Spitzoid melanoma in childhood

ARTICLE

Auteur(s) : Husamettin Top¹, A Cemal Aygit¹, Sedat Bas¹, Omer Yalcin²

¹Trakya, University, Medical Faculty, Department of Plastic, Reconstructive and Aesthetic Surgery, Edirne, Turkey
²Trakya, University, Medical Faculty, Department of Pathology, Edirne, Turkey

accepté le 1 Novembre 2005

Case reports

Case 1

On macroscopic examination, a skin colored polypoid mass measuring 11 × 10 × 5 mm was seen on an excisional skin biopsy measuring 24 × 13 × 10 mm in size. The lesion surface was granular. After overnight fixation in formalin it was sampled and an automatic tissue process was performed. Hemotoxylin and eosin (H&E) stained sections were examined. Then commercially available antibodies; S-100 protein (Neomarkers; Cat. No: MS-296-R7), HMB-45 (Neomarkers; Cat. No: MS-688-R7) were applied to sections using the streptavidin-biotinperoxidase technique for immunohistochemical analysis. Histopathologically, there was epidermal ulceration due to tumor invasion (figure 1A). The lesion was asymmetric with irregular borders infiltrating the surrounding tissue. The tumor cells were spindle atypical melanocytes with abundant eosinophilic cytoplasm, showing focal fine or dusty melanin pigmentation, and contained pleomorphic vesicular nuclei with prominent nucleoli (figure 1B). Intraepidermal pagetoid spread was prominent. Although there was maturation in the reticular dermis, cellular atypia and rare mitotic figures (2/mm²) were still detected in the deepest parts of the tumor. The lower border of tumor was sharply demarcated with focal lymphatic infiltrate. The lesion was localized in the papillary and reticular dermis but not in subcutaneous fat (Clark’s level IV) and had a tumor thickness of 6 mm. Vascular and perineural invasion were not found. Immunohistochemically, the malignant spindle cells were immunoreactive for S-100 protein and HMB-45. 100 percent of tumor cells were positive for S-100 protein and 5 percent for HMB-45, especially in the deeper parts of tumor. Proliferative activity was immunohistochemically assessed by Ki-67 and PCNA antibodies (DAKO, Carpinteria, CA). Ki-67 stained 60 percent of tumor cell nuclei and PCNA stained 90 percent of tumour cell nuclei.

The lesion was diagnosed as a Spitzoid melanoma and wide excision and right inguinal lymph dissection were performed. On histopathological examination, no tumoral infiltration was detected in the re-excisional material. Metastatic tumor infiltration was seen in four of fourteen inguinal lymph nodes. Immunohistochemical and histological analyses of the lymph nodes showed immunoreactivity for S-100 protein (figure 2) and HMB-45 and more than 60 percent of melanoma cells expressed Ki-67 (same as primary tumor), indicating that these cells were metastases of melanoma. The child is under follow-up and has been free of disease for 16 months.

Case 2

Macroscopically, the papule was measured 5 × 5 × 3 mm. On histopathologic examination, there was a melanocytic lesion, consisting of spindle-shaped melanocytes with abundant eosinophilic cytoplasm, and containing pleomorphic vesicular nuclei with prominent nucleoli (figure 4). There was melanin pigmentation in the lesion. Pagetoid spread was evident in the epidermis. Atypical mitotic figures were detected in the superior and middle parts of the tumor (figure 5). Cellular atypia was present in the superior part of epidermis. The lesion was localized in the papillary and reticular dermis but not in subcutaneous fat (Clark’s level IV) and had a tumor thickness of 4 mm. Vascular and perineural invasion were not found. At scanning magnification showing the silhouette of the lesion, it appeared asymmetric, and the extreme crowding of fascicles of melanocytes was present. The tumor cells had burst the surface epithelium at one point (figure 6). Immunohistochemically, the malignant spindle cells were immunoreactive for HMB-45 and S-100 protein, especially in the deeper parts of the tumor. 100 percent of tumor cells were positive for S-100 protein and 10 percent for HMB-45. Proliferative activity was immunohistochemically assessed semiquantitively by Ki-67 and PCNA antibodies (DAKO, Carpinteria, CA). Ki-67 stained 62 percent of tumor cell nuclei (figure 7A) and PCNA stained 92 percent of tumor cell nuclei (figure 7B).

The overall features of the lesion were most consistent with Spitzoid melanoma. Because the initial excision was not complete, wide excision of the tumor and right inguinal lymph node dissection was subsequently performed. Neither the tumor infiltration on the sections of re-excisional material nor the metastasis of inguinal lymph nodes was detected. There was no clinical evidence of tumor recurrence or metastasis two years after the operation.

Discussion

This melanoma has been considered a rare tumor in children [1] but because the incidence of conventional melanomas has increased, so too would the less frequent variants of melanoma be expected to increase, including Spitzoid melanoma. Melanoma in children has been classified by Barnhill into three-subgroups: small cell melanoma, adult-like melanoma, and Spitz-like [3]. The first subgroup is very rare in childhood [9]. Histologically the lesion consists of small roundish lymphocytic-like or naevocytic-like cells arranged in solid sheets of cells. The presence of many mitotic figures, significant thickness, and pleomorphism of the nuclei indicate the melanomatous nature of this subgroup. The small cell melanomas were notable for localization to the scalp, and fatal outcome. The adult-like melanomas resembled typical tumors occurring in adults.

The third subgroup was called Spitz-like melanoma by Barnhill [3]. This subgroup was the rarest in the Barnhill’s study. Spitzoid melanoma is the equivalent term. The histological features of Spitzoid melanoma resemble Spitz’s nevus. In these cases, if the patient is young the wrong diagnosis of Spitz’s nevus may be made. This happens because melanoma is rare in children, in contrast to Spitz’s nevus, which is more common [10].

Although about 35 cases of Spitzoid melanoma in childhood have been published in the literature [3-5, 7, 10-14], only a few of them well are documented [3, 7, 13, 14].

The differential diagnosis of Spitzoid melanoma and Spitz’s nevus is still problematic, in that distant metastases and death of the patient may be the only diagnostic criteria for some cases [3, 6]. Spitzoid melanoma is a malignant melanocytic proliferation of spindle cells, epitheloid cells, or a mixture of both. Its histology is characterized by architectural asymmetry and irregular borders (Table 1). The thickness of lesion usually reaches to the dermosubdermal junction. This feature is also present in those lesions which have small lateral diameters. The growth pattern of Spitzoid melanoma is solid without interspersed collagen fibers. This is an important feature. Because in the dermal component of Spitz’s nevus, cells and collagen fibers are closely intermingled and are organized in an orderly pattern [6, 11]. Both of our cases had a solid growth pattern without interspersed collagen fibers.

Atypical mitotic figures are usually present in the deep portion of Spitzoid melanoma or easily found in a wide distribution that includes the full thickness of the lesions [10]. The presence of mitosis does not contribute to distinguish Spitzoid melanoma from Spitz’s nevus. No mitosis can be found in metastatic Spitzoid melanoma [3, 6]. However, the mitoses (in a large number or even atypical and in a wide distribution including the full thickness) can be found in Spitz’s nevus [9]. One can conclude that, the presence of mitosis is not meaningful on its own. In both cases present here, atypical mitotic figures were present.

The nuclear and nucleolar pleomorphism are present in Spitzoid melanoma, but both of them are absent in Spitz’s nevus [15]. Both of our cases had nuclear pleomorphism.

Although the presence of pigmentation is not a criterion used in the differential diagnosis between Spitzoid melanoma and Spitz’s nevus, irregularly distributed pigment or the presence of pigment in the deepest part of lesion is more in favor of Spitzoid melanoma. The melanin pigmentation was irregular in our cases.

Some criteria usually used in the differential diagnosis between Spitzoid melanoma and Spitz’s nevus are not really useful. These include; the symmetry of lesion, the pagetoid spread, the lateral diameter of lesion, and lack of maturation [9]. In Spitzoid melanoma, the lesion can be quite symmetrical, and pagetoid spread may be absent [6]. The lateral diameter of the lesion is not a reliable feature in differential diagnosis. Spitzoid melanoma less than 10 mm in lateral diameter can be fatal; moreover, very large Spitz’s nevus can be entirely benign [9]. Nevus cell maturity at the base of the tumor may be present and this feature seems an unreliable criterion since it is frequently absent in Spitz’s nevus [16]. The ulceration is an important feature in malignant lesions when present. But, this clue is frequently absent in Spitzoid melanoma [9]. Ulceration was present in Case 1.

Immunohistochemistry does not contribute significantly to the final decision [15]. Although both Spitz’s nevus and Spitzoid melanoma are positively reactive for HMB-45 and S-100, the deeper expression of HMB-45 is more in favor of Spitzoid melanoma than Spitz’s nevus. Ki-67 and PCNA are additional immunohistochemical markers that can prove useful in distinguishing Spitz’s nevus from melanoma. Li et al. investigated immunoreactivty for Ki-67 in compound nevi and melanomas to determine its utility in distinguishing benign nevi from melanoma. Their study demonstrated the mean Ki-67 positive staining in all benign nevi to be less than 1 percent, whereas the mean Ki-67 positive staining in all melanomas was more than 32 percent [17]. In other study, McNutt et al. found Ki-67 and PCNA to be useful for distinguishing Spitz’s nevus from melanoma [18]. In case 2, 62 percent Ki-67 staining and 92 percent PCNA staining with high proliferative activity was in favor of melanoma. Although the Ki-67 and PCNA markers may be highly positive in spitzoid melanoma, it may be also positive at the expansion phase of Spitz’s nevus.

The presence of benign melanocytic cells within the fibrous capsule, trabeculae and even parenchyma of lymph nodes is a well-known phenomenon [19, 20]. These cells could be mistaken for metastatic melanoma. Awareness by the pathologist that nevus cells can be found in lymph nodes, analysis of their morphologic features (including comparison with existing melanoma), and immunoreactivity investigation for Ki-67 and PCNA are important to avoid misdiagnosis [19]. In case 1, the cell aggregates within the marginal sinus of the lymph nodes had similar morphologic features and immunoreactivity to the existing melanoma. Moreover, Sentinel lymph node biopsy aids in confirming a diagnosis of melanoma [21]. Because the status of regional lymph nodes is a powerful predictor of overall survival of melanoma, sentinel lymph node biopsy is both a useful adjunct in the management of histologically difficult melanocytic lesions [22], and identifies patients who may benefit from early therapeutic lymph node dissection and/or adjuvant therapy [21]. In one recent study, 8 of 18 patients (44%) with atypical spitzoid melanocytic lesions were reclassified based on positive sentinel lymph node biopsy results [21]. In another study, 5 of 10 (50%) diagnostically controversial spitzoid lesions metastasized to sentinel lymph nodes [23].

In conclusion it seems that Spitz’s nevus and Spitzoid melanoma display overlapping histopathologic and immunohistochemical features, in that distant metastases and death of the patient may be the only diagnostic criteria for some cases. Spitzoid melanoma does not show a better prognosis than other types of melanoma. When the lesion is diagnosed as a Spitzoid melanoma, wide surgical excision and when necessary, lymph node dissection must be performed.
Table 1 The distinguishing features of spitzoid melanoma and Spitz’s nevus

References

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