Developmental Diseases

OVERVIEW (MIND)

• METABOLIC– INBORN ERRORS– HORMONAL– NUTRITIONAL

• INFLAMMATORY– INFECTIONS– REACTIVE PROLIFERATIONS

• NEOPLASTIC• DEVELOPMENTAL

– CYSTS– FACIAL SYNDROMES

Developmental Soft Tissue Diseases• Genokeratoses• Fissured Tongue• Crenated Tongue• Hairy Tongue• Macroglossia• Fordyce Granules• Congenital pits

– Lip pits– Commissural pits

• Soft tissue cysts– Cyst of the Incisive Papilla– Gingival Cysts– Nasolabial Cyst– Sebaceous Cyst– Thyroglossal Duct Cyst– Branchial Cleft Cyst

Genokeratoses (Genetic White Lesions)• Leukoedema

• White Sponge Nevus

• Hereditary Benign Intraepithelial Dyskeratosis

• Keratosis Follicularis

• Pachyonichia Congenita

• Incontinentia Pigmenti

• Dyskeratosis Congenita

Leukoedema

• Diffuse white lesions bilaterally in the buccal mucosa

• A normal finding among individuals with dark skin

• Stretching of the mucosa causes the whiteness to disappear

• Innocuous finding, no treatment

Leukoedema

White Sponge Nevus (Cannon’s Disease)

• Begins in early childhood• Autosomal Dominant, mutations in cytokeratins 4

and 13• Diffuse white lesions, bilateral, buccal mucosa

and lips• Also affects anal canal and vagina• Microscopic: Parakeratosis with acanthosis and

individual cell keratinization• Benign condition, not precancerous• No Treatment

White Sponge Nevus

White Sponge Nevus

Hereditary Benign Intraepithelial Dyskeratosis (HBID)

• Also known as “Red Eye”• A condition restricted to a racial isolate group in the

Carolinas• Hereditary disorder of keratinization in mucous

membranes> duplication of chromosomes 4q35• White lesions of the buccal mucosa and lips, bilateral• Ocular lesions with keratosis and erythema of conjuntiva,

severity varies with seasons• Microscopic: Keratosis with extensive dyskeratosis

(individual cell keratinization)• No Treatment, not precancerous

Keratosis Follicularis• Darier-White Disease• Autosomal dominant disease of skin with mucosal

involvement. A defect in keratinization• Keratotic yellow papules and white keratoses of the skin• Oral lesions are white and pebbly (cobblestone

appearance)• Microscopic: Keratosis with villous rete pegs exhibiting

suprabasilar clefting. Extensive dyskeratosis (corps ronds – cell within a cell; grains – keratinized spinous layer cells with pycnotic nuclei

• Tx: Vitamin A, Retinoids• Variants:

– Focal Acantholyic Dyskeratosis (Grover’s disease)• Very minor form with just a few lesions, skin and mucosa

– Warty Dyskeratoma• A focal lesion with same histology as keratosis follicularis

Keratosis Follicularis

Corps rond“cell withina cell”

Pachyonychia Congenita (Bloch Sulzberger Syndrome)

• An autosomal dominant defect in keratinization localized to the nails and oral mucosa

• Type I: mutations in cytokeratins 6a, 6b, 16; Type II: mutation in cytokeratin 17

• Pachyonychia > marked keratinized tickening of finger and toe nails

• Focal white lesions of oral mucosa• Nails are often removed surgically

Pachyonichia Congenita

Incontinentia Pigmenti• X linked dominant, lethal for males• Mutation in NEMO ( NFkappa B essential

modulator gene) interferes with NFkappa B signal transduction.

• Cutaneous diffuse pigmentations, verrucoid white lesions, vesicles, alopecia, hypodontia, microdontia, delayed eruption, oral white lesions, nail dystrophy, CNS deficits

Incontinentia Pigmenti

Dyskeratosis Congenita• A genetic defect in telomere regulation• Inherited as 1. autosomal dominant with

mutation in TERC; 2. X-linked recessive with mutation in DKCI a gene that encodes dyskerin. Both are involved with telomerase complex and result in telomere shortening

• Myelodysplastic disease with bone marrow aplasia, oral leukoplakias that progress to SCCA as well as cancers of other organs, premature ageing, skin and nail lesions

Dyskeratosis Congenita

Diffuse petechiae

Hereditary Hemorrhagic Telangiectasia

• Autosomal dominantly inherited disorder • Defect in vascular wall integrety• Mutations in ALK1 and ENG (endoglin) on

chromosomes 9q34.1 and 12q31• Formation of focal vascular dilations, particularly

in mucous membranes, and AV malformations• Petechial like lesions in nasal cavity, oral

mucosa and GI tract mucosa• Epistaxis, GI bleeds• No treatment known

Hereditary Hemorrhagic Telangiectasia

Peutz Jegher Syndrome

• Autosomal Dominant, mutations in the STK11/LKB1 gene

• Intestinal Polyposis Syndrome• Most are hyperplastic polyps without a tendency

for malignant transformation• Oral Manifestations: Perioral melanotic macules

(ephilides)• Palmar and digital pigmented macules

Peutz Jegher Syndrome

Fissured tongueSeen at any age, may collect bacteria with mild pain

Crenated Tongue• Lateral border indentations

from dentition• Macroglossia

Also noteCentral fissure

Fordyce Granules – ectopic oral sebaceous glands

Minute yellowish papules

Congenital Pits• Epithelial lined, blind

invaginations

Commissural pits

Benign Migratory Glossitis

Erythema Migrans

Ankyloglossia

Hairy Tongue

Hairy TongueHyperplasia of the filiform papilla, etiology unknown. The

dorsal tongue is hairy in appearance and may be pigmented yellow, brown or black depending on food, liquid intake

Median Rhomboid Glossitis

• Smooth, flat or raised and nodular• Not seen in infants or young children• Midline location at junction of middle and

posterior third of dorsal tongue• Lesion of unknown etiology, or a Candida

infection?

Median Rhomboid Glossitis

Lingual Thyroid Nodule• The thyroid analagen invaginates at the foramen ceacum

at the posterior third of the tongue (apex of circumvallate papillae)

• The thyroglossal tract invaginates to below the hyoid bone to the paralaryngeal region and differentiates into the thyroid gland.

• Sometimes the tract fails to descend and the thyroid gland develops within the connective tissues of the posterior dorsal tongue

• An Iodine 131 scan will reveal the presence of the ectopic tissue

• Surgical removal would result in hypothyroidism

Lingual Thyroid Nodule

I131 uptake

Macroglossia• Generalized:

Cretinism(congenital hypothyroidism), Amyloidosis

• Unilateral: Hemifacial Hypertrophy

Soft Tissue Developmental Cysts

• Odontogenic (see section on Odontogenic cysts)

• Cyst of the incisive papilla• Nasolabial cyst• Sialocyst• Sebaceous cyst• Thyroglossal tract (duct) cyst• Branchial cleft cyst

Cyst of the Incisive PapillaSoft tissue cyst from epithelial remnants of the incisive canal. Lined soft tissue counterpart to the incisive canal

cyst.

Gingival Cyst of the AdultA cyst derived from the rests of Serres in the gingiva, typically in the mandibular premolar/cuspid region. Most are nonkeratinized SSE,

rarely they are peripheral odontogenic keratocysts

Peripheral odontogenic keratocyst

Nasolabial Cyst• A rare cyst theorized to arise from embryonic

remnants of facial process fusion• Adults, no sex predilection• Fluctuant swelling of the upper lip, elevated the

ala of the nose• Microscopic: Lined by columnar epithelium,

often with cilia• Tx: local excision/enucleation• Does not tend to recur

Nasolabial Cyst

Sialocyst (Mucous Retention Cyst)• A cyst of the oral mucosal tissues derived from

salivary duct epithelium. Some may represent obstructed dilated ducts

• Older adults• Lips and buccal mucosa most common sites• Elevated fluctuant mass, often bluish in color

that resembles a mucocele• Microscopic: lined columnar epithelium, mucous

metaplasia is common, some show oncocytic change and yet others have intraluminal papillary projections

• Tx: Enucleation

Mucous Retention Cyst

Sebaceous Cyst of SkinDermal keratinizing cyst derived from sebaceous gland ducts found on

skin, common on face, neck and salp

Thyroglossal Duct Cyst• A cyst derived from remnants of the thyroglossal

tract, the thyroid analagen• Located at the fexure of the skin in the midline

just above the largynx. The cyst often wraps around the hyoid bone.

• Lined by psuedostratified columnar epithelium, may see thyroid follicles in the cyst wall

• Surgical excision may be complicated by association with hyoid bone.

Thyroglossal Duct Cyst

Branchial Cleft Cyst• A cyst derived from epithelial remnants of the

branchial arch/cleft complex or possible ectopic salivary ductal tissue within a cervical lymph node

• A fluctuant mass in the lateral neck below the angle of the mandible

• Microscopic: Lymphoid tissue with germinal centers surrounding a SSE lined cyst

• Rare cases have undergone malignant transformation: “Branchogenic Carcinoma”. Most such cases turn out to be metastatic carcinoma that has undergone cystic change within a lymph node.

• Tx: simple excision/enucleation

Branchial Cleft Cyst

Continue on with hard tissue developmental diseases