Oral cavity & oropharynx

Oral cavity squamous cell carcinoma


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Deputy Editor-in-Chief: Kelly Magliocca, D.D.S., M.P.H.
Sarah H. Glass, D.D.S.

Last author update: 12 September 2022
Last staff update: 21 February 2023

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PubMed Search: Oral squamous cell carcinoma

Sarah H. Glass, D.D.S.
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Cite this page: Glass SH. SCC-general. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/oralcavityscc.html. Accessed September 22nd, 2023.
Definition / general
  • Malignant neoplasm that arises from the mucosal epithelium of the oral cavity and shows variable squamous differentiation
Essential features
  • Most common cancer of the oral cavity, with a variable clinical appearance and a predilection for the ventrolateral tongue
  • Associated with tobacco, alcohol and betel quid
  • Malignancy of squamous cells with varying degrees of keratinization
ICD coding
  • ICD-10: C00 - C14 - malignant neoplasm of lip, oral cavity and pharynx
  • Can occur at any oral mucosal site (mucosal lip, buccal mucosa, alveolar ridge, floor of the mouth, hard palate, mobile tongue)
  • Classic high risk locations are ventrolateral tongue and floor of mouth
  • Patients can develop second primaries, synchronous or metachronous, with field cancerization as a probable hypothesis (Head Neck 2020;42:1848, Oral Oncol 2015;51:643)
  • Proliferative (verrucous) leukoplakia lesions have a high risk of malignant transformation, especially in locations such as the gingiva (Head Neck Pathol 2021;15:572)
  • Spread typically occurs via the lymphatic system to cervical lymph nodes
  • Multifactorial with accumulation of genetic alterations
    • Loss of function of TP53 mutations and CDKN2A inactivation are frequently seen (Nature 2015;517:576)
  • Oral potentially malignant disorders, many of which harbor some degree of epithelial dysplasia, are associated with a risk of malignant progression (Head Neck Pathol 2019;13:423)
Clinical features
  • Varied clinical presentation, including exophytic, endophytic, white (leukoplakia), red (erythroplakia), nonhealing ulceration
  • May be preceded by or associated with an oral, potentially malignant disorder
  • Clinical factors associated with malignancy include nonhomogenous leukoplakia, erythroplakia, induration, deep ulceration, exophytic component and pain (Oral Surg Oral Med Oral Pathol Oral Radiol 2020;130:264)
  • Patient factors associated with malignant transformation include heavy tobacco smoking (> 20 pack years), heavy alcohol consumption (> 14 drinks/week for women and 21 drinks/week in men), immunosuppression (Head Neck 2021;43:3552)
  • Firm, fixed, nontender cervical lymph nodes may indicate regional spread
Radiology description
  • Invasive, advanced tumors may be detected on dental radiographs as destruction of underlying bone producing an ill defined radiolucency
  • Positron emission tomography (PET), computed tomography (CT) and magnetic resonance imaging (MRI) can be used to determine the presence and extent of disease
  • Carcinomas arising in the jaw bones without a mucosal origin are primary intraosseous squamous cell carcinoma and are not discussed here (Head Neck Pathol 2021;15:608)
Radiology images

Contributed by Sarah Glass, D.D.S.

Mandible invasion

Prognostic factors
Case reports
  • Early staged lesions are often treated with surgery
  • Patients with early stage cancer may benefit from elective neck dissection (N Engl J Med 2015;373:521)
  • Moderate staged lesions are often treated with surgery, radiation therapy or chemotherapy
  • Patients with recurrent or metastatic head and neck cancer may benefit from immunotherapeutic agents (J Immunother Cancer 2019;7:184)
Clinical images

Contributed by Sarah Glass, D.D.S.

Exophytic mass lateral tongue

Ulceration ventrolateral tongue

Red-white maxillary gingiva

Gross description
  • Site of involvement, tumor laterality and operative procedure should be communicated from the surgeon (Arch Pathol Lab Med 2019;143:439)
  • Gross examination of a specimen may not entirely reflect microscopic tumor extent, as dysplasia, ulceration or inflammation may appear as tumor on macroscopic examination (Arch Pathol Lab Med 2019;143:439)
  • White infiltrating tumor on cross section
Gross images

Contributed by Kathleen Higgins, D.D.S., M.S., Stephen Roth, D.D.S. and Kathleen Schultz, D.M.D.

Glossectomy specimen

Glossectomy specimen cross section

lateral view

Resection superior view

Resection anterior view

Glossectomy specimen

Frozen section description
  • Frozen section analysis can be used to evaluate tumor diagnosis and margin status
Frozen section images

Contributed by Kathleen Higgins, D.D.S., M.S. and Kathleen Schultz, D.M.D.

Tumor with margins

Invasive carcinoma

Microscopic (histologic) description
  • Dysplastic stratified squamous epithelium that extends through the basement membrane and into the underlying fibrous connective tissue without attachment to the surface
  • Malignant epithelial cells show eosinophilic cytoplasm, hyperchromatic nuclei, pleomorphism, mitotic activity, individual cell keratinization and intercellular bridging
  • Superficial or microinvasion can be used to describe the earliest moment of invasion
  • Malignant epithelium can invade fibrous connective tissue in islands, cords or individual cells
  • Keratin pearls of round, eosinophilic, concentric layers of keratin can be seen and are associated with well differentiated tumors
  • 3 histologic grades for conventional squamous cell carcinoma include well, moderately and poorly differentiated based on amount of keratinization, mitotic activity, cellular and nuclear pleomorphism, pattern of invasion and host response (Arch Pathol Lab Med 2019;143:439)
  • Histologic variants are listed below (Arch Pathol Lab Med 2019;143:439):
  • Although more often seen in salivary gland neoplasms and odontogenic tumors, oral squamous cell carcinoma may rarely show clear cell change (Cureus 2022;14:e25057)
  • American Joint Committee on Cancer (AJCC) 8th edition is currently used for staging
  • CAP protocol including TNM (CAP: Protocol for the Examination of Specimens from Patients with Cancers of the Lip and Oral Cavity [Accessed 15 August 2022])
  • Data set elements: operative procedure, specimens submitted, tumor dimensions, histologic tumor type, histologic tumor grade, pattern of invasive front, bone invasion, perineural invasion, lymphovascular invasion, margin status, pathologic staging (Arch Pathol Lab Med 2019;143:439)
Microscopic (histologic) images

Contributed by Kathleen Higgins, D.D.S., M.S. Duane Schafer D.D.S., M.S. and Sarah Glass, D.D.S.

Tumor with margins

Basement membrane breach

Keratin pearl

Muscle invasion

Individual cell keratinization

Impressive pleomorphism

Surrounding nerve

Scattered malignant cells

Cytokeratin support

Basaloid variant

Adenosquamous variant

Verrucous variant

Papillary variant

Acantholytic variant

Spindle variant

Cuniculatum variant

Cytology description
  • Cytology is not routinely recommended for evaluation of intraoral lesions suspicious for malignancy (J Am Dent Assoc 2017;148:712)
  • Fine needle aspiration can identify regional spread to cervical lymph nodes
Positive stains
Negative stains
Molecular / cytogenetics description
Sample pathology report
  • Right lateral tongue, incisional biopsy:
    • Squamous cell carcinoma, well differentiated (see comment)
    • Comment: Tumor islands are present at all surgical margins. Depth of invasion is at least 3 mm. Perineural and lymphovascular invasion are identified.
Differential diagnosis
Board review style question #1

A biopsy of a lesion from the lateral border of the tongue in a 63 year old man demonstrates the histopathology seen above. What is the diagnosis?

  1. Epithelial dysplasia
  2. Granular cell tumor
  3. Mucoepidermoid carcinoma
  4. Squamous cell carcinoma
Board review style answer #1
D. Squamous cell carcinoma

Comment Here

Reference: SCC-general
Board review style question #2
What is the most common malignancy of the oral cavity?

  1. Epithelial dysplasia
  2. Granular cell tumor
  3. Mucoepidermoid carcinoma
  4. Squamous cell carcinoma
Board review style answer #2
D. Squamous cell carcinoma

Comment Here

Reference: SCC-general
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