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Desmoplastic malignant melanoma of the gingiva
Desmoplastic malignant melanoma of the gingiva .
.
Kenji Kurihara, MD, PhD,a Eitaro Sanada, DDS,b Shinya Yasuda, DDS,b and Hiroshi Yamasaki DDS, PhD,C Uwajima and Fukuoka, Japan UWAJIMA
CITY
HOSPITAL
AND
FUKUOKA
UNIVERSITY
HOSPITAL
A case of desmoplastic melanoma in a 58-year-old man is reported. This rare malignancy occurred in the maxillary alveolus, appearing as an epulis. Histologically, the tumor was flanked by melanocytic proliferation in the adjacent mucosae. At the time of local recurrence after partial maxillectomy, the tumor showed a polypoid growth, with an increase in cellularity and mitotic rate resembling spindle cell carcinoma. The value of immunostaining for diagnosis is stressed. (ORALSURCORALMEDORALPATHOL~~~~;~~:~O~-~)
I
n 197 1 Conley et al. 1reported a rare variant of malignant melanoma that had the clinical and histologic appearance of a fibrous tumor, for which they coined the term “desmoplastic melanoma.” We report a case of desmoplastic melanoma of the gingiva, with the clinical appearance of an epulis, that resembled spindle cell carcinoma at the time of local recurrence. Immunostaining employing the peroxidase-antiperoxidase (PAP) method proved useful in securing the correct diagnosis. CASE REPORT
In March 1988a 58-year-old man visited the Department of Oral Surgery, Uwajiwa City Hospital, with a complaint of tumor on the gum. The patient first noticed the tumor about 1 year ago, and it had increased in size gradually. Examination revealed a firm elevated tumor with normalappearing mucosa on the right maxillary alveolus in the cuspid-premolar region. The 1.5 cm tumor had a smooth mucosal surface. Adjacent to the main tumor mass were two smaller lesions, including a verrucous mucosal elevation and a brown macular pigmentation (Fig. 1). A clinical diagnosis of epulis was made, and a biopsy was performed. A di-
Fig. 1. Lingual aspect of surgical specimen removed in March 1988 shows elevated lesion similar to epulis.
amination revealed a 2.5 cm polypoid tumor with superficial ulceration of the gingiva adjacent to second premolar
agnosis of epulis fibromatosa with atypical proliferation of
(Fig. 2). Cervical lymph nodes were not palpable,
melanocytes was initially rendered by the hospital pathologist, and a partial maxillectomy was performed (Fig. 1). In October 1989 the patient was admitted again to our institute because of a rapidly growing recurrent tumor. Ex-
whole-body computerized tomography revealed probable maxillary involvement with no other evidence of systemic disease.A biopsy revealed a recurrent melanoma with in-
aDepartment of Pathology, Uwajima City Hospital. bDepartment of Oral Surgery, Uwajima City Hospital. CDepartment of Oral Surgery, Fukuoka University Hospital 7/14/30986
and
creased cellularity. The patient was transferred to another institution for a total maxillectomy and is alive 31 months after the initial surgery.
MATERIAL AND METHODS Routine histologic sections were prepared from the formalin-fixed samples and stained with hematoxylin201
202
Kurihara
et al.
0~41.
SURC ORAL
MED ORAL PATHOL August 1992
Fig. 2. Recurrent tumor shows polypoid growth with ulceration.
eosin and Fontana-Masson. Histologic sections were also examined on the basis of the PAP method for S- 100 protein, neuron-specific enolase, keratin, and vimentin. All the antibodies were obtained from Dako Co. (Glostrup, Denmark). RESULTS Initial specimens:
March 1988
The elevated epulis-like lesion consisted of a mixture of melanoma cells and significant fibrosis (Fig. 394. Melanoma cells were spindle shaped without melanin pigment and exhibited moderate atypia with occasional mitoses. They formed clusters (junctional activity) within the basal layer of mucosal epithelium. In addition, melanoma cells exhibited deep vertical invasion into the submucosa with marked desmoplasia (Fig. 3, A and B). It was not always easy to identify the vertical invasion by hematoxylin-eosin staining, because morphologic similarity between melanoma cells and surrounding fibroblasts was great, and because remarkable desmoplasiaovershadowedmelanoma cells. Immunostaining with S- 100 protein allowed for identification of melanoma cells, which were positive; fibroblasts were negative (Fig. 3, B and C). On the basis of these findings, the lesion was diagnosed as desmoplastic melanoma. The melanoma cells were negative with Masson-Fontana staining because of their amelanotic character. The adjacent verrucous lesion showed intraepithelial nestsconsisting of melanoma cells with moderate atypia and rare mitoses. The surrounding epithelia showednonneoplastic papillary proliferation and ver-
Fig. 3. A, Desmoplastic melanoma shows proliferation of spindle cells and collagen fibers in subepithelial tissue. (Hematoxylin-eosin stain; original magnification, X47.) B, lmmunostaining of desmoplastic melanoma with S-100 protein clearly demonstrates vertical growth from junctional melanocytic activity (arrow) to subepithelial tissues (arrow head). (Original magnification, X234.) C, Desmoplastic melanoma shows scattered melanoma cells (arrows), which are spindle-shaped and positive for S-100 protein, whereas fibroblasts are negative (arrowheads). (Original magnification, X468.)
Desmoplastic melanoma
Volume 74
203
Number 2
Fig. 5. Flat pigmentation adjacent to desmoplastic melanoma shows heavy pigmentation at basal layer. (FontanaMasson stain; original magnification, X 117.) Table I. Staining patterns of melanoma cells and dysplastic melanocytes in initial and recurrent tumors S-100
Neuron-specijc
protein
Initial tumor Desmoplasticmelanoma Verrucouslesion Flat pigmentation Recurrenttumor
+++ +++ + +
enolase
+ ++ + -
FontanaMasson
+++ -
+, mildly positive; ++, moderately positive; +++, strongly positive; k, equivocally positive; -, negative.
Fig. 4. A, Verrucous lesion adjacent to desmoplastic melanoma shows intraepithelial clusters of melanoma cells. B, Higher-power view shows melanoma cells with moderate atypia. (Hematoxylin-eosin stain; original magnifications: A, 47; B, x468.)
tical invasion was not noted (Fig. 4). The melanoma cells were positive for S-100 protein, but FontanaMasson staining was negative. The focus of macular oral melanosis showed increased melanocytes in the lower epithelial strata (Fig. 5). These melanocytes had minimal atypia and rare mitoses, suggesting that these melanocytes were probably nonneoplastic or at most dysplastic. Melanophages were scattered in subepithelial tissues. Both the melanocytes and melanophages stained positive with Fontana-Masson yet were essentially negative for S-100 protein. The staining patterns of melanoma cells and dysplastic melanocytes are summarized in Table I.
Recurrent tumor: October 1989 The polypoid recurrent tumor consisted of proliferating spindle cells in the subepithelial tissue as in the lesion in the initial biopsy in March 1988. However, the recurrent tumor showed much higher mitotic rate and cellularity, indicating a greater stage of malignancy (Fig. 6, A and B). The overlying epithelium showed focal ulceration and elongation of rete ridges. Although the gross appearance and histologic features were similar to spindle cell carcinoma, the tumor cells were positive for vimentin and negative for epithelial membrane antigen, indicating their nonepithelial character (Fig. 6, C and D). Additionally, some tumor cells were positive for S- 100 protein, suggesting melanocytic origin, although the tumor cells stained negatively with Fontana-Masson (Table I). DISCUSSION In 1971 Conley et al.’ reported a rare variant of spindle cell melanoma, generally located in the head
204
Kurihara
et al.
ORAL. SLRG ORAL MED ORAL PATHOL. August 1992
Fig. 6. A, Recurrent tumor shows proliferation of spindle cells in subepithelial tissues. (Hematoxylin-eosin stain; original magnification, ~47.) B, Higher-power view shows high cellularity and mitotic rate mimicking spindle cell carcinoma. (Hematoxylin-eosin stain; original magnification, X468.) C, Spindle cells are positive for vimentin, indicating nonepithelial nature. Vimentin immunostain; original magnification, X234.) D, Spindle cells are negative for keratin, suggesting nonepithelial nature. Keratin immunostain: original magnification, X234.) and neck, and coined the term “desmoplastic
malignant melanoma.” This rare variant evolves through a sequence of events, beginning with an inconspicuous superficial melanocytic lesion culminating in the production of a bulky subcutaneous tumefaction.‘-’ Our review of the literature reveals only two authentic cases of desmoplastic melanoma of oral mucosa including one of the maxillary alveolus and another in the buccal mucosa,4, 9 although several cases of desmoplastic melanoma involving sun-exposed areas of the lips have been reported.9 One of the impressive features of our case was histologic findings in the first tumor in March 1988, including desmoplastic melanoma, verrucous melanocytic lesion, and oral melanosis. These lesions seem to be related to one another because of the intimate topographic relation and the natural growth history of desmoplastic melanoma, which originates as a superficial lesion, progressing to desmoplasia in a vertical growth phase. Our assumption is further supported by Takagi et al., lo who found that most oral malignant melanomas in the Japanese population are associated with oral melanosis of the adjacent mucosa. However, in this instance it was impossible to determine whether the oral melanosis was neoplastic and whether the melanosis preceded the occurrence of desmoplastic
melanoma, because we could not histologically examine the oral mucosa before the development of desmoplastic melanoma. Because melanoma cells of desmoplastic melanoma are spindle shaped and amelanotic in the vertical growth phase, this malignancy often presents diagnostic difficulties to pathologists. Batsakis et a1.,4who reported this malignancy in the gingiva, used electron microscopy to demonstrate premelanosomes to arrive at a definitive diagnosis. In our case immunostaining, especially with S-100 protein, was useful for diagnosis. ‘l-t3 Immunostaining with neuron-specific enolase and Fontana-Masson staining were noncontributory. According to Egbert et al,s the recurrent tumor may represent spindle cell melanoma because a morphologic continuum between desmoplastic melanoma and spindle cell melanoma has been suggested. The histologic features of the recurrent tumor were similar to those of spindle cell carcinoma.r4, I5 Immunostaining with epithelial membrane antigen and vimentin was helpful in discounting an epithelial origin. REFERENCES 1. Conley J, Lattes R, Orr W. Desmoplastic malignant melanoma
(a rare variant of spindle cell melanoma). Cancer 1971;28:91436.
Desmoplastic melanoma
Volume 74 Number 2 2. Valensi QJ. Desmoplastic malignant melanoma: a report on two additional cases. Cancer 1977;39:286-92. 3. Valensi QJ. Desmoplastic malignant melanoma: a light and electron microscopic study of two cases.Cancer 1979;43:114855. 4. Batsakis JG, Batter R, Regezi JA, Campbell T. Desmoplastic melanoma of the maxillary alveolus. ORAL SURG ORAL MED ORAL PATHOL
1979;37:107-9.
5. Dimaio SM, Mackay B, Smith JL, Dickersin GR. Neurosarcomatous transformation in malignant melanoma: an ultrastructural study. Cancer 1982;50:2345-54. 6. From L, Hanna W, Kahn H, Gruss J, Marks A, Baumal R. Origin of the desmoplasia in desmoplastic malignant melanoma. Hum Pathol 1983;14:1072-80. 7. Reiman HM, Goellner JR, Woods JE, Mixter RC. Desmoplastic melanoma of the head and neck. Cancer 1987;60:226974. 8. Egbert B, Kempson R, Sagebiel R. Desmoplastic malignant melanoma: a clinicohistopathological study of 25 cases.Cancer 1988;62:2033-41. 9. Jain S, Allen PW. Desmoplastic malignant melanoma and its variants: a study of 45 cases.Am J Surg Path01 1989;13:35873. 10. Takagi M, Ishikawa G, Mori W. Primary malignant melanoma of the oral cavity in Japan: with special reference to mucosal melanosis. Cancer 1974;34:358-70.
205
11. Springall DR, Gu J, Cocchia D, et al. The value of S-100 protein immunostaining as a diagnostic tool in human malignant melanomas: a comparative study using S-100 and neuron-specific enolaseantibodies. Virchows Arch [A] 1983;400:331-43. 12. Gatter KC, Ralfkiaer E, Skinner J, et al. An immunocytochemical study of malignant melanoma and its differential diagnosis from other malignant tumours. J Clin Path01 1985; 38:1353-57. 13. Schmitt FC, Bacchi CE. S-100 protein: is it useful as a tumour marker in diagnostic immunocytochemistry? Histopathology 1989;15:281-8. 14. Leifer C, Miller AS, Putong PB, Min BH. Spindle-cell carcinoma of the oral mucosa. Cancer 1974;34:597-605. 15. Leventon GA, Evans HL. Sarcomatoid squamous cell carcinoma of the mucous membrane of the head and neck: a clinicopathological study of 20 cases.Cancer 1981;48:994-1003. Reprint requests:
Kenji Kurihara, MD, PhD Department of Pathology Uwajima City Hospital Goten-machi Uwajima Ehime 798, Japan
.
Kenji Kurihara, MD, PhD,a Eitaro Sanada, DDS,b Shinya Yasuda, DDS,b and Hiroshi Yamasaki DDS, PhD,C Uwajima and Fukuoka, Japan UWAJIMA
CITY
HOSPITAL
AND
FUKUOKA
UNIVERSITY
HOSPITAL
A case of desmoplastic melanoma in a 58-year-old man is reported. This rare malignancy occurred in the maxillary alveolus, appearing as an epulis. Histologically, the tumor was flanked by melanocytic proliferation in the adjacent mucosae. At the time of local recurrence after partial maxillectomy, the tumor showed a polypoid growth, with an increase in cellularity and mitotic rate resembling spindle cell carcinoma. The value of immunostaining for diagnosis is stressed. (ORALSURCORALMEDORALPATHOL~~~~;~~:~O~-~)
I
n 197 1 Conley et al. 1reported a rare variant of malignant melanoma that had the clinical and histologic appearance of a fibrous tumor, for which they coined the term “desmoplastic melanoma.” We report a case of desmoplastic melanoma of the gingiva, with the clinical appearance of an epulis, that resembled spindle cell carcinoma at the time of local recurrence. Immunostaining employing the peroxidase-antiperoxidase (PAP) method proved useful in securing the correct diagnosis. CASE REPORT
In March 1988a 58-year-old man visited the Department of Oral Surgery, Uwajiwa City Hospital, with a complaint of tumor on the gum. The patient first noticed the tumor about 1 year ago, and it had increased in size gradually. Examination revealed a firm elevated tumor with normalappearing mucosa on the right maxillary alveolus in the cuspid-premolar region. The 1.5 cm tumor had a smooth mucosal surface. Adjacent to the main tumor mass were two smaller lesions, including a verrucous mucosal elevation and a brown macular pigmentation (Fig. 1). A clinical diagnosis of epulis was made, and a biopsy was performed. A di-
Fig. 1. Lingual aspect of surgical specimen removed in March 1988 shows elevated lesion similar to epulis.
amination revealed a 2.5 cm polypoid tumor with superficial ulceration of the gingiva adjacent to second premolar
agnosis of epulis fibromatosa with atypical proliferation of
(Fig. 2). Cervical lymph nodes were not palpable,
melanocytes was initially rendered by the hospital pathologist, and a partial maxillectomy was performed (Fig. 1). In October 1989 the patient was admitted again to our institute because of a rapidly growing recurrent tumor. Ex-
whole-body computerized tomography revealed probable maxillary involvement with no other evidence of systemic disease.A biopsy revealed a recurrent melanoma with in-
aDepartment of Pathology, Uwajima City Hospital. bDepartment of Oral Surgery, Uwajima City Hospital. CDepartment of Oral Surgery, Fukuoka University Hospital 7/14/30986
and
creased cellularity. The patient was transferred to another institution for a total maxillectomy and is alive 31 months after the initial surgery.
MATERIAL AND METHODS Routine histologic sections were prepared from the formalin-fixed samples and stained with hematoxylin201
202
Kurihara
et al.
0~41.
SURC ORAL
MED ORAL PATHOL August 1992
Fig. 2. Recurrent tumor shows polypoid growth with ulceration.
eosin and Fontana-Masson. Histologic sections were also examined on the basis of the PAP method for S- 100 protein, neuron-specific enolase, keratin, and vimentin. All the antibodies were obtained from Dako Co. (Glostrup, Denmark). RESULTS Initial specimens:
March 1988
The elevated epulis-like lesion consisted of a mixture of melanoma cells and significant fibrosis (Fig. 394. Melanoma cells were spindle shaped without melanin pigment and exhibited moderate atypia with occasional mitoses. They formed clusters (junctional activity) within the basal layer of mucosal epithelium. In addition, melanoma cells exhibited deep vertical invasion into the submucosa with marked desmoplasia (Fig. 3, A and B). It was not always easy to identify the vertical invasion by hematoxylin-eosin staining, because morphologic similarity between melanoma cells and surrounding fibroblasts was great, and because remarkable desmoplasiaovershadowedmelanoma cells. Immunostaining with S- 100 protein allowed for identification of melanoma cells, which were positive; fibroblasts were negative (Fig. 3, B and C). On the basis of these findings, the lesion was diagnosed as desmoplastic melanoma. The melanoma cells were negative with Masson-Fontana staining because of their amelanotic character. The adjacent verrucous lesion showed intraepithelial nestsconsisting of melanoma cells with moderate atypia and rare mitoses. The surrounding epithelia showednonneoplastic papillary proliferation and ver-
Fig. 3. A, Desmoplastic melanoma shows proliferation of spindle cells and collagen fibers in subepithelial tissue. (Hematoxylin-eosin stain; original magnification, X47.) B, lmmunostaining of desmoplastic melanoma with S-100 protein clearly demonstrates vertical growth from junctional melanocytic activity (arrow) to subepithelial tissues (arrow head). (Original magnification, X234.) C, Desmoplastic melanoma shows scattered melanoma cells (arrows), which are spindle-shaped and positive for S-100 protein, whereas fibroblasts are negative (arrowheads). (Original magnification, X468.)
Desmoplastic melanoma
Volume 74
203
Number 2
Fig. 5. Flat pigmentation adjacent to desmoplastic melanoma shows heavy pigmentation at basal layer. (FontanaMasson stain; original magnification, X 117.) Table I. Staining patterns of melanoma cells and dysplastic melanocytes in initial and recurrent tumors S-100
Neuron-specijc
protein
Initial tumor Desmoplasticmelanoma Verrucouslesion Flat pigmentation Recurrenttumor
+++ +++ + +
enolase
+ ++ + -
FontanaMasson
+++ -
+, mildly positive; ++, moderately positive; +++, strongly positive; k, equivocally positive; -, negative.
Fig. 4. A, Verrucous lesion adjacent to desmoplastic melanoma shows intraepithelial clusters of melanoma cells. B, Higher-power view shows melanoma cells with moderate atypia. (Hematoxylin-eosin stain; original magnifications: A, 47; B, x468.)
tical invasion was not noted (Fig. 4). The melanoma cells were positive for S-100 protein, but FontanaMasson staining was negative. The focus of macular oral melanosis showed increased melanocytes in the lower epithelial strata (Fig. 5). These melanocytes had minimal atypia and rare mitoses, suggesting that these melanocytes were probably nonneoplastic or at most dysplastic. Melanophages were scattered in subepithelial tissues. Both the melanocytes and melanophages stained positive with Fontana-Masson yet were essentially negative for S-100 protein. The staining patterns of melanoma cells and dysplastic melanocytes are summarized in Table I.
Recurrent tumor: October 1989 The polypoid recurrent tumor consisted of proliferating spindle cells in the subepithelial tissue as in the lesion in the initial biopsy in March 1988. However, the recurrent tumor showed much higher mitotic rate and cellularity, indicating a greater stage of malignancy (Fig. 6, A and B). The overlying epithelium showed focal ulceration and elongation of rete ridges. Although the gross appearance and histologic features were similar to spindle cell carcinoma, the tumor cells were positive for vimentin and negative for epithelial membrane antigen, indicating their nonepithelial character (Fig. 6, C and D). Additionally, some tumor cells were positive for S- 100 protein, suggesting melanocytic origin, although the tumor cells stained negatively with Fontana-Masson (Table I). DISCUSSION In 1971 Conley et al.’ reported a rare variant of spindle cell melanoma, generally located in the head
204
Kurihara
et al.
ORAL. SLRG ORAL MED ORAL PATHOL. August 1992
Fig. 6. A, Recurrent tumor shows proliferation of spindle cells in subepithelial tissues. (Hematoxylin-eosin stain; original magnification, ~47.) B, Higher-power view shows high cellularity and mitotic rate mimicking spindle cell carcinoma. (Hematoxylin-eosin stain; original magnification, X468.) C, Spindle cells are positive for vimentin, indicating nonepithelial nature. Vimentin immunostain; original magnification, X234.) D, Spindle cells are negative for keratin, suggesting nonepithelial nature. Keratin immunostain: original magnification, X234.) and neck, and coined the term “desmoplastic
malignant melanoma.” This rare variant evolves through a sequence of events, beginning with an inconspicuous superficial melanocytic lesion culminating in the production of a bulky subcutaneous tumefaction.‘-’ Our review of the literature reveals only two authentic cases of desmoplastic melanoma of oral mucosa including one of the maxillary alveolus and another in the buccal mucosa,4, 9 although several cases of desmoplastic melanoma involving sun-exposed areas of the lips have been reported.9 One of the impressive features of our case was histologic findings in the first tumor in March 1988, including desmoplastic melanoma, verrucous melanocytic lesion, and oral melanosis. These lesions seem to be related to one another because of the intimate topographic relation and the natural growth history of desmoplastic melanoma, which originates as a superficial lesion, progressing to desmoplasia in a vertical growth phase. Our assumption is further supported by Takagi et al., lo who found that most oral malignant melanomas in the Japanese population are associated with oral melanosis of the adjacent mucosa. However, in this instance it was impossible to determine whether the oral melanosis was neoplastic and whether the melanosis preceded the occurrence of desmoplastic
melanoma, because we could not histologically examine the oral mucosa before the development of desmoplastic melanoma. Because melanoma cells of desmoplastic melanoma are spindle shaped and amelanotic in the vertical growth phase, this malignancy often presents diagnostic difficulties to pathologists. Batsakis et a1.,4who reported this malignancy in the gingiva, used electron microscopy to demonstrate premelanosomes to arrive at a definitive diagnosis. In our case immunostaining, especially with S-100 protein, was useful for diagnosis. ‘l-t3 Immunostaining with neuron-specific enolase and Fontana-Masson staining were noncontributory. According to Egbert et al,s the recurrent tumor may represent spindle cell melanoma because a morphologic continuum between desmoplastic melanoma and spindle cell melanoma has been suggested. The histologic features of the recurrent tumor were similar to those of spindle cell carcinoma.r4, I5 Immunostaining with epithelial membrane antigen and vimentin was helpful in discounting an epithelial origin. REFERENCES 1. Conley J, Lattes R, Orr W. Desmoplastic malignant melanoma
(a rare variant of spindle cell melanoma). Cancer 1971;28:91436.
Desmoplastic melanoma
Volume 74 Number 2 2. Valensi QJ. Desmoplastic malignant melanoma: a report on two additional cases. Cancer 1977;39:286-92. 3. Valensi QJ. Desmoplastic malignant melanoma: a light and electron microscopic study of two cases.Cancer 1979;43:114855. 4. Batsakis JG, Batter R, Regezi JA, Campbell T. Desmoplastic melanoma of the maxillary alveolus. ORAL SURG ORAL MED ORAL PATHOL
1979;37:107-9.
5. Dimaio SM, Mackay B, Smith JL, Dickersin GR. Neurosarcomatous transformation in malignant melanoma: an ultrastructural study. Cancer 1982;50:2345-54. 6. From L, Hanna W, Kahn H, Gruss J, Marks A, Baumal R. Origin of the desmoplasia in desmoplastic malignant melanoma. Hum Pathol 1983;14:1072-80. 7. Reiman HM, Goellner JR, Woods JE, Mixter RC. Desmoplastic melanoma of the head and neck. Cancer 1987;60:226974. 8. Egbert B, Kempson R, Sagebiel R. Desmoplastic malignant melanoma: a clinicohistopathological study of 25 cases.Cancer 1988;62:2033-41. 9. Jain S, Allen PW. Desmoplastic malignant melanoma and its variants: a study of 45 cases.Am J Surg Path01 1989;13:35873. 10. Takagi M, Ishikawa G, Mori W. Primary malignant melanoma of the oral cavity in Japan: with special reference to mucosal melanosis. Cancer 1974;34:358-70.
205
11. Springall DR, Gu J, Cocchia D, et al. The value of S-100 protein immunostaining as a diagnostic tool in human malignant melanomas: a comparative study using S-100 and neuron-specific enolaseantibodies. Virchows Arch [A] 1983;400:331-43. 12. Gatter KC, Ralfkiaer E, Skinner J, et al. An immunocytochemical study of malignant melanoma and its differential diagnosis from other malignant tumours. J Clin Path01 1985; 38:1353-57. 13. Schmitt FC, Bacchi CE. S-100 protein: is it useful as a tumour marker in diagnostic immunocytochemistry? Histopathology 1989;15:281-8. 14. Leifer C, Miller AS, Putong PB, Min BH. Spindle-cell carcinoma of the oral mucosa. Cancer 1974;34:597-605. 15. Leventon GA, Evans HL. Sarcomatoid squamous cell carcinoma of the mucous membrane of the head and neck: a clinicopathological study of 20 cases.Cancer 1981;48:994-1003. Reprint requests:
Kenji Kurihara, MD, PhD Department of Pathology Uwajima City Hospital Goten-machi Uwajima Ehime 798, Japan