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17.2 Acquired Non-heritable Developmental Pathologies of the OMF
in the absence of prior radiotherapy or tumour metastatic to the jaws. MRONJ occurs in up to
14% of those who have received bisphosphonate (BP) medications. MRONJ presents clinically
with a non- healing mucosal wound and exposed bone at a previous surgical site. Jaw and tooth
pain, swelling and neuropathy can also be present. Associated risk factors include dental surgery
(tooth extractions, implant placement), periodontal or periapical disease and mechanical trauma
(ill- fitting dentures). The drugs that have been associated with MRONJ are BP (i.e. zoledronate,
pamidronate, alendronate, ibandronate, risedronate, clodronate [non- nitrogen containing BP])
and receptor activator of nuclear factor κβ ligand (RANKL) antibody denosumab, both antiresorptive drugs that inhibit osteoclast function. Anti- angiogenic drugs such as bevacizumab
and sunitinib block the formation of new blood vessels by reducing the action of vascular
endothelial growth factor (VEGF) and tyrosine kinases. VEGF appears to have some role in
osteoclast function. The mammalian target of rapamycin (mTOR) inhibitors has also been implicated. While the complete pathogenetic mechanisms remain unclear, invitro studies uniformly
show increased apoptosis and decreased cell proliferation, metabolism and migration of alveolar
osteoblasts, gingival fibroblasts and oral keratinocytes in the presence of BPs. BPs appear to suppress TGF- β and cyclin D activity, interfering ultimately with wound healing and cell prolifera-
tion. Anti- angiogenic drugs downregulate genes essential for bone mineralisation. Speculation
that the mechanical forces involved in the jaw due to mastication promote a higher rate of bone
turnover compared to axial skeletal bones, thus increasing susceptibility to agents that inhibit
osteoclast activity. There appears to be a low prevalence of MRONJ in the paediatric population
where BPs and denosumab have been used increasingly for conditions such as osteogenesis
imperfecta, glucocorticoid- induced osteoporosis, McCune- Albright syndrome and malignant
hypercalcemia(32–35).
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17.2.1.6 FoetalAlcoholSyndrome(FAS)andHemifacialMicrosomia
FAS is the most common teratogen and best- known cause of human developmental disorders.
Children with FAS exhibit several craniofacial dysmorphic features, including small eyelids, flat
philtrum, decreased interpupillary distance and micrognathia. Teeth displacements and impactions often accompany the micrognathia. Ethanol impairs migration of the cranial neural crest
(CNC) cells, perhaps mediated through the Sonic Hedgehog signalling pathway(2, 36).
Hemifacial microsomia and Goldenhar (oculo- auriculo- vertebral) syndrome result from malformation of the first and second pharyngeal arches. Cardiac and central nervous system (CNS) disturbances can also accompany hemifacial microsomia along with vertebral anomalies. In both
cases, disturbed blood flow regionally to these arches is implicated in the pathogenesis.
Development of the upper and lower jaw, outer and middle ear, tongue, palate and teeth can be
impaired(2, 37).
17.2.1.7 CircadianRhythms
A brief mention is the growing interest in investigating transcriptional- translational control of
‘clock’ genes by circadian clock rhythms orchestrated in the hypothalamic suprachiasmatic
nucleus responsive to light. The SCN clock then controls peripheral oscillators or clock genes that
may be more responsive to environmental cues. Emerging evidence shows how the head and
neck, including tooth and salivary gland development, respond to circadian rhythms (38).
Craniofacial tissue cell homeostasis and proliferation, differentiation of salivary gland, oral
epithelium and dental cells are all influenced by circadian control of genetic events. Circadian
rhythm and clock gene expression has been detected in ameloblasts, basal cells of the oral
epithelium, epithelial rests of Malassez, dental pulp and ligament cells and osteoblasts/
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osteoclasts of alveolar bone. All of this leads to control of growth and mineralisation of dental
tissues under the influence of genes, at least in part controlled by circadian rhythms.
17.3 CongenitalNon-acquiredNon-exogenous/Environmental
DevelopmentalDefectsoftheOMF
This section will highlight select developmental lesions of the OMF region that do not have ‘clear’
genetic or environmental causes. As noted throughout, it is likely that many of these pathologies
described here and elsewhere are multifactorial in their pathogenesis, and these categorical distinctions are somewhat arbitrary.
17.3.1 CongenitalNon-solidTumour/Mass-formingLesions
A reasonably comprehensive list and summary of congenital developmental defects of the OMF is
given in Table17.1(39, 40). This list delineates those defects that generally present at or around
birth, do not seem to have a defined known genetic cause yet, and are not typically normal variations seen with some frequency in the population. Although cysts can and do form mass lesions,
they are not solid masses and are benign and included in this table for completeness. Odontogenic
cysts and those generally occurring in the neck or scalp will not be considered here.
17.3.1.1 Non-syndromicOrofacialClefts(OFC)
As is well- known, OFC is the most common craniofacial anomaly, with a reported incidence of 1–2
per 1000live births in caucasian and Asian populations and about 1/2500in Africans. Their origin
is multifactorial with purported genetic and environmental influences, and syndromic associations are clear (e.g. oro- facial- digital, Treacher Collins, DiGeorge, Gorlin–Goltz, Cornelia de Lange,
many others)(41, 42). Their spectrum is broad as they can involve the lip only, palate only, or both
lip and palate and be unilateral, bilateral, complete or incomplete (43). The embryology of the
OMF region, the head and neck (and all organ systems), is very complex under the control of
orchestrated transcriptional control. These details are reviewed elsewhere(41, 42, 44) and in brief,
cleft lip results from failure of fusion of the intermaxillary segment with the maxillary prominences. Cleft palate results ultimately from the failed formation of the secondary palate. Of interest to dental practitioners is the association of OFCs (of any type) with dental anomalies. Multiple
publications and meta- analyses have shown a clear association between OFC and dental anomalies. Overall, these anomalies include agenesis, supernumerary teeth, enamel defects and microdontia/
peg- shaped teeth, with agenesis and supernumerary teeth being the most common. Not surprisingly, anomalies were found more frequently on the side of the cleft, with aplastic teeth seen more
commonly in cleft lip and palate and supernumerary teeth more frequently in patients with cleft
lip(45–48).
17.3.1.2 AbnormalitiesoftheTemporomandibularJoint(TMJ)(MandibularCondyle)
Interestingly, during development, the TMJ develops at a slower pace than other synovial joints
and is not fully developed at birth. A proposed classification of congenital deformities and developmental anomalies of the mandibular condyle divides these into primary hypoplasia/aplasia, secondary hypoplasia, hyperplasia and bifid (rarely trifid) condyle. Primary condylar aplasia and
hyperplasia can occur in syndromic association (Treacher Collins, hemifacial microsomia, Hurler’s
syndrome, Hallerman–Streiff, Goldenhar). Secondary hypoplasia is a result of arrested growth.
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Table17.1 Developmental defects andcysts inthe oral- maxillofacial (OMF) region.
Downloaded from https://onlinelibrary.wiley.com/doi/ by ibrahim ragab - Oregon Health & Science Univer , Wiley Online Library on [07/10/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Defects* Location Description Clinicalassociations
Lip
Double Upper lip
> lower Redundant fold Ascher syndrome
Lip pits
Paramedian Lower lip Invagination Van der Woude syndrome
Commissural Vermillion border Invagination Preauricular pits
Tongue
Macroglossia Diffuse tongue Enlargement Muscle hypertrophy, vascular malformations,
Microglossia (aglossia) Tongue Small or missing OromandibularAnkyloglossia Ventral tongue The short, thick lingual
frenulum
congenital (syndromic) and acquired
limb hypogenesis
Speech, feeding difficulties as neonate
Palate
Lateral soft palate fistula Tonsillar pillar Fistula, tonsillar fossa No true associations
Bone
Coronoid hyperplasia Coronoid process Hyperplasia Usually bilateral M
> F (5:1)
Torus palatinus Palate Exostoses It can be flat, spindle, nodular, lobular
Torus mandibularis Lingual mandible Exostoses Nodular mass of lamellar bone
Stafne defect (static bone cyst,
lingual mandibular salivary
glanddepression
Below mandibular canal of posterior
mandible
Radiolucent defect Usually, normal submandibular gland tissue is
present
(Continued )
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0005802312.INDD 281 09-13-2024 17:51:55
Table17.1 (Continued)
Downloaded from https://onlinelibrary.wiley.com/doi/ by ibrahim ragab - Oregon Health & Science Univer , Wiley Online Library on [07/10/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Cysts Location Description Clinicalassociations
Palatal
Epstein’s pearls Median palatal raphe Small white pearls Squamous epithelium with keratin-
filled
lumen
Bohn’s nodules Over hard palate Small white pearls Same as above
Nasolabial (Klestadt) Upper lip, lateral Elevates nasal ala Lined by pseudostratified columnar
epithelium
Nasopalatine duct Anterior maxilla between central
Remnants in the incisive canal Lined by variable epithelium
incisors
Median palatine Posterior to palatine papilla Expansive radiolucency
midline hard palate
Neurovascular bundles, salivary gland,
cartilage in wall
Epidermoid Skin Follicular infundibulum Stratified squamous with intraluminal keratin
Dermoid Skin, midline Adnexal structures Epidermoid cyst with wall adnexa
Thyroglossal duct Midline neck Remnant of thyroglossal duct Variable lining, sometimes with thyroid
follicles in association
Submandibular duct atresia floor of mouth cyst Floor of mouth or neck mass Epithelial lining as opposed to mucocele/
ranula
* Orofacial clefts, condylar developmental abnormalities, and branchial cleft anomalies are discussed in text and not included in table.
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0005802312.INDD 282 09-13-2024 17:51:55
Common causes are mechanical trauma, infection (of the joint or middle ear) and rheumatoid
arthritis. If bilateral, micrognathia usually results in tooth crowding if severe. Unilateral hypoplasia can result in cross- bite due to continued growth of the contralateral side. Hyperplasia of the
condyle is usually unilateral with poorly understood pathogenesis. The overgrowth on the affected
side can cause cross- bite malocclusion and mandibular prognathism. Rapid chondrogenesis with
ossification is present with the bony trabeculae of the mandibular ramus and body, ultimately
resembling the thickened lamellar bone seen in osteomas(49, 50). A Bifid (double- headed) condyle is usually found incidentally on panoramic radiographs, with a murky pathogenesis. This
condition is usually unilateral. Some have divided bifid condyles into two types: type I, characterised by a shallow groove (condylar notching) and type II, resulting from trauma with two subtypes,
a Y- shaped type from vertical trauma and ones with two separate and anteroposteriorly located
condyles. These type II bifid condyles can have a clinical impact by limiting mobility and subsequent ankylosis(51).
17.3.1.3 BranchialCleftAnomalies(Cyst/Pits/Fistulas/Sinuses)
These are mentioned since they produce external signs (pits, sinus openings, small ‘bumps’) along
the course of the sternocleidomastoid muscle from the ear to the mediastinum and can also have
intraoral/pharyngeal openings. These are somewhat complex embryological developmental anomalies resulting from the persistence of the cervical sinus derived from the first through fourth pharyngeal clefts. These are classified according to anatomic location and based on arch derivation(1–5),
with second cleft anomalies the most frequent (Work Classification). Their development has been
associated somewhat tenuously with a variety of insults during pregnancy, including smoking,
alcohol, Thalidomide, lead and others. Of importance in the oral exam is that second cleft anomalies can have openings in the palatine tonsil, and third cleft anomalies can open in the piriform
sinus of the larynx. Second cleft anomalies that open in the palatine tonsil should be distinguished
from lateral soft palate fistulas. Branchial anomalies (usually multiple or bilateral) can be seen in
association with syndromes, particularly branchio- oto- renal (BOR) and branchio- oculofacial
(BOF)(52–54).
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17.3.1.4 RegionalOdontodysplasia(RO)
RO is an albeit rare developmental anomaly with uncertain aetiology, although, of course, genetic
and environmental factors have been suspected, such as trauma, teratogens, hyperpyrexia during
childhood and local ischemia. RO is characterised by hypoplasia and hypo calcification of dental
hard tissues that affects both primary and secondary teeth and is more common in maxillary teeth,
particularly the left side. The most common clinical signs include yellow–brown discolouration,
delayed tooth eruption with ‘ghost teeth’, and poorly developed tooth buds on radiographical evaluation. Histologically, irregular calcification of dentin is most common, along with hypoplastic and
hypomineralised enamel, irregular dento- enamel junctions and pulpal calcifications(55).
17.3.2 CongenitalBenignandMalignantMass-forming(Tumours)
Again, the goal in this section will be to highlight those tumours and tumour- like lesions that can
or more likely arise in the very young infant or neonate and thus would be considered ‘congenital’.
This is not a comprehensive list, but it covers some prominent entities. While over 90% of oral
lesions, for instance, in infants and children, are benign, the practitioner should be aware that a
not insignificant number of tumours can be malignant and should be included in the differential
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diagnoses. This is crucial since the malignant tumours can often have a very poor prognosis due to
location (incomplete resections due to anatomical considerations), treatment effect and delayed
diagnosis (assuming or treating as a benign entity)(56). This is in sharp contrast to adults, where,
for the most part, tumours are malignant until proven otherwise.
17.3.2.1 BenignTumours
17.3.2.1.1 Heterotopias/Ectopias/Hamartomas/Choristomas
Nowhere else in the body will one find more lesions with the above designations than in the
headand neck. The definitions of ectopia, heterotopia and choristoma reflect tissue or tissue combinations not in the proper location for that or those tissue types. Hamartomas are tissues indigenous to the site but in an abnormal or haphazard configuration. For a more comprehensive
discussion of this perhaps obtuse nomenclature, please see(57). The more common types of
ectopia/heterotopias/choristomas involve thyroid, thymus, neuroglial and salivary gland tissues.
For this segment, the restriction will be to those lesions that involve the OMF, mainly within the
oral cavity. Choristomas of the head and neck containing cartilage, bone, salivary gland, thyroid,
respiratory and gastric/enteric tissue have all been described. Foregut duplication cysts are thought
to arise from the failure of separation of the notochord and foregut and have been reported in the
tongue (lingual choristoma), pharynx and hypopharynx and can cause airway obstruction in neonates. Lingual choristomas have gone by various names, including anterior median lingual cyst,
median lingual cyst, lingual bronchogenic cyst and lingual cyst of foregut origin. Similarly, lingual
cysts lined by gastric or intestinal epithelium have been called enterogenous cysts, gastric mucosal
choristoma, heterotopic gastric mucosal cysts, oral alimentary tract cysts, gastric heterotopia and
enterocytoma. Rarely, intestinal or colonic heterotopias can be present in the oral cavity. Neuroglial
and osseous choristomas have been described in the tongue and can rarely become infected. A
lingual choristoma is shown in Figure17.1a–c. The tongue is a not uncommon site for hamartomatous lesions. In a recent review by Krieger etal. spanning 19 years, hamartomatous lesions of the
tongue were the third most common lesion, representing 13% of tongue lesions behind vascular/
lymphatic and mucus extravasation phenomenon (mucocele, ranula). Fifteen of eighteen (83%)
patients with tongue hamartomas were presented for excision of the lesion within the first two
years of life, 8/18 (44%) were known to be present since birth and 4/18 (22%) were associated with
oral- facial- digital syndrome (OFDS). Microscopically, these lesions exhibited a variety of tissue
types, including smooth muscle, adipose tissue, vessels, nerves and salivary glands. Rarely hair
follicles, cartilage and sebaceous glands were present, bringing into question whether these lesions
were choristomatous (dermoids). Most of the lesions examined in this series contained some
admixture of smooth muscle and adipose tissue, with one tissue type predominating(57–61).
17.3.2.1.2 Vascular Lesions
As a group, vascular anomalies are among the most common congenital lesions in infants and
children. The head and neck, including the intraoral, are a frequent site for the presentation of
International Society for the Study of Vascular Anomalies (ISSVA) classification system as
tumours or malformations, with tumours representing true neoplastic proliferation while malformations are developmental aberrations. The most common vascular tumours in children are
infantile haemangioma, congenital haemangioma, pyogenic granuloma and kaposiform
haemangioendothelioma (KHE)(63–65). Vascular malformations can come in various flavours;
low- flow lesions (venous, lymphatic, venolymphatic) and high- flow lesions (arteriovenous
malformation and fistula and arterial aneurysm/ectasia/stenosis). Haemangiomas, vascular
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(a) (b) (c)
(d)
SQ
(g)
GM
CIL
(e)
VEN
(h) (i)
(j) (k) (l)
PAN
(f)
Figure17.1 (a–l) Lingual choristomas. (a) large dilated cystic space lined by a variety of epithelium (HE,20×)
in the floor of the mouth of a seven- day- old. (b, c) Another lingual choristoma diagnosed as a teratoid cyst in
the floor of the mouth of a 10- month- old. One portion of the cyst was lined by squamous epithelium with
adnexal structures in the wall consisting of sebaceous and hair elements (HE, 100×). (c) Another separate area
of the cyst was highlighted by closely apposed types of epithelium, including squamous (SQ), gastric foveolar
(GM) and ciliated (CIL) (HE, 100×). (d) Infantile hemangioma in the left floor of the mouth of a five- month- old
female showing tightly packed small capillary spaces lined by endothelium with surrounding pericytes
(HE, 100×). (e) Venous malformation in the base of the tongue of a six- week- old. A large ectatic smooth
muscle- lined vascular channel is directly beneath the squamous epithelium (HE, 40×). (f, g) Congenital
granular cell tumour presenting as a polypoid mass on the maxillary alveolus of a newborn just beneath the
squamous epithelium (HE, 40×). The mass was uniformly composed of large cells with small indistinct nuclei
and abundant finely granular cytoplasm within a variably vascularised stroma (PAS, 200×). (h, i) Melanotic
Neuroectodermal Tumour of Infancy (MNTI) presenting as a maxillary mass in a seven- month- old: Low
magnification view shows a somewhat haphazard arrangement of blue cells in a nested pattern (HE, 40×).
(i) Higher magnification view shows cells containing melanin pigment (right) and neuroblastic cells (left)
(HE, 400×). (j) Cervical teratoma presenting in a newborn demonstrating larger dilated ectatic cystic spaces
lined by the epithelium of endodermal derivation with islands of pancreatic tissue interspersed between
them (centre (PAN)) amidst a smooth muscle stroma (HE,40×). (k, l) Representative photomicrographs of
alveolar and embryonal rhabdomyosarcomas, respectively. The alveolar rhabdomyosarcoma comprises
pleomorphic ‘blue’ cells that form more solid nests and intercalate through the skeletal muscle (HE, 200×).
The embryonal rhabdomyosarcoma morphologically is highlighted by sheets of ovoid to spindled cells that,
in some areas have a vague fascicular microarchitecture amidst a myxoid background (HE, 100×).
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malformations and KHE can all present at birth. Approximately 25–30% of vascular malformations
in children can present on the lip or in the oral cavity and are predominantly of the venous and
lymphatic types. Haemangiomas can involve the lip, tongue, buccal mucosa and palate and are
classified as infantile or congenital. Infantile haemangiomas (Figure17.1d) are present at birth or
shortly after, grow rapidly and then involute over years. Pathologically, their diagnosis is confirmed by diffuse endothelial expression of GLUT1. Congenital haemangiomas present at birth
and may rapidly involute (congenital haemangioma, rapidly involuting congenital haemangioma
(RICH) or not involute (non- involuting congenital haemangioma, NICH) and are GLUT1negative. While both haemangiomas and malformations may be present at birth, their manifestation
and diagnosis may be considerably delayed due to location and size. Both haemangiomas and
vascular malformations (Figure17.1e) can present as coloured masses (raspberry or blue), with
rare cases causing airway obstruction and feeding difficulties. Arteriovenous malformations are
relatively uncommon in the head and neck and rare in the oral cavity (63,64,66,67). Treatment
for haemangiomas is mostly ‘wait and see’. Propranolol has been used to shrink haemangiomas
by decreasing endothelial cell proliferation. Sclerotherapy has been the mainstay for venous and
lymphatic malformations of clinical significance(68). KHE is a vascular neoplasm typically presenting in infants and children currently classified as a neoplasm of intermediate biological
potential between haemangioma and angiosarcoma. Less than 10 cases have been reported in the
oral cavity, with locations in the posterior mandible, tongue, palate and tonsil. Pathologically,
these tumours show a proliferation of spindle to ovoid cells resembling Kaposi’s sarcoma. The
vascular channels can be slit- like and staghorn, with both capillary and lymphangiomatous
regions lined by hobnail endothelium. These tumours express CD31 and CD34 but not D2- 40
(lymphatic marker), but can express PROX1(69, 70).
17.3.2.1.3 Congenital Granular Cell Tumour (Congenital Epulis)
Congenital granular cell tumour (CGCT) is yet another lesion that presents in newborns as an oral
mass that can cause airway obstruction and respiratory distress. It occurs two to three times as
often on the maxillary alveolar ridge and has a distinctly female predilection (8–10:1). Most lesions
are solitary and usually less than two centimetres. Histologically, the lesion comprises tightly
packed large cells with small, dark, indistinct nuclei and a granular, slightly eosinophilic cytoplasm (Figure17.1f,g). Their distinction from granular cell tumours elsewhere lies in their universal lack of staining for S100 protein210. CGCT and other granular cell tumours are invariably
positive for vimentin, PGP9.5 and NKI/C3. CGCT is negative for S100, CD68 (KP- 1 and PGM- 1),
inhibin and NGFR/p75. An occasional CGCT is positive for calretinin. In contrast, granular cell
tumours elsewhere, including the oral cavity in older children and adults, show diffuse positivity
for S100, NGFR/p75 and inhibin. CGCT are cured by excision without recurrence. Many cell types
have been proposed inconclusively as the histogenetic origin for CGCT, including histiocytes,
primitive mesenchymal cells, epithelial cells and pericytes(61).
17.3.2.1.4 Melanotic Neuroectodermal Tumour ofInfancy (Melanotic Progonoma, Retinal Anlage
Tumour,Melanotic Ameloblastoma, Melanotic Epithelial Odontoma, Pigmented Epulis)
These tumours likely have neural crest derivation based on ultrastructure, secretion of vanilmandelic acid and expression of melanotransferrin. More than 80% of cases occur in the head and neck
area, typically the anterior maxilla (70%) presenting in the first year of life. The tumours show dual
morphology with a population of small neuroblastic cells and larger melanin- containing epithelial
cells within a dense fibrovascular stroma (Figure 17.1h,i). The larger epithelial cells express
cytokeratin, vimentin and HMB- 45. Neuroblastic cells can express synaptophysin, glial fibrillary
acidic protein (GFAP) and desmin focally. Tumours are generally negative for chromogranin and
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S100. The 15–20% recurrence rates are usually noted within the first year after surgery. Rare cases
have behaved in a malignant fashion with local and widespread metastases(61).
17.3.2.1.5 Teratomas
Teratomas are the most common germ cell tumour in the paediatric age group. Head/neck teratomas
account for about 12% of all teratomas with the nasopharynx, oral cavity, orbit, neck and thyroid
sites outside the central nervous system. Histologically, they should contain derivatives of all three
germ layers: ectoderm, mesoderm and endoderm. They can be cystic or have both solid and cystic
components and mature and immature components (typically neuroectodermal or neuroepithelial)
(Figure17.1j). In contrast to adolescents and adults, the presence of immature components has no
appreciable prognostic significance. Compared to other anatomical locations of teratomas, yolk
sac (endodermal sinus tumour) elements are uncommon in young children’s head and neck teratomas. In this region in children, teratomas generally behave in a benign fashion with complete
surgical removal. However, because of their location and potentially large size at birth, airway
compromise can occur, particularly for those lesions in the oral cavity and cervicothyroid region. If
known prenatally, delivery may need to proceed using the EXIT procedure. Pure teratomas of infancy
and childhood do not show loss of chromosomes 1p and 6q, as seen in yolk sac tumours in this age
group(57, 61).
17.3.2.2 MalignantCongenitalTumours
17.3.2.2.1 Rhabdomyosarcoma (RMS)
RMS is a malignant soft tissue tumour of skeletal muscle ontogenesis that occurs predominantly
in the paediatric population and is in the group of paediatric malignant tumours known as ‘small
round blue cell tumours’ (SRBCT); somewhat of a misnomer since often the cells are not ‘small’ in
comparison to normal cells and usually not ‘round’. Anyway, other tumours in this group can
rarely present in the head and neck in neonates including Ewing sarcoma/primitive neuroectodermal tumour, neuroblastoma as well as malignant rhabdoid tumour (not classically lumped in
SRBCTs)(71, 72). RMS is singled out briefly for several reasons as a non- heritable developmental
lesion in the OMF: (i) While RMS can have specific genetic alterations associated with it and thus
‘heritable’ (germline DICER1mutations in uterine cervix embryonal RMS, t(1:13) [PAX3- FOXO1]
and t(2:13) [PAX&- FOXO1] in alveolar RMS), other subtypes do not (pleomorphic RMS). (ii) The
head and neck region, by far, is the most frequent site of involvement of RMS. (iii) It is in the differential diagnosis with hemangioma, vascular malformations and lymphadenopathy, benign
mimickers. (iv) We have already reviewed the dental abnormalities that can occur in patients posttherapy for head and neck RMS. This is the largest group of childhood survivors of a malignant
tumour with dental abnormalities related to the therapy. In the head and neck, RMS is divided
broadly into orbital, para meningeal (pterygopalatine and infratemporal fossae) and non- orbital,
non- para meningeal sites of involvement, probably based on prognosis since orbital and para
meningeal RMS have a worse prognosis compared to non- orbital, non- para meningeal. About 65%
of head and neck RMS arise in the middle ear, nasopharynx and orbit, while 10–12% arise in the
oral cavity; the tongue (most common), palate and cheek are the most common sites. About 0.4%
of RMS patients present at less than one month of age (neonatal period) and 5% at less than one
year of age. This group’s prognosis is poorer due to delayed diagnosis, treatment effect and PAX3FOXO1 translocation(72, 73). This author has personal experience with the diagnosis and treatment of a neonate presenting with orbital alveolar RMS and can attest to the poor prognosis in this
age group, mainly due to treatment effects. By the 2022World Health Organization (WHO) classification, RMS has four histological subtypes; alveolar (Figure17.1k), embryonal (Figure17.1l),
pleomorphic and spindle/sclerosing(74).
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17.4 Summary
This chapter provides an insightful overview of select pathologies of the OMF complex, emphasising conditions that seemingly lack a specific genetic or heritable basis. Despite the limitations
imposed by space constraints, the discussion strives to cover significant pathologies within the
current literature’s scope, acknowledging that certain conditions could be explored more extensively. This section delineates a clear boundary by excluding well- defined genetic mutations or
syndromic associations, focusing instead on developmental aberrations and congenital tumours. It
brings to light the complexity of craniofacial development and the multifactorial nature of head
and neck pathologies, which may result from environmental factors interacting with a cascade of
molecular interactions. The practitioner should know how common conditions, medications and
cancer- related therapies can affect the developing OMF complex, particularly the tooth organ. The
review emphasises that most craniofacial developmental anomalies are diagnosed through clinical
examination, including radiographically rather than microscopic analysis. However, most masses
and tumours presenting in the OMF region, particularly the oral cavity, will require excision and
pathological diagnosis. In toto, the chapter attempts to navigate through the nuanced classifications of OMF pathologies, recognising the intricate interplay between genetics, environment and
development in the craniofacial region.
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