Inspection and palpation

The diagnosis of skin tumors starts with inspection and palpation. The following information should be recorded: the number of lesions (solitary or multiple), the shape of the lesions (e.g., round, oval, polygonal, geographic, linear, annular), its size, its elevation status (e.g., narrow-pedicled, wide-pedicled, dome-like, hemispherical, flat elevated, umbilicated), its surface status (e.g., smooth, rough, papillary, granular, transudatory, xerophily, ulcerative, erosive, atrophic, lustrous, necrotic), its color (e.g., normal, yellow, pale yellow, erythematous, blackish brown, black, blue, depigmented, pigmented, hyperemic, livid), its hardness (e.g., soft, elastic soft, elastic hard, hard, bone-like hard, fluctuating), its alignment (e.g., localized, disseminated, centrifugal, systematized, singular, symmetric, asymmetric, bilateral), its site, whether there are any subjective symptoms (e.g., pain, itch, contracture sensation, numbness, burning sensation, cold sensation), and the time course of the appearance of the lesion (e.g., acute, subacute, chronic, temporary, recurrent). Color plays a particularly important role in the diagnosis of skin lesions (Box 30.1). The possibility of malignant tumors should be suspected at all times. If the shape, size, elevation status, or color of a lesion changes rapidly, a biopsy should be considered.

Dermoscopy

Dermoscopy is a specialized technique that employs a binocular microscope to observe the skin surface. It is useful for diagnosing pigmented lesions and is necessary for differentially diagnosing malignant melanoma and nevus. It is also required for the diagnosis of seborrheic keratosis, basal cell carcinoma (BCC) and vascular lesions. The Consensus Net Meeting on Dermoscopy 2000¹ has recommended the use of a two-step diagnostic algorithm, in which the first step is to differentiate melanocytic from nonmelanocytic pigmented lesions by using specific dermoscopic criteria. The second step is to differentiate between the various nonmelanocytic lesions by using other specific dermoscopic criteria (Fig. 30.3). The dermoscopic criteria that are used to diagnose melanocytic lesions, seborrheic keratosis, BCC, and vascular lesions are shown in Box 30.2.

Fig. 30.3 Two-step diagnosis using dermoscopy. BCC, basal cell carcinoma.

(Modified from Consensus Net meeting on Dermoscopy. Available at http://www.dermoscopy.org/consensus/.)

Ultrasound and Doppler imaging

To observe skin lesions, high-frequency ultrasound around 20–50 MHz is needed.² However, if the lesion shows extension perpendicular to the skin surface that exceeds a depth of 20 mm, the standard ultrasound (3–10 MHz) should be used. In such cases, computed tomography (CT) and magnetic resonance imaging (MRI) can provide additional information. Ultrasound can be used to determine tumor thickness, its relationship with adjacent structures, and the presence of lymph node metastasis. A variety of ultrasound devices are suitable for this purpose, including mechanical or electron scanning, one-dimensional A-mode, two-dimensional B-mode, and three-dimensional C-mode devices.

Doppler imaging using color Doppler imaging (CDI) or power Doppler imaging is useful for the differential diagnosis of benign and malignant skin tumors, assessing inflammatory reactions, and detecting lymph node metastases. This is because 90% of malignant skin tumors exhibit a high blood flow rate of 3–20 cm/s that is not observed in more than 95% of benign skin tumors. The resolution of power Doppler imaging is higher than that of CDI. M-mode and duplex (a combination of B- and M-mode) scanning are useful for observing hemangiomas or vascular malformations.

X-ray, CT, MRI, angiography, scintigraphy, and positron emission tomography (PET)

X-ray analysis is useful for detecting calcifying lesions such as pilomatricoma and malignant tumors that have necrosis-induced calcifications. Moreover, bone deformation associated with malignant or nonmalignant tumor invasion into bones can be observed by using X-rays.

CT detects metastatic lesions in the bone, lymph nodes, and lungs better than MRI. Helical CT or multidetector low CT can generate three-dimensional and high-resolution images. Contrast-enhanced CT and CT angiography are useful for detecting malignant tumors, vascular regions, and adjacent vascular structures.

MRI detects soft tissues better than CT. In general, malignant tumors present with low-iso signal intensity on T2-weighted images (T2WI) and low signal intensity on T1-weighted images (T1WI), while benign tumors exhibit high signal intensity on T2WI and low signal intensity on T1WI. Magnetic resonance angiography is superior to MRI in determining the nidus and exact nature of the collateral structures in hemangiomas and vascular malformations.

Angiography is an invasive imaging method that was frequently used in the past to investigate vascular lesions. While it detects hemangiomas and vascular malformations readily, its use with pediatric patients requires general anesthesia.

Scintigraphy can be used for metastatic lesion screening. ⁶⁷Ga and ²⁰¹TiCl are used in tumor- or inflammation-seeking scintigraphy, while ⁹⁹Tc-MDP and ^99mTc-HMDP are used in bone scintigraphy. Scintigraphy suffers from low resolution, and this makes it difficult to detect lesions that are less than 2 mm in diameter by this method.

PET is also useful for detecting the metastatic lesions of malignant skin tumors.³ 2-deoxy-2-[¹⁸F] fluoro-d-glucose (FDG) PET (FDG-PET) has been used for the diagnosis and staging of cancers and for monitoring treatment, particularly with regard to Hodgkin’s lymphoma, non-Hodgkin lymphoma, and lung cancer. PET can also sometimes detect many other types of solid tumors that occasionally show up as very highly labeled lesions. FDG-PET is particularly useful for searching for tumor metastasis, or for recurrence after the removal of a primary tumor that was known to be highly active. However, since PET can also detect inflammatory lesions, it will be necessary to exclude the possibility that a PET-detected apparent tumor is not an inflammatory, erosive, or ulcered area.

Pathologic diagnosis

A definitive diagnosis requires a pathologic diagnosis. However, biopsies should only be performed for a clear purpose, such as for the differential diagnosis of benign tumors or to analyze the stage and grade of malignant tumors, which would allow the area to be resected to be determined. Moreover, biopsies should only take place after careful inspection, palpation, and imaging analyses. Depending on the purpose of a biopsy and the lesion characteristics, the surgeon can choose from a range of different biopsy techniques, including punch, incisional, excisional, and mapping biopsies. In the case of incisional biopsies, normal skin should be excised together with early-stage lesions and the characteristic areas of lesions (e.g., inflammatory, erosive, or ulcered areas).

In the case of a possible malignant tumor, an excisional biopsy is recommended to prevent malignant cell dissemination into blood. However, surgeon judgment is needed to determine the amount of normal skin that should be removed. In general, the normal skin margin of an excisional biopsy should be as minimal as possible, especially if the tumor is suspected to be benign. However, if the margins of an excisional biopsy of a malignant tumor are wide enough, such biopsies could actually serve the same purpose as radical resections. Such extensive excisional biopsies could also reduce the number of operations that are needed to treat a tumor. Thus, if a low-grade malignant tumor (e.g., BCC) is suspected, an excisional biopsy that includes several millimeters of normal skin margin may be considered. For high-grade malignant tumors, excisional biopsies will often lead to a pathologic diagnosis that indicates the need for additional wide resection, radiation therapy, and/or chemotherapy.

A way to detect lymph node metastasis that is increasingly being used is to perform sentinel node biopsy, which shows whether the cancer has spread to the very first lymph node.⁴ If the sentinel lymph node does not contain cancer, it is highly likely that the cancer has not spread to any other area of the body. However, this technique is only of therapeutic value for patients with positive nodes: for patients who have negative nodes, the possibility that the lymph node has undetectable cancerous cells should be considered. In addition, there is no compelling evidence that the survival of patients who have a full lymph node dissection as a result of a positive sentinel lymph node biopsy is better than that of those patients who do not have a full dissection until later in the disease, when the lymph nodes can be felt by a physician. Thus, such patients may be subjected unnecessarily to full dissection, which is associated with lymphedema.

The TNM clinical classification system and the pTNM pathologic classification system

The TNM clinical classification^5,6 applies only to malignant tumors (Figs 30.4, 30.5). T indicates the size of the tumor and whether it has invaded nearby tissue, N indicates whether regional lymph nodes are involved, and M indicates the presence of distant metastasis. The TNM classification system is based on clinical evidence acquired before definitive treatment. Once intraoperative and surgical pathologic data become available, the pathologic TMN (pTNM) classification system can be used. The pT, pN, and pM categories correspond to the T, N, and M categories.

Fig. 30.4 The T factor of the TNM classification system, as described by the International Union for Cancer (UICC).

(Used with the permission of the Union for International Cancer Control (UICC), Geneva, Switzerland. The original source for this material is TNM Atlas: Illustrated Guide to the TNM/pTNM Classification of Malignant Tumours 5th edition. Edited by Christian F. Wittekind, Frederick L. Greene, Robert V.P. Hutter, Martin Klimpfinger, Leslie H. Sobin. Springer, 2004, ISBN: 9783540442349.)

Fig. 30.5 The N and M factors of the TNM classification system, as described by the International Union for Cancer (UICC).

(Used with the permission of the Union for International Cancer Control (UICC), Geneva, Switzerland. The original source for this material is TNM Atlas: Illustrated Guide to the TNM/pTNM Classification of Malignant Tumours 5th edition. Edited by Christian F. Wittekind, Frederick L. Greene, Robert V.P. Hutter, Martin Klimpfinger, Leslie H. Sobin. Springer, 2004, ISBN: 9783540442349.)

Regional lymph nodes are those that drain the site of the primary tumor (Fig. 30.6). The pN assessment of the regional lymph nodes requires that a sufficient number of lymph nodes are removed for histologic examination (usually six or more). If the examined lymph nodes are negative but fewer than six lymph nodes were resected, the pN classification is designated pN0.

Fig. 30.6 The regional lymph nodes, as described by the International Union for Cancer (UICC).

(Used with the permission of the Union for International Cancer Control (UICC), Geneva, Switzerland. The original source for this material is TNM Atlas: Illustrated Guide to the TNM/pTNM Classification of Malignant Tumours 5th edition. Edited by Christian F. Wittekind, Frederick L. Greene, Robert V.P. Hutter, Martin Klimpfinger, Leslie H. Sobin. Springer, 2004, ISBN: 9783540442349.)

Box 30.3 shows examples of the TNM classification system, namely the systems used for eyelid, vulva, penis, and soft-tissue sarcomas.

Clinical staging

The TNM system^5,6 is used to show the anatomical extent of malignant tumors. For purposes of tabulation and analysis, it is useful to condense these categories into stages (Table 30.1). To be consistent with the TNM system, carcinoma in situ is categorized as stage 0. In general, tumors that are localized to the organ of origin are categorized as stages I and II, while those that exhibit extensive local spread, particularly to the regional lymph nodes, are classified as stage III. The tumors that have distant metastasis are classified as stage IV. For pathological stage groups, if sufficient tissue has been removed for pathological examination to evaluate the highest T and N categories, M1 may be either clinical (cM1) or pathological (pM1). However, if only a distant metastasis has had microscopic confirmation, the classification is pathological (pM1) and the stage is pathological.

Wide excision

With regard to wide resection of malignant tumors of skin, the horizontal and vertical margins vary depending on the type of tumor. Retrospective histopathologic studies have supported reductions in the horizontal margin in recent years. The horizontal margins that are recommended for particular tumor types are listed in (Box 30.4). In the case of malignant soft-tissue tumors, the type of excision can vary with regard to the extent of the margins around the tumor: curative wide, wide, and marginal excisions indicate margins that are at least 5 cm outside the tumor-reactive layer, less than 5 cm outside the tumor-reactive layer, and within the tumor-reactive layer, respectively. Moreover, Mohs micrographic surgery, where tumors undergo histologic analysis during surgery in such a way that almost all of the surgical margins can be examined for tumor extensions, can help to obtain complete margin control during the removal of a skin cancer and soft-tissue sarcoma.⁷

Lymph node dissection

Reconstructive surgery

Reconstruction via skin grafting is a basic surgical technique that is used to reconstruct the tissue defects that occur after tumor extirpation, that is also useful for early detection of local recurrence. The most ideal approach after tumor extirpation is to suture the wound margins directly together. However, this can only be performed if the wound is not too big and the adjacent skin can be extended sufficiently. One concern with this approach is that malignant cells may be left in the deep margins of the wound. Recent developments in reconstructive techniques, including thin flap-based techniques and wound coverage materials, mean that plastic surgeons can now choose from a wide and rapidly evolving variety of primary and aesthetic secondary reconstruction methods. Given this constantly altering medical (and social) environment, it is difficult to develop up-to-date reconstructive algorithms, and indeed, previous algorithms such as the reconstructive ladder, elevator, and triangle quickly lose favor. Consequently, the techniques that are chosen for primary and secondary reconstruction are largely determined on a case-by-case basis. However, one current and useful model is the reconstructive matrix,⁸ which helps plastic surgeons to determine the best reconstructive solutions for their patients in the context of particular medical and socioeconomic environments by considering aspects of surgical complexity, technological sophistication, and patient surgical risk.

Radiation therapy

Malignant tumors vary in their sensitivity to radiation-induced damage, which directly affects the success of radiation therapy. For example, malignant melanomas are less sensitive to radiation and are therefore rarely treated with radiation therapy. Malignant skin tumors that are relatively sensitive to radiation and are therefore commonly treated with radiation therapy include BCC,⁹ SCC,¹⁰ and Merkel cell carcinoma of the skin.¹¹ Acute skin reactions to radiation therapy occur during the first 7–10 days after treatment and are characterized initially by erythema that then progresses to pigmentation, epilation, and desquamation; this is particularly the case when higher doses are used. Subacute and late complications occur several weeks after radiation therapy and can progress for long periods of time. These complications include scarring, permanent pigmentation, depigmentation, atrophy, telangiectasis, subcutaneous fibrosis, and necrosis.

Chemotherapy

Chemotherapy can be either adjuvant or primary, and all chemotherapies can be administered either systemically or topically. Adjuvant chemotherapy is mainly used for malignant melanoma, while primary chemotherapy is indicated for SCC,¹² angiosarcoma,¹³ and EMPD.¹⁴ However, the radical chemotherapy with which malignant skin tumors are generally treated can sometimes be seen as neoadjuvant chemotherapy before surgery for advanced-stage cancer. Single-agent chemotherapies include peplomycin sulfate and CPT-11¹⁵ for SCC, pacitaxel for angiosarcoma, and docetaxel for angiosarcoma and EMPD. Multiagent chemotherapies includes cisplatin + doxorubicin and cisplatin + 5-fluorouracil (5-FU) + bleomycin for SCC; mesna + doxorubicin + ifosfamide + dacarbazine for angiosarcoma; and 5-FU + mitomycin C, 5-FU + carboplatin + leucovorin, and 5-FU + carboplatin + mitomycin C + epirubicin + vincristine for EMPD.

Laser therapy

Dye lasers or neodymium-doped yttrium aluminum garnet (Nd: YAG) lasers can be used for lesions that are characterized by neoplastic changes or malformations in capillary vessels or their overgrowth, such as hemangiomas,¹⁶ vascular malformations,¹⁷ and keloid/hypertrophic scars.¹⁸ Ruby and alexandrite lasers can be used to treat superficial pigmented lesions whose colors range from brown to black, while Q-switched ruby and alexandrite lasers are useful for intradermal pigmented lesions such as the nevus of Ota.¹⁹ CO₂ lasers and erbium yttrium aluminum garnet (Er: YAG) lasers target the water contents of a lesion,²⁰ which makes them suitable for lesions with various colors like seborrheic keratosis, telangiectatic granuloma, xanthoma, and fibroma.

Others (including immunotherapy, cryotherapy, electrocoagulation therapy, and sclerotherapy)

At this stage, the only indication for immunotherapy is malignant melanoma. Cryotherapy and electrocoagulation therapy induce the freezing and melting of the tumor tissues, which results in their necrosis and/or apoptosis; these methods are suitable for superficial benign or malignant tumors like seborrheic keratosis, fibroma, and BCC. Sclerotherapy, where a sclerosant like ethanol, ethanolamine oleate, polidocanol, or OK-432 is injected into affected vessels, can be used to treat vascular malformations. Promising technologies that may become useful in the near future include: hyperthermic infusion therapy, where the tumor is infused with a substance that makes it more susceptible to locally applied heat; molecular target therapy, which involves drugs or other substances that block the growth and spread of the tumor by interfering with specific tumor growth and progression molecules; and gene therapy and gene cell therapy, where genes are manipulated in target healthy cells (to enhance their cancer-fighting properties) or in target cancer cells (to kill them or inhibit their growth).

Benign epithelial-origin tumors

Epidermal nevus (e.g., verrucous epidermal nevus and linear epidermal nevus)

This nevus is composed of skin cells that normally occur at the affected site but show hyperkeratosis and papillomatosis (Fig. 30.7). It can be considered to be a hamartoma, which is a benign focal, tumor-like malformation that is composed of a mixture of the cells that characterize the tissue of its origin; such nodules grow at the same rate as the surrounding tissues. The dermis below the epithelial nevus is usually normal. Epithelial nevi sometimes exhibit a diffuse or extensive distribution that affects a large area of the patient’s body (termed systematized epidermal nevus); careful observation is necessary in these cases. Systematized epidermal nevus often occurs together with abnormalities in other organ systems. This condition is termed epidermal nevus syndrome,²¹ and has been described as a sporadic neurocutaneous linkage of congenital ectodermal defects in the skin, brain, eyes, and/or skeleton. Laser therapy, cryotherapy, electrocoagulation, surgical abrasion, and excision are suitable for treating epithelial nevi. If abrasion therapy is used, it should be remembered that these lesions are usually limited to the epidermis; thus, to prevent heavy scarring, only the epidermis and the superficial layer of the dermis should be removed.

Fig. 30.7 Epidermal nevus of the upper arm.

Seborrheic keratosis (also known as senile wart)

This is a benign skin growth that originates from the basal and squamous cells in the epidermis (Fig. 30.8). It should be differentiated from nevus cell nevus, senile keratosis, BCC, and malignant melanoma. The sign of Leser–Trélat, which is the dramatic, sudden appearance of multiple seborrheic keratoses, can be a paraneoplastic syndrome, namely an ominous sign of an internal malignancy.²² In such cases, not only do new lesions suddenly appear, pre-existing lesions also frequently increase in size and become symptomatic. This sign should not be overlooked and screening for internal malignancy should be recommended to the patient. Laser therapy, cryotherapy, electrocoagulation, surgical abrasion, and excision are all suitable treatments for seborrheic keratosis. However, if the tumor invades the dermis, which can occur, surgical excision is recommended.

Fig. 30.8 Seborrheic keratosis on the temporal region.

Keratoacanthoma

Keratoacanthoma has been a controversial entity for many years, mainly because it closely resembles SCC²³ (Fig. 30.9). It grows rapidly and can sometimes self-heal. Upon histopathology, atypical squamous cells can be detected, which makes it difficult to distinguish from SCC. For this reason, excisional biopsy should be considered despite the fact that this lesion occasionally self-heals. If the lesion is on the nose and face, Mohs micrographic surgery is particularly suitable since it facilitates good margin control along with minimal tissue removal.

Fig. 30.9 Keratoacanthoma on the nose.

Epidermoid cyst (also known as epidermal cyst and atheroma)

Epidermal cyst is a smooth, dome-shaped, freely movable, somewhat fluctuant subcutaneous swelling that is sometimes attached to the skin by a central pore (Fig. 30.10). It is covered with a stratified squamous epithelium that resembles the epidermis or the follicular infundibulum; thus, there is a granular cell layer adjacent to the keratin-containing cyst lumen. Epidermoid cysts can rupture spontaneously or be ruptured by external mechanical forces. Extremely large epidermoid cysts, also known as giant atheromas (Fig. 30.11), should undergo pathology to rule out malignant change,²⁴ although such changes are rare. Epidermoid cysts that exhibit inflammation or recur should be removed by simple excision. In the case of large cysts, the contents can be removed first, after which the cyst walls can be removed with minimal incision (Fig. 30.12). In cases where pus and blood are excreted, the surgeon should consider incising the cyst and draining it first, and then excising it completely 1–2 weeks later.

Fig. 30.10 Epidermoid cyst with a central pore.

Fig. 30.11 Giant atheroma.

Fig. 30.12 An epidermoid cyst (A) and the removal of the cyst with a minimal incision (B, C).

Dermoid cyst

A dermoid cyst is a congenital subcutaneous cyst that develops along the embryonic lines of closure (Fig. 30.13). It is most common on the head and neck area, particularly the supraorbital region, brow, upper eyelid, glabella, and scalp. These cysts can be easily removed surgically, but care should be taken not to injure the temporal branch of the facial nerve. The cyst lumen contains keratin debris and hair shaft fragments. Preoperative X-rays should be taken to distinguish it from pilomatricoma on the head and neck region, especially in pediatric patients. Since it has been reported that dermoid cysts can exhibit malignant changes, complete surgical removal is recommended.²⁶

Fig. 30.13 (A) Dermoid cyst on the supraorbital region; (B) the excised cyst.

Others

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