)** Antigen induces crosslinking of IgE bound to mast cells - ie. Allergy, Anaphylaxis, Asthma, AFS 2. **Cytotoxic, antibody-dependent IgM, IgG (Type II)** Cytotoxic hypersensitivity with ab directed against cell surface antigen causing cellular destruction - Graves disease - Myasthenia gravis - Autoimmune haemolytic anaemia 3. **Immune complex disease IgG (Type III)** Immune complex mediated with ab-ag complexes depositing in distant tissues to cause inflammatory response - RA - SLE - Post-strep GN 4. **Delayed hypersensitivity/Cell-mediated T cells (Type IV)** Cell-mediated hypersensitivity with sensitized Th1 cells or cytotoxic-T-cells - Mantoux - MS - Transplant rejection - Contact dermatitis

Answer 5

**Gross structure:** - Surrounded by a fibrous capsule - Made up of lobules - Arranged side-by-side and radiating out from the hilum - Anchored to the hilum by its vascular roots **Zones of the node**: 1. **Cortex** outer - Composed of spherical follicles (2 types) - B cells migrate here - Activated B cells migrate to germinal centres Primary follicles: lymphoid follicles without a germinal centre Secondary follicles: lymphoid follicles with a germinal centre (contain activated B-cells) 2. **Paracortex** - Area where T cells accumulate 3. **Medulla inner** - Composed of cords. Between the cords are sinuses - Vessel-like spaces which separate the cords **Inputs/Outputs:** - Afferent channels: multiple afferent channels bring lymph to the node peripherally - Efferent channel: single leaves the hilum of the node **Lymph flow:** Afferent —\> subcapsular sinus —\> cortical sinuses —\> medullary sinuses —\> efferent vessels

Answer 6

**Cell Cycle:** - Progression thru phases is controlled by cyclins and cyclin-dependant kinases, and their inhibitors - CDK's are expressed constitutively during cell cycle but in inactive form - Cyclins activate CDK's, and are synthesised during specific phases in cell cycle (decline rapidly after cell-cycle done) - G1/S is the restriction point - controlled by p53 and Rb. p53 also works at S/G2 transition **G1 phase (gap phase btw mitosis and synthesis):** Replication of cellular machinery (proteins, organelles needed for the S phase) - Cyclin-D + CDK = complex that can phosphorylate Rb (on-off switch) - If Rb+phos means that Rb is no longer bound to E2F (a transcription factor) and hence cell-cycle progression can occur **G1/S phase checkpoint:** - E2F results in transcription of Cyclin-E - Cyclin-E + CDK = moving thru G1/S checkpoint - ie. the S phase is a point of no return hence G1/S checkpoint is most impt for identification of DNA damage. **S phase (synthesis):** DNA synthesis with replication of chromosomal pairs - Now that moved thru checkpoint G1/S, Cyclin-E/CDK complex allows transcription of machinery for DNA synthesis **G2 phase (2nd gap phase btw synthesis and mitosis):** DNA is double checked for errors **G2/M phase checkpoint:** - Transition intiated by Cyclin-A/CDK complex to enter the M phase - Monitors for completion of DNA replication and checks whether cell can safely divide (mitosis) **M phase:** nuclear and cellular division into 2 cells - Cyclin-B/CDK complex causes the breakdown of nuclear envelop and initiates mitosis - At end of the M-phase the phos groups on Rb are removed, therefore Rb+E2F complex is reformed halting cell-cycle again. - Newly divided cells can exit to the G0 phase, or re-enter the G1 phase for continued division.

Answer 7

Gram +ve/-ve staining: +ve = purple, -ve = red Primary stain applied (crystal violet) to a heat-fixed smear of a bacterial culture. Iodide added (binds to crystal violet and traps it in the cell) Rapid decolorization with alcohol or acetone, and Counterstaining with safranin. Differentiates bacteria by the chemical and physical properties of their cell walls by detecting peptidoglycan Gram-positive bacteria —\> retain the crystal violet dye Gram-negative bacteria —\> red or pink coloring (d/t safranin counterstain added after the crystal violet stain)

Answer 8

A group of autoimmune mucocutaneous diseases characterised by intra-epithelial cleaving, which may be fatal **Pathogenesis**: autoimmune disease = genetics + environment **Genetics**: HLA Class 2 alleles Desmoglein 3 = intercellular adhesion molecule of the cadherin family Antibodies directed against Dsg3- IgG antibodies deposit in intracellular space and attack the extracellular component of Dsg - Results in epithelial separation **Pathology**: - Separation/cleavage of basal from suprabasal layers - Basal layers remain attached to LP ('tombstone' appearance)   Pemphigus = staining in intercellular spaces **Investigations**: - Biopsy (see next facet) - Direct immunofluorescence- anti-desmoglein 3 IgG - anti-Ds1antibodies present if skin also involved (Ds1 not present in mucosa)

Answer 9

A heterogenous group of autoimmune subepithelial vesiculobullous diseases **Pathogenesis**: Formation of autoantibodies against molecular components of the BM zone - bullous pemphigoid antigen 2, laminin 5, b1subunit of integrin **Pathology**: Linear deposition of IgG and C3 in BM zone Separation of mucosal epithelium from underlying LP in absence of significant inflammation IF staining- linear continuous/homogenous staining of IgG, IgA and C3 **Investigations**: - Serum autoantibodies to epithelial basement membrane zone (uncommon). Alpha-6 integrin - Epiligrin- rare antibody but assoc with internal malignancy - IgG immune deposits (common)

Answer 10

**Definition**: Mucocutaneous disease of autoimmune immunologic origin, mediated by T cell reaction to surface antigens within epithelium. Commonly affects oral mucosa, skin, genital mucosa, scalp and nails. Affects 0.5-2% of the general population. **Aetiology**: Immunologically-mediated Mosly idiopathic. Significantly greater anxiety/depression observed than in controls Assoc with systemic disease: sclerosing cholangitis, SLE, primary biliary cirrhosis, Sjogren's disease **Pathogenesis**: CD8+ T cell-mediated apoptosis of basal keratinocytes Fibrinogen deposition in these basal layers (diagnostic with direct immunofluorescence) **Pathology**: - Lymphocytic infuiltrate in basal layer, Civatte bodies (degeneration of basal layer keratinocytes), liquafactive necrosis of basal cell layer, saw tooth appearance of Rete pegs - Fibrinogen deposition seen on immunofluorescence!!!!!!!! **Signs and Symptoms:** Bilateral, multifocal lesions helps Dx - Bilateral white lesions in the buccal or lingual mucosa - Reticular - usually asymptomatic, lacy network (Wickham's striae) symmetrically bilateral buccal mucosa - Plaque - multifocal, lateral/ventral tongue and buccal mucosa - Atrophic/Erythematous - reddened areas of mucosa, often coexists with reticular/erosive forms. Gingival mucosa (poor dental appliance hygiene sets up bacteria to create antigens) - Erosive - often superficial, can be deep/painful ulcers, covered with pseudomembrane, often have peripheral striae - As erosions heal, new areas develop - Bullous- rarest form. Bullae range in size up to 1cm. Transient bulla, then ruptures to leave painful ulceration. Assoc with other forms of OLP within the mouth, thus difficult Dx Risk of malignant transformation for atrophic and erosive types (5% over ten years). Least common variants

Answer 11

**Definition**: Clinical not histopathological diagnosis A white mucosal lesion that cannot be rubbed or scraped off and that is not recognised as any other lesion DDx- cheek/tongue biting, OLP, candida, drug reaction, amalgam tattoo, geographic tongue **Aetiology**: Tobacco - disappearance of lesions within 1 year of cessation Trauma - frictional (denture, cheek biting, toothbrushing), chemical (smokeless tobacco, aspirin, peppermint/cinnamon) Microorganisms - Candida albicans, treponema pallidum UV radiation **Pathology**: PRECANCEROUS LESION Macroscopically: Thin vs Thick **Histology**: - Epithelium - hyperkeratosis, acanthosis, parakeratosis - Most are devoid of dysplasia. BUT full range of dysplasia can be present - Submucosa - variable chronic inflammatory cell infiltrate - Fungal stains may be positive. Primary cause vs secondary infiltration - Most Common sites (account for \>2/3) are: vermillion border of lower lip, buccal mucosa, gingiva Risk of severe dysplasia +/- carcinoma is 4-30% **Risk factors for malignant transformation:** - Site - FOM, tongue, vermillion border of lip - Long duration of leukoplakia - Homogenous thick leukoplakia - Surface granularity/verrucous appearance - Female - Absence of a smoking Hx - Presence of dysplasia **Prognosis**: 30% of lesions disappear 30% improve 25% show no change 7.5% demonstrate local spread 6% progress to SCC

Answer 12

**Defintion**: A distinctive asymptomatic white lesion of the oral mucosa **Aetiology**: 1. EBV-related 2. Immunosuppressed patient (i.e. HIV mostly) - ie. requires EBV infection, replications, and expression of EBV latent genes, followed by immune escape (hence assoc with EBV + immunosupression) **Clinical features:** - Often asymptomatic, occasionally symptoms of mild pain, dysesthesia, alteration of taste, and cosmetic concerns. - Side of the tongue with a corrugated or hairy appearance **Pathology**: Hyperkeratosis Irregular surface projections Ballooning degeneration of subsurface layers IHC: EBV Image = vertical corrugated keratotic ridges are seen.

Answer 13

**Defintiion**: A red mucosal lesion that cannot be rubbed off or scraped off and that is not recognised as any other disease More likely than leukoplakia to correlate to underlying severe dysplasia/carcinoma - 90% have evidence of invasive carcinoma, carcinoma in situ or severe dysplasia - \>25% risk of carcinoma **Pathology**: Most have at least severe dysplasia - Surface epithelium devoid of keratinisation - Non-specific submucosal inflammaton and dilated capillaries **Malignant transformation:** 28%

Answer 14

**Definition**: A neoplastic lesion of neural derivation with granularity due to the accumulation of secondary lysosomes in the cytoplasm. **Epidemiology**: Rare F:M = 3:2 Middle aged Black persons 10% of individuals have multiple lesions Benign \> malignant (rare \< 2% of all granular cell tumors) **Aetiology**: Unkown **Pathology** (benign variant): Gross - Pale white/yellow, nonencapsulated, and variably (well to poorly) circumscribed nodules with solid, fleshy cut surfaces that are devoid of liquefaction, necrosis, or bleeding. The overlying skin or mucosa is thickened and may have a cobblestone appearance Histo - Eosinophilic cytoplasmic granules and small round nuclei with dense chromatin, +/- infiltrative margins. Squamous epithelium overlying the peripheral superficial lesions exhibit acanthosis and pseudoepitheliomatous hyperplasia. IHC - Stain +ve for S-100 protein, neuron-specific enolase, and NK1-C3 Classified as malignant if \>3cm, locally destructive changes, cytologic features of malignancy (freq mitoses, vesicular nuclei with prominent nucleoli) or metastasis (lymph nodes or distant sites) or otherwise causes death. **Sx**: Painless nodules with an insidious onset and slow growth rate Head, neck, trunk, extremities **Signs**: Nonulcerated, painless nodule Solitary (may be multiple) \<3cm Tongue (25%) Breast - common Parenchyma, subcutaneous tissue, and dermis (account for 15%) Small—\>medium-sized cranial or spinal nerves, but neurologic deficit is rare Visceral involvement - mucosal or submucosal nodules in the esophagus, larynx, bronchi **Ix**: CT/MRI **Mx**: Benign - surgical excision Malignant - WLE - Chemo/RTx - not effective **Prognosis**: Benign lesions - recurrence rate 2-8% if -ve margin, 20% +ve margin Malignant lesions - aggressive and difficult to eradicate with surgery. Local recurrences 32%, and metastases in 50% within 2 yrs 60% of patients die of the disease within 3 years of detection of the primary tumor. Ki-67 immunoreactivity of 10% or more tumor cells is an adverse prognostic factor.

Answer 15

**Defintion of dysplasia:** Abnormal maturation and differentiation of epithelium with features of an increased: - Nuclear-to-cytoplasmic ratio - Loss of polarity - Increased mitoses - Loss of intercellular adherence (graded as mild, mod, severe) **Mild Dysplasia** = features limited to the lower 3rd of epithelium **Mod Dysplasia** = features limited to 2/3rds of epithelium **Severe Dysplasia** = features extend from 2/3rds to almost complete thickness (but not entire thickness) **Carcinoma in situ** = the above changes, but it involves the entire thickness of the epithelium (doesn't breach BM) **Malignant transformation rate…**. - Mild dysplasia = 10% - Severe dysplasia/CIS = 30-40% (mean time is 4 yrs) **Treatment** Severe dysplasia / Ca in situ = these lesions need treatment, excisional biopsy is preferred Mild/mod dysplasia = predominantly reversible, hence close observation

Answer 16

o Minimal diameter of: 15mm for jugulodigastric nodes located in level, and 10mm for nodes located in other levels o Minimum diameter of 8mm for retropharyngeal nodes o Groups of 3 or more borderline nodes (ie. 1-2mm smaller) o Any node with evidence of central necrosis o Loss of tissue planes (fat planes)

Answer 17

**Acanthosis** = diffuse epidermal hyperplasia (thickening of the skin) - It implies increased thickness of the stratum basale and stratum spinosum **Hyperkeratosis** = Hyperplasia of the stratum corneum associated with qualitative abnormality of the keratin **Parakeratosis** = Persistence of nuclei in the stratum corneum (keratin layer of the squamous epithelium)

Answer 18

**Squamous cells** = flat, scalelike or platelike cells **Stratified** = cells arranged in layers **Pseudostratified** = epithelium appears to be several layers (strata) of cells but cells are actually resting on the base layer (often ciliated and occurs only in mucosa) **Keratinizing** = a protein that is waterproof, contained within squamous cells that are no longer alive, and contain no nucleus, continually lost from the surface of the epithelium, and only occurs on skin normally. i.e.. has a non-living outer surface **Non-keratinizing** = squamous cells that don't contain the keratin, and the cells are living at the surface (ie with nucleus)

Answer 19

**Carcinoma** = a malignant growth made up of epithelial cells that are infiltrating surrounding tissues

Answer 20

**Neoplasm (abnormal proliferation)** - An abnormal mass of tissue that grows by cellular proliferation more rapidly than normal, and continues to grow after the stimuli that initiated the new growth ceases. May be either benign or malignant. **Malignant neoplasm / cancer -** A neoplasm that tends to grow, invade, and metastasize. **Hamartoma (abnormal differentiation, but mature)** - A non-neoplastic developmental anomaly of aberrant tissue differentiation that produces a mass of disorganised but mature tissue indigenous to the particular site **Choristoma** - A non-neoplastic developmental anomaly of essentally normal itssue that is ectopic of its normal location (ie. ectopic endometrial tissue in lung)

Answer 21

**Immunohistochemistry** - differentiation from other small blue cell tumours - S100 -ve (classical for melanoma, Esthesio's, SCUNC) - Synaptophysin -ve (classical for SCUNC) - NSE -ve (neurone specific enolase) (classical for Esthesio's, SCUNC) - HMB-45, Vimentin -ve, Melan A (classical for melanoma) - CD99 -ve (classical for Ewings Sarcoma) - CK7, CK8, CK19 +ve (SNUC's are consistently immunoreactive with epithelial markers for pankeratin and simple keratins)

Answer 22

1. Self-sufficiency of growth signals - EGFR 2. Insensitivity to growth inhibitory signals - Retinoblastoma 3. Evasion of programmed cell death - p53 4. Immortality - p53, Rb, telomerase activation 5. Sustained angiogenesis - VEGF 6. Tissue invasion and metastasis - Growth factors - EGFR - Intercellular adhesion molecules- integrins, c-adherins

Answer 23

**Normal mucosa/skin:** - Reasonable thickness - Polarity or arrangement of cells - Intercellular bridges - Pale nuclei with a small nucleus in abundant pink cytoplasm - Nucleus/cytoplasmic ratio in strong favor of the cytoplasm - All cells/nuclei of approx the same size - Cell resemble fish scales or pavement blocks - Keratin at the surface if keratinizing **Malignancy features:** - Hyperchromatism (dark nuclei, with clumping of chromatin) - Pleomorphism (cells of different sizes and shapes) - Abnormal mitosis - Keratin whorls appearing as roundish, eosinophilic (pink), lamellated 'pearls' - Loss of polarity - low-grade lesions: show maintainence of intercellular bridges, cells resembling those normally found, some adherance to polarity - moderate to poorly differentiated lesions: show significant deviation from normal and may not resemble squamous epithelium

Answer 24

**Verrucous** - Locally destructive, not metastatic (v rarely) - M \> F 60s, tobacco smoking / chewing - Exophytic, broad-based lesion with superficial spreading growth - Blunt incursions, expansile advancing margin, maybe a brisk lymphocytic response - Can be destructive (muscle, cartilage, bone) Mets rare - OC - buccal & HP MC \> Larynx - RTx contraindicated (rare exceptions) —\> anaplastic transformation - Excellent prognosis if neg margins on WLE **Histo** - Well diff, minimal / absent dysplasia / church spire hyperkertosis

Answer 25

**Papillary** - Similar to verrucous but lacks the surface keratinisation - All H&N subsites, including larynx (MC) and hypopharynx - Atypical squamous cells overlying fibrovascular papillary stromal cores - Prognosis - similar to conventional / slightly better

Answer 26

**Spindle cell Carcinosarcoma** - Elderly males, often Hx of RT - Bimorphic tumour - SCC & malignant stromal component - squamous component can be difficult to identify - Areas of typical SCC - Bizarre spindle cell sarcomatoid areas - Upper respiratory tract sites - Poor prognosis Photo - left = spindle, right = SCC

Answer 27

**Basaloid** - High grade, aggressive variant. - Middle aged males- OPx, larynx, HPx - Hard tumours with central necrosis and superficial ulceration - Infiltrative and deeply invasive - Lobular arrangement of pleomorphic cells around a central cystic necrotic focus - May be assoc HPV

Answer 28

**Adenosquamous** - Uncommon, aggressive variant with poor prognosis - Older males, larynx/hypopharynx - Conventional SCC admixed with glanduloductal elements —\> Mucin +ve

Answer 29

1. Classical SCC 2. Verrucous 3. Adenosquamous 4. Basaloid 5. Papillary 6. Spindle cell

Answer 30

**Carcinoma of the nasopharynx demonstrating evidence of squamous differentiation** **Aetiology**: Genetics: 8x risk in a 1st degree relative. HLA subtypes- A, B and D subgroups EBV exposure and reactivation Environment: salted fish (contains nitrosamines) **Pathology**: WHO Classification 1. Keratinising (25%) Pattern consistent with other H&NSCC. \<5% in endemic areas 2. Non-Keratinising (75%) EBV-related, aggressive, radiosensitive, good prognosis a) Differentiated b) Undifferentiated - \>90% in endemic areas

Answer 31

**Histology**: Keratinising SCC - Epitheliod looking, 'scale' like or layered, keratin seen, intercellular bridges Non-keratinising, Undifferentiated (MC) - Round nuclei, prominent eosinophilic (pink) nucleoli, dispersed nuclear chromatin, scant eosinophilic cytoplasm - Cells do not form 'scale' patterns or layers Non-keratinising, Differentiated - Squamous cells seen (ie. epitheliod looking, 'scale' like or layered) - No keratin seen **IHC**: High molecular weight cytokeratin, EBV-latent membrane protein **Other diagnostic tests:** Serology - IgA to viral capsid antigen (VCA), IgG/IgA to Early antigens (EA)

Answer 32

**Pathology**: Cyst lining: stratified squamous epithelium (90%) or respiratory epithelium Cystic contents: fluid contains cholestrol crystals and keratin They may also contain lymphoid tissue as well, salivary tissue Image = Stratified squamous epithelium

Answer 33

**Pathology**: - Cyst lining: Respiratory epithelium-lined - May contain squamous metaplasia (esp if recurrent infection) - Thyroid follicles present in 60%

Answer 34

A malignant epithelial neoplasm with evidence of follicular cell differentiation typically with papillary structures and characteristic nuclear features MC thyroid malignancy (60-80%) Multicentric, lymphotropic FNA: nuclear features are diagnostic - Nuclear enlargement and pleomorphism - Powdery chromatin pattern - Intranuclear incusions, nuclear grooves/indentations (coffee beans) and nuclear overcrowding/overlapping ('basket of eggs') - Chromatin margination **Pathology**: - Papillary growth pattern with fibrovascular core - Psammoma bodies - Intratumoral fibrosis - Orphan Annie cells (optically clear appearing nuclei with chromatin margination) - Nuclear features as per FNA **Aggressive variants:** not independent risk factor for poor prognos - Diffuse sclerosing - Tall cell - Columnar cell - Poorly differentiated, anaplastic **Classification**: - Microcarcinoma - \<1cm, no capsule invasion, no LN mets - Intrathyroid - 1-4cm, confined to gland - Extrathyroid - decreased survival These variants present with features recognised by other staging systems to be associated with worse prognosis, rather than being an independent predictor of poor prognosis

Answer 35

**Definition**: A malignant epithelial tumour showing follicular cell differentiation without architectural or cytonuclear features of papillary thyroid carcinoma (5-15% of all thyroid ca's) 10-20% of thyroid malignancies - Iodine-deificient - Cowden's disease, irradiation FNA - Limited as unable to demonstrate capsular invasion or angioinvasion - The hallmarks of diagnosis **Pathology**: - Encapsulated tumours - Follicular growth rather than papillary - Uniform-appearing colloid-filled follicles - Uniform growth pattern (ie. if a variety then think papillary ca) - Key features: capsular invasion, angioinvasion **Patholgogical Classification** Minimally invasive = limited capsule invasion only or angioinvasion (\<4 vessel, small calibre vessel) Widely invasive = complete capsule invasion or \>4 vessel invasion or large calibre vessel or invasion to adjacent thyroid parenchyma Hurtle cell ca = poorer histological variant of follicular ca (defined as presence of oncocytes ie. eosinophilic grannular cytoplasm due to mitochondria) FNA diagnosis limited --- Ca requires capsular or angio-invasion **Prognosis**: - Minimally invasive = excellent (no mets --- 70-100%, mets --- 50%) - Widely invasive = poor (25-45% --- metastatic propensity)

Answer 36

**A variant of FTC** Follicular cancer with oncocytic cells **Oncocytes** = Epithelial cell characterized by an excessive amount of mitochondria, resulting in eosinophilic (pink), granular cytoplasm. Oncocytes can be benign or can undergo malignant transformation. **Same division as FTC:** 1. Minimally invasive 2. Widely invasive **Prognosis worse than conventional FTC:** Older patients Increased frequency of malignancy (compared with non-oncocytic follicular neoplasms) Redued RAI uptake Increased extra-thyroidal spread **5-year survival:** 30-70% Picture: Cytoplasmic oxyphilia

Answer 37

**A tumour of the C-cells of the thyroid** RET protoncogene mutation (10q11.2) - Sporadic (70%) vs Familial (30%) - Familial = MEN2A, MEN2B, Familial MTC **FNA**: - Increased cellularity with single cells or small cell clusters - Round/oval cells, spindle-shaped, pleomorphic nuclei, coarse chromatin pattern and abundant eosinophilic cytoplasm - Nuclear inclusion and eccentrically placed in cell - Extracellular homogenous eosinophilic to pale orange amorphous clumps/spheres/rods seen = amyloid (congo red stains confirms) - Follicular pattern, papillary structures and colloid is not seen **Pathology**: - Looks like paraganglioma with nest-like structure - Pink amyloid stroma (congo red —\> apple green birefringence) - IHC: neuron specific enolase, synaptophysin, chromagranin - i.e. neuroendocrine tumour - Calcitonin

Answer 38

Picture: Diffuse involvement of the thyroid gland in which mature lymphocytes, with/without germinal centres are present Associated with thyroid lymphoma

Answer 39

Subacute granulomatous thyroiditis Viral cause --- malaise, fever, thyroid pain + tremor/heat intolerance - Thyroid gland = very tender, firm, irregular Lasts 12-16/52 --- period of hypothyroidism (gland unable to produce hormones) **Management**: NSAIDs, b-blocker Prognosis: thyroid damage and recurrence rare Picture: - Thyroid follicles replaced with neutrophils and multi-nucleated giant cells - Colloid still present (floating within neutrophilic cell infiltrate)

Answer 40

**Definition**: Rare but aggressive neuroendocrine tumour arising from the mechanoreceptor Merkel cells of the skin **Aetiology**: UV radiation exposure and immunosuppression appear important **Pathology** A small round blue cell tumour - Arises from Merkel cells in the skin (mechanoreceptors) - Undifferentiated malignant small cell infiltration in dermis and subcutaneous tissues - Generally doesn't involve epidermis - May be separated from epidermis by a rim of papillary dermis - Grenz zone **IHC**: - Cytokeratin 20 (CK-20) positive —\> differentiates from metastatic neuroendocrine small cell cancer of the lung —\> Characteristic perinuclear dot pattern - Neuroendocrine markers may be positive: chromagranin, synaptophysin

Answer 41

**Definition**: Slow-growing, locally invasive malignant epidermal skin tumour **Epidemiology**: MC skin cancer: 800/100,000 **Aetiology**: **Genetics**: Xeroderma pigmentosa - failure of fibroblast repair of DNA damage Gorlin's syndrome - mutliple BCCs, palmar pits, jaw cysts, rib abnormalities, calcification of falx cerebri, characteristic facies (frontal bossing, hypoplastic maxilla, broad nasal root, ocular hypertelorism) - PTCH gene 9q22, AD inheritance **Environment**: UVB \> UVA **Pathology**: BCC subtypes: nodular, superficial, basosquamous, pigmented, sclerosing Arise in continuity with basal cell layer of epidermis or from the adnexae Uniform hyperchromatic (eosinophilic) cells with nuclear pallisading towards edges of tumour nests **IHC**: Bcl2, 60% androgen receptor +ve

Answer 42

**Pathologic subtypes:** Small, blue cell tumour, may see Melanin in tissues, otherwise IHC Dx 1. Superficial spreading 65-75%- pre-existing naevus, radial growth for years prior to development of vertical growth phase 2. Nodular 10-15%- blue-black raised nodule. MC mucosal melanoma. most invasive, poorest prognosis 3. Lentigo maligna melanoma- seen in background of chronic solar damage as Hutchinson's melanocytic freckle (LM) ---5% progress to LMM - LM = melanoma in situ - Subclinical and extensive involvement of periphery --- difficult excision margins 4. Desmoplastic - neurotropic \<1%- locally aggressive, highly aggressive. 75% arise in H&N **IHC**: S-100, tyrosinase (both sensitive, not specific) Melan A, HMB-45, Vimentin (specific, not sensitive --- 15% won't stain for these 3)

Answer 43

Most common primary malignant epithelial salivary gland neoplasm composed of an admixture of epidermoid, mucous and intermediate cells **Cellular components:** 1. Mucous cells - pale-staining, foamy cytoplasm, peripherally -placed nuclei - Associated with cyst formation 2. Epidermoid cells - nests/solid areas in conjunction with mucous cells (absence of keratin and intercellular bridges differentiates it from adenosquamous) 3. Intermediate cells - small basal cells and larger polygonal cells **Growth patterns:** papillary, cystic, glandular, duct-like, solid sheets, cords **Grade**: Low grade = increased mucinous High grade = increased epithelial **AFIP grading system uses the following criteria to determine grading**: - Intracystic component \<20% (i.e. mostly solid) --- 2 points - \>4 mitotic features per 10 HPFs --- 3 points - Cellular anaplasia --- 4 points - Necrosis --- 3 points - Neural invasion --- 2 points - Low grade = 0-4, intermediate = 5-6, high \> 7 - Mortality: low = 0%, high = 45% **IHC**: - Mucinous = PAS, mucin - Epithelial = cytokeratin, EMA **Management**: - Low grade - local Rx alone. PORT only if +ve margins - High grade - local Rx + ND + PORT

Answer 44

Malignant epithelial salivary gland neoplasm of myoepithelial and epithelial cells characterised by tendancy to invade nerves and assume a protracted/relentless course 10% of all malignant salivary gland tumours - 50% of minor salivary gland tumours **Pathology**: - Unencapsulated, infiltrating neoplasm - Neurotropism and invasion beyond the gland (e.g. skeletal muscle) - Microcysts **Growth patterns**: 1. Tubular- least aggressive, may have some cribriform areas 2. Cribriform- 'swiss-cheese' pattern, may include tubular areas, \<30% solid tumour, most common (See Picture) 3. Solid- \>30% solid within a cribriform background, most aggressive **IHC**: - Ductal cells - CK, S-100, EMA, CEA - Myoepithelial cells - S-100, Smooth muscle actin/myosin **Management**: Surgery + RT - RT alone does not cure ACC (50% have early relapse within 18/12) - Surgery alone rarely averts local recurrence - Only Rx neck if involved (rarely) Chemo - palliation only. Symptomatic relief or rapid growth characteristics - Response rates are low and effects are short-lived Targeted therapy - Imatinib is a c-kit tyrosine kinase inhibitor (c-kit known to be an important protoncogene in ACC) - Cetuximab- contradictory responses seen **Prognosis**: Worse prognosis if SMG (more neck disease, higher recurrence) Tendancy for late recurrence (\>10 years). Worse if sinonasal disease - Local failure and distant metastasis (rarely nodal disease) Slow growing tumours, indolent but relentless course

Answer 45

Malignant salivary gland neoplasm with a variety of histologic growth patterns, some cells characterised by cytoplasmic (Zymogen) granules **Epidemiology**: - Male prepondernace - Present in 3rd decade **Pathology**: multiple cell types and growth patterns common - Variable cytologic components: Recapitulate the serous acinar cells of normal salivary tissue - Acinar cells- pathognomonic - Polyhedral, small dark eccentrically placed nuclei - Abundant basophilic cytoplasm with granular cytoplasm (Zymogen granules) - Intercalated, duct-like cells - Vacuolated cells - Clear cells - Reactive lymphoid stroma - Growth patterns- microcystic vs papillary-cystic vs solid vs follicular - Picture = solid and cystic pattern coexisting - Neurotropism - Invasion of adjacent tissue **IHC**: PAS-D (Zymogen granules). Other markers nonspecific **Management**: - Surgery primary Rx - PORT if +ve margins or metastatic disease **Prognosis**: - Generally indolent disease - 1/3 get recurrence (often within 5 years)

Answer 46

Malignant salivary gland characterised by cytologic uniformity, histologic diversity, infiltrative growth pattern and low metastatic potential Low metastatic potential, second MC intraoral salivary malignancy (after MEC) - 60% involve palate (esp hard/soft palate junction) **Pathology**: Cytologic uniformity, histologic diversity, infiltrative growth pattern - Well-circumscribed but unencapsulated - Polymorphic appearance between and within tumours - Solid, glandular, cribriform, ductal, tubular - I.e. many different components to the tumour (see picture- multiple growth patterns)

Answer 47

Epithelial salivary gland malignancy with histologic evidence of arising within a pre-existing pleomorphic adenoma **Pathology**: - Histologically high-grade, overtly infiltrative masses - Mostly high-grade adenocarcinoma (other: SCC, MEC, salivary duct carcinoma) - Need residual evidence of pleomorphic adenoma - 3 types with deteriorating prognosis: - Within a pleomorphic adenoma - Within 1.5cm of a pleomorphic adenoma - Beyond the adenoma **Picture**: pleomorphic adenoma on right = myxochondroid stroma and hypo cellular compared with carcinoma on left = densely cellular

Answer 48

**Benign salivary gland neoplasms:** 1. Monomorphic - Warthin's, basal cell adenoma, canalicular adenoma, myoepithelioma 2. Pleomorphic **Aetiology proposed to be either**: 1. Bicellular reserve theory - Intercalated duct origin --- adenomatoid (pleo, oncoctyoma, Warthin's, acinic cell ca, adenoid cystic ca) - Excretory cell origin --- epidermoid tumours (SCC, MEC) 2. Multicellular theory - Each neoplasm arises from a distinctive cell type

Answer 49

Benign, epithelial-derived tumour composed of both epithelial and mesenchymal cells MC benign salivary gland neoplasm **Aetiology**: Radiation PLAG1 **Pathology**: morphologic variability seen within a single neoplasm - Encapsulated, well-demarcated tumour (low T1, high T2) Multiple components 1. Epithelial- flat cuboidal cells line the ducts 2. Myoepithelial- spindle-shaped hyperchromatic cells 3. Stromal (5 elements) - myxoid, chondroid, fibrous, vascular, osseous - Myxoid tumours more delicate, easily damaged capsule --- prone to recurrence **Risk of malignant transformation 10% over 10 years -** SM gland - Older patient - Size \>4.5cm - Duration

Answer 50

Benign salivary gland neoplasms characterised by a lack of the mesenchymal-like stromal component seen in pleomorphic **Pathology**: - Composed exclusively of the epithelial component - Most commonly epithelial tumours (basal cell adenomas, canalicular cell adneoma) - May be composed solely of myoepithelial components (myoepithelioma) - Lacks the mesenchyme-like stromal component

Answer 51

Benign salivary gland tumour with easily recognisable histologic features: - papillary, cystic, bilayered oncocytic epithelial component and lymphoid follicles 2nd MC salivary gland neoplasm. Lights up on Technitium scan Older men assoc with smoking Bilateral in 10%, multicentric in 10% **Pathology**: Papillary cystadenoma lymphomatosum - Neoplastic transformation of entrapped salivary duct epithelium within intra and periparotid LNs during embryogenesis - Papillary and cystic lesion composed of epithelial and lymphoid components - Epithelium = bilayered granular eosinophilic cells - Oncocytic cells- high mitochondrial content - Lymphoid = lymphoid follicles with germinal centres - Without the lymphoid component = oncocytoma **Misdiagnosis of Warthin's:** SCC or Acinic Cell Carcinoma

Answer 52

**Definition**: A benign, self-healing reactive inflammatory process of minor salivary glands of the palate that may be clinically and histologically mistaken for malignancy **Pathology**: - Trauma —\> interruption of minor salivary gland vascular supply —\> ischaemia - Deep crater-like ulcerative lesion - Ischaemic appearance with reactive background and preservation of surrounding salivary gland architecture - Squamous metaplasia in ducts, retains lobular architecture - Classic misdiagnosis is MEC (or SCC)

Answer 53

Key cell is the Reed-Sternberg cell. Classic Reed-Sternberg cell is 20 to 50 microns in size, with acidophilic or amphophilic cytoplasm, large bilobed or multilobed nucleus with vesicular or coarse chromatin. A large, round, eosinophilic central nucleolus is always present.

Answer 54

**Pathology**: Neoplastic proliferation of RS cells - Large cells (\>45micrometre diameter) with abundant cytoplasm - Multiple nuclei or a single nucleus with multiple nuclear lobes, each with large inclusion-like nucleolus - 'Owls eyes' Surrounded by host inflammatory cells- lymphocytes, plasma cells, neutrophils, eosinophils - Predominantly B cell origin Other conditions in which Reed-Sternberg cells are seen: - Infectious mononucleosis - Solid-tissue cancer - Large-cell NHLs **WHO now classifies 2 types only:** 1. Classical 1. Nodular Sclerosing 2. Lymphocyte-rich 3. Lymphocyte depleted 4. Mixed cellularity 2. Nodular lymphocyte predominant Hodgkin's lymphoma (NLPHL) Therapy and prognosis guided by Ann Arbor staging

Answer 55

**Pathogenesis**: Sublingual gland duct obstruction —\> mucus extravasation —\> pseudocyst formation **Plunging ranula:** 1. Boutonierre deformity- button-hole dehiscence in mylohyoid 2. Intact mylohyoid --- extravasates more postero-lateral around back end of mylohyoid 3. Ectopic sublingual gland- may lie below plane of mylohyoid --- vulnerable to external trauma (i.e. a plunging rannula may develop without the oral component) **Pathology**: No Epithelial Lining Pseudocyst within neck - wall contains granulation tissue with fibroblasts, small vessels, mixed (acute/chronic) inflammatory cell infiltrate, incl foamy histiocytes Salivary gland: dilated ducts, fibrosis, acinar atrophy, chronic inflammation **Image** = pooling mucus, and foamy histiocytes

Answer 56

Idiopathic non-neoplastic ulcerative lesion of the auricle **Aetiology**: - Unknown, theories include……cold exposure, actinic damage, local trauma, pressure necrosis **Clinical**: - M in late middle to older age - Spontaneoulsy occuring unilateral painful nodule, intensely tender 2ndary to perichondrial involvement **Pathology**: - Involved epidermis is ulcerated - Base of ulcer = granulation tissue, oedema, fibrinoid necrosis - Granulation tissue and inflammatory infiltrate extends to and involves perichondrium and cartilage  - Central portion of epidermis is ulcerated - Adjacent epithelium shows acanthuses, hyper and parakeratosis and pseudoepitheliomatous hyperplasia - Base of ulcer shows grannulation tissue, fibrinoid necrosis and inflammatory changes **DDx:** BCC or SCC common misdiagnosis **Treatment**: - Surgical excision is treatment of choice and is curative (wedge excision) - Steriod injection may help in a minority of pts

Answer 57

Likely to be a form of SCC characterised by spontaneous resolution **Clinical course is characteristic:** - Begin as a small papule that rapidly enlarges —\> erythematous nodule with a central keratotic plug - Continued growth over 4-8 weeks, then remains stable - Exquisitely tender - Fleshy rim then recedes —\> keratotic horn - Central plug then falls out and lesion resolves **Pathology**: - Central crater surrounded by hyperkeratosis, parakeratosis, acanthuses - Crater then filled with hyperkeratotic material **Management**: Current management is early excision, rather than waiting for resolution

Answer 58

Rare systemic, relapsing disease characterised by progressive degeneration of cartilage structures throughout the body **Aetiology**: Presumed autoimmune Autoantibodies to Type II collagen **Pathogenesis**: Initial neutrophil infiltration, cartilage loss, later infiltration by histiocytes, plasma cells and lymphocytes, atrophic cartilage with cystic spaces/gelatinous areas **Pathology**: Inflammatory infiltrate around cartilage erosion and replacement by fibrous tissue **Diagnostic criteria** = McAdam criteria (see Staging System cards)

Answer 59

Localised overgrowth of bone - a reactive lesion consisting of a compact proliferation of layers of bone **Differential Diagnosis from Osteoma:** Broad-based Multiple (4, 7, 11 o'clock positions) Dense lamellae of periosteal bone --- dense solid bone on CT **Pathology**: - 'Onion-skin' appearance - Thin periosteum + skin overlying it - Lack of marrow spaces and trabecular architecture **Pathogenesis**: Cold water —\> vasoconstriction of periosteal vessels —\> reflex vasodilation and new bone formation

Answer 60

Hereditary disease of the human otic capsule bone characterised by localised, abnormal bone remodelling Autosomal dominant with incomplete penetrance and variable expressivity **Pathogenesis**: 2 stages 1. Active (otospongiosus) - increased cellularity/vascularity (spongiotic, disorganised bone), bone remodelling, sheets of CT replace bone, enlarged marrow spaces with large vessels +ve Schwartze - continuous active resorption and remodelling 2. Inactive (otosclerosis) - dense sclerotic bone formation with few recognisable Haversian systems in areas of previous resorption Path features of otosclerotic plaques - bone resorption, new bone formation, increased vascularity, CT stroma Blue mantles of Manasse - early feature, more basophilic than normal bone as new bone is rich in amorphous ground substance and deficient with collagen (but over time this is replaced with collagen causing dense sclerotic bone)

Answer 61

**Definition**: A progressive disease of unknown aetiology characterised by exuberant bone remodelling **Genetic** - there is AD inheritance - Sequestsome 1 (SQSTM1) p62 scaffold protein in NF-kB pathway ? viral - paramyxovirus identified in Pagetic osteoclasts ie. viral etiology in genetically susceptible individuals **Pathogenesis/Pathology:** 3 Histologic Stages: 1. Osteolytic phase - excessive osteoclastic activity resulting in bone resorption 2. Mixed phase - new bone formation predominates over bone resorption - deposition of bone adjacent to areas of bone resorption 3. Osteoblastic phase - Increased new bone, dense irregular masses showing mosaic pattern (cement lines)- as per picture Sarcomatous transformation in 1% (osteosarcoma)

Answer 62

A progressive, locally destructive disorder resulting from accumulation of keratinising squamous epithelium within the middle ear or other pneumatised portions of the temporal bone **Pathology**: Cystic mass with a surrounding inflammatory reaction. 3 components: 1. Cyst = keratin 2. Matrix = keratinising stratified squamous epithelium 3. Perimatrix = inflammatory infiltrate/granulation tissue - Proteases and collagenases contribute to local destruction - May have cholesterol clefts also at periphery (hence term 'cholesteatoma')

Answer 63

Benign glandular neoplasm arising from the middle ear mucosa Rare neoplasm. Can be mistaken for metaplasia of glands in CSOM **Pathology**: - Grey-white to red-brown lesion, appears as a relatively avascular soft tissue density - Unencapsulated tumour - Individual or back-to-back growth - Glands = single layer of cuboidal/columnar epithelium

Answer 64

**Formerly Histiocytosis X** Unchecked proliferation of pathologic Langerhan's cells 2nd-3rd decade of life Most lesions are osseous based- incl middle ear and temporal bone **Pathogenesis**: Clonal proliferation of Langerhan's cells (a cellular comonent of the dendritic cell system) Isolated vs systemic proliferation **Encompasses**: 1. Eosinophilic granuloma - single focus (intraosseous), benign, excellent prognosis - Local curettage +/- low dose RT 2. Hand-Schuller-Christian disease - multifocal incl extra osseous + systemic features (DI, exophthalmos) - Low dose chemo for systemic symptoms 3. Letterer-Siwe disease - diffuse involvement, fever, rash, LNpathy, hepatosplenomegaly - Poor prognosis, high mortality- high-dose chemo, + RT, BM transplant **Pathology**: Proliferation of Langerhan's cells - sheets, nests, clusters 1. Nuclei features show longitudinal nuclear groove (as for PTC), and kidney shaped nuclei 2. Inflammatory cell infiltrate (eosinophils seen mainly in eosinophilic granulomas but not other types) **Electron Microscopy:** elongated granules are referred to as 'Birbeck's' granules and are seen in the cytoplasm of Langerhan cells **IHC**: S-100, CD1A

Answer 65

Benign neoplasm arising from the extra-adrenal neural crest-derived paraganglia **Genetics** = Succinyl dehydrogenase subunit mutations (Krebs cycle) Ch 11q23 ie. SDH is a mitochondrial enzyme complex with impt role in oxidative phosphorylation and intracellular oxygen sensing and signaling - SDH-D = MC (PGL1 locus), SDH-C also assoc with PGs (PGL3 locus) - SDH-B = Phaeochromocytoma - SDH-A = Necrotising encephalomyelopathy AD with maternal imprinting (SDH-A and SDH-D is with imprinting). SDH-C and SDH-B are without imprinting. Germline mutations of genes encoding SDHB and SDHC predispose to paraganglioma syndromes (SDHC is very rare) **Pathology**: Gross = encapsulated, well-circumscribed, ovoid, rubbery or firm Nests of Zellballen - Formed by the sustentacular cells, surrounded by prominent vasculature **IHC**: based on cell type: Chief cells - Round or oval with uniform nuclei, dispersed chromatin, abundant eosinophilic, granular or vacuolated cytoplasm - IHC staining with…...chromagranin, synaptophysin, NSE Sustentacular - Represent modified schwann cells (supporting cells) - Located at periphery of cell nests as spindle-shaped (ie. like Antoni A/B cells of AN), basophilic-appearing cells - S-100, GFAP (glial fibrillary acidic protein) Note image = predominantly chief cells with their round/oval uniform nuclei and dispersed chromatin, granular or vacuolated cytoplasm. There is a fibrovascular stroma. The Sustentacular cells are 'spindle shaped' and basophilic (often difficult to see on light microscopy)

Answer 66

**Definition**: A benign tumour affecting the Schwann cells of CN VIII 95% sporadic (unilateral), 5% NF-2 Chromosome 22q12- Merlin (TSG) gene product --- 2-hit hypothesis Mostly affects SVN, arise at Rednik-Obersteiner line (neurilemmal-neuroglial junction where nerve acquires a sheath) **Pathology**: S-100 positive - strongly and diffusely, NSE/chromogranin/synaptophysin -ve! Antoni A - densely packed cells with spindle-shaped, darkly staining nuclei (See picture: whirled appearance with nuclear pallisading = Verocay body) Antoni B - loosely packed cells with vacuolated pleomorphic cells, myxoid stroma (myxoid = 'mucin like') also

Answer 67

Benign neoplasm arising from arachnoid cells forming the arachnoid villi (meningoepithelial cells) - Related to dural venous sinuses 2nd MC CPA lesion, F\>M, 5th decade, previous RT, 18% of IC tumours - May be ectopic in the middle ear or access middle ear by direct spread - May be assoc wtih NF-2 **MC sites:** Parasagittal Falx Olfactory groove Tuberculum sellae Sphenoid ridge Petrous face (CPA) Tentorium/lateral ventricle/Clivus **Imaging**: CT - Hyperostosis in 75% (tumour invades the bone also) MRI - Broad-based lesion, iso/hypointense T1, mod Gad-enhancement (95%) i.e..not as bright as AN, variable T2 (typically 'cellular' therefore less bright than acoustics which have a higher 'water' component) - Dural tail in 60% (seen on gad scan) **Pathology**: - Lobular firm mass. Tumour nests separated by a variable amount of fibrous tissue - Psammoma bodies may be present - Nuclei may have a punched-out appearance **WHO Grading:** 1. Benign (90%) - Slow growing, don't metastasise. May increase during pregnancy 2. Atypical (7%) - More aggressive. Increased mitotic index (4 per HPF) 3. Anaplastic (3%) - Very aggressive (\>20 mitoses/HPF) 4 histologic variants: - Syncytial - Fibroblastic - Transitional (comb of syncytial and fibroblastic) - Angioblastic **IHC**: Vimentin and EMA +ve (-ve for synaptophysin, chromagranin) - Can extend into bone via Haversian canals **Management**: - Total resection is aim - Can do subtotal resection --- adjuvant RT or combined approach (e.g. anterior transnasal approach)

Answer 68

Rare but distinct neoplasm arising from the endolymphatic sac epithelium Sporadic vs von Hippel Lindau - vHL = AD multisystem disorder - cerebellar haemangioblastomas, retinal angiomas, renal cysts, clear cell RCC, other visceral tumours - vHL gene: Ch 3p25 (tumour suppressor gene) - 1/3 of vHL tumours are bilateral **Pathogenesis**: 2-hit hypothesis for the vHL TSG **Pathology**: low-grade adenocarcinoma Variable papillary-glandular appearance - Covered by single row of low cuboidal cells - Have a vascular nature May mimic other tumours - thyroid (papillary), renal/prostate (clear cell Ca), choroid plexus papilloma IHC: Cytokeratin, vimentin, epithelial membrane antigen, S-100, NSE

Answer 69

**Aetiology**: - Represents the a foreign body granulomatous response to cholesterol crystals derived from the rupture of red blood cells with breakdown of the lipid layer of the erythrocyte cell membrane **Pathology**: - Empty grooves surrounded by hemosiderin laden macrophages and foamy histiocytes +/- multinucleated giant cells (FB granuloma) - Cholesterol dissolves in tissues --- needle-shaped clefts (ie. fluid of cyst consists of breakdown products of blood that consists of cholesterol crystals) - Stromal response to haemorrhage ie. surrounding fibrous capsule - Need to exclude a primary pathology (tumour, cholesteatoma) 1. Granulomas (FB) 2. Foamy histiocytes 3. Haemosiderin ladden macrophages 4. Cholesterol clefts 5. Fibrous capsule Image = granulation tissue, multinucleated giant cells, clefts of cholesterol crystals and fresh haemorrhages

Answer 70

Malignant lesion arising from remnants of the notochord - Destructive midline mass **Epidemiology**: - M\>F, 2:1 - Peak incidence in the 8th decade, and rare before the age of 40 **Embryology**: - Notochord develops at 3-4/40 then disappears by 7/40 - Function = is a dorsal organizer region ie. determines the dorsal-ventral axis of neural tube (notochord is ventral to the neural tube), L and R asymmetries, and arterial-vs-venous fates of early blood vessels - Pathway: Exits sphenoid to primitive pharynx then re-enters basiocciput and descends through the centre of vertebral bodies (has a 'serpentine' course thru BOS). Thornwaldt cysts are due to this pathway of communication btw nasopharynx/notocord. - Persists as the nucleus pulposus of intervertebral discs - Chordoma = arise from vestiges of notochord along its path (not from nucleus pulposus) - 35% of chordomas are in the skull base (50% sacrococcygeal, 15% spinal) **Presentation**: Upper brainstem --- CN II, hemianopia etc (like pituitary lesion) Lower branistem --- Lower cranial nerves incl XII - Metastasis - do occur ie. lung/liver/bone but take place late in disease process and don't contribute significantly to overall mortality **MRI**: 'honeycomb' appearance, variable T1 (may be areas of high T1 signal), high T2, marked Gad enhancement (indistinguishable from chondrosarcoma on radiology - except chondrosarcoma's are paramedian and chordomas are midline) **Pathology**: - Pseudo-encapsulated tumour (fibrous outer layer that commuicates with internal septations of lesion) - Lobular growth pattern, exophytic - Physalliferous cells --- 'soap bubble' appearance with vacuolisation of cytoplasm displacing nuclei peripherally, may have chondroid features **IHC**: S-100, cytokeratin, EMA +ve ie. epithelial markers +ve (differentiates from chondrosarcoma) **Chondrosarcoma vs Chordoma**: - lack of 'soap bubbles' - have islands of cartilage (ie. may appear like chondroid chordomas), - lack epithelial antigens on IHC. - Chodrosarcomas are 'mesenchymal origin lesions' vs chordomas are epithelial orgin lesions **Presentation**: Ophthalmoplegia (VI in Dorellos, III, IV. VI in cavernous sinus) or H/A Recurrence --- 5% 5-year survival **Treatment**: - Generally chordomas and chondrosarcomas are considered chemoresistant and relatively radio resistant, hence mainstay is surgical excision - Complete surgical excision of skull base lesions is almost impossible and assoc with high morbidity, therefore often sugical decompression followed by adjuvant RT (proton beam)

Answer 71

**Definition**: A mesenchymal tumour (hence Vimentin staining) arising from petro-occipital cartilage rests **Classification**: Primary - chondrosarcoma in absence of other features Secondary - associated with anchondroma, Olliers disease (multiple cartilage tumours) **MC Sites:** 1. Larynx 2. Petrous apex- arise from cartilage rests: petro-sphenoid and petro-occipital 3. Maxillofacial **Radiology**: key is to differentiate from chordoma CT: destructive, lateral lesion, chondroid calcifications MRI: 'popcorn' appearance, low T1, high T2, heterogenous Gad enhancement **Pathology**: Biphasic tumour: 1. Cellular area = undifferentiated, small round cells 2. Cartilage = relatively bland appearing **High grade vs low grade** - Cellularity, pleomorphism, mitoses and multinucleated cells IHC: Vimentin, CD99, NSE - Negative for epithelial markers

Answer 72

The grading of chondrosarcomas is done on the basis of cellularity and atypia. Mitotic figures are uncommon and are not used in the grading. The tumor shown in the photomicrograph is a Grade 2 chondrosarcoma given the cellularity and pronounced atypia. Between 30% and 40% of all chondrosarcomas are Grade 2.

Answer 73

Acellular hyaline and calcified deposits accumulate within the TM and submucosa of the middle ear **Aetiology**: - Complication of otitis media or trauma - VTs --- 60% (lower for myringotomy alone- 15%) **Pathogenesis**: Destructive process within connective tissue —\> degeneration of collagen and subsequent dystrophic calcification and tympanosclerosis **Pathology**: - Hyalinization of subepithelial connective tissues - TM --- limited to the lamina propria - ME --- most frequent in attic, assoc with ligaments of the malleus head and incus body - Calcification most often present - Osteoneogenesis can occur —\> ossicular fixation **Management**: suggest conservatism as likely variable outcomes - Smyth et al --- 79% hearing restoration with OCR - Used a two-stage technique - Teufert et al --- 60% success in ABG closure to less than 20dB (average pre-op ABG was 30dB) - Gormley et al --- 7% improved to within 20dB

Answer 74

**Definition**: A benign nerve sheath tumour in the peripheral nervous system **Epidemiology**: - Most are single and not assoc with a syndrome - Assoc with NF1 and very rarely NF2 - Localized cutaneous form is MC, plexiform is often assoc with NF1 - NF1 pts often affected as children, and get all types (cutaneous and plexiform) **Pathophysiology**: Biallelic inactivation of the NF-1 gene (17q11.2) that codes for neurofibromin - RAS-inhibitor which mediates cell growth signaling pathways Two-hit hypothesis - Inherited mutation present in NF-1 means only a single hit required to produce a neoplasm **Pathology**: Arises from non-myelinating Schwann cells - Non-myelinating Schwann cells encapsulate small diameter PNS axons with their cytoplasmic processes - Myelinating Schwann cells cover large diameter (\>1pm) PNS axons with myelin In contrast to Schwannomas, although arising from Schwann cells they incorporate many additional types of cells - Fibroblasts, perineural cells, endothelial cells, mast cells - Residual nerve fibers are interspersed in tumour (unlike schwannoma which is eccentric to nerve) - Histology shows spindle cells with wavy nuclei - IHC = S100 +ve **Subtypes**: 1. Dermal - Single peripheral nerve in the skin - 3 types: discrete cutaneous, discrete subcutaneous, deep nodular - Arise in teenage years, often assoc with onset of puberty - Increase in size and number through adult life 2. Plexiform - Multiple nerve bundles - skin or more internal nerve bundles - Difficult to remove completely because they extend through multiple layers of tissue **Clinical Features:** - Typically solitary, unless assoc with NF1 - NF1 features = cafe-au-lait spots, axillary freckling, \>2 neurofibromas, 1 plexiform NF, optic nerve gliomas - Localised cutaneous = are soft, polypoid, painless, slow-growing mass - Diffuse cutaneous = plaquelike thickenings of dermis - Localised intraneural = asymptomatic lump, can cause neuropathic pain or tingling **Prognosis**: - Localised cutaneous don't undergo malignant change - Diffuse cutaneous and intraneural NF's rarely undergo malignant transformation - Plexiform neurofibromas are the MC to undergo malignant transformation

Answer 75

**Definition**: Benign developmental cystic anomaly arising from ectoderm and mesorderm (no endoderm) **Epidemiology**: 34% of all dermoids occur in H&N Most often present 1st decade of life **Aetiology**: Ectodermal differentiation of multipotential cells trapped at the time of closure of the anterior neuropore (hence along midline of neck). Result of entrapment of epithelial and dermal (i.e.. layer just beneath epithelium) elements along embryonic lines of fusion (ie. Median and paramedian) **Pathology**: Lined by stratified squamous epithelium Cutaneous adnexal structures (hair shafts, sebaceous glands, eccrine glands, apocrine glands) in the fibroconnective tissue wall Cyst filled with keratin Rupture results in florid foreign body giant cell reaction Typically midline, usually sub mental - Attached to and move with overlying skin

Answer 76

**Features**: Vascular tumours vs Vascular Malformations **Vascular Tumours** - HOI not present at birth vs Congenital haemangioma present at birth (RICH vs NICH) - Rapid proliferation, then involution - Endothelial hyperplasia with active growth - Multilayered basement membrane - Rapidly dividing endothelial cells - Pathology shows syncytial masses with and without lumina - GLUT-1 receptors present (HOI) **Vascular Malformations** - Present at birth - Growth matches that of child - Endothelial cell hypertrophy (not hyperplasia) - Single layer basement membrane, flat quiescent endothelium - Non-dividing endothelial cells - Pathology shows abnormal dilatation of vascular channels - GLUT-1 receptor absent

Answer 77

A low flow vascular malformation **Embryology/Pathogenesis:** 1. Centripedal theory - Lymphatic channels fail to grow from lymphatics to venous system - Retain proliferative growth potential without connection to normal lymphatic system 2. Centrifugal - Endothelial fibrillar membrane proliferation from walls of the cyst, penetrate surrounding tissue along lines of least resistance **Pathology**: Multiple dilated lymphatic channels - Lined by single layer of flattened endothelium - contains proteinacous fluid and lymphocytes - Intervening stroma - fibrous connective tissue, muscle (smooth/striated), lymphoid aggregates **Subtypes**: Macrocystic (\>2cm3) Microcystic (\<2cm3) Mixed

Answer 78

**Definition**: One of 3 types of Schneiderian papilloma (fungiform/exophytic, cylindrical/columnar, inverting) Schneiderian Papilloma - a benign tumour arising from ectodermally derived Scheiderian mucosa of the sinonasal tract (ie. nasopharynx is endodermal derived) Schneiderian Membrane - histologically distinct in that it is 'mucoperiosteum'. i.e.. a bilaminar membrane with ciliated columnar epithelial cells on the internal side, and periosteum on the osseous side. **Epidemiology**: Exophytic (fungiform or septal) = 50%, Inverting = 47%, Oncocytic (Cylindrical) = 3% Up to 4% of all nasal tumours, M\>F (i.e.. just like Antrochoanal polyps), 5th-6th decade **Pathogenesis/Pathology:** General Features of Schneiderian Papillomas - All show squamous epithelium (arising from normal respiratory epithelium) - All have intra-epithelial mucin and mucocytes Inverted type - Prolif of epithelium with finger-like inversions into underlying stroma (but not through basement membrane!!!!) - Assoc with chronic inflam cells, goblet cells and intra-epithelial mucin microcysts (PAS +ve) Exophytic papilloma - Exophytic type of growth, found mainly on the nasal septum - Squamous epithelium arranged in papillary fronds Cylindrical/oncocytic papilloma - Multilayered epithelium with an eosinophilic cytoplasm Malignant transformation 5-15% - features assoc with malignant transformation: 1. Hyperkeratosis 2. Plasma cells 3. Bilateral disease 4. \> 2 mitotic features

Answer 79

Rapidly growing lesion characterised by proliferation of capillaries in a lobular architecture aka Lobular Capillary Haemangioma --- other haemangiomas are rare in the sinonasal tract A submucosal lesion with thickening of the overlying epithelium Trauma, hormonal (OCP, pregnancy) **Pathologic features:** smooth, lobulated polypoid red mass 1. Lobular capillary proliferation - ectatic vessels with RBCs within them - Lobular architecture differentiates it from granulation tissue 2. Loose CT stroma 3. Inflammatory cell infiltrate - granulation tissue and mixed chronic inflam cell infiltrate No true cytologic atypia

Answer 80

**Definition**: Benign, bone-forming tumours almost exclusive to the craniofacial skeleton M\>F, any age, often asymptomatic, frontal\>ethmoid\>max\>sphenoid Sharply delineated radio-opaque lesion confined to bone or protruding into a sinus Sporadic or assoc with Gardner's syndrome (AD, intestinal polyposis, soft tissue lesions, multiple craniofacial osteomas) Submucosal proliferation of dense, mature, predominantly lamellar bone **Pathology**: Histologically divided into 3 categories 1. Ivory - compact, dense bone. Minimal fibrous tissue, no evidence of Haversian systems 2. Mature - spongy, mature bone. Conspicuous fibrous tissue, fibroblasts, collagen 3. Mixed - components of both ivory and mature

Answer 81

**Definition**: Genetically-based developmental anomaly of bone-forming mesenchyme Benign, idiopathic non-neoplastic bone disease, normal medullary bone replaced by structurally weak fibrosseous tissue Mutation of GNAS1 gene Ch20q13.2 (codes for a subunit of G-protein) **Epidemiology**: Diagnosed in 1st-2nd decade of life **Classification**: 1. Mono-ostotic 2. Poly-ostotic 3. MaCune-Albright syndrome (triad of polyostotic fibrous dysplasia, endocrine dysfunction, cutaenous hyperpigmentation) **Clinical Features:** No specific symptoms, just as a space occuping lesion within the nasal obstruction +/- sinus drainage and obstruction **Pathogenesis**: Defect of bone caused by a defect in osteoblastic differentiation and maturation that leads to replacement of normal bony tissue by fibrous tissue of variable cellularity and immature woven bone. All bone components present but don't differentiate to mature structure Well-circumscribed, intramedullary lesions, expand/distort bone Replacement of medullary bone by fibrous tissue +/- bone metaplasia Chinese characters = curvilinear trabecular of woven bone surr by mod fibroblastic prolif 1. Pagetoid 56% (ground-glass) 2. Sclerotic 23% (least active) 3. Cystic 21% (most active) No osteoblasts at the edges --- differentiates from ossifying fibroma Malignant transformation to osteosarcoma- Mono = low, Poly = 0.5%, MAS = 4% **Investigations**: CT scan = early phases is assoc with a high density of fibrous tissue, and radiolucency or lytic appearance, as amount of bony tissue increases get a ground glass appearance MRI scan = signal reported as variable on T2 weighted sequences, T1 shows hypointensity, nonhomogenous enhancement with gadolinium. **Treatment**: Surgery - To relieve symptoms of visual impairment if compression of optic nerve, and open sinuses if causes concern - Radiotherapy contraindicated because of risk of malignancy Medical - Bisphosphonates to inhibit osteoclastic activity if assoc with disfigurement

Answer 82

**Definition**: A true benign neoplasm Well-demarcated, slow-growing, benign fibro-osseous neoplasm composed of fibrocellular tissue mixed with variable osseous component **Epidemiology**: - Presents in 3rd-4th decade - More common in black women **Pathology**: Origin from periodontal ligament (ie mandible is most common site) Randomly distributed mature lamellar bone spicules rimmed by osteoblasts mixed with a fibrous stroma Osteoblastic rim differentiates it from Fibrous Dysplasia **Psammomatoid (active) OF**: **Investigations**: CT - unifocal lesion, sharply defined, smooth/corticated borders - Early lesions = cyst-like - Later lesions = radio-opaque mass surrounded by radiolucent rim **Management**: Observation - small, asymptomatic lesion Surgery - complete excision more easily obtained than FD -Aim should be radical resection as lesions have high replase rate (44% for ethmoid lesions) with aggressive behaviour if reoccur with invasion of adjacent vital structures **Natural History/Prognosis:** Excellent prognosis with surgical excision - Recurrent tumours can be aggressive No known malignant potential

Answer 83

Variant of ossifying fibroma - Typically occurs in sinonasal tract (ethmoid, supraorbital ridge) - 1st/2nd decade, M\>F, ethmoid or supra-orbital, single or multiple - Very aggressive **Pathology**: Similar to OF but also psammomatoid bodies - Bony spicules/spherules admixed with fibrous stroma - Psammomatoid bodies - central blue-black appearance surrounded by pink-appearing rim and with concentric laminations - Stroma is composed of spindle-shaped or polyhedral cells with basophilic nuclei and scant cytoplasm **Management**: Surgical excision (recurrence rel to incomplete excision). No malignant potential

Answer 84

A type of soft tissue sarcoma that originates in the pericytes in the walls of capillaries Middle age, M=F - A rare sinonasal neoplasm (1%) but 25% of HPC occurs in sinonasal tract **Pathology**: - Macroscopically - beefy red, soft, fleshy/friable masses - Submucosal, circumscribed but unencapsulated cellular tumour - Diffuse growth pattern - Single cell type surrounding endothelial-lined vascular spaces - Uniform, elongated cells with hyper chromatic nuclei - Vessels have a 'staghorn' configuration ('antler-like') **IHC**: Actin, Vimentin

Answer 85

Malignant epithelial neoplasm arising from the surface epithelium with squamous cell differentiation MC sinonasal malignancy. Max \> nasal \> ethmoid \>\> sphenoid/frontal **Risk factors:** - Nickel exposure (250x), textile dust, prior IP **Subtypes**: Keratinising (85%) - Intercellular bridges, hyperchromatic nuclei, mild-mod atypia, low mitotic rate - Well, mod, poorly differentiated carcinomas --- more differentiated- less keratinisation, more nuclear atypia/mitoses - 'Mosaic tile' arrangement - Keratin pearl formation, surface keratinisation - Dysplasia of overlying surface epithelium may also be seen - Stromal invasion: cohesive nests or cords Non-keratinising (15%) - Elongated cells, nuclear pleomorphism, increased N:C, loss of polarity - Papillary or exophytic growth pattern with downward growth as well - Can be confused for inverting papilloma - stromal invasion may be difficult to demonstrate - Hypercellular neoplasm - pleomorphism, hyperchromasia, increased N:C, loss of polarity, atypical mitoses - Variants are rare Overall 5 year survival = 60% - Nasal cavity do better than maxillary sinus (earlier diagnosis)

Answer 86

**Definition**: Malignant glandular epithelium tumour of the sinonasal tract **Epidemiology**: M\>F = 4:1, 5th-7th decades **Aetiology**: Hard wood - 500x risk (wood dust particles rather than chemicals used) - Ebony, oak and beech. Only present in 25% of AdenoCa - Arise in olfactory cleft when assoc with hard wood - Generally T3/T4 at presentation, neck involvement \<10% **Pathology**: Non-Salivary gland origin 1. Intestinal-Type (ITAC) - Barnes classification: Papillary, colonic, solid, mucinous, mixed - Papillary least agressive, solid/mucinous worst prognosis - Hard wood = papillary and colonic 2. Non-intestinal, non-salivary sinonasal adenocarcinoma - Low-grade (ethmoid) vs high-grade (maxillary) - No known occupational associations Salivary gland origin - Adenoid cystic MC (MEC, acininc cell less common) **Histology**: 1. ITAC - so called as may have features of intestinal mucosa (ie. villi, paneth cells, enterochromaffin cells, muscularis mucosa) - Barnes classification- papillary, colonic, solid, mucinous, mixed - IHC: cytokeratin CK-20 (as for colon carcinoma), CDX2 Papillary types (MC, least aggressive) - papillary archietecture with tubular glands, minimal atypia Colonic (MC) - tubuloglandular architecture, rare papillae, increased nuclear pleomorphism/mitosis Solid (poor prognosis) - Loss of differentiation with solid and trabecular growth, marked increase in small cuboidal cells and nuclear pleomorphism/mitosis Mucinous - prominent mucus production, similar to colonic adenocarcinomas Mixed - mixture of the above type 2. Non-salivary, non-ITAC Seromucinous - Low-grade = ethmoid, high grade = maxillary - No known occupational exposures 3. Salivary gland origin - Adenoid cystic is MC in sinonasal tract, identical to other salivary origins histologically ie. cribriform/tubular/solid variants, tumours composed predominantly of abluminal myoepithelial cells and luminal duct lining cells, perineural invasion is high - MEC and acinic cell are less common Ohngren's line for prognosis (angle of mandible to medial canthus) NOTE: adjacent image is ITAC colonic subtype

Answer 87

**Definition**: Highly aggressive and clinicopathologically distinctive carcinoma of uncertain histogenesis, presenting with locally advanced disease (WHO definition) Rare, rapid onset of symptoms No known aetiologic agents Extensively infiltrative at presentation- includes orbit, brain - Also regional and distant (liver, lung, bone) **Pathology**: Squamous and glandular differentiation not present - Hypercellular, variable patterns: nests, lobules, trabeculae, sheets - Pleomorphic tumour cells- similar to large cell Ca or nasopharyngeal Ca or 'Western' type (small nuclei, hyperchromatic with pink cytoplasm). Often polygonal - Frequent necrosis - LVS and PNI is common - IHC: - differentiation from other small blue cell tumours - S100 -ve (classical for melanoma, Esthesio's, SCUNC) - Synaptophysin -ve (classical for SCUNC) - NSE -ve (neurone specific enolase) (classical for Esthesio's, SCUNC) - HMB-45, Vimentin -ve, Melan A (classical for melanoma) - CD99 -ve (classical for Ewings Sarcoma) - CK7, CK8, CK19 +ve (SNUC's are consistently immunoreactive with epithelial markers for pankeratin and simple keratins)

Answer 88

Malignant neuroectodermal neoplasm thought to arise from the olfactory basal reserve cell Bimodal age distribution, no known aetiologic agents **Pathology**: Cell of origin is the olfactory basal reserve cell The great imposter - can be confused with other undifferentiated sinonasal cancers **Hyams tumour grading:** I-IV, generally divided I/II vs III/IV Grade I/II vs III/IV Pleomorphism slight vs prominent/marked Mitosis/necrosis absent/slight vs prominent/marked Neurofibrillary matrix prominent/present vs absent Rossettes are the hallmark! present vs absent Calcification variable vs absent Lobular growth pattern with rosettes - circumferential grouping of cells around the neurofibrillary matrix IHC - Neuron-specific enolase, S-100, chromogranin (-ve for cytokeratin, epithelial markers CEA/EMA) More on rossettes - Homer-Wright- pseudorosettes Hyams I-II (central hub composed of fibre-like process) - Flexner-Wintersteiner - true rosettes Hyams III-IV (central hub has a lumen)

Answer 89

**Definition**: Neural crest-derived neoplasms originating from melanocytes and demonstrating melanocytic differentiation Sinonasal tract is an uncommon site, adults, M\>F Nasal cavity (septum, LNW) more common than sinuses (max\>eth) No known aetiologic agents **Pathology**: can appear very similar to other tumours --- need IHC - Surface ulceration common - Epithelioid or spindle cells, often mixed - Variable growth patterns- solid, organdie, nested, trabeculated, alveolar - Cells: round, marked pleomorphism, increased N:C, hyperchromatic nuclei **IHC**: S-100, HMB-45, Vimentin, Melan A - Gold-standard for diagnosis

Answer 90

Heterogenous group of haematolymphoid malignancies NHL is MC (B cell mostly) NK/T cell lymphoma - Men, age = 6th decade, MC in Asian populations - EBV associated (strongly) - Destructive process of the mid face- septum, palate, orbit - Pathology: granulomatous picture may mimic Wegeners - Angiocentric and angioinvasive lymphoid infiltrate - Atypical PMN cells Lipford classification 1. Perivascular infiltrate of lymphocytes, plasma cells 2. Increasing atypical lymphoid cells with focal necrosis 3. Obvious lymphoma with vascular destruction + extensive necrosis **Disease stages** Prodromal - clear rhinorrhea, NAO Ulcerative - purulent rhinorrhea, ulceration, septal perforation, bone/cartilage destruction Terminal - malaise, fever, sloughed off tissue, gross midface destruction, death B-cell lymphoma - low-grade --- nasal mass assoc with airway obstruction - high-grade --- non-healing ulcer, CN palsies, facial swelling, epistaxis, pain, orbital involvement **IHC**: - CD-45 = Common leukocyte antigen - B-cell = CD-20 - Ki67 = Proliferative index (affects prognosis and treatment) - T-cell = CD-3 - NK-cell = CD-56

Answer 91

Malignant tumour of skeletal muscle phenotype 40% occur in H&N, 20% in sinonasal tract - MC sarcoma in childhood **Pathology**: Spindle cells with hyperchromatic nuclei Myxoid stroma Botryoid type —\> polypoid gross appearance Cambian layer = submucosal hypercellular layer **Pathologic Subtypes**: 1. Embryonal - Botryoid (in picture on this facet), Spindle cell 2. Alveolar - fibrous septae separate clusters of loosely cohesive groups 3. Pleomorphic **IHC**: desmin, actin, fast myosin, myoglobin, MyoD1

Answer 92

**Definition**: A vascular tumour of the nasopharynx arising in adolescent males characterised by vascular spaces embedded in a fibrous stroma Adolescent males 10-25 years old Hamartoma - Composed of tissue elements normally found at the site but growing in a disorganised mass. Benign focal malformation rather than malignant tumour Hormonal influences controversial - ? relationship to estrogen receptor positivity, Genetic changes (Chr 17), Proangiogenic growth factors (VEGF, TGF-b), p53 **Pathogenesis**: Myofibroblast is the cell of origin Arises from superior margin on SP foramen (trifurcation of palatine bone, horizontal ala of vomer, root of pterygoid process) **Pathology**: Vascular spaces with dense stroma Well-circumscribed, lobulated, purple-red mass, with intact mucosa Two components microscopically 1. Fibrous stroma - spindle-shaped cells in dense collagen stroma 2. Vessels - irregular vascular channels (capillary-large venules) = Staghorn vessels (pathognomonic) with loss of muscular layer. **IHC**: smooth muscle actin, vimentin

Answer 93

**Pathology**: Surface epithelium intact (ciliated pseudo stratified) Oedematous stroma Absence of mucoserous glands Mixed chronic inflammatory infiltrate - eosinophils vs neutrophils, plasma cells, lymphocytes 'Pseudogranuloma'- small patches of stromal non-oedematous collagen with inflammatory cells aggregated around periphery Nerves absent- decreased secretion, abnormal vasc perm with oedema

Answer 94

**Pathology**: Similar to inflammatory polyp - No glands in the core - No inflammatory response - Increased fibrosis + squamous metaplasia of the surface epithelium Has a cystic stalk attachment to antrum!

Answer 95

Midline lesion Need to exclude intracranial extension **Pathology**: Fibrillary pattern with large astrocyte cells **IHC**: GFAP- Glial Fibrillary Acidic Protein

Answer 96

**Definition**: A chronic epithelial-lined (pseudostratified columnar), mucus containing sac filling the sinus, capable of expansion, typically caused by sinus outflow obstruction (ie. if sinus isn't expanded then it is just an obstructed sinus) **Epidemiology**: - Rare. All ages, equal gender distribution Aetiology: 1/3 have no predisposing factor Surgery and trauma most common **Pathogenesis**: Consequence of obstruction and inflammation. 3 main theories 1. Pressure erosion 2. Cystic degeneration of glandular tissue 3. Active bone resorption and regeneration **Events** - Obstruction of sinus outflow - Chronic inflam - cytokine production, upregulation of vasc adhesion molecules - Osteoclastic bone resorption, fibroblast proliferation **Pathology**: - Cyst lined with flattened pseudostratified ciliated columnar epithelium --- i.e. near normal respiratory epithelium - Supports not needing to remove the mucocele lining - Reactive bone changes adjacent to cyst epithelium (neo-osteogenesis) **Picture**: herniation of cyst into submucosal tissue adjacent bony wall of sinus

Answer 97

Each cilium has an array of longitudinal microtubules arranged as 9 doublets formed in an outer circle around a central pair (2) Main structural protein of doublets = tubulin. Radial spokes connect the outer doublets with a central sheath of protein around the central pair Inner and outer dynein arms, are attached to the A subunit of each microtubule doublet. Dynein, a type of ATPase, provides energy for microtubule sliding and the longitudinal displacement of adjacent microtubular doublets, resulting in ciliary bending. The protein nexin links the outer microtubular doublets Because nexin links maintain axonemal relationships while the basal bodies anchor the microtubules, the sliding of the outer microtubule results in bending of the cilium.

Answer 98

**Definition**: A rare group of disorders causing defects in the action of cilia lining the respiratory tract, fallopian tube and flagella of sperm **Epidemiology**: Rare, autosomal recessive **Assoc Syndromes:** Kartagener's: triad of situs invertus, CRS and bronchiectasis - \> 1/2 of patients with PCD will have full triad due to loss of functional cilia in embryonic period Young's syndrome: CRS + obstructive azoospermia - Motile cilia and normal CTFR gene separate it from CF and PCD **Pathology**: Ultrastructural defects affecting proteins in the outer and/or inner dynein arms which give cilia their motility - DNAI1 and DNAH5 code for outer dynein arm proteins (38% of cases) Results in severe mucociliary impairment Look for missing outer or inner dynein arms or both!

Answer 99

Low-intermediate grade malignant tumour arising from the embryonic remnants of the notochord Notochord normally disappears by 7/40 - May persist: sacrococcygeal, skull, verebra (C\>L\>T) **Craniocervical chordomas**: dorsum sella, clivus, nasopharyngeal **Pathology**: - Pseudo-encapsulated tumour separated into lobular growth pattern by fibrous CT - Epithelioid cells with vesicular nuclei and abundant, vacuolated-appearing cytoplasm - Physaliferous cells = 'soap-bubble' appearance with vacuolization of cytoplasm displacing nuclei peripherally **IHC**: S-100, cytokeratin +ve, EMA +ve

Answer 100

Face develops from 4-8/40, Palatogenesis = 5-12/40 Face develops from neural crest cells that migrate to form the facial mesenchyme **At 4/40:** 5 processes form around the stomodeum - Frontonasal process (cranial neural crest cells) - Bilateral maxillary processes (arch I) - Bilateral mandibular process (arch I) Thickenings appear on each side of the frontonasal process- the nasal placode - On each side of the placode forms the medial and lateral nasal processes (5/40) - The nasal pit lies between these (also 5/40) The maxillary process then grows under the lateral nasal process to fuse with the already fused medial nasal processes - The primary palate (7/40) - (primary palate formed from fusion of median nasal prominences)

Answer 101

**Primary palate =** central maxillary alveolar arch (4 incisors) and hard palate anterior to incisive foramen - Medial nasal prominence --- philtrum, medial upper lip, nasal tip, columella - Max prominences --- lateral lip and then fuses with MNP Behind the primary palate, the maxillary processes form palatal shelves (6/40) - These grow towards each other, initially facing downward - The medial edge epithelium then rapidly elevate over hours during 7/40 to fuse in the midline and allow the mesenchyme to flow across the palate Palatal fusion progresses anterior-posterior - Incisive foramen at 8/40, completed by 12/40 (uvular fusion) Nasal septum fuses with both primary and secondary palates - In unilateral cleft, it fuses with the normal side only Nose formed from: MNP = tip, collumella and LNP = alar and FNP = nasal bridge