Practical Plastic Surgery

and ulceration. Surgical margins and the need for sentinel node biopsy are based on tumor thickness.

Pathophysiology

The intermittent exposure hypothesis states that intermittent high energy exposure of melanocytes to sunlight is more damaging than the total cumulative dose. This is because continuous exposure can actually increase the amount of melanin (tanning) which protects the nucleus of the cell. People who have had three or more blistering sunburns before age 20 are at increased risk for disease.

Melanoma arises in epidermal melanocytes. Melanocytes produce melanin in response to sunlight and transport it to keratinocytes via dendrites. The keratinocytes regulate melanocyte growth, thus maintaining homeostasis. When these melanocytes escape from regulation, a dysplastic nevus arises. These lesions are premalignant and grow in a radial growth phase, parallel to the skin surface. A primary melanoma arises when a vertical growth phase begins with the capacity to invade deeper structures.

Clinical Characteristics

There are four subtypes of melanoma, each with a different appearance and clinical behavior.

•Superficial spreading melanoma is the most common subtype (70-75%). This type frequently arises from a pre-existing dysplastic nevus and always grows in a radial growth phase. These are characterized by the ABCD’s described below.

•Nodular melanoma is the second most common type (15%). This subtype lacks a radial growth phase, making it very difficult to diagnose at an early stage as it does not arise from a pre-existing pigmented lesion. The appearance of these melanomas is shiny and smooth with a uniform color.

•Acral lentiginous melanoma is a rare subtype with a poor prognosis. These lesions are notoriously difficult to diagnose as they are commonly masked by thick stratum corneum of the palms and soles of the feet or on difficult to find mucosal surfaces. They are flat, dark brown or black and have irregular borders. Subungal

melanomas belong to this category. These lesions occur equally among all races and arise in the nail bed or matrix. Hyperpigmentation of the nail fold (Hutchinson’s

25sign) or a dark band (~3 mm in width) along the nail are presenting signs.

•Lentigo maligna melanoma is the rarest form (5%) and is the least aggressive type. They arise on chronically sun-exposed parts, commonly the face and neck. They are dark brown or black, larger than the other subtypes (1-3 cm diameter) and have highly irregular borders.

Diagnosis

The mainstay of treatment is early diagnosis and excision. A suspicious lesion is any pigmented lesion that is asymmetrical, has border irregularity, color change, and diameter greater than 6 mm (the ABCD’s of malignancy). The presence of red, white or blue variegation in a brown or black lesion is highly suspicious. Any rapidly changing or ulcerating lesion is highly suspicious for melanoma.

Biopsy

Whenever possible, suspicious lesions should undergo complete excisional biopsy with a 1-2 mm rim of normal skin in an elliptical shape. If the lesion is large (over 1.5 cm), or in a location where skin removal is critical, an incisional biopsy

Table 25.1. Guidelines for surgical margins during excision of malignant melanomas

(punch biopsy) should be taken from the most raised or irregular area. If incisional biopsy is used for diagnosis, the management should not be based on the Breslow depth because there may be thicker areas that were not sampled. The biopsy is carried down to normal subcutaneous fat, but not through the underlying muscle fascia. Biopsy can be done in the clinic with local anesthetic (a mixture of 1% lidocaine with 1:100,000 epinephrine, and an equal volume of 0.5% Bupivicaine). One must consider the relaxed skin tension lines and orientation as future wide local excision may be needed. The specimen is handled carefully and sent to the pathologist according to hospital protocol. The skin is closed with care, in layers if necessary, as frequently no more surgery will be required (if the lesion is benign). Subungual lesions are biopsied by removing the nail and performing an excisional biopsy down to, but not including periosteum.

Surgical Treatment

Once the diagnosis of melanoma is made, definitive surgical treatment should be scheduled as expeditiously as possible. The surgical plan is based on the histopathologic depth of the tumor (Breslow depth). For incisional biopsies, one must ensure that the plan is based on the deepest part of the tumor, which may not have been the part first incised. The lesion is staged based on the depth of invasion and the presence of palpable nodes on exam. Tumors can then be categorized into thin

tumors (<1 mm thick) amenable to wide local excision only down to the muscle 25 fascia, intermediate tumors (1-4 mm thick) that need sentinel lymph node biopsy

and possibly total lymph node dissection, and thick tumors (>4 mm thick) that have likely metastasized at the time of diagnosis. The recommended guidelines for margins are shown in Table 25.1.

Wound closure is typically performed immediately after excision. Reconstruction should follow the reconstructive ladder: primary closure when possible, skin grafts and flaps if primary closure is not possible. Complex defects with limited reconstructive options are generally treated with temporary dressings or skin grafts until permanent pathology sections confirm negative margins.

Sentinel Node Biopsy

Indications

Patients with intermediate lesions 1-4 mm thick historically underwent elective lymph node dissection (ELND) with resulting morbidity. The role of sentinel node biopsy (SNB) is to evaluate the local nodal basin for metastases without the morbid-

ity and expense of total lymph node dissection. Any patient with ulceration or regression, males with Clark level III or greater lesions, and patients with intermediate thickness tumors (1-4 mm) should undergo SNB.

Rationale for Sentinel Node Biopsy

The basis for SNB is that nodal metastases follow an orderly progression and that the histology of the sentinel node reflects the entire nodal basin. Therefore, if the sentinel node is free of disease, no further dissection is needed. If tumor is found, a therapeutic nodal dissection is performed removing the entire nodal basin. Palpable nodes (regardless of tumor depth) that are not suspicious can be evaluated with surveillance and fine needle aspiration (or open biopsy). Palpable nodes that are in the basin draining the primary site, or are otherwise suspicious, should undergo elective lymph node dissection without biopsy.

Description of the Procedure

For patients undergoing SNB, preoperative lymphoscintigraphy aids in localization of the tumor. The technique involves the intradermal injection of a radio-la- beled colloid and dynamic imaging over a 2 hour period. This allows the surgeon to find the approximate area of the sentinel node and is especially important for regions with irregular drainage (such as the head and neck). The patient should then be informed of the risks of SNB, specifically the risk that the procedure may need to be converted to a complete lymphadnectomy if the sentinel node is positive. Intraoperative vital blue dye lymphatic mapping (1-3 ml of lymphazurin blue dye injected into the dermis) can be an adjunct to intraoperative lymphoscintigraphy detection. Histologic examination is performed on all excised lymph node using routine and immunoperoxidase S-100 and HMB-45 stains. Intraoperative frozen section is not routinely performed.

Intraoperative complications include anaphylaxis, retained blue hue and inaccurate oxygen saturation readings. Cooperation between the radiologist (lymphoscintigraphy), surgeon (biopsy), and pathologist (histology) is essential to the success of the procedure and has resulted in only a 4-11% false negative rate.

Additional Diagnostic Studies

25 Patients with thin lesions (<1 mm) should be evaluated with liver function studies (LFTs), lactate dehydrogenase (LDH), and chest X-ray. Patients with thicker lesions should undergo chest/abdomen/pelvis CT and possibly MRI of the brain (although prospective studies have shown no survival benefit for CT and MRI in asymptomatic patients). Patients with stage IV disease undergo PET scanning.

Staging and Adjuvant Therapy

Once the tumor size, node status and presence or absence of distant metastases hve been established, the TNM stage is determined. The American Joint Committee on Cancer has recently revised the stage groupings for melanoma (Table 25.2). Stages I and II denote localized disease, stage III indicates nodal involvement and stage IV disease implies distant metastases. The treatment for localized disease (stages I and II) has been described: wide local excision and lymph node dissection if indicated (sentinel node or complete lymph node dissection). High risk stage II and stage III patients, as well as all patients with stage IV disease, should be offered adjuvant treatment. For patients with metastases, surgery is palliative and systemic therapy is the mainstay of treatment.

Table 25.2. A simplified version of the TNM classification and staging scheme for malignant melanoma according to the American Joint Committee on Cancer (AJCC)

-a: no ulceration or level II/III; -b: ulceration or level IV/V

N = Regional Lymph Node Status

N0 No nodal involvement

N1a One microscopic positive node; N1b: one macroscopic positive node N2a 2-3 microscopic positive nodes; N2b: 2-3 macroscopic positive nodes N3 >4 nodes, matted nodes, or nodal involvement as well as in-transit mets

M = Distant Metastases

M0 No evidence of metastasis

M1a Distant skin, subcutaneous, or nodal metastasis M1b Lung mets

M1c All other visceral mets, or metastasis combined with elevated LDH

* T2b (ulcerated) is Stage II

A number of immunomodulators are currently being studied, but only inter- feron-alpha 2b (IFN alpha) has been shown to decrease the rate of disease recurrence and significantly impact relapse-free survival. High dose IFN alpha, when given within 56 days of surgery, decreases recurrence by 26%. Other agents, specifi-

cally interleukin-2 (IL-2), vaccines, and gene therapy are being investigated for their 25 anti-tumor effects and show promise. Chemotherapy with dacarbazine (DTIC) has shown a response rate of 10-20% in certain studies, but its use is considered to be premature outside of clinical trials.

Isolated limb perfusion (hyperand normothermic) with cytotoxic agents has been used for over 30 years in the treatment of melanoma. A prospective study from 1990 demonstrated increased five-year survival with hyperthermic limb perfusion with melphalan for extremity melanomas. In this study, even patients with intermediate thickness tumors (1.5-3 mm) benefitted from perfusion over conventional surgery alone. The value of limb perfusion is even more evident in patients with local recurrences and in-transit metastases. Severe adverse reactions include tissue breakdown and the need for fasciotomies due to post-perfusion leg compartment swelling.

Long-Term Care and Follow Up

All patients with a history of melanoma should undergo an annual skin exam for the the rest of their life. In addition, follow-up is based on the tumor depth at

diagnosis; for patients with stage I disease (<1 mm thick, negative nodes) recommended follow-up is physical examination every 6 months with studies (LDH, LFTs and CXR) every other visit for five years. After 5 years, examine patients every 12 months and obtain studies every 2 years. For patients with intermediate lesions (1-4 mm thick) and negative nodes, physical exam is performed every 4 months and studies every other visit for the first 3 years. After 3 years, follow-up is the same as for thin (<1 mm) tumors. Patients with thick tumors (>4 mm) and negative nodes should be seen every 3-4 months, with studies every other visit, for the first three years. After 3 years, annual follow up with yearly studies is recommended. Patients with positive nodes (and any thickness tumor) should be seen every 3 months for the first three years and then every 6 months for 2 years (with studies every other visit), and yearly for the rest of their lives.

Pearls and Pitfalls

Certain anatomic locations deserve special mention:

•Eyelid lesions are rare and the importance of tumor thickness is uncertain. Recommended treatment is complete excision with a margin of normal skin. One series was unable to show any survival benefit with regional lymph node dissection.

•Tumors of the ear should be resected full-thickness (wedge resection) to the auditory canal. If a wedge resection is not performed, minimum treatment requires excision of the underlying perichondrium. Elective node dissection is of benefit in selected cases (the ear drains to the preauricular and postauricular, parotid, and jugulodigastric nodes).

•Patients with melanomas of the neck and scalp fare worse than those with tumors on the face or ears. Excision should include the underlying galea. The unpredictable lymphatic drainage dictates a complete neck dissection if indicated.

•Subungual melanomas and those of the distal digit are treated with amputation just proximal to the DIP joint (or IP joint of the thumb) regardless of tumor thickness (Fig. 25.2). Amputation at the metatarsal joints is indicated in the toes. Melanoma of the proximal fingers is treated by excision following the recommended soft tissue margins with flap or graft reconstruction.

Suggested Reading

1.Balch CM et al. Efficacy of 2 cm surgical margins for intermediate thickness melanomas (1-4mm). Ann Surg 1993; 218:262.

2.Breslow A. Thickness, cross-sectional areas and depth of invasion in the prognosis of cutaneous melanoma. Ann Surg 1970; 172:902.

3.Clark Jr WH. A classification of malignant melanoma in man correlated with histiogenesis and biological behavior. In: Montagna W, Hu F, eds. Advances in Biology of the Skin, Vol VIII. Elmsford: Pergamon Press, 1967:621-647.

4.Evans GRD, Manson PN. Review and current perspectives of cutaneous malignant melanoma. J Am Col Surg 1994; 178:523.

5.Ho VC, Sober AJ, Balch CM. Biopsy techniques. In: Balch CM, Houghton AN, Sober AJ, Soong SJ, eds. Cutaneous Melanoma. 3rd ed. St. Louis: Quality Medical Publications, 1998, (Chapter 7).

6.Morton DL, Wen DR, Cochran AJ. Management of early stage melanoma by intra-operative lymphatic mapping and selective lymphadenectomy: An alternative to routine lymphadenectomy or “watch and wait.” Surg Oncol Clin N Am 1992; 1:247.

25

Table 26.1. Categorization of vascular lesions

Vascular Tumors

•Hemangioma of infancy

–Superficial

–Deep

–Mixed

•Congenital hemangioma

–Rapidly involuting congenital hemangioma (RICH)

–Noninvoluting congenital hemangioma (NICH)

•Kaposiform hemangioendothelioma

•Tufted angioma

•Pyogenic granuloma

•Hemangiopericytoma

Vascular Malformations

•Simple malformation

–Capillary (port-wine stain)

–Venous

–Lymphatic

–Arteriovenous malformation (AVM)

•Combined malformation

–Capillary-lymphatic-venous

–Capillary-venous

–Capillary-venous with AV shunting and/or fistulae

–Cutis marmorata telangiectatic congenita

least by the practitioner who makes a dedicated investment in the care of patients with these lesions. Although benign in terms of cellular behavior, these lesions can have devastating sequelae on vital organs and may in fact be life-threatening.

Hemangiomas and Other Vascular Tumors

The common hemangioma of infancy (infantile hemangioma) is a unique lesion whose course of rapid growth and delayed involution has eluded a mechanistic explanation to date. It is unknown whether the origin is embryonic, maternal or pla- 26 cental, or whether it arises from a clonal endothelial or vascular progenitor precursor.

There are several statistics associated with these lesions which are worth mentioning:

•Occur in a 3:1 female: male ratio

•Present in 12% of Caucasian infants, with a lower incidence in other races

•Up to 30% incidence in premature infants

•20% occur as multiple lesions

•60% of these lesions are situated in the head and neck area

•25% are found on the trunk

•15% are present on the extremities

In addition, 5% of cases will be complicated by infection, bleeding or ulceration

at some point during their proliferative phase. They may occasionally be associated with a low-grade consumptive coagulopathy but are not a cause of the Kasabach-Merritt syndrome. Although it is classically stated that 50% involute by age 5, true involution likely is complete before this. Most of the changes that occur

140 Practical Plastic Surgery

Table 26.2. Syndromes associated with vascular lesions

past age 3-4 represent post-involutional changes and scar maturation, rather than true involution. Although in the past these lesions were described as either cavernous, strawberry or capillary, these ambiguous terms are now considered obsolete, and instead hemangiomas are described as either superficial, deep, or mixed, depending on their tissue depth.

The histologic appearance of the growing hemangioma of infancy will show rapidly proliferating endothelial cells, displaying numerous mitoses. This is distinct from vascular malformations, where the endothelial cells are flat and nonproliferating, forming ectatic vessels. Recently, the glucose transporter GLUT-1 has been shown to be a universal marker for hemangiomas of infancy; this immunohistochemical marker will in the future undoubtedly be utilized more frequently.

Another type of hemangioma is the congenital hemangioma. This lesion is invariably clinically apparent at birth and is divided into two subtypes: the rapidly involuting congenital hemangioma (RICH), which will involute by 10 months postpartum, and the noninvoluting congenital hemangioma (NICH) which persists. Other vascular tumors are occasionally seen by the plastic surgeon. A pyogenic granuloma is an angioma which appears at any age and is characterized by bleeding dis-

26proportionate to its size. Kaposiform hemangioendothelioma is responsible for most cases of Kasabach-Merritt syndrome. Notably, none of these hemangiomatous lesions express the histochemical marker GLUT-1.

Diagnosis

The diagnosis of hemangioma of infancy is made by clinical observation and a careful history. Pertinent points include the location of the lesion as well as other comorbid conditions. Occasionally, an imaging study may be used. Although computed tomography (CT) can be utilized, the most useful imaging study remains magnetic resonance imaging (MRI). A benefit of MRI is the delineation of flow characteristics, tissue involvement and penetration with excellent resolution of involved adjacent structures, without the risk of ionizing radiation. These advantages are most useful for imaging of hemangiomas of the head and neck, as well as visceral hemangiomas. The reader is referred to radiologic reviews for an overview of imaging characteristics specific to these lesions. A vessel density of greater than 5/cm2

and a peak arterial shift greater than 2 kHz give a positive predictive value greater than 97% for a proliferative hemangioma. Other lesions that can be included in the differential diagnosis in an infant include sarcomas (rhabdomyosarcoma, fibrosarcoma, neurofibroma) as well as other vascular malformations.

Occasionally, the need for definitive distinction between a proliferating and an involuting hemangioma exists. Some markers of proliferating hemangiomas include VEGF, bFGF and PCNA. Involuting hemangiomas will have fewer levels of PCNA, more TIMP, endostatin, angiostatin and IL-12 along with an increased number of mast cells.

Treatment

There are several levels of urgency for treatment. At one end of the spectrum of surgical urgency lie those hemangiomas that mandate immediate intervention. These include airway-obstructing oro-tracheal-laryngeal hemangiomas, hemangiomas of the periorbit that can produce visual disturbances, including blindness, lesions that exhibit severe hemorrhage and ulceration, and the occasional liver hemangioma that can result in cardiac failure. Most hemangiomas, however, can be managed by observation, as they will eventually involute spontaneously. About half of hemangiomas of infancy will involute in a manner that leaves minimal or no disfigurement. However, the rest will leave a conspicuous scar and a residuum of fibro-fatty tissue that can be aesthetically disfiguring. These will require reconstructive interventions following involution to obtain a pleasing cosmetic result.

Recently, a fourth tier of lesions has been defined as those that are best prophylactically removed by surgery before resolution of the involution phase, most commonly to avoid the social-psychological trauma in affected children, or in order to prevent further distortion of structures and avert a more complex reconstruction. This includes hemangiomas of the nasal tip, where the delicate nasal cartilages are often involved. Although the management of hemangiomas requiring urgent treatment is clear, the controversy lies in management of the nonurgent lesions. Unfortunately, there have been few prospective studies to guide the management of these patients. A difficulty in managing these patients is the entrenched belief of many referring physicians, unfortunately communicated to the parents, that hemangiomas should not be treated until involution is complete. One recent useful tool that may assist in therapeutic decision making stratifies patients into groups that are

high or low risk. Those hemangiomas with a significant dermal component will 26 likely leave greater residual cutaneous deformations with post-involution changes

and scarring. The location of hemangiomas is also a significant risk factor, with those of the face having high likelihood of surgical intervention due not only to the involvement of eyes, ears and nose, but also because those in a beard-like pattern have a likelihood of airway involvement. Future research should further define subgroups that will best respond to specific interventions, whether medical or surgical.

Those hemangiomas that need to be urgently treated are first treated with high doses of systemic steroids and intra-lesional steroid injections. Second-level therapeutics for nonresponders or poorly tolerant patients include interferon-α or occasionally vincristine. Interferon-αis less commonly used than in the past because of its side effects, the most serious of which is spastic diplegia. Orbital and airway lesions can be treated with laser cauterization and surgical debulking as a second choice.

The treatment of less catastrophic lesions begins with supportive or hygienic measures; this is particularly important for ulcerated lesions which may benefit from