Review of Pediatric Head and Neck Neoplasms that Raise the Possibility of a Cancer Predisposition Syndrome

Abstract

Cancer predisposition syndromes (CPS) are generally heritable conditions that predispose individuals to develop cancer at a higher rate and younger age than their representative general population. They are a significant cause of cancer related morbidity and mortality in the pediatric population. Therefore, recognition of lesions that may be associated with a CPS and alerting the clinicians to its implications is a crucial task for a diagnostic pathologist. In this review we discuss benign pediatric head and neck lesions associated with CPS namely: odontogenic keratocyst, juvenile nasopharyngeal angiofibroma, ossifying fibroma of the jaw, paraganglioma, plexiform neurofibroma, plexiform schwannoma, mucosal neuroma, and nevus sebaceous syndrome; along with malignant tumors such as squamous cell carcinoma. Several head and neck melanocytic, endocrine, and central nervous system tumors can also be associated with CPS; they are beyond the scope of this article. Nasal chondromesenchymal hamartoma is discussed elsewhere in this issue.

Keywords: Benign; Cancer; Children; Malignant; Mandible; Maxilla; Oral; Syndrome.

Fig. 1

Odontogenic keratocyst in an 8 year old boy presenting with unerupted tooth and lower jaw pain; and also had a history of craniosynostosis and macrocephaly. a Multiloculated cystic neoplasm is seen with mild to moderate lymphocytic inflammation in the cyst wall. (H&E, 40x). b Cyst wall is lined by a relatively flat stratified squamous epithelium (H&E, 200x) that shows a corrugated, undulating or wavy surface (inset, arrow). (H&E, 400x)

Fig. 2

Juvenile nasopharyngeal angiofibroma in a 14 year old boy. a Low power view shows fibrovascular stroma with slit-like to ectatic blood vessels, some of which display a staghorn configuration. (H&E, 40x) b Poorly developed perivascular myoid cells (arrows) give impression of a muscular layer. (H&E, 100x). c Ovoid, plump spindled cells within the fibrous stroma lack significant cytologic atypia. (H&E, 400x). d Beta-catenin immunohistochemistry shows nuclear positivity. (400x)

Fig. 3

Juvenile ossifying fibroma of the right maxilla in an 11 year old boy. a Low power view shows lesion with peripheral mature lamellar bone (arrow) and central cellular fibro osseous component (*). (H&E, 40x). b Central portion of the lesion shows bland fibrous stroma (*) and woven bone with abundant reactive osteoblasts (arrow) (H&E, 200x)

Fig. 4

a Paraganglioma of the carotid body in a 12 year old girl. Large polygonal cells with abundant eosinophilic cytoplasm and central round nuclei are seen in Zellballen pattern. (H&E 100X). b Abrupt bizarre or anaplastic nuclei with pleomorphism is common (H&E 200X). c Tumors are richly vascular with frequent intratumoral acute and remote hemorrhage. (H&E, 200x)

Fig. 5

Plexiform neurofibroma involving the eyelid in a 4 year old girl. a Low power view demonstrates multinodular configuration. (H&E, 40x) b, c Nodules are composed of hypocellular, myxoid stroma containing Schwann cells, fibroblasts and mast cells (arrows). (H&E, 100x and 200x)

Fig. 6

Plexiform schwannoma in a 17 year old girl. a Sub-epidermal multinodular tumor is seen (H&E, 20x) with hypo and hypercellular areas of bland spindle cells in a somewhat fibrillary matrix. (inset, H&E, 200x), b Immunostain for S-100 shows diffuse reactivity. (20x)

Fig. 7

Mucosal neuroma involving the tongue in a 10 year old girl. Uneven, papillomatous and hyperkeratotic squamous mucosa overlying the lesion. Lesion is sub-epithelial and composed of disorganized bundles of neural tissue. (H&E, 40x) Photomicrograph courtesy of Dr. John Hicks, MD PhD

Fig. 8

Nevus sebaceous in an 8 month old infant (panels a, b) and a 13 year old boy (panels c, d). a Low power view of a skin excision showing non-lesional epidermis (thick arrow) adjacent to a papillomatous lesion (arrow head). Lesional dermis shows malformed and aborted hair follicles (*) that do not reach the underlying fat, in comparison to the adjacent normal ones (thin arrow). (H&E, 20x). b An area marked in panel a, under medium power, shows an acanthotic epidermis with proliferation of hair follicle cells. Sebaceous glands are not seen. (H&E, 100x). c Low power view of a skin excision showing non-lesional epidermis (thick arrow) adjacent to a papillomatous lesion (thin arrow). Lesional dermis shows prominent, malformed and aborted pilosebaceous units. (H&E, 20x). d An area marked in panel c, under medium power, shows a hyperplastic sebaceous gland with mature hair follicle and a shaft. (H&E, 100x)