Branchial Cleft Cyst

Metastatic HPV-Related Squamous Cell Carcinoma

Age

Most commonly young adults. Rare in adults older than 50

Adults with peak in fifth and sixth decades

Location

Second branchial cleft cysts occur in lateral neck along anterior aspect of sternocleidomastoid muscle. First branchial cleft abnormalities occur around the ear

Cervical lymph node(s) in level 2 or 3

Symptoms

Often asymptomatic, but when infected can become swollen and painful

Painless swelling of neck. Usually patients have no known primary carcinoma

Signs

Fluctuant masses, not tender to palpation, may become secondarily infected

Cystic mass in lateral neck. Usually, the primary carcinoma is not evident clinically

Etiology

Developmental abnormality of the second branchial cleft (failure to obliterate)

Metastasis to lymph node from an occult primary, almost always from the ipsilateral oropharynx

Histology

1. 
   

   Unilocular or multilocular cyst (Fig. 4.1.1)

   
   
2. 
   

   Cyst lining is usually stratified squamous and can be columnar or glandular with or without cilia (Figs. 4.1.2 and 4.1.3)

   
   
3. 
   

   Surrounding lymphoid infiltrate with germinal centers (Figs. 4.1.1, 4.1.2 and 4.1.3)

   
   
4. 
   

   No extension of cyst lining epithelium into the lymphoid stroma (Figs. 4.1.1, 4.1.2 and 4.1.3)

   
   
5. 
   

   Cyst lining is bland, without significant nuclear hyperchromasia, pleomorphism, or mitotic activity (Fig. 4.1.3)

1. 
   

   Unilocular or multilocular cyst (Fig. 4.1.4)

   
   
2. 
   

   Cyst lining is usually simple squamous; however, in rare examples, columnar or glandular cells may be present, and ciliated cells have been reported (Figs. 4.1.5 and 4.1.6)

   
   
3. 
   

   Background lymph node architecture with germinal centers (Fig. 4.1.4)

   
   
4. 
   

   Almost always some foci of epithelial extension into lymphoid parenchyma (Fig. 4.1.4)

   
   
5. 
   

   The cyst lining epithelium may be deceptively bland in areas, but there are at least some foci with cytologically malignant cells (nuclear hyperchromasia, pleomorphism, and mitotic activity) (Fig. 4.1.5)

Special studies

May be focally positive for p16 by immunohistochemistry, but negative for high-risk HPV by in situ hybridization

Diffusely positive for p16 by immunohistochemistry, and positive for high-risk HPV by in situ hybridization (Fig. 4.1.7)

Treatment

Surgical excision

Neck dissection, along with treatment of primary oropharyngeal carcinoma (surgery with or without postoperative chemotherapy and/or radiation, or chemoradiation without surgery)

Prognosis

Excellent

Good, with 5-year survivals of 70%-80%

Branchial Cleft Cyst

Thyroglossal Duct Cyst

Age

Most commonly young adults. Rare in adults older than 50

Most commonly young adults. Uncommon (˜15%) in adults older than 50

Location

Second branchial cleft cysts occur in lateral neck along anterior aspect of sternocleidomastoid muscle. First branchial cleft abnormalities occur around the ear

Midline neck. Usually involves the hyoid bone

Symptoms

Often asymptomatic, but when infected can become swollen and painful

Neck swelling, when infected can become swollen and painful

Signs

Fluctuant masses, not tender to palpation, may become secondarily infected

Cystic mass that moves upon patient swallowing

Etiology

Developmental abnormality of the second branchial cleft (failure to obliterate)

Failure of thyroglossal duct cyst (the embryologic connection between the foramen cecum at the base of the tongue and the thyroid gland) to completely regress

Histology

1. 
   

   Unilocular or multilocular cyst (Fig. 4.2.1)

   
   
2. 
   

   Cyst lining is usually stratified squamous, epithelium, but can be columnar or glandular with or without cilia (Fig. 4.2.2)

   
   
3. 
   

   Surrounding lymphoid infiltrate with germinal centers (Figs. 4.2.1 and 4.2.2)

   
   
4. 
   

   No thyroid tissue

1. 
   

   Unilocular or multilocular cyst (Fig. 4.2.3)

   
   
2. 
   

   Cyst lining is usually columnar or glandular with or without cilia, may be squamous (Fig. 4.2.4)

   
   
3. 
   

   Typically minimal cyst wall inflammation (Figs. 4.2.3 and 4.2.4)

   
   
4. 
   

   About half of cases have foci of benign thyroid tissue in cyst wall (Figs. 4.2.3 and 4.2.5)

Special studies

Negative for TTF-1 and thyroglobulin

If present, thyroid tissue may be highlighted with TTF-1 and thyroglobulin immunostains (though the cyst lining is negative)

Treatment

Surgical excision

Surgical excision (Sistrunk procedure) of the entire tract, including the hyoid bone

Prognosis

Excellent

Excellent

Cellular Schwannoma

Malignant Peripheral Nerve Sheath Tumor

Age

Wide age range, peak in third to sixth decades

Wide age range, peak in third to sixth decades

Location

Virtually any location, most common in extremities or head and neck

Virtually any location, most common in extremities and trunk. Uncommon in the head and neck

Symptoms

Slow-growing mass, usually painless

Slow-growing mass, sometimes painful

Signs

Variably sized masses usually arising in association with a major nerve

Large, deep-seated mass, usually arising in association with a major nerve

Etiology

A subset of tumors are associated with familial tumor syndromes (schwannomatosis, neurofibromatosis type 2)

A subset occur in the setting of neurofibromatosis type 1. Some arise in preexisting neurofibromas (but almost never in schwannomas)

Histology

1. 
   

   Well-circumscribed, encapsulated proliferation of spindled cells arranged in short fascicles or whorls

   
   
2. 
   

   Predominated by cellular (“Antoni A”) areas admixed with few or no less cellular, myxoid (“Antoni B”) zones (Fig. 4.3.1)

   
   
3. 
   

   Tumor nuclei elongated, wavy, with tapered ends (Fig. 4.3.2)

   
   
4. 
   

   Verocay bodies (palisaded arrangement of tumor nuclei) may be present

   
   
5. 
   

   A lymphoid cuff and hyalinized vessels are also commonly seen (Fig. 4.3.2)

   
   
6. 
   

   May be mitotically active but not in proportion with degree of cellularity. No atypical mitoses or necrosis

   
   
7. 
   

   Some examples demonstrate “ancient changes” in the form of degenerative nuclear atypia, cystic change, hyalinization, hemorrhage, and calcification (Fig. 4.3.3)

   
   
8. 
   

   No heterologous differentiation

1. 
   

   Unencapsulated, infiltrative proliferation of spindled cells, typically arranged in a swirling and/or herringbone-type fascicular pattern (Fig. 4.3.5)

   
   
2. 
   

   Often “dark” hypercellular areas alternate with “light,” less cellular ones, leading to a so-called marbleized appearance (Fig. 4.3.5)

   
   
3. 
   

   Tumor nuclei elongated, wavy, with tapered ends (Fig. 4.3.6)

   
   
4. 
   

   No Verocay bodies, lymphoid cuff, or hyalinized vessels

   
   
5. 
   

   Highly cellular and exhibits nuclear hyperchromasia, pleomorphism, elevated mitotic rates, and necrosis (Fig. 4.3.6)

   
   
6. 
   

   Up to 10%-15% contain heterologous elements, the most frequent of which are foci of rhabdomyoblastic (so-called malignant triton tumor) or epithelial differentiation (Fig. 4.3.7)

Special studies

Diffusely positive for S100 and SOX10 (Fig. 4.3.4)

Focal or negative for S100 and SOX10 (Fig. 4.3.8)

Treatment

Surgical excision

Wide resection, radiation, with or without chemotherapy

Prognosis

Excellent. Recurrences are rare. Schwannomas almost never give rise to malignant peripheral nerve sheath tumors

Poor. Five-year survival 30%-60%

Chordoma

Chondrosarcoma

Age

Adults of a wide age range (mean ˜40), male predominance

Adults of a wide age range (mean ˜60), male predominance

Location

In the head and neck, they arise most often in the base of the skull, especially clivus, and can involve the sinonasal tract or nasopharynx secondarily

Can arise from essentially any location including the skull base. In the head and neck, most common in nasal septum, craniofacial bones, and larynx

Symptoms

Headache, visual disturbances, or other cranial nerve deficits

Depends on location

Signs

Expanding osteolytic mass on radiology

Expanding osteolytic mass on radiology

Etiology

Arise from the vestigial remnants of the notochord, but the etiology is unknown

Unknown

Histology

1. 
   

   Lobules of cells separated by fibrous septa (Fig. 4.4.1)

   
   
2. 
   

   Within the lobules, cells grow singly or as cords, clusters, and sheets in a myxoid stroma (Fig. 4.4.2)

   
   
3. 
   

   Epithelioid tumor cells with clear to eosinophilic cytoplasm (Fig. 4.4.2)

   
   
4. 
   

   A subset of tumor cells have highly vacuolated cytoplasm imparting a “bubbly” appearance (so-called physaliferous cells) (Fig. 4.4.3)

   
   
5. 
   

   Tumor nuclei are uniform, round with mild to moderate pleomorphism (Figs. 4.4.2 and 4.4.3)

   
   
6. 
   

   Necrosis is common, but mitotic activity is low

   
   
7. 
   

   The chondroid variant also exhibits overt cartilage differentiation with tumor cells in lacunae (Fig. 4.4.4)

   
   
8. 
   

   In “dedifferentiated” form, classic or chondroid areas are seen in addition to foci of undifferentiated sarcoma (Fig. 4.4.5)

1. 
   

   Vaguely lobular growth pattern but no welldeveloped fibrous septations (Fig. 4.4.8)

   
   
2. 
   

   Most chondrosarcomas of the head and neck are low grade and show some resemblance to hyaline cartilage. Round or polygonal tumor cells are set within lacunae and typically do not grow as cords and sheets of cells (Figs. 4.4.9 and 4.4.10)

   
   
3. 
   

   Abundant blue-purple matrix typical of hyaline cartilage. Myxoid areas are usually not prominent (Fig. 4.4.10)

   
   
4. 
   

   No physaliferous cells

   
   
5. 
   

   Tumor nuclei are round to oval with minimal to moderate pleomorphism (Fig. 4.4.10)

   
   
6. 
   

   Binucleated lacunae are classic (Fig. 4.4.10)

   
   
7. 
   

   Necrosis is absent and mitotic figures are rare, except in rare grade 3 examples

   
   
8. 
   

   In “dedifferentiated” form, chondroid areas are seen in addition to foci of undifferentiated sarcoma

Special studies

Positive for brachyury, cytokeratins, EMA, S100 (Figs. 4.4.6 and 4.4.7)

Positive for S100, negative for brachyury, cytokeratin, EMA

Treatment

Surgical resection, often followed by radiation therapy if residual tumor remains

Surgical resection sometimes followed by radiation therapy

Prognosis

Fair, with frequent recurrences and 5-year survival of around 50%-70%. The chondroid variant may have an improved prognosis, and the dedifferentiated form has a poor prognosis

Good, with 5-year survival 80%-90%. The dedifferentiated form has a poor prognosis

Nuchal Fibroma

Elastofibroma

Age

Adults, peak in third to fifth decades. More common in men

Adults, peak in sixth and seventh decades. More common in women

Location

Most often dorsal neck, but can involve other sites

Most often scapula and chest wall, involves the head and neck (neck and oral cavity) uncommonly

Symptoms

Slow-growing mass, often asymptomatic

Slow-growing mass, often asymptomatic

Signs

Poorly circumscribed subcutaneous mass

Deep-seated, poorly circumscribed mass

Etiology

Associated with diabetes mellitus. A subset of pediatric cases (often nonnuchal in site) are associated with Gardner syndrome (germ-line APC mutation)

Most likely a nonneoplastic reaction to repetitive injury

Histology

1. 
   

   Paucicellular, ill-defined proliferation of collagen (Fig. 4.5.1)

   
   
2. 
   

   Haphazard collection of thick collagen fibers, but no abnormal elastic fibers or petaloid globules (Fig. 4.5.2)

   
   
3. 
   

   May be misinterpreted as nonlesional tissue

1. 
   

   Paucicellular, ill-defined proliferation of collagen (Fig. 4.5.4)

   
   
2. 
   

   Haphazard collections of linear, thick eosinophilic collagen bundles and elastic fibers, which may be difficult to see on low power (Fig. 4.5.5)

   
   
3. 
   

   Petaloid globules—elastic fibers in cross section with serrated edges (Fig. 4.5.6)

   
   
4. 
   

   May be misinterpreted as nonlesional tissue

Special studies

Positive for CD34 (Fig. 4.5.3). Elastin stains negative

Elastin stains highlight the abnormal elastic fibers, which often have a “beads on a string” appearance (Fig. 4.5.7). Negative for CD34

Treatment

Simple excision

Simple excision

Prognosis

Excellent. Recurrences are rare

Excellent. Recurrences are rare