Pseudoneoplastic Lesions of the Head and Neck
Washington University Medical Center
St. Louis, MO
The terms Pseudoneoplastic lesions or pseudotumors are used here to indicate non neoplastic lesions
that, microscopically, mimic neoplasms. Pseudotumors are encountered throughout the body and in every
organ system. In this discussion, we are interested in lesions that are either exclusive to, or have
special predilection for the anatomic structures of the head and neck. For pathologists with experience
in head and neck pathology, such lesions are routinely encountered, others with occasional exposure to
this sub-specialty it is of importance to become familiar with these entities. Misinterpretation of such
a disease processes may, in some cases, have disastrous consequences.
This presentation deals primarily with pseudotumors of the oral and maxillofacial structures and those
affecting the salivary glands, both minor and major.
Pseudotumors Of The Oral And Maxillofacial Structures
Juxtaoral Organ Of Chievitz (OC):
Juxtaoral OC is an embryonic epithelial structure, intimately associated with peripheral nerve fibers,
which is found in the soft tissues of the retromolar trigone and ascending mandibular ramus area.
Microscopically OC is composed of rounded epithelial nests which may be in continuity with one another.
The constituent cells may be polygonal squamous, columnar, basaloid or may show duct like structures with
intraluminal secretions. The cell nests are associated with nerve fibers which may be present at the
periphery of the structure or between the epithelial nests. It is of importance that the juxtaoral OC be
recognized as a normal structure and not misdiagnosed as squamous cell or mucoepidermoid carcinoma. This
is of particularly significance in evaluation of the surgical margins of resection of these tumors, which
are not uncommon at the retromolar trigone area.
Manifestation of the juxtaoral OC as an intraoral mass is very rare, but has been reported in
Pseudoepitheliomatous Hyperplasia (PEH):
PEH denotes the reactive non-neoplastic downward proliferation of the surface epithelium. The process
may be marked and some sections may show islands of keratinizing squamous epithelium that are difficult
to distinguish form squamous cell carcinoma.
Epithelial hyperplasia is commonly seen at the edges of nonspecific ulcers of the oral cavity. Marked
PEH is also characteristically associated with specific mucosal lesions such as inflammatory papillary
hyperplasia, granular cell tumor and blastomycosis.
1) PEH in inflammatory papillary hyperplasia (IPH):
IPH also known as denture papillomatosis usually develops under dentures which may be ill-fitting with
poor hygiene, particularly when worn for 24 hours. The lesion is commonly seen in the palate.
Microscopically, the surface mucosa is infolded producing papillary projections covered with
hyperkeratotic stratified squamous epithelium. The underlying fibrous connective tissue contains
inflammatory cell infiltrate. Elongated ridges often show PEH. However, the epithelial islands do not
show hyperchromasia or significant atypia. The depth of extension is usually uniform.
2) PEH in granular cell tumor (GCT):
GCT may originate in a variety of tissues especially skin and mucous membrane. Roughly 30% of GCT
arise in the tongue. The lesion typically presents itself as a firm, submucosal nodule.
Microscopically, large polygonal cells with granular eosinophilic cytoplasm and small centrally placed
vesicular nuclei extend deep into the submucosa. PEH is commonly present in this surface mucosa over the
tumor mass. The hyperplastic changes may be so marked that an erroneous diagnosis of squamous cell
carcinoma may be made. Such a serious mistake is more likely to occur in small biopsies that show little
or none of the underlying GCT.
3) PEH associated with blastomycosis:
Blastomycosis of the upper aerodigestive tract is thought arise by hematogenous spread from a primary
pulmonary focus. In the absence of clinically identifiable pulmonary disease, mucosal lesions of
blastomycosis can pose a considerable diagnostic challenge for the clinician as well as the pathologist.
Laryngeal blastomycosis has insidious onset with progressive hoarseness, occasional pain and dysphasia.
The lesions may be erythematous, ulcerated or fungating, mimicking carcinomas in this site.
Microscopically granulomatous inflammation and microabscess formation are seen in association with PEH of
the overlying mucosa. GMS stain demonstrates thick-walled yeast forms, with occasional broad-based
budding, which may be present intracellularly in giant cells or extracellularly.
Odontogenic Pseudoneoplastic Lesions
Hyperplastic Tooth Follicles And Dental Papillae:
Tooth follicle and dental papilla are normal ectomesenchymal components of odontogenesis which are
ubiquitous in the jaws during the period of tooth formation. The dental papilla which forms dentin and
matures into pulp tissue is composed of immature mesenchymal tissue which is loose and myxoid with small
stellate or fusiform cells. The tooth follicle which develops into periodontal membrane and its
attachments is composed of collagenous fibrous tissue with variable myxomatous components. Small islands
and epithelial cell remnants in addition to areas of calcification are commonly encountered. Tooth
follicles and dental papilla are usually presented to the pathologist in specimens associated with
impacted teeth, particularly third molars. These structures are commonly misdiagnosed as odontogenic
tumors, such as odontogenic myxoma, odontogenic fibroma, ameloblastic fibroma and calcifying epithelial
odontogenic tumor. Such misdiagnosis which may result in disfiguring unnecessary surgeries can be
avoided by paying special attention to correlate the histologic findings with complete historical,
clinical and radiographic information. The mentioned odontogenic tumors are expansive, locally
destructive lesions where as the vestigial odontogenic tissues are confined well circumscribed and
symmetrical and never cause osseous destruction.
The term "benign fibro-osseous lesion" is used to describe a wide variety of lesions of the
craniofacial skeleton which include dysplastic, developmental, as well as neoplastic entities. These
lesions are characterized by fibrous stroma containing various combinations of bone and cementum-like
material. The distinction between neoplastic and non-neoplastic entities in this category requires
correlation between historical, clinical and radiographic findings. Non-neoplastic fibro-osseous lesions
are commonly encountered in the jaws and are termed cemento-osseous dysplasia. These are dysplastic
entities that may be focal or diffuse (florid). They should ideally be identified clinically and
radiographically. Surgical intervention is unwarranted and indeed in the case of florid osseous
dysplasia is contra-indicated because even a simple biopsy may result in infection, pain and complicated
Focal cemento-osseous dysplasia may be associated with the apices of the mandibular incisors
(periapical cemental dysplasia), or as isolated lesions typically present in edentulous mandibular molar
areas. Periapical cemental dysplasia is not uncommon. It is usually seen in middle aged black women.
The lesions are non-expansive and asymptomatic. Radiographically, they present as small well defined
radiolucency which in older lesions may become heavily calcified. They may be confused with neoplastic
entities such as cementoma and ossifying fibroma. No treatment is recommended.
Florid osseous dysplasia is almost invariably seen in middle aged and older black female patients.
Radiographically florid osseous dysplasia is characterized by extensive sclerotic and radiolucent areas
symmetrically involving the alveolar process of the mandible and maxilla bilaterally. Focal and florid
cemento-osseous dysplasia are microscopically analogous to one another and are composed of fibrous
connective tissue stroma containing osteoid or bone and cementum-like tissue. Advanced lesions show an
increase in mineralization producing large sclerotic masses that are hypocellular and extremely dense
with little or no marrow spaces found. These structures are termed sclerotic cemental masses. Ossifying
fibroma of the jaws is a true neoplasm. It is usually solitary and expansive. In some types of
ossifying fibroma, such as juvenile ossifying fibroma, the growth rate could be very fast. Although the
microscopic features of ossifying fibroma and cemento-osseous dysplasia are similar, sclerotic cemental
masses do not form in ossifying fibroma.
Pseudotumors Of Salivary Glands
Tumor-like lesions of the salivary glands may occur in minor as well as the major salivary
glands. They may present as masses indurations or ulcerations that may mimic neoplastic disease
clinically as well as microscopically. The following are selected examples.
Polycystic (Dysgenetic) Disease Of The Parotid:
This is a rare condition that resembles polycystic disorders of other organs such as the kidney,
pancreas and lungs. It may occur in one gland but usually affect both glands. It is believed to be
developmental malformation of the ductal system. It presents as a recurrent, fluctuant swelling of the
affected parotid gland, which may be long-standing. It occurs usually during childhood but is
occasionally noted during adult life. It is seen in female patients almost exclusively. There is
usually no significant change in salivary flow.
On microscopic examination, the overall architecture of the gland is preserved. Nevertheless, the
lobules are enlarged and largely replaced by epithelial lined cystic spaces that may contain short septal
projections. The lining epithelial cells may be flat, cuboidal or columnar. Occasionally the cells show
a rounded snout-like luminal surface resembling apocrine cells. Cytoplasmic vacuolization is common.
Remnants of the glandular acini may be found between the cysts. The cystic lumina may contain secretions
and occasionally eosinophilic bodies with concentric radial laminations resembling spherioliths and
Although polycystic disease of the parotid is extremely rare, it is important to be familiar with this
entity in order to avoid misdiagnosis of a cystic neoplasm such as cystadenoma and low grade
mucoepidermoid carcinoma. Cystadenoma is well defined and encapsulated, not diffuse. The epithelial
cyst lining is cuboidal, columnar, or may be oncocytic with mucous cells and tends to show focal
stratifications and papillary projections. The lining cells, unlike those of the cystic parotid are
usually not vacuolated and do not show luminal decapitation profiles or form one cell layer. The cystic
lumina do not contain spherioliths and microlith. These are also lacking in mucoepidermoid carcinoma.
Cystic mucoepidermoid carcinoma have infiltrative growth pattern, the lining cells usually include mucous
cells as well as epidermoid and intermediate cells.
Polycystic disgenetic disease of the parotid is an innocuous condition. Surgery should be done only
for diagnostic or cosmetic purposes.
Necrotizing Sialometaplasia And Non-Necrotizing Squamous Metaplasia Of Salivary Glands:
1) Necrotizing sialometaplasia (NSM):
NSM is not a common condition. It affects predominantly the minor salivary glands of the palate. The
lesions can be easily misdiagnosed as malignancy, both clinically and microscopically. The histologic
hallmark of the condition is mucous acinar necrosis and squamous metaplasia of the ducts. Local ischemia
is believed to play an etiologic role and the term salivary gland infarction has been used to describe
NSM by some authors.
Necrotizing sialometaplasia affects children as well as adults of all ages; however, the mean age of
incidence is 45 years. Males are almost twice as commonly affected as females. The lesions occur
predominantly in the palate but they have been observed in other sites in the mouth as well as extra-oral
locations in the upper aerodigestive tract and in the major salivary glands. In the palate, NSM usually
presents as a deep crater-like ulceration which is usually small measuring 1 to 3 cm and occasionally may
take the form of a non-ulcerating sub-mucosal nodule. Most cases are asymptomatic although a few
patients complain of numbness or burning sensation. The lesions develop rapidly and heal spontaneously
in a few weeks.
Microscopically, the salivary gland lobules show complete or partial necrosis of the mucous acini.
Pools of mucin occasionally form in the lobules. Acute inflammatory cells as well as foam cell
macrophages are usually present. Squamous metaplasia of the ducts produce scattered epithelial islands
which may show reactive atypia but their distribution generally follows the lobular architecture. The
squamoid nests may occasionally show residual luminal spaces and mucous cells may be present in the
islands thus simulating the appearance of mucoepidermoid carcinoma. However, the lack of invasion in the
surrounding structure, the preservation of the lobular architecture and clinical history mitigates
against the diagnosis of malignancy. Before the identification of MSN in 1973 some lesions were treated,
as malignant tumors usually squamous cell carcinoma or mucoepidermoid carcinoma, with radical surgery.
2) Squamous metaplasia of salivary glands (SMS):
SMS is much more commonly seen than MSN. It is encountered in head and neck surgical specimens,
particularly in cases with history of previous surgery or radiotherapy. Acinic necrosis is not always
present but like necrotizing sialometaplasia, islands and nests of squamous cells are seen
microscopically. Occasional lumina and mucous cells may also be present. Cellular atypia may be marked.
Special attention should be given to identifying the clustering patterns suggestive of lobular
architecture and lack of frankly invasive morphology.
Oncocytosis And Nodular Oncocytic Hyperplasia:
Florid oncocytic metaplasia of salivary glands may be accompanied with glandular swelling suggesting
the presence of a neoplasia and prompting excisional or incisional biopsies. However, the majority of
oncocytosis are incidental findings seen in specimens removed for other reasons such as oncocytoma,
Warthin's tumor, pleomorphic adenoma and acinic cell carcinoma. Oncocytosis is usually seen in adults
with an age range of 28-87 years. There may be a female bias. The parotid is the most common site. The
submandibular and minor salivary glands of the mouth are much less frequently affected. Microscopically,
oncocytosis may be represented by scattered foci of enlarged polygonal cells with eosinophilic granular
cytoplasm and centrally placed nuclei. The cells may form ductal or acinar structures or sheets and
trabeculae. The overall lobular architecture of the gland is preserved.
Clear cell changes are not uncommon in oncocytosis and are believe to be due to accumulation of
intracytoplasmic glycogen. Oncocytes stain positively with phosphotungstic acid hematoxylin (PTAH).
Ultrastructurally, the cytoplasm of such cells is packed with pleomorphic mitochondria that may have
vesicular aberrant cristae. Oncocytoma can be distinguished from oncocytosis because it is well defined,
solitary and commonly encapsulated. In contrast oncocytosis is multifocal and does not disrupt nodular
architecture of the glandular parenchyma. The multiple scattered clear cell foci that are seen
occasionally in cases of oncocytosis can lead to erroneous diagnosis of metastatic clear cell carcinoma
most notably of renal origin. In contra-distinction to metastatic neoplastic disease, oncocytosis lacks
the invasive growth pattern and the typical eosinophilic oncocytes are commonly present. The clear cell
groups of metastatic renal cell carcinoma demonstrate more cellular and nuclear pleomorphism and show
more prominent vascularity. If the distinction is difficult it may be prudent to evaluate the kidneys
2) Nodular oncocytic hyperplasia:
This term refers to two or more tumor-like nodules that show hyperplasia of metaplastic oncocytes. It
has been suggested that oncocytoma may develop from some examples of nodular oncocytic hyperplasia by
progressive enlargement of the latter. The presence of focal, ductal and acinar oncocytic metaplasia in
other parts of the gland, in addition to presence of normal acini at the periphery of the large nodules
in nodular oncocytic hyperplasia may be useful in distinguishing this lesion from true oncocytoma.
Salivary Gland Hamartoma Of The Nasopharynx
(Salivary Gland Anlage Tumor; Congenital Pleomorphic Adenoma):
Salivary gland hamartoma of the nasopharynx is relatively recently defined lesion that affects newborn
infants. It presents as a polypoid mass of the nasopharynx which may be a few centimeters in diameter.
It may cause respiratory distress at birth or during the first few days of life. Microscopically, the
lesion is surfaced with non-keratinizing stratified squamous mucosa with focal projections of epithelial
nests and duct-like structures extending into superficial myxoid spindle cell stroma. This zone is
interposed between the mucosal surface and more central region composed of densely cellular stromal
spindle cell nodules. The nodules are interspersed with keratinizing and non-keratinizing nests and
duct-like structures. Mitotic activity may be observed and in some cases can be brisk.
Immunohistochemical staining shows reactivity for cytokeratin and epithelial membrane antigen in the
peripheral epithelial components. The cells of the central stromal nodules show variable reactivity for
cytokeratin, vimentin, and muscle specific actin. Both components react positively for salivary gland
amylase. The histologic and immunophenotypic features of this lesion are similar to those of developing
salivary glands. The hamartomatous nature of this congenital salivary gland lesion is suggested by its
limited growth potential, location in the midline and histopathologic similarity to salivary gland
anlage. Salivary gland hamartoma of the nasopharynx should be differentiated from neoplastic lesions
that it may suggest such as pleomorphic adenoma, teratoma, sialoblastoma and synovial sarcoma.
Pleomorphic adenoma is extremely rare as a congenital lesion in the midline of the nasopharynx.
Salivary gland hamartoma lacks the chondroid and myxoid stroma commonly seen in pleomorphic adenoma and
the growth of epithelial buds from surface epithelium is not seen in pleomorphic adenoma. Teratomas can
present as a midline mass at birth. Nevertheless, they are composed of complex mixtures of mature and
immature tissue derived from the three germ cell layers; most notably neuroepithelium, cartilage,
respiratory epithelium and enteric elements. Sialoblastoma is a congenital salivary gland neoplasm which
presents at birth as a large mass occurring exclusively in the parotid gland. Microscopically, the tumor
is composed predominantly of solid epithelial nests composed of large cells with polygonal hyperchromatic
nuclei. The dual composition of salivary gland hamartoma of epithelial and spindle cells may recall the
biphasic histology of biphasic synovial sarcoma. Synovial sarcoma is extremely rare as a congenital
lesion. Budding of surface epithelium is not seen and the spindle cells are arranged in fascicles in
synovial sarcoma rather than nodules.
- El-Mofty SK. Pseudoneoplastic lesions of the head and neck. Wick MR, Humphrey PA, Ritter JH editors. Pathology of Pseudoneoplastic lesions. Philadelphia: Lippincott-Ravin; 1997, p. 69-96.
- Soucy P, Cimone G, Carpenter B. An unusual intraoral mass in a child:The organ of Chievitz. J Ped Surg 1990;25:1200.
- Neville BW, Damm DD, Allen CM, Bouquet JE, editors. Oral and Maxillofacial Pathology, 2nd ed. Philadelphia: WB Saunders Co. 2002.
- Stewart CM, Watson RE, Eversole LR, Fischlschweiger W, Leider AS. Oral granular cell tumors:a clinicopathologic and immunocytochemical study. Oral Surg Oral Med Oral Pathol 1988;65(4):427-35.
- Hanson JM, Spector G, El-Mofty SK. Laryngeal blastomycosis:A commonly missed diagnosis;Report of two cases and review of the literature. Ann Otol Rhinol Laryngeal 2000;109:281-6.
- Kim J, Ellis GL. Dental follicular tissue:misinterpretation as odontogenic tumors. J Oral Maxillofac Surg 1993;51(7):762-7.
- Gardener DG, Radden B. Multiple calcifying hyperplastic dental follicles. Oral Surg Oral Med Oral Pathol Oral Endodont 1995;79:603-6.
- Melrose RJ, Abrams AM, Mills BG. Florid osseous dysplasia. Oral Surg Oral Med Oral Pathol 1976;41:62-81.
- Waldron CW. Fibroosseous lesions of the jaws. J Oral Maxillofac Surg 1985;43:249-62.
- El-Mofty SK. Psammomatoid and trabecular juvenile ossifying fibroma of the craniofacial skeleton:Two distinct clinicopathologic entities. Oral Surg Oral Med Oral Pathol Oral Radiol Endo 2002;93:296-304.
- Dobson CM, Ellis HA. Polycystic disease of the parotid glands:case report of a rare entity and review of the literature. Histopathology 1987;11(9):953-61.
- McFerran DJ, Ingrams DR, Gallimore AP, Grant HR. Polycystic disease of salivary glands. J Laryngol Otol 1995;109(2):165-7.
- Abrams AM, Melrose RJ, Howell FV. Necrotizing sialometaplasia. A disease simulating malignancy. Cancer 1973;32(1):130-5.
- Brannon RB, Fowler CB, Hartman KS. Necrotizing sialometaplasia. A clinicopathologic study of sixty-nine cases and review of the literature. Oral Surg Oral Med Oral Pathol 1991;72(3):317-25.
- Wenig BM. Necrotizing sialometaplasia of the larynx. A report of two cases and a review of the literature. Am J Clin Pathol 1995;103(5):609-13.
- Walker GK, Fechner RE, Johns ME, Teja K. Necrotizing sialometaplasia of the larynx secondary to atheromatous embolization. Am J Clin Pathol 1982;77(2):221-3.
- Palmer TJ, Gleeson MJ, Eveson JW, Cawson RA. Oncocytic adenomas and oncocytic hyperplasia of salivary glands:a clinicopathological study of 26 cases. Histopathology 1990;16(5):487-93.
- Takeda Y. Diffuse hyperplastic oncocytosis of the parotid gland. Int J Oral Maxillofac Surg 1986;15(6):765-8.
- Ellis GL. Clear cell" oncocytoma of salivary gland. Hum Pathol 1988;19(7):862-7.
- Dehner LP, Valbuena L, Perez-Atayde A, Reddick RL, Askin FB, Rosai J. Salivary gland anlage tumor ("congenital pleomorphic adenoma"). A clinicopathologic, immunohistochemical and ultrastructural study of nine cases. Am J Surg Pathol 1994;18(1):25-36.