eMedicine Specialties > Dermatology > Malignant Neoplasms
Squamous Cell Carcinoma: Differential Diagnoses & Workup
Updated: Mar 18, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Differential Diagnoses
| Actinic Keratosis | Warts, Genital |
| Atypical Fibroxanthoma | Warts, Nongenital |
| Basal Cell Carcinoma | |
| Keratoacanthoma | |
| Pyoderma Gangrenosum |
Workup
Imaging Studies
Imaging is not routinely indicated for diagnosing cutaneous squamous cell carcinoma (SCC). However, radiologic imaging should be obtained in patients with regional lymphadenopathy and/or neurologic symptoms suggestive of perineural involvement. CT scanning, MRI, ultrasonography, or positron-emission tomography (PET) scanning may be used depending on the specific question being addressed, although the selection of one modality over another is often based on clinician and institutional preference. Currently, no formal guidelines regarding the use of radiologic imaging in cutaneous squamous cell carcinoma have been developed.
Disease staging workup in high-risk squamous cell carcinoma
- Physical examination of lymph nodes: In all squamous cell carcinoma patients, the draining nodal basins should be palpated. If nodes are palpable, a biopsy should be performed using FNA or excision. If lymph nodes are clinically negative but the tumor meets high-risk criteria, little data are available to guide what should be done next. Subsequently, management currently varies with regard to further staging.32,33 See "High-risk squamous cell carcinoma" in Prognosis.
- Radiologic staging
- Only a few studies have reported on the utility of radiologic imaging in cutaneous squamous cell carcinoma. One study of MRI and CT scanning in patients with histologically proven perineurally invasive squamous cell carcinoma showed only 20% of asymptomatic patients to have positive findings discovered from imaging studies. Thus, CT scanning and MRI appear to be poor in detecting asymptomatic nerve involvement. However, positive imaging findings did correlate with worse outcomes. The 5-year survival rate was 50% if CT scanning or MRI findings were positive, versus 86% if they were negative.34
- Two studies reported on radiologic imaging for detecting subclinical nodal metastasis.35 The first, a study of vulvar squamous cell carcinoma, indicated that ultrasonography followed by FNA for suspicious nodes was superior to CT scanning in staging subclinical nodal metastasis, with ultrasound-guided FNA demonstrating 80% sensitivity and 100% specificity. The second is a small study of PET scanning in 9 patients with high-risk squamous cell carcinoma. PET scanning detected subclinical nodal metastasis in 3 of 9 patients.36 Thus, PET scanning and ultrasound-guided FNA may be capable of detecting many cases of subclinical nodal metastasis.
- Sentinel lymph node biopsy (SLNB): A review of the 85 reported cases of SLNB in high-risk, nonanogenital cutaneous squamous cell carcinoma showed that 21% of cases were positive based on SLNB findings. This indicates that SLNB likely can detect many cases of subclinical nodal metastasis. How the sensitivity of SLNB compares with that of PET scanning or ultrasound-guided FNA and whether detection of subclinical nodal metastasis impacts survival are unknown. However, because the 5-year survival rate of patients with nodal metastasis is as high as 73% with aggressive treatment,14 early detection of nodal metastasis may prove more beneficial in squamous cell carcinoma than in melanoma.
- Summary: Little data are available to guide decisions about staging of nodal basins in high-risk squamous cell carcinoma. However, PET scanning, ultrasound-guided FNA, and SLNB all appear to offer a good chance of detecting subclinical nodal metastasis with low morbidity. Thus, nodal staging may be considered in patients with high-risk squamous cell carcinoma. Development of prognostic models that better predict the risk of nodal metastasis will allow for more rational decisions about which patients should undergo nodal staging.
Procedures
Skin biopsy
Although the diagnosis of squamous cell carcinoma is often strongly suspected based on clinical findings, a skin biopsy is required for definitive diagnosis. A shave biopsy, punch biopsy, incisional biopsy, or excisional biopsy may be used. The biopsy is routinely performed in the physician's office after the patient is given a local anesthetic.
All skin biopsy samples obtained to diagnose squamous cell carcinoma must reach at least the depth of the mid dermis to allow for a determination of the presence or absence of invasive disease. For high-risk lesions, a larger sample may be helpful to assess for perineural invasion and other histologic features that confer a greater risk of metastasis. Given recent information about depth being an important prognostic factor (analogous to melanoma), a large punch biopsy through the center of the lesion or excisional biopsy may be best, particularly in high-risk lesions or immunosuppressed patients.37
Pathologic analyses may be completed by a dermatologist or a general pathologist, but they are preferably completed by a dermatopathologist with extensive experience in squamous cell carcinoma.
Patients with regional lymphadenopathy identified by clinical examination or imaging studies should undergo a lymph node biopsy or FNA for histologic evaluation. SLNB has been used to identify micrometastasis in patients with high-risk squamous cell carcinoma and clinically negative nodes, with 21% positivity.38 While SLNB appears to be able to detect most subclinical metastasis, whether early detection of lymph node metastasis leads to enhanced survival in squamous cell carcinoma is unknown, because controlled studies have not been conducted. Complete lymphadenectomy of the draining nodal basin has also been suggested for high-risk tumors with an estimated metastatic risk of 20% or greater. However, because prognostic models do not exist, knowing precisely which patients fall into this category is difficult. Thus, when it is feasible, SLNB offers a low-morbidity approach to accurately staging high-risk squamous cell carcinoma.
Histologic Findings
The biopsy report for squamous cell carcinoma often carries prognostic implications. Recognizing the implications of the various histologic subtypes of squamous cell carcinoma is important, and the astute clinician uses his or her understanding of histopathology to advantage in planning the appropriate therapeutic intervention.
Squamous cell carcinoma in situ is characterized by an intraepidermal proliferation of atypical keratinocytes. Hyperkeratosis, acanthosis, and confluent parakeratosis are seen within the epidermis, and the keratinocytes lie in complete disorder, resulting in the classic "windblown" appearance. Cellular atypia, including pleomorphism, hyperchromatic nuclei, and mitoses, is prominent. Atypical keratinocytes may be found in the basal layer and often extend deeply down hair follicles, but they do not invade the dermis.
The main feature that distinguishes invasive squamous cell carcinoma from squamous cell carcinoma in situ is invasion of malignant keratinocytes through the basement membrane and into the dermis. Keratinization results in the production of squamous eddies or keratin pearls. The neoplastic cells may demonstrate varying degrees of squamous differentiation and atypia. If the tumor is poorly differentiated, this fact is typically reported by the dermatopathologist because the degree of differentiation has prognostic implications (ie, poorly differentiated tumors have been associated with a higher risk of metastasis).
Several variants of squamous cell carcinoma can be distinguished by clinical and/or histologic criteria. In some cases, these tumors may be difficult to distinguish from other malignancies based on routine histology findings alone. Therefore, immunohistochemical staining with antibodies to cytokeratins and epithelial membrane antigen is often used to confirm the epithelial (ie, keratinocyte) origin of the tumor. The salient features of keratoacanthoma, spindle cell squamous cell carcinoma, acantholytic (adenoid) squamous cell carcinoma, and verrucous carcinoma are highlighted in the following table.
Histologic and Clinical Features of Squamous Cell Carcinoma Variants
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Table
| Tumor | Histologic Characteristics | Clinical Characteristics |
| Keratoacanthoma | Keratin-filled crater Well-differentiated (mild atypia) Neutrophil microabscesses Eosinophils in dermal infiltrate | Solitary nodule Central craterlike depression Rapid growth May spontaneously involute |
| Spindle cell SCC | Atypical spindle cells Foci of squamous differentiation May resemble other spindle cell tumors (eg, atypical fibroxanthoma) | Resembles typical SCC May be clinically aggressive |
| Acantholytic (adenoid) SCC | Glandlike differentiation Acantholysis May resemble adenocarcinoma or sweat gland carcinoma | Arises on sun-damaged skin Elderly patients Resembles typical SCC Clinically aggressive |
| Verrucous carcinoma | Well-differentiated (minimal atypia) Resembles verruca Bulbous downward proliferation "Bulldozing" invasion | Oral, genital, or plantar foot Indolent growth Locally destructive Rarely metastasizes |
| Sarcomatoid SCC | Poorly differentiated cells resembling sarcoma | Clinical appearance may be that of typical SCC or may have more nodular appearance with less surface change Elevated risk of local recurrence and metastasis |
| Tumor | Histologic Characteristics | Clinical Characteristics |
| Keratoacanthoma | Keratin-filled crater Well-differentiated (mild atypia) Neutrophil microabscesses Eosinophils in dermal infiltrate | Solitary nodule Central craterlike depression Rapid growth May spontaneously involute |
| Spindle cell SCC | Atypical spindle cells Foci of squamous differentiation May resemble other spindle cell tumors (eg, atypical fibroxanthoma) | Resembles typical SCC May be clinically aggressive |
| Acantholytic (adenoid) SCC | Glandlike differentiation Acantholysis May resemble adenocarcinoma or sweat gland carcinoma | Arises on sun-damaged skin Elderly patients Resembles typical SCC Clinically aggressive |
| Verrucous carcinoma | Well-differentiated (minimal atypia) Resembles verruca Bulbous downward proliferation "Bulldozing" invasion | Oral, genital, or plantar foot Indolent growth Locally destructive Rarely metastasizes |
| Sarcomatoid SCC | Poorly differentiated cells resembling sarcoma | Clinical appearance may be that of typical SCC or may have more nodular appearance with less surface change Elevated risk of local recurrence and metastasis |
Staging
Squamous cell carcinoma is staged according to American Joint Committee on Cancer guidelines, which use the TNM classification system. Most cutaneous squamous cell carcinomas are not metastatic at the time of presentation; therefore, the tumor stage in such cases is based solely on the characteristics of the primary lesion. Staging of metastatic disease takes into account the presence or absence of regional lymph node and distant metastasis. The staging system is currently being updated to incorporate more information about tumor factors that impact prognosis. The new staging system will be available in 2010. Meanwhile, current classification of the primary tumor is described below.
- TX - Primary tumor cannot be assessed
- T0 - No evidence of primary tumor
- Tis - Carcinoma in situ
- T1 - Tumor less than 2 cm in greatest diameter
- T2 - Tumor 2-5 cm in greatest diameter
- T3 - Tumor greater than 5 cm in greatest diameter
- T4 - Tumor with deep invasion into cartilage, muscle, or bone
More on Squamous Cell Carcinoma |
| Overview: Squamous Cell Carcinoma |
 Differential Diagnoses & Workup: Squamous Cell Carcinoma |
| Treatment & Medication: Squamous Cell Carcinoma |
| Follow-up: Squamous Cell Carcinoma |
| Multimedia: Squamous Cell Carcinoma |
| References |
| « Previous Page | Next Page » |
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Further Reading
Keywords
squamous cell carcinoma, skin cancer, SCC, actinic keratoses, SCC in situ, Bowen disease, Bowen's disease, keratotic invasive SCC, leukoplakia, erythroplasia of Queyrat, nodular SCC, periungual SCC, Marjolin ulcer, actinically derived SCC, adenoid squamous cell carcinoma, ASCC, adenosquamous cell carcinoma, verrucous carcinoma, keratoacanthoma, oral florid papillomatosis, epithelioma cuniculatum, giant condyloma of Buschke and Löwenstein, malignant tumor of keratinocytes, sun-induced cancerous lesions
