Tumour of the = Ear,Nose, Throat

Tumors=20 of the Ear, Nose, Throat

V=20 Srinivas & Bhaskar Mukherjee, Army RR Hospital New=20 Delhi

Evidence=20 of head and neck carcinomas has been found in ancient skulls. Some = historians=20 speculate that there may have been a high incidence of nasopharyngeal = cancer=20 in some ancient population because of the inhalation of wood smoke = in poorly=20 ventilated huts.

Head=20 and Neck Cancer-More=20 that 90% of cancers of the head and neck are squamous cell carcinomas = (SCCs) or=20 one of its variants, including lymphoepithelioma, spindle cell = carcinoma,=20 primarily involving the nasopharynx, oral cavity osopharynx, and = larynx=20 Metastatic lymph node involvement is the most important prognostic = factor=20 affecting patient survival.Imaging modalities have improved the = diagnostic=20 accuracy of Head and Neck cancers. PET helps in localizing unknown = primary=20 lesions (1,2) Combined PET/CT increases the accuracy of PET = interpretations.=20 Etiologic agents associated with various degrees of risk in the = development of=20 SCC of the head and neck include use of tobacco or alcohol:age: genetic=20 predisposition:nutritional status:chronic irritation; exposure to = industrial=20 products or heavy metal (e.g.) asbestos), ionizing radiation, or = viruses. In the=20 arena of head and neck cancer, EBV and human papilloma virus (HPV) are = both=20 prominent. These etiologic agents are, however, of limited predictive = value in=20 any given individual.

Ear-The=20 large variety of epithelial tumours of the ear-external, middle, = internal-are=20 rare save for basal cell or SCCs of the pinna (external ear). These = carcinomas=20 tend to occur in elderly men and are thought to be associated with = actinic=20 radiation. The tumours within the anal tend to be SCCs, occur in middle = aged to=20 elderly women and are not associated with sun exposure. Neither the = basal cell=20 nor the SCCs of the pinna extend beyond local invasion. However the = SCCs,=20 arising in the external canal may invade the cranial cavity or = metastasize to=20 regional lymph nodes.

External=20 Ear

Benign=20 tumors

● =20 Squamous papillomas: = present as=20 branching polypoid structures in the external auditory=20 canal.

● =20 Other benign tumours = involving the=20 external ear are adnexal tumours commonly pilomatrixoma, ceruminomas,=20 pleomorphic adenoma and syringocystadenoma papilliferum nevi: osteomas = are also=20 occasionally encountered here.

Malignant=20 tumors

● =20 Basal cell carcinoma: is a common tumour of the = auricle=20 and external auditory canal. In the auricle, BCC predominates over=20 SCC.

● =20 Squamous cell carcinoma: The=20 tumours are more common in the auricle (particularly the helix) than in = the=20 canal. They are the = convential SCC,=20 pseudo-glandular, verrucous or sarcomatoid type.

● =20 Malignant melanomas: of the=20 external ear comprise about 10% of all melanomas of the head and neck=20 region. Nearly all are = located in=20 the auricle rather than the canal.

● = Other=20 malignant tumours:=20 involving the external ear are adenocarcinoma, adenoid cystic = caracinoma,=20 rhabdomyosarcoma, myxoid chondrosarcomas.

Middle=20 and inner ear

Benign=20 tumors

Paraganglioma:=20 of=20 the glomus jugulare is the most common neoplasm of the middle = ear. In contrast to = paragangliomas of other=20 sites, those of the middle ear region have a marked predilection for=20 females. Clinically, = the typical=20 presentation is that of a red mass protruding behind the tympanic = membrane or=20 extending into the canal.=20
Middle=20 ear adenoma and carcinoid tumour: Middle=20 ear adenoma (MEA) is a distinctive benign tumour seen in patients = between 20=20 and 40 years of age. = MEA and=20 carcinoid tumour are now known to be the same tumor showing various = degrees of=20 combined exocrine (mucinous) and neuroendocrine differentiation. The lesion on gross is = grayish white,=20 firm, and is relatively well circumscribed. Microscopically, the pattern = of growth=20 may be solid, glandular, or trabecular. =20 The tumour cells are uniform, cuboidal with moderate cytoplasm, = sometimes acquiring plasmcytoid appearance. Mitoses are exceedingly = rare,=20 pleomorphism is minimal, and necrosis is absent (3).=20
Other=20 tumours: seen here are meningioma = arising from=20 the petrous bone and acoustic neuroma (schwannoma). Rare primary benign tumors = seen here=20 are lipoma, haemangioma, osteoma and glioma. =

Malignant=20 tumors

=A7 =20 Adenocarcinoma: is a=20 controversial entity. It = is a=20 papillary tumour composed of uniform cuboidal cells with clear to = acidophilic=20 cytoplasm forming papillary structures that rest on a vascular = stroma. They have been referred to as = aggressive=20 papillary middle ear tumour (APMET) favouring an origin from the middle=20 ear/mastoid epithelium. = The=20 low-grade adenocarcinoma (Heffner tumour) favour an origin from = endolymphatic=20 sac epithelium.

=A7 =20 Squamous=20 cell carcinoma: of the=20 middle ear typically presents in older patients with a history of = long-standing=20 ear discharge. = Microscopically, it=20 is a typical SCC with various degrees of differentiation=20 (4).

=A7 =20 Rhabdomyosarcoma:=20 of the=20 middle ear occurs almost exclusively in children. Microscopically, the tumor can = be of the=20 embryonal or botryoid type.

NOSE

Nasal=20 Vestibule

Tumors=20 of the nasal vestibule are considered separately from nasal cavity = tumors=20 because they are essentially skin cancers and have a different natural=20 history. Lesions of the = nasal=20 vestibule present with symptoms of a slow-growing mass with attendant = crusting,=20 and occasional minor bleeding. =20 Pain, if it occurs, is usually modest, even with destruction of = cartilage=20 or involvement of the lip. = Septal=20 perforation may occur.

Benign=20 Tumors: Many=20 so-called benign tumors destroy bone and soft tissues and, if = uncorrected, cause=20 death. The management of = some of=20 these problems is not unlike cancer treatment. Benign odontogenic = tumors occur=20 in this area.

Malignant=20 Tumors: Almost=20 all malignant tumors arising in the nasal vestibule are SCCs; basal cell = carcinomas and adnexal carcinomas have = occasionally=20 been reported.

Nasal=20 Cavity and Paranasal Sinuses (often=20 grouped under the term =91sinonasal=92).

Benign=20 Tumours

=A7 =20 Sinonasal=20 papillomas: are=20 benign neoplasms, usually unilateral, most commonly presenting in adult = men with=20 nasal stuffiness nasal obstruction, or epistaxis. They are also called as = inverted,=20 cylindrical cell, transitional, squamous and Schneiderian = papillomas. For practical reasons they are = best=20 considered malignant because they may have an aggressive clinical = picture=20 requiring cancer-type management and may be associated with a = carcinoma.

=20 The=20 histologic picture is that of a papilloma growing into the stroma rather = than=20 growing outward. = Microscopically,=20 the neoplasmis composed of proliferating columnar and/or squamous = epithelial=20 cells and numerous microcysts. = The=20 importance ofsinonasal papilloma lies in the fact that they have a = tendency to=20 recur, with a potential for malignant transformation and 3% of them have = a focus=20 of invasivecarcinoma at the time of diagnosis (5). The presence of HPV 6/11 has = been well=20 documented (6).

=A7 =20 Angiofibroma:=20 Juvenile=20 angiofibroma (JNA) is a benign tumor occurring almost exclusively in the = nasopharynx of prepubertal and adolescent males. JNA accounts for 0.05% of all = head and=20 neck tumors. JNA is rare = in=20 patients older than 25 years.

=20 The=20 lesion originates in close proximity to the posterior attachment of the = middle=20 turbinate, near the superior border of the sphenopalatine foramen. A hormonal theory, that the = lesion is=20 androgen-dependent, has been suggested because of the great predilection = for=20 youngmales (7). Other theory includes a desmoplastic response of the=20 nasopharyngeal periosteum or the embryonic fibrocartilage between the=20 basiocciput and the basisphenoid. =20 Etiology from nonchromaffin paragangliomic cells of the terminal = branches=20 of the maxillary artery has also been considered.

=20 The most frequent symptom, especially in initial stages is nasal=20 obstruction (80-90%). = Other=20 symptoms include epistaxis-mostly unilateral andrecurrent; headache, = facial=20 swelling unilateral rhinorrhea, anosmania, hyposmia, rhinolalia, = deafness,=20 otalgia, swelling of the palate and deformity of the cheek. Clinical examination reveals a = nasal=20 mass (80%), orbital mass, proptosis, serous otitis, zygomatic swelling, = trismus=20 and decreasing vision. = JNA may also=20 be complicated by a DIC like picture (8).

=20 On gross examination, the tumor is usually sessile, lobulated, = rubbery,=20 red-pink to tan-gray in appearance. =20 In rare cases, the tumor is polypoid or pedunclulated. Microscopically, JNA is = usually=20 encapsulated and composed of vascular tissue and fibrous stroma with = coarse or=20 fine collagen fibres. = Vessels are=20 thin-walled, lack elastic fibres, have absent or incomplete smooth = muscle, and=20 vary in appearance from stellate or staghorn to barely conspicuous = because of=20 stromal compression. = Stromal cells=20 have plump nuclei and tend to radiate around the vessels. When examined under electron = microscope,=20 stromal cells are mostly bibroblasts and show intensive immunostaining = for=20 vimentin. However, = myofibroblasts=20 may occur focally in connection with fibrotic areas and are = characterized by the=20 coexpression of vimentin and smooth muscle actin = (9).

=A7 =20 Other=20 benign tumors: noted=20 here, albeit rarely, are meningioma, nasal gliomas, haemangiomas,=20 schwannomas and = paragangliomas=20 (10).

=20 Malignant=20 Tumors

=20 General:

=20 Primary tumors arising from the nasal cavity and paranasalsinuses = are=20 considered together because the lesions are frequently advanced when = first seen=20 andit is not always = possible=20 to determine the site of origin with certainty. SCC or one of its variants is = the most=20 common neoplasm. Minor = salivary=20 gland tumors account for 10% to 15% of neoplasms in this region. Lymphoma and melanoma account = for=20 approximately 5% and 1% of cases, respectively. These cancers occur more often = in men (2=20 to 1) and usually appear after the age of 40 except for tumors of minor = salivary=20 gland origin and esthesioneuroblastomas, which may even appear before = the age of=20 20. Nasal cavity and = ethmoid sinus=20 adenocarcinomas have been linked to occupations associated with wood = dust: those=20 in the furniture industry, sawmill work, and carpentary. Thorotrast is a known = etiologic agent in=20 maxillarysins carcinomas. = Some=20 workers suggest that sinonasal carcinoma and Head and Neck SCC have = quite=20 different molecular backgrounds regarding carcinogenesis=20 (11).

= The=20 commonest malignancy seen here is SCC. =20 Other variants of SCC seen rarely are verrucous carcinoma, = basaloid SCC=20 and sarcomatoid carcinoma. =20 Adenocarcinomas usually arise on the middle turbinate or ethmoid = sins and=20 can be colorectal type or enteric type. =20 A miscellaneous group of malignant tumors includes melanoma,=20 plasmacytoma, JNA, carcinosarcoma, sarcomas, nonchromaffin = paragangliomas, and=20 minor salivary gland tumors. =20 Whereas almost all adult nasopharyngeal cancers are carcinomas, = only=20 20-35% of nasopharyngeal malignancies are carcinomas in children. In the pediatric population, = most=20 nasopharyngeal malignancies are rhabdomyosarcomas or=20 lymphomas.

=A7 =20 Nasopharyngeal=20 carcinoma (NPC):=20 The most common presenting complaint is a painless upper neck mass or = masses due=20 to lymph-node metastasis form the tumor. =20 Other complaintsd include nasal obstruction, epistaxis, otitis = media,=20 occipital or temporal headache, proptosis and trsmus. Neurologic symptoms and signs = occur in=20 approximately 25% of patients. =20

&n= bsp; =20 The most frequent site of origin is the fossa of = Rosenmuller. NPC has a bimodal age = distribution. A small peak is observed in = late=20 childhood (usually a disease of adolescence), and a second peak occurs = in people=20 aged 50-60 years. NPC = affects males=20 more frequently than females at a ratio of roughly 3:1. Diatary factors are also of = particular=20 interest. = Nitrosamine-rich fish is=20 a large part of the diet in many regions where NPC is=20 prevalent.

&n= bsp; =20 The accumulated evidence strongly suggests that this tumour = results from=20 the combined action of genetic predisposition, environmental factors, = and the=20 Epstein-Barr virus (EBV) (12). = In=20 the case f NPC, malignant epithelial cells harboring EBV have been = demonstrated=20 onin situ hybridization, PCR tests, immunohistochemical analysis, and=20 ultrastructral studies. = Clonal EBV=20 DNA is found in cells in preinvasive lesions, suggesting that it is = directly=20 related to the process of transformation. =20 The histocompatibility locus human leukocyte antigen (HLA)-A2 may = be a=20 marker for susceptibility to this tumor. =20 Other loci also being considered include HLA-B17 and=20 HLA-Bw46.

Histologic=20 Findings: The World Health Organisation = (WHO) has=20 classified NPC into 3 categories. =20 WHO-1 (well-to-moderately differentiated squamous or transitional = cell=20 carcinoma with keratin production), WHO-2 (nonkeratinizing carcinoma) = and WHO-3=20 (undifferentiated carcinoma, including = lymphoepithelioma).

The=20 current classification system has been simplified as=20 follows:

(1) = SCC=20 (Keratinizing SCC) or

(2) = Nonkeratinizing=20 carcinoma, which is subdivided as

(a) = differentiated=20 or

(b) = undifferentiated=20 (undifferentiated carcinoma of nasopharyngeal = type).

=A7 =20 Keratinizing=20 SCC: As=20 elsewhere, keratinizing SCC is a dysplastic, invasive epithelial = malignancy with=20 intercellular bridges, keratin pearls and intracellular keratin. This is the least common form = of=20 NPC. EBV is not as = frequently=20 identified here.

=A7 =20 Nonkeratinizing=20 SCC-Differentiated type and undifferentiated type: The=20 nonkeratinizing squamous carcinoma is most frequently seen where the = neoplasmis=20 endemic. It is therefore = the most=20 common variety. Virtually = all=20 patients have antibodies to EBV antigens, and EBV is extremely = frequently=20 identified in tumor cells. =20

=20 On=20 histology, the differentiated variety has distinctly epithelial cells = with=20 polyhedral outlines and distinct cell borders on most cells arranged in = a=20 reticular pattern. In the = undifferentiated type, extracellular or intracellular keratinization is = rare or=20 absent. Epithelial = differentiation=20 on light microscopy is so initially the tumor was suspected of having both lymphoid and = epithelial=20 origins. The cells may be = round,=20 ovoid, polyhedral, or spindled. =20 Nevertheless, immunoperoxidase stains do proveall these variants = are=20 epithelial in origin.

=A7 =20 Sinonasal=20 undifferentiated carcinoma (SNUC):=20 SNUC is an uncommon malignancy of the sinonasal tract. It is a highly aggressive = malignant=20 neoplasm and is often difficult to distinguish from other poorly = differentiated=20 carcinomas arising in the sinonasal tract (13). It has been recently = classified as a=20 large cell subtype of poorly differentiated neuroendocrine = carcinoma. Common initial symptoms = include nasal=20 obstruction, epistaxis, and facial pain. =20 Late-state SNUC may exhibit an orbital mass, causing proptosis, = diplopia,=20 and visual loss. Orbital = invasion=20 may occur.

=A7 =20 Small=20 cell beuroendocrine carcinoma: has a=20 morphologic, immunohistochemical, and ultrastructral appearance similar = to its=20 pulmonary homolog.

=A7 =20 Undifferentiated=20 (anaplastic) carcinoma: show=20 tumour cells in nests, trabeculae with sheets of medium sized cells = having a=20 high mitotic rate, extensive necrosis and prominent vascular = invasion. They do not show any = neuroendocrine=20 differentiation.

=A7 =20 Malignant=20 lymphomas: Most=20 nasal/nasopharyngeal lymphomas (14). =20 Midline lethal granuloma is a natural killer nasal T-cell = lymphoma that=20 is a progressively destructive condition involving the nose paranasal = sinuses=20 and hard palate, produces a secondary erosion of contiguous = structures. Death results form extension = to the CNS,=20 hemorrhage, sepsis, or inhalation.

=A7 =20 Esthesioneuroblastoma=20 (ENB) or olfactory neuroblastoma: is a=20 rare malignant neoplasm arising from the neuroepithelial elements in the = olfactory membrane or neuroectodermal elements in the olfactory placode=20 (15). Its aggressive = biologic=20 behavior is characterized by inapparent submucosall spread, local = recurrence,=20 atypical distant metastases, and poor lng-term prognosis (16). It occurs at all ages, with = cases=20 commonly seen in the second and third decades.

=20 ENB should be seen as a = distinct=20 entity from PNET and the Ewing sarcoma family of tumors because recent = studies=20 using fluorescent in situ hybridization and reverse transcriptase = polymerase=20 chain reaction (PCR) have failed to confirm translocation t(11:22) = regarded as a=20 specific molecular abnormality for Ewing sarcoma (17, 18).

&n= bsp;=20 Well-differentiated ENBs exhibit homogenous small cells with = uniform=20 round-to-oval nuclei with true rosette (i.e., Flexner-Wintersteiner[FW]) = or=20 Homer Wright (HW) rosette formation and eosinophilic fibrillary = intercellular=20 background material. In undifferentiated ENB characterized by anaplastic = hyperchromatic small cells with numerous mitoses and scant cytoplasm,=20 differentiation from other small-cell nasal neoplasms (malignant = melanoma,=20 embryonal rhabdomyosarcoma, malignant lymphoma, extramedullary = plasmacytoma,=20 and, sinonasal undifferentiated carcinoma and sinonasal neuroendocrine=20 carcinoma.) via light microscopy becomes difficult. ENB can be assigned four = grades=20 according to Hyams (1988)

Histopathologic=20 Grading

Grade=20

Lobular=20 Architecture

Preservation

Mitotic=20

Index

Nuclear

Polymorphism

Fibrillary

Matrix

Rosettes=20

Necrosis=20

zero

None

Prominent

HW=20 rosettes

None

Low

Low=20

Present

HW=20 rosettes

None

III

+/-

Moderate

Low

FW=20 rosettes

Rare

+/-

High

High=20

absent

None

Frequent=20

=20 On immunohistorchemistry the tumor is positive for neuroendocrine = markers=20 such as chrmogranin, synaptophysin, neuron-specific enolase, S-100 = protein and=20 protein gene product 9.5. = It is=20 negative for cytoderatin, desmin, vimentin, actin, glial fibrillary = acidic=20 protein, HMB 45, and common leukocytic antigen.

=20 The demonstration of HASH gene expression, although still=20 investigational, could become the diagnostic procedure of choice. ENB could be distinguished = from other=20 sinonasal, poorly differentiated tumors by real time PCR assay of Hash1 = mRNA=20 levels. =

Other=20 tumours: A wide range of soft tissue and bone sarcomas is reported for = the=20 nasal cavity and paranasal sinus region, including chondrosarcoma,=20 osteosarcoma, and Ewing=92s sarcoma.

Larynx

Benign=20 tumors

Squamous=20 paplilloma and papillomatosis: laryngeal=20 squamous papillomas are benign neoplasms and rarely more than 1 cm in=20 diameter. The = papillomas are made=20 up of slender, finger-like projections supported by central = fibro-vascular=20 cores and covered by an orderly, typical, stratified squamous = epithelium. Papillomas are usually = single in=20 adults but are often multiple in children, in whom they are referred = to as=20 juvenile papillomatosis. = The=20 lesions are caused by HPV types 6 and 11. The viral aetiology of = juvenile=20 laryngeal papillomatosis has been proved by ultrastructural = examination,=20 immunohistochemical demonstration of HPV antigens, and in situ=20 hybridization. = Cancerous=20 transformation is rare, though they frequently = recur.=20
Other=20 benign tumours: noted=20 here are haemagniomas, granular cell tumours. = Chondromas.=20

Malignant=20 tumors

General=20

Laryngeal=20 cancer generally is a disease of the elderly, with a peak incidence in = the 50s=20 and 60s. Smoking is = casually=20 associated with laryngeal cancer incidence and mortality in both men and = women=20 (19, 20).. The risk of death due to laryngeal cancer is 10 to 13 times = higher=20 among smokers than among nonsmokers and is exacerbated by heavy alcohol=20 consumption.

= A=20 spectrum of epithelial alterations starting from hyperplasia to atypical = hyperplasia to dysplasia (mild-moderate-severe) to carcinoma in situ to = invasive=20 carcinoma are seen in the larynx. =20 Angiogenesis (formation of new blood vessels) is associated with = tumor=20 growth and metastasis in patients with solid tumors, including those of = the head=20 and neck. Nitric oxide = (NO)=20 production may contribute to these processes (21, 22). =

(1) Squamous cell carcinoma: = About 95%=20 of laryngeal carcinomas are SCCs. =20 They are graded into well, moderately, and poorly differentiated = on the=20 basis of differentiation, cellular pleomorphism, and mitiotic = activity. Variants of SCC are papillary = SCC,=20 verrucous SCC, sarcomatoid carcinoma. =20 Rarely adenocarcinomas are seen. =20 These tumours have been traditionally divided, into four major=20 types:-

1.=20 Glottic (60-65% of all cases)-remain localized for long periods = because=20 of the surrounding cartilaginous wall and the paucity of lymphatic=20 vessels.

2.=20 Supraglottic (30-35% of all cases)-have a marked tendency to = spread=20 toward the preepiglottic space.

3.=20 Transglottic (< 5% of all the cases)-highest incidence of = lymph node=20 involvement.

4.=20 Infraglottic (subglottic) (< 5% of all the cases)-lateral spread = to the=20 cricoid cartilage is the rule. = Also=20 common is destruction by tumour of the weak interthyrocricoid membrane, = with=20 invasion of the prelaryngeal wall and thyroid = gland.

=A7 =20 Basaloid=20 SCC: Basaloid=20 SCC is less common and considerably more aggressive than convential SCC = of the=20 head and neck. Men are 4 = times more=20 likely than women to have this cancer, and most patients are aged 40-70=20 years.

=20 Almost=20 all basaloid SCCs have regions with convential SCC. In addition, they have a = follicular or=20 lobular pattern of invasion, with peripheral, slightly elongated, = palisaded=20 cells surrounding each lobule. = The=20 lobules often contain central comedo necrosis with visible necrotic=20 material. CK stains are = usually=20 positive, with 34BE12, AE3 and CAM5.2 positive in about 80% of = tumors. Increasing evidence suggests = that HPV is=20 involved in the genesis of at least some of these lesions. Furthermore, HPV-positive = basaloid SCCs=20 may be less aggressive than HPV-negative basaloid SCCs. In fact, some oncologic = pathologists=20 contend that HPV-positive basaloid squamous cell carcinoma is less = aggressive=20 than any other type of SCC in the same anatomic = location.

=A7 =20 Verrucous=20 carcinoma: is a=20 lesion with a gross appearance of a verruca wart. Verrucous carcinomas are often = immense=20 in size at presentation. = Depite=20 their size, however, pure forms of verrucous carcinoma rarely, if ever,=20 metastasize. The = architecture=20 is that of a broad, pushing, and expansile epithelial lesion that = extends into=20 the stroma. The most = important=20 consideration in = diagnosing=20 verrucous carcinoma is that an unknown percentage of these lesions = contain a=20 focus or foci of standard SCC. = When=20 this is found, the neoplasm has the potential of convential carcinomas = to=20 metastasize. Given the = large size=20 of verrucous carcinomas on presentation, the entire specimen is not = examined=20 histologically SCCs. = Therefore, the=20 pathologist must adequately sample all putative verrucous carcinomas to = rule out=20 SCC of the usual type. = Verrucous=20 carcinoma is effectively treated by means of surgical excision.

=A7 =20 Papillary=20 SCC: Papillary=20 SCC is uncommon. = Papillary=20 SCCs have been reported in both sexes and in patients aged 30-80 = years. The mean age of presentation = is in the=20 60s, and women are affected less often than men. The lesions range from <1 = to=20 >5.0 cm. In the larynx, hoarseness is = by far the=20 most common first indication of the neoplasm.

On=20 histology, in situ or invasive papillary SCCs have similar = architectures. They contain benign, = fibrovascular cores=20 with overlying squamous epithelium. =20 The epithelial layer may be keratinizing or nonkeratinizing and, = with in=20 situ lesions or full-thickness atypia along with koilocytotic change (related = to HPV=20 infection of the cells). =20

=20 Papillary SCC does present a unique difficulty to the pathologist = and=20 surgeon. The very = architecture of=20 this neoplasm leads to sampling errors. =20 The base of the lesion is often not represented in the biopsy = sample, or=20 the histologic technicians do not cut them thoroughly enough. It is absolutely necessary to = evaluate=20 the epithelial and/or strmal interface of the entire lesion to rule out=20 invasion. The treatement = of=20 papillary SCC, for both in situ and the invasive types, is excision with = free=20 margins.

=A7 =20 Sarcomatoid=20 carcinoma (Spindle=20 cell SCC): has a high predilection for the upper aero-digestive = tract. It may be monophasic or = biphasic with=20 respect to the presence of an epithelial component (23). Many examples show positive=20 immunohistochemical staining for epithelial markets (CK and EMA), but = this may=20 be very focal. = Furthermore,=20 positive staining for vimentin neither excludes a diagnosis of carcinoma = nor=20 confirms a suspicion of sarcoma. = In=20 the most difficult cases, performing electorn microscopy to search for=20 tonofilaments and rudimentary desmosomes can be=20 diagnostic.

=A7 =20 Other=20 malignant tumors: The=20 larynx is also the site of atypical carcinoid tumor and large cell=20 neuroendocrine carcinoma. = Other=20 malignant tumours noted here are angiosarcomas, rhabdomyosarcomas in = children,=20 chondrosarcomas, liposarcomas. = The=20 most common form of salivary gland-type tumor of the larynx is adenoid = cystic=20 carcinoma (24). = Cartilaginous=20 tumors are the most common mesenchymal neoplasms of the larynx arising = from the=20 crcoid cartilage (25).

Trachea=20

Benign=20 tumors

Papilloma=20 and papillomatosis: of=20 the trachea are morphologically similar to the homonymous lesions seen = in the=20 larynx.=20
Other=20 benign tumors: are=20 rare and include pleomorphic adenoma of the salivary gland-type and = glomus=20 tumor paraganglioma. =

Malignant=20 tumors

Squamous=20 cell carcinoma: is=20 the most common primary tumor of the trachea. Adenoid cystic carcinoma is = the second=20 most common type.=20
Other=20 malignant tumors: are=20 rare and include small cell carcinoma, mucin secreting adenocarcinoma, plasmacytoma and NHL.=20
Secondary=20 tumors: are=20 much more common than primary neoplasms. =20 Most of them arise in the bronchi, oesophagus, or larynx and = involve=20 the trachea by direct extension. =

References=20

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Som=20 PM. The present = controversy over=20 the imaging method of choice for evaluating the soft tissues of the = neck. Am J Neruoradiol = 1997;18:1869. Pub=20 Med.=20
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Hwang=20 HC, Mills SE, Patterson K, Gown AM. =20 Expression of androgen receptors in nasopharyngeal = angiofibroma: an=20 immunohistochemical study of 24 cases. =20 Mod Pathol 1998; 11: 1122-26.=20
Baguley=20 C, Sandhu G, = O=92Donnell J, Howard=20 D: Consumptive coaglopathy complicating juvenile angiofibroma. J Laryngol Otol 2004 Nov; = 118 (11):=20 835-9 Medline.=20
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Uryu=20 H, Oda Y, Shiratsuchi H, Oda S, Yamamoto H, Komune S, Tsuneyoshi M.=20 Microsatellite instability and proliferating activity in sinonasal = carcinoma:=20 molecular genetic and immunohistochemical comparison with oral = squamous cell=20 carcinoma. Oncol Rep = 2005=20 Nov;14(5): 1133-42.=20
Gaffey=20 MJ, Weiss LM. = Association of=20 Epstein-Barr virus with human neoplasia. =20 Pathol Annu 1992; 27(Ptl):55-74.=20
Franchi=20 A, Moroni M, Massi D, Paglierani M, Santucci M. Sinonasal = undifferentiated=20 carcinoma (SNUC) of the nasal and paranasal sinuses. Am J Surg Pathol 2002 Dec;=20 26(12):1597-604.=20
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Davis=20 RE, Wessler MC. =20 Esthesioneuroblastoma and neck metastasis. Head Neck. 1992 Nov-Dec;=20 14(6):477-82.=20
Argani=20 P, Perez-Ordonez B, Xiao H, Caruana SM, Huvos AG, Ladanyi M. Olfactory = neuroblastoma is not related to the Ewing family of tumours: absence = of=20 EWS/FLI1 gene fusion and MIC2 expresion. =20 Am J Surg Pathol 1998; 22: 391-8).=20
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