—  NORTH AMERICAN SOCIETY OF HEAD & NECK PATHOLOGY   —

Variants of Oral Squamous Cell Carcinoma


Kevin Torske
Armed Forces Institute of Pathology
Washington, DC


Multiple variants of squamous cell carcinoma have been documented within the oral cavity region:

  • Verrucous Carcinoma
  • Spindle cell (sarcomatoid) carcinoma
  • Basaloid squamous cell carcinoma
  • Adenosquamous carcinoma
  • Papillary squamous cell carcinoma
  • Adenoid (acantholytic) squamous cell carcinoma
  • Lymphoepithelial carcinoma

    • Verrucous carcinoma

    • Definition
      • A rare variant of squamous cell carcinoma characterized by a papillary/verrucous clinical appearance, bland cytomorphology with "pushing" borders, and a relatively good prognosis
    • Clinical
      • 1-9% of all oral SCC's
      • M>F
      • Average age: 65 years
      • Associated with tobacco use (smoking and smokeless)
      • Usually affects the buccal mucosa, gingiva, and alveolar mucosa, although any oral mucosal area may be affected
      • Diffuse, well-demarcated painless thick plaque with papillary or verrucous surface projections
      • Tumor bluntly invades the underlying soft tissues and may become fixed to the periosteum
        • May subsequently directly invade the bone
      • Patient may present with clinically enlarged cervical lymph nodes
        • Almost always caused by inflammatory/reactive changes as true verrucous carcinomas do not metastasize
      • May be associated with proliferative verrucous leukoplakia
        • Characterized by the development of multiple, persistent keratotic plaques that over time progress to SCC
          • Verrucous hyperplasia ® verrucous carcinoma ® invasive squamous cell carcinoma
          • Lesions rarely regress despite therapy
          • Strong female predilection and only minimal association with smoking
    • Histology
      • Papillary-to-verrucous architectural pattern with a broadly based and invasive "pushing" margin
      • Abrupt transition between normal epithelium and the lesion
        • Margin retracts down with the carcinoma
      • Large, blunt rete ridges
      • Parakeratin crypting common
      • Lack of cytomorphologic features of malignancy
        • Suprabasilar mitoses may be seen
      • Stroma adjacent to tumor with lymphoplasmacytic infiltrate
      • May contain frank areas of invasive SCC
        • This lesion may be termed a "hybrid tumor" or simply invasive squamous cell carcinoma
        • VC's should be thoroughly sampled to ensure no areas of traditional invasive SCC
    • Treatment
      • Surgical excision is the treatment of choice
        • Traditional excision or Moh's
        • 74% cure rate
          • 26% recurrence rate
        • Neck dissection is not indicated
      • Radiation therapy alone is far less effective
        • 43% local control rate
        • 6-7% risk of anaplastic transformation
      • Chemotherapy of indeterminate value
    • Prognosis
      • Overall better prognosis than traditional SCC
      • An unknown number of recurrent verrucous carcinomas may transform into invasive squamous cell carcinoma
        • Prognosis then similar to traditional SCC
        • Prognosis of true anaplastic transformation following radiotherapy is dismal
      • As there is a 26-57% chance of recurrence, close long term follow-up is required
    Spindle cell (sarcomatoid) carcinoma
    • Definition
      • A malignant biphasic or monophasic neoplasm composed of squamous cell carcinoma (either in-situ or invasive) and a malignant spindle-cell population
    • Clinical
      • Average presentation in 7th decade with male predilection
      • Occurs predominantly in the upper aerodigestive tract
        • Larynx and oral cavity are most common
      • Typically appears as a polypoid mass
      • Tends to grow rapidly and metastasize early
    • Histology
      • Biphasic neoplasm with conventional squamous epithelial dysplasia and/or carcinoma and pleomorphic spindle cells
        • Epithelial areas may be scant as the surface is often ulcerated
          • Epithelium commonly absent in small incisional biopsies
        • Locating the epithelial component may require extensive sampling
          • Most consistently identified at the base of the lesion, at the advancing margins, or the nonulcerated areas
      • Spindle cells often comprise the bulk of the lesion and may be arranged in fascicular, whorled, storiform, herringbone, or haphazard patterns.
        • May mimic sarcomas such as MFH, fibrosarcoma, or leiomyosarcoma, or other entities such as nodular fasciitis or fibromatosis
      • Spindle cells may blend with or "drop off" the overlying epithelium
      • Mild-to-moderate pleomorphism with variable mitotic activity
      • May occasionally exhibit other sarcomatous features with osteosarcoma, or chondrosarcoma-like areas
      • Multinucleated giant cells may be present
      • EM demonstrates spindle cells with epithelial, "transitional", and mesenchymal characteristics
      • Invasion into deeper structures (e.g. skeletal muscle, minor salivary glands, or bone) associated with a poorer prognosis
      • Immunohistochemistry may be misleading to unhelpful
        • Cytokeratin: 60-70%
          • Cytokeratin reactivity usually patchy and focal
          • AE1/AE3, EMA, K1, K18, K14 found to be most reactive
        • Vimentin: 60-100%
          • Vimentin and cytokeratin reactivity may be seen in the same cells
        • Smooth muscle actin: 32%
        • S-100: 0-5%
    • As true sarcomas are quite unusual in the upper aerodigestive tract, spindle cell carcinoma should be at the top of the list when confronted with a spindle cell malignancy of the head and neck mucosal tissues
    • Treatment and prognosis
      • Treatment similar to traditional SCC of similar stage
        • Surgery, with or without adjuvant radiotherapy
        • Those managed by radiotherapy alone have a poorer prognosis
      • Prognosis within the oral cavity worse than that of the larynx
        • 60% lethality for oral lesional as compared to 30% for laryngeal neoplasms
    Basaloid squamous cell carcinoma
    • Definition
      • An aggressive biphasic variant of squamous cell carcinoma consisting of a high-grade basaloid epithelial proliferation and traditional SCC or epithelial dysplasia
    • Clinical
      • Tendency to originate within the oropharynx
        • Base of tongue, pyriform sinus, supraglottic larynx, and tonsil
        • Oral sites may include floor of mouth, palate, and buccal mucosa
      • Primarily affects males in 7th decade of life
      • Commonly presents with cervical metastasis at diagnosis
        • Presenting symptoms may include neck mass, dysphagia, pain, hoarseness, weight loss, and cough
    • Histology
      • Biphasic epithelial malignancy with traditional squamous cell carcinoma (invasive or in-situ) and mostly undifferentiated basaloid cells
        • May be an abrupt transition between the two elements
        • Basaloid cells are small with scant cytoplasm and hyperchromatic nuclei, with or without nucleoli
      • Usually closely apposed to the surface mucosa and may be in nests, solid sheets, festoon, cribriform, pseudoglandular, or trabecular growth patterns
      • Other features may include…
        • Brisk mitotic rate
        • Lobules with central comedonecrosis
        • Peripheral palisading of the basaloid cells
        • Small cyst-like areas containing mucinous material
        • Hyalinization of the stroma with microcyst formation
        • Focal spindle cell component
      • IHC:
        • Usually cytokeratin reactive
          • AE1/AE3, CAM 5.2, 34ßE12, CK7, EMA
        • May be weakly NSE reactive but non-reactive for chromogranin, synaptophysin, or other neuroendocrine markers
        • Vimentin reactivity in a delicate perinuclear rim, frequently with a small dot
    • Treatment and prognosis
      • Surgical excision with radical neck dissection and adjuvant radiotherapy
        • Chemotherapy for distant metastases
      • More aggressive and poorer prognosis than traditional SCC
        • Cervical lymph node metastasis in 64%
        • Distant spread in 44%
          • Lungs, liver, bones, brain, and skin
        • Mortality: 38% at 17 months median follow-up
    Adenosquamous carcinoma
    • Definition
      • A rare, aggressive variant of SCC with histomorphologic features of traditional SCC and adenocarcinoma
    • Clinical
      • A rare lesion usually involving the tongue, floor of the mouth, and the tonsillar pillars
        • Upper lip, palate, buccal mucosa, and alveolus have also been reported
      • Presenting symptoms similar to traditional SCC
      • Male predominance
      • 6th–7th decades of life
    • Histology
      • Displays features of traditional SCC and adenocarcinoma
      • SCC component originating from the mucosal surface with gradual transition into adenocarcinoma deeper within the tissue
        • SCC in-situ may be the only evidence of squamous differentiation
      • Adenocarcinoma component usually unclassifiable as any specific type
        • True ductal lumina are present
    • Treatment and prognosis
      • Limited reports hamper a conclusive review…
      • Surgical resection of the tumor and regional lymph nodes
        • Adjuvant radiotherapy may also be indicated
      • Aggressive neoplasm with frequent local recurrence and early metastasis to regional lymph nodes
        • Distant metastases (liver, lung, bone) in 20%
        • 50% of reported patients have died within 5 years of initial presentation
    Papillary squamous cell carcinoma
    • Definition
      • A variant of squamous cell carcinoma composed of an exophytic, cytologically malignant epithelial proliferation in a papillary architectural pattern
    • Clinical
      • Rare tumor with indistinct clinical features
        • Very poorly delineated within the literature, especially in the oral cavity region
        • Commonly confused with the "hybrid tumor" of verrucous carcinoma with focal features of traditional squamous cell carcinoma
      • More common within the larynx
      • Male predominance with presentation in the 6th decade
    • Histology
      • Exophytic neoplasm with papillary and broad-based growth patterns
      • Fibrovascular cores surfaced by markedly dysplastic epithelium
        • If no invasion is noted, then "non-invasive PSCC" or "papillary dysplasia" may be used
        • Invasion, however, may be noted if enough sections are reviewed
    • Treatment and prognosis
      • Similar treatment to traditional SCC
      • Prognosis difficult to define due to the lack of definitive literature on the subject

    References

    • General

    1. Gnepp DR. Diagnostic Surgical Pathology of the Head and Neck. Saunders 2001; 19-78.
    2. Barnes L. Surgical Pathology of the Head and Neck. 2nd Ed. Marcel Dekker 2001; 369-410.
    3. Neville BW, Damm DD, Allen CM, Bouquot JE. Oral and Maxillofacial Pathology. 2nd Ed. Saunders 2002; 356-371
    4. American Cancer Society, Cancer Facts and Figures 2001
    • Verrucous Carcinoma
    1. Ferlito A, Rinaldo A, Mannara GM. Is primary radiotherapy an appropriate option for the treatment of verrucous carcinoma of the head and neck? J Laryngo and Oto, Feb 1998; 112: 132-139.
    2. Bouquot JE. Oral verrucous carcinoma, incidence in two U.S. populations. Oral Surg Oral Med Oral Pathol 1998; 86 (3): 318-24
    3. Schwartz RA. Verrucous carcinoma of the skin and mucosa. J Am Acad Derm 1995; 32(1): 1-21
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    • Spindle Cell Carcinoma
    1. Thompson LD, Wieneke JA, Miettinen M, Heffner DK. Spindle cell (sarcomatoid) carcinoma of the larynx. Am J Surg Pathol 2002; 26(2): 2002
    2. Batsakis JG, Saurez P. Sarcomatoid carcinomas of the upper aerodigestive tracts. Adv Anat Pathol 2000; 7(5):282-293
    3. Berthelet E, Shenouda G, Black MJ, et al. Sarcomatoid carcinoma of the head and neck. Am J Surg 1994; 168: 455-458
    4. Weidner N. Sarcomatoid carcinoma of the upper aerodigestive tract. Sem Diag Pathol 1987; 4(2): 157-168
    5. Ellis GL, Langloss JM, Heffner DK, Hyams VJ. Spindle-cell carcinoma of the aerodigestive tract. Am J Surg Pathol 1987, 11(5): 335-342
    6. Zarbo RJ, Crissman JD, Venkat H, Weiss MA. Spindle-cell carcinoma of the upper aerodigestive tract mucosa. Am J Surg Pathol 1986; 10(11): 741-753
    7. Leventon GS, Evans HL. Sarcomatoid squamous cell carcinoma of the mucous membranes of the head and neck. Cancer 1981; 48: 994-1003
    • Basaloid squamous cell carcinoma
    1. Paulino AF, Singh B, Shah JP, Huvos AG. Basaloid squamous cell carcinoma of the head and neck. Laryngoscope 2000; 110: 1479-1482
    2. Wieneke JA, Thompson LD, Wenig BM. Basaloid squamous cell carcinoma of the sinonasal tract. Cancer 1999; 85(4): 841-854
    3. Morice WG, Ferreiro JA. Distinction of basaloid squamous cell carcinoma from adenoid cystic and small cell undifferentiated carcinoma by immunohistochemistry. Hum Pathol 1998; 29(6): 609-612
    4. Winzenburg SM, Niehans GA, George E, et al. Basaloid squamous cell carcinoma: a clinical comparison of two histologic types with poorly differentiated squamous cell carcinoma. Oto Head Neck Surg 1998; 119(5): 471-475
    5. Hoang JT, Foss RD, Nowaki MR, Kelly KE. Basaloid squamous cell carcinoma and fine needle aspiration: a potential diagnostic pitfall. Oto Head Neck Surg 1998; 119(6): 655-657
    6. Barnes L, Ferlito A, Altavilla G, et al. Basaloid squamous cell carcinoma of the head and neck: clinicopathologic features and differential diagnosis. Ann Otol Rhinol Laryngol 1996; 105: 75-82
    7. Muller S, Barnes L. Basaloid squamous cell carcinoma of the head and neck with a spindle cell component. Arch Pathol Lab Med 1995; 119: 181-182
    8. Hellquist HB, Dahl F, Karlsson MG, Nilsson C. Basaloid squamous cell carcinoma of the paate. Histopathol 1994; 25: 178-180
    9. Raslan WF, Barnes L, Krause JR, et al. Basaloid squamous cell carcinoma of the head and neck: a clinicopathologic and flow cytometric study of 10 new cases with review of the english literature. Am J Oto 1994; 15(3): 204-211
    10. Klijanienko J, El-Naggar A, Ponzio-Prion A, et al. Basaloid squamous carcinoma of the head and neck. Immunohistochemical comparison with adenoid cystic carcinoma and squamous cell carcinoma. Arch Oto Head Neck Surg 1993; 119: 887-890
    11. Coppola D, Catalano E, Tang CK, et al. Basaloid squamous cell carcinoma of the floor of mouth. Cancer 1993; 72(8): 2299-2305
    12. Campman SC, Gandour-Edwards RF, Sykes JM. Basaloid squamous carcinoma of the head and neck: report of a case in the floor of the mouth. Arch Pathol Lab Med 1994; 118: 1229-1232
    13. Banks ER, Frierson HF, Mills SE, et al. Basaloid squamous cell carcinoma of the head and neck: a clinicopathologic and immunohistochemical study of 40 cases. Am J Surg Pathol 1992; 16(10): 939-946
    14. Lovejoy HM, Matthews BL. Basaloid squamous carcinoma of the palate. Otol Head Neck Surg 1992; 106: 159-162
    15. Luna MA, El-Naggar A, Parichatikanond P, et al. Basaloid squamous carcinoma of the upper aerodigestive tract: clinicopathologic and DNA flow cytometric analysis. Cancer 1990; 66: 537-542
    16. Wain SL, Kier R, Vollmer RT, et al. Basalid-squamous carcinoma of the tongue, hypopharynx, and larynx: report of ten cases. Hum Pathol 1986; 17(11): 1158-1166
    • Adenosquamous carcinoma
    1. Scully C, Porter SR, Speight PM, et al. Adenosquamous carcinoma of the mouth: a rare variant of squamous cell carcinoma. Int J Oral Maxillofac Surg 1999; 28: 125-128
    2. Izumi K, Nakajima T, Maeda T, et al. Adenosquamous carcinoma of the tongue: report of a case with histochemical, immunohistochemical, and ultrastructural study and review of the literature. Oral Surg Oral Med Oral Pathol 1998; 85(2): 178-184
    3. Napier SS, Gormley JS, Newlands C, et al. Adenosquamous carcinoma: a are neoplasm with an aggressive course. Oral Surg Oral Med Oral Pathol 1995; 79(5): 607-611
    4. Ellis GL, Auclair PL, Gnepp DR. Surgical pathology of the salivary glands. Saunders 1991: 455-459
    • Papillary squamous cell carcinoma
    1. Batsakis JG, Suarez P. Papillary squamous cell carcinoma: will the real one please stand up? Adv Ana Pathol 2000; 7(1): 2-8
    2. Thompson LD, Wenig BM, Heffner DK, Gnepp DR. Exophytic and papillary squamous cell carcinomas of the larynx: a clinicopathologic series of 104 cases. Oto Head Neck Surg 1999; 120 (5): 718-724
    3. Ishiyama A, Eversole LR, Ross DA, et al. Papillary squamous neoplasms of the head and neck. Laryngoscope 1994; 104: 1446-1452
    4. Crissman JD, Kessis T, Shah KV, et al. Squamous papillary neoplasia of the adult upper aerodigestive tract. Hum Pathol 1988; 19(12): 1387-1396