AULA DA SESSÃO DE ORL_CCP UERJ -HUPE

1. Cirurgia de Cabeça e Pescoço
Lesões Pré Malignas de Laringe
Dr. Leonardo Guimarães Rangel
nancy and no treatment is recommended.
Squamous cell hyperplasia. This is a benign change in
which the epithelium becomes thicker without cellular
FIGURE 2. Pseudostratified ciliated columnar ("respiratory’’)
epithelium with interspersed goblet cells. [Color figure can be
viewed in the online issue, which is available at
wileyonlinelibrary.com.]

2. Epitélio Normal
Erythroleukoplakia. This clinical term describes mixed forms
of white and red mucosal changes and the lesion has similar
implications as an erythroplakia.
Pachydermia. This is another descriptive clinical term,
now largely historical, indicating extensive thickening of
the mucosa. It is not a histologic diagnosis.
Histopathologic terminology
Squamous metaplasia. A term describing the replacement
of normal respiratory epithelium by stratified squamous
epithelium, a change common even in the subglottic
region of the nonsmoking, nonbronchitic urban adult15
and in the human fetal larynx.16
The process usually
involves only the superficial epithelium, but may extend
into the seromucinous laryngeal glands. Squamous meta-
plasia can follow persistent trauma or chronic irritation.
There is no evidence that this lesion predisposes to malig-
nancy and no treatment is recommended.
Squamous cell hyperplasia. This is a benign change in
which the epithelium becomes thicker without cellular
atypia. The thickening is due to an increase in the prickle
cell (acanthosis) and/or basal cell layers. Epithelial hyper-
plasia may be covered with a conspicuous keratin layer
(Figure 3). Squamous cellular differentiation is well pre-
served, and this type of epithelial change is reversible.
Squamous cell hyperplasia usually represents a response
to injury and is not regarded as a precancerous lesion. Bi-
opsy may be performed to establish a definitive diagnosis.
Pseudoepitheliomatous hyperplasia (pseudocarcinomatous hyper-
plasia). This term describes an exuberant reactive or repar-
ative overgrowth of squamous epithelium with extension
of bulbous rete processes into the lamina propria. The
hyperplastic epithelium may simulate well-differentiated
squamous cell carcinoma, especially when it appears
detached from the surface as a result of cross-cutting. The
absence of epithelial cellular atypia and the presence of
an inflammatory infiltrate are useful diagnostic pointers.
Pseudoepitheliomatous hyperplasia may be associated
with a granular cell tumor, several specific chronic
inflammatory conditions (tuberculosis in particular),
mycotic diseases and, occasionally, primary eosinophilic
granuloma of the larynx17
(Figure 4). Also, it may mimic
recurrent tumor in biopsies taken from patients previously
irradiated for treatment of laryngeal squamous cell carci-
noma. There is no evidence that pseudoepitheliomatous
hyperplasia is a potentially malignant lesion, and
FIGURE 1. Nonkeratinized epithelium of the vocal cord. [Color
figure can be viewed in the online issue, which is available at
wileyonlinelibrary.com.]
SQUAMOUS EPITHELIAL CHANGES OF THE LARYNX
Erythroleukoplakia. This clinical term describes mixed forms
of white and red mucosal changes and the lesion has similar
implications as an erythroplakia.
Pachydermia. This is another descriptive clinical term,
now largely historical, indicating extensive thickening of
the mucosa. It is not a histologic diagnosis.
Histopathologic terminology
Squamous metaplasia. A term describing the replacement
of normal respiratory epithelium by stratified squamous
epithelium, a change common even in the subglottic
region of the nonsmoking, nonbronchitic urban adult15
and in the human fetal larynx.16
The process usually
involves only the superficial epithelium, but may extend
into the seromucinous laryngeal glands. Squamous meta-
plasia can follow persistent trauma or chronic irritation.
There is no evidence that this lesion predisposes to malig-
nancy and no treatment is recommended.
Squamous cell hyperplasia. This is a benign change in
which the epithelium becomes thicker without cellular
atypia. The thickening is due to an increase in the prickle
cell (acanthosis) and/or basal cell layers. Epithelial hyper-
plasia may be covered with a conspicuous keratin layer
(Figure 3). Squamous cellular differentiation is well pre-
served, and this type of epithelial change is reversible.
Squamous cell hyperplasia usually represents a response
to injury and is not regarded as a precancerous lesion. Bi-
opsy may be performed to establish a definitive diagnosis.
Pseudoepitheliomatous hyperplasia (pseudocarcinomatous hyper-
plasia). This term describes an exuberant reactive or repar-
ative overgrowth of squamous epithelium with extension
of bulbous rete processes into the lamina propria. The
hyperplastic epithelium may simulate well-differentiated
squamous cell carcinoma, especially when it appears
detached from the surface as a result of cross-cutting. The
absence of epithelial cellular atypia and the presence of
an inflammatory infiltrate are useful diagnostic pointers.
Pseudoepitheliomatous hyperplasia may be associated
with a granular cell tumor, several specific chronic
inflammatory conditions (tuberculosis in particular),
mycotic diseases and, occasionally, primary eosinophilic
granuloma of the larynx17
(Figure 4). Also, it may mimic
recurrent tumor in biopsies taken from patients previously
irradiated for treatment of laryngeal squamous cell carci-
noma. There is no evidence that pseudoepitheliomatous
hyperplasia is a potentially malignant lesion, and
FIGURE 1. Nonkeratinized epithelium of the vocal cord. [Color
figure can be viewed in the online issue, which is available at
wileyonlinelibrary.com.]
FIGURE 2. Pseudostratified ciliated columnar ("respiratory’’)
epithelium with interspersed goblet cells. [Color figure can be
viewed in the online issue, which is available at
wileyonlinelibrary.com.]
FIGURE 3. Epithelial hyperplasia with keratosis. Epithelial
maturation is without any abnormalities and surface is covered
with a conspicuous keratin layer. [Color figure can be viewed in
the online issue, which is available at wileyonlinelibrary.com.]
SQUAMOUS EPITHELIAL CHANGES OF THE LARYNX
HEAD & NECK—DOI 10.1002/HED DECEMBER 2012 1811
ep estratificado
não
queratinizado
ep
pseudoestratificado
colunar ciliado

3. Alterações Intra-epiteliais
Clínica
Leucoplasia
Eritroplasia
Leucoeritroplasia
Paquidermia

4. Alterações Intra-epiteliais
Clínica
Leucoplasia
Lesão branca que não pode ser
removida com manobras e que
não pode ser atribuída a condição
específica (cândida)
Sem Correlação Histológica

5. Alterações Intra-epiteliais
Clínica
Eritroplasia
placa avermelhada na mucosa
Não é diagnóstico Histológico
Associado com Atipias e
Carcinoma

6. Alterações Intra-epiteliais
Clínica
Leucoeritroplasia
placa avermelhada e branca na
mucosa
Não diagnóstico Histológico
Associado com Atipias e
Carcinoma

7. Alterações Intra-epiteliais
Clínica
Paquidermia
Espessamento
Não diagnóstico Histológico
característica histórica

8. Próximo passo ?

9. Alterações Intra-epiteliais
HistológicaMetaplasia Escamosa
Hiperplasia C. Escamosas
Hiperplasia Pseudocarcinomatosa
Queratose
Ortoqueratose
Paraqueratose

10. Alterações Intra-epiteliais
HistológicaMetaplasia Escamosa
Subst de epitélio respiratório por escamoso
é comum : subglote (fetos, adultos urbanos)
trauma persistente
inflamação crônica
sem aumento de risco para malignização Robbins- pathology

11. Alterações Intra-epiteliais
HistológicaHiperplasia C. Escamosas
aumento da espessura do epitélio
camadas basais aumentadas
sem atipías
reversível
sem associação a malignidade
Erythroleukoplakia. This clinical term describes mixed forms
of white and red mucosal changes and the lesion has similar
implications as an erythroplakia.
Pachydermia. This is another descriptive clinical term,
now largely historical, indicating extensive thickening of
the mucosa. It is not a histologic diagnosis.
Histopathologic terminology
Squamous metaplasia. A term describing the replacement
of normal respiratory epithelium by stratified squamous
epithelium, a change common even in the subglottic
region of the nonsmoking, nonbronchitic urban adult15
and in the human fetal larynx.16
The process usually
involves only the superficial epithelium, but may extend
into the seromucinous laryngeal glands. Squamous meta-
plasia can follow persistent trauma or chronic irritation.
There is no evidence that this lesion predisposes to malig-
nancy and no treatment is recommended.
Squamous cell hyperplasia. This is a benign change in
which the epithelium becomes thicker without cellular
plasia). This term describes an exuberant reactive or repar-
ative overgrowth of squamous epithelium with extension
of bulbous rete processes into the lamina propria. The
hyperplastic epithelium may simulate well-differentiated
squamous cell carcinoma, especially when it appears
detached from the surface as a result of cross-cutting. The
absence of epithelial cellular atypia and the presence of
an inflammatory infiltrate are useful diagnostic pointers.
Pseudoepitheliomatous hyperplasia may be associated
with a granular cell tumor, several specific chronic
inflammatory conditions (tuberculosis in particular),
mycotic diseases and, occasionally, primary eosinophilic
granuloma of the larynx17
(Figure 4). Also, it may mimic
recurrent tumor in biopsies taken from patients previously
irradiated for treatment of laryngeal squamous cell carci-
noma. There is no evidence that pseudoepitheliomatous
hyperplasia is a potentially malignant lesion, and
FIGURE 1. Nonkeratinized epithelium of the vocal cord. [Color
figure can be viewed in the online issue, which is available at
wileyonlinelibrary.com.]

12. Alterações Intra-epiteliais
HistológicaHiperplasia Pseudocarcinomatosa
aumento da espessura do epitélio
invadem lâmina própria
sem atipías
processo inflamatório
simula malignidade
pensar em tuberculose, fungo, granuloma eosinofílico
http://anatpat.unicamp.br

13. Alterações Intra-epiteliais
HistológicaQueratose
deposição anormal de queratina na superfície do epitélio
como o epitélio não é queratinizado é errado termo hiperqueratose
resposta a um mecanismo traumático ao epitelio

14. Alterações Intra-epiteliais
HistológicaQueratose
Associada a Acantose
etapas da maturação preservada
sem atipias
não é pré cancerígena
queratose
acantose
proc inflam crônico
http://anatpat.unicamp.br

15. Alterações Intra-epiteliais
HistológicaOrtoqueratose
deposição anormal de queratina
na superfície do epitélio
Não há núcleo
(aumento da camada Granular)
http://anatpat.unicamp.br

16. Alterações Intra-epiteliais
Histológica
Paraqueratose
Deposição de Queratina
Com núcleos
maturação errada
turnover aumentado do epitelio
http://anatpat.unicamp.br

17. Lesões Prémalignas

18. Lesões pré-malignas
Neoplasia Intraepitelia ≈ Displasia
se refere a alteração arquitetural do epitélio
é a primeira lesão com alteração neoplásica
Atipia
se refere a alteração celular

19. Sistemas de Classificação
✤ OMS
✤ Sistema de Displasia Epitelial (NIC)
✤ Sistema Ljubljana
São Diferentes e
não intercambiáveis

20. ✤ Laryngeal Intraepithelial neoplasia
✤ (LIN) : I-III
✤ LIN I - displasia mínima
Friedmann I, Ferlito A. Granulomas and neoplasms of the larynx. 1988
CLINICAL REVIEW David W. Eisele, MD, Section Editor
Squamous Epithelial Changes of the Larynx: Diagnosis and Therapy
Alfio Ferlito, MD, DLO, DPath, FRCSEd ad hominem, FRCS (Eng, Glasg, Ir) ad eundem, FDSRCS ad eundem, FHKCORL, FRCPath, FASCP, IFCAP,1
Kenneth O. Devaney, MD, JD, FCAP,2
Julia A. Woolgar, FRCPath, PhD,3
Pieter J. Slootweg, MD, DMD, PhD,4
Vinidh Paleri, MS, FRCS (ORL-HNS),5
Robert P. Takes, MD, PhD,6
Primozˇ Strojan, MD, PhD,7
Patrick J. Bradley, MB, BCh, BAO, DCH, MBA, FRCS (Ed, Eng, Ir), FHKCORL, FRCSLT (Hon), FRACS
(Hon),8
Alessandra Rinaldo, MD, FRCSEd ad hominem, FRCS (Eng, Ir) ad eundem, FRCSGlasg1
1
ENT Clinic, University of Udine, Udine, Italy, 2
Department of Pathology, Allegiance Health, Jackson, Michigan, 3
Cellular Pathology, University Hospital Aintree, Longmoor Lane,
Liverpool, United Kingdom, 4
Department of Pathology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands, 5
Department of Otolaryngology–Head and Neck
Surgery, Newcastle upon Tyne Foundation Hospitals NHS Trust, Newcastle upon Tyne, United Kingdom, 6
Department of Otolaryngology–Head and Neck Surgery, Radboud
University Nijmegen Medical Center, Nijmegen, The Netherlands, 7
Department of Radiation Oncology, Institute of Oncology, Ljubljana, Slovenia, 8
Department of
Otolaryngology–Head and Neck Surgery, Nottingham University Hospital, Queens Medical Centre, Nottingham, United Kingdom.
Accepted 20 May 2011
Published online 3 October 2011 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/hed.21862
ABSTRACT: It can be confusing for clinicians to work their way through
the tangle of pathologic terms used in surgical pathology reports to
describe squamous abnormalities in laryngeal biopsies. After a brief
review of the normal microscopic anatomy of the larynx and time-
honored clinical designations for surface-based abnormalities, this
report sorts pathologic changes into 2 groups: those changes that do
not carry a premalignant potential (including squamous metaplasia,
squamous hyperplasia, pseudoepitheliomatous hyperplasia, keratosis,
and parakeratosis) and those that do (including dyskeratosis, laryngeal
intraepithelial neoplasia [LIN], atypia, dysplasia, and carcinoma in situ).
Generally, lesions in the first group do not require additional therapy or
close follow-up; lesions in the second group, however, demand either
some form of local therapy or close follow-up to monitor for the
development of a more aggressive pathology. VC 2011 Wiley Periodicals,
Inc. Head Neck 34: 1810–1816, 2012
KEY WORDS: squamous epithelial changes, histopathologic
classification, larynx, pathology, therapy, prognosis
Several identical squamous epithelial changes that can be
identified in the larynx and are presumed to have the
potential to develop into invasive cancer are, depending
on the particular author writing the report, variously
described in the current literature as field cancerization,
potentially cancerous/malignant lesion, precancerous/pre-
malignant lesion, or latent cancer. If nothing else, this
plethora of different terms serves to point out our imper-
fect ability to relate morphologic changes to biologic
potential.1
The profusion of competing proposals for the
categorization of laryngeal squamous intraepithelial
changes2–12
is evidence of the continuing debate and con-
troversy throughout the multidisciplinary team with
respect to recognition, classification, histologic diagnosis
and standardization, management, and prognosis of these
challenging lesions.
Normal histology
In health, the anterior epiglottic surface, the upper half
of the posterior epiglottic surface, the superior margin of
region are lined with pseudostratified ciliated columnar
epithelium, with interspersed goblet cells (Figure 2).
Seromucinous glands are present in the lamina propria
and are particularly numerous on the posterior epiglottic
surface, false cords, ventricle, saccule, and subglottis.
These glands, however, are sparse or absent in the vocal
cord.
Intraepithelial changes
Both types of normal laryngeal epithelium, stratified
squamous and respiratory epithelium, are subject to a spec-
trum of abnormal epithelial proliferation. The following
terminology has evolved:
Clinical terminology
Leukoplakia. The term means "white plaque’’ and is a
clinical term describing any white lesion on a mucous
membrane that cannot be wiped off or ascribed to any
specific condition (eg, Candidal infection). The term has
no histologic implications13
and is not synonymous with
FIGURE 5. In mild dysplasia, cytologic atypia remains confined to
the lower third part of the epithelial thickness. Surface shows
slight keratosis. [Color figure can be viewed in the online issue,
which is available at wileyonlinelibrary.com.]

21. ✤ Laryngeal Intraepithelial neoplasia
✤ (LIN) : I-III
✤ LIN II - displasia moderada
Friedmann I, Ferlito A. Granulomas and neoplasms of the larynx. 1988
CLINICAL REVIEW David W. Eisele, MD, Section Editor
Squamous Epithelial Changes of the Larynx: Diagnosis and Therapy
Alfio Ferlito, MD, DLO, DPath, FRCSEd ad hominem, FRCS (Eng, Glasg, Ir) ad eundem, FDSRCS ad eundem, FHKCORL, FRCPath, FASCP, IFCAP,1
Kenneth O. Devaney, MD, JD, FCAP,2
Julia A. Woolgar, FRCPath, PhD,3
Pieter J. Slootweg, MD, DMD, PhD,4
Vinidh Paleri, MS, FRCS (ORL-HNS),5
Robert P. Takes, MD, PhD,6
Primozˇ Strojan, MD, PhD,7
Patrick J. Bradley, MB, BCh, BAO, DCH, MBA, FRCS (Ed, Eng, Ir), FHKCORL, FRCSLT (Hon), FRACS
(Hon),8
Alessandra Rinaldo, MD, FRCSEd ad hominem, FRCS (Eng, Ir) ad eundem, FRCSGlasg1
1
ENT Clinic, University of Udine, Udine, Italy, 2
Department of Pathology, Allegiance Health, Jackson, Michigan, 3
Cellular Pathology, University Hospital Aintree, Longmoor Lane,
Liverpool, United Kingdom, 4
Department of Pathology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands, 5
Department of Otolaryngology–Head and Neck
Surgery, Newcastle upon Tyne Foundation Hospitals NHS Trust, Newcastle upon Tyne, United Kingdom, 6
Department of Otolaryngology–Head and Neck Surgery, Radboud
University Nijmegen Medical Center, Nijmegen, The Netherlands, 7
Department of Radiation Oncology, Institute of Oncology, Ljubljana, Slovenia, 8
Department of
Otolaryngology–Head and Neck Surgery, Nottingham University Hospital, Queens Medical Centre, Nottingham, United Kingdom.
Accepted 20 May 2011
Published online 3 October 2011 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/hed.21862
ABSTRACT: It can be confusing for clinicians to work their way through
the tangle of pathologic terms used in surgical pathology reports to
describe squamous abnormalities in laryngeal biopsies. After a brief
review of the normal microscopic anatomy of the larynx and time-
honored clinical designations for surface-based abnormalities, this
report sorts pathologic changes into 2 groups: those changes that do
not carry a premalignant potential (including squamous metaplasia,
squamous hyperplasia, pseudoepitheliomatous hyperplasia, keratosis,
and parakeratosis) and those that do (including dyskeratosis, laryngeal
intraepithelial neoplasia [LIN], atypia, dysplasia, and carcinoma in situ).
Generally, lesions in the first group do not require additional therapy or
close follow-up; lesions in the second group, however, demand either
some form of local therapy or close follow-up to monitor for the
development of a more aggressive pathology. VC 2011 Wiley Periodicals,
Inc. Head Neck 34: 1810–1816, 2012
KEY WORDS: squamous epithelial changes, histopathologic
classification, larynx, pathology, therapy, prognosis
Several identical squamous epithelial changes that can be
identified in the larynx and are presumed to have the
potential to develop into invasive cancer are, depending
on the particular author writing the report, variously
described in the current literature as field cancerization,
potentially cancerous/malignant lesion, precancerous/pre-
malignant lesion, or latent cancer. If nothing else, this
plethora of different terms serves to point out our imper-
fect ability to relate morphologic changes to biologic
potential.1
The profusion of competing proposals for the
categorization of laryngeal squamous intraepithelial
changes2–12
is evidence of the continuing debate and con-
troversy throughout the multidisciplinary team with
respect to recognition, classification, histologic diagnosis
and standardization, management, and prognosis of these
challenging lesions.
Normal histology
In health, the anterior epiglottic surface, the upper half
of the posterior epiglottic surface, the superior margin of
region are lined with pseudostratified ciliated columnar
epithelium, with interspersed goblet cells (Figure 2).
Seromucinous glands are present in the lamina propria
and are particularly numerous on the posterior epiglottic
surface, false cords, ventricle, saccule, and subglottis.
These glands, however, are sparse or absent in the vocal
cord.
Intraepithelial changes
Both types of normal laryngeal epithelium, stratified
squamous and respiratory epithelium, are subject to a spec-
trum of abnormal epithelial proliferation. The following
terminology has evolved:
Clinical terminology
Leukoplakia. The term means "white plaque’’ and is a
clinical term describing any white lesion on a mucous
membrane that cannot be wiped off or ascribed to any
specific condition (eg, Candidal infection). The term has
no histologic implications13
and is not synonymous with
The lesion is always contained at its deep aspect by the
basal lamina,24
although the underlying ducts may be
involved. In carcinoma in situ, all layers of the epithelium
are replaced by malignant cells, whereas in severe dyspla-
sia, some rudimentary maturation in the most superficial
epithelial layers is preserved. Stratification is lacking.4
The lesion may be multicentric in origin and may be
found in all laryngeal regions, although it is most frequent
in the vocal cords and, particularly, in the anterior half of
the true vocal cords. The role of human papillomavirus,
in the genesis of these lesions, if any, is unknown.29
The first descriptions of this lesion were published early
in the 20th century30
and the term "carcinoma in situ’’
(Figure 8) (also called intraepithelial, or superficial, or pre-
invasive carcinoma, or stage 0) was introduced by Broders
in 1932.31
There are considerable discrepancies in the
reported incidence, generally cited as 0.4 cases per 100,000
in the general population,32
rising in "high risk’’ cohorts.
Carcinoma in situ may be accompanied by undiagnosed
invasive areas resulting in understaging of the lesion fol-
lowing pathologic examination23,33,34
and the inclusion of
cases with microinvasive cancers distorts findings on the
outcome and prognosis of this lesion. Therefore, the diag-
nosis of carcinoma in situ on the basis of a small biopsy
specimen can be accepted only with reservations.35
For reli-
able assessment a full excisional biopsy is mandatory and
multiple sections from the whole surgical specimen should
be examined to rule out invasion. Carcinoma in situ adja-
cent to invasive cancer is a mundane finding. Areas sug-
gesting carcinoma in situ have been found in spindle cell
carcinoma,36
in basaloid squamous cell carcinoma,36
and in
form of intraepithelial neoplasm and that the term "laryn
geal intraepithelial neoplasia’’ would encompass both car
cinoma in situ and all grades of dysplasia. Like cervica
intraepithelial neoplasia, its laryngeal counterpart may be
defined as "a spectrum of intraepithelial change which
begins as a generally well-differentiated neoplasm, tradi
tionally classified as mild dysplasia, and ends with inva
sive carcinoma.’’40
Blackwell et al7
found that the histol
ogy of biopsies demonstrating severe dysplasia did no
differ significantly from biopsies demonstrating carci
noma in situ, implying that severe dysplasia and carci
noma in situ both represent the same intraepithelial neo
plastic change.
FIGURE 6. Moderate dysplasia shown at the right side in
comparison with normal epithelial maturation at the left side.
Atypical cells with prominent nucleoli occupy the entire lower
halve of the epithelium. Keratosis is confined to the dysplastic
area. [Color figure can be viewed in the online issue, which is
available at wileyonlinelibrary.com.]
the lower third part of the epithelial thickness. Surface shows
slight keratosis. [Color figure can be viewed in the online issue,
which is available at wileyonlinelibrary.com.]

22. ✤ Laryngeal Intraepithelial neoplasia
✤ (LIN) : I-III
✤ LIN III -
✤ displasia grave
✤ Ca in situ
Friedmann I, Ferlito A. Granulomas and neoplasms of the larynx. 1988
CLINICAL REVIEW David W. Eisele, MD, Section Editor
Squamous Epithelial Changes of the Larynx: Diagnosis and Therapy
Alfio Ferlito, MD, DLO, DPath, FRCSEd ad hominem, FRCS (Eng, Glasg, Ir) ad eundem, FDSRCS ad eundem, FHKCORL, FRCPath, FASCP, IFCAP,1
Kenneth O. Devaney, MD, JD, FCAP,2
Julia A. Woolgar, FRCPath, PhD,3
Pieter J. Slootweg, MD, DMD, PhD,4
Vinidh Paleri, MS, FRCS (ORL-HNS),5
Robert P. Takes, MD, PhD,6
Primozˇ Strojan, MD, PhD,7
Patrick J. Bradley, MB, BCh, BAO, DCH, MBA, FRCS (Ed, Eng, Ir), FHKCORL, FRCSLT (Hon), FRACS
(Hon),8
Alessandra Rinaldo, MD, FRCSEd ad hominem, FRCS (Eng, Ir) ad eundem, FRCSGlasg1
1
ENT Clinic, University of Udine, Udine, Italy, 2
Department of Pathology, Allegiance Health, Jackson, Michigan, 3
Cellular Pathology, University Hospital Aintree, Longmoor Lane,
Liverpool, United Kingdom, 4
Department of Pathology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands, 5
Department of Otolaryngology–Head and Neck
Surgery, Newcastle upon Tyne Foundation Hospitals NHS Trust, Newcastle upon Tyne, United Kingdom, 6
Department of Otolaryngology–Head and Neck Surgery, Radboud
University Nijmegen Medical Center, Nijmegen, The Netherlands, 7
Department of Radiation Oncology, Institute of Oncology, Ljubljana, Slovenia, 8
Department of
Otolaryngology–Head and Neck Surgery, Nottingham University Hospital, Queens Medical Centre, Nottingham, United Kingdom.
Accepted 20 May 2011
Published online 3 October 2011 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/hed.21862
ABSTRACT: It can be confusing for clinicians to work their way through
the tangle of pathologic terms used in surgical pathology reports to
describe squamous abnormalities in laryngeal biopsies. After a brief
review of the normal microscopic anatomy of the larynx and time-
honored clinical designations for surface-based abnormalities, this
report sorts pathologic changes into 2 groups: those changes that do
not carry a premalignant potential (including squamous metaplasia,
squamous hyperplasia, pseudoepitheliomatous hyperplasia, keratosis,
and parakeratosis) and those that do (including dyskeratosis, laryngeal
intraepithelial neoplasia [LIN], atypia, dysplasia, and carcinoma in situ).
Generally, lesions in the first group do not require additional therapy or
close follow-up; lesions in the second group, however, demand either
some form of local therapy or close follow-up to monitor for the
development of a more aggressive pathology. VC 2011 Wiley Periodicals,
Inc. Head Neck 34: 1810–1816, 2012
KEY WORDS: squamous epithelial changes, histopathologic
classification, larynx, pathology, therapy, prognosis
Several identical squamous epithelial changes that can be
identified in the larynx and are presumed to have the
potential to develop into invasive cancer are, depending
on the particular author writing the report, variously
described in the current literature as field cancerization,
potentially cancerous/malignant lesion, precancerous/pre-
malignant lesion, or latent cancer. If nothing else, this
plethora of different terms serves to point out our imper-
fect ability to relate morphologic changes to biologic
potential.1
The profusion of competing proposals for the
categorization of laryngeal squamous intraepithelial
changes2–12
is evidence of the continuing debate and con-
troversy throughout the multidisciplinary team with
respect to recognition, classification, histologic diagnosis
and standardization, management, and prognosis of these
challenging lesions.
Normal histology
In health, the anterior epiglottic surface, the upper half
of the posterior epiglottic surface, the superior margin of
region are lined with pseudostratified ciliated columnar
epithelium, with interspersed goblet cells (Figure 2).
Seromucinous glands are present in the lamina propria
and are particularly numerous on the posterior epiglottic
surface, false cords, ventricle, saccule, and subglottis.
These glands, however, are sparse or absent in the vocal
cord.
Intraepithelial changes
Both types of normal laryngeal epithelium, stratified
squamous and respiratory epithelium, are subject to a spec-
trum of abnormal epithelial proliferation. The following
terminology has evolved:
Clinical terminology
Leukoplakia. The term means "white plaque’’ and is a
clinical term describing any white lesion on a mucous
membrane that cannot be wiped off or ascribed to any
specific condition (eg, Candidal infection). The term has
no histologic implications13
and is not synonymous with
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n
l
t
w
s
w
f
c
t
e
e
v
t
i
t
g
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FIGURE 7. Severe dysplasia is characterized by full-thickness
epithelial atypia with some preserved maturation indicated by
FERLITO ET AL.

23. ✤ Laryngeal Intraepithelial neoplasia
✤ (LIN) : I-III
✤ LIN III -
✤ displasia grave
✤ Ca in situ
Friedmann I, Ferlito A. Granulomas and neoplasms of the larynx. 1988
CLINICAL REVIEW David W. Eisele, MD, Section Editor
Squamous Epithelial Changes of the Larynx: Diagnosis and Therapy
Alfio Ferlito, MD, DLO, DPath, FRCSEd ad hominem, FRCS (Eng, Glasg, Ir) ad eundem, FDSRCS ad eundem, FHKCORL, FRCPath, FASCP, IFCAP,1
Kenneth O. Devaney, MD, JD, FCAP,2
Julia A. Woolgar, FRCPath, PhD,3
Pieter J. Slootweg, MD, DMD, PhD,4
Vinidh Paleri, MS, FRCS (ORL-HNS),5
Robert P. Takes, MD, PhD,6
Primozˇ Strojan, MD, PhD,7
Patrick J. Bradley, MB, BCh, BAO, DCH, MBA, FRCS (Ed, Eng, Ir), FHKCORL, FRCSLT (Hon), FRACS
(Hon),8
Alessandra Rinaldo, MD, FRCSEd ad hominem, FRCS (Eng, Ir) ad eundem, FRCSGlasg1
1
ENT Clinic, University of Udine, Udine, Italy, 2
Department of Pathology, Allegiance Health, Jackson, Michigan, 3
Cellular Pathology, University Hospital Aintree, Longmoor Lane,
Liverpool, United Kingdom, 4
Department of Pathology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands, 5
Department of Otolaryngology–Head and Neck
Surgery, Newcastle upon Tyne Foundation Hospitals NHS Trust, Newcastle upon Tyne, United Kingdom, 6
Department of Otolaryngology–Head and Neck Surgery, Radboud
University Nijmegen Medical Center, Nijmegen, The Netherlands, 7
Department of Radiation Oncology, Institute of Oncology, Ljubljana, Slovenia, 8
Department of
Otolaryngology–Head and Neck Surgery, Nottingham University Hospital, Queens Medical Centre, Nottingham, United Kingdom.
Accepted 20 May 2011
Published online 3 October 2011 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/hed.21862
ABSTRACT: It can be confusing for clinicians to work their way through
the tangle of pathologic terms used in surgical pathology reports to
describe squamous abnormalities in laryngeal biopsies. After a brief
review of the normal microscopic anatomy of the larynx and time-
honored clinical designations for surface-based abnormalities, this
report sorts pathologic changes into 2 groups: those changes that do
not carry a premalignant potential (including squamous metaplasia,
squamous hyperplasia, pseudoepitheliomatous hyperplasia, keratosis,
and parakeratosis) and those that do (including dyskeratosis, laryngeal
intraepithelial neoplasia [LIN], atypia, dysplasia, and carcinoma in situ).
Generally, lesions in the first group do not require additional therapy or
close follow-up; lesions in the second group, however, demand either
some form of local therapy or close follow-up to monitor for the
development of a more aggressive pathology. VC 2011 Wiley Periodicals,
Inc. Head Neck 34: 1810–1816, 2012
KEY WORDS: squamous epithelial changes, histopathologic
classification, larynx, pathology, therapy, prognosis
Several identical squamous epithelial changes that can be
identified in the larynx and are presumed to have the
potential to develop into invasive cancer are, depending
on the particular author writing the report, variously
described in the current literature as field cancerization,
potentially cancerous/malignant lesion, precancerous/pre-
malignant lesion, or latent cancer. If nothing else, this
plethora of different terms serves to point out our imper-
fect ability to relate morphologic changes to biologic
potential.1
The profusion of competing proposals for the
categorization of laryngeal squamous intraepithelial
changes2–12
is evidence of the continuing debate and con-
troversy throughout the multidisciplinary team with
respect to recognition, classification, histologic diagnosis
and standardization, management, and prognosis of these
challenging lesions.
Normal histology
In health, the anterior epiglottic surface, the upper half
of the posterior epiglottic surface, the superior margin of
region are lined with pseudostratified ciliated columnar
epithelium, with interspersed goblet cells (Figure 2).
Seromucinous glands are present in the lamina propria
and are particularly numerous on the posterior epiglottic
surface, false cords, ventricle, saccule, and subglottis.
These glands, however, are sparse or absent in the vocal
cord.
Intraepithelial changes
Both types of normal laryngeal epithelium, stratified
squamous and respiratory epithelium, are subject to a spec-
trum of abnormal epithelial proliferation. The following
terminology has evolved:
Clinical terminology
Leukoplakia. The term means "white plaque’’ and is a
clinical term describing any white lesion on a mucous
membrane that cannot be wiped off or ascribed to any
specific condition (eg, Candidal infection). The term has
no histologic implications13
and is not synonymous with
Such an approach has significant implications: the
changes occurring in LIN are considered as morphologic
manifestation of a neoplastic process, not as a precancer-
ous lesion.21,22,41
In contrast, the current literature sug-
gests that many observers believe laryngeal dysplasia to
be a precancerous or premalignant condition, and not a
discrete neoplastic process in its own right.42–44
This con-
fusion in terminology occurs because the term "cancer’’
is typically associated with an invasive process, which is
not the case in LIN. Since some lesions are reversible
and others do not progress, "potentially cancerous’’ is
offered as a more meaningful term than "precancerous.’’
For classification purposes, 3 stages of carcinoma in
situ, similar to those described for the more common
squamous cell carcinoma, have been distinguished: (1)
well-differentiated (grade I); (2) moderately differentiated
(grade II); and (3) poorly differentiated (grade III). This
histopathologic entity45
is represented under both the
Union Internationale Contre le Cancer (UICC)46
and the
American Joint Committee on Cancer (AJCC)47
classifi-
cation as "Tis.’’
Development of Invasive Cancer
It is difficult to accurately predict the development of
invasive laryngeal malignancy in these lesions. Widely
varying differences with respect to the probability of ma-
tein expression is probably an early event in oral carcino-
genesis in the floor of the mouth and is associated with
dysregulation of cell proliferation at this site. However, a
recent meta-analysis of biomarkers in laryngeal dysplasia
concluded that currently there is no good evidence for the
use of biomarkers in predicting the future behavior of la-
ryngeal dysplastic lesions.58
Interobserver Variability
It should be acknowledged that there is an element of
subjectivity in the diagnosis of dysplastic (LIN) lesions
of the larynx. This, in part, is why there are
FIGURE 7. Severe dysplasia is characterized by full-thickness
epithelial atypia with some preserved maturation indicated by
flattening of the cells in the upper epithelial layers. [Color figure
can be viewed in the online issue, which is available at
wileyonlinelibrary.com.]
FIGURE 8. In carcinoma in situ, cellular maturation has entirely
disappeared. Superficial cells show the same abnormalities as the
ones lying in the more basal part. At the left side, remaining normal
epithelium shows surface maturation. [Color figure can be viewed
in the online issue, which is available at wileyonlinelibrary. com.]

24. ✤ LIN I
✤ LIN II
✤ LIN III
Weller MD, Nankivell PC, McConkey C, Paleri V, Mehanna HM. The risk
and interval to malignancy of patients with laryngeal dysplasia; a sys-
tematic review of case series and meta-analysis. Clin Otolaryngol 2010;
CLINICAL REVIEW David W. Eisele, MD, Section Editor
Squamous Epithelial Changes of the Larynx: Diagnosis and Therapy
Alfio Ferlito, MD, DLO, DPath, FRCSEd ad hominem, FRCS (Eng, Glasg, Ir) ad eundem, FDSRCS ad eundem, FHKCORL, FRCPath, FASCP, IFCAP,1
Kenneth O. Devaney, MD, JD, FCAP,2
Julia A. Woolgar, FRCPath, PhD,3
Pieter J. Slootweg, MD, DMD, PhD,4
Vinidh Paleri, MS, FRCS (ORL-HNS),5
Robert P. Takes, MD, PhD,6
Primozˇ Strojan, MD, PhD,7
Patrick J. Bradley, MB, BCh, BAO, DCH, MBA, FRCS (Ed, Eng, Ir), FHKCORL, FRCSLT (Hon), FRACS
(Hon),8
Alessandra Rinaldo, MD, FRCSEd ad hominem, FRCS (Eng, Ir) ad eundem, FRCSGlasg1
1
ENT Clinic, University of Udine, Udine, Italy, 2
Department of Pathology, Allegiance Health, Jackson, Michigan, 3
Cellular Pathology, University Hospital Aintree, Longmoor Lane,
Liverpool, United Kingdom, 4
Department of Pathology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands, 5
Department of Otolaryngology–Head and Neck
Surgery, Newcastle upon Tyne Foundation Hospitals NHS Trust, Newcastle upon Tyne, United Kingdom, 6
Department of Otolaryngology–Head and Neck Surgery, Radboud
University Nijmegen Medical Center, Nijmegen, The Netherlands, 7
Department of Radiation Oncology, Institute of Oncology, Ljubljana, Slovenia, 8
Department of
Otolaryngology–Head and Neck Surgery, Nottingham University Hospital, Queens Medical Centre, Nottingham, United Kingdom.
Accepted 20 May 2011
Published online 3 October 2011 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/hed.21862
ABSTRACT: It can be confusing for clinicians to work their way through
the tangle of pathologic terms used in surgical pathology reports to
describe squamous abnormalities in laryngeal biopsies. After a brief
review of the normal microscopic anatomy of the larynx and time-
honored clinical designations for surface-based abnormalities, this
report sorts pathologic changes into 2 groups: those changes that do
not carry a premalignant potential (including squamous metaplasia,
squamous hyperplasia, pseudoepitheliomatous hyperplasia, keratosis,
and parakeratosis) and those that do (including dyskeratosis, laryngeal
intraepithelial neoplasia [LIN], atypia, dysplasia, and carcinoma in situ).
Generally, lesions in the first group do not require additional therapy or
close follow-up; lesions in the second group, however, demand either
some form of local therapy or close follow-up to monitor for the
development of a more aggressive pathology. VC 2011 Wiley Periodicals,
Inc. Head Neck 34: 1810–1816, 2012
KEY WORDS: squamous epithelial changes, histopathologic
classification, larynx, pathology, therapy, prognosis
Several identical squamous epithelial changes that can be
identified in the larynx and are presumed to have the
potential to develop into invasive cancer are, depending
on the particular author writing the report, variously
described in the current literature as field cancerization,
potentially cancerous/malignant lesion, precancerous/pre-
malignant lesion, or latent cancer. If nothing else, this
plethora of different terms serves to point out our imper-
fect ability to relate morphologic changes to biologic
potential.1
The profusion of competing proposals for the
categorization of laryngeal squamous intraepithelial
changes2–12
is evidence of the continuing debate and con-
troversy throughout the multidisciplinary team with
respect to recognition, classification, histologic diagnosis
and standardization, management, and prognosis of these
challenging lesions.
Normal histology
In health, the anterior epiglottic surface, the upper half
of the posterior epiglottic surface, the superior margin of
region are lined with pseudostratified ciliated columnar
epithelium, with interspersed goblet cells (Figure 2).
Seromucinous glands are present in the lamina propria
and are particularly numerous on the posterior epiglottic
surface, false cords, ventricle, saccule, and subglottis.
These glands, however, are sparse or absent in the vocal
cord.
Intraepithelial changes
Both types of normal laryngeal epithelium, stratified
squamous and respiratory epithelium, are subject to a spec-
trum of abnormal epithelial proliferation. The following
terminology has evolved:
Clinical terminology
Leukoplakia. The term means "white plaque’’ and is a
clinical term describing any white lesion on a mucous
membrane that cannot be wiped off or ascribed to any
specific condition (eg, Candidal infection). The term has
no histologic implications13
and is not synonymous with
Malignização 14% em 5.8 anos
0- 30 %
0-40 %
20-57 %

25. conduta
✤ Lesões sem potencial maligno
✤ seguimento 4/4 meses
✤ avaliação das causas com possível modificação
✤ Tabagismo, DRGE, lesão estrutural…..

26. conduta
✤ Lesões com potencial maligno
✤ seguimento mensal por 3 meses / bimestral 2x/
trimestral 2x/ semestral ……
✤ resseção completa se possível
✤ avaliação das causas com possível modificação
✤ Tabagismo, DRGE, lesão estrutural…..

27. obrigado