Pathology of the Head and Neck

178 S. Regauer6sphenopalatine foramen with extension to the uppermedial pterygoid plate [118]. Nasopharyngeal angiofibromasare unencapsulated, lobulated, firm, grey totan tumours. Abnormal blood vessels of different sizesand irregular architecture in arbitrary arrangement areembedded in a myofibroblastic stroma. The proportionsof both components can vary considerably (Fig. 6.3).The vascular component can be divided into small sinusoidalvessels and large muscular vessels with irregularand incomplete smooth muscle layers with abrupttransitions from a muscular coat to an endothelial celllining only. Irrespective of their architecture, all vesselsare lined with a continuous layer of single regular endothelialcells. The stromal component varies in amountand cellularity. The majority of stromal fibroblasts areplump and stellate, others assume an elongated spindledconfiguration. Mitoses are inconspicuous. The majorityof stromal cells react with vimentin only, while a subpopulationis characterised by co-expression of vimentinand smooth muscle actin.Despite the body of literature, there is still uncertaintyabout the aetiology of nasopharyngeal angiofibromas.They have been called haemangioma and vascular hamartomaarising from ectopic vascular tissue of the inferiorturbinate. Other theories have included overgrowthof paraganglionic tissue, hyperplasia in response to allergicstimulus, fibromatosis, teratoma arising from theoccipital plate, but also an androgen-dependent neoplasticprocess due to an imbalance of the pituitary–androgenitalsystem [9]. A concomitant presentation of nasopharyngealangiofibromas and the familial adenomatouspolyposis syndrome has been reported in 4 out of825 patients at the Johns Hopkins’ Registry for familialcolonic polyposis [47, 62]. A mutation in the APC gene,however, was not demonstrated in 9 patients with nasopharyngealangiofibroma, and a comparative genomichybridisation study describes a normal chromosome5 in 3 patients with nasopharyngeal angiofibroma [70,170]. The same study reports gains on chromosome 8at the site of the genes for TGF-ß inducible early growthresponse and LYN (v-yes-1 Yamaguchi sarcoma viral-relatedoncogene homologue), and on chromosome 6, onwhich the gene for the vascular endothelial growth factoris located [170]. The additional complex gains on theX chromosome and losses on the Y chromosome may explainthe exclusive occurrence in male patients. The interpretationof nasopharyngeal angiofibromas as a vascularmalformation has proved to be the most consistenttheory over the past few decades. A recent publicationproposes that nasopharyngeal angiofibromas arise froman embryological vascular remnant of the first pharyngealarch artery, which normally regresses to a vascularplexus, giving rise to the maxillary artery [75, 153, 171].Incomplete involution leaves behind vascular remnantsin the lateral nasal wall in the area of the sphenopalatineforamen from where nasopharyngeal angiofibromasoriginate. This theory explains the abnormal vascularstructures and the complex anatomical extensionsof nasopharyngeal angiofibromas. The growth stimulationduring puberty and the restriction to males remainunexplained by this theory, however. Treatment of nasopharyngealangiofibromas is surgical after embolisation,although radiation therapy and hormonal therapyhave been used extensively in the past [15, 37]. Nasopharyngealangiofibromas have no malignant potential, exceptfor radiation-related malignant transformation.6.2.4.2 Respiratory EpithelialAdenomatoid HamartomaRespiratory epithelial adenomatoid hamartoma (or polypoidhamartomas) typically arises within the nasal cavityand paranasal sinuses (see also Chap. 2), but has alsobeen reported in the nasopharynx [199]. Patients areadults with an age range of 24–81 years. The polypoidexophytic hamartomas are rubbery, tan to brown andcan reach up to 6 cm in size. They are lined with ciliatedrespiratory epithelium with mucin-secreting gobletcells. The widely spaced glandular proliferations arisefrom invagination of the surface epithelium. A thickeosinophilic basement membrane surrounds the glandsand surface epithelium. The ample stroma may be oedematousand well-vascularised or fibrous with varyingamounts of lymphocytes and inflammatory cells(Fig. 6.4). Glandular acinar proliferations may be scantand large cysts may predominate when the fibrous stromapredominates [206]. Some nasopharyngeal hamartomasinclude a chondro-osseous component and cystslined with squamous epithelium. Due to overgrowth ofa single mesenchymal element, respiratory epithelialadenomatoid hamartomas may resemble fibromas, lipomasor chondromas [199]. Treatment of choice is surgery.The differential diagnoses of respiratory epithelialadenomatoid hamartoma include inverted papillomaand adenocarcinoma. The presence of excess glands andthe respiratory epithelium distinguish the hamartomareadily from an inverted papilloma. The lack of malignantcytological and histological features and invasiondistinguishes the respiratory epithelial adenomatoidhamartoma from an adenocarcinoma.6.2.4.3 NasopharyngealInverted PapillomaICD-O:8121/1Inverted papillomas (or Schneiderian papillomas) arisingoutside the sinonasal tract are extremely rare. Onepublication reported 15 pharyngeal inverted papillomas,11 of which arose in the nasopharynx [183]. The pink orgrey firm polyps had a convoluted surface, which cor-