---

CARCINOMA OF THE TONGUE

A Comprehensive 20-Mark Answer (RGUHS Pattern)

---

1. SURGICAL ANATOMY

• Freely mobile, demarcated posteriorly by the circumvallate papillae (sulcus terminalis - V-shaped line)
• Subdivisions: tip, dorsum, lateral borders, ventral surface
• WHO classification: ICD-10 C02
• Dorsum and tip: specialized gustatory mucosa with thick keratinized epithelium
• Ventral/lateral surfaces: lining mucosa with non-keratinizing stratified squamous epithelium

• Part of oropharynx (ICD-10 C01)
• Not visible on routine examination
• Lymphoid tissue-rich (lingual tonsil)

• Intrinsic: superior/inferior longitudinal, transverse, vertical
• Extrinsic: genioglossus, hyoglossus, styloglossus, palatoglossus

┌─────────────────────────────────────────────────────┐
│          LYMPHATIC DRAINAGE OF TONGUE               │
│                                                     │
│  Tip & Midline  ─────────────► BILATERAL drainage   │
│  (crosses midline)             (both Level I-IV)    │
│                                                     │
│  Lateral border ─────────────► IPSILATERAL          │
│  (away from midline)           Level I, II, III     │
│                                                     │
│  Base of tongue ─────────────► BILATERAL            │
│                                Level II, III, IV    │
│                                                     │
│  ⚠️ SKIP METASTASES: Levels I & II bypassed,       │
│  presenting at Level III (15.8% - Byers et al.)    │
└─────────────────────────────────────────────────────┘

---

2. EPIDEMIOLOGY

• Incidence: 22-39% of all oral cancers arise on the oral tongue (most common oral cancer site in populations without tobacco chewing habits) - Scott-Brown's
• Site distribution within tongue: Middle third > lateral border most common; ventral surface next; only 4-5% on dorsum - Scott-Brown's
• Age: 6th-8th decade; 90% over 40 years
• Sex: Slight male predominance (M:F ratio decreasing due to increased female alcohol consumption)
• Risk factors:
  • Tobacco (smoked and smokeless/chewed)
  • Alcohol (synergistic with tobacco)
  • Poor oral hygiene
  • Betel nut (paan, gutka - highly relevant in Indian population - Dhingra/Hazarika)
  • Chronic irritation (sharp tooth, ill-fitting dentures)
  • Immunosuppression
  • HPV (particularly base of tongue)
  • Plummer-Vinson syndrome (iron deficiency dysphagia triad)

---

3. PATHOLOGY

• Leukoplakia: white patch that cannot be scraped off - floor of mouth leukoplakia has 1-2.9% annual malignant transformation rate
• Erythroplakia: red, inflammatory lesion - most common presentation of early SCC (K.J. Lee)
• Submucous fibrosis (SMF) - common in India
• Lichen planus (erosive type)

• 90%: Squamous cell carcinoma (SCC)

• Others: adenocarcinoma (minor salivary gland), lymphoma (base of tongue), verrucous carcinoma

• Grade I (well-differentiated): keratin pearls, intercellular bridges
• Grade II (moderately differentiated)
• Grade III (poorly differentiated): worst prognosis

• Ulcerative (most common) - indurated, rolled everted edges
• Proliferative/exophytic
• Infiltrative - worst prognosis, highest rate of occult metastasis

---

4. TNM STAGING (AJCC 8th Edition - 2017)

DOI = depth of invasion ≠ tumor thickness - measured from the level of the basement membrane of the nearest normal adjacent mucosa

┌─────────────────────────────────────────────────────┐
│           TNM CLASSIFICATION (AJCC 8th ed.)         │
│                 ORAL CAVITY (including tongue)      │
├──────┬──────────────────────────────────────────────┤
│  T1  │ ≤ 2 cm AND DOI ≤ 5 mm                        │
│  T2  │ ≤ 2 cm with DOI 5-10 mm, OR                  │
│      │ > 2 cm but ≤ 4 cm with DOI ≤ 10 mm           │
│  T3  │ > 4 cm, OR any T with DOI > 10 mm            │
│  T4a │ Invades adjacent structures:                  │
│      │ cortical bone, extrinsic tongue muscles,      │
│      │ maxillary sinus, facial skin                  │
│  T4b │ Invades masticator space, pterygoid plates,   │
│      │ skull base, encases carotid artery            │
├──────┼──────────────────────────────────────────────┤
│  N0  │ No regional nodes                             │
│  N1  │ Single ipsilateral ≤ 3 cm, ENE(-)            │
│  N2a │ Single ipsilateral 3-6 cm, ENE(-)            │
│  N2b │ Multiple ipsilateral ≤ 6 cm, ENE(-)          │
│  N2c │ Bilateral or contralateral ≤ 6 cm, ENE(-)    │
│  N3a │ Any node > 6 cm, ENE(-)                      │
│  N3b │ Any node with clinical ENE(+)                │
├──────┼──────────────────────────────────────────────┤
│  M0  │ No distant metastasis                         │
│  M1  │ Distant metastasis                            │
└──────┴──────────────────────────────────────────────┘
ENE = Extranodal Extension

---

5. CLINICAL FEATURES

• Pain or ulcer on lateral border of tongue
• Erythroplakia (most common early sign)
• A lump or mass
• History of 4-6 months before seeking advice is common

• Tongue fixation (infiltration of extrinsic muscles)
• Decreased tongue sensation (lingual nerve involvement)
• Altered speech (dysarthria)
• Dysphagia
• Otalgia (referred pain via CN V - auriculotemporal; auricular branch of vagus)
• Cervical lymphadenopathy
• Fetor oris (foul smell)
• Bleeding from ulcer
• Weight loss/cachexia

• Typically Stage III/IV at diagnosis
• Dysphagia, throat discomfort, referred otalgia
• "Hot potato" voice
• Neck mass (often first presentation)

---

6. WORKUP / INVESTIGATIONS

┌────────────────────────────────────────────────────────┐
│          INVESTIGATIONS IN CA TONGUE                   │
├────────────────────────────────────────────────────────┤
│ HISTORY & PHYSICAL                                     │
│  - Full H&N examination (bimanual palpation)           │
│  - Nasopharyngoscopy / flexible laryngoscopy           │
├────────────────────────────────────────────────────────┤
│ BIOPSY                                                 │
│  - Incisional (wedge) - include deep margin            │
│  - Multifactorial histological malignancy grading      │
│  - Intraoral sonography for tumour thickness           │
├────────────────────────────────────────────────────────┤
│ IMAGING                                                │
│  - MRI: best for soft tissue extent, DOI, nerve inv.  │
│  - CT (with contrast): bone invasion, neck nodes      │
│  - PET-CT: distant metastasis, unknown primary        │
│  - OPG: mandibular involvement                        │
│  - CXR/CT chest: distant mets, second primary        │
├────────────────────────────────────────────────────────┤
│ LABORATORY                                             │
│  - CBC, LFT, RFT, coagulation                         │
│  - HPV testing (p16 IHC) - especially base of tongue  │
├────────────────────────────────────────────────────────┤
│ PANENDOSCOPY (EUA)                                     │
│  - Direct laryngoscopy, esophagoscopy, bronchoscopy   │
│  - Second primary tumour in 10% (Dhingra)             │
└────────────────────────────────────────────────────────┘

• DOI on MRI predicts occult neck metastasis
• CT: assess cortical bone erosion
• PET-CT: recommended for advanced-stage disease
• Grainger & Allison: "What is the depth of invasion? Are extrinsic tongue muscles involved? Is there extension across midline?"

---

7. MANAGEMENT

FLOWCHART: OVERALL MANAGEMENT ALGORITHM

           DIAGNOSED Ca ORAL TONGUE
                    │
        ┌───────────┴────────────┐
        │    STAGING WORK-UP     │
        │ (MRI + CT + PET-CT)    │
        └───────────┬────────────┘
                    │
          ┌─────────┴──────────┐
    T1-T2 N0                  T3-T4 or N+
          │                        │
    Partial Glossectomy      MDT Discussion
    (Transoral / WLE)              │
          │                ┌───────┴────────┐
    DOI ≤ 4mm          Surgery +          Chemo-RT
    Observe neck       Adjuvant RT/CRT    (selected T4b
          │                │              unresectable)
    DOI > 4mm      Reconstruct defect
    Elective ND    (free flap if >1/2
                    tongue resected)

A. SURGICAL MANAGEMENT

• T1/T2 lesions: Transoral partial glossectomy with 1-1.5 cm margin. Reconstruction by primary closure, secondary intention, or skin graft.
• T3/T4 lesions: Extended partial, near-total, or total glossectomy. Access via pull-through or mandibulotomy.
• Mandible involvement:
  • Periosteum free: periosteal margin
  • Periosteal adherence: marginal mandibulectomy (horizontal or sagittal)
  • Cortical erosion/medullary invasion: segmental mandibulectomy
  • Edentulous mandible: higher chance of segmental resection (less bone stock)

• Clear margin: >5 mm (some advocate >2.2 mm - Zanoni et al.)
• DOI >2 mm, moderately/poorly differentiated = risk for occult metastasis
• 100% of patients with occult metastases had DOI ≥ 2 mm

B. MANAGEMENT OF THE NECK

┌──────────────────────────────────────────────────────────┐
│             NECK MANAGEMENT ALGORITHM                     │
│                                                          │
│  DOI < 4mm, T1, N0 ─────────────► OBSERVE               │
│  (low risk of occult mets)        (though END better)   │
│                                                          │
│  DOI ≥ 4mm, T2+, N0 ────────────► ELECTIVE NECK         │
│  OR poor histology                 DISSECTION (END)      │
│                                    Levels I-IV           │
│                                    (due to skip mets)    │
│                                                          │
│  Midline/bilateral lesion ─────────► BILATERAL ND        │
│                                                          │
│  N+ (clinical) ─────────────────► THERAPEUTIC ND        │
│                                    + Adjuvant RT/CRT     │
│                                                          │
│  T1-T2 N0 (selected) ───────────► SLNB (sentinel)       │
│                                    (accurate for staging)│
└──────────────────────────────────────────────────────────┘

• 500 patients (T1-T2 oral cavity SCC, N0)
• END vs. therapeutic ND
• 3-year OS: 80% (END) vs 67.5% (therapeutic) - p=0.01
• Disease-free survival: 69.5% vs 45.9% - p<0.001
• Conclusion: Elective neck dissection for N0 oral tongue cancer improves survival

• Supraomohyoid neck dissection (SOHND): Levels I-III - standard minimum
• Extended SOHND: Levels I-IV - preferred for tongue (due to skip metastases to Level III/IV)
• Levels I-IV mandatory as skip metastases to Level III occur in 15.8% (Byers et al.)

• Feasible and accurate for T1-T2, N0 oral cavity cancers (K.J. Lee)
• Recent advances: SPECT-CT guided, fluorescent dye techniques
• Can avoid full END in SLNB-negative patients

C. RECONSTRUCTION

┌───────────────────────────────────────────────────────┐
│          RECONSTRUCTIVE LADDER - CA TONGUE            │
│                                                       │
│  <1/4 resected ────────────► Primary closure or      │
│                               secondary intention     │
│                                                       │
│  1/4 to 1/2 resected ──────► STSG (split-thickness  │
│                               skin graft)             │
│                                                       │
│  ~1/2 tongue resected ─────► Radial forearm free     │
│                               flap (RFFF) -          │
│                               pliable, thin          │
│                                                       │
│  >1/2 tongue resected ─────► Anterolateral thigh     │
│                               (ALT) free flap        │
│                               Pectoralis major flap  │
│                                                       │
│  Near-total/total ─────────► ALT + laryngectomy may  │
│  glossectomy                  be needed (aspiration) │
└───────────────────────────────────────────────────────┘

• Preserve tongue mobility for speech and swallowing
• Palatal augmentation prosthesis if tongue contact with palate lost
• Radial forearm free flap: most commonly used (pliable, thin, sensate option)
• ALT: for larger defects, less donor site morbidity

D. RADIATION THERAPY

• External beam RT (EBRT): 60-66 Gy in 30-33 fractions (standard)
• Brachytherapy: Interstitial iridium-192 implant for T1-T2a - comparable results to surgery for early lesions (Scott-Brown's, Royal Berkshire data)
• IMRT (Intensity Modulated Radiotherapy): Standard of care - spares parotid gland, reduces xerostomia
• Indications for adjuvant RT:
  • Positive or close margins (<5 mm)
  • Multiple positive nodes
  • Perineural invasion (PNI)
  • Lymphovascular invasion (LVI)
  • T3/T4 primary
• Indications for adjuvant CRT (chemotherapy + RT):
  • Extranodal extension (ENE)
  • Positive margins

E. CHEMOTHERAPY

• Concurrent cisplatin: Standard for adjuvant CRT (100 mg/m² every 3 weeks or 40 mg/m² weekly)
• Induction (neoadjuvant) chemotherapy: TPF regimen (docetaxel + cisplatin + 5-FU) for advanced disease
• Palliative: EXTREME protocol (cetuximab + platinum + 5-FU) - first-line

---

8. PROGNOSIS

• 5-year survival (Scott-Brown's, K.J. Lee):
  • Stage I: ~80-90%
  • Stage II: 60-75%
  • Stage III/IV: 25-40%
  • With regional metastasis (salvage): 35-40%
• Favorable prognostic factors:
  • Early stage (I/II)
  • Well-differentiated
  • Small DOI (<3 mm = near 100% 5-year survival)
  • No cervical metastasis
  • Adequate surgical margins
• Adverse prognostic factors (Scott-Brown's):
  • Tumor thickness >9 mm (5-year survival 66% vs 100% for <3 mm)
  • Perineural invasion
  • Lymphovascular invasion
  • Extranodal extension
  • Positive/close margins
  • Poor differentiation
  • Young patients (<40 years) have higher locoregional failure rates
• Locoregional recurrence: 80% occur within first 2 years
• Second primary tumors: ~10% of patients (field cancerization)

---

9. BASE OF TONGUE CARCINOMA (Brief)

• Part of oropharynx (different from oral tongue)
• Usually Stage III/IV at diagnosis
• HPV-positive tumors: better prognosis, respond well to chemoradiation
• Treatment: concurrent chemoradiation (organ-preservation) preferred over surgery for most
• Surgery: transoral robotic surgery (TORS) for selected cases
• Bilateral neck dissections always required

---

10. RECENT ADVANCES (2023-2026)

A. Sentinel Lymph Node Biopsy (SLNB)

• SPECT-CT + technetium-99m nanocolloid has high accuracy in T1-T2 N0 cases
• Fluorescent-guided SLNB using indocyanine green (ICG) under NIR camera
• Reduces unnecessary full neck dissections

B. Depth of Invasion (DOI) - AJCC 8th Ed. (2017)

• DOI incorporated into T-staging - major advance
• Machine learning models now predict occult nodal metastasis using DOI and other features (Zhu R et al., Int J Surg, 2025, [PMID: 40479496])
• Advanced diffusion-relaxation MRI for DOI assessment and metastasis prediction (Li S et al., Eur Radiol Exp, 2025, [PMID: 41060516])

C. Immunotherapy

• Pembrolizumab (anti-PD-1): FDA-approved as first-line for recurrent/metastatic H&N SCC (KEYNOTE-048)
• Nivolumab + CRT post-surgery (GORTEC 2018-01 NIVOPOST-OP trial): Bourhis J et al., Lancet, 2026 - nivolumab added to adjuvant CRT evaluated in high-risk HNSCC [PMID: 41448222]
• Atezolizumab (anti-PD-L1): Phase III trial (JAMA, 2025) in locally advanced H&N SCC [PMID: 40079944]
• PD-L1 CPS (Combined Positive Score) now routinely tested for immunotherapy eligibility

D. HPV-Related Tongue Base Cancer

• HPV-positive oropharyngeal SCC (mainly base of tongue + tonsil) have distinct biology
• Therapeutic options for HPV+ base of tongue cancer - review by Zupancic M et al., J Intern Med, 2025 [PMID: 40246777]
• De-escalation protocols (reduced-dose RT) being studied for HPV+ cases

E. Transoral Robotic Surgery (TORS)

• For base of tongue and select oral tongue cancers
• Reduces morbidity vs open surgery
• Improved functional outcomes for swallowing and speech

F. Molecular/Genomic Advances

• Spatial transcriptomics revealing molecular mechanisms of early-onset tongue cancer (Patysheva MR et al., Sci Rep, 2024, [PMID: 39482351])
• Multi-omics analyses for precision patient stratification in OSCC (Wu CS et al., Cancer Lett, 2025, [PMID: 39842500])
• Fluorescence molecular imaging for early diagnosis (Fu J et al., 2023, [PMID: 37634605])

G. Reconstruction Advances

• Systematic review on reconstruction of tongue malignancy defects: treatment algorithm (Gearing PF et al., Microsurgery, 2025, [PMID: 40503748])
• Innervated free flaps for improved sensory rehabilitation
• Perforator-based ALT flaps for optimized donor site morbidity

H. Post-op Radiotherapy in Early Stage

• Tian Q et al., J Clin Oncol, 2024 [PMID: 38560819]: Impact of postoperative RT in pT1-2N0 oral tongue SCC - better locoregional control but balanced against toxicity

---

SUMMARY TABLE

---

KEY POINTS FOR EXAM (RGUHS 20-mark pattern)

1. Most common site for oral tongue cancer: lateral border, middle third
2. DOI is the most important prognostic and staging parameter (AJCC 8th ed.)
3. Skip metastases occur in 15.8% - hence extend ND to Level IV
4. D'Cruz trial settled the debate: END is superior to therapeutic ND in N0 oral tongue cancer
5. Occult metastases: 25-33% clinically detectable; 20-25% occult
6. Tumor thickness >9 mm: 5-year survival drops to 66%
7. Radial forearm free flap: most common reconstruction for partial glossectomy
8. Elective neck dissection threshold: DOI >4 mm (some guidelines: >3-4 mm)
9. Adjuvant CRT mandatory for ENE and positive margins
10. Pembrolizumab: first-line immunotherapy for recurrent/metastatic disease

---