FRCPath 2 teaching H&N 2023

FRCPath Part 2 Surgical Course

Head & Neck Pathology

Eranga Nissanka-Jayasuriya Consultant Head & Neck Pathologist William Harvey Hospital, Ashford, Kent

Marking Scheme 3.5

3.0

2.5

2.0 1.5 1.0

Case 1

Case 1

26-year-old, Female, Parotid tumour

PART 2 SURGICAL COURSE - HEAD AND NECK PATHOLOGY PREETHA CHENGOT

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Case 1- Salient points • Circumscribed salivary tumour, infiltrative periphery • Papillary cystic, microcystic patterns, hobnailing • Solid sheets of large polygonal cells with granular eosinophilic cytoplasm and vesicular nuclei • Secretory material –colloid-like eosinophilic secretions • Occasional mitotic figures

• Work up? PAS, DPAS, • CK7, S100, DOG1, Mammoglobin

Case 1 Diagnosis

Secretory carcinoma

Discussion Differential diagnoses • Acinic cell carcinoma • Secretory carcinoma (previously called MASC) • MEC • 90% -ETV6::NTRK3 fusion -chromosomal rearrangement, t(12;15) (p13;q25) • ETV6::RET, ETV6::MET, ETV6::MAML3 • ETV6 translocation-negative secretory carcinoma.

• Similar to Acinic cell carcinoma • But S100+, Mammoglobin+, DOG1-

Mammaglobin

S100

GATA3

ETV6 FISH

WHO 5th ed Essential and desirable diagnostic criteria • Essential: single cell type with vacuolated colloid-like secretory material; no zymogen cytoplasmic granules; IHC positivity for S100 protein, SOX10, and mammaglobin; lack of IHC staining for p40 and/or p63 • Desirable: ETV6 or RET rearrangement demonstrated by FISH, RNA sequencing, or PCR • Low grade • Lymph node metastases are reported in as many as 25% of cases

Case 2 56-year-old, Male Dysphagia And Lump In Pharynx

56-year-old, Male Dysphagia And Lump In Pharynx.

Case 2- Salient points • Multicystic and solid • Epidermoid, clear cells and mucous cells • Low grade- predominantly cystic • Work up? ABPAS, DPAS • CK7, P63 • Molecular: translocation at t(11;19)(q21;p13) expressing CRTC1::MAML2 fusion gene • DD-papillary cystadenoma, mucous retention cyst

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Case 2 Diagnosis

Mucoepidermoid carcinoma, low grade

MEC Grading

commonest grading system: https://www.ncbi.nlm.nih.gov/pubmed/1544111 -Intracystic component <20% -Neural invasion -Necrosis -Mitoses >4/10 hpf -Ananplasia Other grading systems: https://www.ncbi.nlm.nih.gov/pubmed/9529011, https://www.ncbi.nlm.nih.gov/pubmed/11420454, https://www.ncbi.nlm.nih.gov/pubmed/25040772

Selected Geneticalterations Alterations in in Salivary Glandtumours Tumors Selected genetic salivary Tumor

Alteration

% cases

Acinic cell carcinoma

NR4A3 fusions HTN3-MSANTD3 fusion

95% 5%

Adenoid cystic carcinoma

MYB-NFIB MYBL1-NFIB MYB activation/amplification

~80%

Basal cell adenoma/ Basal cell carcinoma

CTNNB1 or CYLD mutation

40-80% (adenoma) 5-30% (carcinoma)

Clear cell carcinoma

EWSR1-ATF1

~80-90%

Epithelial-Myoepithelial Carcinoma

PLAG1 or HMGA2 fusions HRAS mutations

~50%

Low-grade intraductal carcinoma

NCOA4-RET

~50%

Mucoepidermoid carcinoma

CRTC1-MAML2 CRTC3-MAML2

~70-80%

Pleomorphic adenoma and carcinoma expleomorphic adenoma

PLAG1 or HMGA2 fusions

~60-90%

Polymorphous adenocarcinoma

ARID1A-PRKD1 DDX3X-PRKD1 Other PRKD2 and PRKD3 fusions

~20-50%

Salivary duct carcinoma

TP53, HRAS, PIK3CA, PTEN mutations ERBB2 amplification PLAG1 or HMGA2 fusions

90-100%

Secretory carcinoma

ETV6-NTRK3 ETV6-RET ETV6-MET

100%

Case 3

21-year-old, Female, Lump In Floor Of Mouth.

Case 3- Salient points • Pseudocyst lined by compressed rim of foamy macrophages • No epithelial lining • Associated with atrophic minor salivary glands

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Case 3 Diagnosis

Mucous extravasation cyst (extravasation mucocoele)

HN4

Case 4

• Female 40 years Firm nodule dorsum of tongue. Present for months. Case type Oral.

Specimen: Tongue.

Macroscopic description: Mucosa 15 x 12 mm with firm tissue to depth of 9 mm.

Immunohistochemistry: None.

Case 4- Salient points • Nodular mucosa with circumscribed tumour with infiltrative periphery • Large cells with eosinophilic granular cytoplasm • Is surface epithelium normal?

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Case 4 Diagnosis

Granular cell tumour

Case 5 16-year-old, Female, Cyst Associated With Unerupted Lower Wisdom Tooth.

Case 5- Salient points • Non-specific thin squamous epithelial lined cyst • No keratinisation, basal palisading • Largely uninflamed fibrous cyst wall

• Location + histology

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Case 5 Diagnosis

Dentigerous cyst

Common odontogenic cysts & tumours • Dentigerous cyst • Radicular cyst • Odontogenic keratocyst • Orthokeratinised odontogenic cyst • Ameloblastoma • Radiology is a must- Location, relationship to tooth and nature of radiolucency can give diagnostic cluses

Case 6 28-year-old, Male Nasal Polyp.

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Salient points • Laminated mucin • Degenerate eosinophils • Charcot-Leyden crystals • Fungal hyphae (usually fungal ball)

Case 6 Diagnosis

Allergic fungal rhinosinusitis

Case 7 62-year-old, Female Block From Maxillectomy Specimen.

Case 7- Salient points • SCC • Is lymphoid tissue normal- small monotonous sheets, no follicles • Work up- IHC

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Case 7 Diagnosis

Squamous cell carcinoma and Lowgrade small cell lymphoma (Grade 1 follicular type NHL)

Case 8 • Male 14 years

Spontaneous swelling of the lower lip and mucosa generally. Unresponsive to antivirals. No other relevant medical history.

Specimen: Left buccal mucosa.

Macroscopic description: punch biopsy 4x3x3mm.

Immunohistochemistry: D/PAS negative.

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Case 8 Diagnosis

Oral granulomatous inflammation likely orofacial granulomatosis

• Cobblestone cheek swelling and lip swelling • Children, young adults

• Associated with sarcoidosis and Crohn’s disease (could be the presenting feature before GI symptoms start)

Case 9

38-year-old Female, Cyst Associated With Unerupted Wisdom Tooth.

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Case 9 Diagnosis

Odontogenic keratocyst

Salient points •Basal cell palisading •Corrugated parakeratosis •Focal inflammation –loss of above and “non-specific” features •Consistent loss of PTCH tumour suppressor gene- GorlinGoltz syndrome •Tendency for recurrence

Case 10 66-year-old Excision Of Tumour Tongue / Floor Of Mouth.

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Case 10 Diagnosis

Mucosal melanoma

• • • • • • • •

80% of head and neck MM- nasal cavity, septum, maxillary sinus In the oral cavity-maxillary gingiva and palate Flat pigmented lesions Tumour cells are polymorphic Lentiginous/pagetoid growth pattern All head and neck mucosal MM are T3–4 and stage III-IV T3 Tumour limited to the epithelium and/or submucosa (mucosal disease) T4a Tumour invades deep soft tissue, cartilage, bone, or overlying skin

• Oral pigmented patches DD • • • •

Melanotic macule Smokers melanosis Amalgam tattoo Naevi

Case 11

Numbness Of Face (Distribution Of Infraorbital Nerve) Biopsy From Infratemporal Fossa.

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Case 11 Diagnosis

Amyloidosis

Salient points • Deposition of hyalinised eosinophilic material in stroma •Congo red +++ •Consider type •? Assoc with plasma cell dyscrasia –Kappa and lambda check plasma cells at edge of lesion •Systemic investigations for AL ? Myeloma, H&N AL commonest •AA / hereditary

Case 12

55-year-old, Male Lump In Parotid.

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Case 12 Diagnosis

Acinic cell carcinoma

Notes • Lymphoid stroma • ACC • MEC • Prognostic factor- better prognostic indicator • ACC can undergo HG transformation

Case 13 • Female 24 years Lesion left forehead with a 6-8 week history of recurrent headaches. ? cause.

Specimen: Skull.

Macroscopic description: Disc of bone covered on one surface by elevated soft tissue. Cut sections reveal a central bone cavity filled with granular material.

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Case 13 Diagnosis

Langerhans cell histiocytosis

• Langerhans cell histiocytosis (LCH) is a clonal neoplastic proliferation of myeloid dendritic cells expressing LC phenotype • Single system/ multisystem involvement • cranial and facial bones, skin, gingiva, or cervical lymph nodes • intra-osseous ill-defined unilocular radiolucency with gingival involvement and tooth mobility.

• >99% survival for unifocal disease LCH cell clusters are diagnostic, but caution is needed in lymph nodes because paracortical dendritic/LCs are indistinguishable from sinus-based LCH cells.

Case 14

42-year-old, Female Lump In Neck.

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Case 14 Diagnosis

Carotid body tumour

• Well differentiated non-epithelial neoplasms derived from paraganglion cells of the autonomic nervous system.

• Hereditary predisposition- 40% • Hereditary paraglanglioma syndrome • Germline mutation in SDHD (47%), SDHB (30%), SDHC (16%) • 3-4% risk of metastasis DDThyroid- medullary carcinoma Laryngeal neuroendocrine tumours Parathyroid tumours

HN15 60-year-old, Male Epistaxis, Numbness Of Cheek And Proptosis.

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Case 15 Diagnosis

Sinonasal undifferentiated carcinoma (SNUC)

Sinonasal round blue cell tumours broad variants •Epithelial •Mesenchymal •Neuroectodermal •Haematolymphoid

pancytokeratin p63 (or p40) synaptophysin chromogranin S100 desmin CD45 CD99

Epithelial • non-keratinizing squamous cell carcinoma (NKSqCC) • non-keratinizing nasopharyngeal carcinoma (NKNPC) • basaloid squamous cell carcinoma (BSqCC) • NUT midline carcinoma (NMC) • lymphoepithelial carcinoma (LEC) • adenoid cystic carcinoma (solid pattern) (AdCC) • small cell carcinoma, neuroendocrine type (SmCCNET) • HPV related multiphenotypic sinonasal squamous cell carcinoma • SMARCB1/SMARCA4- deficient CA • sinonasal undifferentiated carcinoma (SNUC)

Neuroectodermal • Olfactory neuroblastoma (ONB) • Ewing sarcoma/peripheral primitive neuroectodermal tumour (ES/pPNET) • Malignant mucosal melanoma (MM) Haematolymphoid • Extranodal NK/T-cell lymphoma (NK/TCL); • Diffuse large B-cell lymphoma (DLBCL) and other B- and T-cell lymphomas; • Extramedullary myeloid sarcoma (myeloid sarcoma; MS) • Plasmacytoma Mesenchymal • Rhabdomyosarcoma (RMS) • Synovial sarcoma (SS) • Mesenchymal chondrosarcoma • Also metastases from other sites should be considered

Case 16 16-year-old, Male Epistaxis, Biopsy Of Mass, Upper Part Of Nasal Cavity.

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Case 16 Diagnosis

Nasopharyngeal angiofibroma

• Puberty onset • Essential and desirable diagnostic criteria • Essential: male patient; posterior nasal cavity/nasopharynx location; numerous vessel types and sizes, some with muscular walls; stromal stellate fibroblasts with variably collagenized stroma • Desirable: ß-catenin and androgen receptor + in stromal cells

Case 17 71-year-old, Female Large Cystic Lesion Posterior Mandible.

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Case 17 Diagnosis

Ameloblastoma

Case 18

28-year-old, Female Palatal Swelling.

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Case 18 Diagnosis

Polymorphous adenocarcinoma (PLGA)

Case 19 Male 64 years, Left parotid gland mass.

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Case 19 Diagnosis

Extranodal marginal zone lymphoma (MALT)

• H&N 2nd most common site after GI tract • Small lymphocytes and marginal zone cells • Monocytoid cells with abundant pale cytoplasm are sometimes present • Remnants of reactive follicles are common, sometimes with follicular colonization. Wellformed lymphoepithelial lesions

• Positive for CD20, CD22, PAX5), usually IgM, occasionally IgG or IgA, and rarely IgD, CD43 or TBX21 (T-bet) • Negative for CD5, CD10, BCL6, CD23, cyclin D1, SOX11, and EBV • Immunoglobulin light chain monotypia of B cells or plasma cells

Case 20 34-year-old, Male Nasal Tumour

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Case 20 Diagnosis

NUT midline carcinoma

More common in young adults Foci of abrupt keratinization Pancytokeratin+, p63+, p40+, NUT1+ t(15;19); BRD4-NUT gene fusion

Case 21

Cyst From Apex Of Non-Vital Incisor Tooth

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Case 21 Diagnosis

Radicular cyst

Case 22

19-year-old, Female Lymph Node Post Auricular Area.

Salient points Classic Triad • Reactive follicular hyperplasia, • Perifollicular / interfollicular epithelioid histiocytes -granulomas • Aggregates of monocytoid B cells.

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Case 22 Diagnosis

Toxoplasmosis lymphadenitis

Case 23

22-year-old Female. Lymph Node From Neck.

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Case 23 Diagnosis

Kikuchi Fujimoto disease (Kikuchi

histiocytic necrotizing lymphadenitis)

• Self-limiting, unknown etiology • Young adults of Asian origin • Histologic patterns: proliferative, necrotizing, and xanthomatous.

• DD- infectious lymphadenitis, autoimmune lymphadenopathy (primarily systemic lupus erythematosus), and lymphoma • Histomorphologic diagnosis • The histiocytes + lysozyme, myeloperoxidase, CD68, CD163, and CD4.

• The lymphocytes CD3-positive T cells demonstrating a predominance of CD8 compared with CD4, very few CD20positive B cells. Plasmacytoid dendritic cells - CD123+

Case 24 55-year-old, Male Parotid Swelling

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Case 24 Diagnosis

Pleomorphic adenoma with ossification and atypia

Case 25 79-year-old, Male Parotid Swelling.

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Case 25 Diagnosis

Warthin tumour with Small lymphocytic lymphoma

Case 26 46-year-old, Female Lump On Gum

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Case 26 Diagnosis

Peripheral ameloblastoma

Case 27 • Female 74 years 18 year history of submandibular swelling that has recently increased in size.

Specimen: submandibular gland.

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Case 27 Diagnosis

In-situ carcinoma ex pleomorphic adenoma

Case 28 39-year-old, Male White Patch Buccal Mucosa, Smoker.

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Case 28 Diagnosis

Lichenoid mucositis –lichen planus or lichenoid reaction

Case 29 57-year-old, Male White Patch Buccal Mucosa, Smoker.

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Case 29 Diagnosis

Chronic hyperplastic candidosis

HN30 45-year-old M, Previous Multiple Excisions Of Nasal Tumour, Further Resection.

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Case 30 Diagnosis

Squamous cell carcinoma arising in sinonasal inverted papilloma

Case 31 • Female 56 years

Slow growing lesion left neck from dorsal root C3. ? Nerve. Left posterior triangle. Present 20 years. Case type Combined.

Specimen: Neck.

Macroscopic description: Five bosselated nodules of soft tissue collectively measuring 55 x 45 x 15 mm.

Immunohistochemistry: S100 positive.

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Case 31 Diagnosis

Ancient schwannoma

Case 32 • Male 58 years

Leukoplakia present 3/12.

Specimen: Incisional biopsy right side of tongue.

Macroscopic description: Mucosa 11 x5 x3mm.

Immunohistochemistry: none.

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Case 32 Diagnosis

HPV related Oral intraepithelial neoplasia (Koilocytic dysplasia)