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17 Paediatric Head andNeck Pathology andSurgery
417
cells, desmoplastic response of the nasopharyngeal periosteum, embryonic brocartilage and
nonchromafn paraganglionic cells of the terminal branches of the maxillary artery. JNA is noted
to demonstrate superior level of hormone receptors and vascular endothelial growth receptor
(VEGF), which indicates possible interaction
between receptors and VEGF [87].
It is noteworthy that the tumour’s blood supply is mainly derived from ipsilateral sphenopalatine branch of maxillary artery, a branch of
external carotid artery [88]. Other contributing
vessels are ascending pharyngeal artery, vidian
artery and contralateral vessels. It is noteworthy
that bilateral vascular supply, albeit rare, has
been reported [89].
17.5.5 Presentation
JNA involves adolescent males with the mean age
of 15years upon presentation [82]. Nasal obstruction, epistaxis and nasopharyngeal mass have been
reiterated as the three most common presentations
for years [90]. Nasal obstruction is usually progressive and painless, whereas epistaxis is spontaneous, painless and usually severe requiring
attention. Other clinical manifestations include
headache, facial swelling, cheek numbness and
deformity, unilateral rhinorrhea, olfactory disturbances, otalgia, aural fullness and reduced hearing. It is noteworthy that clinical manifestations
result from mass effect of the tumour. It is noteworthy that patients with JNA seek treatment after
6–12months of having symptoms [91]. If delayed,
the tumour will progressively grow causing devastating clinical manifestations such as ptosis, cranial nerve palsies, blurring of vision, diplopia and
even blindness [91, 92], which denotes advanced
stage of disease.
17.5.6 Diagnosis
tial in all patients suspected with JNA.Presence
of vascular mass at the nasopharynx, particularly
the posterolateral wall, should raise suspicion. It
is of utmost importance that biopsy is not performed as torrential bleed will ensue if proceeded. Additionally, otoscopic examination,
ocular examination as well as exible nasopharyngolaryngoscopy need to be carried out to
appraise the extension of the tumour.
17.5.7 Imaging
CT and MRI are both favoured imaging tools. CT
enables tumour delineation along with this extension and detects bony erosion particularly the
skull base. Classical ndings include HolmanMiller sign which encompasses the anterior bowing of the posterior wall of maxilla,
dumb-bell-shaped or bilobed tumour, erosion of
sphenoid bone particularly the greater wing of
sphenoid as well as hyperintensity owing to the
extensive vascular supply of the tumour. CT
angiography is able to detect the specic feeding
vessel and to look for tumour blush, as well as is
used for preoperative embolisation.
MRI has superior soft-tissue tumour delineation, along with tumour extension, intracranial
extension, perineural invasion as well as orbital
extension. Avid enhancement is seen in a contacted T1-weighted image, whilst multiple signal
voids are seen in T2-weighted images.
17.5.8 Histology
JNA is an encapsulated mass, which comprises
vascular tissue and brous stroma and collagen
bres. The aficted vessels are commonly thin
walled and lack elastic bres with absence of
smooth muscles. Plump cells within the stromal
cells radiate around the vessels.
A meticulous history taking along with complete
physical examination would lead to the suspicion
of JNA.Thorough physical examination complemented by cranial nerve examination is deemed
necessary. Nasoendoscopic examination is essen-
17.5.9 Staging
Fisch staging and Radkowski staging are the
most prevalent staging systems used in myriad
studies.
418
J. Saniasiaya and N. Mat Lazim
17.5.9.1 Fisch Staging
I: Tumours limited to nasal cavity and nasophar-
ynx with no bony destruction
II: Tumours invading the pterygomaxillary fossa
and paranasal sinuses with bony destruction
III: Tumours invading the infratemporal fossa,
orbit and parasellar region, remaining lateral
to the cavernous sinus
IV: Tumours with invasion to the cavernous
sinus, optic chiasmal region and pituitary
fossa
17.5.9.2 Radkowski Staging
Stage
IA: Limited to nose and nasopharyngeal area
IB: Extension into one or more sinuses
IIA: Minimal extension into pterygopalatine fossa
IIB: Occupies pterygopalatine fossa with or with-
out orbital region
IIC: Infratemporal fossa extension with or with-
out cheek or pterygoid plate involvement
IIIA: Erosion of the skull base (middle cranial
fossa or pterygoids)
IIIB: Erosion of the skull base with intracranial
extension with or without cavernous sinus
involvement
17.5.10 Treatment
Surgery is the primary mode of treatment.
However, amongst patients not t for surgery,
other modalities including radiotherapy, chemotherapy as well as medical therapy exist.
17.5.10.1 Surgery
Surgery has been reiterated as the rst-line treatment. Despite the myriad surgical armamentarium which exists to date, best surgical approach
does not exist. It is noteworthy that surgical
approach relies chiey on tumour extension.
Surgical approaches have evolved over the last
decade, whereby surgical approach can mainly
be divided into open, endoscopic or a combined
approach. Open approaches include transpalatal,
transpharyngeal, transfacial via lateral rhinotomy, midfacial degloving, LeFort I osteotomy,
and infratemporal and subtemporal lateral
approaches [93, 94]. It is noteworthy that
advances in imaging as well as preoperative
embolisation have enabled better preoperative
management as well as aided in tumour resection. Intraoperative bleeding has been the most
devastating complication feared by most surgeons. Availability of cell savage machine as well
as haemostat materials such as absorbable gelatine, powder, sponge oxidised regenerated cellulose, microbrillar collagen, brin and synthetic
sealant aids to control bleeding [95].
With the advent of endoscope, endoscopic
tumour resection has enabled surgeons to resect
tumour with reduced morbidity. Mass involving nasopharynx, nasal cavity, paranasal sinuses
and pterygopalatine fossa could be removed
through endoscopic approach successfully [96].
Endoscopic resection is feasible for tumours
involving Radkowski I–IIIA [97], as well as extension into orbit, parasellar region and infratemporal
region by experienced surgeons [93, 97, 98].
17.5.10.2 Outcome
Nearly 18% recurrence rate is demonstrated with
long-term disease-free survival rate of 87% [91,
92]. Yet, recurrence rate of up to 50% has been
reported [99]. Notable risk factors contributing
to recurrence include advanced stage at presentation, extensive tumour especially tumour in
pterygoid fossa and basisphenoid, clival erosion,
intracranial extension and younger age at
diagnosis.
17.5.10.3 Complications
Complications can occur from surgery or from
tumour extension. Most common complications
are from the sinonasal and neurologic concerns.
Prominent complications include bleeding,
nasopharyngeal stenosis, epiphora, impaired
facial growth, facial deformity, scar and blindness. Trismus may ensue from infratemporal
approach whilst paraesthesia on the cheek from
Weber- Ferguson incision or midfacial degloving
approach. Albeit rare, meningitis and blindness
following JNA surgery have been reported. It is
noteworthy that transient blindness may ensue
embolisation.
17 Paediatric Head andNeck Pathology andSurgery
419
17.5.10.4 Radiotherapy
Radiotherapy is not the rst line in view of the
strings of complications which follow notable
radiation-induced malignancy. Yet, radiotherapy
is recommended in patients with unresectable
tumours or incomplete tumour removal. Residual
lesions in vital regions which are progressively
increasing in size warrant radiotherapy [98].
Recurrence rate following primary radiotherapy
with 30–55Gy revealed recurrence rate of 15%
[100]. Intensity-modulated radiotherapy revealed
favourable outcome in patients with extensive or
persistent JNA with no recurrence noted [101].
17.5.10.5 Chemotherapy
Chemotherapy has revealed successful outcome
in numerous patients [102, 103]. Goepfert etal.
advocated the usage of two chemotherapy protocols: doxorubicin and dacarbazine or vincristine,
and dactinomycin and cyclophosphamide with
successful outcome [102].
17.5.10.6 Hormonal Therapy
Hormonal therapy has revealed promising results
especially with oestrogen and androgen receptor
blocker [104]. Flutamide, a non-steroidal androgen receptor blocker, revealed tumour regression
of 44% in four cases [105]. Parallel to that, utamide revealed regression of tumour in 20
advanced-stage post-pubertal patients [106].
17.5.10.7 Spontaneous Regression
Spontaneous regression was demonstrated
amongst young adults aged between 20 and 25,
especially in patients with post-resection residual
tumour [107].
1 cm or mixed [109]. LM presents at birth in
almost 60% of infants and in 90% of children
within 2years. Macrocystic LM within the cervical region is termed as cystic hygroma [109].
17.6.2 Genetics
Albeit the genetic causes of LM are unknown, in
a small number of children, LM is linked with
numerous syndromic disorders such as Turner
syndrome, Proteus syndrome, KlippelTrenaunay- Weber and congenital lipomatous
overgrowth, vascular malformations and
CLOVES syndrome [110].
17.6.3 Clinical Presentation
Clinical manifestation relies on the anatomical location. LM may present as small swelling to a diffusely large area compromising adjacent area [111].
Approximately 75% of LM can be discovered in the
cervicofacial region [112]. In any case, if the LM is
present within the aerodigestive tract, airway compromise, swallowing as well as speech disturbance
may occur [113–115]. LM presenting in orbital area
may lead to visual disturbance, ptosis, diplopia and
dystopia. Besides that, LM had been reported within
the chest, axilla, mediastinum, retroperitoneum,
buttocks as well as anogenital region [116] and
extremities. As LM expands, it can cause severe
functional impairment as well as cosmetic deformity, pain and bleeding. It is noteworthy that children with LM may develop lymphopenia resulting
in high risk of developing infection [114, 117].
17.6 Lymphatic Malformation
17.6.1 Introduction
Lymphatic malformation (LM) is characterised
by low-ow vascular tumour of the lymphatic
system, which affects 1 patient among 2000–
4000 live births [108]. LM is classied into macrocystic with a diameter measuring more than
1cm and microcystic with a diameter of less than
17.6.4 Diagnosis
LM can be identied at early stage during prenatal follow-up through ultrasound within the second or third trimester. Foetal MRI is a superior
diagnostic modality to outline the mass as well
as its extension and to look for any associated
anomaly [118]. It is also noteworthy that foetal
MRI enables decision of treatment or mode of
delivery such as the need for ex utero intrapar-
420
J. Saniasiaya and N. Mat Lazim
tum treatment (EXIT) procedure. If not diagnosed prenatally, LM can be diagnosed at birth
or early infancy period with appearance of ballotable mass. LM usually enlarges slowly as the
child grows; occasionally, sudden or rapid
increase in mass size may occur following infection, haemorrhage or trauma. Additionally, usage
of lymphoscintigraphy to diagnose LM has been
reported.
17.6.5 Treatment
Aims of treatment in LM include to maintain
function, control symptoms as well as preserve
cosmesis [119, 120]. Prior to deciding on the
mode of treatment, a multi-unit team discussion
including otorhinolaryngologists, paediatricians,
dieticians, reconstructive surgeons, speech therapists, audiologists and psychologists together
with parents is deemed necessary.
17.6.5.1 Observation
Albeit surgical approach is considered the gold
standard, some authors have advocated observation in uncomplicated cases whereby the LM
does not cause functional decit. Gilony et al.
found that 45% of patients who were observed
demonstrated spontaneous regression [121].
Additionally, Gilony discovered that most
patients can be observed initially prior to intervention [121].
17.6.5.2 Sclerotherapy
Sclerotherapy has demonstrated promising
results in treating macrocystic LM [111, 122].
Popular sclerosants include picibanil (OK-432),
doxycycline, bleomycin, ethanol, acetic acid,
sodium tetradecyl sulfate and hypertonic saline
[119, 120]. Sclerosants are administered intralesionally after aspirating cystic uid. Side
effects include soft-tissue oedema, skin necrosis
and neuropathy [111]. It is noteworthy that aspirating the cystic uid is carried out to aid in
diagnosis, to create space for sclerosants as well
as to increase surface area between the sclerosants and LM wall.
17.6.5.3 Surgery
Surgical choice relies mainly on anatomical location as well as extension of the LM.Additionally,
surgery can be performed in conjunction with
sclerotherapy. Both open and endoscopic
approaches have been performed. In cases of
abdominal LM, laparoscopic approach has been utilised. Complications of surgery include cranial
nerve injury, incomplete resection, scar and
recurrence.
17.6.5.4 Other Modalities
Microcystic LM usually is difcult to manage as
compared to macrocystic. Radiofrequency ablation (RFA) has shown promising results over the
recent years in managing microcystic LM [114,
123]. RFA can be delivered via high-frequency or
low-frequency mode. RFA has proved to reduce
LM within the oral cavity and improve pain,
bleeding and infection [124].
Apart from RFA, other modalities such as carbon dioxide laser and pulsed dye laser can be utilised especially for cutaneous LM.
17.6.5.4.1 Novel Agents
With the advancement of technologies, newer
therapies are resurfacing with promising results.
Recent data has demonstrated that novel oral medications including propranolol, sildenal and sirolimus have been proven to be effective [125–127].
17.7 Cystic Hygroma
Cystic lymphangioma is a congenital malformation which most commonly occurs in infants and
young children. These abnormalities usually
occur in the neck and axillary region, but may
occur in other parts of the body, such as the mediastinum, pelvis, retroperitoneum and solid organs
[128]. It is histologically benign, but it inltrates
deep into the tissue and tends to recur.
These lesions are classied into capillary
lymphangioma, cavernous lymphangioma and
cystic lymphangioma. It appears as a cavernous
lymphangioma when a lymphangioma is conned to fairly dense tissue, such as the tongue. A
17 Paediatric Head andNeck Pathology andSurgery
421
cystic lesion occurs when it develops in the relatively loose fascia of the neck. The cystic hygromas account for around 90% of the
lymphangiomas in the region of the head and
neck [129]. Current literature has revealed that
there is an association between cystic hygroma
and hereditary lymphoedema. The cystic
hygroma can be inherited in autosomal recessive
as well as autosomal dominant similar to lymphoedema, with the latter most likely associated
with a better prognosis [130].
Lymphangiomas are seen as large, cystic
masses on imaging studies. As the rst diagnostic
workup, ultrasound is preferable and can classify
the subtype of lymphangioma and it can assess
the size of the cysts. The characteristics of the
mass, the involvement of critical and vital structures and the extent of the tumour can be evaluated by CT and MRI. These two imaging
modalities can yield an accurate preoperative
evaluation of lymphangiomas and other vascular
lesions [131].
At this juncture, there is no consensus on the
best treatment options for cystic hygroma.
Depending on the size of the lesion, anatomical
localisation and complications, the treatment
should be individualised. Some of the treatment
options include observation, aspiration, injection,
cryotherapy, electrocautery, radiation, laser, ligation and excision. In addition, surgical excision is
reserved for recurrent tumours that persist despite
conservative therapy and the tumour that is
symptomatic.
OK-432 sclerotherapy has become the rstline therapy for cystic lymphangioma in recent
years, and many reports have highlighted about
its usage and therapeutic benet. In polycystic
cases and cases with small cystic areas, however,
it is difcult to achieve a complete response with
OK-432 and it can be occasionally ineffective
[132]. Other proponents have reported that in
properly selected patients affected by lymphangiomas, OK-432 therapy is a safe and effective
option [133].
Of all vascular malformations, the most difcult pathology to eradicate is lymphatic malformations. Their inltrating nature, coupled with
the difculty in distinguishing important head
and neck structures from adjacent normal tissues,
makes it even harder to achieve a complete surgical extirpation [134]. Therefore, the probability
of postsurgical recurrence and complications is
greater than that of other vascular lesions. The
selection of treatment modalities should depend
on the status of patients and the available techniques. In order to obtain the best treatment outcomes, the treatment protocol should be
individualised and comprehensive as well as
sequential [134].
Other treatment options, such as sclerotherapy, have been proposed as an alternative to
reduce the impact and complications of surgery,
and surgical resection remains the best treatment for lymphangiomas. As sclerotherapy
agents, various products have been used, such as
sodium morrhuate, dextrose, tetracycline, doxycycline, bleomycin, ethibloc and OK-432. The
other agents were reported to cause perilesional
brosis in addition to OK-432 and thus to complicate eventual surgical excision [129]. In addition, cervicofacial macrocystic lesions can be
treated with sclerotherapy, whilst laser therapy
is used for supercial mucosal microcystic
lesions [135].
17.7.1 Surgical Treatment
foraRecurrent Cystic
Hygroma: Illustration
ofaCase
A 9-year-old Malay girl has been diagnosed
with cystic hygroma since birth. The tumoural
mass has grown in size over the years, where
it necessitates tracheostomy to relieve airway
obstruction. The patient had multiple sclerotherapies for her tumour but with limited
response. In addition, the patient had a history of surgical resection of residual mass
post sclerotherapy, with evident right marginal mandibular nerve paresis. On follow up, there was recurrent tumour on the same
side, and after multiteam discussion, it was
decided for a re-surgery (Figs. 17.6, 17.7,
17.8, 17.9, 17.10, 17.11, 17.12, 17.13, 17.14,
and 17.15).
422
J. Saniasiaya and N. Mat Lazim
Fig. 17.6 On clinical examination, there was a surgical
scar at the lateral neck due to previous surgery with the
evidence of marginal mandibular nerve paralysis. There
was a submandibular mass at level Ib, rm in consistency,
and measuring 4.0cm × 5.0cm. The tracheostomy tube
was in situ and patent. There was no granulation tissue
around the stoma
Fig. 17.7 Intraoperatively, the same skin incision for
submandibulectomy is used. A subplatysmal skin ap is
raised with caution to preserve the residual marginal mandibular nerve function. There was thick granulation tissue
overlying the mass due to previous surgery
Fig. 17.9 The dissection deepened around the mass,
exposing the mass. The mass is retracted with Allis forceps to facilitate the ligation of the facial artery and vein
Fig. 17.10 Superiorly, the mass extends to the oor of
mouth level, where only small thin mucosa is felt during
dissection deep to the mass, medial to the mandible. The
dissection continues supero-inferiorly and mediallaterally of the mass
Fig. 17.8 The dissection is deepened. The tissue was
brotic and difcult to dissect. The marginal mandibular
nerve cannot be identied since tissues were all whitish
and thickened
Fig. 17.11 The hypoglossal and lingual nerves cannot be
identied due to dense brotic tissues. Anteriorly, the
mylohyoid muscle is adherent and blended to the mass
ab
cd
17 Paediatric Head andNeck Pathology andSurgery
423
Fig. 17.12 The mass is removed in total which measures
7.0cm × 5.0cm. The mass is sutured to orientate the histopathology examination by the pathologist
Fig. 17.13 The wound is closed in two layers; the size 10
drain is secured. The tracheostomy tube is kept in situ
Fig. 17.14 (a–d) Post-operatively at 4months, the appearance of scar is lessened
424
J. Saniasiaya and N. Mat Lazim
e
Fig. 17.15 (e, f) Post-operatively at 8months, the sub-
mandibular swelling has reduced signicantly, the scar
follows the previous old scar and the marginal mandibular
17.8 Lymphoma
Lymphoma constitutes 10–15% of all malignancy in childhood. Lymphoma can be divided
into Hodgkin’s lymphoma and non-Hodgkin’s
lymphoma. It is noteworthy that the most common presentation of HL and NHL in children is
cervical lymphadenopathy.
17.8.1 Hodgkin’s Lymphoma
Hodgkin’s lymphoma (HL) is one of the most
common malignancies accounting for 4% in
children aged between 0 and 14years and 12%
amongst children aged between 15 and 30years
[136]. Male predominance is noted amongst
children under 10years of age, whereas amongst
adolescence there is no gender predilection
[137]. To date, the exact aetiology of HL is still
unknown. Epstein-Barr virus (EBV) has long
been associated with HL. Approximately
40–50% of HL in developed countries has been
linked to EBV.Additionally, HL incidences are
seen amongst certain immunodeciency disorders such as ataxia telangiectasia, WiskottAldrich syndrome as well as Bloom syndrome
[138].
f
nerve remains similar. The patient was happy with surgical treatment outcomes
Histologically, classical HL feature is the
presence of large, multinucleated Reed-Sternberg
cells which are B cell in origin. Additionally,
lymphocytes are present in HL.Histological classication of HL is based on Rye classication:
lymphocytic predominance, mixed cellularity,
lymphocytic depletion and nodular sclerosis
[139].
17.8.2 Non-Hodgkin’s Lymphoma
Non-Hodgkin’s lymphoma (NHL) can be divided
into mature B cell lymphoma (Burkitt lymphoma,
diffuse large B cell lymphoma and primary mediastinal large B cell lymphoma), lymphoblastic
lymphoma of precursor B or T cell and anaplastic
large-cell lymphoma. It is noteworthy that the
incidence of NHL varies according to different
geographic regions [140].
17.8.3 Clinical Presentation ofHL
andNHL
Most common presentation for both HL and NHL
amongst children is cervical lymphadenopathy. It
is important that the presentation of lymph node is
17 Paediatric Head andNeck Pathology andSurgery
425
not taken lightly as persistent adenopathy beyond
2weeks should raise suspicion. In a study by Oguz
etal., 98.2% of chronic adenopathy turned out to
be lymphoma [141]. Head and neck involvement
of lymphoma is between 42% and 60% [142].
Cervical lymph node is affected by lymphoma
almost 66% [142]. As for extranodal involvement, initial manifestation may involve tonsils,
base of tongue and nasopharynx. According to a
study by Roh et al., extranodal involvement of
lymphoma affects 40.5% [142]. Extralymphatic
involvement mainly affects NHL. Weisberger
et al., in their series, found that 4 out of 15
children presented with extralymphatic involvement of lymphoma, which includes maxillary
and ethmoid sinus, mandible, thyroid gland,
parotid and pharynx [143].
Besides that, mediastinal lymphadenopathy
causing lymphoma may lead to superior vena
cava syndrome causing dyspnoea, headache, and
facial and arm swelling. Other symptoms such as
fever, bleeding symptoms and bone pain may
ensue. Adenopathy can be xed and nontender,
and it can involve any lymph node. Additionally,
cutaneous lesion secondary to lymphoma may
occur [144].
17.8.4 Diagnosis
17.8.4.3 Surgery
Tissue biopsy is deemed superior as histological
typing is required for diagnosis as well as treatment plan. In a large mass, excision biopsy can
be performed.
17.8.5 Classication
HL is classied based on Ann Arbor classication system, whilst St. Jude Children’s Research
Hospital staging classication is used for NHL
(Tables 17.4 and 17.5).
17.8.6 Treatment ofHL
HL in children has been associated with excellent
prognosis with a 5-year disease-free survival rate
from 80% to 95%. Poor prognosis indicator
includes presence of B symptoms and bulky
mediastinal lymph node, extranodal extension
and advanced stage of disease (III–IV). Gold
standard treatment is combination of chemoradiotherapy. Various regime protocols have been
developed, which have evolved over the years.
COPP (cyclophosphamide, vincristine (VCR),
procarbazine, prednisone) was initially used for
HL.Then, ABVD (adriamycin, bleomycin, vin-
17.8.4.1 Haematology
Blood investigations including full blood picture,
erythrocyte sedimentation rate, lactate dehydrogenase, ferritin and C-reactive protein are suggestive of lymphoma. Bone marrow aspirate,
biopsy as well as cerebrospinal uid analysis can
determine lymphoma.
17.8.4.2 Imaging
Ultrasonography is the rst line in diagnostic
approach as it is non-invasive and rapid and does
not require sedation. Suspicious lymph node can
be detected via ultrasonography as it detects vascularisation, number, size and anatomical relation. Computed tomography (CT), magnetic
resonance imaging and positron emission tomography (PET) enable staging and treatment plan as
well as follow-up.
Table 17.4 Ann Arbor staging classication of
Hodgkin’s lymphoma
Stage IInvolvement of a single lymph node region (I)
or of a single extralymphatic organ or site
(IE)
Stage IIInvolvement of two or more lymph node
regions on the same side of the diaphragm (II)
or localised involvement of an extralymphatic
organ or site and of one or more lymph node
regions on the same side of the diaphragm
(IIE)
Stage
Involvement of lymph node regions on both
III
sides of the diaphragm (III), which may also
be accompanied by localised involvement of
an extralymphatic organ or site (IIIE) or by
involvement of the spleen (HIS) or both
(HISE)
Stage IVDiffuse or disseminated involvement of one
or more extralymphatic organs or tissues with
or without associated lymph node
enlargement
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J. Saniasiaya and N. Mat Lazim
Table 17.5 St. Jude staging classication system
Stage IA single tumour (extranodal) or single
anatomical area (nodal) with the exclusion of
the mediastinum or abdomen
Stage IIA single tumour (extranodal) with regional
node involvement
Two or more nodal areas on the same side of
the diaphragm
Two single (extranodal) tumours with or
without regional node involvement on the
same side of the diaphragm
A primary gastrointestinal tract tumour,
usually in the ileocecal area with or without
involvement of associated mesenteric nodes
only, grossly completely resected
Stage
Two single tumours (extranodal) on opposite
III
sides of the diaphragm
Two or more nodal areas above and below the
diaphragm
All the primary intrathoracic tumours
(mediastinal, pleural, thymic)
All extensive primary intra-abdominal
disease, unresectable
All paraspinal or epidural tumours, regardless
of other tumour site(s)
Stage IVAny of the above with initial central nervous
system and/or bone marrow involvement
blastine and dacarbazine) became popular
amongst children with localised, early-stage disease. COPP-ABV protocol along with low-dose
radiotherapy was developed to treat children with
advanced stage of disease [145, 146].
17.8.7 Treatment ofNHL
Treatment in children with NHL depends on the
subtypes as the clinical features and molecular
and cellular biology vary [147]. For example,
treatment in children with B-NHL is usually of
short duration and comprises intensive chemotherapy with CPM, high-dose (HD) methotrexate (MTX), cytarabine (ARA-C), doxorubicin,
VCR, etoposide, ifosfamide and corticosteroids
(CTS).
17.8.7.1 Radiation Therapy
Although chemotherapy is the main treatment
modality, radiation therapy plays an important
role in certain subtypes of lymphoma.
17.9 Langerhans Cell Histiocytosis
Langerhans cell histiocytosis (LCH) is regarded
as an uncommon condition that incorporates the
dendritic Langerhans cell [148]. The hallmark of
the disease is the polyclonal proliferation of
Langerhans cells, which are macrophages located
within the dermis [149]. Owing to its aggressive
nature, osteolysis, recalcitrance and propensity to
produce synchronous lesion, it is often confused
with malignancy. Historically, LCH was termed
as eosinophilic granuloma, Hand-ChristianSchuller disease and Letterer-Siwe disease.
However, in a workshop in Philadelphia in 1985,
the term LCH was coined ensuing the histologic
as well as pathologic features of the entity.
17.9.1 Epidemiology
LCH has been reported to affect approximately
5.4 cases per 1 million [149]. This entity has
shown male predilection with peak incidence
affecting children with age ranging from 1 to
4years [150]. Although LCH is regarded as a disease of childhood, cases involving adult patients
have been reported [151]. Approximately 80% of
LCH consists of the head and neck region,
whereby temporal bone involvement is reported
to be between 15% and 60%. Additionally, nearly
4–25% of patients with temporal bone LCH present with otoneurological symptoms [152]. Risk
stratication is classied into three systems:
single- system LCH, low-risk multisystem LCH
and high-risk multisystem.
17.9.2 Pathogenesis
The pathogenesis of LCH is still a conundrum to
date. Over the past decade, myriad hypothesis
regarding the pathogenesis of LCH has emerged
including the most prominent theory: that is,
either a reactive disease or a neoplastic entity
[153]. Spontaneous remission, vast multiple
cytokines by dendritic cells and T cells in LCH