ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

Cutaneous squamous cell carcinoma (cSCC): Clinical features and diagnosis

Cutaneous squamous cell carcinoma (cSCC): Clinical features and diagnosis
Literature review current through: Jan 2024.
This topic last updated: Oct 20, 2022.

INTRODUCTION — Cutaneous squamous cell carcinoma (cSCC) is a malignant tumor arising from epidermal keratinocytes [1]. In individuals with lightly pigmented skin, it typically develops in areas of photodamaged skin and presents with a wide variety of cutaneous lesions, including papules, plaques, or nodules, that can be smooth, hyperkeratotic, or ulcerated (picture 1A-B). A skin biopsy is required to confirm the diagnosis. Biopsies also provide information that is useful for staging and management.

The clinical presentation and diagnosis of cSCC will be reviewed here. The epidemiology and risk factors for the development of squamous cell carcinoma (SCC) and the treatment of cSCC are reviewed separately.

(See "Cutaneous squamous cell carcinoma: Epidemiology and risk factors".)

(See "Treatment and prognosis of low-risk cutaneous squamous cell carcinoma (cSCC)".)

(See "Recognition and management of high-risk (aggressive) cutaneous squamous cell carcinoma".)

(See "Systemic treatment of advanced basal cell and cutaneous squamous cell carcinomas not amenable to local therapies".)

(See "Evaluation for locoregional and distant metastases in cutaneous squamous cell and basal cell carcinoma".)

CLINICAL FEATURES

Location — cSCC can develop on any cutaneous surface, including the head, neck, trunk, extremities, oral mucosa, periungual skin, and anogenital areas (picture 2A-D). In individuals with lightly pigmented skin, cSCCs most commonly arise in sites frequently exposed to the sun.

Non-sun-exposed areas represent the most common location for cSCC in individuals with darkly pigmented skin. In Black individuals, common sites for cSCC include the lower legs, anogenital region (picture 3), and areas of chronic inflammation or scarring (picture 4) [2-6]. Lesions that develop in relation to chronic scarring processes account for 20 to 40 percent of cSCCs in Black patients [2]. (See "Cutaneous squamous cell carcinoma: Epidemiology and risk factors", section on 'Skin pigmentation and ancestry' and "Cutaneous squamous cell carcinoma: Epidemiology and risk factors", section on 'Chronic inflammation'.)

Genital and periungual cSCC lesions are less common and are usually related to infection with high-risk human papillomavirus (HPV) [7]. (See "Cutaneous squamous cell carcinoma: Epidemiology and risk factors", section on 'Human papillomavirus infection'.)

Genital lesions may also arise as a consequence of the administration of psoralen plus ultraviolet A (PUVA) phototherapy without genital shields [8]. Of note, tumors arising on the ear, preauricular surfaces, or at mucocutaneous interfaces (ie, lips, genitalia, and perianal area) tend to be more aggressive, with rates of metastasis estimated to range from 10 to 30 percent [9-11]. (See "Recognition and management of high-risk (aggressive) cutaneous squamous cell carcinoma", section on 'Clinical features'.)

Cutaneous squamous cell carcinoma in situ (Bowen's disease) — cSCC in situ (Bowen's disease) typically presents as an erythematous, well-demarcated, scaly patch or plaque (picture 5A-B) located in sun-exposed areas, such as the head and neck and extremities. Lesions can also be skin colored or pigmented, particularly in individuals with darkly pigmented skin. Lesions of cSCC in situ tend to grow slowly, enlarging over the course of years. Unlike the inflammatory disorders that may resemble cSCC in situ, such as psoriasis or chronic eczema, cSCC in situ lesions are usually asymptomatic. (See 'Differential diagnosis' below.)

"Erythroplasia of Queyrat" is a term used to describe cSCC in situ involving the penis. This condition presents as a well-defined, velvety, red plaque (picture 2D). Patients may experience pain, bleeding, or pruritus. (See "Carcinoma of the penis: Clinical presentation, diagnosis, and staging", section on 'Premalignant lesions'.)

Invasive cutaneous squamous cell carcinoma — The clinical appearance of invasive cSCC often correlates with the level of tumor differentiation. Well-differentiated lesions usually appear as indurated or firm, hyperkeratotic papules, plaques, or nodules (picture 1A-B, 2A, 2E). Lesions are usually 0.5 to 1.5 cm in diameter but may be much larger. Ulceration may or may not be present.

In contrast, poorly differentiated lesions are usually fleshy, granulomatous papules or nodules resembling pyogenic granuloma that lack the hyperkeratosis that is often seen in well-differentiated lesions (picture 6A-B). Poorly differentiated tumors may have ulceration, hemorrhage, or areas of necrosis.

Lesions of invasive cSCC are often asymptomatic but may be painful or pruritic. Local neurologic symptoms (eg, numbness, stinging, burning, paresthesias, paralysis, or visual changes) occur in approximately one-third of patients with high-risk cSCC showing histologic perineural invasion [12]. (See "Recognition and management of high-risk (aggressive) cutaneous squamous cell carcinoma", section on 'Clinical features'.)

CLINICAL VARIANTS

Keratoacanthoma — Keratoacanthomas are keratocytic epithelial tumors that clinically and histologically resemble squamous cell carcinoma (SCC). It is controversial whether keratoacanthomas represent a subtype of well-differentiated cSCC or a separate entity. Keratoacanthomas are usually found on actinically damaged skin. Lesions typically exhibit rapid initial growth, manifesting as dome-shaped or crateriform nodules with a central keratotic core that develop within a few weeks (picture 7). (See "Keratoacanthoma: Epidemiology, risk factors, and diagnosis".)

Verrucous carcinoma — Verrucous carcinoma is a rare variant of cSCC that presents with well-defined, exophytic, cauliflower-like growths that resemble large warts. Lesions are subclassified according to site:

Oral florid papillomatosis – Verrucous carcinoma of the oral mucosa (picture 8A-B)

Anogenital (also known as giant condyloma acuminatum of Buschke-Löwenstein) – Verrucous carcinoma involving the penis, scrotum, or perianal region (picture 9) (see "Carcinoma of the penis: Epidemiology, risk factors, and pathology", section on 'Pathology')

Epithelioma cuniculatum – Verrucous carcinoma on the plantar foot (picture 10)

Verrucous carcinoma may also occur in other locations.

Cutaneous squamous cell carcinoma of the lip — SCC of the lip primarily occurs on the lower lip. Lesions may present as nodules, ulcers, or indurated, white plaques (picture 11). (See "Oral lesions", section on 'Oral squamous cell carcinoma'.)

Oral squamous cell carcinoma — Oral SCC usually presents as an ulcer, nodule, or indurated plaque involving the oral cavity (picture 2C, 2F). 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 12). Oral SCC is often associated with a history of tobacco or heavy alcohol use. (See "Oral leukoplakia" and "Oral lesions", section on 'Oral squamous cell carcinoma'.)

Marjolin's ulcer — "Marjolin's ulcer" is a term used to describe a rare type of cSCC arising in sites of chronic wounds or scars [13-15]. The malignant transformation is usually slow, with an average latency time of approximately 30 years [13,16].

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 scars are typically aggressive and are associated with a poor prognosis [17]. The risk of local recurrence after treatment or metastasis is approximately 20 to 30 percent [13,18-20].

Lymphoepithelioma-like carcinoma of the skin — Primary lymphoepithelioma-like carcinoma of the skin is a very rare, indolent, malignant skin tumor of epithelial origin, considered a variant of cSCC [21]. Clinically, it presents as a flesh-colored, firm nodule or plaque, most often located in the head and neck region. Histopathologically, it shows islands of poorly differentiated epithelial cells with a dense lymphoid infiltrate, resembling undifferentiated nasopharyngeal carcinoma. (See "Epidemiology, etiology, and diagnosis of nasopharyngeal carcinoma".)

DIAGNOSIS — Although clinical and dermoscopic findings may strongly suggest a diagnosis of cSCC, 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.)

Dermoscopy — On dermoscopic examination, cSCC in situ (Bowen's disease) displays dotted and/or glomerular vessels, white to yellowish surface scales, and a red-yellowish background color (picture 13). Pigmented cSCC in situ typically shows a structureless, brown pattern with hypopigmented areas (skin colored or white) often eccentrically located and brown dots arranged as radial lines at the periphery (picture 14). Key dermoscopic features of invasive cSCC are white circles; white, structureless areas; and hairpin and linear-irregular vessels (picture 15). (See "Dermoscopic evaluation of skin lesions", section on 'Criteria for cutaneous squamous cell carcinoma' and "Dermoscopy of facial lesions", section on 'Invasive squamous cell carcinoma'.)

Biopsy and histopathology — 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 cSCC, biopsies that extend at least into the mid-reticular dermis are preferred to allow for adequate evaluation of invasive disease [22]. More superficial biopsies may be performed in patients with lesions that are suggestive of in situ squamous cell carcinoma (SCC). (See "Skin biopsy techniques".)

When submitting biopsy specimens for histopathologic diagnosis, important elements that should be provided to the pathologist include anatomic location of the tumor, clinical size of the lesion, and whether the patient has additional risk factors for cSCC, such as immunosuppression, radiation therapy, or solid organ transplantation [22]. Histopathologic evaluation of skin biopsy specimens is ideally performed by a dermatologist or pathologist who is experienced in diagnosing cutaneous tumors.

Cutaneous squamous cell carcinoma in situ — cSCC 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 [23,24]. 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 cSCC in situ, actinic keratoses demonstrate only partial-thickness epidermal dysplasia.

Invasive cutaneous squamous cell carcinoma — Invasive cSCCs have dysplastic keratinocytes involving the full thickness of the epidermis that penetrate the epidermal basement membrane to involve the dermis or deeper tissues. Well-differentiated cSCCs contain atypical keratinocytes that are slightly enlarged with abundant amounts of cytoplasm. Keratinization is usually present. In poorly differentiated cSCC, 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. Perineural infiltration, a recognized risk factor for recurrence and metastasis, can be noted more frequently in poorly differentiated cSCC.

Several histopathologic variants of invasive cSCC exist, including spindle cell SCC, acantholytic (adenoid) cSCC, clear cell cSCC, adenosquamous (mucin-producing) cSCC, desmoplastic cSCC, single-cell cSCC, and others [25-27].

DIFFERENTIAL DIAGNOSIS — Multiple other skin lesions, including premalignant, malignant, and inflammatory lesions, can resemble cSCC clinically and, in some cases, histopathologically. In particular, superficial basal cell carcinoma and cSCC in situ are especially difficult to differentiate clinically and dermoscopically from each other and sometimes from a psoriasis plaque.

Premalignant lesions

Actinic keratoses — The most common clinical diagnostic dilemma involves actinic keratoses. Actinic keratoses are rough, scaly, erythematous macules that develop on sun-damaged skin and demonstrate keratinocytic atypia on histopathologic examination (picture 16). Although the rate of transformation of actinic keratoses to squamous cell carcinoma (SCC) is very low, estimated at less than 1 percent in one year, approximately 60 percent of SCCs arise from actinic keratoses [28-30].

Actinic keratoses are often found in close proximity to cSCCs and can resemble cSCC in situ or early cSCC. Tenderness, bleeding, and palpable underlying substance suggest the possibility of cSCC and indicate the need for biopsy. (See "Actinic keratosis: Epidemiology, clinical features, and diagnosis".)

Bowenoid papulosis — Bowenoid papulosis is a premalignant focal epidermal dysplasia characterized by multiple red- to brown-colored, small papules that primarily arise on genitals, although extragenital cases have also been reported (picture 17) [31]. 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 [32]. On histopathologic examination, lesions demonstrate focal epidermal hyperplasia and partial-thickness to full-thickness epidermal dysplasia [33].

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 [34,35]. Because bowenoid papulosis has the potential to undergo malignant transformation, follow-up evaluation is warranted if the lesions recur or undergo rapid enlargement. (See "Carcinoma of the penis: Clinical presentation, diagnosis, and staging".)

Inflammatory skin disorders — The well-demarcated, scaling, pink plaques of cSCC in situ can resemble inflammatory skin disorders, including:

Nummular eczema (picture 18) (see "Nummular eczema")

Psoriasis (picture 19) (see "Psoriasis: Epidemiology, clinical manifestations, and diagnosis")

Inflamed seborrheic keratosis (picture 20) (see "Overview of benign lesions of the skin", section on 'Seborrheic keratosis')

Prurigo nodularis (picture 21A-B) (see "Prurigo nodularis")

Pyoderma gangrenosum (picture 22A-B) (see "Pyoderma gangrenosum: Pathogenesis, clinical features, and diagnosis")

Venous stasis ulcers (picture 23) (see "Clinical assessment of chronic wounds", section on 'Venous ulcers')

Other malignant skin tumors — A number of malignant skin tumors may share clinical features with cSCC:

Merkel cell carcinoma (picture 24A-B) (see "Pathogenesis, clinical features, and diagnosis of Merkel cell (neuroendocrine) carcinoma")

Basal cell carcinoma (picture 25A-C) (see "Basal cell carcinoma: Epidemiology, pathogenesis, clinical features, and diagnosis")

Atypical fibroxanthoma (picture 26) (see "Atypical fibroxanthoma")

Amelanotic melanoma (picture 27A-B) (see "Melanoma: Clinical features and diagnosis")

STAGING — At the time of diagnosis, patients with invasive cSCC should be given a full body skin examination that includes palpation of regional lymph nodes to evaluate for additional cSCCs and clinical signs of metastatic disease. The staging of cSCC is discussed separately. (See "Evaluation for locoregional and distant metastases in cutaneous squamous cell and basal cell carcinoma", section on 'Cutaneous squamous cell carcinoma' and "Recognition and management of high-risk (aggressive) cutaneous squamous cell carcinoma", section on 'Staging'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Cutaneous squamous cell carcinoma".)

SUMMARY

Clinical presentation Cutaneous squamous cell carcinoma (cSCC) can develop on any surface of the skin, but sun-exposed sites are the most common locations in individuals with lightly pigmented skin. Involvement of other areas, in particular the lower legs and anogenital region, is more common in people with darkly pigmented skin (see 'Location' above):

Cutaneous squamous cell carcinoma in situ – cSCC in situ (Bowen's disease) typically presents as an erythematous, well-demarcated, scaly patch or plaque (picture 5A-B) located in sun-exposed areas. cSCC in situ involving the penis (erythroplasia of Queyrat) presents as a well-defined, velvety, red plaque (picture 2D). (See 'Cutaneous squamous cell carcinoma in situ (Bowen's disease)' above.)

Invasive cutaneous squamous cell carcinoma – Invasive cSCC often correlates with the level of tumor differentiation. Well-differentiated lesions usually appear as indurated or firm, hyperkeratotic papules, plaques, or nodules of 0.5 to 1.5 cm (picture 1A-B, 2A, 2E), although some lesions may be much larger. (See 'Invasive cutaneous squamous cell carcinoma' above.)

Clinical variants – Clinical variants of cSCC include keratoacanthoma (picture 7), verrucous carcinoma (picture 9), squamous cell carcinoma (SCC) of the lip (picture 11), oral SCC (picture 2F), cSCC arising at sites of chronic inflammation and scarring (Marjolin's ulcer), and primary lymphoepithelioma-like carcinoma of the skin. (See 'Clinical variants' above.)

Diagnosis – 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 mid-reticular dermis is preferred. (See 'Biopsy and histopathology' above.)

Staging – Patients with a confirmed diagnosis of invasive cSCC should be given a full body skin examination that includes palpation of regional lymph nodes to evaluate for additional cSCCs and clinical signs of metastatic disease. The staging of cSCC is discussed separately. (See "Evaluation for locoregional and distant metastases in cutaneous squamous cell and basal cell carcinoma", section on 'Locoregional evaluation' and "Recognition and management of high-risk (aggressive) cutaneous squamous cell carcinoma", section on 'Staging'.)

  1. Waldman A, Schmults C. Cutaneous Squamous Cell Carcinoma. Hematol Oncol Clin North Am 2019; 33:1.
  2. Gloster HM Jr, Neal K. Skin cancer in skin of color. J Am Acad Dermatol 2006; 55:741.
  3. Asuquo ME, Ngim O, Ugare G, et al. Major dermatologic malignancies encountered in a teaching hospital surgical department in South Nigeria. Am J Clin Dermatol 2008; 9:383.
  4. Mora RG, Perniciaro C. Cancer of the skin in blacks. I. A review of 163 black patients with cutaneous squamous cell carcinoma. J Am Acad Dermatol 1981; 5:535.
  5. Hogue L, Harvey VM. Basal Cell Carcinoma, Squamous Cell Carcinoma, and Cutaneous Melanoma in Skin of Color Patients. Dermatol Clin 2019; 37:519.
  6. Higgins S, Nazemi A, Chow M, Wysong A. Review of Nonmelanoma Skin Cancer in African Americans, Hispanics, and Asians. Dermatol Surg 2018; 44:903.
  7. Eliezri YD, Silverstein SJ, Nuovo GJ. Occurrence of human papillomavirus type 16 DNA in cutaneous squamous and basal cell neoplasms. J Am Acad Dermatol 1990; 23:836.
  8. Stern RS, Bagheri S, Nichols K, PUVA Follow Up Study. The persistent risk of genital tumors among men treated with psoralen plus ultraviolet A (PUVA) for psoriasis. J Am Acad Dermatol 2002; 47:33.
  9. Veness MJ. Defining patients with high-risk cutaneous squamous cell carcinoma. Australas J Dermatol 2006; 47:28.
  10. Weinberg AS, Ogle CA, Shim EK. Metastatic cutaneous squamous cell carcinoma: an update. Dermatol Surg 2007; 33:885.
  11. Rowe DE, Carroll RJ, Day CL Jr. Prognostic factors for local recurrence, metastasis, and survival rates in squamous cell carcinoma of the skin, ear, and lip. Implications for treatment modality selection. J Am Acad Dermatol 1992; 26:976.
  12. Reule RB, Golda NJ, Wheeland RG. Treatment of cutaneous squamous cell carcinoma with perineural invasion using Mohs micrographic surgery: report of two cases and review of the literature. Dermatol Surg 2009; 35:1559.
  13. Kerr-Valentic MA, Samimi K, Rohlen BH, et al. Marjolin's ulcer: modern analysis of an ancient problem. Plast Reconstr Surg 2009; 123:184.
  14. Pekarek B, Buck S, Osher L. A Comprehensive Review on Marjolin's Ulcers: Diagnosis and Treatment. J Am Col Certif Wound Spec 2011; 3:60.
  15. Choa R, Rayatt S, Mahtani K. Marjolin's ulcer. BMJ 2015; 351:h3997.
  16. Chang JB, Kung TA, Cederna PS. Acute Marjolin's ulcers: a nebulous diagnosis. Ann Plast Surg 2014; 72:515.
  17. Tobin C, Sanger JR. Marjolin's Ulcers: A Case Series and Literature Review. Wounds 2014; 26:248.
  18. Al-Zacko SM. Malignancy in chronic burn scar: a 20 year experience in Mosul-Iraq. Burns 2013; 39:1488.
  19. Kadir AR. Burn scar neoplasm. Ann Burns Fire Disasters 2007; 20:185.
  20. Copcu E, Aktas A, Sişman N, Oztan Y. Thirty-one cases of Marjolin's ulcer. Clin Exp Dermatol 2003; 28:138.
  21. Welch PQ, Williams SB, Foss RD, et al. Lymphoepithelioma-like carcinoma of head and neck skin: a systematic analysis of 11 cases and review of literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2011; 111:78.
  22. Work Group, Invited Reviewers, Kim JYS, et al. Guidelines of care for the management of cutaneous squamous cell carcinoma. J Am Acad Dermatol 2018; 78:560.
  23. Cassarino DS, Derienzo DP, Barr RJ. Cutaneous squamous cell carcinoma: a comprehensive clinicopathologic classification--part two. J Cutan Pathol 2006; 33:261.
  24. Cassarino DS, Derienzo DP, Barr RJ. Cutaneous squamous cell carcinoma: a comprehensive clinicopathologic classification. Part one. J Cutan Pathol 2006; 33:191.
  25. Yanofsky VR, Mercer SE, Phelps RG. Histopathological variants of cutaneous squamous cell carcinoma: a review. J Skin Cancer 2011; 2011:210813.
  26. Petter G, Haustein UF. Histologic subtyping and malignancy assessment of cutaneous squamous cell carcinoma. Dermatol Surg 2000; 26:521.
  27. Auerbach A, Mulvaney P, Goldberg D, et al. Single-Cell Squamous Carcinoma: An Underreported High-Risk Variant. Dermatol Surg 2016; 42 Suppl 1:S2.
  28. Marks R, Rennie G, Selwood TS. Malignant transformation of solar keratoses to squamous cell carcinoma. Lancet 1988; 1:795.
  29. Criscione VD, Weinstock MA, Naylor MF, et al. Actinic keratoses: Natural history and risk of malignant transformation in the Veterans Affairs Topical Tretinoin Chemoprevention Trial. Cancer 2009; 115:2523.
  30. Jeffes EW 3rd, Tang EH. Actinic keratosis. Current treatment options. Am J Clin Dermatol 2000; 1:167.
  31. Johnson TM, Saluja A, Fader D, et al. Isolated extragenital bowenoid papulosis of the neck. J Am Acad Dermatol 1999; 41:867.
  32. Shim WH, Park HJ, Kim HS, et al. Bowenoid Papulosis of the Vulva and Subsequent Periungual Bowen's Disease Induced by the Same Mucosal HPVs. Ann Dermatol 2011; 23:493.
  33. Gross G, Hagedorn M, Ikenberg H, et al. Bowenoid papulosis. Presence of human papillomavirus (HPV) structural antigens and of HPV 16-related DNA sequences. Arch Dermatol 1985; 121:858.
  34. Shabbir M, Minhas S, Muneer A. Diagnosis and management of premalignant penile lesions. Ther Adv Urol 2011; 3:151.
  35. Lucker GP, Speel EJ, Creytens DH, et al. Differences in imiquimod treatment outcome in two patients with bowenoid papulosis containing either episomal or integrated human papillomavirus 16. J Invest Dermatol 2007; 127:727.
Topic 16225 Version 21.0

References

آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟