A 34-year-old man with cellular blue nevus developed some subcutaneous tumors on his left upper arm is reported. The blue macula appeared since vaccination on the same region at the age of seven. The macula subsequently increased in size rapidly and some tumors were formed for a year. The regional lymph nodes were palpable. 
Histopathologically, the tumor had a biphasic pattern with pigmented areas alternating with cellular islands, and infiltrated along vessels, nerve trunks and cutaneous appendages. The tumor cells were demonstrated in regional lymph nodes. 5-S-cysteinyldopa (5-SCD) in urine was in a borderline level. 
The diagnosis of cellular blue nevus with malignant potentiality was made.departmental bulletin pape

Emi YASUDA

Hidenari KUSAKABE

Kimihiro KIYOKANE

Minoru YASUHARA

English

Osaka Medical and Pharmaceutical University Repository

A Case of Cellular Blue Nevus言語: English出版者: Osaka Medical College公開日: 2024-06-05キーワード (Ja): キーワード (En): 作成者: Hidenari KUSAKABE, Emi YASUDA, KimihiroKIYOKANE, Minoru YASUHARAメールアドレス: 所属: メタデータhttps://ompu.repo.nii.ac.jp/records/2000194URL<Case Report> A Case of Cellular Blue Nevus Hidenari KUSAKABE, Emi YASUDA, Kimihiro KIYOKANE, and Minoru YASUHARA Department of Dermatology, Osaka Medical College, 2-7, Daigakumachi, Takatsuki City, Osaka 569, JapanKey Words: Cellular blue nevus, Lymph nodes, 5-SCD, Malignant potentiality ABSTRACT A 34-year-old man with cellular blue nevus developed some subcutaneous tumors on his left upper arm is reported. The blue macula appeared since vaccination on the same region at the age of seven. The macula subsequently increased in size rapidly and some tumors were formed for a year. The regional lymph nodes were palpable. Histopathologically, the tumor had a biphasic pattern with pigmented areas alternating with cellular islands, and infiltrated along vessels, nerve trunks and cutaneous append­ages. The tumor cells were demonstrated in regional lymph nodes. 5-S-cysteinyldopa (5-SCD) in urine was in a borderline level. The diagnosis of cellular blue nevus with malignant potentiality was made. INTRODUCTION Cellular blue nevus (CBN) was originally classified by DARRlER (1925) as a variant of malignant melanoma, but ALLEN in 1949 pointed out that CBN was a benign tumor and had been diagnosed in the past commonly as melanosarcoma and then in 1953 it was reclassified by ALLEN et al (1953) as a type of blue nevus (BN). Malignant transformation of CBN is a relatively rare occurrence (LEVER et al, 1990). However, some cases could not be easily determined from the histopathological findings whether they were benign or malignant (RODRIGUES et al, 1968; STERCHI et al, 1987). CBN tend to occur in the deep dermis and ex­tend into the adjacent subcutaneous tissues, where they may be mistaken for a metastatic melanoma (HERNANDES, 1973 ; OKUN, 1973). Nodal aggregates of BN cells associated with CBN have been found in the subcapsular periph-eral sinuses or parenchyma of the regional lymph nodes (ALLEN et al, 1953 ; COFFEY et al, 1951 ; DORSEY et al, 1954 ; GRICOUROFF et al, 197 4), as are most early foci of metastatic can­cer, and might represent passively transport to the lymph nodes, that is, benign metastasis (RODRIGUEZ et al, 1968; BHARGAVA, 1974). A malignant variant of CBN exists as a separate entity from malignant melanoma and CBN that has benign metastasis (FISHER, 1956 ; KWITTKEN et al, 1966 ; MONTGOMERY, 1967 ; HOURIHANE, 1970 ; MISHIMA, 1970 ; SPEAKMAN et al, 1973; REISS et al, 1975), but its differen­tial diagnosis is very difficult and sometimes confused (RODRIGUEZ et al, 1968 ; DORSEY et al, 1954 ; LUND et al, 1962). We report herein a case of a young man who had a cellular blue nevus, its infiltrating along vessels, nerve trunks and cutaneous appendages, and blue nevus cells in the capsules of regional lymph nodes. REPORT OF A CASE Clinical course A 34-year-old man had a light blue macula on his left upper arm measuring 4 cm in diame­ter which had been noticed since a vaccination there at the age of seven. The macula, which had become bluish-black, developed an in­duration in the subcutaneous tissue increas­ingly measuring 8 cm in diameter for just a year. The lesion had eight elastic-hard tumors measuring 1 to 4 mm (Fig. 1). The left axillary lymph nodes were palpable. The diagnosis, which was confirmed by a skin biopsy, was CBN that might have malignant potentiality. The laboratory findings were within normal limits except for 5-S-cysteinyldopa (5-SCD) (MORISHIMA et al, 1981) in urine (1.146 µ mol/day: normal range is 0.51 ± 0.3 µ moll day). Gallium scintigraphy revealed no hot lesion. The first combination chemotherapy, which consisted of DTIC (dimethyltriazeno imidazole carboxaroide), ACNU (amino-meth­yl-pyrimidinyl methyl-chloroethyl nitrosourea hydrochloride), VCR (vincristine) and lnterfer on-β, was performed before operation. A wide­radical excision was accomplished ; the mass with the overlying skin and partial axillary lymph nodes were removed. The lesion  infiltrated into the deltoid muscle, which was also removed. After the operation the second che­motherapy was done, but a week later he got a severe liver disfunction. The third chemother­apy could not be achieved. A level of 5-SCD in urine increased once at the first chemotherapy but after the operation it decreased almost in normal range. He has been free of both local re­currence and metastasis (Fig. 2). Histopathological findings Light microscopic examination The epidermis and dermal-epidermal junction were not involved by the tumor cells. Numer­ous pigmented spindle-shaped cell masses were extended into the subcutaneous tissue. No ne­crosis was seen (Fig. 3). Heavily pigmented and spindle-shaped tumor cells were character­ized by bipolar and dendritic processes. Most of them were filled with numerous fine melanin granules (Fig. 4). The island of closely aggre­gated spindle-shaped tumor cells with ovoid nuclei and abundant pale cytoplasm contain­ing little melanin was demonstrated, which resembled the storiform pattern seen in a neu­rofibroma. Inflammatory cells and prolifer­ations of vessels were not seen (Fig. 5). Thus tumor cells showed a biphasic pattern with pig­mented areas alternating with cellular islands. Fig. 1 The bluish-black macula, measuring 8 cm in diameter, had a induration in the subcutaneous tissue and some elastic-hard tumors. Fig. 2 Clinical course and the level of 5-SCD in urine Tumor cells infiltrated along vessels (Fig. 6), nerve trunks (Fig. 7) and cutaneous append­ages, and extended to the underlying subcutane­ous tissue and the fascia of the deltoid muscle. On the bleached preparation, the nuclei of the cells were neither atypical nor hyperchromatic (Fig. 8). Some of the axillary lymph nodes were black appearance, about 1 cm in diameter. The lymph follicles were intact but the capsule of lymph node had pigmented spindle and epithelioid cells. Some of pigmented spindle cells were in peripheral subcapsular sinus of lymph nodes (Fig. 9). Fig. 3 The epidermis and dermal-epidermal junc­tion were not involved by melanotic tu­mor cells. Numerous pigmented spindle­shaped cell masses were showed in the dermis extending into the subcutaneous fat. (hematoxylin-eosin, original magni­fication x 17) Fig. 4 Heavily pigmented and spindle-shaped tumor cells were characterized by bipolar and dendritic processes. Most of them were filled with numer­ous fine melanin granules. (hematoxylin-eosin, original magnification x85) Fig. 5 The island of spindle-shaped tumor cells containing little melanin extended in various directions, which resemble the storiform pattern seen in a neurofibroma. (hematoxylin-eosin, original magnification x85) Electron microscopic examination In the dermis, large numbers of melanosomes varying in size were noted in the tumor cells and had almost maxinum electron density, some of which were premelanosomes of consid­erably lower electron density. There were lo-cated freely and individually within the cyto­plasm, closely associated with intermediate vesicles and the Golgi complex and showed melanogenic activity. A spindle-shaped cell ex­hibited a fewer melanosomes (Fig. 10). Fig. 6 Heavily pigmented and spindle-shaped cells infiltrated along vessels. (hematoxylin-eosin, original magnification X43) Fig. 7 Heavily pigmented and spindle-shaped cells infiltrated along nerve trunks. (hematoxylin-eosin, original magnification x43) DISCUSSION ALLEN and SPITZ (1953) established CBN as a clinicopathological entity and defined a malignant transformation of CBN as malig­nant blue nevus (MBN), which has been reported sporadically (DORSEY et al, 1954 ; FISHER, 1956; KWITTKEN et al, 1966 ; MISHIMA, 1970 ; MERKOW et al, 1969). In DORSEY and MONTGOMERY's (1954) report on 3 cases of "metastatic blue nevi", they suggested that BN Fig. 8 By the bleached preparation, the nuclei of the cells were atypical but a very few mitoses were present. (hematoxylin-eosin, original magnification x 200) Fig. 9 The regional lymph follicle was intact but in its capsule pigmented spindle and epithelioid cells were found. (hematoxylin-eosin, origi­nal magnification x34) Fig. 10 Large numbers of melanosomes varying in size were noted in the bipolar cells and almost maxinum electron density, some of which were premelanosomes of con­siderably lower electron density. One of the tumor cells exhibited a fewer melanosomes. (original magnification x 7500) might go through cellular transformation simi­larly to CBN when turning malignant. How­ever, malignant degeneration of CBN can rarely occur (LEVER et al, 1990). In Japan, no more than 20 patients having CBN have been re­ported, and only a little more than 10 patients with MBN have been encountered to data. In Japan IKEDA et al (1981) suggested malignant transformation of BN, and SATO et al (1985) and FUKUI et al (1989) reported mixed cases of BN, CBN and MBN, suggesting that BN pro­gressed to CBN which in turn led to MBN. In FISHER's (1956) report on cases of BN leading to MBN, he indicated that atavistic features of BN such as fasciculation of tumor cells, inter­mingled chromatophores and sclerosis of vary­ing degree were usually observed in the malignant variant. YAMAMURA  and MISHIMA (1990) also suggested that BN progressed to premalignant CBN ending in MBN. In other words, not only pigmented cell tumors but all other kinds of tumors go through a process of incessant canceration, that is, they are preceded by precancerous prodromal symptoms. AVIDOR et al (1977) reported three cases of "atypical" blue nevus which had presented almost identical histological findings differed from CBN and MBN. In their paper "atypical" blue nevus that had cellular pleomorphism with numerous bizarre, multinucleated cells, giant cells and a few mitoses suggested malignancy, however, the prolonged follow-up (19 years) without re­currence or metastases indicated that their pig­mented tumor was a benign variant of CBN. In our case the tumor cells which were heav­ily pigmented and spindle-shaped cells infil-trated along vessels, nerve trunks and cutaneous appendages and extended to the fascia of the muscle, although, the focus was poor in atypical cells and was hardly mitotic figure. On the other hand, nodal aggre­gates of nevus cells associated with CBN were found in the subcapsular peripheral si­nuses and parenchyma of the regional lymph nodes. RODRIGUES and ACKERMAN (1968) de­scribed CBN with regional lymph nodes in the marginal sinuses had not represented true me­tastases but been passively transported to the lymph nodes and lodged there as inert deposits. BHARGAVA (1974) represented such condition to be benign metastasis of nevus cells. Our case may therefore be better diagnosed as CBN rather than as MBN. It could not be easily de­termined from the histopathological findings whether this tumor was benign or malignant. The subsequent clinical strategy greatly differs according as the tumor is diagnosed as being benign or malignant. The definite diagno­sis is closely concerned with the decision whether or not the patient should undergo seri­ous surgical intervention. There is no time left for long-term follow-up in our case. (1) The lesion showed a rapid growth in a short period of time, and some tumors were formed.Urinalysis showed that 5-SCD was at a bor­derline level of 1.146 µmol/day. According to (2) MORISHIMA et al (1981) malignant melanoma can spread in stage 1 or 2 when 5-SCD in the urine reaches a borderline level. Such border­line values strongly suggest malignant trans­formation of pigmented cell tumors. Based on the above findings, we are inclined to conclude that our case is not MBN but rather CBN which might have malignant poten­tiality. ACKNOWLEDGEMENTS We thank Eiichi FUKAE M.D., Yoshio TANAKA M.D. and Professor Sadao TAZIMA, department of Plastic and Reconstruction Sur­gery, Osaka Medical College, for surgical treat­ment. We thank Kazumasa WAKAMATSU Ph.D., Fuzita Health University, School of Hy­giene, for measuring 5-SCD in urine. REFERENCES ALLEN AC : A reorientation on the histogenesis and clinical significance of cutaneous nevi and melanomas, Cancer 2 : 28-56, 1949 ALLEN AC, SPITZ S : Malignant melanoma. 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A Case of Cellular Blue Nevus

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A Case of Cellular Blue Nevus

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