Molavi Chapter 4 - Complex Epithelia

Question 1

Dyskeratosis

Answer 1

Abnormal, premature keratinization below the stratum granulosum.

In this case, note also the loss of cell-cell adhesions and the pyknotic nucleus – the cell indicated by the arrow is dying.

Question 2

What’s going on in this skin biopsy?

Answer 2

Invasive squamous cell carcinoma

Note the irregular nests of keratinocytes and abberant keratinization in the stroma.

Question 3

Eggs-nuclei vs boulder-nuclei

Answer 3

Reactive nuclei may enlarge, but should stay smooth and round to oval. Chromatin is grey-blue.

Dysplastic or immature nuclei appear to have too much chromatin for their nuclear membrane to contain and appear angulated with irregular borders. Chromatin is uniformly dense and dark, like charcoal.

Question 4

Presence of a nucleolus

Answer 4

Generally suggestive of reactive changes rather than dysplasia

Squamous cells usually don’t take acquire large dark nucleoli until they become invasive.

Question 5

N/C ratio in a squamous epithelium

Answer 5

Should decrease as you get closer to the surface.

If not, this is suggestive of dysplasia

Question 6

Parakeratosis

Answer 6

Retention of small pyknotic nuclei in the surface keratin

Question 7

Orthokeratosis

Answer 7

“Normal” anucleate keratin with a basket-weave pattern

Question 8

Hyperkeratosis

Answer 8

Too much keratin, often accompanied by parakeratosis

Question 9

What’s going on in this skin biopsy?

Answer 9

This is a squamous papilloma

It has squamous epithelia overlying a branching fibrovascular core.

Question 10

Pseudoepitheliomatous hyperplasia

Answer 10

Benign, reactive condtion that can mimic invasive squamous cell carcinoma.

It has a characteristic look “as though someone dragged the epithelium down into the stroma with a toothpick.” The individual nuclei should look reactive, not dysplastic, and there should be no deep keratinization.

May be provoked by a granular cell tumor.

Question 11

Verrucous

Answer 11

Warty, exophytic growth pattern with prominent hyperkeratosis (and often parakeratosis)

“Church-spire” (pointy) or “cauliflower” (rounded) projections.

Question 12

What’s going on in this cervical biopsy?

Answer 12

These are koilocytes.

Note the perinuclear halo with prominent, crinkled, dark nuclei. The nuclei get larger as you approach the surface, indicating dysplasia. Bunicleate cells are also present.

Question 13

What’s going on in this cervical biopsy?

Answer 13

Normal glycogenated cervical epithelium. Don’t be fooled into thinking that these are koilocytes!

They have prominent perinuclear halos, but the nuclei at the surface are tiny and pyknotic. They are also more uniform than you may expect in HPV-mediated dysplasia.

Question 14

Cervical cancer microstaging/grading (LSIL, CIN)

Answer 14

Question 15

Condyloma vs LSIL

Answer 15

Shown in condyloma accuminata

They have the same changes as LSIL, but with a verrucous architecture.

Question 16

Features of benign urothelium

Answer 16

• 5-7 cells thick
• Umbrella cell layer at the top

Question 17

Flat vs papillary urothelial carcinomas

Answer 17

Flat: Progress from dysplasia to CIS to invasive carcinoma without making an exophytic lesion

Papillary: For urothelial lesions, may be graded as benign (papilloma), borderline (papillary urothelial neoplasm of low malignant potential), or cancer (low- and high-grade papillary urothelial carcinoma).

Question 18

von Brunn’s nests

Answer 18

Invaginated folds of normal urothelium, which can simulate invasion

Question 19

Features of urothelial cancer

Answer 19

• Increased number of cell layers (usually in papillary lesions)
• Loss of polarity (loss of parallel array of nuclei)
• Increased mitoses, above the basal layer
• Enlarged, irregular, or hyperchromatic nuclei
• Discohesive cells or partially denuded epithelium

Question 20

Features of a laryngeal/oropharyngeal squamous lesion concerning for carcinoma

Answer 20

• Usually HPV driven, so benign lesions may have the typical low-grade HPV changes
• More concerning lesions have:
  
  • High-grade dysplasia
  • Significant atypia
  • Warty architecture (church-spire keratosis)
  • Severe keratinizing dysplasia (Note: In the orophaynx/larynx, unlike the cervix, mucosa tends to keratinize in dysplasia. These lesions may not be full thickness, but may still behave like carcinoma-in-situ)

Question 21

Features of squamous dysplasia in the oropharynx/larynx

Answer 21

• Loss of cell polarity and maturation arrest
• Dyskeratosis, hyperkeratosis, acanthosis
• Increased mitoses or mitoses above the basal layer
• Cellular and nuclear pleoorphism (Note: in the oropharynx unlike other places, dysplastic nuclei tend to show prominent nuclei and nuclear membranes, more like an invasive carcinoma).
• Variable N/C ratio
• Not necessarily full-thickness involvement, even in severe dysplasia

Question 22

What’s going on in this biopsy of an oral lesion?

Answer 22

Squamous dysplasia

Note: The parakaratosis present at the surface will appear as a white oral plaque clinically.

Note: Unlike in the cervix, prominent nucleoli may be a feature of dysplasia and do not necessarily suggest carcinoma.

Question 23

Schneiderian papillomas

Answer 23

• Fancy name for “sinonasal” papillomas
• Lined with nonkeratinizing squamous or transitional epithelium, 5-30 cells thick
• May have ciliated or mucous lining
• Neutrophils are common
• May be fungiform (exophytic, septal) or inverted (inward growing)
• Should have only mild atypia, orderly cells, and few mitoses
• Features that suggest carcinoma instead: atypia, pleomorphism, increased mitotic activity, cells invading as nests and cords

Question 24

Generally in the esophagus, squamous mucosa is not usually. . .

Answer 24

. . . a bad actor

More often it is glandular, seen in the setting of Barret’s esophagus.

Mild reactive changes are very common and correspond to reflux changes, and sometimes to infection.

If squamous dysplasia or carcinoma is found, it is typically in the upper esophagus in the setting of alcohol + smoke.