CAMEO
MALIGNANT SPITZ NEVUS CDR HENRY G. SKELTON 111, MC USN, LTC KATHLEEN J. SMITH, MC USA, CDR THERESA T. HOLLAND, MC USN, COL MARIA-MAGDALENA TOMASZEWSKI, MC USA, AND COL GEORGE P. LUPTON, MC USA
Tbe patient Is a 22-year-old white woman, who was 16 years of age at the time of initial presentation. At that time, a lesion was removed from her left cheek, which was diagnosed as dermatofibrosarcoma protuberans. Four years later, a physical examination of the patient revealed an enlarged lymph node in the lower midline neck area. The lymph node was biopsied and both lesions were sent for further histopathologic examination. Histopathology: The original lesion was composed of densely cellular fascicles of plump spindle-shaped cells extending into the subcutaneous fat with a pushing not infiltrating margin (Fig. 1). Examination at higher power showed regular fascicles of plump spindle-shaped cells with prominent nucleoli. Occasional mitotic figures were seen, some present deep within the lesion (Fig. 2). The lymph node biopsy showed similar fascicles of spindled cells within the parenchyma surrounded by normal lymphoid tissue (Figs. 3 and 4). Mitotic figures were not found. Between the fascicles were areas of fibrosis. Both the skin and lymph node biopsies showed positive staining with S-100 protein (Chemicon 1:2000, ABC method). Tbe patient has bad no evidence of recurrence or further spread now 5.5 years after excision of the original lesion.
Figure 1. "Malignant Spitz nevus" of this case showing sharp lateral demarcation and a deep pushing margin extending into the subcutaneous fat. (hematoxylin and eosin, original magnification X 75)
DISCUSSION
Before Dr. Sophie Spitz established criteria for the diagnosis of spindle cell and epithelioid cell nevi (S&E neyi) in 1948, these lesions were considered histologically indistinguishable frotn malignant tnelanomas (MM).'-McWhorter and Woolner confirmed the benign clinical behavior of these lesions after reviewing similar lesions that had been seen at the Mayo Clinic' Specific criteria
reported by Alien and Spitz, which could be used to differentiate S&E nevi frotn MM, included (1) features of a compound nevus, (2) edetna and telangiectasia in the upper portion of the dermis, (3) nests of cells sharply separated from the surroutiditig keratinocytes, (4) large spindle or epithelioid cells, (5) Touton-like giatit cells, (6) abrupt transition between acantholytic cells in the junctional nests and the intact epidertnis, (7) relative sparsity of pigmentation, and (8) relative superficiality of the major latidtnarks of the lesions.' In 1989 a group of lesions were reported that had, in addition to the above features, a diatneter of greater than 1 cm, extension into the subcutaneous fat with a pushing as opposed to infiltrating margin, and in some cases lytnph node metastases.' Additional histologic features cotntnon to these lesions atid found within the spectrum of lesion classified as S&E nevi were mitoses, which could be present deep within the lesions; lack of
From the Department of Dermatopathology, Armed Forces Institute of Pathology, and the Walter Reed Army Institute for Research, Washington, DG. The opinions or assertions contained herein are the private views of the authors and are not to be considered as official or as reflecting the views of the department of the Army, or Navy or of the Department of Defense. Address for correspondence: Henry G. Skelton, M.D., Department of Dermatopathology, Armed Fot-ces Institute of Pathology, Washington, DG 20306. 639
International Journal of Dermatology Vol. 31, No. 9, September 1992
The present case as well as the previous cases of "malignant Spitz nevi" fit within the spectrum of histologic features seen in S&E nevi. The large size and deep extension are probably the most characteristic features of these lesions. These features as well as the clinical appearance in many cases increased the suspicion that these represent malignant lesions. The presence of nodal metastasis in sotne cases further complicated the decisions concerning diagnosis, therapy, and prognosis. Although metastatic spread is usually associated with malignant behavior, "benign metastasis" has been reported from other organs including mullerian foci seen in pelvic lymph nodes, benign thyroid tissue found in cervical nodes, and "benign metastasizing leiotnyomas" seen in women of child-bearing age.''"'' All these lesions are felt to have a litnited capacity to metastasize. They do not tnetastasize widely or lead to significant morbidity or mortality. The presence of benign melanocytes in lymph nodes occurs in two different forms. Cellular blue nevi have been found within the sinuses and parenchyma of local lymph nodes. This location is suggestive of true metastatic spread, and these lesions are all associated with a local skin lesion.^-** The other presentation of benign nodal melanocytic lesions is in the capsule and trabeculae of lymph nodes. This tnay be a result of aberrant embryonic migration of precursors cells and is usually not associated with a skin lesion.^"''' Although documented nodal metastasis of S&E nevi is rare, there is both clinical and histologic evidence that the potential for metastasis may be present. Lymphatic invasion in S&E nevi was a fairly frequent finding in a study of S&E nevi reported by Howat and Variend.'° In addition, there have been several reports of S&E nevi occurring as multiple, eruptive, or dissetninated lesions."""' Finally, the presence of plasma cells in the inflammatory infiltrate of melanomas is consid-
Figure 2. Fascicular arrangement of plump densely cellular spindle cells showing prominent nucleoli in a "malignant Spitz nevus." (hematoxylin and eosin, original magnification x 75)
Figure 3. Lymph node associated with the above lesion showing similar cells located in the sinuses and parenchyma, (hematoxylin and eosin, original magnification x 30) maturation of the melanocytes; a fascicular arrangement of cells within the lesion; dense cellularity; moderate to marked cellular pleomorphism; loss of cellular cohesion; ulceration; and sharp lateral circutnscription (Fig. 5).' When inflatned, these lesions contained lymphoid aggregates surrounding the lesion and within the lesion in a perivascular pattern. The infiltrate often contained plasma cells similar to other S&E nevi.^ In cases with lymph node metastasis, only one node was involved in all cases, and the nevus cells were similar to the cells in the original lesion (Fig. 6). Probably because of their large size and the frequent presence of ulceration, a number of these lesions were clinically felt to be malignant melanomas.' However, in spite of these histologic and clinical features and the presence of lymph node metastasis iti six cases, all lesions showed a benign biologic behavior with no evidence of recurrence or further metastasis.
Figure 4. Higher power view of the lymph node in Figure 3 shows a pattern of spindle cells and epithelioid cells similar to the skin lesion in Figure 2. (hematoxylin and eosin, original magnification x 75) 640
Malignant Spitz Nevus Skelton ct al.
Figure 5. "Malignant Spitz nevus" showing sharp lateral demarcation and a deep pushing margin extending into the subcutaneous fat. The lesion shows lymphoid aggregates around the lesion and perivascular within the lesion that contain many plasma cells, (hematoxylin and eosin, original magnification x 15) ered a prognostic indicator of lymph node tnetastasis, and plasma cells may be found in the inflatntnatory infiltrates of S&E nevi.'-'^ Possible explanations for the rarity of docutnented nodal metastasis are the young age of tnost patients with S&E nevi and tendency for these lesiotis to regress over titne.^ Since the original report, we have seen several cases referred to as "tnalignant Spitz nevus." Most of the cases have been nodular malignant melanomas. In each of these cases the pritnary histologic feature that differentiated the lesion from a "tnalignant Spitz nevus" was the presence of infiltrating margitis as opposed to well demarcated lateral margins and the rounded, pushing deep margin found in "tnalignant Spitz nevus." We report an additional case of "malignant Spitz nevus" with lymph node tnetastasis. It is important to report these lesions because they have itnplications for both treatment and prognosis of the patient.
Figure 6. Lymph node associated with above lesion showing similar cells located in the sinuses and parenchyma, (hematoxylin and eosin, original magnification x 75) 8.
9. to.
REEERENCES
1.
Spitz S. Melanomas of children. Am J Pathol 1948; 24:591-609.
2.
Paniago-Perreira G, Maize JG, Ackerman AB. Nevus of large spindle and/or epithelioid cells (Spitz's nevus). Arch Dermatol 1978; 114:1811-1823. Smith KJ, Barrett TL, Skelton HG, et al. Spindle cell and epithelioid cell nevi with atypia and metastasis (malignant Spitz nevus). Am J Surg Pathol 1989; 13:931-939. Meyer JS, Steinberg LS. Microscopically benign thyroid follicles in cervical lymph nodes. Gancer 1969; 24: 302-311.
3.
4.
5. 6.
7.
11. 12.
13.
14. 15.
Farhi DG, Silverberg SG. Pseudometastases in female genital cancer. Pathol Ann 1982; 1:47-74. Thomsen S, Morales AR. Soft tissue tumors. In: Silverberg SG, ed. Principles and practice of surgical pathology. New York: Wiley, 1983:222. McGarthy SW, Palmer AA, Bale PM, et al. Naevus cells in lymph nodes. Pathology 1974; 6:351-358.
16.
17.
641
Rodriquez HA, Ackerman LV. Gellular blue nevus. Glinicopathologic study of forty-five cases. Gancer 1968; 21:393-405. Johnson WT, Helwig EB. Benign nevus cells in the capsule of lymph nodes. Gancer 1969; 23:747-753. Howart AJ, Variend S. Lymphatic invasion in Spitz nevi. Am J Surg Pathol 1985; 9:125-128. Orita M, Obara K, Irimajiri T, et al. Multiple agminated juvenile melanoma. Dermatologica 1986; 172:58-61. Krakowsky A, Tur E, Brenner S. Multiple agminate juvenile melanoma: a case with a sunburn history and a review. Dermatologica 1975; 163:270-275. Patics GT, Borroni G, Rosso R, et al. Relapsing eruptive multiple spitz nevi or metastatic spitzoid malignant melanoma? Am J Dermatopathol 1987; 9:520-527. Prigent R. Spitz juvenile melanoma (multiple form). Ann Pediatr 1984; 31:673-675. Prose NS, Heilman E, Felman YM, et al. Multiple benign juvenile melanoma. I Am Acad Dermatoi 1983; 9: 236-242. Weimar VH, Zuehike RL. Multiple agminate spindle and epithelioid cell nevi in an adult. Arch Dermatol 1978; 114:1383-1384. Weissmann A, Harris MN, Roses DF, et al. Predication of lytnph node metastases from the histologic features of primary cutaneous malignant melanomas. Am J Dermatopathol 1984; 6:35-41.
MALIGNANT SPITZ NEVUS CDR HENRY G. SKELTON 111, MC USN, LTC KATHLEEN J. SMITH, MC USA, CDR THERESA T. HOLLAND, MC USN, COL MARIA-MAGDALENA TOMASZEWSKI, MC USA, AND COL GEORGE P. LUPTON, MC USA
Tbe patient Is a 22-year-old white woman, who was 16 years of age at the time of initial presentation. At that time, a lesion was removed from her left cheek, which was diagnosed as dermatofibrosarcoma protuberans. Four years later, a physical examination of the patient revealed an enlarged lymph node in the lower midline neck area. The lymph node was biopsied and both lesions were sent for further histopathologic examination. Histopathology: The original lesion was composed of densely cellular fascicles of plump spindle-shaped cells extending into the subcutaneous fat with a pushing not infiltrating margin (Fig. 1). Examination at higher power showed regular fascicles of plump spindle-shaped cells with prominent nucleoli. Occasional mitotic figures were seen, some present deep within the lesion (Fig. 2). The lymph node biopsy showed similar fascicles of spindled cells within the parenchyma surrounded by normal lymphoid tissue (Figs. 3 and 4). Mitotic figures were not found. Between the fascicles were areas of fibrosis. Both the skin and lymph node biopsies showed positive staining with S-100 protein (Chemicon 1:2000, ABC method). Tbe patient has bad no evidence of recurrence or further spread now 5.5 years after excision of the original lesion.
Figure 1. "Malignant Spitz nevus" of this case showing sharp lateral demarcation and a deep pushing margin extending into the subcutaneous fat. (hematoxylin and eosin, original magnification X 75)
DISCUSSION
Before Dr. Sophie Spitz established criteria for the diagnosis of spindle cell and epithelioid cell nevi (S&E neyi) in 1948, these lesions were considered histologically indistinguishable frotn malignant tnelanomas (MM).'-McWhorter and Woolner confirmed the benign clinical behavior of these lesions after reviewing similar lesions that had been seen at the Mayo Clinic' Specific criteria
reported by Alien and Spitz, which could be used to differentiate S&E nevi frotn MM, included (1) features of a compound nevus, (2) edetna and telangiectasia in the upper portion of the dermis, (3) nests of cells sharply separated from the surroutiditig keratinocytes, (4) large spindle or epithelioid cells, (5) Touton-like giatit cells, (6) abrupt transition between acantholytic cells in the junctional nests and the intact epidertnis, (7) relative sparsity of pigmentation, and (8) relative superficiality of the major latidtnarks of the lesions.' In 1989 a group of lesions were reported that had, in addition to the above features, a diatneter of greater than 1 cm, extension into the subcutaneous fat with a pushing as opposed to infiltrating margin, and in some cases lytnph node metastases.' Additional histologic features cotntnon to these lesions atid found within the spectrum of lesion classified as S&E nevi were mitoses, which could be present deep within the lesions; lack of
From the Department of Dermatopathology, Armed Forces Institute of Pathology, and the Walter Reed Army Institute for Research, Washington, DG. The opinions or assertions contained herein are the private views of the authors and are not to be considered as official or as reflecting the views of the department of the Army, or Navy or of the Department of Defense. Address for correspondence: Henry G. Skelton, M.D., Department of Dermatopathology, Armed Fot-ces Institute of Pathology, Washington, DG 20306. 639
International Journal of Dermatology Vol. 31, No. 9, September 1992
The present case as well as the previous cases of "malignant Spitz nevi" fit within the spectrum of histologic features seen in S&E nevi. The large size and deep extension are probably the most characteristic features of these lesions. These features as well as the clinical appearance in many cases increased the suspicion that these represent malignant lesions. The presence of nodal metastasis in sotne cases further complicated the decisions concerning diagnosis, therapy, and prognosis. Although metastatic spread is usually associated with malignant behavior, "benign metastasis" has been reported from other organs including mullerian foci seen in pelvic lymph nodes, benign thyroid tissue found in cervical nodes, and "benign metastasizing leiotnyomas" seen in women of child-bearing age.''"'' All these lesions are felt to have a litnited capacity to metastasize. They do not tnetastasize widely or lead to significant morbidity or mortality. The presence of benign melanocytes in lymph nodes occurs in two different forms. Cellular blue nevi have been found within the sinuses and parenchyma of local lymph nodes. This location is suggestive of true metastatic spread, and these lesions are all associated with a local skin lesion.^-** The other presentation of benign nodal melanocytic lesions is in the capsule and trabeculae of lymph nodes. This tnay be a result of aberrant embryonic migration of precursors cells and is usually not associated with a skin lesion.^"''' Although documented nodal metastasis of S&E nevi is rare, there is both clinical and histologic evidence that the potential for metastasis may be present. Lymphatic invasion in S&E nevi was a fairly frequent finding in a study of S&E nevi reported by Howat and Variend.'° In addition, there have been several reports of S&E nevi occurring as multiple, eruptive, or dissetninated lesions."""' Finally, the presence of plasma cells in the inflammatory infiltrate of melanomas is consid-
Figure 2. Fascicular arrangement of plump densely cellular spindle cells showing prominent nucleoli in a "malignant Spitz nevus." (hematoxylin and eosin, original magnification x 75)
Figure 3. Lymph node associated with the above lesion showing similar cells located in the sinuses and parenchyma, (hematoxylin and eosin, original magnification x 30) maturation of the melanocytes; a fascicular arrangement of cells within the lesion; dense cellularity; moderate to marked cellular pleomorphism; loss of cellular cohesion; ulceration; and sharp lateral circutnscription (Fig. 5).' When inflatned, these lesions contained lymphoid aggregates surrounding the lesion and within the lesion in a perivascular pattern. The infiltrate often contained plasma cells similar to other S&E nevi.^ In cases with lymph node metastasis, only one node was involved in all cases, and the nevus cells were similar to the cells in the original lesion (Fig. 6). Probably because of their large size and the frequent presence of ulceration, a number of these lesions were clinically felt to be malignant melanomas.' However, in spite of these histologic and clinical features and the presence of lymph node metastasis iti six cases, all lesions showed a benign biologic behavior with no evidence of recurrence or further metastasis.
Figure 4. Higher power view of the lymph node in Figure 3 shows a pattern of spindle cells and epithelioid cells similar to the skin lesion in Figure 2. (hematoxylin and eosin, original magnification x 75) 640
Malignant Spitz Nevus Skelton ct al.
Figure 5. "Malignant Spitz nevus" showing sharp lateral demarcation and a deep pushing margin extending into the subcutaneous fat. The lesion shows lymphoid aggregates around the lesion and perivascular within the lesion that contain many plasma cells, (hematoxylin and eosin, original magnification x 15) ered a prognostic indicator of lymph node tnetastasis, and plasma cells may be found in the inflatntnatory infiltrates of S&E nevi.'-'^ Possible explanations for the rarity of docutnented nodal metastasis are the young age of tnost patients with S&E nevi and tendency for these lesiotis to regress over titne.^ Since the original report, we have seen several cases referred to as "tnalignant Spitz nevus." Most of the cases have been nodular malignant melanomas. In each of these cases the pritnary histologic feature that differentiated the lesion from a "tnalignant Spitz nevus" was the presence of infiltrating margitis as opposed to well demarcated lateral margins and the rounded, pushing deep margin found in "tnalignant Spitz nevus." We report an additional case of "malignant Spitz nevus" with lymph node tnetastasis. It is important to report these lesions because they have itnplications for both treatment and prognosis of the patient.
Figure 6. Lymph node associated with above lesion showing similar cells located in the sinuses and parenchyma, (hematoxylin and eosin, original magnification x 75) 8.
9. to.
REEERENCES
1.
Spitz S. Melanomas of children. Am J Pathol 1948; 24:591-609.
2.
Paniago-Perreira G, Maize JG, Ackerman AB. Nevus of large spindle and/or epithelioid cells (Spitz's nevus). Arch Dermatol 1978; 114:1811-1823. Smith KJ, Barrett TL, Skelton HG, et al. Spindle cell and epithelioid cell nevi with atypia and metastasis (malignant Spitz nevus). Am J Surg Pathol 1989; 13:931-939. Meyer JS, Steinberg LS. Microscopically benign thyroid follicles in cervical lymph nodes. Gancer 1969; 24: 302-311.
3.
4.
5. 6.
7.
11. 12.
13.
14. 15.
Farhi DG, Silverberg SG. Pseudometastases in female genital cancer. Pathol Ann 1982; 1:47-74. Thomsen S, Morales AR. Soft tissue tumors. In: Silverberg SG, ed. Principles and practice of surgical pathology. New York: Wiley, 1983:222. McGarthy SW, Palmer AA, Bale PM, et al. Naevus cells in lymph nodes. Pathology 1974; 6:351-358.
16.
17.
641
Rodriquez HA, Ackerman LV. Gellular blue nevus. Glinicopathologic study of forty-five cases. Gancer 1968; 21:393-405. Johnson WT, Helwig EB. Benign nevus cells in the capsule of lymph nodes. Gancer 1969; 23:747-753. Howart AJ, Variend S. Lymphatic invasion in Spitz nevi. Am J Surg Pathol 1985; 9:125-128. Orita M, Obara K, Irimajiri T, et al. Multiple agminated juvenile melanoma. Dermatologica 1986; 172:58-61. Krakowsky A, Tur E, Brenner S. Multiple agminate juvenile melanoma: a case with a sunburn history and a review. Dermatologica 1975; 163:270-275. Patics GT, Borroni G, Rosso R, et al. Relapsing eruptive multiple spitz nevi or metastatic spitzoid malignant melanoma? Am J Dermatopathol 1987; 9:520-527. Prigent R. Spitz juvenile melanoma (multiple form). Ann Pediatr 1984; 31:673-675. Prose NS, Heilman E, Felman YM, et al. Multiple benign juvenile melanoma. I Am Acad Dermatoi 1983; 9: 236-242. Weimar VH, Zuehike RL. Multiple agminate spindle and epithelioid cell nevi in an adult. Arch Dermatol 1978; 114:1383-1384. Weissmann A, Harris MN, Roses DF, et al. Predication of lytnph node metastases from the histologic features of primary cutaneous malignant melanomas. Am J Dermatopathol 1984; 6:35-41.
