Squamous cell carcinoma

Joaquin, Daryll

Case
LR, a 64 year-old female who presented with a
non-healing ulcer on the tongue.

History of Present Illness

3 months prior

Ulcer on the left lateral aspect of the anterior tongue.

Persistent tongue pain 7/10
Difficulty eating
No bleeding, and dysarthria

2 months prior
Ulcer persisted, as well as pain and dysphagia
With dysarthria
White tongue mass with bleeding after contact

Consult at a local hospital (ENT)

Biopsy was done, with an impression of SCCA.

Advised surgery
Consulted to our institution

Past History
Adult medical illnesses
(+) PTB, treated
No history of asthma, heart disease, kidney disorders,
diabetes, hypertension.

No previous operations, accidents, and injuries.

Family history
Mother breast cancer

Non-smoker, non-alcoholic beverage drinker, no

history betel nut or paan chewing

PE

Conscious, coherent, ambulatory

In persistent pain (5/10)
Stable vital signs RR 18, HR 80, BP 110/70, T 36.7
No active dermatoses
Normocephalic, atraumatic head
Normal conjunctiva, anicteric sclera, PERRLA
Normoset ears, nontender, intact TM both, no hearing
loss
Septum midline, patent nostrils, no discharge or
bleeding

PE
3x2cm hard mass on the left anterior tongue, crossing
midline. With white ulceration measuring 1cm at the
left anterior tongue. No active bleeding.
Neck supple, trachea midline, no palpable cervical
lymphadenopathies
Symmetric chest expansion, clear and equal breath
sounds
Adynamic precordium, good cardiac tones, no murmur
Soft, globular, nondistended, nontender abdomen,
normoactive bowel sounds.
Full pulses.

CT scan
isodense ovoid soft tissue mass
on the tongue with irregular
enhancement in the L crossing
towards R
3.8 x 2.8 x 3.0 cm
No plane of cleavage with the left
mylohyoid, left hyoglossus and
both genioglossus muscles.
Hypodense nodules in both
thyroid lobes
Calcification in the left tonsil
Parotid and submandibular
glands are not enlarged and
normal in attenuation
No evidence of enlarged lymph
nodes.

Endoscopy
showed no nasopharynx, oropharynx, or
laryngeal mass.

Final Procedure
Near Total Glossectomy; Bilateral Neck
Dissection; Supraomohyoid; Reconstruction
using Left Supraclavicular Island Pedicle Flap.
Patient tolerated the procedure.
The rest of the hospital stay was
unremarkable.
Discharged after 7 days of hospital stay.

Differentials
Recurrent Aphthous Ulcer
Recurrent Intraoral Herpes
Simplex Ulcer
Traumatic Ulcer
Leukoplakia
Squamous Cell Carcinoma

Diagnosis
Tongue Squamous Cell Carcinoma

Epidemiology
Oral cancer accounts for less than 3% of all
cancers in the US
11th most common cancer worldwide
Approximately 90% of all oral malignancies are
squamous cell carcinoma.
The tongue is the most common site of all
intraoral malignancies.

Etiology
Tobacco and alcohol abuse are the strongest
predictors of developing oropharyngeal
carcinoma
HPV infection is strongly implicated in people
not exposed to smoking or alcohol
mainly tonsillar carcinoma and, to a lesser extent,
base of tongue carcinoma

Familial associations
Actinic radiations
Betel nut and paan chewing
Poor diet

Pathophysiology
P16 inactivation loss of inhibitor of cdk and
progression to hyperplasia & hyperkeratosis
P53 mutations progression of dysplasia
Gross genomic alterations progression to
malignancy
Cyclin D1 overexpression active cell cycle
progression

Natural History
Persistent nonhealing ulcer with/without
associated pain
Difficulty with deglutition and speech
History of leukoplakia
Rate of growth
Lesion thickness
Cervical metastases

Gross
Early lesions appear as
pearly white to gray
circumscribed thickenings
of the mucosa.
They may grow in an
exophytic fashion to
produce a palpable
nodular fungating lesions
Or they may assume an
endophytic invasive
pattern with central
necrosis creating a
cancerous ulcer.

Histology
Squamous cell carcinoma arises from
dysplastic surface epithelium and is
characterized histopathologically by invasive
islands and cords of malignant squamous
epithelial cells.
The lesional epithelium is capable of inducing
the formation of new small blood vessels
(angiogenesis) and, occasionally, dense
fibrosis (desmoplasia or scirrhous change).
Hyperchromatic

Histology
Well-differentiated squamous
cell carcinoma.
A, Low-power
photomicrograph showing
islands of malignant
squamous epithelium
invading into the lamina
propria.
B, High-power view showing
dysplastic epithelial cells with
keratin pearl formation.

Histology

Moderately differentiated squamous

cell carcinoma. Although no
keratinization is seen in this mediumpower view, these malignant cells are
still easily recognizable as being of
squamous epithelial origin.

Poorly differentiated squamous cell

carcinoma. The numerous
pleomorphic cells within the lamina
propria represent anaplastic
carcinoma.

Metastasis
The metastatic spread of
oral squamous cell
carcinoma is largely through
the lymphatics
The most common sites of
distant metastasis are the
lungs, liver, and bones
Metastasis is not an early
event for carcinomas of the
oral cavity.
However, because of delay
in the diagnosis,
approximately 21% of
patients have cervical
metastases at diagnosis

Diagnostic Investigations
biopsy of lesion
Assesses tumor histology
atypical keratinocytes with
pleomorphism
hyperchromatic nuclei
mitosis invading the
basement membrane

PET-CT of the head and

neck
tumor size, extension,
presence or absence of
involved neck nodes,
distant metastases, and
second primary

Diagnostic Investigations
CT scan
establish the location, size, and extent of the
tumor

MRI
tumor size, extension, presence and absence of
neck nodes, nerve infiltration, and bone marrow
infiltration

Endoscopy
detects second primary or tumor not visible on
imaging for blind biopsy

Neck node biopsy

Tumor grading

Glossectomy
performed mainly for cancers of the tongue
Partial glossectomy
Total glossectomy
severe dysfunction with swallowing and resultant
aspiration
performed along with a total laryngectomy in
order to prevent aspiration and pneumonia

A neck dissection is also often indicated for

tongue cancers

Glossectomy
Complications
Infection
Bleeding
Dysarthria
Dysphagia
Aspiration
Salivary fistula

Treatment
stage I or II (early stage disease)
1. Surgery
fatal complications of 3.2% to 3.5%
non-fatal severe complications 23% to 32%

2. Radiotherapy
fatal complications 0.2% to 0.4%
Non-fatal severe complications 3.8% to 6%

Treatment
stage III and IVA (Locally advanced stages Resectable)

1. Surgery + postoperative radiotherapy

2. Chemoradiotherapy
Chemotherapy

Cisplatin or Fluorouracil or Carboplatin

Radiotherapy
Adjunct induction chemotherapy

Docetaxel, cisplatin, and fluorouracil

3. Cetuximab + radiotherapy
For patients with resectable locally advanced
disease unable to tolerate chemotherapy or

Treatment
stage IVB (locally advanced and unresectable)
1. chemoradiotherapy adjuvant
chemotherapy
Cisplatin and radiotherapy
OR

Cisplatin and radiotherapy and adjuvant

chemotherapy

2. induction chemotherapy +
chemoradiotherapy
triple-drug induction chemotherapy - docetaxel,
cisplatin, and fluorouracil

Treatment
stage IVC (distant metastases at presentation)
chemotherapy cetuximab
Should be treated with chemotherapy.
Conventional chemotherapy is usually a platinum
agent with fluorouracil.
Cisplatin or carboplatin AND fluorouracil and
cetuximab

Treatment
Recurrent Disease
For recurrent disease after previous local
therapy without any evidence of distant
metastases, salvage with surgery,
radiotherapy, or chemoradiotherapy may be
considered on an individual basis

Emerging Treatments
Anti-epidermal growth factor and anti-angiogenesis
agents
anti-epidermal growth factor receptor agents such as
erlotinib
anti-angiogenesis agents such as bevacizumab
anti-epidermal growth factor receptor monoclonal
antibody, panitumumab

Biomarkers
presence of oncoprotein E6 may confer a survival
advantage for HPV-16-induced oropharyngeal cancer
Increased expression of epidermal growth factor receptor
(EGFR) in the tumor specimen may confer a poor prognosis

Tomotherapy-based image-guided radiotherapy

Complications
oral mucositis
speech alteration after surgery
dysphagia and aspiration after surgery or
radiotherapy
xerostomia after radiotherapy
hearing loss after chemotherapy and
radiotherapy
hypothyroidism after neck radiotherapy

Follow-up
FBC, chemical profile, albumin, and prealbumin
modified barium swallow or endoscopic
examination
PET-CT
Thyroid function tests

Prognosis
Overall survival is approximately 50%.
Rates of survival at 5 years by stage are the
following:
stage I, 80%
stage II, 60%
stages III and IV, 15% to 35%.

The presence of lymph node metastases

decreases the survival rate by 50%.

Gross
A white tan, solid mass measuring 4.4x3x1.8cm is
grossly noted 0.7cm away from the anterior tissue
edge, 0.4cm away from medial tissue edge, and
grossly abuts the posterior, inferior and lateral tissue
edges.

Microscopic
Microsections disclose infiltrating nests of
neoplastic squamous cells exhibiting
individual cell dyskeratosis, significant nuclear
pleomorphism and increased mitotic activity
(including atypical forms) and necrosis.

Histology

Surgical Pathology
Invasive Squamous Cell Carcinoma,
Keratinizing, Moderate to Poorly
Differentiated Involving Extrinsic Tongue
Musculature
Extensive Perineural Invasion
Lymphovascular Invasion
Metastatic SCC on 1/10 lymph nodes from R
supraomohyoid neck at Level I
Metastatic Papillary thyroid CA on 1/10
lymph nodes from R supraomohyoid neck at
Level III

Incidence of occult metastatic PTC in

a primary SCC
Incidence of metastatic PTC in a primary oral
SCC ranges 0.31.9%
most common lymph nodes involved by metastatic
thyroid carcinoma are level IV, level III, and level II.

Mechanism
lesions arise from benign lateral aberrant
thyroid tissue in the lymph nodes which have
undergone malignant transformation.
BRAF mutation - thyroid gland cancer
tumorigenesis and occurring in approximately
40% of papillary cancer incidences, has been
found in head and neck cancer as well

Conclusion
look for primary focus of carcinoma in the thyroid

Thyroid function studies

TSH suppression test
Thyroid ultrasound
Fine-needle aspiration biopsy (FNAB)

Total thyroidectomy should be only done in the

presence of clinically palpable nodule in thyroid.
Outcome of the patient depends on the behavior
of the primary tumor and not by thyroid lesion.

References

ALTUMBABID, H., & SALKID, A. (2010). Incidental Metastasis of Papillary Thyroid Carcinoma in Lymph Nodes of Patient with Squamous
Cell Carcinoma of the Oral Cavity: a Case Report. Acta Med Sal, 39(2), 104-106.
Barnes, L., Eveson, J. W., Reichart, P., & Sidransky, D. (2005). World Health Organization classification of tumours: pathology and
genetics of head and neck tumours. Word Health Organization Classification of Tumours: Pathology and genetics of head and neck
tumors.
Blanchard, P., Baujat, B., Holostenco, V., Bourredjem, A., Baey, C., Bourhis, J., & Pignon, J. P. (2011). Meta-analysis of chemotherapy in
head and neck cancer (MACH-NC): a comprehensive analysis by tumour site. Radiotherapy and Oncology, 100(1), 33-40.
Egner, J. R. (2010). AJCC cancer staging manual. JAMA, 304(15), 1726-1727.
Harrison, L. B., Zelefsky, M. J., Armstrong, J. G., Carper, E., Gaynor, J. J., & Sessions, R. B. (1994). Performance status after treatment for
squamous cell cancer of the base of tonguea comparison of primary radiation therapy versus primary surgery. International Journal of
Radiation Oncology* Biology* Physics, 30(4), 953-957.
Licitra, L., & Felip, E. (2009). Squamous cell carcinoma of the head and neck: ESMO clinical recommendations for diagnosis, treatment
and follow-up. Ann Oncol, 20(Suppl 4), 121-122.
Olthof, D. C., Bun, R. J., Dutrieux, R. P., & Houdijk, A. P. J. (2016). An unexpected finding in the resection specimen of a carcinoma of the
oral cavity: A case report. International journal of surgery case reports, 19, 55-59.
Rsli, C., Tschudi, D. C., Studer, G., Braun, J., & Stoeckli, S. J. (2009). Outcome of patients after treatment for a squamous cell
carcinoma of the oropharynx. The Laryngoscope, 119(3), 534-540.
Shiboski, C. H., Schmidt, B. L., & Jordan, R. C. (2005). Tongue and tonsil carcinoma. Cancer, 103(9), 1843-1849.
Soo, K. C., Tan, E. H., Wee, J., Lim, D., Tai, B. C., Khoo, M. L., ... & Lu, P. (2005). Surgery and adjuvant radiotherapy vs concurrent
chemoradiotherapy in stage III/IV nonmetastatic squamous cell head and neck cancer: a randomised comparison. British journal of
cancer, 93(3), 279-286.
Verma, R. K., Tripathi, N., Aggarwal, P., & Panda, N. K. (2014). Metastatic papillary carcinoma thyroid co-existing with oral cavity
squamous cell carcinoma: A case report and review of literature. Egyptian Journal of Ear, Nose, Throat and Allied Sciences, 15(2), 125128.