Journal ofDermatologica1
Science, 4 (1992) 185-192 0 1992 Elsevier Science Publishers B.V. All rights reserved. 0923- 18 1l/92/$05.00
185
DESC 00165
Malignant
blue nevus: a report of eight cases
David A. Mehregan,
Lawrence
E. Gibson and Amir H. Mehregan
Department of Dermatology, Ma_yo Clinic, Rochester, MN, USA and Pinkus Dermatopathology Laboratory, Monroe. MI, USA
(Received 3 October 1991; accepted 28 July 1992)
Key words: Malignant blue nevus; Metastasis;
DNA flow cytometry; Histopathology
Abstract
Malignant blue nevus is uncommon compared to its benign counterpart and is regarded as a rare form of malignant melanoma. We report the clinical and histological findings in eight cases. Histologically, all eight specimens showed no epidermal involvement and had contained within or were adjacent to portions of blue nevus or cellular blue nevus. Proliferation of bundles of bipolar spindle shaped cells with marked cellular atypia, mitotic figures, foci of necrosis, and inflammatory cell infiltrate were noted. Two of the cases were studied by DNA flow cytometry and the populations of tumor cells were found to be diploid. Two cases have died secondary to metastasis. Although malignant blue nevi may not behave as aggressively as nodular malignant melanoma, they have definite potential to do so and therefore should be removed by wide surgical excision.
Introduction Blue nevi are relatively common skin tumors, first described by Tieche [ 1] in 1906. Three variants are recognized; the common blue nevus, the cellular blue nevus and the combined nevus. Recently, Kamino and Tam [2] reported another variety, a compound blue nevus characterized by junctional dendritic melanocytic hyperplasia overlying dermal melanocytosis. Clinically, all variants appear as dome-shaped, smooth blue, or blue-black lesions. The cellular blue nevus is often larger and more protuberant. Blue nevi are usually present at birth or appear early in life and persist with no change. Common blue nevi are Correspondence to: David A. Mehregan, M.D., Pinkus Dermatopathology Laboratory, P.C., 1314 North Macomb Street; P.O. Box 360, Monroe, MI 48161, USA.
more often found on the dorsum of hands and feet while the cellular blue nevi are usually located on the scalp and buttocks. Allen [ 31 was first to describe histological differentation between the common blue nevus and the cellular blue news. The common blue nevus shows massive proliferation of pigment forming dermal melanocytes embedded in a matrix of collagenous and elastic fibers. The cellular blue nevus is characterized by heavily cellular intersecting bundles and islands of large spindle shaped cells with abundant pale staining cytoplasm, often without melanin. Malignant blue nevus is uncommonly compared to its benign counterpart and is regarded as a rare form of malignant melanoma. Review of the literature reveals only 33 cases [4-l 11, with the majority of the reports being single cases. The largest series include that of Allen and Spitz [lo] who described six cases and a series of 12 cases
186
recently reported by Connolly and Smith [ 141 from the files of the University of Texas MD Anderson Cancer Center. It is generally believed that the malignant blue nevus originates within a pre-existing cellular blue nevus, a nevus of Ota, common blue nevus or, rarely, even de novo. Review of the files at the Mayo Clinic and a private dermatopathology laboratory revealed eight cases of malignant blue nevi. We are reporting the clinicopathological features of these cases as well as the result of DNA flow cytometry findings in two of the cases in this series. Materials
and Methods
cases, the patients indicated recent change in size, irritation, superficial erosion, and development of pain. The lesions were between one and two centimeters in diameter. Clinical diagnosis included blue nevus and sclerosing hemangioma (Table I). In all eight cases, the lesion was removed by complete surgical excision and all specimens included the subcutaneous fat tissue. Formalin or alcohol fixed and paraffin embedded tissue sections were stained using hematoxylin-eosin technique. Flow cytometry was done in two cases. Fifty-micron sections from paraffin embedded blocks were used for flow cytometry studies by the technique previously described [ 151. Histological
findings
Eight cases with malignant blue nevus consisted of six women and two men with their ages ranging between 22 and 52 years (average 37 years). Four lesions occurred on the buttocks, three over the dorsum of the foot, and one on the scalp. Typically the lesions were described as single blue to blue-black, dome-shaped nodular growths, often present since birth (Fig. 1). In three
Epidermal involvement was not observed in any of the eight specimens reviewed, but four cases showed marked epidermal atrophy without superficial ulceration. Low power evaluation revealed the growth to be frequently multilobulated and fairly well defined, involving the middle and
Fig. 1. Malignant blue nevus forming a blue-black nodule over the dorsal aspect of the right foot (Case 6).
Fig. 2. Part of a well-defined nodular growth that appears encapsulated. H&E, x 25.
187 TABLE
I
Case
Age/sex
Location
Clinical data
Clinical diagnosis
Case 1
35/M
Buttock
Sclerosing hemangioma
Case 2 Case 3
53/F 16/F
scalp Gluteal cleft
Case 4
52/M
Buttock
Case 5
25/F
Scalp
Case 6
22/F
Dorsum of foot
Case 7 Case 8
59/F 35/F
Dorsum of foot Dorsum of foot
1 cm firm blue-black nodule present since birth 1.5 cm bluish nodular growth 2.5 cm elevated and pigmented growth present since birth 1 cm dome-shaped and deeply pigmented growth Recent development of a 3 cm nodular growth within a blue nevus present since birth 1.5 cm blue-black nodule present since birth with recent increase in size and development of pain 2 cm elevated blue-black nodular growth 1.5 cm blue-black nodule present at birth with recent development of erythema and swelling
Blue nevus Blue nevus Blue nevus Large blue nevus
Blue nevus
Blue nevus Blue nevus
Fig. 3. Malignant blue nevus. Both areas show proliferatron of elongated dermal melanocytes forming densely cellular bundles. Macrophages containing melanin granules are scattered between the tumor cell bundles. H&E, x 100.
188
deep dermis with extension into the panniculus in seven cases. Four specimens showed the growth to be surrounded by a fibrous pseudocapsule along its lower border (Fig. 2). Pigmentation varied from moderate to focally heavy, or dense throughout the same lesion. The melanin pigment granules were contained predominantly in the tumor spindle cells and infrequently in scattered macrophages. The tumor cells were predominantly spindle shaped with elongated nuclei. Some epithelioid cells containing less pigment were also present. The spindle cells formed two major patterns: (A) all eight lesions showed the characteristic fascicular pattern with densely cellular and intersecting bundles of bipolar spindle cells (Fig. 3) similar to those seen in cellular blue
kig. 4. Malignant
blue nevus.
nevi; (B) in four lesions, numerous small groups of tumor cells gathered in a pseudoglandular pattern (Fig. 4). In all specimens, the spindle tumor cells were moderately to highly pleomorphic (Figs. 5, 6) with many cells showing irregularly shaped, multilobulated and hyperchromatic nuclei, with six lesions showing prominent nucleoli. Typical and atypical mitoses were present in all but two specimens and ranged from one to seven per five high power fields. Areas of tumor cell necrosis were evident in four cases with larger lesions. Inflammatory cell infiltrate was seen in seven lesions at the periphery of the growth and consisted mainly of lymphocytes. DNA flow cytometry in two cases (Cases l&2) revealed the population of the tumor cells to be diploid (Fig. 7).
Left: areas with massive proliferation of elongated and epithelioid with pseudoglandular arrangement. H&E, x 100.
type cells. Kight:
nests
of cells
Fig. 5. Malignant blue nevus. Both areas show marked cellular atypia. The tumor cells show abnormally large, irregularly shaped and hyperchromatic nuclei. H&E, x 225.
Comments
Malignant blue nevus is a rare neoplasm of dermal melanocytes. Approximately 33 cases have been reported. In 17 of the 33 cases the lesion was located on the scalp. Seven lesions were located over the trunk, six on the extremities, and three over the face and neck areas. The lesions measured from 1 to 3 cm in diameter. The average age at the time of diagnosis was 45 years. In our series of eight cases, two lesions were located on the scalp, three appeared over the dorsum of the foot, and three occurred over the buttock and gluteal cleft areas. The age of the patients at the
time of diagnosis ranged from 22 to 59 years, with an average of 37 years. The size of the lesions varied from 1 to 3 cm. Histopathological differentiation of malignant blue nevus from cellular blue nevus and nodular malignant melanoma can be difficult. The histological features we found to be significant included: (A) complete absence of epidermal involvement with atypical melanocytic proliferation or junctional nest formation; (B) marked cellular atypia with cells having multilobulated and hyperchromatic nuclei and prominent nucleoli; (C) presence of mitotic figures and atypical mitoses; (D) heavily cellular bundles of bipolar spindle shaped cells and areas with
Fig:. 6. Malignant blue nevus. Both areas show numerous atypical dermal melanocytes with irregularly shaped and hyperchromatic nuclei and scattered mitotic figures. H&E, x 225.
pseudoglandular cell arrangement; (E) the presence of areas of tumor cell necrosis and foci of inflammatory cell reaction. No single histological feature seems to be diagnostic. Necrosis was present in only three cases. Other reports have also mentioned lack of tumor cell necrosis [ 10-121. Temple-Camp et al. [6] have suggested that 7 y0 of cellular nevi may show areas of cell necrosis. They have also indicated that 27% of cellular blue nevi may show areas with pseudoglandular cell arrangement. Others have noted that within a large lesion the histological findings can show variation and may lead to misdiagnosis if the entire lesion is not removed and histologically investigated.
DNA flow cytometry has been utilized in several series of cases as another procedure for differentiation of malignant melanoma from benign [ 161, dysplastic [ 171 and Spitz [18] nevi. We performed DNA flow cytometry in two of our cases and in both instances we found the population of tumor cells to be diploid. The DNA histograms in both of our cases show a large peak containing diploid cells in G,/G, phase representing those cells with diploid amount of DNA content. The second smaller peak showing cells in the G,/M phase represent those cells ready to or undergoing mitosis and containing a tetraploid amount of DNA content. These are typical histograms for normal human somatic cell popula-
191
1000 Case
CELL COUNT
Case
1
2
i
DNA Fig. 7. DNA
CONTENT
histograms
for Cases
1 and 2, showing
tions. If a difference of DNA content (i.e., aneuploidy or tetraploidy) was to be seen, this would appear as distinct peaks separate from these. However, flow cytometric analysis only evaluates the population of tumor cells in active cycling at the time of tumor removal. The nodular malignant melanoma, which is the neoplasm histologically most akin to the malignant blue nevus, usually shows numerous mitotic figures and frequently is found to have an aneuploid cell population. Malignant blue nevi often show very few mitoses and this may explain the result of DNA flow cytometry. Since the majority of tumor cells are not actively reproducing (low S phase), those that are may be overshadowed and lost in the analysis. The low mitotic rate, representing a relatively more benign biological potential, may also explain why some malignant blue nevi have a long latency period before metastasis, sometimes more than ten years after the removal of the original lesion. In a recent review by Herzberg [ 191 of DNA ploidy in cutaneous lesions, the author noted tumors with diploid nuclear content to have a less aggressive course than aneuploid tumors and this may be so in the case of malignant blue nevi. However, only two of our cases were available for flow cytometry and we feel further studies of these tumors are necessary to define if DNA
a normal
diploid
DNA
content
in malignant
blue nevi.
ploidy analysis may be useful in diagnosis and determination of prognosis. The incidence of metastasis and death have ranged between 55 and 80% [14] in cases of malignant blue nevus. In our series, follow-up information was available in four cases. Cases 1, 2 have shown no evidence of recurrences or metastasis after 2.5 and 2 years, respectively. Case 5 died of central nervous system metastases. Case 6 died from generalized metastasis, with predominantly pulmonary involvement. Although malignant blue nevi may not generally behave as aggressively as nodular malignant melanoma, they have definite potential to produce generalized metastasis and fatal outcome in the majority of cases. Therefore, malignant blue nevi should be removed by wide surgical excision and the patient should be followed up periodically for a period of at least 5 years.
References Tieche M: Uber benigne melanome (“chromatophorome”) der haut “bhre naevi”. Arch Pathol Anat 186: 212-229, 1906. Kamino H, Tam ST: Compound blue nevus: a variant of blue nevus with an additional junctional dendritic component.
Arch
Dermatol
126: 1330-1333,
1990.
192
3 Allen AG: A reorientation on the histogenesis and clinical significance of cutaneous nevi and melanomas. Cancer 2: 28-56, 1949. 4 Goldenhersh MA, Savin RC, Barnhill RL, Stenn KD: Malignant blue nevus. J Am Acad Dermatol19: 717-722, 1988. 5 Moldy C, Wood C, Horn T: Metastatic malignant melanoma arising from a common blue nevus in a patient with subacute cutaneous lupus erythematosus. Dermatologica 178: 171-175, 1989. 6 Temple-Camp CRE, Saxe N. King H: Benign and malignant cellular blue nevus: a clinicopathologic study of 30 cases. Am J Dermatopathol 10: 289-296, 1988. 7 Kuhn A, Groth W, Gartmann H, Steigleder GK: Malignant blue nevus with metastases to the lung. Am J Dermatopathol 10: 436-441, 1988. 8 Kwittken J, Negri L: Malignant blue nevus. Case report of a negro woman. Arch Dermatol 94: 64-69, 1966. 9 Rubinstein N, Kopolovic J, Wexler MR, Peled IJ: Malignant blue nevus. J Dermatol Surg Oncol 11: 921-923, 1985. 10 Shallman RW, Hoehn JL, Lawton BR, Dickenson KB: Malignant cellular blue nevus: unusual case of a rare tumor. Wise Med J 87: 16-18, 1988. 11 Fisher ER: Malignant blue nevus. Arch Dermatol 74: 227-23 1, 1956.
12 Reiss RF, Gray GF: Malignant blue nevus. NY State J Med 75: 1749-1751, 1975. 13 Allen AC, Spitz S: Malignant melanoma. A clinicopathological analysis of the criteria for diagnosis and prognosis. Cancer 6: l-45, 1953. 14 Connelly J, Leslie Smith J Jr: Malignant blue nevus. Cancer 67: 2653-2657, 1991. 15 Oliver GF, Reiman HNM, Gonchoroff NJ, et al.: Cutaneous and subcutaneous leiomyosarcoma: a clinicopathologic review of 14 cases with reference to anti-desmin staining and nuclear DNA patterns studied by flow cytometry. Br J Dermatol 124, 1991. 16 VonRoenn JH, Kheir SM, Wolter JM, Coon JS: Signiticance of DNA abnormalities in primary malignant melanoma and nevi, a restropective flow cytometric study. Cancer Res 46: 3192-3195, 1986. 17 Fleming MG, Wied GL, Dytch HE: Image analysis cytometry of dysplastic nevi. J Invest Dermato195: 287-291. 1990. 18 Chi HI, lshibashi Y, Shima A, et al.: Use of DAPI cytofluorometric analysis of cellular DNA content to differentiate Spitz nevus from malignant melanoma. J Invest Dermat01 95: 154-157, 1990. 19 Hertzberg AJ: Significance of DNA ploidy in cutaneous lesions. Arch Dermatol 128: 663-672, 1992.
Science, 4 (1992) 185-192 0 1992 Elsevier Science Publishers B.V. All rights reserved. 0923- 18 1l/92/$05.00
185
DESC 00165
Malignant
blue nevus: a report of eight cases
David A. Mehregan,
Lawrence
E. Gibson and Amir H. Mehregan
Department of Dermatology, Ma_yo Clinic, Rochester, MN, USA and Pinkus Dermatopathology Laboratory, Monroe. MI, USA
(Received 3 October 1991; accepted 28 July 1992)
Key words: Malignant blue nevus; Metastasis;
DNA flow cytometry; Histopathology
Abstract
Malignant blue nevus is uncommon compared to its benign counterpart and is regarded as a rare form of malignant melanoma. We report the clinical and histological findings in eight cases. Histologically, all eight specimens showed no epidermal involvement and had contained within or were adjacent to portions of blue nevus or cellular blue nevus. Proliferation of bundles of bipolar spindle shaped cells with marked cellular atypia, mitotic figures, foci of necrosis, and inflammatory cell infiltrate were noted. Two of the cases were studied by DNA flow cytometry and the populations of tumor cells were found to be diploid. Two cases have died secondary to metastasis. Although malignant blue nevi may not behave as aggressively as nodular malignant melanoma, they have definite potential to do so and therefore should be removed by wide surgical excision.
Introduction Blue nevi are relatively common skin tumors, first described by Tieche [ 1] in 1906. Three variants are recognized; the common blue nevus, the cellular blue nevus and the combined nevus. Recently, Kamino and Tam [2] reported another variety, a compound blue nevus characterized by junctional dendritic melanocytic hyperplasia overlying dermal melanocytosis. Clinically, all variants appear as dome-shaped, smooth blue, or blue-black lesions. The cellular blue nevus is often larger and more protuberant. Blue nevi are usually present at birth or appear early in life and persist with no change. Common blue nevi are Correspondence to: David A. Mehregan, M.D., Pinkus Dermatopathology Laboratory, P.C., 1314 North Macomb Street; P.O. Box 360, Monroe, MI 48161, USA.
more often found on the dorsum of hands and feet while the cellular blue nevi are usually located on the scalp and buttocks. Allen [ 31 was first to describe histological differentation between the common blue nevus and the cellular blue news. The common blue nevus shows massive proliferation of pigment forming dermal melanocytes embedded in a matrix of collagenous and elastic fibers. The cellular blue nevus is characterized by heavily cellular intersecting bundles and islands of large spindle shaped cells with abundant pale staining cytoplasm, often without melanin. Malignant blue nevus is uncommonly compared to its benign counterpart and is regarded as a rare form of malignant melanoma. Review of the literature reveals only 33 cases [4-l 11, with the majority of the reports being single cases. The largest series include that of Allen and Spitz [lo] who described six cases and a series of 12 cases
186
recently reported by Connolly and Smith [ 141 from the files of the University of Texas MD Anderson Cancer Center. It is generally believed that the malignant blue nevus originates within a pre-existing cellular blue nevus, a nevus of Ota, common blue nevus or, rarely, even de novo. Review of the files at the Mayo Clinic and a private dermatopathology laboratory revealed eight cases of malignant blue nevi. We are reporting the clinicopathological features of these cases as well as the result of DNA flow cytometry findings in two of the cases in this series. Materials
and Methods
cases, the patients indicated recent change in size, irritation, superficial erosion, and development of pain. The lesions were between one and two centimeters in diameter. Clinical diagnosis included blue nevus and sclerosing hemangioma (Table I). In all eight cases, the lesion was removed by complete surgical excision and all specimens included the subcutaneous fat tissue. Formalin or alcohol fixed and paraffin embedded tissue sections were stained using hematoxylin-eosin technique. Flow cytometry was done in two cases. Fifty-micron sections from paraffin embedded blocks were used for flow cytometry studies by the technique previously described [ 151. Histological
findings
Eight cases with malignant blue nevus consisted of six women and two men with their ages ranging between 22 and 52 years (average 37 years). Four lesions occurred on the buttocks, three over the dorsum of the foot, and one on the scalp. Typically the lesions were described as single blue to blue-black, dome-shaped nodular growths, often present since birth (Fig. 1). In three
Epidermal involvement was not observed in any of the eight specimens reviewed, but four cases showed marked epidermal atrophy without superficial ulceration. Low power evaluation revealed the growth to be frequently multilobulated and fairly well defined, involving the middle and
Fig. 1. Malignant blue nevus forming a blue-black nodule over the dorsal aspect of the right foot (Case 6).
Fig. 2. Part of a well-defined nodular growth that appears encapsulated. H&E, x 25.
187 TABLE
I
Case
Age/sex
Location
Clinical data
Clinical diagnosis
Case 1
35/M
Buttock
Sclerosing hemangioma
Case 2 Case 3
53/F 16/F
scalp Gluteal cleft
Case 4
52/M
Buttock
Case 5
25/F
Scalp
Case 6
22/F
Dorsum of foot
Case 7 Case 8
59/F 35/F
Dorsum of foot Dorsum of foot
1 cm firm blue-black nodule present since birth 1.5 cm bluish nodular growth 2.5 cm elevated and pigmented growth present since birth 1 cm dome-shaped and deeply pigmented growth Recent development of a 3 cm nodular growth within a blue nevus present since birth 1.5 cm blue-black nodule present since birth with recent increase in size and development of pain 2 cm elevated blue-black nodular growth 1.5 cm blue-black nodule present at birth with recent development of erythema and swelling
Blue nevus Blue nevus Blue nevus Large blue nevus
Blue nevus
Blue nevus Blue nevus
Fig. 3. Malignant blue nevus. Both areas show proliferatron of elongated dermal melanocytes forming densely cellular bundles. Macrophages containing melanin granules are scattered between the tumor cell bundles. H&E, x 100.
188
deep dermis with extension into the panniculus in seven cases. Four specimens showed the growth to be surrounded by a fibrous pseudocapsule along its lower border (Fig. 2). Pigmentation varied from moderate to focally heavy, or dense throughout the same lesion. The melanin pigment granules were contained predominantly in the tumor spindle cells and infrequently in scattered macrophages. The tumor cells were predominantly spindle shaped with elongated nuclei. Some epithelioid cells containing less pigment were also present. The spindle cells formed two major patterns: (A) all eight lesions showed the characteristic fascicular pattern with densely cellular and intersecting bundles of bipolar spindle cells (Fig. 3) similar to those seen in cellular blue
kig. 4. Malignant
blue nevus.
nevi; (B) in four lesions, numerous small groups of tumor cells gathered in a pseudoglandular pattern (Fig. 4). In all specimens, the spindle tumor cells were moderately to highly pleomorphic (Figs. 5, 6) with many cells showing irregularly shaped, multilobulated and hyperchromatic nuclei, with six lesions showing prominent nucleoli. Typical and atypical mitoses were present in all but two specimens and ranged from one to seven per five high power fields. Areas of tumor cell necrosis were evident in four cases with larger lesions. Inflammatory cell infiltrate was seen in seven lesions at the periphery of the growth and consisted mainly of lymphocytes. DNA flow cytometry in two cases (Cases l&2) revealed the population of the tumor cells to be diploid (Fig. 7).
Left: areas with massive proliferation of elongated and epithelioid with pseudoglandular arrangement. H&E, x 100.
type cells. Kight:
nests
of cells
Fig. 5. Malignant blue nevus. Both areas show marked cellular atypia. The tumor cells show abnormally large, irregularly shaped and hyperchromatic nuclei. H&E, x 225.
Comments
Malignant blue nevus is a rare neoplasm of dermal melanocytes. Approximately 33 cases have been reported. In 17 of the 33 cases the lesion was located on the scalp. Seven lesions were located over the trunk, six on the extremities, and three over the face and neck areas. The lesions measured from 1 to 3 cm in diameter. The average age at the time of diagnosis was 45 years. In our series of eight cases, two lesions were located on the scalp, three appeared over the dorsum of the foot, and three occurred over the buttock and gluteal cleft areas. The age of the patients at the
time of diagnosis ranged from 22 to 59 years, with an average of 37 years. The size of the lesions varied from 1 to 3 cm. Histopathological differentiation of malignant blue nevus from cellular blue nevus and nodular malignant melanoma can be difficult. The histological features we found to be significant included: (A) complete absence of epidermal involvement with atypical melanocytic proliferation or junctional nest formation; (B) marked cellular atypia with cells having multilobulated and hyperchromatic nuclei and prominent nucleoli; (C) presence of mitotic figures and atypical mitoses; (D) heavily cellular bundles of bipolar spindle shaped cells and areas with
Fig:. 6. Malignant blue nevus. Both areas show numerous atypical dermal melanocytes with irregularly shaped and hyperchromatic nuclei and scattered mitotic figures. H&E, x 225.
pseudoglandular cell arrangement; (E) the presence of areas of tumor cell necrosis and foci of inflammatory cell reaction. No single histological feature seems to be diagnostic. Necrosis was present in only three cases. Other reports have also mentioned lack of tumor cell necrosis [ 10-121. Temple-Camp et al. [6] have suggested that 7 y0 of cellular nevi may show areas of cell necrosis. They have also indicated that 27% of cellular blue nevi may show areas with pseudoglandular cell arrangement. Others have noted that within a large lesion the histological findings can show variation and may lead to misdiagnosis if the entire lesion is not removed and histologically investigated.
DNA flow cytometry has been utilized in several series of cases as another procedure for differentiation of malignant melanoma from benign [ 161, dysplastic [ 171 and Spitz [18] nevi. We performed DNA flow cytometry in two of our cases and in both instances we found the population of tumor cells to be diploid. The DNA histograms in both of our cases show a large peak containing diploid cells in G,/G, phase representing those cells with diploid amount of DNA content. The second smaller peak showing cells in the G,/M phase represent those cells ready to or undergoing mitosis and containing a tetraploid amount of DNA content. These are typical histograms for normal human somatic cell popula-
191
1000 Case
CELL COUNT
Case
1
2
i
DNA Fig. 7. DNA
CONTENT
histograms
for Cases
1 and 2, showing
tions. If a difference of DNA content (i.e., aneuploidy or tetraploidy) was to be seen, this would appear as distinct peaks separate from these. However, flow cytometric analysis only evaluates the population of tumor cells in active cycling at the time of tumor removal. The nodular malignant melanoma, which is the neoplasm histologically most akin to the malignant blue nevus, usually shows numerous mitotic figures and frequently is found to have an aneuploid cell population. Malignant blue nevi often show very few mitoses and this may explain the result of DNA flow cytometry. Since the majority of tumor cells are not actively reproducing (low S phase), those that are may be overshadowed and lost in the analysis. The low mitotic rate, representing a relatively more benign biological potential, may also explain why some malignant blue nevi have a long latency period before metastasis, sometimes more than ten years after the removal of the original lesion. In a recent review by Herzberg [ 191 of DNA ploidy in cutaneous lesions, the author noted tumors with diploid nuclear content to have a less aggressive course than aneuploid tumors and this may be so in the case of malignant blue nevi. However, only two of our cases were available for flow cytometry and we feel further studies of these tumors are necessary to define if DNA
a normal
diploid
DNA
content
in malignant
blue nevi.
ploidy analysis may be useful in diagnosis and determination of prognosis. The incidence of metastasis and death have ranged between 55 and 80% [14] in cases of malignant blue nevus. In our series, follow-up information was available in four cases. Cases 1, 2 have shown no evidence of recurrences or metastasis after 2.5 and 2 years, respectively. Case 5 died of central nervous system metastases. Case 6 died from generalized metastasis, with predominantly pulmonary involvement. Although malignant blue nevi may not generally behave as aggressively as nodular malignant melanoma, they have definite potential to produce generalized metastasis and fatal outcome in the majority of cases. Therefore, malignant blue nevi should be removed by wide surgical excision and the patient should be followed up periodically for a period of at least 5 years.
References Tieche M: Uber benigne melanome (“chromatophorome”) der haut “bhre naevi”. Arch Pathol Anat 186: 212-229, 1906. Kamino H, Tam ST: Compound blue nevus: a variant of blue nevus with an additional junctional dendritic component.
Arch
Dermatol
126: 1330-1333,
1990.
192
3 Allen AG: A reorientation on the histogenesis and clinical significance of cutaneous nevi and melanomas. Cancer 2: 28-56, 1949. 4 Goldenhersh MA, Savin RC, Barnhill RL, Stenn KD: Malignant blue nevus. J Am Acad Dermatol19: 717-722, 1988. 5 Moldy C, Wood C, Horn T: Metastatic malignant melanoma arising from a common blue nevus in a patient with subacute cutaneous lupus erythematosus. Dermatologica 178: 171-175, 1989. 6 Temple-Camp CRE, Saxe N. King H: Benign and malignant cellular blue nevus: a clinicopathologic study of 30 cases. Am J Dermatopathol 10: 289-296, 1988. 7 Kuhn A, Groth W, Gartmann H, Steigleder GK: Malignant blue nevus with metastases to the lung. Am J Dermatopathol 10: 436-441, 1988. 8 Kwittken J, Negri L: Malignant blue nevus. Case report of a negro woman. Arch Dermatol 94: 64-69, 1966. 9 Rubinstein N, Kopolovic J, Wexler MR, Peled IJ: Malignant blue nevus. J Dermatol Surg Oncol 11: 921-923, 1985. 10 Shallman RW, Hoehn JL, Lawton BR, Dickenson KB: Malignant cellular blue nevus: unusual case of a rare tumor. Wise Med J 87: 16-18, 1988. 11 Fisher ER: Malignant blue nevus. Arch Dermatol 74: 227-23 1, 1956.
12 Reiss RF, Gray GF: Malignant blue nevus. NY State J Med 75: 1749-1751, 1975. 13 Allen AC, Spitz S: Malignant melanoma. A clinicopathological analysis of the criteria for diagnosis and prognosis. Cancer 6: l-45, 1953. 14 Connelly J, Leslie Smith J Jr: Malignant blue nevus. Cancer 67: 2653-2657, 1991. 15 Oliver GF, Reiman HNM, Gonchoroff NJ, et al.: Cutaneous and subcutaneous leiomyosarcoma: a clinicopathologic review of 14 cases with reference to anti-desmin staining and nuclear DNA patterns studied by flow cytometry. Br J Dermatol 124, 1991. 16 VonRoenn JH, Kheir SM, Wolter JM, Coon JS: Signiticance of DNA abnormalities in primary malignant melanoma and nevi, a restropective flow cytometric study. Cancer Res 46: 3192-3195, 1986. 17 Fleming MG, Wied GL, Dytch HE: Image analysis cytometry of dysplastic nevi. J Invest Dermato195: 287-291. 1990. 18 Chi HI, lshibashi Y, Shima A, et al.: Use of DAPI cytofluorometric analysis of cellular DNA content to differentiate Spitz nevus from malignant melanoma. J Invest Dermat01 95: 154-157, 1990. 19 Hertzberg AJ: Significance of DNA ploidy in cutaneous lesions. Arch Dermatol 128: 663-672, 1992.
