III.6 Combined Nevus

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III.6.1 Definition

There is no consistent and reproducible definition of combined nevus available in the litera- ture. Some authors only refer to an association of a blue nevus and another melanocytic nevus as combined nevus; however, in our under- standing, the most comprehensible and logical approach is to define a combined nevus as the association of two distinctive benign melanocytic proliferations in one biopsy specimen. Any combination of two kinds of melanocytic nevi is possible, but since blue nevi, Clark’s nevi, Mie- scher nevi, Unna nevi, and Spitz nevi are the most common melanocytic skin lesions, they are most likely to collide.

A combined blue nevus is then the conflu- ence of a blue nevus with another nevus, in most cases a common acquired melanocytic nevus or congenital melanocytic nevus. On occasion, a special combination can be the association of a blue nevus with a Spitz nevus [2, 9], sometimes also referred to as “blitz”. (The German word

“Blitz” means lightning in English)

Combined Nevus

Horacio Cabo

III.6

Contents

III.6.1 Definition . . . .97

III.6.2 Clinical Features . . . .97

III.6.3 Dermoscopic Criteria . . . .98

III.6.4 Differential Diagnosis . . . .98

III.6.5 Histopathology . . . .98

III.6.6 Management . . . .98

References . . . .99

Combined nevus is a subcategory of the so- called collision tumors or compound tumors. A collision tumor is a side-by-side occurrence of two distinctive neoplastic skin lesions, just ca- sually colliding within the same biopsy specimen [4, 6, 12]. This can be, for example, the con- fluence of a seborrheic keratosis and a basal cell carcinoma, which is a quite common combination, or the rare combinations of basal cell carcinoma and melanoma in one lesion, or the combination of an angioma and a Clark nevus. Some authors argue that there are collision tumors which might have a pathogenic relationship [3].

Most frequently colliding lesions are represent- ed by a combination of the followings: seborrheic keratosis; basal cell carcinoma; melanoma;

melanocytic nevus; hemangioma; squamous cell carcinoma; and dermatofibroma.

III.6.2 Clinical Features

The clinical features of combined nevi are vari- able depending on the two individual nevus types belonging to the same lesion. As a result of the combined features of two nevus cell populations, combined nevi may often be asymmetric and difficult to differentiate from melanoma [5]. For example, it is important to remember what a blue nevus is like clinically to understand the combined blue nevus. The blue nevus can be common or cellular. The common blue nevus is a small nodule (<0.5 cm), slate blue or bluish black in color. It is generally solitary and occurs in any part of the body, although it is most frequently found on the dorsum of the hands and feet, as well as on the scalp and mucosa. Al- though it most frequently appears in infancy, there are instances of late onsets in adults. The

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III.6

cellular blue nevus is a nodule larger than 0.5 cm (2–3 cm), blue or black in color, preferably lo- cated in the gluteus or sacrococcygeal region.

Very rarely a melanoma can arise within a pre- existing cellular blue nevus [2, 9].

Combined blue nevi are usually small lesions typified by a small blue to black spot (corre- sponding to the blue nevus component) in the context of a larger area of brown color (corre- sponding to the common nevus) surrounding the blue nevus [7]; the latter is known as the targetoid combined blue nevus type [1].

III.6.3 Dermoscopic Criteria

Dermoscopic criteria also depend on the individual nevus types belonging to the same lesion.

These features are described in the correspond- ing chapters of this book. Combined blue nevi are generally round, symmetric lesions with two colorations: a deep blue color in the central part, and a more superficial light brown or dark brown color at the periphery. In the blue nevus part a homogeneous blue pattern is observed, whereas brown coloration, regular pigment net- work, brown globules, and brown structureless areas typify the common nevus component.

When the combination does not include a blue nevus component, dermoscopic features are less specific and more difficult to interpret [1, 7].

III.6.4 Differential Diagnosis

The clinical and dermoscopic features of combined nevi are due to their protean nature and are not at all well described. Differential diagnoses include a number of benign melanocytic proliferations, among them blue nevi, dysplastic nevi, and, Spitz nevi. Most relevant, however, is that combined nevi frequently simulate melanoma clinically by being asymmetric and re-

vealing markedly irregular pigmentation. Fea- tures that allow distinction from melanoma are the sharp circumscription and the overall ap- pearance of the lesion, which shows a well-cir- cumscribed hyperpigmented spot usually sur- rounded by a less-pigmented area. Other rarer differential diagnoses of combined nevi are basal cell carcinomas and cutaneous metastases.

III.6.5 Histopathology

Histopathological features depend on the nevi that are combined within the lesion. The most frequent scenario is the association of a common melanocytic nevus and a blue nevus, either common or cellular type. Less frequent are the associations of a blue nevus with a Spitz nevus or a Spitz nevus with a Clark nevus (Spark). Ba- sically the histopathological findings of a combined nevus reflect the morphological features of its components [2, 5, 10, 11]. So, histopatho- logically there are several types of combined nevi, characterized by the combination of any morphological expression of congenital and/or acquired nevi.

Combined nevi can be distinguished from melanoma by the absence of features of melanoma in situ in the intraepidermal portion of the neoplasm, the maturation of melanocytes with progressive descent into the dermis, and the absence of nuclear atypia (with the excep- tion of cells of Spitz’s nevi). Combined nevi show overlapping features with many other variants of benign nevi, including proliferating nodules in congenital nevi and cellular blue nevi, among others.

III.6.6 Management

As distinction from melanoma often cannot be clearly made, complete surgical excision is rec- ommended.

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C

Core Messages

■ A combined nevus is the combination of two distinctive benign melanocytic proliferations, whereas a combined blue nevus is the combination of a blue nevus with another nevus type.

■ Clinical features, dermoscopic features, and histopathology are protean and depend on the two individual nevus types belonging to one lesion.

■ They frequently simulate melanoma by being asymmetric and heavily pigmented, and therefore should be excised when the diagnosis of combined nevus is not clear-cut.

References

1. Argenziano G. Dermoscopy of melanocytic neoplasms. Targetoid combined blue nevi. Arch Der- matol 2004;140:1576

2. Cabrera H, Garcia S. Aspectos particulares de los nevos melanociticos. In: Cabrera H (ed) Nevos. Edi- torial Actualizaciones Médicas, 1998, Buenos Aires.

Argentina

3. Cascajo C, Riechel M, Sanchez J. Malignant neoplasms associates with seborrheic Keratosis: an análisis of 54 cases. Am J Dermophatol 1996;18:278–

4. Cosme Alvarez Cuesta C, Vazquez Lopez F, Perez 282 Oliva N. Dermatoscopy in the diagnosis of cutaneous collision. Clin Exp Dermatol 2004;29:199–200 5. Giorgi V de, Massi D, Salvini C, Trez E, Mannone F,

Carli P. Dermoscopic feature of combined melanocytic nevi. J Cutan Pathol 2004;31:600–604 6. Giorgi V de, Massi D, Sestini B, Alfaioli B, Carelli

G, Carli P. Cutaneous collision tumour (melanocytic naevus, basal cell carcinoma, seborrheic kere- tosis): a clinical, dermoscopic and pathological case report. Br J Dermatol. 2005;152:787–790

7. Dermoscopy of melanocytic neoplasms. Combined blue nevi. Arch Dermatol 2004;140:902

8. Ferrara G, Zalaudek I, Cabo H, Soyer HP, Argenzia- no G. Collision of basal cell carcinoma with sebor- rhoeic keratosis: a dermoscopic aid to histopathology? Clin Exp Dermatol 2005;30:586–587

9. Fitzpatrick TB, Jonson RA, Polano MK, Suurmond D, Wolf K. Common melanocytic nevocellular nevi.

In: Fitzpatrick TB (ed) Color atlas and synopsis of clinical dermatology, McGraw-Hill, New York, 10. Scolyer RA, Zhuang L, Palmer AA, Thompson JF, 1992 McCarthy SW. Combined naevus: a benign lesion frequently misdiagnosed both clinically and patho- logically as melanoma. Pathology 2004;36:419–427 11. Strungs I. Common and uncommon variants of me-

lanocytic naevi. Pathology 2004;36:396–403 12. Zaballos P, Llambrich A, Puig S, Malvehy J. Der-

moscopy is useful for the recognition of benign- malignant compound tumours. Br J Dermatol 2005;

153:653–656

13. Zabel R, Vinson R, McCollough M. Malignant melanoma arising in a seborrheic keratosis. J Am Acad Dermatol 2000;42:831–833

Fig. III.6.1. a Congenital nevus with two cell popula- tions, clinical view. b Congenital nevus with two cell populations, dermoscopy view. Note the blue color in the central part of the lesion

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Fig. III.6.2. a Combined blue nevus, clinical view.

b Combined blue nevus, dermoscopy view. Blue color in central part and light brown color at the periphery

Fig. III.6.3. a Combined blue nevus, clinical view.

b Combined blue nevus, dermoscopy view. Blue-gray pigmentation and light brown color correspond to the two different cell populations

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Fig. III.6.4. a Combined blue nevus, histopathology.

The upper part of the lesion is composed by pigmented dendritic cells, whereas the lower part shows small nevus cells (hematoxylin–eosin, ¥50). b Combined blue nevus, histopathology. Pigmented dendritic melanocytes intermingled with melanophages typical for a blue nevus (hematoxylin–eosin, ¥312.5). c Combined blue nevus, histopathology. Small nevus cells in the lower half of the lesion characteristic of a classical dermal nevus (hematoxylin–eosin, ¥312.5)