Oral Cavity



Oral Cavity






5.1 ACANTHOLYTIC VARIANT OF SQUAMOUS CELL CARCINOMA VS. ANGIOSARCOMA


















































Acantholytic Variant of Squamous Cell Carcinoma


Angiosarcoma


Age


Typically elderly adults


Typically elderly adults


Location


Most common in the skin. In the upper aerodigestive tract, most commonly affects the oral cavity, particularly the vermillion border of the lip


May occur at essentially any site, but most common in the skin and soft tissues of the head and neck, especially the scalp. Often multifocal. Rare in the mucosal head and neck


Symptoms


Dependent on site. In the oral cavity, a mass, often with associated pain


Dependent on site


Signs


Irregular fleshy mass, often large and exophytic


Varies from a red-purple plaque to large irregular fleshy masses


Etiology


Disruption of intercellular connections in the nests of invasive carcinoma. Tumors of the vermillion border often seen in association with chronic sun exposure


Risk factors include long-standing lymphedema, therapeutic radiation, and exposure to Thorotrast


Histology




  1. Highly infiltrative, unencapsulated proliferation of anastomosing slit-like structures that merge with other foci of recognizable squamous cell carcinoma with overt cytoplasmic keratinization, keratin pearls, and intercellular bridges (Figs. 5.1.1 and 5.1.2)



  2. The pseudovascular spaces represent foci of dyscohesion in the squamous carcinoma



  3. Pseudovascular spaces are ragged and usually contain cellular debris or dyskeratotic cells within the false lumen (i.e., acantholysis) (Fig. 5.1.2)



  4. Overlying surface epithelium typically demonstrates squamous dysplasia or carcinoma in situ (Fig. 5.1.3)



  5. Marked cellular atypia, with frequent mitotic figures and atypical mitotic figures (Fig. 5.1.2)




  1. Highly infiltrative, unencapsulated proliferation of anastomosing slit-like structures, without recognizable squamous cell carcinoma (overt cytoplasmic keratinization, keratin pearls, and intercellular bridges) (Fig. 5.1.5)



  2. Vascular spaces often contain blood, hemosiderin, and inflammatory cells but not dyskeratotic cells (Figs. 5.1.6 and 5.1.7)



  3. No squamous dysplasia or carcinoma in situ of the overlying squamous epithelium



  4. Variably cellular atypia in the form of nuclear enlargement, hyperchromasia, pleomorphism, frequent mitotic figures, and atypical mitotic figures (Figs. 5.1.6 and 5.1.7)


Special studies




  • The tumor—including the pseudovascular spaces—is diffusely positive for squamous markers p63, p40, and CK5/6 (Fig. 5.1.4)



  • Negative for vascular markers CD31, CD34, and ERG




  • Positive for vascular markers CD31, CD34, and ERG (Fig. 5.1.8)



  • May be positive for cytokeratins (epithelioid angiosarcoma) but typically negative for squamous markers p63, p40, and CK5/6


Treatment


Similar to mucosal squamous cell carcinoma: surgical excision usually with adjuvant radiation and chemotherapy


Resection, external beam radiation therapy, and/or chemotherapy


Prognosis


Does not seem to have a prognosis that differs from conventional squamous cell carcinoma


Poor, with 5-year survival of approximately 30%-50%. Recurrences and metastases (lymph node and lung) are common







Figure 5.1.1 Acantholytic variant of squamous cell carcinoma with numerous, anastomosing vascular-like spaces lined by dark, atypical cells, mimicking angiosarcoma.






Figure 5.1.2 Acantholytic variant of squamous cell carcinoma with vascular-like spaces (right) merging with areas of conventional squamous cell carcinoma (left) that demonstrate overt keratinization.






Figure 5.1.3 Acantholytic variant of squamous cell carcinoma arising from a surface epithelium that contains squamous carcinoma in situ.






Figure 5.1.4 Acantholytic variant of squamous cell carcinoma is diffusely positive for the squamous immunohistochemical marker p40.







Figure 5.1.5 Angiosarcoma consisting of anastomosing vascular channels in the submucosa. The overlying squamous epithelium is not dysplastic.






Figure 5.1.6 Angiosarcoma with vascular spaces filled with red blood cells and hemosiderin and lined by enlarged, hyperchromatic cells.






Figure 5.1.7 Angiosarcoma with marked cellular atypia in the form of nuclear pleomorphism, prominent nucleoli, and at atypical mitotic figure.






Figure 5.1.8 Angiosarcoma is consistently positive for the vascular immunohistochemical marker CD34.



5.2 ADENOSQUAMOUS CARCINOMA VS. ACANTHOLYTIC VARIANT OF SQUAMOUS CELL CARCINOMA


















































Adenosquamous Carcinoma


Acantholytic Variant of Squamous Cell Carcinoma


Age


Adults, peak in seventh and eighth decades


Typically elderly adults


Location


Almost always mucosal sites, especially the larynx, oral cavity, and oropharynx


Most common in the skin. In the upper aerodigestive tract, most commonly affects the oral cavity, particularly the vermillion border of the lip


Symptoms


Dependent on site. In the oral cavity, a mass, often with associated pain


Dependent on site. In the oral cavity, a mass, often with associated pain


Signs


Irregular fleshy mass, often large and exophytic


Irregular fleshy mass, often large and exophytic


Etiology


Glandular component could represent divergent differentiation from squamous cell carcinoma or perhaps a component that arose from seromucinous glands. A subset of oropharyngeal and nasal cases harbor highrisk HPV


Disruption of intercellular connections in the nests of invasive carcinoma. Tumors of the vermillion border often seen in association with chronic sun exposure. An HPV-related form has not been described


Histology




  1. Highly infiltrative, unencapsulated proliferation of squamous nests and tumor glands



  2. Squamous and glandular components are typically separate and distinct, with the glandular component often in the deeper portions of the tumor (Fig. 5.2.1)



  3. Glandular component consists of punched-out ductal structures and/or scattered mucinous cells (Fig. 5.2.2)



  4. Marked cellular atypia, with frequent mitotic figures in both squamous and glandular components (Fig. 5.2.2)




  1. Highly infiltrative, unencapsulated proliferation of gland-like structures that merge with other foci of recognizable squamous cell carcinoma (Fig. 5.2.5)



  2. The pseudoglandular spaces represent foci of dyscohesion in the squamous carcinoma and not true glands (Fig. 5.2.6)



  3. Pseudoglandular spaces are ragged and usually contain cellular debris or dyskeratotic cells within the false lumen (Figs. 5.2.6 and 5.2.7)



  4. Mucinous cells are absent



  5. Marked cellular atypia, with frequent mitotic figures


Special studies




  • The squamous component is diffusely positive for squamous markers p63, p40, and CK5/6



  • Glandular component is negative for p63, p40, CK5/6, and positive for CK7 (Fig. 5.2.3)



  • Mucin stains are positive in scattered mucinous cells in the glandular component (Fig. 5.2.4)



  • A subset of oropharyngeal and nasal cases harbor high-risk HPV




  • The tumor—including the pseudoglandular spaces—is diffusely positive for squamous markers p63, p40, and CK5/6 (Fig. 5.2.7)



  • Negative for CK7 and mucin (Fig. 5.2.8)



  • An HPV-related form has not been described


Treatment


Similar to mucosal squamous cell carcinoma: surgical excision usually with adjuvant radiation and chemotherapy


Similar to mucosal squamous cell carcinoma: surgical excision usually with adjuvant radiation and chemotherapy


Prognosis


Poor, with 5-year survivals of 20%-40%


Does not seem to have a prognosis that differs from conventional squamous cell carcinoma







Figure 5.2.1 Adenosquamous carcinoma with two separate, distinct components: squamous cell carcinoma (left) and adenocarcinoma (right).






Figure 5.2.2 Adenosquamous carcinoma with glandular differentiation in the form of punched-out glandular spaces.






Figure 5.2.3 Adenosquamous carcinoma with diffuse immunoreactivity for CK7.






Figure 5.2.4 Adenosquamous carcinoma with mucin highlighted by a mucicarmine stain.







Figure 5.2.5 Acantholytic variant of squamous cell carcinoma with pseudoglandular spaces (right) merging with conventional-appearing squamous cell carcinoma (left).






Figure 5.2.6 Acantholytic variant of squamous cell carcinoma with numerous pseudoglandular spaces, many of which are filled with necrotic debris.






Figure 5.2.7 Acantholytic variant of squamous cell carcinoma is diffusely positive for p40 in the pseudoglandular areas.






Figure 5.2.8 Acantholytic variant of squamous cell carcinoma is negative for mucin by mucicarmine staining.



5.3 ORAL CANDIDIASIS VS. SQUAMOUS DYSPLASIA

















































Oral Candidiasis


Squamous dysplasia


Age


Young infants and elderly patients most commonly affected


Adults, peak in sixth to eighth decades


Location


Anywhere in the oral cavity, most commonly buccal mucosa, oropharynx, and lateral tongue


Most commonly the tongue, floor of the mouth, and palate


Symptoms


Burning sensation, tenderness, and dysphagia


Usually asymptomatic


Signs


Four clinical forms in order of frequency: (1) pseudomembranous (thrush), (2) erythematous, (3) hyperplastic, and (4) angular cheilitis


White (leukoplakia), red (erythroplakia), or mixed (speckled leukoplakia) plaques in the oral cavity


Etiology


Candida spp., most commonly C. albicans. Patients often immunocompromised (HIV/AIDS, chronic steroid therapy, diabetes, undergoing chemotherapy)


Accumulation of genetic alterations including p53 mutations, usually secondary to smoking. Rare examples of bowenoid dysplasia harbor high-risk HPV


Histology




  1. Varying degrees of squamous hyperplasia with hyperkeratosis and parakeratosis, increasing with the chronicity of infection (Fig. 5.3.1)



  2. Presence of a neutrophilic infiltrate and/or microabscesses in the squamous epithelium is an important clue (Fig. 5.3.1). The more acute the infection is, the more inflammation is seen



  3. Some reactive cellular and architectural atypia typically present in the form of bulbous rete, enlarged nuclei, and elevated mitotic rate, but the severity is usually mild (Fig. 5.3.2)



  4. Variable numbers of fungal hyphae in the superficial epithelial layers, particularly in foci of parakeratosis (Fig. 5.3.3)



  5. Fungal elements usually visible by routine histology, consisting of refractile elements, often arranged perpendicularly to the surface (Fig. 5.3.3)




  1. Combination of cytologic and architectural atypical features



  2. Atypical cytologic features include nuclear enlargement, nuclear hyperchromasia, prominent nucleoli, and abnormal mitotic figures



  3. Atypical architectural features include dropshaped rete ridges, basal layer hyperplasia, mitotic figures above the basal layer, irregular stratification, deep keratin pearls, and dyskeratotic cells



  4. Graded as mild, moderate, or severe based largely on how much of the epithelium is involved (lower one-third for mild, midthird for moderate, upper-third for severe) (Figs. 5.3.5, 5.3.6 and 5.3.7)



  5. Candida organisms not typically seen. If present, the degree of atypia must be beyond what can be accounted for by candidiasis


Special studies


Special stains for fungi (GMS or PAS) highlight the fungal organisms (Fig. 5.3.4)


Special stains for fungi (GMS or PAS) typically negative for the fungal organisms


Treatment


Antifungal agents (either topical or systemic) and attention to any underlying disease process


Mild dysplasia: excision or close follow-up. Mild/severe: surgical excision


Prognosis


Benign process. When predisposing conditions present, recurrence is common


Rate of malignant transformation is low overall (5%-20%); risk rises with increasing severity








Figure 5.3.1 Oral candidiasis with squamous hyperplasia, parakeratosis, and a patchy intraepithelial infiltrate of neutrophils.






Figure 5.3.2 Oral candidiasis with mild architectural atypia in the form of bulbous rete and basal layer hyperplasia.






Figure 5.3.3 Oral candidiasis with refractile, hyaline fungal elements in the parakeratosis, oriented perpendicular to the epithelium.






Figure 5.3.4 Oral candidiasis with numerous fungal forms highlighted by PAS staining.







Figure 5.3.5 Mild squamous dysplasia with acanthosis, drop-shaped rete, and basal layer hyperplasia. Atypical changes are limited to the lower one-third of the epithelium. This degree of dysplasia overlaps considerably with the architectural changes that can be seen in candidiasis.






Figure 5.3.6 Moderate squamous dysplasia with architectural (broad rete, basal layer hyperplasia, and disorganization) and cytologic (nuclear enlargement and hyperchromasia) atypia, confined to the lower half of the epithelium. This degree of atypia is far beyond that which could be accounted for by candidiasis.






Figure 5.3.7 Severe squamous dysplasia with marked architectural (broad rete, basal layer hyperplasia, and disorganization) and cytologic (anaplasia, atypical mitotic figures) atypia involving almost the entire thickness of the epithelium. This degree of atypia is far beyond that could be accounted for by candidiasis.



5.4 GRANULAR CELL TUMOR VS. CONGENITAL EPULIS

















































Granular Cell Tumor


Congenital Epulis


Age


Wide age range, most often third to fifth decades


Newborn infants, usually girls


Location


Most frequently larynx and oral cavity (especially tongue)


Usually anterior maxillary alveolus


Symptoms


In the larynx, hoarseness. Elsewhere, painless nodule


May interfere with breathing or feeding


Signs


Small, nontender, circumscribed nodule


Pedunculated fleshy gingival mass


Etiology


Unknown. Granular cell tumor is of nerve sheath origin


Unknown


Histology




  1. Unencapsulated sheet-like proliferation of large polygonal cells with pale, granular amphophilic to eosinophilic cytoplasm (Fig. 5.4.1)



  2. Often associated with a striking pseudoepitheliomatous hyperplasia of the overlying surface epithelium that can mimic squamous cell carcinoma and obscure the granular cell tumor (Fig. 5.4.2)



  3. No significant nuclear atypia, mitoses, or necrosis




  1. Unencapsulated sheet-like proliferation of large polygonal cells with pale, granular amphophilic to eosinophilic cytoplasm (Figs. 5.4.4 and 5.4.5)



  2. No pseudoepitheliomatous hyperplasia. In fact, in some cases, the overlying epithelium is atrophic



  3. No significant nuclear atypia, mitoses, or necrosis (Fig. 5.4.5)


Special studies


Diffusely positive for S100, SOX10, and inhibin (Fig. 5.4.3). Negative for desmin and myogenin


Negative for S100, SOX10, and inhibin


Treatment


Surgical excision


Surgical excision or observation


Prognosis


Excellent. Low risk of recurrence


Excellent. Some tumors may regress spontaneously








Figure 5.4.1 Granular cell tumor with sheets and nests of polygonal, round to spindled cells with abundant granular eosinophilic cytoplasm, set in a sclerotic stroma.






Figure 5.4.2 Granular cell tumor associated with striking pseudoepitheliomatous hyperplasia.






Figure 5.4.3 Granular cell tumor is diffusely positive for S100.






Figure 5.4.4 Congenital epulis with a collection of large, pale, granular cells in the submucosa.






Figure 5.4.5 Congenital epulis consists of clusters of large, polygonal histiocyte-like cells with abundant, granular eosinophilic cytoplasm.



5.5 HECK DISEASE (FOCAL EPITHELIAL HYPERPLASIA) VS. SQUAMOUS DYSPLASIA

















































Heck Disease (Focal Epithelial Hyperplasia)


Squamous Dysplasia


Age


Can affect any age, but most commonly children and young adults. Often American Indians or Inuits, but not restricted to these populations


Adults, peak in sixth to eighth decades


Location


Labial, lingual, or buccal mucosa


Most commonly the tongue, floor of the mouth, and palate


Symptoms


Usually none


Usually asymptomatic


Signs


Multiple small, clustered fleshy papules or nodules


White (leukoplakia), red (erythroplakia), or mixed (speckled leukoplakia) plaques in the oral cavity


Etiology


Human papillomavirus types 13 or 32


Accumulation of genetic alterations including p53 mutations, usually secondary to smoking. Rare examples of bowenoid dysplasia harbor high-risk HPV


Histology




  1. Squamous hyperplasia with expansion and fusion of rete ridges (Fig. 5.5.1)



  2. Koilocytes—squamous cells with hyperchromatic, wrinkled appearing nuclei, and paranuclear haloes—may be seen (Fig. 5.5.2)



  3. Mitosoid body—squamous cell with peculiar fragmentation of chromatin, resembling an atypical mitotic figure—haphazardly distributed throughout squamous epithelium (Fig. 5.5.3)



  4. No other significant cytologic or architectural atypia




  1. Combination of cytologic and architectural atypical features



  2. Atypical cytologic features include nuclear enlargement, hyperchromasia, prominent nucleoli, and abnormal mitotic figures



  3. Atypical architectural features include dropshaped rete ridges, basal layer hyperplasia, mitotic figures above the basal layer, irregular stratification, deep keratin pearls, and dyskeratotic cells (Fig. 5.5.4)



  4. Graded as mild, moderate, or severe based largely on how much of the epithelium is involved (lower one-third for mild, mid-third for moderate, upper-third for severe)


Special studies


HPV in situ hybridization for HPV types 13 and 32


Negative for HPV types 13 and 32


Treatment


None or simple excision


Mild dysplasia: excision or close follow-up. Mild/severe: surgical excision


Prognosis


Excellent. Some cases spontaneously regress


Rate of malignant transformation is low overall (5%-20%); risk rises with increasing severity








Figure 5.5.1 Heck disease with squamous hyperplasia demonstrating elongated rete ridges that fuse together.






Figure 5.5.2 Heck disease with scattered koilocytic cells scattered in the upper layers of the squamous epithelium.






Figure 5.5.3 Heck disease with scattered mitosoid bodies—squamous nuclei with chromatin fragmentation. These bodies mimic atypical mitotic figures, but unlike squamous dysplasia, there are no other atypical cellular or architectural features.






Figure 5.5.4 Severe squamous dysplasia with atypical mitotic figures in addition to marked nuclear pleomorphism and hyperchromasia and minimal maturation.



5.6 INJECTED COSMETIC MATERIAL VS. ATYPICAL LIPOMATOUS TUMOR (WELL-DIFFERENTIATED LIPOSARCOMA)

















































Injected Cosmetic Material


Atypical Lipomatous Tumor (Well-Differentiated Liposarcoma)


Age


Adults, ranging from 21 to 81, with mean 50 years. Women more common than man


Adults ranging from 25 to 83, mean age approximately 50


Location


Upper and/or lower lip, nasolabial fold, and buccal mucosa


Can rarely involve virtually any head and neck site, most often oral cavity and larynx. In areas like oral cavity that are accessible for complete excision, the term “atypical lipomatous tumor” is used, while identical tumors that are deep-seated tumors are referred to as welldifferentiated liposarcoma


Symptoms


None or pain


Painless, slow-growing mass


Signs


Nodule(s) or swelling


Circumscribed mass, yellow on cut section


Etiology


Cosmetic injection of various biomaterials (silicone, collagen, hyaluronic acid, and others)


Unknown


Histology




  1. Permeation of soft tissues by clusters, sheets and individual histiocytes (Figs. 5.6.1 and 5.6.2)



  2. The histiocytes often exhibit clear cytoplasmic vacuoles that indent the nucleus, closely mimicking lipoblasts (Fig. 5.6.3)



  3. No cells with large, hyperchromatic nuclei




  1. Variably circumscribed proliferation of mature-appearing fat divided into lobules by fibrous septa (Fig. 5.6.5)



  2. Diagnostic cells are large, hyperchromatic spindled cells scattered among the matureappearing lipocytes, often in the fibrous septa (Fig. 5.6.6)



  3. Lipoblasts—fatty cells with fat vacuoles that crisply indent the tumor cell nucleus—are scant and often not seen at all (Fig. 5.6.7)


Special studies


Positive for CD68, negative for MDM2 (Fig. 5.6.4)


Positive for MDM2, negative for CD68 (Fig. 5.6.8)


Treatment


Excision and/or steroids (intralesional or systemic)


Wide local excision


Prognosis


Benign, but can be a disfiguring process


Good. Low risk of recurrence when completely excised

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Sep 23, 2018 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Oral Cavity

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