Head & Neck Flashcards
Carcinoma ex pleomorphic adenoma is subdivided into what 3 prognostic subtypes?
Noninvasive, minimally invasive, and invasive. Noninvasive carcinomas arising in PA are sometimes referred to as in situ or intracapsular carcinomas. These tumors are characterized by relatively abrupt transitions between histologically bland PA and areas with obviously malignant cytologic features but are limited to the confines of the PA without extracapsular invasion. The noninvasive carcinoma may invade the matrix of the preexisting PA but is not considered clinically invasive until it penetrates beyond the capsule of the PA. Minimally invasive CaExPA is defined as a carcinoma that invades no more than 1.5 mm beyond the capsule of the PA. Distinguishing between a benign pseudopod and true invasion may be difficult. A desmoplastic reaction, if present, is helpful. So-called lateral extension (mushroom-type invasion) into and through the capsule, akin to that seen in some thyroid carcinomas, also implies malignancy, as does perineural invasion. In addition, the invasive component should demonstrate atypical cytologic and architectural features.
Discuss the 3 growth patterns seen in adenoid cystic carcinoma.
Cribriform, tubular, and solid. The cribriform subtype is the MC. It is composed of islands of basaloid cells surrounding variably sized cystlike spaces forming a “Swiss cheese” or sievelike pattern. The cystlike spaces are referred to as “pseudocysts” b/c they do not represent true glandular lumina and are contiguous with the surrounding stroma. The pseudocysts contain basophilic glycosaminoglycans and/or eosinophilic, PAS-positive basal lamina material. Rare, true glandular lumina composed of cuboidal cells showing ductal differentiation can also be found scattered throughout and their presence greatly aids in diagnosis. The tubular pattern shows similar cytology with the tumor cells arranged in nests surrounded by variable amounts of eosinophilic, often hyalinized stroma. Occasionally, the stromal component is increased, compressing the tumor cells into thin strands, forming a “trabecular” pattern. Well-formed ducts with recognizable inner epithelial and outer myoepithelial layers are more prominent than in the cribriform pattern. The continuity of the pseudocysts with the surrounding stroma is also more prominent. The solid pattern contains aggregates of basaloid cells without tubular or cystic formation. Although the basaloid cytology of the tumor cells is retained, the tumor cells may be larger and nuclear pleomorphism may be more pronounced. Mitoti figures and comedonecrosis may also be seen. As in the cribriform pattern, true ducts will occasionally be seen scattered among the sheets of cells. This feature, along with accompanying areas of cribriform or tubular growth, can aid in differentiation from other basaloid neoplasms. A combination of patterns can be seen, which could be considered a fourth pattern.
Malignant mixed tumors of the salivary glands can be classified as what 3 types?
- Carcinoma ex pleomorphic adenoma. 2. “Benign” metastasizing pleomorphic adenoma. 3. Carcinosarcoma. >90% of all malignant mixed tumors are CaExPAs and most are high grade, with salivary duct carcinoma; adenocarcinoma NOS; undifferentiated carcinoma; and myoepithelial carcinoma being the most common subtypes.
Myoepithelial neoplasms of the salivary glands.
Some authors believe these should be purely myoepithelial, while some believe a minor ductal component can be present (typically <5%). Myoepithelial neoplasms can be benign (myoepithelioma) or malignant (myoepithelial carcinoma or malignant myoepithelioma). 10-20% are malignant. MC sites are parotid gland and palate. Most myoepitheliomas occur in the 5th and 6th decades of life and most myoepithelial carcinomas occur in the 6th and 7th decades of life. Myoepithelial tumors can be difficult to recognize histologically because of variety in their architectural and cytologic appearances. 6 characteristic growth patterns of myoepithelial tumors: solid, nodular, mucinous, trabecular, pseudoglandular, reticulated. 5 characteristic cell types of myoepithelial tumors: spindled, plasmacytoid-hyaline, clear, epithelioid, oncocytic.
Nasolabial cysts.
The nasolabial cyst is a benign, slow-growing, locally expansile lateral extraosseous lesion below the nasal ala and the medial nasolabial fold. Although often classified as a jaw cyst, the nasolabial cyst is purely a cyst of soft tissue. Alternative, older, or less common names for this lesion include Klestadt cyst, nasal vestibule cyst, nasal wing cyst, and mucoid cyst of the nose. Because the cyst does not involve the dental alveoli, the sometimes also encountered term nasoalveolar cyst is not recommended. Nasolabial cysts can be observed at any age, but MC in 30-50 yo, and F:M = ~3:1. They are typically unilateral and slow-growing. They are found near the distal portion of the nasolacrimal duct and its opening into the inferior nasal meatus. It is believed that nasolabial cysts are hamartomatous developmental lesions, arising from the lower anterior portion of the nasolacrimal duct. Grossly, nasolabial cysts are pink to tan, soft to rubbery-firm, and have variably cystic and fibrous areas filled with clear viscous fluid. Histologically, there is a bilayered epithelium with a cuboidal basal layer and a columnar luminal layer that contains interspersed scattered mucinous goblet cells. To variable extents, nasolabial cysts can also be lined by multilayered or pseudostratified, cuboidal to columnar epithelium. Focal squamous metaplasia or apocrine changes may also be present. Ciliated cells are not present. Cyst wall stroma is composed of hypocellular, collagen-rich fibrovascular tissue with variable amounts of chronic inflammatory cells.
Osteoblastomas associated with a tooth root are called ___.
Osteoblastomas associated with a tooth root are called cementoblastomas. Osteoblastoma occurs more often in the mandible than the maxilla. It is often associated with the root of a tooth, where it forms an ossified, well-demarcated tumor. Microscopically, the bony matrix tends to be abundant in these tumors and to radiate from the tooth root in parallel arrays.
Papillary thyroid carcinoma, cribriform morular variant. What stains can be helpful? This variant is associated with (syndrome) ~25% of the time.
This variant’s unique histology and reactivity with thyroglobulin, TTF-1, and beta-catenin help to distinguish it. This variant is associated with FAP ~25% of the time.
Papillary thyroid carcinoma, diffuse sclerosing variant. In what age group does it occur? What is the histologic appearance?
A rare variant that occurs in children and young adults. It has conventional papillary architecture and PTC nuclear features, but has squamoid changes and abundant psammoma bodies, a dense lymphocytic and sclerotic background, and extensive lymphatic permeation.
Papillary thyroid carcinoma, oncocytic variant. What is the gross and histologic appearance?
This variant is grossly mahogany brown. Microscopically, while it has conventional papillary architecture, it is oncocytic with focally prominent nucleoli and often has psammoma bodies (about 33 %).
PIOLs?
Primary Intraocular Lymphomas. Is a subset of PCNSL. Is usually a DLBCL. They arise from the retina (a suggested renaming for PIOL is primary retinal lymphoma) and rarely from the uvea. Usually presents as a chronic intermediate uveitis unresponsive to corticosteroids in a median age in the 60s. The Dx is based on ID of atypical lymphoid cells in the eye, but b/c PIOL is a subset of PCNSL, the Dx can be made if the lymphoma cells are found in CSF, and an LP is less invasive than a diagnostic vitrectomy or a vitreous or aqueous aspiration anyway. The atypical lymphoid cells are usually large and pleomorphic, with scant basophilic cytoplasm and large nuclei. Other findings include hypersegmented, round, or clover-shaped nuclei with prominent nucleoli and rare mitoses.
Pleomorphic adenoma of salivary gland?
AKA benign mixed tumor. MC salivary gland tumor, accounting for almost 2/3 of all salivary gland tumors. PAs are composed of both epithelial cells and myoepithelial cells, which produce a mesenchymal stromal component that is often myxoid or chondromyxoid. Varying amounts and arrangements of the epithelial, myoepithelial, and stromal components give rise to a broad degree of morphologic diversity. The distinction between a cellular PA, basal cell adenoma, or myoepithelioma can be subjective. An acellular PA can resemble a soft tissue chondroma or myxoma. ~6% of PAs harbor malignancy. PAs are usually well circumscribed and encapsulated in the major salivary glands and nonencapsulated in the minor salivary glands.
Polymorphous low-grade adenocarcinoma of the salivary glands?
PLGA occurs almost exclusively in the minor salivary glands of the oral cavity and oropharynx. They tend to be nonpainful and slow growing, M:F = 1:2, and occurs over a broad age range (average 50-60). Histologically, PLGA is characterized by a triad of infiltrative growth, multiple architectural growth patterns, and cytologic uniformity. Characteristic growth patterns include solid, trabecular, glandular, cribriform, fascicular, cordlike and papillary, with the first 3 patterns being the MC. Typically, the central portion consists of the more solid growth patterns, with the glandular and cordlike elements seen more often at the periphery. Mitoses are rare and necrosis is unsually not seen. PNI is common and can have a targetoid arrangement which is very characteristic of PLGA. The tumor cells are cytologically bland and can be cuboidal, columnar, or spindled, with a mixture being most common.
Salivary duct carcinoma.
SDC is one of the most aggressive salivary gland carcinomas and histologically resembles HG ductal adenocarcinoma of breast. Can be seen in a wide age range but most are in >50 (mean of 60-79). M:F = 3-4:1. It can arise de novo or in the setting of a pleomorphic adenoma (SDCExPA). Parotid gland is the MC tumor site. Microscopically, SDCs are characterized by both infiltrative and intraductal carcinoma resembling breast ductal carcinoma. The most characteristic histologic feature is variably sized, rounded nodules with a cribriform, solid, cystic, or papillary architecture. These so-called ductal lesions frequently demonstrate comedo necrosis, which may undergo calcification. Cytologically high grade and numerous mitoses. The cells have moderate to abundant amounts of eosinophilic to amphophilic cytoplasm, fequently imparting an apocrine-like phenotype. For IHC, most tumors are positive for androgen receptor and SDC is now virtually defined by expression of this. SDCs are often positive for BRST-2 and CEA and >2/3 are positive for HER-2 overexpression, but almost all are negative for ER and PR. Prognosis is dismal.
The most common primary lymphoma subtype occuring in the ocular adnexa?
Low-grade, malignant, extranodal, marginal zone B-cell lymphoma of MALT type.
Uveal malignant melanoma?
… is the most common primary intraocular malignancy in the adult population. It comprises ~5% of all melanomas, and 85% of ocular melanomas are uveal in origin. Mortality, principally from liver metastasis, has historically been ~50%. Features correlating with poor prognosis include: large size, epithelioid cell type, presence of PAS positive vascular mimicry patterns (or extracellular matrix patterns), and ciliary body involvement. Chromosomal changes of prognostic significance include monosomy 3, and alterations of 8q and 6p.
What is HPT-JT syndrome?
HPT-JT (hyperparathyroidism-jaw tumor) syndrome is an inherited disorder with incomplete penetrance. The disorder may be characterized by parathyroid adenoma or carcinoma, benign fibro-osseous lesions of the mandible or maxilla, and renal cysts or tumors. Approximately 80% of patients have hyperparathyroidism and up to 15% of these patients have parathyroid carcinoma. The HRPT2 gene (for ‘‘hyperparathyroidism 2’’) is a putative tumor suppressor gene that was identified and has been mapped to 1q25–q31. The gene encodes a protein named parafibromin for its relationship to parathyroid disease and fibro-osseous jaw lesions. While HPT-JT syndrome is an exceedingly uncommon entity, with an unknown incidence or prevalence, like MEN, it should be considered in the differential diagnosis for the adolescent presenting with hyperparathyroidism.
What is the most common tumor of the paranasal sinuses?
Osteoma. Osteomas are benign, generally slow-growing, bone-forming tumors limited almost exclusively to craniofacial and jaw bones. They can be subdivided into bone surface tumors (or exostoses) that primarily involve the cranial vault, mandible, and external auditory canal and the more common sino-orbital (or paranasal sinus) osteomas that arise from bones that define the paranasal sinuses, nasal cavity, and orbit. Frontal, ethmoid, maxillary, and sphenoid sinuses are most frequently affected in that order. Histologically, while surface exostoses are usually formed of compact bone, sino-orbital osteomas are composed of variable amounts of compact and cancellous bone. Some osteomas have been designated as “osteomas with osteoblastoma-like features” and are difficult to distinguish from osteoblastomas or osteoid osteomas. Osteoblastoma is most commonly located in the vertebrae and long bones, but mandible is also a relatively common location, where it is often associated with the root of a tooth and referred to as cementoblastoma. However, primary osteoblastoma of the paranasal sinuses is very rare. Osteoid osteomas are vary rare in the craniofacial and jaw bones. They are distinguished from osteoblastoma only by size with a nidus usually less than 1 cm, since the histologic features are essentially indistinguishable. Microscopically, although focally indistinguishable from osteoblastoma, osteoma with osteoblastoma-like features has much more mature bone in the form of solid/compact (ivory osteoma) and dense cancellous (mature osteoma) bone. In addition, the outer contour of an osteoma has a smooth rounded surface, often lined by respiratory mucosa, representing the outer surface of its polypoid growth within the sinus cavity. True osteoblastomas, in contrast, will from an expansible intramedullary or periosteal bone tumor.
What HPV types (in order of frequency) are seen mostly commonly in the following lesions? Plantar wart, common wart, flat (juvenile) wart, oral squamous papilloma, oral focal epithelial hyperplasia (Heck disease), epidermodysplasia verruciformis, laryngeal papillomas, condyloma acuminatum, cervical LSIL, cervical HSIL, cervical AIS and invasive cervical adenocarcinoma.
Plantar wart: 1, 2. Common wart: 2, 1, 4, (HPV 7 in fish and meat handlers). Flat (juvenile) wart: 3, 10. Oral squamous papilloma: 6, 11. Oral focal epithelial hyperplasia (Heck disease): 13, 32. Epidermodysplasia verruciformis: 2, 3, 10, 5, 8. Laryngeal papillomas: 6, 11. Condyloma acuminatum: 6, 11. Cervical LSIL: 6, 11. Cervical HSIL: 16, 18, 31, 33, 35. Cervical AIS: 18. Invasive cervical adenocarcinoma: HPV 16 and 18 are detected with equal prevalence in most subtypes of cervical adenocarcinoma.
What are 2 risk factors for development of ameloblastoma?
Dentigerous cyst. Impacted teeth.
___% of medullary thyroid carcinomas occur in a relatively young population in association with MEN2 syndrome; the remainder are sporadic and may occur at any age.
15-20% of medullary thyroid carcinomas occur in a relatively young population in association with MEN2 syndrome; the remainder are sporadic and may occur at any age.
How does medullary thyroid carcinoma appear on FNA?
FNA biopsy yields neoplastic neuroendocrine cells and amyloid in variable proportions. The cellularity of the smears is usually inversely proportional to the amount of amyloid produced by the tumor. The neoplastic cells are dispersed or form loose clusters, rarely forming microfollicles or papillae. MTC is a great mimicker. The tumor cells may have spindly, plasmacytoid, polygonal, hurthloid or giant cells appearances; may demonstrate mild pleomorphism; and may be bi- or multinucleated. The nuclei often have a “salt-and-pepper” or “speckled” chromatin pattern on Pap stain. Nucleoli may be seen, but are usually inconspicuous. Intranuclear cytoplasmic inclusions are frequently identified, and are morphologically identical to those seen in papillary thryoid cancer. Mitotic figures are present in 15% of cases. On Diff-Quik staining, red cytoplasmic granules, corresponding to neurosecretory granules containing calcitonin, may be seen.
What is seen on FNAs in Hashimoto thyroiditis?
Smears from Hashimoto’s thyroiditis show a polymorphous lymphoplasmacytic infiltrate with germinal center formation. Lymphoid tangles, lymphohistiocytic aggregates, tingible body macrophages, and background lymphoglandular bodies may be the overwhelming findings on the smears. Multinucleated histiocytes may be seen. Oncocytic (Hurthle cell) metaplasia is usually prominent. Hurthle cells are epithelial cells with abundant, finely granular cytoplasm and enlarged, variably sized, typically round nuclei that may display prominent nucleoli.
Warthin’s tumor epidemiology.
Warthin’s tumor AKA papillary cystadenoma lymphomatosum AKA adenolymphoma is the second most common benign neoplasm of salivary glands. It arises from ducts trapped during embryologic development of lymph nodes in the parotid glands, explaining why Warthin’s tumor almost always occurs in or around the parotid gland. It often affects people in the fourth to seventh decades of life, with M:F=5:1. Smokers have a higher risk of developing Warthin’s tumors. Warthin’s tumor are multifocal in ~25% of patients and are bilateral in ~5-7.5%. Most of them are cystic, feel “doughy” upon palpation, and yield cloudy fluid on FNA.
How does Warthin’s tumor appear on FNA?
Most of them are cystic, feel “doughy” upon palpation, and yield cloudy fluid on FNA. Smears are hypocellular, but scattered flat sheets of oncocytic cells and lymphocytes are likely to be found. Corpora amylacea and mast cells may be seen. Aspiration of more peripheral solid regions of the lesion may yield more cells. Oncocytic metaplasia is common in elderly males. Therefore, identification of all three components - oncocytic cells, lymphocytes, and cyst contents - is important for diagnosis.
How does pleomorphic adenoma/benign mixed tumor appear on FNA?
BMTs present as painless, slowly growing masses, and are the most common type of salivary gland tumor, especially in the parotid. Aspirates of BMT contain a combination of myxoid matrix, sheets and clusters of epithelial cells, and mesenchymal cells. The mesenchymal cells are of myoepithelial origin and are spindle shaped. “Hyaline cells” are modified myoepithelial cells which appear plasmacytoid with dense, glassy cytoplasm. They tend to present singly and may also be embedded within the fibrillary chondromyxoid stroma. Their presence is quite characteristic of BMT. Electron microscopy demonstrates that intermediate prekeratin filaments account for the dense, glassy appearance of the cytoplasm of hyaline cells. The chondromyxoid stroma is believed to be produced by myoepithelial cells. Tyrosine-rich crystals with radiating, flower-shaped or “daisy head” appearances stain orangeophilic on Pap stain and are not pathognomonic but, when present, support the diagnosis of BMT. They are detectable in less than 10% of BMTs. BMTs may show considerable epithelial atypia, but the atypia is limited and focal. If an aspirate contains features of BMT, but with readily identifiable, highly atypical epithelial cells, high mitotic activity, atypical mitotic figures and necrosis, malignant transformation should be suspected.
What tumors are seen in the subtypes of MEN syndrome?
MEN1: Pancreatic tumors (gastrinoma 50%, insulinoma 20-30%, VIPoma 12%, glucagonoma 33%. MEN 2B: Medullary thyroid carcinoma 85%, pheochromocytoma 50%, mucosal neuroma 100%, marfanoid body habitus 80%. FMTC: Medullary thyroid carcinoma 100%.
The granularity of oncocytes is due to __.
The granularity of oncocytes is due to an excessive amount of mitochondria, resulting in an abundant acidophilic, granular cytoplasm.
Benign lymphoepithelial cystic lesions in the salivary gland are seen in association with HIV infection. Describe.
Salivary gland enlargement associated with a significant lymphoid infiltrate is recognized in HIV-positive patients. Because the lymphoid tissue usually exhibits morphologic and immunophenotypic features similar to those seen in florid follicular hyperplasia and the lesions often occur in association with enlarged lymph nodes, benign lymphoepithelial cystic lesions are thought to represent a manifestation of persistent, generalized lymphadenopathy. AKA benign lymphoepithelial lesion, benign lymphocpithelial cyst, cystic lymphoid hyperplasia, and HIV-related salivary gland disease. The lesion most commonly arises in the parotid gland where it occurs in 3-6% of adults and 1-10% of children with HIV. Overall, benign lymphoepithelial cystic lesions account for ~25% of enlarged salivary glands in the HIV positive patient population. The lesions are often cystic, bilateral, multiple, and associated with lymphadenopathy. Morphologically, they are characterized by epithelial-lined cysts, often with squamous metaplasia, follicular hyperplasia, glandular atrophy, and in some cases epimyoepithelial islands. In many patients, treatment with HAART results in smaller lesions or their complete resolution.
The HIV-related plasmablastic lymphomas characteristically arise in what location?
The HIV-related plasmablastic lymphomas characteristically arise in the oral cavity (60% of cases); however, they can also occur in other mucosal sites, such as the sinonasal cavity and the GI tract, and in nonmucosal sites, such as the skin, soft tissue, and lymph nodes.
What lymphoid proliferations are seen in association with HIV?
Progressive HIV-related lymphadenopathy/HIV-related benign lymphadenopathy. Benign lymphoepithelial cystic lesions. Multicentric Castleman disease. Lymphomas associated with HIV can be subcategorized as those occuring (1) also in immunocompetent patients (most cases), (2) more specifically in HIV+ patients (~5% of cases), and (3) in other immunodeficiency states (<5% of cases). The main entities in (1) are BL (~30% of HIV-related lymphomas), DLBCL (~40%), and cHL (~5-15%). These neoplastic entities account for most of the HIV-related lymphoma, although only the first 2 entities are AIDS-defining diseases. The neoplasms in (2) are highly associated with infection by EBV, KSHV/HHV8, or both. They include: Plasmablastic lymphoma. KSHV+/HHV8+ large B-cell lymphoma associated with MCD. Primary effusion lymphoma/Extracavitary primary effusion lymphoma. In (3), the HIV polymorphic lymphoid proliferations, which resemble the polymorphic poasttransplant-associated lymphoproliferative disorders seen in solid organ transplant recipients, comprise thie category of HIV-related lymphoma/lymphoma-like lymphoproliferative disorders.
What entities are in the differential diagnosis of adenomyoepithelioma of the breast?
Papilloma with prominent myoepithelial cells (the cases with only myoepithelial cells lining the papillae and forming the basal layer below the epithelial elements and without nests, nodules, or an increased proportion of myoepithelial cells are categorized as such). Nipple adenoma (favored by the presence of florid ductal hyperplasia and the pseudoinfiltrative pattern of stromal sclerosis entrapping glandular epithelium without an entrapped fibrous tissue or supporting fibrovascular cores). Clear cell carcinoma (can confirm AME by positive IHC for both epithelial and myoepithelial cell types). Metaplastic tumors associated with papilloma. The adenosis variant of AME has an infiltrative growth pattern that resembles microglandular adenosis (the latter is characterized by an absence of myoepithelial layer and S100 positivity). If the AME predominantly displays a spindle cell component, it may morphologically be mistaken for myoid hamartoma or leiomyoma (AMEs will have strong positivity for S100 and p63, and are negative for actin and cytokeratin). Lesions composed exclusively of benign myoepithelial cells suggest myoepithelioma (do thorough sampling to identify a luminal epithelial component). Adenoid cystic carcinoma (ACC has infiltrative borders, cribriform architecture, and the myoepithelial cells of ACC tend to be smaller, more hyperchromatic, basaloid appearing, and have much less cytoplasm than do those of an AME). Pleomorphic adenoma (hyaline matrix with chondroid areas and distinct encapsulation are more prominent in PA).
How is an adenomatoid hyperplastic nodule of the thyroid defined?
Adenomatoid hyperplastic nodule on the other hand is defined by a follicular nodule that lacks a capsule but otherwise resembles a follicular adenoma.
Papillary thyroid carcinoma metastasizes via (hematogenous/lymphatic) spread. Follicular thyroid carcinoma metastasizes vie (hematogenous/lymphatic) spread.
PTC usually spreads via lymphatics and metastasizes first to lymph nodes. In comparison, FTC usually metastasizes directly to distant organs by hematogenous routes.
What additional histologic features are seen in follicular variant of papillary thyroid carcinoma, in addition to the nuclear features of usual papillary thyroid carcinoma?
In addition to the nuclear features of PTC, FVPTC is frequently associated with other morphologic abnormalities. Other secondary or “soft” features of FVPTC include irregularly shaped, elongated and branching follicles with hypereosinophilic colloid within the lumens, and multinucleated giant cells within the lumen of the follicles. Stromal sclerosis is another feature that is often encountered in these tumors, as well as psammoma bodies. Approximately 33% of cases are encapsulated. Occasionally, abortive papillary structures can also be identified focally in these tumors. The diagnosis of FVPTC is notoriously difficult to make on fine needle aspiration cytology or on frozen section examination. When in doubt, it is better to defer to permanent sections for a more definitive diagnosis.
Primary ciliary dyskinesia AKA immotile cilia syndrome is associated in ~50% of patients with ___ syndrome.
Primary ciliary dyskinesia AKA immotile cilia syndrome is associated in ~50% of patients with Kartagener syndrome AKA situs inversus totalis. Chronic bronchitis, recurrent pneumonia, and atelectasis is virtually pathognomonic for Kartagener syndrome, and in this situation, cilia evaluation is not required for diagnosis.
What is a white sponge nevus?
AKA Cannon disease AKA familial white folded mucosal dysplasia AKA hereditary leukokeratosis. An AD disease with incomplete penetrance and variable expressivity. Prominent parakeratosis, acanthosis, and spongiosis of nonkeratinized squamous mucosa. Rete are blunted. Inflammation is usually not present. Pathognomonic: Pap stain of exfoliative cytology shows a characteristic perinuclear eosinophilic condensation of keratin tonofilaments. Most commonly intraoral, with buccal mucosa most common intraoral site. DDx: hereditary benign intraepithelial dyskeratosis, leukoedema, oral hairy leukoplakia.
What is hairy leukoplakia AKA oral hairy leukoplakia?
An EBV-associated epithelial hyperplasia usually on the lateral tongue in immunocompromised patients, most commonly HIV+ males. The disease correlated with viral load and CD4 counts. Although not an AIDS-defining disease, is a marker of HIV disease progression. Micro: Marked acanthosis and parakeratosis. Epithelial hyperplasia with elongation of rete ridges. Viral cytopathic effect (balloon cells) in spinous layer. Candida can be seen in superficial keratin - coinfection is a common finding in OHL. Very little if any inflammation. No dysplasia. DDx: Frictional keratosis. Hyperplastic candidiasis. Leukoplakia. Lichen planus.
Is oral hairy leukoplakia an AIDS-defining illness?
No. OHL is an EBV-associated epithelial hyperplasia usually on the lateral tongue in immunocompromised patients, most commonly HIV+ males but seen in transplant patients as well. The disease correlated with viral load and CD4 counts. Although not an AIDS-defining disease, is a marker of HIV disease progression.
What is herpangina?
Herpangina is a common viral infection of young children associated with blisters of soft palate or tonsillar pillars. It is caused by viruses belonging to the Enterovirus group (coxsackievirus, poliovirus, echovirus). Coxsackie A16 virus is the most common cause. Transmission is direct contact, usually oral-fecal route.
What virus is the most common cause of herpangina?
Herpangina is a common viral infection of young children associated with blisters of soft palate or tonsillar pillars. It is caused by viruses belonging to the Enterovirus group (coxsackievirus, poliovirus, echovirus). Coxsackie A16 virus is the most common cause, but other coxsackie viruses usually associated include A1 to A6, A8, A10, or A22.
What is hand, foot, and mouth disease?
A common viral illness of infants and children, which causes fever and blister eruptions of mouth and/or skin. Caused by virus belonging to Enterovirus group. Transmission is by direct contact. Virus is found in secretions, including saliva, nose and throat secretions, blister fluid, and stools.
What is Heck disease?
AKA focal epithelial hyperplasia AKA multifocal epithelial hyperplasia. A benign, virus-induced epithelial proliferation of oral mucosa associated with HPV types 13 and 32. Majority of cases are in children. Micro: Prominent acanthosis and elongated broad rete ridges (since the thickened epithelium extends upward, elongated rete are at same depth as adjacent normal rete ridges). May see papillary surface. Mitosoid cells (represents ballooning and nuclear degeneration; represents an altered nucleus resembling a mitosis in an otherwise normal stratified squamous epithelium; can be seen throughout epithelium); do not misinterpret mitosoid cells as atypia. Koilocytic change in superficial keratinocytes can be seen. No dyskeratosis and/or atypia. DDx: Papilloma. Condyloma acuminatum. Oral verruca vulgaris.
What HPV types cause Heck disease (focal epithelial hyperplasia/multifocal epithelial hyperplasia)?
HPV types 13 and 32.
What sites are affected in pemphigus vulgaris?
PV is an autoimmune mucocutaneous disease characterized by intraepithelial blistering. Etiology is circulating autoantibodies to desmoglein 1 and 3 adhesion molecules of squamous epithelium, which inhibit cell-cell adhesion resulting in acantholysis and blister formation. Mucous membranes: oral, nasal, esophagus, larynx, nasopharynx, conjunctivae, genitalia, anal mucosa. Cutaneous sites are mostly on intertriginous areas, trunk, head, and neck. Mucosal PV may be the only manifestation of disease or may precede cutaneous PV by an average of 5 months. >90% of patients will have oral involvement during disease course.
What is the etiology of pemphigus vulgaris?
PV is an autoimmune mucocutaneous disease characterized by intraepithelial blistering. Etiology is circulating autoantibodies to desmoglein 1 and 3 adhesion molecules of squamous epithelium, which inhibit cell-cell adhesion resulting in acantholysis and blister formation (suprabasal bullae formation with intraepithelial clefting).
What is the characteristic direct immunofluorescence finding in pemphigus vulgaris?
Homogenous staining (“fishnet” pattern) of IgG in intercellular desmosomal areas at all levels of the epidermis.
What sites are affected in mucous membrane pemphigoid AKA cicatricial pemphigoid?
MMP is a chronic, blistering mucocutaneous autoimmune disease generally presenting in 6th or 7th decade and M:F=1:2. Oral cavity is frequently affected, with gingival involvement seen in >60%. Ocular lesions occur in ~40% of patients with oral MMP. Upper aerodigestive tract can also be affected. Micro shows subepithelial clefting, intact basal cells, and a sparse inflammatory cell infiltrate in superficial lamina propria.
What is the characteristic direct immunofluorescence finding in mucous membrane pemphigoid (cicatricial pemphigoid)?
Micro shows subepithelial clefting, intact basal cells, and a sparse inflammatory cell infiltrate in superficial lamina propria. Direct immunofluorescence shows a continuous linear band of IgG and C3 at basement membrane zone (can also see IgM and IgA).
What is seen in direct immunofluorescence of lichen planus?
DIF is not specific or diagnostic. May show linear or granular deposits of fibrin or fibrinogen. Deposits of C3, IgM, IgG, and IgA occasionally seen.
What is Riga-Fede disease?
AKA traumatic ulcer, traumatic ulcer with stromal eosinophilia, eosinophilic granuloma of tongue, traumatic granuloma, atypical histiocytic granuloma. It is a chronic traumatic ulceration of oral mucosa with unique histopathologic features. Riga-Fede disease specifically refers to trauma to the soft tissue (ventral tongue or inner lower lip) in newborns or infants from natal or neonatal teeth. In children, traumatic ulcer is often due to thermal or electrical burns or parafunctional habits. In adults, traumatic ulcer is often due to fractured and/or malposed teeth or parafunctional habits. Micro: Ulcer bed composed of granulation tissue with mixed inflammatory cell infiltrate of lymphocytes, histiocytes, neutrophils, and occasionally plasma cells. Inflammation including scattered eosinophils extends into underlying muscle.
What oral lesions are associated with pseudoepitheliomatous hyperplasia?
Granular cell tumor. Hyperplastic candidiasis. Inflammatory papillary hyperplasia. Median rhomboid glossitis. Necrotizing sialometaplasia. Mucosal ulcers (traumatic ulcers, aphthous ulcers, herpetic ulcers, nonhealing extraction sockets). Although PEH can have rete deeply extending into lamina propria, anastamosing of rete, and keratin pearl formation, there will be no or very little cytologic atypia, and while mitotic figures can be present, they will not be atypical.
What is necrotizing sialometaplasia?
A reactive, self-healing inflammatory condition of salivary glands leading to coagulative necrosis of salivary acini and squamous metaplasia of ductal structures. Likely due to vascular compromise leading to ischemic necrosis; associated with trauma due to dental treatment, surgery, or other iatrogenic events. Majority of lesions affect minor salivary glands, especially of hard and soft palate. DDx: Squamous cell carcinoma (In spite of necrosis and possible pseudoepitheliomatous hyperplasia, in NSM the lobular architecture of salivary gland is maintained, and nests of metaplastic squamous cells are round to ovoid with no cytologic atypia). Mucoepidermoid carcinoma (Although mucin pools and squamous epithelium may suggest MEC, in NSM there is a maintained lobular salivary gland architecture, no invasion, minimal cyst formation, no intermediate or clear cell proliferation, and there is formation of true squamous cells (rather than the epidermoid cells of MEC)).
What is the microscopic appearance of, and differential diagnosis of amalgam tattoo in oral tissues?
Amalgam tattoo is a localized area of blue, gray, or black pigmentation caused by amalgam (commonly used dental amalgam contains silver, tin, mercury, and other materials) embedded into oral tissues, usually during dental procedures. Microscopically, is fine black granules scattered within superficial connective tissue. Pigment can be seen in collagen, histiocytes, fibroblasts, elastic fibers, and around blood vessel walls. Usually no inflammation associated with the pigment. Foreign body multinucleated giant cell reaction seen in ~40%. DDx: Pigmented intraoral lesions such as intraoral melanocytic nevus, oral melanotic macule, and oral melanoma. Varicosities. Unintentional mucosal tattoos, such as from accidental placement of foreign material (eg pencil graphite).
What are Fordyce granules?
AKA ectopic sebaceous glands AKA Fordyce condition AKA Fordyce spots. Are benign, ectopic sebaceous glands most common on lateral margins of upper and lower lips and buccal mucosa. Considered a normal variant and thought to arise from ectoderm inclusions during fusion of mandible and maxilla. Micro: Normal sebaceous glands lacking hair follicles. May consist of only 1 lobules but usually multiple acinar lobules in superficial lamina propria. Central duct extending to surface epithelium can be seen. Sebaceous hyperplasia can occur, particularly with advanced age. Glands can become obstructed, forming pseudocysts with the lumen containing keratin, sebum, or mucin.
What is the juxtaoral organ of Chievitz?
A normal anatomic structure located in buccotemporalis fascia bilaterally along medial surface of ascending ramus. It persists throughout life and has no known function. Rare reports of hyperplasia of the juxtaoral organ of Chievitz, but none of carcinoma arising from it. Size ranges from 0.7-1.7 cm in length and 0.1-0.2 cm in width. Is composed of circumscribed nests of squamous cells within fibrous stroma. No mitoses, no or little pleomorphism, no keratinization, no desmoplasia, no inflammation. Duct-like lumina may be present. Stroma is rich in nerves (small nerve branches of buccal nerve), and epithelial islands are often intimately associated with them (intra- and perineural involvement). DDx: Invasive neurotropic squamous cell carcinoma. Mucoepidermoid carcinoma. Adenoid cystic carcinoma. Odontogenic carcinoma.
What is a ranula?
A ranula is a mucocele found on the floor of the mouth. When it is confined to the floor of the mouth it is a simple/oral ranula. A variant is the cervical/diving/plunging ranula, which can dissect the mylohyoid muscle, produce neck swelling, and large lesions may need sublingual gland excision. The term ranula is derived from the Latin word rana, meaning frog, and describes a blue translucent swelling in the floor of the mouth reminiscent of the bulging throat or underbelly of a frog.
What are the definitions of squamous papilloma, verrucae vulgaris, and condyloma accuminatum?
SP: Benign proliferation of squamous epithelium in exophytic pattern with branching fibrovascular tissue cores exhibiting papillary pattern causally related to HPV infection (subtypes 6 and 11 detected in ~50% of cases, rarely HPV 16 detected). VV (AKA common wart or oral wart): Benign HPV-induced (subtypes 2, 4, 6, 40, or 57 detected in 100% of cases) proliferation of squamous epithelium, usually on skin, but also in oral cavity. CA (AKA veneral wart): HPV-related (subtypes 2, 6, 11, 53, or 54 in oral area, rarely 16, 18, or 31 (usually anogenital)) proliferation of squamous epithelium of genitalia, perianal region, oral cavity, or larynx.
What is an Abrikossoff tumor?
AKA granular cell tumor AKA granular cell myoblastoma AKA granular cell nerve sheath tumor AKA granular cell schwannoma.
What is a gingival granular cell tumor of infancy?
AKA Neumann tumor AKA congenital epulis of the newborn. A rare, benign congenital growth on alveolar mucosa in neonates. M:F = 1:8-10. Maxilla:mandible = 3:1. Can be histologically indistinguishable from granular cell tumor, but unlike GCT, develops in newborns to infants only and is S100 negative. Also, while ~50% of GCTs of the oral cavity have pseudoepitheliomatous hyperplasia, congenital epulis never has it. Not to be confused with “nonneural granular cell tumor,” which is a tumor in adults that is S100 negative.
What are etiologies for pyogenic granuloma in the oral cavity? What is the epidemiology?
Pyogenic granuloma AKA lobular capillary hemangioma AKA epulis granulomatosus AKA pregnancy tumor (epulis gravidarum). Etiologies include poor oral hygiene, local irritants (fractured tooth, poor restoration), localized trauma (biting), and hormones (increased in pregnancy and oral contraceptive use. Most common in children and young adults. In up to age 18, M>F but in adults M:F = 1:2. About 1% of pregnant women develop PG, and is related to hormonal influences on vessels. Gingiva is the most common site of oral cavity PG.
What is the cell of origin for pyogenic granuloma/lobular capillary hemangioma?
Bicellular origin from endothelial and pericyte cells.
Peripheral ossifying fibroma.
AKA peripheral fibroma with calcification. Is a reactive proliferation of fibrous tissue with mineralization exclusive to gingiva. May be associated with chronic irritation. Origin is cells from periosteum and/or periodontal ligament. Micro: Cellular fibroblastic stroma with a mineralized component (trabecular bone, woven bone, dystrophic calcification, cementum, or a combination of the above). Surface may be ulcerated.
Mucosal neuroma. What syndromes are associated with it?
Multiple endocrine neoplasia, specifically MEN2B. Most cases of multiple mucosal neuromas are associated with MEN2B. Also, mucosal neuromas are associated with PTEN hamartoma tumor syndrome (PHTS), including Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome.
Mucosal neuroma.
Proliferation of nerves, often in a plexiform pattern. Seen on tongue and lips most commonly. Most cases of multiple lesions are seen in patients with MEN2B. Micro: Nonencapsulated, with a haphazard distribution. Hyperplasia of nerve bundles. Prominent thickening of perineurium. DDx: Neurofibroma (may blend with surrounding tissue, has spindle cells with variable collagen). Traumatic neuroma (lacks the prominent perineurium seen in mucosal neuroma). Palisaded encapsulated neuroma (encapsulated at least partially, has spindle cells). Schwannoma (neurilemoma) (characteristic Antoni A and B areas, Verocay bodies, and hyalinized vessels).
What is an epignathus?
A teratoma that arises in the oral cavity. Most common sites are palate and tongue.
Teratomas of the oral cavity.
AKA epignathus. Rare; 1 in 4000 live births have teratoma, and 1-2% of those involve head and neck. Most common sites of teratoma of the oral cavity are palate and tongue. Prenatally, can have polyhydramnios due to impaired fetal swallowing, and AFP concentrations are increased. At birth, can have significant respiratory distress. Top DDx: dermoid cyst or encephalocele.
What is oropharyngeal carcinoma?
Basically is a squamous cell carcinoma of oropharynx, the sites including soft palate, tonsils, uvula, base of tongue, and oropharyngeal wall comprising Waldeyer ring. Is also called oropharyngeal squamous cell carcinoma (OPSCC). What is typically called oral squamous cell carcinoma involves the sites of tongue (lateral and ventral), floor of mouth, lip, retromolar trigone, gingiva, buccal mucosa, and palate. HPV+ OPSCC is nonkeratinizing, while HPV- OPSCC is keratinizing. Other subtypes include: Hybrid-type OPSCC, which has features of both nonkeratinizing OPSCC and keratinizing SCC; is HPV+ most of the time. Lymphoepithelial-like OPSCC, which is similar in histology to EBV-related nasopharyngeal carcinoma; is HPV+. Papillary OPSCC, which is an uncommon variant; most are HPV+.
What are the top 3 most common metastatic tumors to the oral cavity in males and females?
Males: lung > kidney > prostate. Females: breast > genital organs > kidney.
What entities are in the differential diagnosis of osteomyelitis in the head and neck region?
Osteomyelitis AKA osteitis is inflammation or infection of bone and bone marrow. Top differential diagnoses include inflammatory reaction (inflammation part of fracture repair; present at tumor borders; lack of acute inflammation and dead bone), lymphoma (atypical lymphoid infiltrate with bone remodeling and dense fibrosis), sarcoid (noncaseating, tight, well-formed granulomas), bisphosphonate therapy (bone necrosis with death, followed by active remoderling; more often a chronic process), and radiation osteitis (bone necrosis and death with chronic inflammation).
What is cherubism?
Cherubism is an inherited disease characterized by progressive, painless, symmetrical expansion of the jaws, resulting in a cherubic facial appearance. M:F = 2:1, with 100% penetrance in males and 50-70% penetrance in females. Mutations in the SH3BP2 gene have been identified in about 80 percent of people with cherubism. In most of the remaining cases, the genetic cause of the condition is unknown. There are germline point mutations in the SH3BP2 gene on chromosome 4p16.3.
What is the most common type of rhabdomyosarcoma?
Embryonal rhabdomyosarcoma is the most common type (65% of RMS cases) and usually occurs in children ages 3-10 in the head and neck (nasal and oral cavities, orbit, ear), prostate or paratesticular regions. Subtypes of embryonal rhabdomyosarcoma include embryonal NOS, anaplastic, botryoid, and spindle cell, with embryonal NOS being the most common subtype (75%).
What is the most common subtype of embryonal rhabdomyosarcoma?
Embryonal rhabdomyosarcoma is the most common type of rhabdomyosarcoma (65% of RMS cases) and usually occurs in children ages 3-10 in the head and neck (nasal and oral cavities, orbit, ear), prostate or paratesticular regions. Subtypes of embryonal rhabdomyosarcoma include embryonal NOS, anaplastic, botryoid, and spindle cell, with embryonal NOS being the most common subtype (75%).
What is a central giant cell lesion?
AKA central giant cell granuloma AKA giant cell reparative granuloma AKA giant cell tumor. A potentially locally aggressive osteolytic lesion of gnathic bones. Neoplastic process is favored over reactive. The mandible is most commonly affected, with the anterior region more common. It frequently crosses the midline. Histologically, the tumor is composed of giant cells and stroma. The giant cells are most likely related to osteoclasts, can be focal collections or diffusely distributed, have variable size and shape, and can have up to 20 nuclei per cell. The stroma can be loosely arranged to fibrous, is cellular, and can have erythrocyte extravasation with hemosiderin. Do not confuse this entity with the other “giant cell tumor” which is thought to occur exclusively in long bones.
What is osteitis deformans?
Osteitis deformans is a synonym for Paget disease of bone, which is a localized skeletal disorder characterized by osteoclasts of increased number and size containing multiple nuclei. There is excessive breakdown and formation of bone tissue. Most common sites of involvement are: pelvis (70%) > femur (55%) > lumbar spine (50-55%) > skull (40%) > tibia (30%).
True or false. In Paget disease of bone, serum calcium is elevated.
False. Total serum alkaline phosphatase is elevated in over 85% of patients, and may be useful in monitoring the disease. Serum calcium, phosphorus, and aminotransferase are normal in Paget disease of bone.
Risk of secondary sarcoma is __% in Paget disease of bone.
Risk of secondary sarcoma is 4-10% in Paget disease of bone. Secondary sarcomas are generally high grade. The most common types are osteosarcoma and malignant fibrous histiocytoma, but fibrosarcoma and giant cell tumor of bone may also be seen.
What is the etiology of Paget disease of bone?
Unknown. Infectious agents have been proposed based on electron microscopy data, but there is no conclusive proof. The disease occurs in familial clusters and sporadically. 15-40% of patients have a positive family history. Familial cases display an autosomal dominant pattern of inheritance with variable penetrance. Cytogenetic studies of families with Paget disease of bone have identified numerous involved chromosomal loci. Nongenetic factors are also involved in the appearance of the disease, as there is variable penetrance in families, and the fact that the disease has a highly localized nature.
What are the histologic features of Paget disease of bone?
Findings reflect the stage of disease. The initial stages are reflective of osteoclastic activity: numeous osteoclasts, increased vascularity, and numerous resorptive surfaces. Mid-stage shows a mix of patterns: osteoclastic resorption, increased vascularity, and numerous surfaces covered with active osteoblasts. End stage is primarily sclerotic.
What is a simple bone cyst of the head and neck region?
Simple bone cyst AKA traumatic bone cyst AKA traumatic bone cavity AKA solitary bone cyst AKA hemorrhagic cyst. Is a benign empty or fluid-filled cavity within bone most commonly in the mandible. Histologically, will have small fragments of fibrovascular connective tissue, small fragments of bone that are reactive with cellular trabeculae, red blood cells, rare giant cells, dystrophic calcifications, and no epithelial lining. The differential diagnosis includes developmental odontogenic cysts such as dentigerous cyst or lateral periodontal cyst (both have a cyst lining), or reactive odontogenic lesions such as radicular cyst (has a cyst lining) or periapical granuloma (dense inflammatory infiltrate).
Dentigerous cyst. Definition, etiology, and epidemiology.
AKA follicular cyst. Is a developmental cyst surrounding the crown of an impacted tooth and attached to cemento-enamel junction. It develops by accumulation of fluid between reduced enamel epithelium and crown of a tooth. It is the most common developmental cyst (25% of all jaw cysts). Peak incidence 2nd to 3rd decade. Slight male predilection. Most commonly associated with mandibular 3rd molars or maxillary canines.
Dentigerous cyst. Microscopic appearance. DDx.
AKA follicular cyst. It a developmental cyst surrounding the crown of an impacted tooth and attached to the cemento-enamel junction. Dentigerous cysts can be noninflamed or inflamed. Noninflamed: fibrous to fibromyxoid connective tissue; 2-3 layers of cuboidal to ovoid epithelium; occasional mucous cells; rare ciliated cells; occasional dystrophic calcifications; odontogenic epithelial rests. Inflamed: fibrous connective tissue; proliferative epithelium; hyperplastic rete ridges; chronic inflammatory cells; acute inflammatory cells, usually associated with oral communication; cholesterol clefts; Rushton bodies (AKA hyaline bodies in odontogenic cysts feature as eosinophilic, straight or curved, irregular or rounded structures within the epithelial lining of odontogenic cysts); rare mucous cells; rare ciliated cells; rare sebaceous cells. DDx: enlarged dental follicles (has no cystic epithelium).
What are Rushton bodies?
Rushton bodies AKA hyaline bodies in odontogenic cysts feature as eosinophilic, straight or curved, irregular or rounded structures within the epithelial lining of odontogenic cysts. They are present exclusively within odontogenic cysts, and are found almost always within the epithelial lining and only rarely in the fibrous capsule. Rushton bodies may show up in examination of the gross specimen as small, white, dome-shaped swellings measuring up to 0.1 mm on the epithelial surface and protruding into the cyst cavity. In microscopic sections, they appear as eosinophilic, linear, straight or curved or hairpin shaped, circular or polycyclic forms, often with a granular core and sometimes concentrically laminated. They were thought to be of hematogenous origin, but it has been found that Rushton bodies are a secretory product of odontogenic epithelium deposited on the surface of particulate matter like cell debris or cholesterol crystals.
Periapical cyst/granuloma.
Periapical cyst AKA periradicular cyst AKA apical periodontal cyst. Periapical granuloma AKA periradicular granuloma AKA periradicular periodontitis. Definition: inflamed tissue associated with apex or root surface of nonvital tooth. Natural history: caries causes cavitation of tooth; bacterial invasion of pulp tissue; toxins are generated; pulp tissue becomes devitalized. Periapical cysts make up ~75% of periapical lesions, and are the most common cyst of the jaw; periapical granulomas are less common. Microscopic: fibrous tissue; variable inflammation (chronic and acute: lymphocytes, plasma cells, multinucleated giant cells, histiocytes, eosinophils, and neutrophils); dystrophic calcifications; cholesterol clefts; foreign material if previously endodontically treated; periapical cyst will have stratified squamous epithelial lining.
Ameloblastoma. Definition. Epidemiology. Treatment. Transformation?
Definition: Benign, slowly growing, locally aggressive neoplasm of odontogenic epithelium. Most common odontogenic tumor excluding odontomas. 80-85% occur in the posterior mandible. Peripheral ameloblastoma (found on gingiva, usually anterior mandible) is the most common peripheral odontogenic tumor. Intraosseous type - average age 36; unicystic type - 75% found in 2nd to 3rd decade; peripheral type - average age 51. Equal gender distribution. Conventional ameloblastomas generally require en bloc resection. Unicystic lesions are treated with local enucleation. Peripheral lesions are easily treated with local excision. Rare transformation to ameloblastic carcinoma (destructive growth, cytologic features of malignancy including pleomorphism and increased mitoses) or malignant ameloblastoma (required development of metastatic deposits, which are usually in lung).
Ameloblastoma. Microscopic appearance. Variants.
Odontogenic epithelial islands: centrally, stellate reticulum composed of loosely arranged angular cells; surrounded by single layer of ameloblast-like cells; nuclei are located away from basement membrane (reverse polarity AKA Vickers-Gorlin change); basal cytoplasmic vacuolization. Stroma is variable and can be loose or dense. Numerous patterns can be seen (a single pattern may predominate, or a combination of patterns can be seen). Invasive. Variants: plexiform, follicular, desmoplastic, basaloid, granular cell, acanthomatous, unicystic.
