DEFINITION

Squamous cell carcinoma (SCC) and melanoma are malignant transformations of normal epidermal cells in either cutaneous or noncutaneous regions of the body.

Both SCC and melanoma demonstrate the ability to extend locally, involve regional lymph node basins, and metastasize to distant sites. SCC is also prone to locally extending along nerves sheaths.

Early diagnosis, accurate histopathologic evaluation, detailed staging, appropriate surgical, and medical management as well as appropriate follow-up are critical to the management of SCC and melanoma of the hand.

 

 

ANATOMY

 

Intact skin is composed of epidermis and dermis. These act as physiologic barriers to infection and malignant spread. SCC and melanoma develop from different epidermal layers.

 

 

SCCs develop from epidermal keratinocytes.

 

Melanomas derive from dendritic (neural crest) cells within the epidermis. Melanomas are typically pigmented; however, amelanotic melanomas (nonpigmented melanoma) represent 5% of all melanomas.

 

PATHOGENESIS

 

The typical SCC lesion is a firm, scaly papule or nodule containing a central ulcer surrounded by an indurated raised border (FIG 1).

 

Risk factors include the following:

 

 

 

Repetitive damage from sun, heat, and wind Severe burns and chronic ulcers

 

Advanced age

 

 

Immune compromise (organ transplantation and AIDS) Major risks for melanoma include the following:

 

Personal or family history of melanoma

 

 

Propensity for sunburn with excessive sun exposure Immune compromise

 

 

 

FIG 1 • The typical SCC lesion is a firm, scaly papule or nodule containing a central ulcer surrounded by an indurated raised border.

 

 

Previous skin cancers

 

Exposure to coal tar, radiation, or radium

 

NATURAL HISTORY

 

SCC is the second most common type, behind basal cell carcinoma (BCC).

 

The American Cancer Society estimates more than 1 million new diagnoses of cutaneous BCC and SCC are made annually. However, BCC and SCC account for less than 0.1% of patient deaths caused by all cancers.

 

The American Cancer Society anticipates approximately 60,000 new melanoma cases each year, with an estimated 8110 deaths.

 

The probability of developing melanoma from birth to death is 2.04 (1 in 49) in males and 1.38 (1 in 73) in females.

 

Nail matrix SCC or melanoma account for less than 1% of their respective cutaneous malignancies. The histologic features of the epidermis and dermis, including physiologic barriers, are absent in the nail complex. In the nail complex, the matrix is adherent to the underlying phalanx.

 

PATIENT HISTORY AND PHYSICAL FINDINGS

 

Patients typically present for evaluation after noting the recent appearance of, or changes to, an existing lesion.

 

Change in size, shape, coloration, the presence of satellite lesions, or ulceration of a lesion should prompt a thorough evaluation and possible biopsy with histopathologic analysis (FIG 2).

 

Melanoma and SCC can metastasize. Regional lymph node beds (axillary) should be routinely examined in all suspected cases of upper extremity skin cancer.

 

The presence of a Hutchinson sign (extension of brown-black pigment from the nail bed, matrix, or nail plate onto the adjacent cuticle and proximal or lateral nail folds) is consistent with a subungual melanoma (FIG 3). Subungual melanoma should also be suspected when the nail bed contains a new or enlarging pigmented streak wider than 3 mm (FIG 4).

 

 

 

FIG 2 • Change in size, shape, border irregularity, coloration, the presence of satellite lesions, or ulceration should prompt a thorough evaluation and biopsy.

 

 

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FIG 3 • A Hutchinson sign, extension of brown-black pigment from the nail bed, matrix, and nail plate onto the adjacent cuticle and proximal or lateral nail folds, is consistent with a subungual melanoma.

 

 

Although there have been reports of amelanotic melanoma of the nail bed, the actual incidence is unknown.

 

IMAGING AND OTHER DIAGNOSTIC STUDIES

 

Radiographic evaluation of the hand with plain view x-rays are helpful and may reveal bone involvement (FIG 5).

 

For both SCC and melanoma, a chest radiograph, complete blood count, and liver panel may be obtained. If these labs reveal abnormality, prompt evaluation by an internist or oncologist is appropriate.

 

More detailed imaging studies (computed tomography [CT], magnetic resonance imaging [MRI], and positron emission tomography [PET]) may be performed to evaluate specific organ systems (central nervous system, pulmonary, gastrointestinal, and others) if indicated.

 

The diagnosis of skin cancer requires adequate histopathologic evaluation with a full-thickness (surface to full depth) specimen.

 

 

Suspicious pigmented lesions must never be shaved, cauterized, or vaporized for fear of losing the

opportunity to accurately identify the lesion depth.

 

SCC is graded 1 to 4 based on the proportion of differentiating cells present and the frequency of atypical tumor cells.

 

Melanoma subtypes include the following:

 

 

 

Superficial spreading: most common, 70% Nodular: 15% to 30%, more aggressive

 

 

Lentigo maligna: most common subtype among Asians and African Americans Acral lentiginous (palmar-plantar and subungual)

 

Miscellaneous unusual types are as follows:

 

 

Mucosal lentiginous (oral and genital)

 

 

 

 

FIG 4 • Subungual melanoma should also be suspected when the nail bed contains a new or enlarging pigmented streak wider than 3 mm.

 

 

 

FIG 5 • Radiographic evaluation of the hand with plain view x-rays are helpful and may reveal bone involvement.

 

 

 

Desmoplastic Verrucous

 

Malignant melanoma staging is determined by histopathologic evaluation of the vertical thickness of the lesion in millimeters (Breslow classification) or the anatomic level of local invasion (Clark classification).

 

Along with the presence of ulceration, Breslow thickness more accurately predicts melanoma behavior in lesions thicker than 1.5 mm. Estimates of prognosis should be modified by sex and anatomic site in coordination with clinical and histologic evaluation.

 

The Clark classification ranges from level I (in situ lesions involving only the epidermis) to level V (invasion through the reticular dermis into the subcutaneous tissue).

 

 

Micrometastases are diagnosed by elective sentinel lymphadenectomy.

 

Macrometastases are defined as clinically detectable lymph node metastases confirmed by therapeutic lymphadenectomy or when any lymph node metastasis exhibits gross extracapsular extension.

 

Clinical staging includes microstaging of the primary melanoma and clinical or radiologic evaluation of potential metastases. With the exception of clinical stage 0 or stage IA patients (who have a low risk of lymphatic involvement and do not require pathologic evaluation of the lymph nodes), pathologic staging includes microstaging of the primary melanoma and pathologic information about the regional lymph nodes after sentinel node biopsy and, if indicated, complete lymphadenectomy.

 

DIFFERENTIAL DIAGNOSIS OF SQUAMOUS CELL CARCINOMA AND MELANOMA

 

 

 

 

Seborrheic keratosis Pigmented actinic keratosis Hemangioma Dermatofibroma

 

Blue nevus

 

Basal cell carcinoma

 

 

Cutaneous T-cell lymphomas (eg, mycosis fungoides) Kaposi sarcoma

 

 

Extramammary Paget disease Apocrine carcinoma of the skin

 

Metastatic malignancies from various primary sites

 

The differential diagnosis of subungual lesions includes chronic paronychia and onychomycosis, subungual hematoma, pyogenic granuloma, and glomus tumor.

 

 

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NONOPERATIVE MANAGEMENT

Squamous Cell Carcinoma

 

Topical fluorouracil (5-FU) may be helpful in the management of selected preinvasive, in situ SCC (Bowen disease).

 

The deepest lesion extent may not be reached by topical 5-FU. In these instances, recurrence or progression can occur despite the belief that adequate treatment has been accomplished. Therefore, close follow-up with thorough evaluation is required.

 

Electrodesiccation and curettage and cryosurgery may be useful for small (<2 cm), well-defined in situ tumors in patients with medical conditions limiting excisional surgery.

 

Depth of treatment may not extend to the depth of tumor and therefore may be inadequate.

 

Cryosurgery and electrodessication and curettage should not be used for SCC with suspected extension through the dermis.

 

Carbon dioxide (CO2) laser treatment may be useful in a subset of medically compromised patients with small SCC in situ.

 

Because the CO2 laser coagulates, this technique is also valuable for patients with a bleeding diathesis.

 

Radiation therapy is a logical treatment option and is particularly useful when treating poor operative candidates, locally challenging lesions, or tumors extending over large areas.

 

Radiation therapy can also be used for recurrent lesions after a primary surgical removal.

 

Radiation therapy is contraindicated for use in patients with prior radiation to the affected site, xeroderma pigmentosum, epidermodysplasia verruciformis, or basal cell nevus syndrome.

 

SURGICAL MANAGEMENT

 

The fundamental oncologic principle of tumor clearance first, then reconstruction must be followed without compromise. As always, tumor clearance must be prioritized over any eventual coverage/reconstruction.

 

Wide local excision +/− lymph node sampling is recommended for melanomas.

 

Melanoma in situ requires a 5 mm negative margin. Melanomas of less than 1 mm thickness require a 1 cm clear margin. Melanomas of 1 to 4 mm in thickness require a 2 cm clear margin. Finally, melanomas of greater than 4 mm thickness require a 3 cm clear margin.

 

Clinical appearance of lymph node involvement or evidence of lymphatic bed extension as shown by sentinel lymph node biopsy should prompt lymphadenectomy.

 

Cutaneous Squamous Cell Carcinoma

 

The two primary methods of SCC treatment are surgical excision with frozen or permanent histopathologic sections and Mohs micrographic surgery (FIG 6).

 

When surgically excising SCC of the hand, the surgeon should maintain at least a 3 mm margin of disease-free tissue.

 

Mohs resection of hand SCC results in the highest cure rate (98%) with maximal preservation of normal tissue.

 

Nail Matrix Squamous Cell Carcinoma

 

For SCC of the nail matrix without bone involvement, tumor resection with 3 mm clear margins and tumor-free deep margins containing subcutaneous fat is appropriate. Mohs resection has also proven useful (FIG 7).

 

 

 

 

FIG 6 • Excision of digital SCC may be accomplished with either excisional biopsy or Mohs micrographic surgery.

 

 

For SCC of the nail matrix involving bone, the appropriate technique is amputation at the distal joint.

 

Melanoma

 

Malignant melanoma can spontaneously regress, but the incidence of spontaneous, complete regressions is less than 1%.

 

Without nail matrix involvement, invasion of osseous cortices or perineural invasion, wide local excision should be directed by Breslow depth.

 

Melanoma of the hand with less than 1.5 mm thickness has a low incidence of nodal metastases and is treated effectively with wide local excision of the primary tumor with a 1- to 2-cm margins.

 

Thicker melanomas are associated with more than 50% rate of regional or systemic spread. In the absence of metastatic disease, these individuals should undergo local excision with a 2-cm margins and sentinel lymph

node biopsy followed by lymphadenectomy if the sentinel node is positive (FIG 8A,B).

 

Melanomas of the nail complex are especially concerning due to the absence of the usual skin barrier as well as proximity of the underlying phalanx and tendons. Due to these circumstances, Breslow depth and Clark levels are irrelevant.

 

Total digital (ray) amputation of the fingers results in significant functional deficits without significant survival benefit.

 

The respective digit is amputated at the joint level proximal to the lesion. In the case of nail matrix melanomas, amputation of the digit just proximal to the distal interphalangeal joint (DIPJ) is appropriate.

 

 

 

FIG 7 • For SCC of the nail matrix without bone involvement, tumor resection with 3-mm clear margins and tumor-free deep margins containing subcutaneous fat is appropriate.

 

 

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FIG 8 • A. Invasive melanoma treated initially with cutaneous laser ablation. B. Intraoperative invasive melanoma lesion with margins marked out and after injection of isosulfan blue. Note visible adenopathy in anterior superior axilla.

 

 

For more proximal digital melanoma with bone involvement or perineural invasion, either complete digital (ray) amputation is indicated.

 

Specific recommendations are individualized for each patient. Other significant factors, such as the primary tumor anatomic location, specific tumor features, healing ability, and medical risk factors, must be considered. The surgical goal is to minimize local and regional recurrence and metastasis while maintaining acceptable risks to minimize morbidity and mortality.

 

Coverage and Reconstruction

 

After wide local excision, most wounds can be closed primarily without tension using minimal perimeter undermining and closure.

 

If an extended time period is required to establish final histopathology, local wound care using clean dressings or negative pressure wound system can temporarily be used.

 

Coverage options include allowing secondary closure, primary closure, skin graft, local flap, regional flap, and free flap coverage. Use of alloplasts, such as Integra, may also be helpful.

 

Exposed vessels, nerves, tendons, and bone should prompt flap coverage or use of alloplast materials.

 

Skin grafting can be either split or full thickness depending on the wound bed vascularity, anatomic area, and aesthetics. Typically, split-thickness skin grafts are useful on the dorsal surface of the hand. Full-thickness skin grafts are helpful on the volar surface.

 

Digital V-Y flaps, cross-finger flaps, hypothenar flaps, flag flaps, dorsal metacarpal artery flaps, and radial forearm flaps are common flap options as well.

Preoperative Planning

 

To direct management of local tumor, regional lymph nodes, and metastatic disease, the patient must be staged. The histopathology of the primary tumor is determined by an accurate histopathologic diagnosis.

 

Mohs micrographic surgery requires the assistance of a trained surgeon or physician, such as a dermatologist. Before resection, plans must be made for coverage.

Positioning

Positioning should allow access to the primary tumor and the regional lymph node basin if necessary.

A sterile tourniquet is used. When access to the axillary lymph nodes is required, the tourniquet is removed.

 

Approach

For wide local excision, the primary lesion is marked and the indicated margin is measured around the lesion using calipers and/or a ruler.

Wide local excision includes the intact tumor or biopsy site en bloc with a defined perimeter of normal skin and underlying subcutaneous tissue. The underlying muscular fascia is not included.

For primary closure, an ellipse is marked out incorporating the required margins for wide local excision. The excised length-to-lesion diameter is at least 3:1.

For amputation, the appropriate joint level is marked, along with planned fish-mouth dorsal and volar flaps.

For selective lymph node sampling, a grid is marked over the axillary area. The point of highest radioactivity is marked on the grid.

 

TECHNIQUE

• Mohs Micrographic Surgery

Mohs micrographic surgery is performed by a Mohs-trained surgeon (often a dermatologist) who both excises the lesion as well as performs immediate histopathologic staining and analysis.

Excise a thin layer of tissue with 2- to 3-mm margins.

Map the tissue with color-coded three-dimensional orientation.

Both the deep and peripheral margins are examined in one horizontal plane by frozen section analysis with theoretically 100% margin control.

With immediate performance of histologic interpretation, the precise anatomic location of any residual tumor is identified and reexcised until tumor-free three-dimensional margins are obtained.

Multiple excisions with immediate staining and evaluation may be performed multiple times in order to obtain clear tissue margins.

 

 

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PEARLS AND PITFALLS
			Send tissue biopsy for histopathologic evaluation and culture

 

(bacterial, fungal, and tuberculosis).

Chronic or nonhealing skin or matrix lesion

 

Patient referred for treatment with histopathologic report

• Obtain and review original histopathologic slides before treatment.

 

Nonpigmented chronic or nonhealing skin or matrix lesion

• Remember amelanotic melanoma. Send tissue biopsy for histopathologic evaluation and culture (bacterial, fungal, and tuberculosis).

 

POSTOPERATIVE CARE

 

 

 

Initial postoperative care focuses on pain control and surgical site wound care. Occupational therapy is by protocol, depending primarily on the coverage performed. Patients must be monitored.

 

Both SCC and melanoma have metastatic potential. Patients should be reexamined every 3 months for the first several years, then every 6 months for 3 years, and then yearly indefinitely. Evaluation should focus on the potential for local recurrence, lymph node involvement, metastasis, and the appearance of additional skin cancers.

 

For melanoma, the follow-up schedule for patients who have surgically resected disease is based on the primary lesion's thickness and nodal involvement. Patients with thin primary melanoma and negative nodes are followed with clinical examination every 6 months for the first 2 to 3 years, then yearly for 2 to 3 years. Patients with intermediate or thick melanomas and negative regional nodes are followed every 3 to 6 months for the first 2 to 3 years and every 6 to 12 months for the next 2 to 3 years. Patients with resected regional disease require follow-up every 3 to 4 months for the first 2 years, then every 6 months up to year 5, and yearly beyond that.

 

All patients diagnosed with SCC or melanoma should maintain routine lifelong dermatologic screening. Patients with prior SCC or melanoma remain at higher than average risk for a second skin cancer.

 

OUTCOMES

SCC is the second most common type of skin malignancy behind BCC. Although the BCC and SCC are the most common of all malignancies, they account for less than 0.1% of cancer deaths.

The overall cure rate for SCC is directly related to the stage of the disease and the type of treatment used.

Melanoma 5-year survival rates are related to stage and range from 18% for stage IV to 99% for stage IA.

 

 

COMPLICATIONS

The most common complications of sentinel lymph node biopsy are hematoma and seroma. The rate of lymphedema after sentinel lymph node biopsy is 0.7% to 1.7%, compared with 4.6% (axillary) and 31.5%

 

(inguinal) with complete lymphadenectomy.

Positive margins on final pathology for SCC or melanoma must be addressed by reexcision.

 

 

SUGGESTED READINGS

1. Abide JM, Nahai F, Bennett RG. The meaning of surgical margins. Plast Reconstr Surg 1984;73:492-497.

    

    

2. Balch CM, Urist MM, Karakousis CP, et al. Efficacy of 2-cm surgical margins for intermediate-thickness melanomas (1 to 4 mm): results of a multi-institutional randomized surgical trial. Ann Surg 1993;218: 262-269.

    

    

3. Cottel WI. Perineural invasion by squamous-cell carcinoma. J Dermatol Surg Oncol 1982;8:589-600.

    

    

4. Essner R, Conforti A, Kelley MC, et al. Efficacy of lymphatic mapping, sentinel lymphadenectomy, and selective complete lymph node dissection as a therapeutic procedure for early-stage melanoma. Ann Surg Oncol 1999;6:442-449.

    

    

5. Gershenwald JE, Thompson W, Mansfield PF, et al. Multi-institutional melanoma lymphatic mapping experience: the prognostic value of sentinel lymph node status in 612 stage I or II melanoma patients. J Clin Oncol 1999;17:976-983.

    

    

6. Hochwald SN, Coit DG. Role of elective lymph node dissection in melanoma. Semin Surg Oncol 1998;14:276-282.

    

    

7. Lee ML, Tomsu K, Von Eschen KB. Duration of survival for disseminated malignant melanoma: results of a meta-analysis. Melanoma Res 2000;10:81-92.

    

    

8. Leo F, Cagini L, Rocmans P, et al. Lung metastases from melanoma: when is surgical treatment warranted? Br J Cancer 2000;83:569-572.

    

    

9. Morton DL, Cochran AJ, Thompson JF, et al. Sentinel node biopsy for early-stage melanoma: accuracy and morbidity in MSLT-I, an international multicenter trial. Ann Surg 2005;242:302-313.

    

    

10. Mraz-Gernhard S, Sagebiel RW, Kashani-Sabet M, et al. Prediction of sentinel lymph node micrometastasis by histological features in primary cutaneous malignant melanoma. Arch Dermatol 1998;134:983-987.

     

     

11. Ollila DW, Hsueh EC, Stern SL, et al. Metastasectomy for recurrent stage IV melanoma. J Surg Oncol 1999;71:209-213.

     

     

12. Preston DS, Stern RS. Nonmelanoma cancers of the skin. N Engl J Med 1992;327:1649-1662.

     

     

13. Thomas JM, Newton-Bishop J, A'Hern R, et al. Excision margins in high-risk malignant melanoma. N Engl J Med 2004;350:757-766.

     

     

14. Thomas RM, Amonette RA. Mohs micrographic surgery. Am Fam Physician 1988;37:135-142.

     

     

15. Veronesi U, Cascinelli N. Narrow excision (1-cm margin): a safe procedure for thin cutaneous melanoma. Arch Surg 1991;126:438-441.

     

     

16. Veronesi U, Cascinelli N, Adamus J, et al. Thin stage I primary cutaneous malignant melanoma: comparison of excision with margins of 1 or 3 cm. N Engl J Med 1988;318:1159-1162.

     

     

17. Wagner JD, Gordon MS, Chuang TY, et al. Current therapy of cutaneous melanoma. Plast Reconstr Surg 2000;105:1774-1801.