H+N Flashcards
(50 cards)
What are the types of differentiated thyroid carcinoma. What is their IHC profile. What are the differences microscopically.
Papillary thyroid carcinoma: branching papillae with fibrovascular stalks. Epithelium covering stalks cuboidal. Psammoma bodies
Follicular thyroid carcinoma: uniform cells forming small follicles containing colloid
Positive: PAX8, TTF1, thyroglobulin, broad spectrum CK
No IHC markers with adequate sensitivity to distinguish papillary from thyroid.
What are the epidemiological differences between papillary and follicular thyroid carcinoma
Papillary: most common, 85% of cases. Most common age 25-50. Form most associated with ionising radiation
Follicular: more common in regions of iron deficiency. Females more common 3:1. Age 40-60
What is the cell of origin of medullary thyroid carcinoma. What is the microscopic appearance
Parafollicular C cells that normally secrete calcitonin.
5% of thyroid tumours
Large lesions contain haemorrhage and necrosis.
Spindle shaped cells forming nests and trabeculae. Amyloid deposits in stroma (derived from calcitonin polypeptides)
What is the IHC profile for medullary thyroid neoplasms
Positive: TTF1, calcitonin, AE1/AE3, neuroendocrine markers. Congo red (amyloid deposits), CEA
Negative: thyroglobulin
Variable: PAX8
What is the microscopic appearance of anaplastic thyroid carcinoma
Minimal follicular differentiation, intratumoral necrosis, frequent mitosis.
Pleomorphic giant cells and/or spindle cells.
What is the usual IHC profile of anaplastic thyroid carcinoma
Positive: (usually) AE1/AE3, cam5.2
Negative: thyroglobulin, TTF1.
Variable: pax8
What are the normal microscopic appearances and IHC profile of parathyroid tumours
Microscopic: uniform cells resembling normal parathyroid cells. Enclosed by dense fibrous capsule.
Cytology unreliable for diagnosing carcinoma vs benign, invasion of surrounding tissues or mets are key features.
IHC: PTH+, GATA3+, neuroendocrine markers +
What is MEN2 syndrome
Autosomal dominant
Near 100% incidence of medullary thyroid carcinoma.
Mutation in RET proto-oncogene (RET is a tyrosine kinase): constitutively activated.
What driver mutations are frequent in papillary thyroid carcinoma
RET or NTRK gene translocations resulting in gene fusions
BRAF point mutations (gain of function): in 50-80% of papillary cancers. Most common V600E. Associated with lower expression of thyroglobulin and higher recurrence risk
What driver mutations are found in follicular thyroid carcinoma
RAS mutations (gain of function). 30-50%. Associated with retained thyroglobulin expression
t(2;3) involving PAX8
PI3K gain of function mutations
PTEN loss of function mutations
What mutations are commonly found in anaplastic thyroid carcinoma
TP53 point mutation
B-catenin point mutation
TERT point mutation (related to telomerase)
What is the difference in prognosis and extra thyroid spread patterns of papillary and follicular thyroid carcinoma
Papillary: spread to nodes, but Mets less common. Better prognosis, indolent
Follicular: less spread to nodes, Mets to lung and bone. Worse prognosis, but still indolent
What is the typical presentation of anaplastic thyroid cancer
20% have history of differentiated thyroid carcinoma
45% distant Mets at presentation. Lung and bone most common
Extremely aggressive, rapidly enlarging neck mass.
Always classified as stage 4
What are the three main patterns of upper aerodigestive tract mucosa abnormal appearances
Leukoplakia: white plaque on mucus membrane
Erythroplakia: red plaque. Higher risk of dysplasia
Speckled erythroplakia: mixed red and white plaque
What are common genetic abnormalities in H+N non-HPV SqCC
Genomically unstable with chromosome loss or gain
TP53 mutation
How is H+N squamous dysplasia classified
Low grade: maintained stratification/maturation. Minimal atypia, rare mitoses
High grade: abnormal cells in at least half of epithelium thickness. Increased mitoses, increased N:C ratio. Conspicuous atypia
What are some features of invasion of H+N conventional SqCC
Downward growth of islands
Cords or isolated tumour cells
Irregular interface
Desmoplastic response
LVI
PNI
What is the microscopic appearance of verrucous SqCC of the H+N
Dramatic acanthosis. marked “church spire” keratinisation
Well defined pushing invasion. Infiltrative growth would mean conventional SqCC rather than verrucous
What is the prognosis of the following subtypes of H+N SqCC in comparison to conventional SqCC
Verrucous
Spindle cell
Basaloid
Papillary
Verrucous: locally destructive, but does not metastasise
Spindle cell: similar prognosis
Basaloid: more aggressive
Papillary: better prognosis
What is the morphological appearance of HPV positive H+N SqCC
Non keratinizing
High N:C ratio (Basaloid appearance)
Frequent mitosis
Apoptotic figures
Lymphocytes/lymphocytic stroma
Grading is not applicable
What is the typical epidemiological pattern of HPV associated SqCC
Increasing incidence
Associated with oral sex
Typically white men in 50’s
Radiological what is the key feature of HPV positive lymph node Mets
Cystic
What are different forms of developmental cysts that can present as neck lumps
Thyroglossal duct cysts
Branchial cleft cyst: malformations of bronchial apparatus
Thymic cyst: contain thymic tissue
Bronchogenic cyst: lined by respiratory type epithelium
What are the microscopic contents of granulomas, and what are different causes
Collections of histiocytes and multinucleated cells
Sarcoidosis
TB
Fungal infections
