Benign and malignant nonmelanocytic tumors of the skin and soft tissue

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 29.1 ). 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. Marghoob et al . have recommended the use of a revised 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 ( Algorithm. 29.1 ). The dermoscopic criteria that are used to diagnose melanocytic lesions, seborrheic keratosis, BCC, and vascular lesions are shown in Box 29.2 .

Algorithm 29.1

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

Two-step diagnosis using dermoscopy. BCC, Basal cell carcinoma.

Ultrasound and Doppler imaging

To observe skin lesions, high-frequency ultrasound around 20–50 MHz is needed. 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 T ₂ -weighted images (T2WI) and low-signal intensity on T ₁ -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. ⁶⁷ Ga and ²⁰¹ TiCl are used in tumor- or inflammation-seeking scintigraphy, while ⁹⁹ Tc-MDP and ^99m Tc-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. 2-deoxy-2-[ ¹⁸ F] 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.

The TNM clinical classification system and the pTNM pathologic classification system

The TNM clinical classification applies only to malignant tumors ( Figs. 29.3 & 29.4 ). 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.

Regional lymph nodes are those that drain the site of the primary tumor ( Fig. 29.5 ). 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.

Box 29.3 shows examples of the TNM classification system, namely the systems used for carcinoma of skin and eyelid.

Clinical staging

The TNM system 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 29.1 ). 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 29.4 . 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, 1–2 cm outside the tumor-reactive layer, and within the tumor-reactive layer, respectively. It is now considered that wide excision is appropriate margin for soft tissue sarcoma. 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.

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, 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.

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, angiosarcoma, and EMPD. However, the radical chemotherapy that malignant skin tumors are generally treated with can sometimes be seen as neoadjuvant chemotherapy before surgery for advanced stage cancer. Single-agent chemotherapies include peplomycin sulfate and CPT-11 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, vascular malformations, and keloid/hypertrophic scars. 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. CO ₂ lasers and erbium yttrium aluminum garnet (Er: YAG) lasers target the water contents of a lesion, which makes them suitable for lesions with various colors like seborrheic keratosis, telangiectatic granuloma, xanthoma, and fibroma.