spindle and epithelioid cell nevi in the adult. clinicopathologic report of 26 cases

SPINDLE AND EPITHELIOID CELL NEVI IN THE ADULT Clinicopathologic Repor t of 26 Cases

R E N ~ ECHEVARRIA, MD, AND LAUREN V. ACKERMAN, MD

The spindle and epithelioid cell nevi occur in adults rarely but should not be confused with malignant melanomas. One criteria for differentiation is the homogeneity of the spindle cell nevus. Twenty-six of these lesions in adults were essentially similar histologically to those in children. Clinically the dis- tribution also compares but the lesions tended to be more pigmented and often feared to be malignant. The nevus may arise de novo in adult life or may have been present since childhood and then grow and increase in pigmentation. I n no instance was spontaneous ulceration present. The pure spindle cell nevus is the most frequent whereas pure spindle cell melanomas are rare. Pure epithelioid cell nevi were not found in adults. Adequate local excision is the

may follow inadequate excision but is treatment of choice. Local recurrence not evidence of malignancy.

HE VARIETY OF COMPOUND NEVI THAT SPITZ T described in children in 194815 and designated “juvenile melanoma” has received con- siderable attention. I n 1953 Allen and Spitz2 reported the same lesion in adolescents and adults and in Iater papers Allen stated that about 15% of juvenile melanomas he had seen occurred in adults.4r5 The occurrence of these nevi in adults was also pointed out by Helwig.13 By 1957 Allen had examined 34 cases in adults, the oldest being a 56 year old woman? Kernen and Ackerman reviewed the literature in 1960 and stated that only 4 well- documented cases of juvenile melanoma in adults could be found.10 Recently, a number of reports of these lesions occurring in persons older than 20 have appeared in the European literature: Duperrat, 4 cases;? Gartmann, 5 cases;8 Schuhmachers-Brendler, 8 cases.14 Most of these patients were between ages 20 and 40; the oldest patient was age 48.8

Many pathologists may not have seen this lesion in adults or, in some instances, may have diagnosed i t as malignant melanoma. During the last 19 years, 26 examples of these nevi in adults have been seen at Barnes Hospital, Washington University School of Medicine, Division of Surgical Pathology, which will be reported here in some detail.

From the Division of Surgical Pathology, Washington Universitv School of Medicine. 660 South Euclid. St. Louis, Mb. 63110.

Received for publication June 30, 19GG.

MATERIALS AND METHODS

Ninety-one cases of spindle cell nevus or epithelioid cell nevus were seen in this institu- tion from 1946 to 1965. Of these 65 occurred in children and teenagers. The remaining 26 lesions excised from persons older than 20 form the basis of this report. Seventeen of these were submitted by outside pathologists for consultation. The remaining 9 came from patients in this hospital. As there are approxi- mately 17,000 surgical specimens per year in this service, the infrequency with which the lesion comes to attention is evident. Cases 1 through 6 were reported previously.1°

CLINICAL FEATURES (TABLE 1)

About half of the patients were between ages 20 and 30. The ages of the remainder were evenly distributed up to 65. Three nevi occurred in individuals in their sixties. All patients were Caucasian, of whom 16 were women and 10 were men. The most common sites of the lesion was the face (10 cases); the remaining lesions were located in the upper extremities (7), the lower leg (3) and the trunk (6).

Twenty nevi presented as raised dome- shaped lesions (Fig. 1). T h e remaining were flat spots. Discoloration was present in prac- tically every instance. About half of the nevi were described as brown or black. The classi- cal red, hemangiomatous or granulomatous appearance as reported in children was described in only 3 of the adult cases.

175

176 CANCER February 1967 Vol. 20

TABLE 1. ~~ - ~~

Case S.P. Pathological Clinical Size Con- no. no. Age Sex Race diagnosis diagnosis Location (cm) Color figuration

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

21

22

23

24

25

26

54155

56010

51-5875

54-6689

57-5401

59-2967

59-4260

59-6783

59-9591

60-4659 60-5076 61-1412

61-7527

62-3 175 62-3733

62-3549

62-3718

62-7694

63-3105

63-6400

63-5814

63-6006

63-9107

64-4252

65-5513

65-7323

65-99 17

65-9918

65

64

62

56

21

28

41

40

39

26

57

22

52

40

27

22

20

38

55

20

22

42

24

34

44

20

F W

M W

F W

F W

M W

F W

F W

M -

M W

F W

F -

F W

F W

M -

M W

M W

F W

F W

F W

M W

F W

M W

F W

F W

M W

F W

Spindle cell nevus Spindle cell nevus Spindle cell nevus Spindle cell nevus Spindle cell nevus Spindle cell nevus Spindle cell nevus Spindle cell nevus Spindle cell nevus Spindle cell nevus Mixed

Spindle cell nevus Mixed

Spindle cell nevus Spindle cell nevus Spindle cell nevus Spindle cell nevus Spindle cell nevus Spindle cell nevus in a compound nevus Spindle cell nevus Mixed

Spindle cell nevus Spindle cell nevus Spindle cell nevus Spindle cell nevus Spindle cell nevus

Melanoma

“Growth”

Mole

Senile keratosis Nevus

Pigmented nevus

-

Pigmented basal cell ca. Nevus

Mole

Carcinoma vs. lympho- cytoma cutis -

Nevus

Benign nevus

Mole

Hemangioma

Basal cell cell

-

Cystic mass

Melanoma

Check

Ear

Dorsum of hand Forearm, ext. surf. Upper lip

Back of axilla Lower leg

Arm

Cheek

Buttock

Outer canthus Leg

Cheek

Canthus

Forehead

Chest

Back

Cheek

Shoulder

Flank

Nose tip

Back

Dorsum of hand Dorsum of wrist Chest

Lower leg

1 x 2

0.5

2

0.7

0.2 X0.3

0.8

2 X 3

0.1

0.8

1 x1.2

- “Small”

1

0.5

1

0.4

0.8

1

3 X 2

0.6

0.3

0.5

2

1 X0.4

0.5

1.2 x1.5

Black

Purple

Blue

Black

Brown

Blue-brown

Brown

Brown-black

Pigmented

Brown

Pigmented

Pigmented

Red

- Flesh

Red-black

Tan

Tan

Pigmented

Red

Flesh

Blue-brown

Red

Yellow

-

Purple

Elevated

Elevated

Flat

Flat

Elevated

Elevated

Flat

Flat

Raised

Raised

Flat

Elevated

Raised

Raised

Raised

Raised

Flat

Raisd

Raised

Raised

Raised

Raised

Raised

Raised

Raised

Raised

The two largest lesions measured 3 x 2 cm; three others were 2 cm and the remainder were 1 cm or smaller.

The reported duration of the lesions varied from 2 months to “since early childhood.” Most often the lesion had been noticed for a period of 2 to 6 months. The majority were said to have grown slowly. Bleeding upon trauma occurred in only 2 cases. Of signifi- cance is that spontaneous ulceration was not present in a single case. This is in contrast to

the frequent spontaneous ulceration of malignant melanomas.

CLINICAL DIAGNOSIS (TABLE 1)

T h e neval nature of these lesions was sus- pected in 10 cases. Most frequently i t was thought of as a benign nevus rather than a malignant melanoma. Basal cell carcinoma, senile keratosis and hemangioma were the other clinical diagnoses. A preoperative diag-

No. 2 SPINDLE AND EPITHELIOID CELL NEVI - Echeuawia and Ackerman 177

FIG. 1. Case 22. Spindle cell nevus in a 42-year-old woman. Low-power view demonstrates the typical dome-shaped lesion, delimited by an epidermal collarette, sharply circumscribed, very cellular and divided into nests. Note pushing margins (Surg. path. 64-4252; W.U. neg. 66-552; X29).

nosis of spindle cell nevus or “juvenile melanoma” was not made in any instance.

TREATMENT (TABLE 2)

In all cases local surgical excision was done. Four patients had re-excision of the area without finding residual tumor. In one of these (case 19) regional lymph node dissection was done and no tumor was found in the nodes.

FOLLOW-UP (TABLE 2)

Follow-up information was obtained in 22 of the 26 patients. The remaining 4 could not be traced.

Local persistence of the lesion occurred in one patient (case 14). This was excised and the patient died 4 years after the original excision of metastatic colonic cancer, without further trouble from his nevus.

HISTOLOGIC FEATURES

The cells composing these nevi are of 3 types: spindle, epithelioid and multinucleated giant cells. The spindle cells are cigar-shaped

and distinguishable from the cells of the common nevi mainly by their larger size, distinct cytoplasm and larger nuclei with prominent nucleoli (Fig. 2, 3, 6). The epithelioid cells are large, polygonal with distinct borders and nuclei which are similar to those of the spindle cell (Fig. 5, 9). The multinucleated giant cells are larger epithelioid cells with up to 10 or 20 nuclei (Fig. 5). Whereas the spindle cells are fairly uniform in size and shape in a given tumor, epithelioid and giant cells tend to vary much more in these respects (Figs. 8,

The nevi in this series were classified according to the predominance of the above cell types. No pure epithelioid cell nevus was found. There were 23 spindle cell nevi and 3 of mixed cell type. The nevi were considered of mixed cell type when the epithelioid ele- ments were fairly abundant and distributed evenly throughout the lesion (Fig. 8, 9). A few epithelioid cells were present in all spindle cell nevi but they were limited to the junctional theques and superficial areas of the lesion (Fig. 5). Multinucleated giant cells were con- spicuous in only 5 cases (Fig. 5).

One of the lesions (Case 19) consisted of a

9) *


TABLE 2. Case Stated duration no. of lesion Symptoms Therapy Follow-up

12.5 yr. 12 yr. 9 yr. 4 yr., 5 mo. 7+ yr.

6 yr. 5 yr. (dead of metastatic colon carcinoma) Lost to follow-up Lost to follow-up 1 yr., 8 mo. (dead of diseminated ad- enocarcinoma from cervix)

1 yr., 7 mo. Local recurrence, excision 2 yr. later; 4 yr.: dead of met. colon cancer 2 yr., 4 mo. 2 yr.

1 yr., 4 mo.

2 yr. 2 yr.

Lost to follow-up Lost to follow-up

1 2 3 4 5

6 7

8 9

10

11 12 13 14

15 16

17

18 19

20

21

22 23

24 25 26

15 yr. 20 yr.

Enlarged for 4 mo. Enlarged in last yr.

Enlarged Cut shaving

Enlarged

-

-

Local excision Local excision Local excision Local excision Local excision

Local excision Local excision

1 yr. 6 mo.

Since early childhood

3 yr. Since childhood

Local excision Local excision Local excision, re-excision : no tumor

Local excision Local excision Local excision Local excision

- 19 yr.

Since childhood -

Changed color: brown to blue

- -

Enlarged -

I f yr.

Local excision Local excision

Local excision

Local excision Local excision, re-excision, lymph node dissection (no tumor) and perfusion Local excision, re-excision, no tumor 1 mo.

4 mo. 1 yr.

Some time

Enlarged Enlarged and increased

pigmentation Enlarged

(during pregnancy)

Enlarged -

Enlarged 9 mo. 6 mo.

later Local excision, skin 9 mo.

2 mo. 9 mo.

Enlarged

Enlarged and bled -

1 yr., 4 mo.

7 mo. 1 yr.

graft Local excision

“Electrosurgery with dessication of base” re-excision, no tumor

Local excision Local excision Local excision

7 mo. 10 mo. 6 nio.

- - 3 mo.

focus of spindle cell nevus in a common compound nevus. Similar occurrence of spindle cell nevi in common compound nevi have been reported in children.l0,13

According to the presence of junctional theques as defined by Helwig,9 there were 16 compound, 8 intradermal and 2 junctional nevi in this series.

Mitoses were rare in all but 3 lesions. In most cases from 2 mitoses per section to one every 3 or 4 sections were present. In 4 lesions no mitoses were found: 2 nevi had 2 or 3

mitoses in nearly every high power field (hpf) examined (Fig. 3) and a third one had one mitosis every 5 or 6 hpf. There was no correla- tion between the number of mitoses and the cellularity or fibrosis of the lesion. Of the 3 nevi with many mitoses 2 were cellular lesions and one was fibrotic. Of the 4 nevi without mitotic activity one was cellular and three were fibrotic. Atypical mitotic figures were not found.

Melanin pigment was present in 10 tumors, usually outside the nevus cells, within melano-

rn FIG. 2. Case 22. Whorled pattern of spindle cells and absence of pleomorphism. Cells are

compactly arranged (Surg. path. 64-4252; W.U. neg. 66-562; ~ 3 0 0 ) . FIG. 3. Case 26. Plump spindle cells like these, with uniform nuclei and abundant distinct

cytoplasm are most characteristic of many spindle cell nevi. They are easily distinguished from the spindle cells of malignant melanoma (Figs. 1 1 and 13) (Surg. path. 65-9918: ~300).

No. 2 SPINDLE AND EPITHELIOID CELL NEVI - Echevarria and A c k e r m m 179

phages or free. Microscopically, heavy pigmentation was only present in 3 cases. In a few nevi most of the pigment accumulated be- neath the lesion.

In all the nevi the cells were compactly or cohesively grouped (Fig. 1 4 , 6). Shrinkage of the cells away from each other was present only in junctional theques and in the most superficial areas (Figs. 4, 5, 7). The pattern of the groupings of the cells was variable but consistent for any given lesion. In 5 cases there was marked segregation into sharply circumscribed nests of cells (Fig. 1). Whorling pattern was striking in 4 other cases (Fig. 2). Seven lesions showed grouping in interlacing bundles (Fig. 6). The so-called “rained down” pattern of the spindle cells was present in 10 tumors, always in the upper dermis (Fig. 4). The deeper parts of 4 of the latter lesions showed the interlacing swirls of spindle cell arrangement (Fig. 6).

The epidermis overlying these nevi was never ulcerated except where previous biopsy had been taken. In 9 instances hyperkeratosis

180 CANCER February 1967 VOl. 20

was present (Fig. 4); pigment and pyknotic cells were seen focally in the stratum corneum in some of these. Acanthosis was present in 7 cases (Fig. 4). The remainder showed thin- ning of the overlying epidermis (Fig. 1). A common feature, irrespective of the epidermal thickness, was the elongation of the rete ridges (Fig. 4, 7). When the lesion was elevated, the acanthotic ridges tended to circumscribe the tumor with a sort of “epidermal collarette” similar to the one usually seen in the granu- loma pyogenicum (Fig. 1).

Telangiectasis, usually limited to the sub- epidermal area, were prominent in 7 lesions (Fig. 4). A more or less defined narrow band of edematous collagen separated the bulk of the tumor from the overlying epidermis in the intradermal lesions (Fig. 4). The deep margin of 18 of the tumors was sharp, giving them a well-circumscribed appearance on low-power examination. In 7 of these the deep margin was pushing in character, with compressed appearance of the underlying collagen (Fig. 1). Fibrosis of an appreciable degree was present

FIG. 4. Case 23. Spindle cell nevus in a 24-year-old woman. “Rained down” pattern with telangiectasis and band of collagen separating the lesion from the epidermis. There is hyperkeratosis and elongation of the rete (Surg. path. 65-5513; W.U. neg. 66-558; ~ 8 5 ) .

No. 2 SPINDLE AND EPITHELIOID CELL NEVI - Echevawia and Aclzermapz 181

FIG. 5. Case 23. Superficial area of spindle cell nevus in Figure 4, showing multinucleated giant cells and epithelioid cells (Surg. path. 65-5513; x300).

in 10 nevi and was prominent in 5 of these. In the latter cases the fibrotic reaction separated the individual cells (Figs. 7, 8 and 9). These nevi did not have a sharp deep margin due to the blending of the fibrous reaction with the surrounding fibrous tissue (Fig. 7). The deep margin of the tumor was at the level of the upper dermis in 9 instances, at the mid- dermis in 5, and at the level of the lower dermis wrapping about the sweat glands in 6. In 2 instances the nevus reached the subcutaneous fat; in one it was compressing it, in another the neval cells were admixed diffusely with fat cells.

The amount of lymphocytic reaction was marked in only 4 cases, moderate in 10 and

absent or minimal in 12. In 10 instances a band of lymphocytes tended to demarcate the deep margin of the lesion.

The recurrent lesion (case 14, SP 62-3549) showed large discrete compact nests of whorled spindle cells in the muscle and subcutaneous tissue, with pushing borders and marked surrounding lymphocytic reaction.

Perineural sheath growth of spindle cells was found in one recent case (26, Table 2). This lesion showed all the typical features of a spindle cell nevus. Another benign lesion which has been reported before to show perineural sheath growth, is sclerosing adenosis of the breast.1

Comparison with spindle and epithelioid


FIG. 6. Case 23. The spindle cells in this case are thinner, with less distinct cytoplasm than those in Figure 3. Individually they are difficult to differentiate from those of the spindle cell melanoma in Figures 11 and 13, however, there is a fair amount of fibrilar collaeen in the background and- a compact appearance lacking in the spindle cell melanoma ({urg. path. 65-5513; W.U. neg. 66-563; x300).

cell nevi of children: The clinical features of these nevi in adults have been very similar to those of the lesion in children. Whether adults or children, both sexes were about equally affected; all patients were Caucasian; the preferred location was the face, followed by the extremities and trunk, and most lesions were elevated above the skin surface. The clinical diagnosis in children were more varied. In about one third of the instances the lesions were believed to be some form of melanotic tumor, usually benign nevus. In only about 4 cases was malignant melanoma feared. In 2 cases the correct preoperative diagnosis was made. Other diagnoses were along the same lines reported previously.10

The size of the lesion in children com- pared with that of the adults is usually smaller than 1.5 cm in diameter. Growth of the nevus was reported in 19 instances. Clinical ulceration of the nevus was seen in the case of a 19- month-old child. To date, there have been 3

local recurrences of the lesions in children, the longest interval between excision and this event having been 4 years. In 2 of these the persistence of the tumor followed treatment of the initial lesion with cautery. Radical treatment was carried out elsewhere in an 18-year- old boy with a leg lesion. An inguinal node dissection showed all nodes examined to be free of tumor. Four years later there was no further evidence of disease.

Histologically most of the nevi in adults were pure spindle cell type and a few were mixed spindle-epithelioid cell type. No pure epithelioid cell nevus was found in adults. In contrast there were 6 pure epithelioid cell nevi in children. It has been suggested that some differences can be detected in the histologic pattern of the adult and juvenile lesions. For instance Allen found, as a rule, involutional fibrosis and extension to a greater depth in the adult tumor.5 Kernen and Ackerman stated that the only difference seemed to be

No. 2 CANCER February 1967 183

FIG. 7. Case 6. Spindle ccll nevus in a 28-year-old woman said to have been present 3 years. This case illustrates fibrosis in the deeper parts of the lesion with blending deep margin. The deeper cells are smaller and approach the size and appearance of mature intradermal nevus cells (Surg. path. 59-2967; X54).

a greater amount of pigment in the adult lesion;1° this review corroborates this finding. The deep dermal and even subcutaneous extension appears also fairly frequent. 0 therwise the nevi in adults were as cellular as those in children and as stated fibrosis was striking in only 5 cases. “Maturation” in the depth of the lesion was present in one instance (Fig. 7).

COMMENT

At Washington University Medical School these lesions are designated “spindle cell nevus” after Helwigg or epithelioid cell nevus.g.10,13 The term “juvenile melanoma” is not used because the same lesion appears in

adults. The word “melanoma” is avoided because this word, particularly in the United States, indicates a malignant lesion.

The clinicopathologic concept of spindle cell nevi in children is well established. With the relative infrequency of malignant melanomas in early life, a diagnosis of benign lesion can be made in most cases. On the other hand, in adults malignant melanomas are more frequent than spindle cell nevi. There is then a danger here of mistaking a spindle cell nevus for a malignant melanoma, which may lead to radical surgery such as a lymph node dissection. It is important to keep in mind the existence of this rare benign neval lesion in adults.


FIG. 8. Case 13. Fifty-two-year-old woman. Example of mixed spindle-epithelioid cell nevus. There is marked fibrosis of the lesion. The presence of epithelioid cells imparts a more pleomorphic appearance to the pattern (Surg. path. 62-3175; xl60).

FIG. 9. Case IS. High power detail of epithclioid and spindle cells in same nevus as Figure 8 (Surg. path. 62.3175; x300).

No. 2 SPINDLE AND EPITHELIOID CELL NEVI - Echevarria and Ackerman

FIG. 10. Selected area in a malignant melanoma with fascicles of spindle cells. Small nevus- like cells are present in alveolar arrangement in the upper part of the field, and in noncohesive sheet in the lower part. The latter cell type is not found in a spindle cell nevi (Surg. path. 63-8836; XISO).

FIG. 11. High-power detail of spindle cells and small nevus-like cells of the lesion in Figure 10. The spindle cells are very similar to those of the spindle cell nevus in Figure 6. There is no fibrosis, however, and the cells are loosely arranged (Surg. path. 63-8836; ~460).

185


FIG. 12. This bulky ulcerated lesion of the sole of the foot is an uncommon pure spindle cell melanoma (W.U. neg. 66-555; x85).

FIG. 13. Detail of spindle cell melanoma in Figure 12. The similarity of these to those of the spindle cell nevus is obvious (compare with Figure 6). Note bizarre nucleus (lower center) and loose arrangement of cells (W.U. neg. 66-564; ~300).

No. 2 SPINDLE AND EPITHELIOID CELL NEVI - Echeuarria and Ackerman

FIG. 14. Pure epithelioid cell lesion originally misdiagnosed as epithelioid cell nevus, from the shoulder of a 27-year-old man. One month after excision an axillary lymph node dissection showed metastatic malignant melanoma. Death 2 years later with disseminated disease. Nesting and well-differentiated epithelioid cells, similar to epithelioid cell nevi of children, were mislead- ing. Lesion had undergone spontaneous ulceration (Surg. path. 61-9196; W.U. neg. 66-557; ~ 8 5 ) .

187

FIG. 15. Detail of epithelioid cells of the lesion in Figure 14. The lack of coherence of the cells is characteristic of malignant melanomas. Only an occasional mitosis was present in this lesion (Surg. path. 61-9196; W.U. neg. 66-561).


FIG. 16. Selected area in a malignant melanoma to show epithelioid and multinucleated giant cells. Individually both types may he very similar to those found in junctional and superficial areas or in the mixed spindle-epithelioid cell nevi (Surg. path. 63-610; ~ 4 6 0 ) .

There is no single histologic criterion to label a particular lesion benign or malignant. Originally,l5 the multinucleated giant cells were thought to be the only distinctive feature to permit a diagnosis of benign lesion. Al- though helpful when present, giant cells indis- tinguishable from these may be present in malignant melanomas (Fig. 16). The typical spindle cell nevus of the adult is elevated, dome-shaped, likely to be located in the face or extremities, somewhat pigmented, smaller than 1.5 cm in diameter, not ulcerated and slowly enlarging. It probably will have been excised locally, the surgeon suspecting malignant melanoma. Histologically, most often it will be compound and well be composed of spindle cells with some epithelioid cells present in junctional position. Reassuring features will be the pushing margins, the nesting of the cells, the compactness of the packing of the cells except in the junctional theques and superficial dermis, a band of edematous collagen separating the bulk of the tumor from the overlying often compressed

epidermis and sometimes the marked fibrosis of the lesion. In the presence of these findings extension deep in the dermis or even to the subcutaneous fat need not be worrisome. The lesion will appear cytologically benign with little pleomorphism. There will be few mitoses although exceptionally as many as 2 or 3 mitoses per hpf may be found. Atypical mitotic figures, however, will not be present.

Malignant melanomas are composed of epithelioid cells, spindle cells and small nevus- like cells.12 The characteristic small nevus- like cells (Fig. 10, 11) are not present in the benign lesion so the findings of such areas is important in the differential diagnosis. Usually malignant melanomas are not homo- genous and areas composed of each of the 3 cell types can be found in any given lesion (Fig. 10).

If a lesion is composed exclusively of epithelioid cells, it is likely to be a malignant melanoma (Fig. 14-16). Pure epithelioid cell nevi in adults have not been seen in this series. When a lesion is composed of both

No. 2 SPINDLE AND EPITHELIOID CELL NEVI - Echeuarria and Ackerman 189

spindle and epithelioid cells it may appear quite pleomorphic. The 3 such mixed cell type benign lesions in this series have shown much fibrosis (Figs. 8, 9). Malignant melanomas composed solely of spindle cells are fortunately exceptional (Figs. 12, 13). These may be very difficult to differentiate from spindle cell nevi that may be as cellular and may have many mitoses occasionally. In this situation it may

prove worthwhile to cut multiple sections and look for other areas where the more easily recognizable malignant epithelioid and nevus- like cells may be present. If the lesion is ulcerated (Fig. 12), it is probably malignant. Lack of cohesion of the cells throughout the lesion, not limited to junctional areas and upper dermis, favors the diagnosis of malignant melanoma (Fig. 10-16).

REFERENCES

1. Ackerman, L. V.: In Proceedings of the Twenty- second Seminar of the American Society of Clinical Pathologists. American Society of Clinical Pathologists, 1957; p. 65, Fig. 37.

2. Allen, A. C., and Spitz, S.: Malignant melanomas -A clinicopathologic analysis of the criteria for diagnosis and prognosis. Cancer 6:l-45, 1953.

3. ~ : Juvenile melanoma and malignant mcla- noma. Surg. Gynec. Obstet. 104:753-754, 1957.

4. ___ : Juvenile melanomas of children and adults and melanocarcinomas of children. A M A Arch. Dermutol. 82:325-335, 1960.

5. ___ : Juvenile melanomas. In The Pigment Cell -Molecular, Biological and Clinical Aspects-Part I. Ann. N.Y. Acud. Sci. 100:29-48, 1963.

6. Duperrat, M. B.: The juvenile melanoma. BuZ. SOC. Franc. Derm. Syph. 62:500-504, 1955.

7. ___ , and Mascaro, J. H.: Anatomoclinical study of four cases of Spitz tumor in adults. Zbid. 68:

8. Gartmann, H.: Das sog. juvenile melanom. Munchen. M e d . Wschr. 104:587-592, 1962.

9. Helwig, E. B., Seminar on skin neoplasms and dermatoses. In Proccedings of the 20th Seminar of the American Society of Clinical Pathologists, Sept. 11,

472-478, 1961.

1954. American Society of Clinical Pathologists, 1955: p. 63-67.

10. Kernen, J. A., and Ackerman, L. V.: Spindle cell nevi and epithelioid cell nevi (so-called juvenile melanoma) in children and adults-A clinicopathologic study. Cancer 13:612-625, 1960.

11. Kopf, A. W., and Andrade, R.: A histologic study of the dermoepidermal junction in clinically “intradermal nevi” employing serial sections-I. Junc- tional theques. In The Pigment Cells-molecular, biological and clinical aspects-Part I. Ann. N . Y . Acud. Sci. 1OO:ZOO-218, 1963.

12. Lund, H. Z., and Kress, J. H.: Melanotic tumors of the skin. In Atlas of Tumor Pathology, sec. 1, fasc. 3, Washington, D. C. Armed Forces Institute of Path- ology p. 51-54.

13. McWhorter, H. E., and Woolner, L. B.: Pig- mented nevi, juvenile melanomas and malignant melanomas in children. Cancer 7:564-585, 1954.

14. Schuhmachers-Brendler, R.: Beitrag zur klinik und histologie der naevocellulares-Sowie des juvenilen melanoms-11. Mitteilung-Die Sonderstellune des juvenilen melanoms-Arch. I&. Exp. Derm. 21f600- 626, 1963.

15. Spitz, S.: Melanomas of childhood. A m . J . Path. 24~591.609, 1948.

spindle and epithelioid cell nevi in the adult. clinicopathologic report of 26 cases

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