Clinical Features and Diagnosis of Cutaneous Squamous Cell Carcinoma (SCC) - UpToDate PDF

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Clinical features and diagnosis of cutaneous squamous cell carcinoma (SCC)
Authors: Jean Lee Lim, MD, Maryam Asgari, MD, MPH
Section Editors: Robert S Stern, MD, June K Robinson, MD
Deputy Editor: Rosamaria Corona, MD, DSc
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Jun 2018. | This topic last updated: Mar 08, 2017.
INTRODUCTION — Cutaneous squamous cell carcinoma (SCC) presents with a wide variety of clinical
manifestations, including papules, plaques, or nodules, and smooth, hyperkeratotic, or ulcerative lesions. Skin
biopsies are required to confirm the diagnosis. Biopsies also provide information that is useful for staging.
The clinical presentation and diagnosis of SCC will be reviewed here. The epidemiology and risk factors for
the development of SCC and the treatment of cutaneous SCC are reviewed separately. (See "Epidemiology
and risk factors for cutaneous squamous cell carcinoma" and "Evaluation for locoregional and distant
metastases in cutaneous squamous cell and basal cell carcinoma" and "Treatment and prognosis of
cutaneous squamous cell carcinoma".)
CLINICAL FEATURES
Location — SCC can develop on any cutaneous surface, including the head, neck, trunk, extremities, oral
mucosa, periungual skin, and anogenital areas (picture 1AD). In fairskinned individuals, SCCs most
commonly arise in sites frequently exposed to the sun. In a cohort of 145 patients with SCC in Australia, the
following distribution of SCC was observed [1].
● Head and neck (55 percent)
● Dorsum of the hands and forearms (18 percent)
● Legs (13 percent)
● Arms (3 percent)
● Shoulder or back (4 percent)
● Chest or abdomen (4 percent)
The development of SCC on nonsunexposed skin is less common overall, but represents the most common
distribution in individuals with dark skin. This finding is likely related to the protective effect of epidermal
melanin against the carcinogenic effects of ultraviolet light. In black individuals, common sites for SCC include
the legs, anus, and areas of chronic inflammation or scarring [24]. Lesions that develop in relation to chronic
scarring processes account for 20 to 40 percent of SCCs in black patients [2]. (See "Epidemiology and risk
factors for cutaneous squamous cell carcinoma", section on 'Ethnicity' and "Epidemiology and risk factors for
cutaneous squamous cell carcinoma", section on 'Chronic inflammation'.)
Genital and periungual SCC lesions are rare and are usually related to infection with highrisk human
papillomavirus (HPV) [5]. Genital lesions may also arise as a consequence of the administration of psoralen
plus ultraviolet A (PUVA) phototherapy without genital shields [6]. Of note, tumors arising on the ear,
preauricular surfaces, or at mucocutaneous interfaces (ie, lips, genitalia, and perianal area) tend to be more
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aggressive, with rates of metastasis estimated to range from 10 to 30 percent [79]. (See "Virology of human
papillomavirus infections and the link to cancer".)
Clinical findings — The clinical appearance of cutaneous SCC is influenced by the lesion type and site.
SCC in situ (Bowen's disease) — Cutaneous SCC in situ typically presents as a welldemarcated, scaly
patch or plaque (picture 2). Lesions are often erythematous but can also be skin colored or pigmented. SCC
in situ lesions tend to grow slowly, enlarging over the course of years. Unlike the inflammatory disorders that
may resemble SCC in situ, lesions are usually asymptomatic. (See 'Differential diagnosis' below.)
Erythroplasia of Queyrat — Erythroplasia of Queyrat is a term used to describe SCC in situ involving
the penis. This condition presents as a welldefined, velvety, red plaque (picture 1D). Patients may experience
pain, bleeding, or pruritus. (See "Carcinoma of the penis: Clinical presentation, diagnosis, and staging",
section on 'Premalignant lesions'.)
Invasive SCC — The clinical appearance of invasive SCC often correlates with the level of tumor
differentiation. Welldifferentiated lesions usually appear as indurated or firm, hyperkeratotic papules, plaques,
or nodules (picture 1A, 1EG). Lesions are usually 0.5 to 1.5 cm in diameter, although some are much larger.
Ulceration may or may not be present.
In contrast, poorly differentiated lesions are usually fleshy, soft, granulomatous papules or nodules that lack
the hyperkeratosis that is often seen in welldifferentiated lesions (picture 3). Poorly differentiated tumors may
have ulceration, hemorrhage, or areas of necrosis.
Lesions of invasive SCC are often asymptomatic but may be painful or pruritic. Local neurologic symptoms
(eg, numbness, stinging, burning, paresthesias, paralysis, or visual changes) occur in approximately onethird
of patients with histologic perineural invasion by the tumor [10]. Perineural invasion is a poor prognostic factor
[11]. (See 'Staging' below.)
Other variants
Oral SCC — Oral SCC usually presents as an ulcer, nodule, or indurated plaque involving the oral
cavity (picture 1C, 1H). The floor of the mouth and lateral or ventral tongue are the most common sites for
these tumors. Lesions may arise in sites of erythroplakia (premalignant, persistent, red patches in the oral
cavity) or leukoplakia (oral, persistent, white plaques) (picture 4). Oral SCC is often associated with a history
of tobacco or heavy alcohol use. (See "Oral lesions", section on 'Squamous cell carcinoma'.)
Keratoacanthoma — Keratoacanthomas are keratocytic epithelial tumors that clinically and
histologically resemble SCC. It is controversial whether keratoacanthomas represent a subtype of well
differentiated SCC or a separate entity. (See "Keratoacanthoma: Epidemiology, risk factors, and diagnosis".)
Keratoacanthomas are usually found on actinically damaged skin. Lesions typically exhibit rapid initial growth,
manifesting as domeshaped or crateriform nodules with a central keratotic core that develop within a few
weeks (picture 5).
Verrucous carcinoma — Verrucous carcinoma is a subtype of SCC that presents with welldefined,
exophytic, cauliflowerlike growths that resemble large warts. Lesions are subclassified according to site:
● Oral florid papillomatosis – Verrucous carcinoma of the oral mucosa (picture 6AB)
● Anogenital (also known as giant condyloma acuminatum of BuschkeLoewenstein) – Verrucous
carcinoma involving the penis, scrotum, or perianal region (picture 7) (see "Carcinoma of the penis:
Epidemiology, risk factors, and pathology", section on 'Pathology')
● Epithelioma cuniculatum – Verrucous carcinoma on the plantar foot
Verrucous carcinoma may also occur in other locations.
SCC of the lip — SCC of the lip primarily occurs on the lower lip. Lesions may present as nodules,
ulcers, or indurated, white plaques (picture 8). (See "Oral lesions", section on 'Squamous cell carcinoma'.)
Marjolin's ulcer — Marjolin’s ulcer is a term used to describe a rare type of SCC arising in sites of
chronic wounds or scars [1214]. The malignant transformation is usually slow, with an average latency time
of approximately 30 years [12,15].
The tumor may initially present as an ulceration that fails to heal; nodules may develop as the lesion
progresses. Other clinical signs include rolled or everted wound margins, excessive granulation tissue, rapid
increase in size, and bleeding on touch.
SCCs arising in the setting of chronic wounds or scar are typically aggressive and are associated with a poor
prognosis [16]. The risk of local recurrence after treatment or metastasis is approximately 20 to 30 percent
[12,1719].
Cutaneous metastases — The most frequent site of metastasis for cutaneous SCC is the regional lymph
nodes; other potential sites for metastasis include the lungs, liver, brain, skin, or bone. Metastases to the skin
can present with erythematous papules or nodules that resemble primary lesions of cutaneous SCC (picture
9). (See "Treatment and prognosis of cutaneous squamous cell carcinoma", section on 'Prognosis'.)
DIAGNOSIS — Although clinical findings may strongly suggest a diagnosis of SCC, histopathologic
examination is necessary to confirm the diagnosis. Histopathologic examination is also useful for assessment
for perineural invasion, tumor differentiation, and tumor depth, factors that are important for tumor staging and
prognosis. (See 'Staging' below.)
Biopsy — Shave, punch, or excisional biopsies may be used for diagnosis. Regardless of the biopsy
technique selected, for lesions that are papular, nodular, or otherwise suspicious for invasive SCC, biopsies
that extend at least into the midreticular dermis are preferred to allow for adequate evaluation of invasive
disease. More superficial biopsies may be performed in patients with lesions that are suggestive of in situ
SCC. (See "Skin biopsy techniques".)
SCC in situ — SCC in situ (Bowen’s disease) is diagnosed when histopathologic examination reveals
keratinocytic dysplasia involving the full thickness of the epidermis without infiltration of atypical cells into the
dermis. The keratinocytes are pleomorphic with hyperchromatic nuclei, and numerous mitoses are present.
Frequently, there is associated thickening of the epidermis (acanthosis), as well as hyperkeratosis and
parakeratosis of the stratum corneum. In contrast to SCC in situ, actinic keratoses demonstrate only partial
thickness epidermal dysplasia.
Invasive SCC — Invasive SCCs have dysplastic keratinocytes involving the full thickness of the epidermis
that penetrate the epidermal basement membrane to involve the dermis or deeper tissues. Welldifferentiated
cutaneous SCCs contain atypical keratinocytes that are slightly enlarged with abundant amounts of
cytoplasm. Keratinization is usually present.
In poorly differentiated SCC, keratinocytes are anaplastic, with little evidence for differentiation or
keratinization. Multiple mitoses are often seen. Occasionally, the keratinocytic origin of the cells can only be
determined by immunohistochemical stains.
Several histopathologic variants of invasive SCC exist, including spindle cell SCC, acantholytic (adenoid)
SCC, clear cell SCC, adenosquamous (mucinproducing) SCC, desmoplastic SCC, singlecell SCC, and
others [2022].
DIFFERENTIAL DIAGNOSIS — Multiple other skin disorders can resemble cutaneous SCC.
Actinic keratoses — The most common clinical diagnostic dilemma involves actinic keratoses. Actinic
keratoses are rough, scaly, erythematous macules that develop on sundamaged skin and demonstrate
keratinocytic atypia on histopathologic examination (picture 10AB). Although only a fraction of 1 percent of
actinic keratoses progress to SCC, approximately 60 percent of SCCs arise from actinic keratoses [2325].
(See "Epidemiology, natural history, and diagnosis of actinic keratosis", section on 'Progression to skin cancer'
and "Epidemiology, natural history, and diagnosis of actinic keratosis".)
Actinic keratoses are often found in close proximity to SCCs and can resemble SCC in situ or early SCC.
Tenderness, bleeding, and palpable underlying substance suggest the possibility of SCC and indicate the
need for biopsy.
Bowenoid papulosis — Bowenoid papulosis is a premalignant focal epidermal dysplasia characterized by
multiple, red to browncolored, small papules that primarily arise on genitals, although extragenital cases also
have been reported (picture 11) [26]. The condition is classified as a transitional state between genital warts
and SCC in situ.
Bowenoid papulosis is induced by human papillomavirus (HPV) infection. Although the most common inciting
agent is HPV 16, other HPV types have been implicated [27]. On histopathologic examination, lesions
demonstrate focal epidermal hyperplasia and partialthickness to fullthickness epidermal dysplasia [28].
The rate of malignant transformation of bowenoid papulosis to SCC is low (estimated to be 1 to 2.6 percent),
and the majority of lesions can be treated successfully with simple, local destruction or topical
immunomodulators [29,30]. Because bowenoid papulosis has the potential to undergo malignant
transformation, followup evaluation is warranted if the lesions recur or undergo rapid enlargement. (See
"Carcinoma of the penis: Clinical presentation, diagnosis, and staging".)
Other disorders — The welldemarcated, scaling, pink plaques of SCC in situ can resemble inflammatory
skin disorders or other malignancies. The differential diagnosis often includes:
● Nummular eczema (picture 12AB)
● Psoriasis (picture 13)
● Inflamed seborrheic keratosis (picture 14)
● Viral warts
● Superficial basal cell carcinoma (picture 15)
● Amelanotic melanoma (picture 16)
● Paget disease (picture 17)
Welldefined papules or nodules of welldifferentiated SCC can resemble:
● Viral warts (picture 18AB)
● Prurigo nodules (picture 19AB)
● Merkel cell carcinoma (picture 20AB)
● Basal cell carcinoma (picture 21)
● Atypical fibroxanthoma (picture 22)
● Amelanotic melanoma (picture 23)
● Cutaneous metastases of internal malignancy
Granulomatous or verrucous lesions may mimic:
● Pyogenic granuloma (picture 24AB)
● Mycobacterial or deep fungal infections (picture 25)
The differential diagnosis for SCC manifesting as nonhealing ulcers includes:
● Basal cell carcinoma (picture 26)
● Pyoderma gangrenosum (picture 27AB)
● Venous stasis ulcers
● Traumatic ulcers
STAGING — At the time of diagnosis, patients with SCC should be given a fullbody skin examination that
includes palpation of regional lymph nodes to evaluate for additional cutaneous SCCs and clinical signs of
metastatic disease. (See "Evaluation for locoregional and distant metastases in cutaneous squamous cell and
basal cell carcinoma", section on 'Squamous cell carcinoma'.)
In September 2016, the American Joint Committee on Cancer (AJCC) and the Union for International Cancer
Control (UICC) issued the 8th Edition of staging guidelines [31]. The new guidelines contain an updated
cutaneous SCC staging system encompassing tumors located on the head and neck only, since the
system was developed within the AJCC's head and neck committee. The new cutaneous SCC staging system
has expanded the criteria for upstaging to T3. A table that demonstrates the updated AJCC staging criteria for
head and neck SCC is provided (table 1).
SUMMARY
● Squamous cell carcinoma (SCC) is a common cutaneous malignancy that can occur on any surface of
the skin. Sunexposed sites are the most common locations for SCC in fairskinned individuals;
involvement of other areas is more common in people with dark skin. (See 'Location' above.)
● The clinical findings of cutaneous SCC depend on the type of lesion and location of involvement. SCC
frequently manifests as erythematous papules, plaques, or nodules. Hyperkeratosis, ulceration, or
hyperpigmentation also may be present. (See 'Clinical findings' above.)
● SCC can develop in sites of chronic wounds, chronic inflammation, or scarring. Nonhealing ulcers or
nodules in these sites can be a manifestation of SCC. (See 'Marjolin's ulcer' above.)
● Biopsy is necessary to confirm the diagnosis of SCC. For lesions clinically suspected to be invasive, a
shave, punch, or excisional biopsy that extends at least into the midreticular dermis is preferred. (See
'Biopsy' above.)
● Actinic keratoses can resemble lesions of SCC. Lesions that are tender, painful, or that have underlying
substance should be biopsied to evaluate for SCC. (See 'Differential diagnosis' above.)
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REFERENCES
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4. Mora RG, Perniciaro C. Cancer of the skin in blacks. I. A review of 163 black patients with cutaneous
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5. Eliezri YD, Silverstein SJ, Nuovo GJ. Occurrence of human papillomavirus type 16 DNA in cutaneous
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8. Weinberg AS, Ogle CA, Shim EK. Metastatic cutaneous squamous cell carcinoma: an update. Dermatol
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9. Rowe DE, Carroll RJ, Day CL Jr. Prognostic factors for local recurrence, metastasis, and survival rates
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10. Reule RB, Golda NJ, Wheeland RG. Treatment of cutaneous squamous cell carcinoma with perineural
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Surg 2009; 35:1559.
11. Farasat S, Yu SS, Neel VA, et al. A new American Joint Committee on Cancer staging system for
cutaneous squamous cell carcinoma: creation and rationale for inclusion of tumor (T) characteristics. J
Am Acad Dermatol 2011; 64:1051.
12. KerrValentic MA, Samimi K, Rohlen BH, et al. Marjolin's ulcer: modern analysis of an ancient problem.
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13. Pekarek B, Buck S, Osher L. A Comprehensive Review on Marjolin's Ulcers: Diagnosis and Treatment.
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15. Chang JB, Kung TA, Cederna PS. Acute Marjolin's ulcers: a nebulous diagnosis. Ann Plast Surg 2014;
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16. Tobin C, Sanger JR. Marjolin's Ulcers: A Case Series and Literature Review. Wounds 2014; 26:248.
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18. Kadir AR. Burn scar neoplasm. Ann Burns Fire Disasters 2007; 20:185.
19. Copcu E, Aktas A, Sişman N, Oztan Y. Thirtyone cases of Marjolin's ulcer. Clin Exp Dermatol 2003;
28:138.
20. Yanofsky VR, Mercer SE, Phelps RG. Histopathological variants of cutaneous squamous cell carcinoma:
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21. Petter G, Haustein UF. Histologic subtyping and malignancy assessment of cutaneous squamous cell
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22. Auerbach A, Mulvaney P, Goldberg D, et al. SingleCell Squamous Carcinoma: An Underreported High
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31. Part II Head and Neck. In: AJCC Cancer Staging Manual, 8th ed, Amid MB (Ed), Springer, New York 20
17. p.53.
Topic 16225 Version 14.0
GRAPHICS
Cutaneous squamous cell carcinoma
Keratotic, cutaneous horn on an erythematous base on the preauricular skin.
Reproduced with permission from: www.visualdx.com. Copyright Logical Images, Inc.
Graphic 74240 Version 5.0
Periungual squamous cell carcinoma
An ulcerated papule is present on the periungual skin.
Squamous cell carcinoma of the tongue
This nodule on the ventral surface of the tongue is a squamous cell carcinoma.
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Erythroplasia of Queyrat
Bowen's disease (cutaneous squamous cell carcinoma in situ)
An erythematous, scaly, thin plaque is present on the skin.
An erythematous, hyperkeratotic papule is present on the skin.
An erythematous scaly papule is present on the lower leg.
Red papulonodule with scale on dorsal hand.
Poorly differentiated cutaneous squamous cell carcinoma
A soft, fleshy, granulomatous tumor is present on the skin.
Squamous cell carcinoma on the gingiva
This ulcerated nodule involving the gingiva represents a squamous cell
carcinoma.
Leukoplakia
A white plaque is present on the hard palate and gingiva.
Keratoacanthoma
Crateriform nodule with central hyperkeratosis.
Verrucous carcinoma of the oral cavity
Verrucous carcinoma of the oral cavity.
Courtesy of Vaibhav Parekh, MD MBA.
Verrucous carcinoma of the oral cavity
Verrucous carcinoma of the oral cavity (oral florid papillomatosis).
Verrucous carcinoma (also known as giant condyloma of
BuschkeLowenstein)
Squamous cell carcinoma on the lip
This erythematous, crusted nodule on the lip represents a squamous cell
carcinoma.
Squamous cell carcinoma metastasizing to the skin
Renal transplant recipient with locally recurrent squamous cell carcinoma and in
transit metastasis.
Actinic keratosis
Actinic keratosis. Scale overlies erythematous macules.
Actinic keratosis
Muliple actinic keratoses present as rough scaly red macules on sundamaged
skin.
Reproduced from: Fitzpatrick TB, Johnson RA, Wolff K, Suurmond D. Color Atlas and
Synopsis of Clinical Dermatology. Common and Serious Diseases. (4th Ed), McGraw
Hill, New York 2001. p.220.
Bowenoid papulosis
Multiple reddish, small papules on the penis of this patient with Bowenoid
papulosis.
Nummular eczema
These coinshaped, scaly lesions on the thigh show evidence of
postinflammatory hyperpigmentation.
Reproduced with permission from: Goodheart HP. Goodheart's Photoguide of
Common Skin Disorders, 2nd ed, Lippincott Williams & Wilkins, Philadelphia 2003.
Copyright © 2003 Lippincott Williams & Wilkins.
Nummular eczema
"Coinshaped" patches and plaques are located on the legs.
Reproduced with permission from: Goodheart HP. Goodheart's Photoguide of
Common Skin Disorders, 2nd ed, Lippincott Williams & Wilkins, Philadelphia 2003.
Plaque psoriasis
An erythematous plaque with coarse scale is present on the knee of this patient
with psoriasis.
Inflamed seborrheic keratosis
Inflamed and hyperpigmented seborrheic keratosis.
Superficial basal cell carcinoma
This erythematous, slightly scaly patch is representative of a superficial basal
cell carcinoma.
Amelanotic melanoma
Amelanotic melanoma presenting as a red, nonspecific lesion with slightly
elevated borders.
Vulvar Paget's disease
Reproduced with permission from Lynne J Margesson, MD.
Verruca vulgaris
A welldefined, keratotic papule is present on the dorsal finger in this patient
with verruca vulgaris (common wart).
Verruca vulgaris
A keratotic papule with peripheral hyperpigmentation is present on the hand of
this patient with verruca vulgaris (common wart).
Prurigo nodularis
Discrete, excoriated nodules on the leg of a patient with nodular prurigo.
Prurigo nodularis
Multiple nodules, some of which excoriated, on the lower limb of a patient with
nodular prurigo.
Merkel cell carcinoma
This bluered, domeshaped papule on the forehead is a Merkel cell carcinoma.
Merkel cell carcinoma
This bluered, domeshaped nodule is a Merkel cell carcinoma.
Nodular basal cell carcinoma
This pearly papule with telangiectasias is representative of a nodular basal cell
carcinoma.
Atypical fibroxanthoma
An erythematous, domeshaped papule is present on the face.
Amelanotic melanoma
Amelanotic melanoma presenting as a red, excoriated, papular lesion.
Pyogenic granuloma
A red, protruding vascular papule consistent with a pyogenic granuloma is
present on the chest.
Pyogenic granuloma on the finger
A rapidly growing, red, domeshaped, friable papule with a collarette of scale is
consistent with a pyogenic granuloma.
Reproduced with permission from: Fleisher GR, Ludwig S, Baskin MN. Atlas of
Pediatric Emergency Medicine, Lippincott Williams & Wilkins, Philadelphia 2004.
Disseminated blastomycosis
Verrucous plaque on the upper cheek due to disseminated blastomycosis.
Courtesy of Charles V Sanders, MD. Reproduced with permission from The Skin and
Infection: A Color Atlas and Text. Sanders, CV, Nesbitt, LT Jr (Eds) Williams and
Wilkins, Baltimore 1995. p.174.

http://www.lww.com
Destructive basal cell carcinoma
Large basal cell carcinoma causing destruction of the nose.
Pyoderma gangrenosum
This purulent ulcer with a ragged and violaceous border is consistent with
pyoderma gangrenosum.
Pyoderma gangrenosum
This purulent ulcer with a ragged and violaceous border is consistent with
pyoderma gangrenosum.
Cutaneous squamous cell carcinoma of the head and neck TNM staging AJCC UICC
2017
Primary tumor (T)
T category T criteria
TX Primary tumor cannot be assessed
Tis Carcinoma in situ
T1 Tumor smaller than 2 cm in greatest dimension
T2 Tumor 2 cm or larger, but smaller than 4 cm in greatest dimension
T3 Tumor 4 cm or larger in maximum dimension or minor bone erosion or perineural
invasion or deep invasion*
T4 Tumor with gross cortical bone/marrow, skull base invasion and/or skull base foramen
invasion
T4a Tumor with gross cortical bone/marrow invasion
T4b Tumor with skull base invasion and/or skull base foramen involvement
* Deep invasion is defined as invasion beyond the subcutaneous fat or >6 mm (as measured from the granular
layer of adjacent normal epidermis to the base of the tumor); perineural invasion for T3 classification is defined
as tumor cells within the nerve sheath of a nerve lying deeper than the dermis or measuring 0.1 mm or larger in
caliber, or presenting with clinical or radiographic involvement of named nerves without skull base invasion or
transgression.
Regional lymph nodes (N)
Clinical N (cN)
N category N criteria
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Metastasis in a single ipsilateral lymph node, 3 cm or smaller in greatest dimension
and ENE(–)
N2 Metastasis in a single ipsilateral node larger than 3 cm but not larger than 6 cm in
greatest dimension and ENE(–); or
Metastases in multiple ipsilateral lymph nodes, none larger than 6 cm in greatest
dimension and ENE(–); or
In bilateral or contralateral lymph nodes, none larger than 6 cm in greatest dimension
and ENE(–)
N2a Metastasis in a single ipsilateral node larger than 3 cm but not larger than 6 cm in
greatest dimension and ENE(–)
N2b Metastasis in multiple ipsilateral nodes, none larger than 6 cm in greatest dimension
and ENE(–)
N2c Metastasis in bilateral or contralateral lymph nodes, none larger than 6 cm in greatest
dimension and ENE(–)
N3 Metastasis in a lymph node larger than 6 cm in greatest dimension and ENE(–); or
Metastasis in any node(s) and clinically overt ENE [ENE(+)]
N3a Metastasis in a lymph node larger than 6 cm in greatest dimension and ENE(–)
N3b Metastasis in any node(s) and ENE(+)
NOTE: A designation of "U" or "L" may be used for any N category to indicate metastasis above the lower
border of the cricoid (U) or below the lower border of the cricoid (L).
Similarly, clinical and pathological ENE should be recorded as ENE(–) or ENE(+).
Pathological N (pN)
N category N criteria
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
and ENE(–)
and ENE(+); or
Larger than 3 cm but not larger than 6 cm in greatest dimension and ENE(–); or
Metastases in multiple ipsilateral lymph nodes, none larger than 6 cm in greatest
dimension and ENE(–); or
In bilateral or contralateral lymph node(s), none larger than 6 cm in greatest
dimension, ENE(–)
N2a Metastasis in a single ipsilateral lymph node, 3 cm or smaller in greatest dimension
and ENE(+); or
A single ipsilateral node larger than 3 cm but not larger than 6 cm in greatest
dimension and ENE(–)
N2b Metastasis in multiple ipsilateral nodes, none larger than 6 cm in greatest dimension
and ENE(–)
N2c Metastasis in bilateral or contralateral lymph node(s), none larger than 6 cm in
greatest dimension and ENE(–)
N3 Metastasis in a lymph node larger than 6 cm in greatest dimension and ENE(–); or
In a single ipsilateral node larger than 3 cm in greatest dimension and ENE(+); or
Multiple ipsilateral, contralateral, or bilateral nodes, any with ENE(+); or
A single contralateral node 3 cm or smaller and ENE(+)
N3a Metastasis in a lymph node larger than 6 cm in greatest dimension and ENE(–)
N3b Metastasis in a single ipsilateral node larger than 3 cm in greatest dimension and
ENE(+); or
Multiple ipsilateral, contralateral, or bilateral nodes, any with ENE(+); or
A single contralateral node 3 cm or smaller and ENE(+)
NOTE: A designation of "U" or "L" may be used for any N category to indicate metastasis above the lower
border of the cricoid (U) or below the lower border of the cricoid (L).
Similarly, clinical and pathological ENE should be recorded as ENE(–) or ENE(+).
Distant metastasis (M)
M category M criteria
M0 No distant metastasis
M1 Distant metastasis
Prognostic stage groups
When T is... And N is... And M is... Then the stage group
is...
Tis N0 M0 0
T1 N0 M0 I
T2 N0 M0 II
T3 N0 M0 III
T1 N1 M0 III
T2 N1 M0 III
T3 N1 M0 III
T1 N2 M0 IV
T2 N2 M0 IV
T3 N2 M0 IV
Any T N3 M0 IV
T4 Any N M0 IV
Any T Any N M1 IV
TNM: tumor, node, metastasis; AJCC: American Joint Committee on Cancer; UICC: Union for International Cancer Control;
ENE: extranodal extension.
Used with permission of the American College of Surgeons, Chicago, Illinois. The original source for this information is the
AJCC Cancer Staging Manual, Eighth Edition (2017) published by Springer International Publishing.
Contributor Disclosures
Jean Lee Lim, MD Nothing to disclose Maryam Asgari, MD, MPH Grant/Research/Clinical Trial Support:
Pfizer [Psoriasis (Anti-tumor necrosis factor-alpha inhibitor, immunosuppressants)]; Valeant [Atopic dermatitis
(Pimecrolimus, topical corticosteroid, topical calcineurin inhibitor)]. Robert S Stern, MD Consultant/Advisory
Boards: Bristol-Myers Squibb [Advance skin cancer (Checkpoint inhibitors)]; Plexxikon [Advance skin cancer
(Various drugs)]; Hydra [Advance skin cancer (Various drugs)]; Vertex Pharmaceuticals [Skin reactions, cystic
fibrosis (Medications under development)]. Other Financial Interest: Mylan [Skin reactions (Expert in product
liability case concerning phenytoin skin reaction)]; United States Department of Justice [Malpractice
defense]; Pfizer [Psoriasis (Expert in patent litigation concerning adalimumab)]. June K Robinson,
MD Nothing to disclose Rosamaria Corona, MD, DSc Nothing to disclose
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must
conform to UpToDate standards of evidence.
Conflict of interest policy

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