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G. Nayak et al.
6.4.3 Benign Tumours
It Includes salivary gland tumours, hyperplastic
lymphoid tissue, adenoid hypertrophy, nasopharyngeal cyst, papilloma, juvenile angiobroma,
and choanal polyps.
Malignant Tumours Include lymphomas, sali-
vary gland tumours, and NPC.
6.4.4 Nasopharyngeal Carcinoma
Nasopharyngeal carcinoma (NPC) has unique
epidemiology, pathogenesis, and evolving treatment modalities which have undergone several
paradigm shifts over the last 30 years. Recent
advances in the treatment planning and delivery
of radiation therapy and the better understanding
of the delivery of chemotherapeutic agents over
the decades have contributed to the improvement
in prognosis. Globally NPC is a rare cancer with
80,000 new cases reported per year and accounts
for 0.7% of all cancers [64]. Compared with
other cancer types, NPC is uncommon with a
very unique pattern of geographical distribution.
In non-endemic areas like North America and
Europe, the incidence rate is low (<1 case per
100,000 population) whereas in high-risk areas
such as Hong Kong and Southern China, the
annual age-standardised incidence rate among
male is as high as 20–30 cases per 100,000 population and 8–15 cases per 100,000 population
[65, 66]. A most common site is the fossa of
Rosenmüller followed by the superior posterior
wall of the nasopharynx.
Aetiology
ciated with NPC include Epstein–Barr Virus
(EBV), genetic and environmental factors.
• Epstein–Barr Virus: Epstein–Barr Virus is a
The main factors believed to be asso-
herpesvirus with a central DNA core and an
enveloped capsid. Infection with EBV occurs
in early childhood and tends to be asymptomatic. In acute and convalescent phase of infection, the immunoglobulins (IgG and IgM) to
antigens (nuclear core early antigen [EA] or
the viral capsid antigen [VCA]) rises. Hence,
in the majority of any population, IgG VCA
and EA will be raised; however, in NPC, the
IgA VCA and EA raises [
67]. EBV antigens
are also present on NPC cells and express lytic
antigens (latent membrane proteins 1, 2, 3)
and nuclear antigens (Epstein–Barr nuclear
antigens 1–6). In NPC, EBNA-1 is always
expressed and LMP-1 is consistently
expressed in signicant levels. EBNA-1 is
responsible for maintaining viral episome in
the tumour cells, whereas LMP-1 has been
shown to induce cellular growth by inducing
epithelial hyperplasia and altered keratin gene
expression [
68, 69]. In addition, expression of
LMP-1 and EBNA-1 is not seen in normal
nasopharyngeal epithelium cells.
• Genetic factor: The association of human leu-
kocyte antigen (HLA) alleles with NPC is
well established; HLA A2, Bw46, B17,
Bw58, DR3, and DR9 have been consistently
found more prevalent in NPC in contrast to
the general population [70]. These haplotypes
are associated with an increased risk for
NPC.Deletions in chromosomes 3, 9, and 11
have been described in NPC.Family clusters
with NPC are not uncommon as NPC in a
rst-degree family member could be as high
as eight times [71].
• Environment factors: It has been seen that
diets high in preservatives containing nitrosamines such as salted sh, eggs, and vegetables
are associated with NPC.Other environmental
factors associated with NPC include chemical
fumes and wood dusts [
72].
Clinical Features The most common presentation in NPC is palpable cervical lymphadenopathy (50%) mainly high level V and level II.Others
may present with nasal symptoms (30%), otological symptoms (20%), cranial nerve palsy
20% (III, IV, V, VIth nerves), or distant metastasis
3% (spine is the commonest site of distant metastasis). Unilateral secretory otitis media presenting as deafness (30%) in adults is a warning sign
and is believed to be secondary to eustachian tube
dysfunction.
Around 1% of NPC cases may have dermato-
myositis as a paraneoplastic syndrome which can
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develop concurrently with NPC, late after diagnosis, or months before the NPC is clinically
apparent [73].
Assessment Patients should be assessed with
rigid and bro-optic nasal endoscopy which
reveals exophytic mass that may occupy the
whole postnasal space (Fig. 6.27). Ulcerated
growth may be present and in about 10% of NPC
patients, the lesion is submucosal.
Fig. 6.27 Endoscopic view of nasopharyngeal tumour: A
tumour can be seen obliterating the right nasal choana
Multislice computed tomographic scan of
head, neck, and chest is an essential investigation particularly useful in delineating clival and
skull base erosion. Magnetic resonance imaging
provides superior denition in detecting soft tissue changes and intracranial involvement
(Fig.6.28a, b).
Diagnosis The gold standard in the diagnosis
of NPC is the histopathological conrmation.
The immunohistochemical markers such as
cytokeratin, epithelial cell markers, and
Epstein–Barr encoded ribonucleic acid (EBER)
will help in differentiating NPC from other
malignancies.
Cytology Fine-needle aspiration with immuno-
histochemical staining for EBER from enlarged
neck lymph node can often differentiate between
metastasis from undifferentiated carcinoma and
squamous cell carcinoma.
Other Staging Investigations Other staging
investigations include chest radiograph, CT scan
of lungs and liver, liver ultrasound, and bone
scan. Among these, bone scan has the highest
pick-up rate, which is consistent with the skeleton being the most common distant site of metastasis. Positron emission tomography (PET-CT) is
another imaging tool; however, literature is scant
a
Fig. 6.28 (a) Contrast-enhanced computed tomography (axial section) of left nasopharyngeal carcinoma. (b) T2w
axial section, left nasopharyngeal carcinoma
b
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G. Nayak et al.
on the efcacy and cost-effectiveness of using
PET-CT as a sole staging tool to assess the primary and regional metastasis. A recent metaanalysis has conrmed the reliable performance
of PET-CT in the evaluation of distant metastasis,
with a pooled sensitivity of 83% and specicity
of 97% [74].
EBV DNA copies may be measured by polymerase chain reaction techniques which correlate
with the stage of disease and are useful as an indicator of treatment response. Immunoserology
(VCA-IgA, EA-IgA, EBVNA1-IgA) and EBV
DNA can be used as screening methods.
Pathology: WHO histological classication:
Three types:
Type I—Keratinising squamous cell carcinoma
•
• Type IIa—Differentiated non-keratinising
carcinoma
• Type IIb—undifferentiated non-keratinising
carcinoma
• Type III—Basaloid squamous cell carcinoma
In endemic areas, the non-keratinising subtype constitutes most cases (>95%) and is invariably associated with EBV infection. On
histopathology, abundant lymphoid cells are seen
intermixed with malignant epithelial cells.
Staging of Nasopharyngeal Cancers
The
eighth edition of AJCC Classication and staging
[59] is given in Table6.7.
• Differential diagnoses include lymphoma,
extramedullary plasmacytoma, melanoma,
rhabdomyosarcoma, and adenoid cystic
carcinoma.
Treatment: Non-keratinising NPC is a radiosensitive tumour and radiotherapy is the mainstay
of treatment, whereas surgery is reserved for salvage of radiation failure.
• Intensity-modulated radiation therapy tech-
niques are the standard of care, and integrating
CT or MRI images into the 3D planning sys-
tem provides accurate spatial information on
the normal organ and tumour target which
enables more exible adjustment of the beam
direction.
• Radiotherapy (RT) is the mainstay for the radical treatment of NPC (stage I).
• Concurrent chemoradiotherapy followed by
adjuvant cisplatin and uorouracil or neoadjuvant chemotherapy followed by concurrent chemoradiotherapy offers signicant
improvement in overall survival in stage III
and IV diseases [75, 76].
NCCN Guideline [77]
• T1, N0, M0: Denitive radiotherapy to nasopharynx and elective RT to neck.
• T1, N1–3; T2–4, N0–3: Clinical trials (preferred) or Concurrent chemo/RT followed by
adjuvant chemotherapy or induction chemotherapy followed by chemo/RT or concurrent
chemo/RT not followed by chemotherapy.
• Any T, any N, M1: Clinical trials (preferred)
or Platinum-based combination chemotherapy
followed by RT or concurrent systemic therapy/RT as clinically indicated or observation
or concurrent chemo/RT or RT or surgery in
select patients with oligometastatic disease.
• Cetuximab or nimotuzumab, monoclonal antibodies in combination with induction chemotherapy has shown better overall survival and
3-years’ disease-free survival in patients with
locally advanced NPC treated with intensitymodulated radiotherapy [78].
Treatment of Local Recurrence
Brachytherapy, high-dose external reirradiation,
or surgery has comparable results in terms of
treatment outcome in patients with early local
recurrence, but their toxicity prole is quite different. Nasopharyngectomy is mainly reserved
for lesions that do not involve skull base or internal carotid artery (rT1 and limited rT2) whereas
external beam reirradiation is an alternative to
surgery for rT2 disease and is often the only
option for more advanced disease (advanced rT2,
rT3–4). Brachytherapy is only suitable for small
recurrences conned to the central nasopharynx.
Few radioresistant tumours like adenoid cystic
carcinoma should be treated with upfront surgery
followed by radiotherapy.
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Table 6.7 Staging: eighth edition of AJCC Classication and staging
T category T criteria
Tx Primary tumour cannot be assessed.
T0 No tumour recognised, but EBVT1 Tumour limited to nasopharynx, or involvement of oropharynx and/or nasal cavity
without parapharyngeal space inltration.
T2 Tumour with involvement to parapharyngeal space and/or neighbouring soft tissue
involvement (medial pterygoid, lateral pterygoid, prevertebral muscles).
T3 Tumour with inltration of bony structures at the skull base, cervical vertebra,
pterygoid structures, and/or paranasal sinuses.
T4 Tumours with intracranial extension, involvement of cranial nerves, hypopharynx,
orbit, parotid gland, and/or extensive soft tissue inltration beyond the lateral
surface of the lateral pterygoid muscle.
N category N criteria
Nx Regional lymph nodes cannot be assessed.
N0 No regional lymph node metastasis.
N1 Unilateral metastasis in cervical lymph node(s) and/unilateral or bilateral metastasis
in retropharyngeal lymph node(s), 6cm or smaller in greatest dimensions, above the
caudal border of cricoid cartilage.
N2 Bilateral metastasis in cervical lymph node(s) 6cm or smaller in greatest dimension,
above the caudal border of the cricoid cartilage.
N3 Unilateral or bilateral metastasis in cervical lymph node(s), larger than 6cm in
greatest dimension, and/or extension below the caudal border of cricoid cartilage.
M category M criteria
M0 No distant metastasis
M1 Distant metastasis
When T is … And N is… And M is… Then the stage group is…
Tis N0 M0 Stage 0
T1 N0 M0 Stage I
T1,N0 N1 M0 Stage II
T2 N0 M0 Stage II
T2 N1 M0 Stage II
T1,T0 N2 M0 Stage III
T2 N2 M0 Stage III
T3 N0 M0 Stage III
T3 N1 M0 Stage III
T3 N2 M0 Stage III
T4 N0 M0 Stage IVA
T4 N1 M0 Stage IVA
T4 N2 M0 Stage IVA
Any T N3 M0 Stage IVA
Any T Any N M1 Stage IVB
positive cervical lymph node(s).
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Surgery in form of nasopharyngectomy should
be considered as a rst-line treatment of residual
or recurrence disease at the primary site (rT1 and
limited rT2).
Surgical Approaches to Nasopharynx
Anterior approaches:
1. Trans-palatine approaches
Indications:
• Benign and malignant tumours of the posterior nasopharyngeal wall (2cm or less in size)
• Access to tumour extending to clivus and
craniocervical junction
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Contraindications:
• Nasopharyngeal tumours size >2cm
• Signicant intracranial extension
• Tumours extending to parapharyngeal
space, infratemporal fossa, cavernous
sinus, and peritubal space
2. Transmandibular–transcervical approach:
Indications:
• Nasopharyngeal tumours extending into
the anterior infratemporal fossa
Contraindications:
• Dural invasion >2 cm2 and intracranial
involvement
• Invasion of parasellar and posterior infra-
temporal region
3. Lateral approaches: infratemporal fossa
type C:
Indications:
• Tumour that extends into the temporal
bone with the involvement of the
epipharynx
• Contraindications:
• Advanced disease extending to sella,
contralateral middle fossa, anterior skull
base
4. Anterolateral approach: Maxillary swing
technique (Fig.6.16)
Indications:
• Nasopharyngeal tumours with limited exten-
sion into the anterior infratemporal region
Contraindications:
• Lesions involving petrous ICA and petrous
apex
• Lesions extending into parasellar and/or
posterior infratemporal region
5. Combined approaches: Subtemporal–preauricular infratemporal fossa approaches
(Fig.6.17)
Indications:
• Large tumours (T4) involving infratempo-
ral space extending into the nasopharynx,
cavernous sinus, and middle cranial fossa
Contraindications:
• Bilateral ICA involvement
• Bilateral involvement of optic chiasma
• Lesion extending into posterior cranial
fossa
6. Facial translocation:
Indications:
• Extensive tumours (T4) of anterior and
middle skull base extending into orbit,
paranasal sinus, and posterior cranial fossa
with intracranial involvement
• Contraindications:
• Bilateral involvement of ICA
• Bilateral involvement of optic chiasma
• Lesion extending into posterior cranial
fossa
Robotic Nasopharyngectomy Transoral robotic
nasopharyngectomy has many advantages which
include good visualisation of the lateral aspect
of nasopharynx and avoidance of cutting palatal
muscles including tensor veil palatine which
can cause velopharyngeal insufciency. This
new technique is a feasible operation for salvage
of recurrent nasopharyngeal carcinoma mainly
rT1 and limited rT2 NPC. Early results have
shown a high control rate, low morbidity, and
comparable operating time to open surgeries. It
is indicated in [79]:
1. Smaller tumours in posterior wall/roof of
nasopharynx.
2. Fossa of Rosenmuller without lateral
extension.
3. Tumour should be more than 1cm from ICA
and the course of ICA should not be medial to
the medial pterygoid plate.
Contraindications:
1. Tumour located less than 1cm from ICA
2. Tumour extending lateral to lateral pterygoid
plate
3. Tumour with invasion of pterygopalatine
fossa or maxillary sinus
A major disadvantage is the lack of tactile
sensation which makes the surgeon unaware
that the tip of the instrument has reached the
bony clivus or the inability to palpate ICA
which is in the lateral aspect of the area of
dissection.
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Endoscopic Nasopharyngectomy A minimally
invasive, safe, and efcacious option for selected
primary and locally radiorecurrent tumours with
comparable survival to open approaches. This
technique approaches the nasopharynx through
the natural orices with added high magnication and avoids the inherent morbidities associated with open procedures. However, long-term
evaluation with longer follow-up data is required.
Three types of nasopharyngeal endoscopic resection (NER) are:
1. Type I NER: Involves resection of posterior
wall of nasopharynx
2. Type II NER: Involves resection of tumours
extending superiorly to the sphenoid sinus
3. Type 3 NER: Is trans-pterygoid approach to
posterolateral nasopharynx with removal of
eustachian tube and pterygoid plates
Initial results are promising with local control
comparable to conventional open surgical techniques, with most series having a 2-years’ local
control of over 80% [80, 81].
Treatment of Regional Recurrence
Reirradiation
for nodal failure is associated with poor results and
high complications. Neck dissection remains the
treatment of choice for residual or metastatic neck
disease whenever possible. Prognosis often
remains poor in neck residue patients. Surgical
salvage of nodal recurrence has a 5-years’ local
control of 66% and 5-years’ overall survival of
37% [82].
Distant Recurrence
The traditional rst-line
chemotherapeutic regimen for metastatic NPC is
a combination of cisplatin and 5-uorouracil and
the median overall survival is around 12months.
Brachytherapy This modality can be used
either as a primary treatment modality or in the
management of recurrent cancers. For patients
with T1–2 NPC, it can be used either as twodimensional high-dose-rate brachytherapy or
three-dimensional image high-dose-rate brachytherapy with acceptable complications. For
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recurrent NPC, image-guided
I is an effective
treatment modality with better survival and minimal damage [83].
Immunotherapy Expression of EBV antigens
is important as these antigens are being targeted
in immunotherapy such as viral-specic adoptive
cell therapy. These strategies may emerge as the
main modality of treatment and can offer a durable remission in advanced nasopharyngeal carcinoma [84].
Photodynamic Therapy (PDT)
FDA-approved
therapy involves a combination of light-activated
photosensitiser, visible light, and molecular oxygen to selectively destroy tissue. Antitumour
effect is derived by three mechanisms: the
destruction of tumour-associated vasculature,
direct cytotoxic effect, and induction of inammatory reaction against tumour cells. Photofrin,
rst-generation FDA-approved photosensitiser,
is administered via intravenous injections with
24–48hours incubation with light of wavelength
630nm. Its longer clearance time is a drawback
of photofrin-mediated PDT.A number of secondgeneration photosensitisers (5-Aminolevulinic
acid, hexyl-ALA, and Meta-tetra (hydroxyphenyl) chlorine) were discovered and have potential
advantages over rst-generation drugs including
better tumour selectivity, faster clearance, and
higher chemical purity. Light sources commonly
used for PDT include laser diode, laser, ltered
broadband light, and light-emitting diodes. It can
be used in residual and recurrent cases and initial
studies have shown improvement in recurrent
tumours of less than 10mm in depth [85].
Follow-Up With the introduction of a concur-
rent chemoradiation regimen, recurrence has
dropped to less than 10%. Most failures occur
within 2years of treatment. Patients with NPC
cases are followed up and assessed with ofcebased rigid and/or bro-optic nasal endoscopy.
Positron emission tomography–computed
tomography, CT, or MRI scan should be carried
out at 3 months from completion of treatment to
assess response.
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Outcome In general, patients with non-viral-
associated nasopharyngeal carcinoma (i.e. HPVnegative, EBV-negative tumours) had worse
outcomes than patients with viral-associated
tumours. The average 5years survival rates with
treatment are [86]:
•
Stage I: 100%
• Stage II: 90%
• Stage III: 67%
• Stage IV A: 67%
• Stage IV B: 69%
Stage IV C:18%
•
Adenoid Cystic Carcinoma
Adenoid cystic
carcinoma (ACC) arising from minor salivary
glands in this region is relatively rare and has a
progressive clinical course. These lesions are
characterised by local inltration and neural
invasion and can extend from the nasopharynx
into the orbital cavity, along the cranial nerve
canal and anterior skull base. Most often, they
tend to be locally aggressive and have high tendency of recurrence. Magnetic resonance imaging is the investigation of interest as it detects
perineurial invasion and has a superior denition
in detecting soft tissue changes. It is widely used
for monitoring the response of treatment.
Complete surgical resection is an important goal
in the treatment; however, close resection margins in an anatomically complex area, adjuvant
therapy becomes an integral part of treatment
[87]. Endoscopic surgery is becoming a promising approach for early-stage disease.
ACC grows slowly, recurs frequently, and
metastasises to distant organs, particularly lungs,
and therefore, its long-term prognosis is poor.
The solid component of tumour on histology,
advanced tumour stage, and the perineurial invasion appears to be associated with an unfavourable prognosis.
Nasopharyngeal Papillary Adenocarcinoma
Primary nasopharyngeal papillary ade-
nocarcinoma is an extremely rare tumour which
is reported to occupy 0.48% of all types of NPC
[88]. These tumours have features resembling
papillary carcinoma thyroid with nuclear positive
expression of thyroid transcription factor-1 (TTF-
1) and therefore can be confused with metastatic
papillary thyroid carcinoma histologically but
these lesions are thyroglobulin-negative.
These tumours commonly arise from surface
epithelium in the posterior and superior aspect of
the nasopharynx. Histologically, tumour cells
have a papillary architecture with mild nuclear
atypia and invasive growth pattern. On immunohistochemistry, these tumours are TTF-1 V,
CK-7, CK-19, and CEA positive. Complete surgical excision is the treatment. Adjuvant radiation therapy is advised in case of incomplete
excision [
Chordoma
89].
Chordoma is a low-grade malig-
nant tumour arising from notochord remnants
showing epithelial–mesenchymal differentiation. They mostly arise from clivus in the head
and neck region in 25–35% of cases. These
lesions are slow-growing and invade local structures, and malignant transformation occurs in
third to fourth decade of life. Metastasis is rare
and if occurs, metastasise to lungs, bones, skin,
and lymph nodes. They can have varied presentations, depending on their location. Cranial
tumours may present with chronic intractable
headache, cranial neuropathy, inferior extension
results in nasal or nasopharyngeal mass, nasal
obstruction, nasal bleeding, and cerebrospinal
rhinorrhoea. Histologically shows lobular
growth pattern separated by connective tissue
septae (typical multivacuolated physaliferous
cells). Immunohistochemistry shows positivity
for cytokeratin, vimentin, and S-100 [90].
Staging is done by radiological investigations
(CECT/CEMRI) and is a prerequisite for appropriate management. Treatment options include
surgery (gross total resection) +/− radiotherapy
or radiotherapy. Endonasal endoscopic skull
base approach has allowed a high rate of gross as
well as microscopic clearance of disease [91].
Due to the locally invasive nature of the lesion,
complete excision may not be possible leading
to a high recurrence rate. Five and 10years overall survival rates are 50% and 20%. Tumour
necrosis and volume of tumour more than 70ml
are independent poor prognostic factors.
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6.5 Part E: Pathology ofLesions
oftheNose andParanasal
Sinuses
Lesions of the nose and paranasal sinuses include
inammatory lesions as well as benign and
malignant neoplasms. With increasing ease of
availability of high-throughput molecular diagnostic platforms, newer genetically dened entities are being identied, leading to escalating
complexity of classication systems. This chapter covers the salient diagnostic features and
genetic alterations in the frequently encountered
lesions of this region.
6.5.1 Sinonasal Neoplasms
The nasal cavity and paranasal sinuses play host
to a wide spectrum of benign and malignant neoplasms. These neoplasms may be exclusive to
this region, may occur here more frequently than
at other head and neck sites, or may occur else-
where in the body but are important in the sinonasal tract due to differential diagnostic
considerations. They include benign and malignant tumours of epithelial, mesenchymal, neuroectodermal, and hematolymphoid origin, as
shown in Table6.8 [92, 93].
6.5.2 Carcinomas
Carcinomas are tumours of epithelial origin.
Sinonasal carcinomas represent fewer than 5% of
all head and neck tumours. They may arise from
the respiratory epithelium of the sinonasal region,
or from the subepithelial mucoserous glands.
They are diagnosed primarily based on morphology and immunohistochemistry. However,
improvements in molecular techniques in recent
years have led to a more specic categorisation of
sinonasal carcinomas, with many poorly differentiated tumours being redened into more specic categories based on molecular genetic
features.
Table 6.8 Classication of sinonasal tumours
Epithelial Mesenchymal Others
Malignant Benign Malignant Borderline Benign
Squamous cell
carcinoma and
variants
SMARCB1decient
sinonasal
carcinoma
NUT carcinoma Salivary gland
Neuroendocrine
carcinomas
Adenocarcinoma Rhabdomyosarcoma Meningioma
Sinonasal
undifferentiated
carcinoma
(SNUC)
Sinonasal
papillomas
Respiratory
epithelial
lesions
Respiratory
epithelial
adenomatoid
hamartoma
Seromucinous
hamartoma
tumours
Pleomorphic
adenoma
Biphenotypic
sinonasal sarcoma
Undifferentiated
pleomorphic
sarcoma
Malignant
peripheral nerve
sheath tumour
Fibrosarcoma Epithelioid
Synovial sarcoma
Leiomyosarcoma
Angiosarcoma
Glomangiopericytoma Leiomyoma Neuroectodermal
Solitary brous tumour Hemangioma Lymphomas
Fibromatosis Schwannoma Sinonasal
hemangioendothelioma
Olfactory
neuroblastoma
Ewing sarcoma
Mucosal melanoma
Extranodal NK/T cell
lymphoma
Plasmacytoma
Plasmablastic
lymphoma
teratocarcinosarcoma
Neurobroma Ectopic pituitary
adenoma
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6.5.2.1 Squamous Cell Carcinoma (SCC)
SCC is a carcinoma with squamous differentiation, arising from the sinonasal surface epithelium. SCCs occur de novo, or, less frequently, by
malignant transformation of sinonasal papillomas. They are classied as keratinising and nonkeratinising types. The keratinising type of SCC
is associated with smoking and resembles keratinising SCC at other head and neck sites. It displays nests and cords of atypical squamous cells
with evidence of maturation, i.e. keratinisation, in
a desmoplastic stroma. Keratinising SCCs are
graded as well into moderately or poorly differentiated tumours based on the extent of keratinisation (Fig.6.29a). Non-keratinising SCC has been
found to be associated with transcriptionally
active high-risk HPV.It is morphologically characterised by ribbon-like and nested architecture,
and pushing borders (Fig. 6.29b). Tumour cells
appear basaloid, with scant cytoplasm and ovoid
nuclei (Fig.6.29c). These tumours are not graded
as keratinising SCC are HPV-related tumours
demonstrate diffuse p16 staining, and are HPV
positive by in DNA and mRNA situ hybridisation
techniques. Rare morphological subtypes of SCC
occasionally encountered in the sinonasal tract
include spindle cell (sarcomatoid) SCC, lymphoepithelial carcinoma, papillary SCC, basaloid
SCC, and verrucous carcinoma. SCCs are immunopositive for cytokeratins including CK5/6, epithelial membrane antigen (EMA), and squamous
markers p63 and p40. Staining with these markers
is extremely helpful in establishing the diagnosis
of spindle cell SCC [94].
6.5.2.2 SMARCB1-Decient Sinonasal
Carcinoma
SMARCB1-decient sinonasal carcinomas are
recently identied aggressive neoplasms characterised by biallelic inactivating alterations (deletions, intragenic mutations) in the SMARCB1
tumour suppressor gene on 22q11.2, which can
be demonstrated by loss of immunoexpression of
INI1, the protein product of this gene. Prior to
their identication, they were mostly diagnosed
as non-keratinising SCC or sinonasal undifferentiated carcinoma (SNUC). These tumours show a
variable admixture of basaloid (Fig.6.30a), plasmacytoid (Fig. 6.30b), and rhabdoid cells with
abundant eccentric eosinophilic inclusion-like
cytoplasm (Fig. 6.30c). In addition, they may
also show oncocytic cells in a glandular pattern,
mimicking adenocarcinomas. Inverted papillomalike growth, pagetoid spread along respiratory
epithelium, and clefting artefact around tumour
islands are other features that may be present.
Necrosis, frequent mitoses, and intracytoplasmic
clear vacuoles are present in the tumour cells. On
immunohistochemistry, they show loss of INI1
immunostaining (Fig. 6.30d), are diffusely
cytokeratin- positive, and show variable staining
with p63, p40, CK5/6, and neuroendocrine markers [95, 96].
6.5.2.3 NUT Carcinoma
NUT carcinoma is a novel, poorly differentiated,
aggressive carcinoma characterised by NUTM1
gene rearrangements with various fusion partners, most frequently BRD4. NUT carcinomas
Fig. 6.29 Keratinising squamous cell carcinoma showing irregular nests of cells with abundant pink cytoplasm
and keratin pearls (a); non-keratinising squamous cell car-
cinoma showing large rounded nests with smooth borders
(b) containing tumour cells with scant cytoplasm (c)
ab
cd
ef
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Fig. 6.30 SMARCB1-decient sinonasal carcinoma with
“blue” basaloid cells showing empty vacuoles (a), “pink”
plasmacytoid (b) and rhabdoid (c) cells, and loss of INI1
have been described at midline locations in the
head and neck including the sinonasal region and
parotid gland, and in the mediastinum and lung.
These tumours are composed of sheets and nests
of undifferentiated basaloid cells (Fig. 6.30e),
with foci of abrupt squamous differentiation
including clear cells and squamous eddies
(Fig.6.30f). The tumour cells may display spindling and peripheral palisading. Interspersed
inammatory cells may be present. The tumour
cells show diffuse immunopositivity with cytokeratin, p63, p40, and NUT protein [97].
staining (d); NUT carcinoma showing undifferentiated
basaloid cells (e) with foci of abrupt squamous differentiation (f)
lining epithelium of the sinonasal region. They
present as exophytic masses that extensively
invade surrounding tissue. They show a variety of
histological patterns, including papillary
(Fig.
6.31a), tubular, solid, and mucinous. Mixed
patterns are frequent. Mucinous, goblet, and
signet- ring cells containing intracytoplasmic
mucin are present; intraluminal and extracellular
mucin may also be seen. The tumour cells are
cuboidal to columnar with pseudostratied nuclei
6.31b) showing variable crowding and loss
(Fig.
of polarity which increase with increasing grade
from low through intermediate to high. The
6.5.2.4 Adenocarcinoma
Sinonasal adenocarcinomas are glandular neoplasms that arise from glandular cells in the
respiratory mucosa. Non-salivary-type sinonasal
adenocarcinomas are classied as intestinal and
non-intestinal types.
Intestinal-type adenocarcinomas (ITACs) are
sinonasal glandular neoplasms that resemble gastrointestinal adenocarcinomas, hence the name.
They develop through intestinal metaplasia of the
tumour cells are immunopositive for CK20,
CDX2 (Fig.6.31c), villin, and MUC2, similar to
colonic adenocarcinomas; variable staining for
CK7, EMA, and CEA is also seen. Focal positivity for neuroendocrine markers is frequent.
Mutations have been identied in KRAS, HRAS,
TP53 genes, like in colonic adenocarcinomas.
Solid, mucinous, and signet ring patterns have
been found to be associated with poor prognosis
in these tumours [98].
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