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means of the classical histological technique and by means of the Haematoxylin eosin staining. The analysis of the structural aspect of the investigated ...

Annals of RSCB

Vol. XVI, Issue 2/2011


Summary The goal of the morphological analysis, which was carried on, was to observe the modifications that occur at the level of the structural compounds of the skin, under the conditions of noticing certain types of benign melanocytic tumours in children. The structural investigation of these structures is necessary because of the increased incidence of the benign nevi in children but also of their potential malign degeneration. Even if considered benign structures, it was noticed that under certain conditions, they may malignly degenerate. There were investigated two categories of nevi, identified in four children, aged differently. The first category refers to the Spitz juvenile melanoma and the second one refers to the dermal nevocelullar nevi. The Spitz nevus was investigated in two patients aged 1,2 and respectively 2,6 years, being located at the level of the face. We practiced the excision biopsy of the lesions, followed by the histopathological examination, for the confirmation of the diagnosis. The Spitz nevi considerably vary at the level of the dimensions, being subcentimetric and coloured in nuances of pink, red and brown. The third investigated case implies the morphological analysis of a dermal nevocellular nevus placed in the right lumbar region of a 16 years old patient and the fourth case presents the same type of nevus placed at left lumbar level. As a consequence of establishing the diagnosis, the structure was surgically extirpated, being followed by a histopathological examination, which was necessary in order to confirm the diagnosis. The dermal nevocellular nevus presents millimetric sizes but it may be shaped in larger sizes, when it is accompanied by pilosity. The histopathological characteristics of the investigated nevi were emphasized by means of the classical histological technique and by means of the Haematoxylin eosin staining. The analysis of the structural aspect of the investigated congenital nevi was possible, by means of a photonic microscope mark Nikon, equipped with enhancing objectives of x20 and x40. Key words: Spitz nevus, dermal nevocellular nevus, children, extirpation, microscopic examination

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not be taken for lesions. The confrontation with the normal aspect of the skin is achieved by means of the biopsy, after the surgical extirpation of a tegumentary pathological structure (Kopf et al., 1966; Jaeger et al., 2006). For the purpose of establishing a correct histopathological diagnosis, drawing of a sample, by means of this type of examination, must be sufficiently profound in order to allow the diagnosis of the dermal-hypodermic lesions

Introduction The aspects concerning the pathology of the skin present certain characteristics that must be taken into account, for the purpose of establishing a correct diagnosis. In this context, the macroscopic examination must be completed after the correct surgical excise, by the histopathological examination, which enables the confirmation of the diagnosis. From this point of view, the normal regional variations of the skin must 142

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(Bastian, 2003; Fujiwara et al., 2008). In order to identify the benign or malign origin of the melanocytic tumours, there may occur difficulties in establishing the cert diagnosis and the differential one. Consequently, the identification of the benign or malign origin of the cutaneous structures is based on preestablished criteria. These aim at preserving the topographic reports with the annexes of the skin, with the localization of the structure at the level of a certain cutaneous territory and with the particularities that result from the histopathological examination (Bastian et al., 2002). According to the classification, there are recognised lesions of the melanogenic system that are divided in benign tumours or nevi, precancerous conditions, malign tumours and non-tumour pigmented lesions (Bittencourt et al., 2000; Clarke et al., 2007). The incidence of the Spitz juvenile melanoma occurrence was high in the first two decades of the life, mainly in the case of the females, white race (Oanta, 2004). This type of melanoma is also characterised by the high frequency of the giant multiple nuclei cells (Clarke et al., 2005; Gosain et al., 2001). The structural characteristic is represented by the aspect of the nevus created by an intense junction activity (Glasgow et al., 2005; Kantrow et al., 2001; Ribé et al., 2009.). In the context of the presence of an extremely high junction activity, there can be noticed monstrous cells, typical from the structural point of view and the presence of the cellular mitosis that may request a differential melanoma with the malign melanoma (Okun, 1979). Furthermore, we may mention that the histopathological aspects previously described must not be considered alarming signs in the case of localising them at the central level of the nevus lesion, not even if

observed at persons aged less than 20 years (Oanta, 1998). From the clinical point of view, the Spitz nevus occurs under the shape of a sole tumour or as an asymptomatic nodule, with dome aspect. It has a round or oval shape, and its surface is smooth, rarely presenting mammilla or papilloma shapes, of pink, red, brown colour. The consistency is firm, elastic or tough, fibrous. Generally, the sizes are less than one centimetre. The localizations are frequently on the face, on the head and on the neck (Oanta, 2004). The recognition of the structural elements of the Spitz nevus enables its distinguishing from the malign melanoma (Ribé et al., 2003). In this context, a differentiating criterion from the malign melanoma is constituted by the presence of the specific sanguine eosinophilic elements, noticeable at the level of the dermalepidermal junction. These are observed in 60% of the cases of Spitz juvenile melanoma and only in 2-3% of the cases of malign melanoma (Oanta, 1998). The dissemination potential of the Spitz juvenile melanoma enabled the observance of the insulated or grouped, epithelioid or fusiform nevus cells, in the lumen of the lymphatic perilesional vessels. This type of lymphatic extension is difficult to be interpreted, because of the observance also in the case of other benign nevus structures. Supporting the benignity of the Spitz nevus, we may state that, in what concerns the description of the ganglion metastasis description with the emphasis of the nevus cells, within the sinuses or parenchyma, which is not followed by local relapses or by distanced metastasis after the excise of the affected ganglions (Oanta, 1998). Considering all of these, we may conclude that the Spitz nevus represents a benign lesion, without degenerating in a malign 143

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melanoma with a reduced potential of dissemination, respectively up to the level of the regional lymphatic ganglions (PaniagoPereira et al., 1978; Watt et al., 2004). The nevocellular nevi are defined as circumscribed cutaneous dysphasia, that are generally pigmented and that are constituted of nevus cells, located at the level of the dermal-epidermal junction. From the histopathological point of view, the nevocellular nevi are formed of Unna nevus cells, which are grouped in nests and in cases. These formations are present at the level of the dermal-epidermal junction, having a typical disposition. According to the localization of the nevocytes nest, the nevocellular nevi are structurally classified in junction, intradermal and compounded nevi. There are also nevocellular nevi that are distinguished from the common nevi, both in terms of the clinical aspect and also of the histopathological one. According to the clinical aspect, these are atypical nevi and according to the histopathological aspect, they are dysphasic nevi (Pearson et al., 2005; Zembowicz et al., 2007). The later are characterised by their sizes, which are larger than the ones of the common nevi, slowly evolutionary, up to 1-1,5 cm, generally with round shape or slightly epithelioid or asymmetric, usually, with irregular contour and coloration, from pink to dark brown or black (Weedon et al., 1977; Sigg, 1988). Histopathologically, characterised by architectural disorder, the dysphasic nevi present ubiquity localization, occurring in comparison with the common nevi, especially at the level of the areas that are not exposed to the sun. The dysphasic nevus is currently considered a gained pigmented lesion, constituting a risk marker for the melanoma, respectively a potential precursor of the degeneration in malign melanoma.

Material and methods The investigation of the analysed pigmented nevi was possible by means of the collaboration between the Cellular Biology Laboratory, within the Faculty of Medicine in Brasov with the Pathological Anatomy Service of the Clinical Children Hospital in Braşov. In order to compare the morphological aspects of the benign melanoma in children, there were investigated four cases. These refer to the Spitz juvenile melanoma and to the dermal nevocellular nevi. The morphological observations were possible as a consequence of the surgical extirpation of these structures and of the histopathological examination. There were registered modifications concerning the aspect of the nests of nevus cells and the possible signs of the associated inflammatory reaction, emphasised at the association of an adjacent inflamed hairy follicle. These were compared to the normal structural aspect noticed at the level of the epidermis. In order to morphologically study the congenital nevi in children, the piece was surgically extirpated and there was requested a histopathological examination, for the confirmation and the support of the diagnosis. The taken out pieces were kept 10%, in formalin. Then, we undertook the stages of the classical histological technique. After the taking and fixing stages, we achieved the inclusion in paraffin, the section to rotary microtome and then the Haematoxylin eosin staining, the assembling with Canadian balsam, the labelling and the storage within the histotech. The histopathological examination, by means of the Haematoxylin eosin staining, enabled the observation of the characteristics of the characteristics of the two categories of 144

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investigated benign melanoma, establishing in the end and supporting the diagnosis of the surgically extirpated pieces. For the study, there was used a photonic microscope mark Nikon. The structural compounds were noticed by means of the enhancing objectives of x20 and of x40.

Results and Discussion

Figure 2. Spitz Nevus –detail. Haematoxylin eosin staining x40

The emphasis of the microscopic aspect of the Spitz juvenile melanoma is achieved on a microscopic image, in semi-detail. There were noticed certain characteristics specific to a compound nevus that presents fascicules of round or fusiform elements, with typical pigment and epithelioid aspect (figure 1).

Furthermore, we may notice by means of the photonic microscope the coverage of the dermal nevocellular nevus, by the intact atrophic epidermis, which under certain conditions may be associated with folliculitis. Within the context, the image observed by means of the enhancing photonic microscope, emphasises nests of nevus cells at the level of the derma (figure 3).

Figure 1. Spitz-semi-detail Nevus Haematoxylin eosin staining. x20

The aspect of the described Spitz nevus may be analysed on a permanent microscopic substance, by means of the enhancing objective of x40. The epithelioid fascicles are emphasised in detail, together with round or fusiform elements, that are specifically pigmented (figure 2).

Fig. 3 Dermal nevocellular – detail Haematoxylin eosin staining x40 On an image in semi-detail, at the photonic microscope, we may notice signs of acute inflammation and of specific glaucomatous reaction. These occur because of the sebaceous gland annexed to the hairy follicle adjacent to the dermal nevocellular nevus (figure 4).


Annals of RSCB

Vol. XVI, Issue 2/2011

structures without the pre-existence of the precancerous type lesions. To the malign degeneration of a nevus, concur the environment factors, the inadequate exposure to the ultraviolet radiations, the local pathology that at the level of the skin may be associated with infections, involuntary traumatisms in the affected region, and also the incomplete surgical excision, practiced at the level of these tegumentary structures.

Fig. 4 Dermal nevocellular nevus– semidetail. Haematoxylin eosin staining x20



Bastian B C., Xiong J., Frieden I.J., Williams M.L., Chou P., Busam K., Pinkel D., LeBoit P.E., Genetic changes in neoplasms arising in congenital melanocytic nevi: differences between nodular proliferations and melanomas. Am. J. Pathol., Oct;161(4):11639,2002. Bastian B.C., Understanding the progression of melanocytic neoplasia using genomic analysis: from fields to cancer. Oncogene. May 19; 22(20):3081-6, 2003. Bittencourt F.V., Marghoob A.A., Kopf A.W., Koenig K.L., Bart R.S., Large congenital melanocytic nevi and the risk for development of malignant melanoma and neurocutaneous melanocytosis., Pediatrics. Oct; 106(4):736-4, 2000. Clarke L.E., Fountaine T.J., Hennessy J., Bruggeman R.D., Clarke J.T., Mauger D.T., Helm K.F., Spitz nevi and atypical Spitz nevi/tumors: a histologic and immunohistochemical analysis. Mod Pathol. Feb;18(2):197-204, 2005. Clarke L.E., Fountaine T.J., Hennessy J., Bruggeman R.D., Clarke J.T., Mauger D.T., Helm K.F., Expression of activated Akt in benign nevi, Spitz nevi and melanomas. J. Cutan. Pathol. Aug; 34(8):593-6,2007. Fujiwara M., Nakamura Y., Fukamizu H. Treatment of giant congenital nevus of the back by convergent serial excision, J. Dermatol. Sep; 35(9):608-10,2008.

Even if the congenital pigmented nevi are benign in most of the cases, under the influence of certain risk factors, certain categories of these structures may become malign. Generally, the malignisation of a benign pigmented nevus is preceded by a series of characteristic signs and symptoms, called agitation signs. Due to the malignisation potential and of the rapid metastasis, it is recommended to macroscopically analyse the modification of the tegument. From this point of view, the aspect of the congenital or obtained pigmented nevus is analysed together with the apparition of certain signs that might reveal the malign degeneration. This fact obliges the patient to require a specialty examination. Even if the previously presented cases are benign, in children, there may be cases of nevi that might become malign. This fact was proven due to the increased incidence of the skin cancer, even since childhood. The studies revealed that the topography and the incidence of malign melanoma do not coincide to the ones of the benign melanoma. This fact pleads for indicating a number of potential cases of malignisation that develop from the level of the skin 146

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Ribé A., McNutt N.S.,S100A6 protein expression is different in Spitz nevi and melanomas., Mod. Pathol. May;16(5):50511,2003. Ribé A., McNutt N.S., Cdc7 expression in melanomas, Spitz tumors and melanocytic nevi. J. Cutan. Pathol. Apr;36(4):433-8,2009. Sigg Ch, Schnyder W. Welche malignen Melanome sind genetisch determiner? Hautarz 1988; 39:409-412. Zembowicz A., Knoepp S.M., Bei T., Stergiopoulos S., Eng C., Mihm M.C., Stratakis C.A., Loss of expression of protein kinase a regulatory subunit 1alpha in pigmented epithelioid melanocytoma but not in melanoma or other melanocytic lesions. Am. J. Surg. Pathol. Nov;31(11):176475,2007. Watt A.J., Kotsis S.V., Chung K.C., Risk of melanoma arising in large congenital melanocytic nevi: a systematic review, Plast. Reconstr. Surg. Jun; 113(7):1968-74, 2004. Weedon D., Little G.H., Spindle and epitheloid cell nevi in children and adults. A review of 211 cases of the Spitz naevus.Cancer 40:21725, 1977.

Glasgow M.A., Lain E.L., Kincannon J.M., Agminated Spitz nevi: report of a child with a unique dermatomal distribution., Pediatr. Dermatol. Nov-Dec;22(6):546-9,2005. Gosain A.K., Santoro T.D., Larson D.L., Gingrass R.P., Giant congenital nevi: a 20-year experience and an algorithm for their management. Plast. Reconstr. Surg., Sep 1;108(3):622-36, 2001. Jaeger M.R., Zuker R.M., Congenital giant nevocellular nevus of the back with deep extension to the fat and fascia. Can. J. Plast. Surg. Spring; 14(1):45-8,2006. Kantrow S.M., Boyd A.S., Ellis D.L., Nanney L.B., Richmond A., Shyr Y., Robbins J.B., Multiple agminated Spitz nevi arising on a café au lait macule: review of the literature with contribution of another case. Pediatr Dermatol. Nov-Dec; 18(6):494-7, 2001. Kopf A.W., Andrade R., Benign juvenile melanoma. In: Kopf AW, Andrade R., eds Yearbook of dermatology. Chicago; Year Book, 1966. Oanta A., Diaconu J.D., Leasu T., Nedelcu L., Aspecte histologice particulare de nevi nevocelulari care pun probleme de diagnostic cu melanomul malign (Particular histological aspects of nevocellular nevi that determine diagnosis problems, with the malign melanoma) Dermatology-Venereology Buc. 43(1): 73-78, 1998. Oanta A., Nevii nevocelulari si potentialul lor de transformare în melanom malign (Nevocellular nevi and their transformation potential in malign melanoma) “Transilvania” University in Brasov, 2004. Okun M.R., Melanoma ressembling spindle and epitheloid cell nevus. Arch. Dermatol. 115:1416-20, 1979. Paniago-Pereira C., Maize J.C., Ackerman A.B., Nevus of large spindle and/or epitheloid cell (Spitzs nevus). Arch. Dermatol., 114:18111923, 1978. Pearson G.D., Goodman M., Sadove A.M., Congenital nevus: the Indiana University's approach to treatment. J. Craniofac. Surg.Sep; 16(5):915-20, 2005.


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