Paranasal Sinuses and Nasopharynx Flashcards
Sinusitis
Clinical:
* Most commonly –> Maxillary sinus
* Acute –> may be post viral
* Chronic –> Secondary to fungal or bacterial organisms
Macro:
* Oedematous
* Reddish-grey
* Soft Tissue
Micro:
* Repiratory mucosa
* Mixed inflammatory infiltrate
* Oedema
* Glandular hyperplasia
* Basement membrane thickening
* Squamous metaplasia
IHC:
* Fungal infection should be excluded by GMS and PAS
Nasal Polyp
- Benign, nonneoplastic inflammatory outgrowth of sinonasal mucosa
- Most common type of sinonasal polyp
- Most common space occupying lesion of the sinonasal tract
Cause:
* Inflammation
* Allergy
* Mucoviscidosis (Cystic Fibrosis)
* Mucopolysaccharidosis (Hurler Syndrome)
Macro:
* Usually multiple and bilateral and involve nasal cavity and paranasal sinuses
* Have translucent, moist or edematous cut surface
* Broad base of attachment is present
* Usually not destructive
Micro:
* Edematous, fibrotic or loosely myxoid stroma covered by respiratory epithelium
* Infiltrated by mixed inflammatory cells, including lymphocytes, plasma cells, eosinophils, neutrophils and mast cells
* Surface epithelium can show ulceration or squamous metaplasia
* May have bizarre stromal cells (large and pleomorphic)
* Concurrent fungal infection may be seen
* Rarely, osseous metaplasia may be present
Sinonasal Tract Angiofibroma
- Affecting adolescent or young male patients
- Arises in the nasopharynx or posterolateral wall of nasal cavity
- May be locally aggressive, show extension into paranasal sinus, pterygopalatine fossa, infratemporal fossa and orbit
- 10 - 37% have intracranial extension, usually into the middle cranial fossa
- Highly vascular lesion with one or more feeding arterials
- The most common feeding vessel is the internal maxillary artery, a branch of the external carotid artery
Micro:
* Vascular space of various sizes, ranging from dilated branching vessel of various thickness to slit-like capillaries
* Fibrous or collagenous stroma with fibroblasts
* Central area of the tumor is typically cellular, composed of fibroblasts or myofibroblasts with spindle, round or stellate morphology
* Fibrinous thrombi may be seen in dilated vessels
* Frequently contain (abundant) mast cells
* Mitotic figures are usually absent
Molecular:
* Somatic mutation of CTNNB1 (beta catenin) gene in 75% of cases
IHC:
* SMA, HHF35 / h-caldesmon in smooth muscle wall of large vasculature
* CD31, CD34 and ERG highlight endothelial cells of vasculature
* AR is positive in stroma cells in 40 - 75% cases
* Beta catenin: nuclear staining in stromal cells (fibroblasts)
Sinonasal Papilloma
- Sinonasal papilloma is a benign epithelial neoplasm of sinonasal tract
- WHO has divided sinonasal papilloma into 3 distinct types:
Inverted papilloma
Exophytic papilloma
Oncocytic papilloma
Micro:
Inverted papilloma:
- Most common
- Lateral nasal wall / paranasal sinus
- 5th to 6th decades
- High risk HPV and Low risk HPV
- Squamous, transitional or respiratory Lining
- Prominent downward endophytic growth
- Epithelium is hyperplastic (5 - 30 cell layers in thickness)
- Neutrophils and neutrophilic microabscesses
- EGFR activating mutation
Exophytic papilloma:
- Second most common
- Nasal septum
- 3rd to 5th decades
- Low risk HPV
- Squamous, respiratory or transitional lining.
- Filiform or papillary arrangement with delicate fibrovascular core
- May contain mucus secreting cells and goblet cells
- Variable koilocytosis may be present
- Minimal inflammatory cells
- No reported mutations
Oncocytic papilloma:
- Least common
- Lateral nasal wall / paranasal sinus
- 5th to 6th decades
- No association with HPV
- Oncocytic lining (pseudostratified and columnar with abundant eosinophilic granular cytoplasm)
- May have endophytic (inverted) or exophytic growth patterns
- Intraepithelial mucin filled cysts with neutrophilic microabscesses may be seen
- KRAS mutation
Malignant transformation (carcinoma ex sinonasal papilloma):
Most common type of carcinoma arising in sinonasal papilloma is squamous cell carcinoma
Rhinoscleroma
- Rare; chronic granulomatous disease of nasal cavity (95 - 100%), nasopharynx (18 - 43%), larynx (15 - 40%), trachea (12%) or bronchi (2 - 7%)
- Caused by Klebsiella rhinoscleromatis
- Identified on Warthin-Starry Stain
- Endemic in central America, India
Micro:
* Initially: squamous metaplasia and inflamed granulation tissue
* Later: pseudoepitheliomatous squamous hyperplasia with foamy macrophages (Mikulicz cells containing bacteria), plasma cells with Russell bodies and granulomatous inflammation
* Late: fibrosis, lymphocytes and plasma cells but no Mikulicz cells
Rhinosporidiosis
- Rhinosporidiosis is a chronic infectious disease of the upper respiratory tract (nasal cavity and nasopharynx)
- Characterized by development of polypoid masses caused by the sporulating organism Rhinosporidium seeberi (fungus-like parasite)
- Transmitted through bathing or working in stagnant water
Micro:
* Intense acute and chronic inflammation and numerous large, round, thick walled sporangia that may rupture
* Hyperplasia with squamous metaplasia may be seen in overlying epithelium
* Thick cyst walls are birefringent
* Largest, most mature cysts are arranged closest to the mucosal surface
IHC:
* GMS
* PAS
Wegener’s Granulomatosis
- AKA Granulomatosis with polyangiitis (GPA)
- T-Cell mediated hypersensitivity reaction
- Triad:
Necrotising angiitis
Aseptic necrosis of upper respiratory tract and lungs
Focal glomerulonephritis
Serum marker:
* c-ANCA is positive in 90%
Micro:
* Liquifactive or coagulative necrosis
* Profuse eosinophiles
* Multinucleated giant cells –> poorly formed granulomas, surrounded by palisading histocytes and giant cells
* Destructive leukocystic angiitis of arteries and veins outside of the necrotic granuloma by neutrophils, plasma cells and eosinophils
* Scanty lymphocytes and plasma cells
Treatment:
* Cyclophosphamide
* Steroids
* TNF-agonists
Olfactory neuroblastoma
- Malignant neuroectodermal tumor commonly located at superior aspect of nasal cavity showing neuroblastic differentiation
- Patients of all ages, 2 to 90 years
- No obvious gender, ethnic or familial predilection
- Roof of nasal cavity
Macro:
* Red-gray, highly vascular, polypoid mass
Micro:
* Originated and centered around cribriform plate of nasal cavity
* Small blue round cell tumor with lobulated growth pattern and abundant neurophil
* Homer Wright pseudorosettes and Flexner-Wintersteiner rosettes may be seen
* The most important prognostic factors are Hyams grade and Kadish stage
IHC:
- Synaptophysin, chromogranin, CD56, neurofilament, S100 in sustentacular cells at periphery of cell nests
- Keratins, e.g. cytokeratin AE1/AE3, CAM5.2 and CK18, are commonly negative, but up to a third may show focal positivity
- INI1
- Area of rhabdomyoblastic differentiation if present is positive for desmin and myogenin
- Calretinin
Sinonasal glomangiopericytoma
- Uncommon soft tissue tumor of perivascular myoid differentiation with hemangiopericytoma-like vasculature
Clinical
* Nasal obstruction, mass, polyps, difficulty breathing
* Sinusitis, discharge, change in smell
* Broad age range (5 - 90 years); mean in seventh decade
* F > M (1.2:1)
Micro:
* Surface respiratory epithelium or metaplastic squamous epithelium is intact
* Subepithelial proliferation separated from surface (grenz zone)
* Diffuse growth with fascicular, solid or focally whorled pattern of spindled or round / oval tumor cells that arrange themselves around prominent, small, thin walled submucosal blood vessels
* Cells occasionally are multinucleated
* Minimal atypia, no necrosis, no / rare mitotic activity
* Vessels are prominent with staghorn appearance and perivascular hyalinization
* Inflammatory cells including mast cells and eosinophils are often present
Molecular:
* CTNNB1 mutation
* Single nucleotide substitutions with exon 3 codons
IHC:
* Beta catenin: nearly all tumor cells with nuclear and cytoplasmic staining
* Cyclin D1
* CD99
* Vimentin (98%)
* SMA (92%),
* Factor XIIIa (78%)
* laminin (52%)
* D2-40
NUT carcinoma
- Highly aggressive malignancy
- Median survival of < 1 year
- Probable poorly differentiated subtype of squamous carcinoma
- Common in midline including sinonasal region
Macro:
* Highly infiltrative tumor frequently involving multiple anatomic subsites
* Nonspecific white-tan cut surface commonly demonstrating prominent necrosis
Micro:
* Primitive small to medium sized cells with minimal indistinct to clear cytoplasm
* Monotonous round to oval nuclei with variably prominent nucleoli
* High mitotic rate
* Prominent tumor necrosis
* Foci of abrupt squamous differentiation with clear to eosinophilic cytoplasm
* Keratin pearl formation
* Areas of spindled cells frequently present
* Dense neutrophil infiltrate seen in subset of cases
Molecular:
* Defined by translocations involving the NUT gene on 15q14
* BRD4-NUT (19p13) fusion is present in 67% of cases
* Other cases show BRD3-NUT or NSD3-NUT fusions
* NUT –> “nuclear protein in testis”
IHC:
* NUT1 diffuse speckled nuclear positivity is 87% sensitive and 100% specific
* Pancytokeratin, EMA consistently positive
* p63 / p40 ~67%
* CD34 ~30 - 50%
* INI1 retained
Sinonasal undifferentiated carcinoma (SNUC)
- Undifferentiated carcinoma lacking evidence of differentiation (such as squamous, glandular or neuroendocrine differentiation) by histology and immunohistochemistry
- Diagnosis of exclusion
- Lacks specific viral etiologies, such as HPV and EBV
- Rare; 3 - 5% of all sinonasal carcinomas
- Median age at presentation: 50 - 60 years
- Male predominance with M:F = 2 - 3
- Presenting symptoms are variable, including nasal obstruction, epistaxis, facial pain and headache to severe visual symptoms (proptosis, diplopia and impaired visual acuity) and cranial nerve palsies
Macro:
* Usually > 4 cm
* Tend to be fungating, with ill defined borders and frequent invasion into adjacent structures
Micro:
* Nests, lobules, trabeculae and sheets of medium sized cells
* Mitotic activity is very high
* Tumor necrosis and apoptoses are frequent
* Lymphovascular invasion and perineural invasion are common
* Lacks any definite lineage of differentiation
Molecular:
* IDH2 or IDH1 mutations in > 80% cases, the most common being IDH2 R172 mutation
* In situ hybridization for high risk HPV and EBV is consistently negative
IHC:
* Pancytokeratin AE1 / AE3
* Low molecular weight cytokeratin (CAM 5.2)
* CK7: expressed in half of SNUC
* Rare –> focal synaptin, chromogranin
Nasopharyngeal carcinoma
- Nasopharyngeal carcinoma originates from the nasopharyngeal mucosa showing histologic or immunophenotypic evidence of squamous differentiation
- Originates from nasopharynx
- Most are positive for Epstein-Barr virus (EBV)
- Epstein-Barr encoded RNA (EBER) in endemic areas (China, Southeast Asia and North Africa)
- Peak incidence in fourth to sixth decades
- less than 20% occur in pediatric age group
- Affects nasopharynx, with nasopharyngeal recess (i.e. fossa of Rosenmüller) as the most common affected site, followed by superior posterior wall
- Extension to adjacent organs (e.g., nasal cavity, paranasal sinus, oropharynx, bone, orbit and infratemporal fossa) is common
- Environmental factors: nitrosamines-salted fish, smoking, formaldehyde, EBV infection
- WHO classification of nasopharyngeal carcinoma:
-
Nonkeratinizing squamous cell carcinoma
Differentiated subtype
Undifferentiated subtype - Keratinizing squamous cell carcinoma
- Basaloid squamous cell carcinoma
Micro:
Nonkeratinizing, undifferentiated subtype
* Either syncytial arrangement of cohesive cells with indistinct cell margins (Regaud pattern) or diffuse cellular infiltrate of noncohesive cells (Schmincke pattern) resembling non-Hodgkin lymphoma (growth patterns have no clinical significance)
* No significant keratinization
* Apoptosis and brisk mitotic activity are invariably present
* Usually (but not always) prominent nonneoplastic lymphoplasmacytic infiltrate accompanying the tumor
* Necrosis is uncommon
Nonkeratinizing, differentiated subtype
* Usually interconnecting cords or trabeculae
* Little or no keratinization; growth pattern is similar to urothelial carcinoma
* Tumor cells show well defined cell borders with variable intercellular bridges
* Background stroma demonstrates variable lymphoplasmacytic infiltrate
* Usually no desmoplastic response to invading tumor
* Subclassification of nonkeratinizing nasopharyngeal carcinoma into differentiated and undifferentiated subtypes is optional as it is not clinically or prognostically significant; if there is overlapping histology within the same tumor, classify according to the dominant component
Keratinizing subtype
* Indistinguishable from keratinizing squamous cell carcinoma of other body sites
* Obvious squamous differentiation as intercellular bridges and keratinization
* Can grade as well differentiated, moderately differentiated or poorly differentiated
* Desmoplastic response common
Basaloid subtype
* Indistinguishable from basaloid squamous cell carcinoma of other body sites
* Tumor cells have high nuclear / cytoplasmic ratio with scanty cytoplasm, giving the basaloid appearance
* Basaloid tumor nests and sheets, often with peripheral palisading
* Central comedo type necrosis
Molecular:
* Detection of Epstein-Barr virus (EBV) by PCR or ISH found in 75 - 100% of cases
IHC:
* EBV (LMP-1) by IHC
* EBV-encoded RNA is more sensitive
* Pancytokeratin, high molecular weight CK (CK 5/6), p63 and p40 are strongly positive
Sinonasal Adenocarcinoma
Clinical:
* Arise from eother respiratory epithelium or seromucinous glands
* Obstruction and epistaxis
* Three distinct types of adenocarcinoma –> Enteric type, non-enteric type, salivary type
Enteric Type:
* Associated with woodwork (hardwood exposure), leather, some chemical manufacturing.
* Arises from Schneiderian surface mucosa involving ethmoids, then nasal, then maxillary
* M:F = 9:1
* RAS and TP53 mutations
Macro:
* Fungating mass –> may show ulceration, haemorrage
* Friable grey mass with mucoid material
Micro:
* Hyperchromatic, atypical columnar epithelium
* Invasion and desmoplasia present
* Mucin and goblet cells frequently present
* Intestinal metaplasia of Schneiderian mucosa without atypia may be present
IHC:
* CK7 and CK20 +
* CDX2 often +
Non-Enteric Type:
* Classified as low or high grade non-enteric seromucinous adenocarcinoma
* Arise from seromucinous glands
* Wide age range, low grade –> 50 years, high grade –> 60 years
Macro:
* Varies based on grade
Micro:
Low Grade
* Relatively cytologically bland proliferation of seromucinous glands
* Small glands are back to back or papilary growth
* Atypical mitoses and necrosis generally absent
High Grade
* Solid growth pattern is common
* Moderate to marked pleomorphism
* High mitotic rate, prominent necrosis
IHC:
* CK 7 +
* May express S100
Salivary Type:
* Morphologically identical to those in the salivary gland region.
* Adenoid cystic carcinoma is the most frequent type
Macro:
* Submucosal mass with infiltration
Micro:
* Morphologies include those in the salivary regions
* Pleomorphic adenoma, adenoid cystic carcinoma, acinic cell carcinoma
* Polymorphous low-grade carcinoma
IHC:
* CK 7 +
* May express S100
