PathElective Head and Neck Flashcards
1
Q
Part of the Waldeyer Ring covered by squamous mucosa
A
The tonsils
2
Q
Part of the Waldeyer Ring covered by respiratory mucosa
A
The adenoids
3
Q
Histologic appearance of salivary glands
A
4
Q
Features to evaluate on salivary glands
A
- Can you identify ductal lumens?
- Are the nuclei eccentric? (they should be!)
- Can you identify myoepithelial cells?
- Are the cells granular (serous), agranular (mucinous), or a mixture with half-moon arrangement?
5
Q
Follicular cell stains
A
Thyroglobulin
TTF-1
PAX8
6
Q
Parafollicular cell stains
A
Calcitonin
CEA
7
Q
C-cell/Parafollicular cell architecture
A
Arranged into nests.
Have larger nuclei than follicular cells and are granular. May appear bluish or clearish depending upon the quality of the stain.
8
Q
Cells of the parathyroid
A
9
Q
Fat and muscle on a thyroid biopsy suggests. . .
A
. . . posterior origin of the biopsy.
This means it is taken close to the parathyroids, and can be a useful hint.
10
Q
Normal tooth histology
A
11
Q
What part of the tooth is often lost in processing?
A
The enamel
It melts away with decalcification, which is usually necessary since these biopsies often contain cortical bone from the mandible or elsewhere.
12
Q
Waldeyer’s Ring
A
13
Q
Salivary gland anatomy
A
14
Q
Salivon structure
A
15
Q
Neuronal control of salivation
A
16
Q
Frey’s syndrome
A
Caused by injury to the auriculotemporal nerve, which passes through the parotid.
Results in “gustatory sweating”, or hemifacial diaphoresis with eating.
17
Q
Non-keratinizing SCC tends to occur in. . .
A
. . . specialized squamous sites, such as Waldeyer’s ring
18
Q
Non-keratinizing SCC is often caused by. . .
A
. . . a virus (EBV in the nose or HPV in the oropharynx)
19
Q
Mild/Moderate/High grade dysplasia in a squamous surface
A
1/3->2/3->all the way through the epithelium
20
Q
“Dyskeratosis”
A
Presence of apoptotic keratinocytes
21
Q
Origin and clinical presentation of EBV/HPV-mediated squamous cell carcinomas of the head and neck
A
Tend to originate in the deep crypts of Waldeyer’s ring. Here, they are more connected to lymphatics, and thus they tend to metastasize earlier to lymph nodes.
They will often present as a neck mass
22
Q
Most common HPVs
A
Low risk: 6, 11 (usually give rise to warts/papillomas)
High risk: 16, 18, 31, 33, 45, etc (usually give rise to dysplasia/cancer)
23
Q
Features to help you identify SCC from background in the tonsils
A
- Large, pleomorphic nuclei
- Mitotic figures
- Infiltrating lymphocytes
24
Q
Staining for an HPV-mediated tumor
A
p16 (strong, diffuse pattern, nuclear and cytoplasmic)
HPV ISH or genotyping
25
"Nonkeratinizing SCC with focal maturation"
26
It is easier for tumors to invade bone than cartilage. Why?
Cartilage is much less vascular than bone. Less angiogenesis needs to happen.
27
Larynx cross-section (interior to anterior)
28
Vocal cord polyps
29
Only the true vocal cord connects to. . .
. . . the vocalis muscle
30
Tumors of the tonsil often appear as. . .
"blue on blue"
31
The triad of laryngeal disease
Dysphonia
Dysphagia
Dyspnea
32
Mycetoma
The nasal (or rarely pulmonary) fungus ball
Usually aspergillus, usually in a very allergic individual (septate, acute-branching hyphae).
Differentiated from invasive fungal sinusitis by the absence of vascular/tissue invasion -- mycetomas just fill the potential space, they do not invade.
33
Allergic fungal sinusitis
Hypersensitivity to inhaled fungal elements in atopic individuals.
Usually related to Dematiaceous fungal elements -- however the fungus itself is NOT present in the tissue, this is not a mycetoma. Where you WILL see fungal elements is in the mucus, along with some Charcot-Leyden crystals. Silver GMS stain on allergic mucus is a standard part of the workup.
Histologically, characterized by subepithelial chronic inflammatory infiltrate with prominent eosinophils.
34
Inflammatory nasal polyp
Formed by chronic inflammation (chronic sinusitis, especially in cystic fibrosis)
Characterized by cobblestone endoscopic appearance, thick basement membrane, and a myxoid stroma with numerous eosinophils. Glands are often cystically dilated.
35
Invasive fungal sinusitis
A mycetoma that became invasive. Angioinvasion, tissue invasion, and tissue necrosis are all common features.
Usually only occurs in immunocompromised individuals, including Mucor in diabetic patients. Aspergillus and candida in more severe immunodeficiencies.
36
Granulomatosis with polyangitis, nasopharyngeal manifestations
Characterized by granulomatous vasculitis and inflammatory polyposis of the nasopharynx.
Of course, there will often be renal involvement. ANCA should be sent, and c-ANCA will be positive in 50-90% of cases.
37
DDx for destructive midline nasopharyngeal processes
Neoplasms
Fungal sinusitis
Sarcoidosis
Granulomatosis with polyangitis (Wegner's)
Atypical mycobacteria
Cocaine-related tissue damage
38
Histologic triad of Wegner's granulomatosis (GPA)
Granulomas
Vasculitis
Neutrophilic microabscesses
39
Most sinonasal tumors arise in the ___ sinus
Maxillary
40
Sinonasal/Schneiderian Papilloma
41
Histology of the "classical" inverted-type sinonasal papilloma
42
As a quick rule of thumb, the __ __ sinonasal papillomas are the ones that are likely to progress to cancer.
Inflammatory
| ie, the ones with neutrophil microabscesses
43
Nasopharyngeal angiofibroma
Occurs exclusively in adolescent males (especially those with familial adenomatous polyposis). Tumor will be clinically bloody.
Full of slit-like blood vessels which are surrounded by thick, eosinophilic bands of stromal tissue containing bland spindle cells.
The stromal cells highly express the androgen receptor and are also beta-catenin positive (due to a mutation).
Treated surgically or via embolization. Definitive therapy preceded by hormone therapy.
44
Nasopharyngeal carcinoma
Very blue-appearing tumor which can look similar to lymphoma. Be careful not to confuse this with Burkitt's Lymphoma or Extranodal NK/T cell Lymphoma, nasal type. They will be epithelial cells -- NOT lymphoid cells, so staining clears this up quickly.
Most often squamous cell carcinoma driven by EBV, especially in males from southern China, or Africa, or Inuit/Alaska natives.
Aggressive malignancy with early lymph node metastases.
Other risk factors:
Preserved foods (nitrosamines)
Smoke
Genetic polymorphisms
45
How do you remember which one the ethmoid sinus is?
E is for eye
It is next to the eyes, in the bridge of the nose.
46
How do you remember which one the sphenoid sinus is?
S is for sella
The sphenoid is the sinus that sits just in front of the sella turcica
47
Why is colonization by Berkholderia cepacia of such consequence for CF patients?
Not only does it carry poor outcomes, like Pseudomonas, but the outcomes do not improve following transplant.
So, if you diagnose BC colonization, **you are taking the patient off the transplant list. It is a big deal. **
48
Nasal meati and what they drain
Superior meatus: Sphenoid, posterior ethmoid.
Middle meatus: Maxillary (against gravity), frontal, anterior ethmoid.
Inferior meatus: Nasolacrimal duct
49
The Dangerous Triangle of the face
Region in which sinusitis or a tumor may cause cavernous sinusitis and cavernous sinus thrombosis
Top of the nose to the corners of the mouth. Includes the sphenoid and ethmoid sinuses.
50
Symptoms of cavernous sinus thrombosis
Abrupt onset of:
Unilateral periorbital edema
Headache
Photophobia
Orbital swelling +/- proptosis
Chemosis (swelling of the conjunctiva)
CN palsies (III, IV, V1, V2, VI -- aka occulomotor and upper facial sensation)
51
As a quick rule of thumb, almost all cancers are more common in males than females EXCEPT for these:
Thyroid cancer
Gall bladder cancer
Any female-specific tissue cancer
52
Difference between Sjogren's associated and RA associated sialoadenitis
Sjogren's: Affects minor salivary glands
RA: Affects major salivary glands
53
Three subtypes of nasopharyngeal carcinoma
1. Keratinizing
2. Non-keratinizing
3. Basaloid
54
Nasopharyngeal carcinoma may present as ___ __ syndrome
Cavernous sinus syndrome
55
Mucocele
A mucocele is the result of a pseudocystic reaction to mucus extravasation. It most commonly affects the minor glands due to lip biting/trauma.
A "ranula" is a type of mucocele in the floor of the mouth. "Plunging ranula" is present in the neck.
Presents clinically as a fluctuant mass (waxing/waning)
Lined by macrophages and granulation tissue without a true epithelium.
56
Sialometaplasia
Squamous metaplasia of salivary ducts and acini. Occasional goblet cells may be retained among the squamous cells.
Occurs in the setting of chemo/radiation. May appear as a solitary ulcerated lesion, or multiple lesions throughout an area.
57
Milan system for grading of a salivary biopsy
58
Most common metastatic tumors to the salivary glands
SCC or melanoma of the skin
This is important to remember, as metastatic disease is a key differential in salivary tumors.
59
Pleomorphic adenoma
Most common salivary tumor
Not really pleomorphic cells, but polymorphous architecture. Well circumscribed tumors with a myxoid background/matrix. Has a distinct epithelial and myoepithelial layer in the ductal wall.
Benign PA tends to recur (so margins are important), and may transform into malignancy (carcinoma ex PA) -- this starts as transformation within the ductal lumen, then invades.
Genetics: 70% either PLAG1 or HMGA2 rearrangement.
60
Warthin tumor
Often multifocal or bilateral! Especially in smokers!
Cystic to solid grossly, may fluctuate in size. Much greater incidence in smokers. Uptakes technetium on scintigraphy due to lymphoid stroma.
Circumscribed border, rich lymphoid stroma, chords and cysts/clefts lined by a bilayered oncocytic epithelium.
61
Oncocytic cell on EM
Note that it is plump full of mitochondria!
62
Mucoepidermoid carcinoma
The most common malignant salivary tumor. Occurs in adults and children.
3 subtypes: Mucinous, intermediate, and squamoid. May also be cystic or solid.
Low-intermediate grade are monitored, but high grade tumors get neck dissection and chemoradiation.
Genetics: CRTC1-MAML2 fusion, or CRTC3-MAML2 fusion.
63
Adenoid cystic carcinoma
2nd most common malignant salivary tumor
Frequently exhibits perineural invasion, presenting with nerve pain. Highly infiltrative tumor.
Contains 2 cell types: Ductal epithelial (c-KIT+) and myoepithelial (p63+), with wrinkled nuclei. Often one epithelial layer is sandwiched between two myoepithelial layers. Appear as tubular (low grade), cribriform (intermediate grade), or solid (high grade) growth. Cribriform is most common. Often there is a blue-gray myxoid layer just underneath the myoepithelial layer, representing abnormally thickened basement membrane secreted by myoepithelial cells.
De-differentiation in high grade neoplasms is assessed by nuclear features. Better differentiated tumors have dark, homogeneous nuclei. Higher grade tumors have grayish nuclei with prominent nucleoli. ("high grade transformation" or "dedifferentiation")
Genetics: MYB-NFIB translocation -- t(6::9)(q22-23;p23-24). Results in MYB activation.
64
What are these?
Tyrosine crystals!
Sometimes seen in the context of pleomorphic adenoma.
65
Myoepithelioma
A tumor of entirely myoepithelial cells. They do exist! But they are very rare.
4 cell types: epithelioid, spindle cell, plasmacytoid, clear cell
Myoepi cell markers:
- epithelioid: keratin, EMA
- myoid: SMA, GFAP, S100, calponin, p63, p40
66
Myoepithelial carcinoma
Like a myoepithelial tumor, but with infiltrative/destructive growth (ie, malignant)
Uncommon. Usually arises from the parotid. 50% are transformed pleomorphic adenoma, 50% are de novo.
Morphologically, often rhabdoid or plasmacytoid cells in cords on a mucinous stroma.
Genetics: PLAG or HMGA2 rearrangement (if PA origin), EWSR (if clear cell morphology)
67
Oncocytoma (salivary origin)
Salivary tumor of oncocytic cells. Histologically differentiated from Warthin's tumor by:
* Lack of lymphoid stroma
* Lack of cysts/papillae
* Solid or trabecular architecture
It is important to differentiate this from simple oncocytic metaplasia / hyperplasia (especially in elderly patients)
68
What's goin' on in this salivary gland?
Oncocytosis, or oncocytic hyperplasia
Note how focal it is. Common in elderly patients.
69
What's goin' on in this salivary gland?
Oncocytosis with clear cell change
70
Basal Cell Adenoma
Rare tumor, usually found in the parotid.
Histology shows epi and myoepi cells with squamoid eddies. Architecture is solid, trabecular, or tubular. Peripheral palisading is classical. Pink, hyalinized stroma and eosinophilic globules (of basement membrane material) are often present.
Genetics: CTTNB1 mutation or CYLD1 mutation (the latter represents Brooke-Spiegler syndrome). Some with beta catenin mutations and nuclear beta catenin staining, but not universally.
71
What is this syndrome?
Brooke-Spiegler syndrome
Caused by mutations in the CYLD gene, encoding CYLD lysine 63 deubiquitinase
72
Canalicular adenoma
Rare tumor, typically of the upper lip in an older female.
Monotypic tumor with thin cords (1-2 layers) of cells on a myxoid, vascular stroma -- but NOT epithelial/myoepithelial. Diffusely S100+, GFAP+ at periphery/lumen.
No known malignant counterpart -- this is benign.
73
PAS with Diastase
PAS stains both mucin and glycogen
However, adding diastase (basically amylase) will digest the glycogen, leaving behind only the stained mucin. Zymogen granules will also remain.
This stain is useful for differentiating squamous cell versus mucoepidermoid carcinoma with squamous differentiation.
74
Polymorphous adenocarcinoma
Most commonly arise from the palate. Good prognosis -- PNI may be present, but rarely metastasizing (unless cribriform)
Single cell type with pale, oval, vesicular nuclei (like adenoid cystic carcinoma), but various architectural patterns: single file, whirling, lobular, papillary, cystic, cribriform, trabecular, ductal
Infiltrative growth pattern, often with perineural invasion. S100+, p40-.
-> Here, p40- is key to rule out pleomorphic adenoma and adenoid cystic carcinoma.
Genetics: PRKD1 mutation
75
Polymorphous adenocarcinoma - cribriform variant
More aggressive than most polymorphous adenocarcinoma -- frequent nodal metastases.
Mostly arises from the tongue or minor salivary glands. Papillary thryoid cancer-like (Orphan Annie) nuclei are a defining feature.
Genetics: PRKD1,2, or 3 rearrangements
76
Acinic Cell Carcinoma
80% arise in the parotid gland, 16% of cases with death or early metastasis
Resemble serous acinar cells, but grow in sheets without ducts or fat. May or may not have a lymphoid stroma. Cells have a granular cytoplasm with PAS+ and diastase-resistant granules. (Picture with normal parotid on left, tumor on right)
Generally low grade, but aggressive features include:
>2/10 mitoses, necrosis, LVI, PNI, pleomorphism, de-differentiation/high-grade transformation
Genetics: NR4A3, MSANTD3
77
Secretory carcinoma (salivary)
Analogue of the breast secretory carcinoma. Also carries the same translocation: ETV6::NTRK3. 70% arise from the parotid.
Generally low-grade, slow-growing, and painless. But, can undergo high-grade transformation.
Histology: Bland, monotonous cells in a microcystic architecture with intraluminal secretions. Lacks zymogen granules. Diffusely S100+ and mammoglobin+.
78
Salivary ductal carcinoma
Always high grade, resembles high-grade DCIS. Androgen receptor+, sometimes with Her2/NEU amplification, and can often be treated with androgen antagonists. Always ER/PR negative (positivity would suggest breast metastasis).
Like high-grade DCIS, large nests of apocrine-like cells with peripheral cribriforming and central necrosis.
May arise de-novo or out of a pleomorphic adenoma.
79
Intraductal carcinoma (salivary)
Resembles low-grade DCIS/ADH. This is **NOT** considered a variant of salivary ductal carcinoma. Excellent prognosis.
Bounded by a myoepithelial layer. Cribriform, papillary, or solid growth pattern. S100+.
80
Epithelial-Myoepithelial Carcinoma
Rare, but with striking histologic features. 14% metastasize, 10% death rate.
Bi-layered tubules with clear myoepithelial cells, sometimes with solid areas of myoepithelial cells punctuated by small, pink ducts.
Genetics: HRAS mutation in ~25-35%
81
Clear cell carcinoma (salivary)
Formerly "hyalinizing" CCC. Can have stromal hyaline, but doesn't have to.
Monomorphous clear cells with wrinkled nuclei. Bands of (sometimes hyalinized) septae punctuating.
Positive stains: Keratin, HMWK, p40, p63
Negative stains: S100, GFAP, SMA, calponin
Genetics: EWSR-ATF1 translocation.
"Looks like a myoepithelial carcinoma, stains like a squamous cell carcinoma"
82
What's going on in this image?
Salivary ductal carcinoma ex pleomorphic adenoma
The pleomorphic adenoma here is the loosely organized purple tumor with gray myxoid stroma on the right. The loosely organized ductal elements to the right are vacuolar and pleomorphic on high power.
83
Lymphoepithelial cyst
Cystic dilation of the salivary gland ducts, associated with HIV or autoinflammatory disease (ex, Sjogren's, RA). Painless, unilocular mass within or adjacene to the salivary gland. Sporadic/rheum are usually unilateral, HIV frequently bilateral.
Lymphoid stroma (frequently with follicles), epithelially-lined unilocular cyst.
84
Rhinosporidiosis
Fungal infeciton of the nasal mucosa. Causes nasal discharge. Has a coccidoimycosis-like appearance on histology.
85
Low-grade polymorphous adenocarcinoma:
Looks like pleomorphic adenoma, but with clear invasion of the surrounding fatty tissue.
86
Mucoepidermoid carcinoma, epidermoid type
87
Adenocystic carcinoma
88
High-grade salivary ductal carcinoma
This was in the parotid gland based on surrounding serous salivary glands and a section of the facial nerve was present adjacent to the tumor. Be mindful and be wary of perineural invasion in parotid tumors!
89
Basal cell adenocarcinoma, well-differentiated
90
Cystic papillary acinic cell carcinoma
91
Chronic sialoadenitis
Note that there is a mucoid/myxoid stromal background similar to pleomorphic/polymorphous, however the salivary elements are arranged in well-formed ducts and acini and are well-differentiated.
The lymphoid infiltration with lymphoid follicle formation is a tip-off.
Remember:
Minor gland - Sjogren's
Major gland - RA
