1

Head & Neck Squamous Carcinoma: Artifacts, Challenges, and

Controversies

1

ControversiesJennifer L. Hunt, MD, MEd

Aubrey J. Hough Jr, MD, Endowed Professor of PathologyChair of Pathology and Laboratory MedicineUniversity of Arkansas for Medical Sciences

jhunt2@uams.edu

Agenda

• Precursor lesions

• Conventional squamous carcinoma

• Lymph node dissections

• Sentinel lymph nodes

2

Sentinel lymph nodes

2

General Reactions

• Metaplasia

• Hyperplasia

• Ulceration and inflammation

• Keratosis

5

Keratosis

• Neoplasia• Dysplasia

• Carcinoma

Normal Epithelium

6

3

Dysplasia Continuum

7

Moderate DysplasiaSevere

DysplasiaMild DysplasiaNormal

Squamous Dysplasia

• Architectural features• Organization

• Maturation

• Mitotic activity

8

Normal Organization

4

Normal Maturation

Abnormal Mitoses

Squamous Dysplasia

• Cytologic features• Hyperchromasia

• Higher N:C ratio (basaloid)

• Nuclear membrane irregularities

12

5

Reactive Atypia Dysplasia

Abnormal Cytology

1414Normal Reactive Mild dysplasia

1515Reactive AtypiaModerate dysplasia

6

Grading Dysplasia

• Usually a three-tiered system• Mild, moderate, severe dysplasia

• Low grade, intermediate, high grade

• Mild, moderate and severe atypia

16

Grading Terminology

17

Dysplasia Continuum

18

Moderate DysplasiaSevere

DysplasiaMild DysplasiaNormal

7

19Mild dysplasia

Moderate dysplasia

Severe dysplasia

8

22Mild-moderate dysplasia

Moderate to severe dysplasia

Moderate to severe dysplasia

9

Low Grade Atypia

• Inflammatory atypia vs. mild dysplasia• Look for hints that it might not be dysplastic

• Inflammation

• Ulceration or ulcer debris

• Organisms

25

• Organisms

• Metaplasia

• Tangential sectioning

Inflammatory Atypia

Hyperplastic Candidiasis

10

Hyperplastic Candidiasis

Carcinoma After Dysplasia

20%

25%

30%

29

0%

5%

10%

15%

Negative Mild Moderate Severe

Barnes, L. Head & Neck Pathology

Squamous Cell Carcinoma

• Histologic Subtypes• Conventional

• Grading

• T N M staging

3030

11

3131Well Differentiated SCCA

3232Poorly Differentiated SCCA

Moderately Differentiated SCCA

12

Prognostic Factors

• Perineural invasion

• Angiolymphatic invasion

• Tumor size or depth

• Lymph node metastasis

3434

Lymph node metastasis

3535

3636

13

Invasion

• Tumor that has breached the basement membrane• Access to lymphatics

• Potential to metastasize

37

Superficial invasion

Depth of Invasion

39

14

Metastases

• Regional lymph nodes• Size of node

• Location (ipsilateral vs. contralateral)

• Extracapsular extension

40

4141

Purpose of Node Dissections

• To gather information• Treatment planning

• Staging

• Prognostication

42

• For treatment• “Debulking”

15

Treating the N0 Neck

• If risk of metastasis is >20%

• If high risk factors present• Perineural invasion

• Angiolymphatic invasion

43

• Deep invasion

• Not differentiation and mitotic index

Empiric risk in cN0 Neck

LocationLocation Occult MetastasisOccult Metastasis

EpiglottisEpiglottis 15%15%

Vocal CordVocal Cord 15%15%

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Floor of mouthFloor of mouth 25%25%

TonsilTonsil 36%36%

Tongue BaseTongue Base 55%55%

Oral TongueOral Tongue 60%60%

Pyriform sinusPyriform sinus 65%65%

Head and Neck Cancer

• Elective neck dissection• Over-treatment for many (>75%)

• Therapeutic for few (<25%)

• Morbidity of neck dissection

4545

• Morbidity of neck dissection

16

Morbidity

• Nerve damage

• Disfiguration and edema

• Infection

• Hematoma

4646

Hematoma

Theory of SLN

Afferent lymphatics

Theory of SLN

Efferent lymphatics

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Benefits of SLN

• Limited procedure

• Decreased morbidity

• Focused pathologic analysis

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Maximal Benefit of SLN

• Staging relies on nodal status

• Risk of metastasis low

• Staged procedures are feasible

D i tt i t t

50

• Drainage patterns are consistent

History of SLN

• Penile Carcinoma (1977)

• Melanoma (1992)

• Breast Carcinoma (1993)

5151

18

Radiation Exposure Issues

• Storage containers (shielded)

• Specimen transport• Training

• Labeling

52

• Waste disposal• > 3 days of storage

Frozen Section

• Risk• False negative & false positive

• Sampling

• Frozen section artifact

Tiss e aste

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• Tissue waste

• Benefit• Immediate completion for positive

5454

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Data on Frozen Section

Tumor Tumor typetype

Frozen Frozen sectionsection

SensitivitySensitivity

Cytology Cytology smear smear SensitivitySensitivity

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BreastBreast 59% 59% -- 78%78% 57%57%

MelanomaMelanoma 38% 38% -- 47%47% 38% 38% -- 46%46%

MacroMacro--

metsmets

>99%>99% >90%>90%

HNSCCHNSCC 93%93% ??

Frozen Section Analysis

56

Frozen Section Analysis

57

20

Experiment

• Lymph node 1• Pre-frozen weight: 279 mg

• Post-frozen weight: 220 mg ((--21%)21%)

6060

• Lymph node 2• Pre-frozen weight: 623 mg

• Post-frozen weight: 354 mg ((--43%)43%)

21

Head and Neck SLN

• Balance for intraoperative assessment• Detect macro-metastases

• Preserve micro-metastases

61

Optimal Final Work-up

• Levels• How many?

• What frequency?

• Stains

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• How many?

• Which?

Sampling Error

63

22

Sampling Error

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Diminishing Returns

0.25 mm metastasis = 23 sections

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Thomsen J Oral Pathol Med, 34:65, 2005

FS

1.8 mm metastasis = 3 sections

Optimal Work-up

~2-3 mm

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CK HE CK HE CK

HEHE

23

6767

Maximal Benefit in SLN

• Staging relies on nodal status

• Risk of metastasis low

√

√

6868

• Staged procedures are feasible

• Drainage patterns are consistent

√

√

?

Arguments for SLN

• Helps to identify unusual drainage

• Significant upstaging of cN0 necks

6969

Significant upstaging of cN0 necks

• Allows for focused pathology analysis

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Arguments against SLN

• Morbidity is already low

• Less reliable after radiation

7070

• Skip metastases

• Increased cost and time

Micrometastases

• Incidence is high (20-30% of cN0)

• Controversial clinical significance• Regional recurrence may be higher

• May behave similar to N0 population

7171

Summary

• Precursor lesions

• Conventional squamous carcinoma

• Lymph node dissections

• Sentinel lymph nodes

72

Sentinel lymph nodes