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Head & Neck Squamous Carcinoma: Artifacts, Challenges, and
Controversies
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ControversiesJennifer L. Hunt, MD, MEd
Aubrey J. Hough Jr, MD, Endowed Professor of PathologyChair of Pathology and Laboratory MedicineUniversity of Arkansas for Medical Sciences
Agenda
• Precursor lesions
• Conventional squamous carcinoma
• Lymph node dissections
• Sentinel lymph nodes
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Sentinel lymph nodes
2
General Reactions
• Metaplasia
• Hyperplasia
• Ulceration and inflammation
• Keratosis
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Keratosis
• Neoplasia• Dysplasia
• Carcinoma
Normal Epithelium
6
3
Dysplasia Continuum
7
Moderate DysplasiaSevere
DysplasiaMild DysplasiaNormal
Squamous Dysplasia
• Architectural features• Organization
• Maturation
• Mitotic activity
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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
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Grading Dysplasia
• Usually a three-tiered system• Mild, moderate, severe dysplasia
• Low grade, intermediate, high grade
• Mild, moderate and severe atypia
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Grading Terminology
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Dysplasia Continuum
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Moderate DysplasiaSevere
DysplasiaMild DysplasiaNormal
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19Mild dysplasia
Moderate dysplasia
Severe dysplasia
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22Mild-moderate dysplasia
Moderate to severe dysplasia
Moderate to severe dysplasia
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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
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Hyperplastic Candidiasis
Carcinoma After Dysplasia
20%
25%
30%
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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
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3131Well Differentiated SCCA
3232Poorly Differentiated SCCA
Moderately Differentiated SCCA
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Prognostic Factors
• Perineural invasion
• Angiolymphatic invasion
• Tumor size or depth
• Lymph node metastasis
3434
Lymph node metastasis
3535
3636
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Invasion
• Tumor that has breached the basement membrane• Access to lymphatics
• Potential to metastasize
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Superficial invasion
Depth of Invasion
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Metastases
• Regional lymph nodes• Size of node
• Location (ipsilateral vs. contralateral)
• Extracapsular extension
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4141
Purpose of Node Dissections
• To gather information• Treatment planning
• Staging
• Prognostication
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• For treatment• “Debulking”
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Treating the N0 Neck
• If risk of metastasis is >20%
• If high risk factors present• Perineural invasion
• Angiolymphatic invasion
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• 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
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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
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• Drainage patterns are consistent
History of SLN
• Penile Carcinoma (1977)
• Melanoma (1992)
• Breast Carcinoma (1993)
5151
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Radiation Exposure Issues
• Storage containers (shielded)
• Specimen transport• Training
• Labeling
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• 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
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Frozen Section Analysis
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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%)
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Head and Neck SLN
• Balance for intraoperative assessment• Detect macro-metastases
• Preserve micro-metastases
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Optimal Final Work-up
• Levels• How many?
• What frequency?
• Stains
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• How many?
• Which?
Sampling Error
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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
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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
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Sentinel lymph nodes